Editors: Bergin, James D.

Title: Advanced Medicine Recall, 1st Edition

Copyright 2009 Lippincott Williams & Wilkins

> Front of Book > Editors

Editor
James D. Bergin MD
Professor of Medicine
Division of Cardiovascular Medicine, University of Virginia Health System,
Charlottesville, Virginia

Recall Series Editor

Lorne H. Blackbourne MD, FACS
Trauma, Burn, and Critical Care Surgeon
San Antonio, Texas

Contributors
Editor
James D. Bergin MD
Professor of Medicine

Associate Editor
Amy West MD
Chief Medical Resident

Allergy and Immunology

Jeffrey Culp MD
Fellow
Division of Allergy and Immunology

Sean R. Lucas MD, MPH

Clinical Instructor of Medicine

Cardiology
Kavita Sharma
Medical student, class of 2007
Matthew Trojan MD
Clinical Instructor of Medicine

James D. Bergin MD
Professor of Medicine

Endocrinology
Sacchin Majumdar MD
Resident
Department of Internal Medicine

Shetal Padia MD
Fellow
Division of Endocrinology

Alan Dalkin MD
Associate Professor of Medicine

Gastroenterology
Kavita Sharma
Medical student, class of 2007

Josh Hall MD
Resident
Department of Medicine

Vanessa Shami MD
Assistant Professor of Medicine

Hematology
Christine Lin MD
Resident
Department of Medicine

David Mack MD
Fellow
Division of Hematology

Gail Macik MD
Associate Professor of Medicine and Pathology

Infectious Disease
Tedra M. Claytor MD
Fellow
Division of Infectious Disease

Brian Wispelwey MS, MD

Professor of Medicine

Nephrology
Joshua King MD
Resident
Department of Medicine

Melisha Bissram MD
Fellow
Division of Nephrology

Mitch Rosner MD
Assistant Professor of Medicine

Oncology
Heather West MD
Fellow
Division of Hematology and Oncology

Heidi Gillenwater MD
Assistant Professor of Medicine

Pulmonology
Brian Hanrahan MD
Resident
Department of Medicine

Steven Koenig MD
Professor of Medicine
Rheumatology
Ashok Jacob MD
Fellow
Division of Rheumatology

Wael Jarjour MD
Associate Professor of Medicine

Dermatology
Rebecca Rudd Barry MD
Resident
Department of Dermatology

R. Carter Grine MD
Resident
Department of Dermatology

Barbara Braunstein Wilson MD

Associate Professor of Dermatology

Environmental Medicine
Barbara Wiggins PharmD

James D. Bergin MD
Professor of Medicine

Neurology
Lee Kubersky MD
Resident
Department of Neurology

Russell H. Swerdlow MD
Associate Professor of Neurology

Barnett R. Nathan MD
Associate Professor of Neurology

Nathan B. Fountain MD
Associate Professor of Neurology
Pharmacology
Barbara Wiggins PharmD

James D. Bergin MD
Professor of Medicine

Psychiatry
Kurt Miceli MD
Resident
Department of Psychiatry

Suzanne Holroyd MD
Professor of Medicine

The Consultant
James D. Bergin MD
Professor of Medicine
Editors: Bergin, James D.
Title: Advanced Medicine Recall, 1st Edition
Copyright 2009 Lippincott Williams & Wilkins

> Front of Book > Dedication

Dedication

To my children, Christopher and Laura, and my wife, Leslie, for all their support.
Editors: Bergin, James D.
Title: Advanced Medicine Recall, 1st Edition
Copyright 2009 Lippincott Williams & Wilkins

> Front of Book > Acknowledgments

Acknowledgments

I would like to recognize the hard work of the current authors as well as the
contributions from the previous authors whose efforts we have built upon.
Editors: Bergin, James D.
Title: Advanced Medicine Recall, 1st Edition
Copyright 2009 Lippincott Williams & Wilkins

> Table of Contents > Section I - Overview > Chapter 1 - Introduction

Chapter 1
Introduction

A few years ago it was clear that Medicine Recall was becoming too large a book to
be easily carried around. Feedback from medical students included comments that
their coat pockets were being stretched and that they were leaning to one side. We
therefore undertook two projects. The first was to shorten Medicine Recall to be
more concise and pocket friendly, and the second was to write Advanced Medicine
Recall to target fourth-year students and residents. Advanced Medicine Recall is an
attempt to focus more on the advanced features of the disease processes. With that
in mind, all the sections in Advanced Medicine Recall have been reviewed by a Chief
or Advanced Medical Resident with the thought that the information presented is
something that fourth-year students and interns should be expected to know. There
is some (<10%) deliberate repetition between Medicine Recall and Advanced
Medicine Recall, and there are several reasons for this. First, the medical students
who reviewed the chapters may have felt that some of the information needed to
be there. Second, the Chief Medical Resident and the Attending authors may have
felt that some of the information was worthy of repetition or, in some cases, that it
made sections flow better. In many instances, when the questions between the two
books are similar, answers in Advanced Medicine Recall have been adjusted to
reflect a higher level of knowledge. Readers are, therefore, referred to Medical
Recall to review the more basic material for each section.

Like all of the other books in the Recall series, this book is organized in a self-
study/quiz format with questions on the left and answers on the right. It may be
worthwhile for the reader, while reading through the book, to cover the right-hand
column with the enclosed bookmark. As in the previous version of Medicine Recall,
the chapters are organized by systems, with section abbreviations and definitions
preceding each discussion. When applicable, a list of appropriate landmark clinical
trials completes the chapter.

We hope that you will find this book a helpful addition to your library.

Pearls
As with Medicine Recall:
Remember to wash your hands. Patients really notice this and it is critical. This
is one of the few things we can do to prevent the spread of infection. Do it in
front of the patient (at the end of the exam or preferably both at the beginning
and the end).

P.3
Respect the patient's modesty. Always use curtains, gowns, and other
appropriate coverings.

The patient's confidentiality should be maintained beyond the patient's room

(e.g., the patient's case should not be offhandedly discussed in an elevator,
while eating, or while traveling to and from work); the patient's family or friends
or others may overhear.

Remember not to neglect your private life. Relationships require time and effort
to build and keep strong. If you are unhappy in your private life you will likely
also be unhappy in your professional life.

In delivering bad news, it is often best to diminish the patient's anxiety by sitting
and delivering the information without delay. Because much of the remainder of
the conversation will often be forgotten, it is often best to return to the patient
later to review important data.

Depression is common. Approximately 60% of medical patients have depression as

an important aspect of their illness.

Heart disease, smoking-related illness, and cancer are common illnesses. One or
more of these should always be considered in the differential diagnosis.

A common illness presenting in an uncommon fashion is more common than an

uncommon illness presenting in a common fashion. (In other words, when you
hear hoofbeats, always think of horses, not zebras.) Furthermore, the diagnosis
should be in the differential the majority of the time after a careful history and
physical. A shotgun approach in ordering labs and tests is generally
nonproductive and almost always not cost-effective or helpful. This approach can
lead to false-positive test results, which can derail a workup.

Never talk disparagingly about your colleagues. Talking in a disparaging fashion

about referring colleagues only undermines the patient's confidence in the
referring physician or in you. If the patient has had a long-term relationship with
the referring physician, the patient may trust the other physician's word over
yours, regardless of who is right. On the attending level, talking negatively about
another physician may eventually sever a referral source, and it is just plain
wrong to do.

Before ending an interview or discussion with a patient, always ask whether the
patient has questions (and not as you are going to the door).

Remember to think at least twice before answering emails to make sure that the
email conveys what you want it to and nothing more. Emails can easily be
copied, sent along, and saved forever. They can come back to haunt you.

When you write something in the chart, think how it would sound were it to be
read aloud in court. If you write your notes that way, you will always be safe.
Editors: Bergin, James D.
Title: Advanced Medicine Recall, 1st Edition
Copyright 2009 Lippincott Williams & Wilkins

> Table of Contents > Section II - The Specialties > Chapter 2 - Allergy and Immunology

Chapter 2
Allergy and Immunology

Abbreviations
ABPA Allergic bronchopulmonary aspergillosis

APC Antigen-presenting cell

AIRE Autoimmune regulator

APS Autoimmune polyglandular syndrome

AR Autosomal recessive

CGD Chronic granulomatous disease

C 1INH C 1 esterase inhibitor

CVID Common variable immunodeficiency

EBV Epstein-Barr virus

ELISA Enzyme-linked immunosorbent assay

FESS Functional endoscopic sinus surgery

HIM Hyperimmunoglobulin M

HIV Human immunodeficiency virus

HLA Human leukocyte antigen

ICF Immunodeficiency centromeric instability and facial anomalies

ICOS Inducible T-cell costimulator gene

IFN Interferon

IL Interleukin

IVIG Intravenous immunoglobulin (IgG)

LAD Leukocyte adhesion deficiency

LPS Lipopolysaccharide

MCP Monocyte chemoattractant protein

MHC Major histocompatibility complex

NARES Nonallergic rhinitis with eosinophilia syndrome

NK Natural killer

NSAID Nonsteroidal anti-inflammatory drug

PAMP Pathogen-associated molecular patterns

PCP Pneumocystis jiroveci pneumonia

PSS Progressive systemic sclerosis

RANTES Regulated on activation, normal T-cell expressed, and secreted

chemokine

SADNI Specific antibody deficiency with normal immunoglobulins

SCID Severe combined immunodeficiency

TACI Transmembrane activator, calcium modulator, and cyclophilin ligand

interactor

TLR Toll-like receptor

UP Urticaria pigmentosa

WHIM Warts, hypogammaglobulinemia, infection, myelokathexis

 XLA X-linked agammaglobulinemia

XLP X-linked lymphoproliferative syndrome

P.8

Definitions
Define the following:

Innate immunity Hard-wired responses encoded by host germ-line genes

that recognize patterns on many foreign microbes
(nonspecific immunity)

Adaptive Responses encoded by gene elements that have

immunity undergone rearrangement resulting in assembly of
antigen-binding structures with high specificity for unique
microbial antigens (specific immunity)

Chemokines Small molecules that induce chemotaxis through G

proteincoupled receptors

Antigen A protein (or carbohydrate) recognized by the immune

system

Immunoglobulins Protein products of mature plasma cells

Antibodies Immunoglobulins that recognize specific antigens

MHC The major histocompatibility complex (MHC), or HLA in

humans, is the genetic region housing the loci of genes
encoded on chromosome 6 (HLA I, II, III). They are
responsible for generating cell surface glycoproteins that
bind peptides made in cells (MHCI) or ingested by cells
and processed (MHCII). These glycoproteins are necessary
for the presentation of foreign proteins to T lymphocytes.
The absence of MHC may cause a severe
immunodeficiency. The presence of different forms
(polymorphisms) is associated with the potential for
specific disease states (e.g., HLA-B27 and ankylosing
spondylitis).

P.9
P.10
P.11
Basic Immunology
What makes the Recognition of self from nonself by key effector systems
basic function of
the immune
system possible?

List four 1. Physical barriers (e.g., skin)

nonspecific 2. Complement
components of 3. Phagocytic cells, many with TLRs that recognize
the innate microbial patterns
immune system 4. Cytokines

Where do All lymphocytes arise in bone marrow; 85% are T cells.

lymphocytes
arise?

Where do T cells mature in the thymus and B cells mature in the

lymphocytes fetal liver and adult bone marrow.
undergo
maturation?

What is the To facilitate resistance to intracellular microorganisms

function of T (e.g., mycobacteria, viruses, fungi, and parasites) and
cells (cell- tumors and to regulate specific antibody production by B
mediated cells
immunity)?

What is the Located on the cell surface, CD4 and CD8 receptors are
difference important in determining the recognition of antigen. T cells
between CD4 + bearing CD4 can recognize only antigen embedded in MHC
class II, which is found only on the surface of a few
and CD8 + T
specialized cells (APCs). T cells bearing CD8 recognize
cells?
antigen on MHC class I, which is found on all nucleated
cells.

What cell CD3, a marker used for all T cells.

markers might be CD4, a marker for T-helper cells. It generally defines 60%
useful clinically? to 70% of T cells in the peripheral blood and lymphoid
tissue and is the receptor for HIV.
CD8, a marker for cytotoxic T cells.
CD19 or CD20, B-cell markers.
CD16 and 56, markers for NK cells.
What is the T-cell markers (e.g., CD4 and CD8) have functional
difference significance, whereas B-cell markers (e.g., CD19 and CD20)
between T- and are primarily of maturational significance.
B-cell markers?

What is the To mature into plasma cells and produce antibody. They
function of B can also act as macrophages and APCs.
cells (humoral
immunity)?

What are the five IgA, IgD, IgE, IgG, and IgM
major classes
(isotypes) of
immunoglobulins?

What is the basic A combination of two heavy chains and two light chains
structure of
immunoglobulins?

What are the two Kappa and lambda

types of light
chains?

What is the role Recognition and binding of specific extracellular antigens

of and activation of cells or of the complement-binding
immunoglobulin? system

What are the Recognition, amplification, and response

three phases of
the immune
response?

Describe each
phase of the
immune
response:

Recognition Foreign antigen patterns (e.g., bacterial LPSs) are

recognized by the innate immune system.

Amplification Signals are generated leading to the release of cytokines

that attract other immune components to the site of
foreign invasion.

Response The stimulating antigen is cleared from the system by

 effector mechanisms such as inflammation, further innate
effector mechanisms (e.g., phagocytosis), and initiation of
the adaptive immune response.

What are the Granule-associated mediators (e.g., histamine, tryptase,

basic mast cell heparin), lipid derived mediators (e.g., leukotrienes),
products? cytokines/chemokines (e.g., IL-5)

What are the Mast cells, basophils, and eosinophils. Mast cells and
effectors of an basophils are the source of histamine and leukotrienes
IgE-mediated released in an allergic response. Eosinophils are important
response? in the IgE-mediated killing of helminths. IgE and
eosinophils are both produced in response to cytokines
expressed by Th2 cells.

What does Complement, a component of the innate immune system,

complement do? lyses pathogens via the membrane activation complex
(MAC) in the absence of specific immunity, opsonizes
pathogens to target them for destruction, and recruits
other cells and proteins to help with target destruction.

P.12
P.13
P.14
P.15
P.16

Immunodeficiency
How are primary 1. Antibody/B cell deficiencies [Bruton's X-linked
immunodeficiencies agammaglobulinemia, AR agammaglobulinemia,
involving known CVID (ICOS and TACI deficiencies), HIM (AR), ICF
molecular defects syndrome]
classified? 2. Cellular deficiencies (IFN-!/IL-12 axis, APS type
1, defective NK function)
3. Combined [SCID, Wiskott-Aldrich, DiGeorge,
ataxia telangiectasia, HIM (AR), XLP syndrome,
WHIM syndrome, caspase 8 deficiency]
4. Complement
5. Phagocytic (CGD, Chediak-Higashi syndrome,
LAD, specific granule deficiency, cyclic
neutropenia, X-linked neutropenia)

What are some 1. Selective IgA deficiency

common primary 2. CVID
immunodeficiencies
immunodeficiencies 3. SADNI
with no known 4. Hyper-IgE syndrome
molecular defect? 5. Cartilage hair hypoplasia
6. Idiopathic CD4 lymphocytopenia (Nezelof
syndrome)

What are common 1. Immunosuppression (chemotherapy, steroids,

causes of secondary immunomodulators, antilymphocyte antibodies)
immunodeficiency? 2. Infections (HIV, herpes, parasites)
3. Malignancy (Hodgkin's, leukemia, myeloma)
4. Autoimmune disease (diabetes, lupus)
5. Malnutrition
6. Environmental exposure (radiation, chemical)
7. Other (uremia, intestinal lymphangiectasia,
pregnancy, aging, stress, hyposplenism)

In general, what does a Intact cellular immunity

history of contact
dermatitis (e.g., poison
ivy) suggest?

What is a simple test The anergy panel skin test (e.g., PPD, Candida,
for T-cell function? Trichophyton, tetanus toxoid, saline control) is a
measure of delayed-type hypersensitivity; a positive
test requires intact T-cell function.

What interferes with an 1. Corticosteroids (topical or higher-dose systemic)

anergy panel? 2. Anticoagulants (induration is the result of fibrin
deposition)
3. Technique (failure to place antigen
intradermally)
4. Infection (HIV, EBV, TB, leprosy)
5. Autoimmune disease (sarcoid, lupus, rheumatoid
arthritis)
6. Malnutrition
7. Pregnancy
8. Malignancy (e.g., Hodgkin's lymphoma)

What assays are Flow cytometry for CD3, CD4, CD8, CD45, T-cell
available to test for T receptor
cells?

What assays are CD19, CD20, CD21, Ig-associated

available to test for B
cells?

What assays are CD16/CD56

available to test for NK
cells?

What assays are useful Pre- and postimmunization pneumococcal,

in the evaluation of diphtheria, tetanus titers, isohemagglutinins
patients with
borderline IgG levels or
recurrent
sinopulmonary
bacterial infections?

What is the treatment Antibiotics for specific infections and, sometimes,

for IgA deficiency? prophylactic antibiotics. IgA-deficient patients who
are unable to mount a response to polysaccharide
vaccines are occasionally given IVIg.

Are blood transfusions No. Some IgA-deficient patients with anti-IgA

safe in patients with antibodies are at increased risk of a severe reaction
IgA deficiency? to trace IgA from IVIg and from blood transfusions
(washed packed cells should be given if transfusion
is needed).

What constitutes the Total serum IgGs are reduced to >2 standard
diagnosis of CVID? deviations below the age-adjusted mean as well as
impaired production of specific antibodies
(isohemagglutinins or poor response to vaccines
above).

What infections are Most common, sinopulmonary infections

seen in IgG Common, central nervous system, joint, and
deficiencies? gastrointestinal tract infections

What organisms are the Most common, encapsulated bacteria such as

most common causes Haemophilus influenzae or Streptococcus
of infection in patients pneumoniae
with IgG deficiencies? Common, Staphylococcus aureus, meningococci,
Pseudomonas, Campylobacter, Ureaplasma, and
Mycoplasma, Giardia

Are persons with IgG As a rule, no. However, IgG-deficient patients are
deficiencies more susceptible to polioviruses (and should not receive
susceptible to viral live virus vaccine) and to hepatitis B and C. In
infections? patients with XLA (but not CVID or HIM), a chronic
meningoencephalitis, which is ultimately fatal, can
develop with enteroviruses (echovirus or coxsackie)
infection.

What are the Low IgG, IgA, IgE, variable IgM. B cells (CD19) are
laboratory and present in the peripheral blood and sometimes in
radiographic findings in exuberant lymphoid tissue. Commonly these patients
CVID? (25%) have bronchiectasis on high-resolution
computed tomography (CT) of the chest.

When are patients with Generally, boys with XLA are seen after the first 6
agammaglobulinemia months of life (after maternal antibodies are gone)
first seen? and within the first 2 years of life.

What are laboratory XLA patients have essentially no B cells (CD19) in

and radiographic circulation and no discernible lymphoid tissue (a
findings in lateral neck view showing no adenoidal tissue is a
agammaglobulinemia? diagnostic test in children).

What infections are Sinopulmonary bacterial infections, enterovirus

common in patients meningoencephalitis
with
agammaglobulinemia?

Can a patient have an Yes, there have been reports of patients with B-cell
antibody deficiency immunodeficiency in spite of a normal total IgG
with a normal total IgG level.
level?

How are patients with Most of these patients have an inability to mount a
B-cell response to polysaccharide antigens (pneumococcus
immunodeficiency and or unconjugated Haemophilus).
normal total IgG level
recognized?

How should patients The patient should receive vaccination with

with recurrent unconjugated pneumococcal vaccine and tetanus
pneumonia or other toxoid; then prevaccination and postvaccination (3
serious bacterial to 4 weeks) titers of antibodies to at least 14
infections be pneumococcal serotypes assayed simultaneously. An
evaluated? adequate response is a fourfold increase in antibody
titers between the paired serums. Vaccination with
H. influenzae (type b) conjugated to a protein may
be useful for protecting these patients but is usually
 not helpful in diagnosis.

What is the treatment Monthly infusions of pooled IVIg. The dose is

for IgG deficiencies? generally begun at 200 to 400 mg/kg and is titrated
to maintain an IgG trough level of >400 mg/dL
obtained immediately before the next infusion (or
sometimes to an adequate clinical response). Despite
IgG infusions, many patients with CVID require
prophylactic antibiotics.

Name some of the ADA deficiency (most common)

different types of SCID. PNP deficiency
RAG1, RAG2 (Omenn syndrome)
Defective cytokine signaling
X-linked (common gamma chain)
Autosomal recessive (IL2, IL7 receptor)

For each of the following, list the lymphocyte defect and major
abnormalities:

DiGeorge syndrome T cell; cardiac defects (great vessels) and

hypocalcemia (failure of development of the
parathyroids), absent thymus, abnormal ears,
shortened philtrum, micrognathia, and hypotelorism

Idiopathic CD4 T cell; DiGeorge syndrome without the associated

lymphocytopenia congenital anomalies; resembles HIV (failure to
(Nezelof syndrome) thrive, candidiasis, anemia, thrombocytopenia,
cancer)

SCID T and B cell; may be X-linked or autosomal

recessive. Affected infants rarely survive the severe
immunodeficiency state beyond 1 year. They often
present with failure to thrive, diarrhea, respiratory
infection, and disseminated infection.

ADA Most common type of SCID; T and B cells; a form of

SCID with deficient purine metabolism (adenosine
deaminase)

PNP Type of SCID; T cells; similar to ADA with deficient

purine metabolism leading to toxic intracellular
levels of deoxyguanosine triphosphate

Wiskott-Aldrich T and B cell; low serum levels of IgM and increased

syndrome levels of IgE; eczema, thrombocytopenia, repeated
infections (encapsulated organisms), lymphoreticular
malignancies, and anergy

Ataxia-telangiectasia T and B cells; cerebellar ataxia and oculocutaneous

telangiectasia (butterfly rash over the sclera, face,
and ears), truncal ataxia, ovarian agenesis,
sinopulmonary infections leading to bronchiectasis
and lymphomas, and high levels of !-fetoprotein and
carcinoembryonic antigen; highly susceptible to
radiation-induced chromosomal injury and
subsequent tumors.

Chronic T cell; superficial candidiasis (not systemic)

mucocutaneous associated with single or multiple endocrinopathies,
candidiasis iron deficiency, and anergy; molecular defect in AIRE
(autoimmune
polyglandular syndrome
type I)

Hyperimmunoglobulin Uncertain, with increased serum levels of IgE (up to

E 10 times normal); recurrent infections of the skin
and sinopulmonary tract with S. aureus, H.
influenzae, and Aspergillus; coarse facial features;
delayed shedding of primary teeth; and chronic
eczematous rashes

Do any of the T- and CVID; chronic mucocutaneous candidiasis and

B-cell primary hyperimmunoglobulin E are disorders compatible
immunodeficiencies with living to adulthood; the other T-cell or
discussed occur in combined immunodeficiencies listed above are
adults? severe and generally present early in life; without
bone marrow transplantation, they are generally
fatal.

In general, how are T- Bone marrow, fetal liver, and thymus transplantation
cell and combined may have a role. Gamma globulin infusions
immunodeficiencies antibiotics may be given for patients who are IgG
treated? deficient or with SADNI. Fresh frozen plasma may be
given for other immunoglobulin-deficient states.
Good postural drainage helps prevent sinopulmonary
infections. Live vaccines, blood transfusions, and x-
rays avoided in patients with T-cell deficiencies.
Splenectomy, chemotherapy, immunomodulators,
antifungals, and antivirals are needed in rare cases.
HIV
See Chapter 7 (Infectious Disease) and Medicine Recall, 3rd ed. for more
discussion of HIV.

P.17

Complement Deficiency
Are complement deficiencies No, they are rare (prevalence = 0.03%).
common?

Name the most common C2, C9, MBL

complement deficiencies.

How are most inherited? Autosomal recessive

What diseases are seen in 1. Autoimmune disease

patients with complement 2. Recurrent infections
deficiency?

What is a common C2 deficiency is seen in approximately 1 in

complement deficiency? 25,000 Caucasians, in whom there is an
increased tendency for autoimmune disease.

What immune issues do Persons are rarely clinically affected by a

patients with complement decreased ability to opsonize pyogenic
deficiency have troubles bacteria.
with?

In what ethnic groups are These deficiencies are probably more common
terminal complement in ethnic groups other than Caucasians.
deficiencies seen?

What infections are most People with terminal complement component

common with this problem? deficiencies (C5 to C9) are predisposed to
Neisseria infections.

What complement deficiency Deficiency of C 1 INH

is associated with recurrent
episodes of angioedema?

What types of processes 1. Autoimmune disease (lupus, rheumatoid

cause complement arthritis, vasculitis)
consumption?
 consumption? 2. Infections
3. Serum sickness

Autoimmunity
See Medicine Recall, 3rd ed.

P.18

Anaphylaxis
What is the Stop the causative agent (e.g., penicillin infusion), provide
acute treatment basic life support, and:
for anaphylaxis? 1. Epinephrine, intramuscular injections of 0.3 to 0.5 mL of
1:1000 every 5 minutes as necessary to control
symptoms.
2. IV fluids for hypotension.
3. H1 blockers (diphenhydramine, >50 mg up to 300
mg/day) and H2 blockers (cimetidine, 4 mg/kg)
intravenously.
4. Glucagon, atropine, dopamine if patient is on beta
blockers or refractory to epinephrine.

Why should Episodes can recur for up to several hours after the event.
patients who
have had an
anaphylactic
reaction be
monitored after
successful
therapy?

What are some Drugs: antibiotics (particularly beta lactams), protamine,

of the drug and insulin, muscle relaxants, general anesthetics, and vaccines
food causes of Food: peanuts, tree nuts, fish, shellfish, milk, and eggs
anaphylaxis? (including vaccines made from egg products, such as the
influenza vaccine)

What are other Antitoxins, insect venom, latex, exercise, exercise within 4
common causes to 6 hours of ingesting certain foods (e.g., wheat, celery),
and causative systemic mastocytosis, malignancy, semen, and unknown or
agents of idiopathic causes
anaphylaxis?

How is the History is the major diagnostic modality (most cases present
 correct diagnosis with urticaria and decreased blood pressure, increased
of anaphylaxis heart rate). Specific IgE testing [either by skin testing or by
made? IgE immunoassays (ELISA), formerly done with radiation and
known as radioallergosorbent tests or RASTs] may be
helpful when IgE is suspected.
Skin testing should be performed more than 6 weeks after
the event or else false-negative tests will be more common
due to the anergic state of mast cells after anaphylaxis.

What blood test Serum tryptase (within 3 to 4 hours of the event)

can be
evaluated to
confirm
anaphylaxis?

What is an It is clinically similar to anaphylaxis but is not IgE-

anaphylactoid mediated. Agents such as radiocontrast media, NSAIDs,
reaction and muscle relaxants, and paclitaxel cause direct stimulation of
what agents mast cells and basophils. Anaphylactoid reactions can often
usually cause be prevented with glucocorticoids and antihistamines.
them?

Can people with Yes, there is no relationship between fish allergy and
fish allergy adverse reactions to contrast media.
tolerate IV
contrast media?

P.19
P.20
P.21

Urticaria and Angioedema

What are the causes Dermographism, cold, heat, sun, cholinergic
of physical stimulation, vibration, exercise
urticaria/angioedema?

What are the Hereditary and acquired angioedema, necrotizing

complement- vasculitis, serum sickness, reactions to blood products,
mediated causes of viral infections including hepatitis B and EBV, and
urticaria (and pregnancy
angioedema)?

What are the Opiates (direct histamine release from mast cell),
nonimmunologic (non vancomycin, dextran, radiocontrast, acetylsalicylic
IgE mediated) causes acid, NSAID, azo dyes, and benzoates
of urticaria (and
angioedema)?

What is the most After excluding acute and physical urticarias,

common cause of etiologies of chronic urticaria may be found in <2% of
chronic urticaria? cases.

What factors should Thyroid disease, physical urticarias, food sensitivity,

be considered in the drug reaction, chronic infections (sinus, dental, and
evaluation of the genitourinary), systemic disease (vasculitides), and
patient with chronic malignancy
urticaria?

What tests/labs CBC with differential, sedimentation rate, thyroid

should one evaluate antibodies, thyroid function, liver function; consider
for chronic urticaria? autologous serum skin testing to demonstrate
autoantibodies to Fc receptor; urinalysis if symptoms
of UTI or history of recurrent UTI, skin biopsy for
atypical urticaria (painful, residual bruising, if lesions
last more than 24 to 48 hours, or other systemic
complaints) to rule out vasculitis

What organs other There is submucosal edema of the gastrointestinal

than skin are affected system (lips, esophagus, gastrointestinal tract),
in angioedema? nasopharynx, larynx, trachea, or urogenital system.

Is the differential Yes; isolated angioedema is much less common than

diagnosis different for chronic urticaria with or without angioedema. Isolated
angioedema than for angioedema suggests drug allergy; C 1 INH deficiencies,
urticaria? either hereditary or acquired; and vasculitis.

What are the causes Same as urticaria with the addition of ACE inhibitors
of angioedema?

What is the time This side effect is most commonly seen in the first
course of ACE week of treatment but may occur any time, affecting
inhibitorrelated at least 3 in 1000 patients.
angioedema?

If a patient has a If the patient is taking an ACE inhibitor, it should be

history of stopped, because the side effect of angioedema is
angioedema, must the life-threatening. Most patients with ACE inhibitor
ACE inhibitor be related angioedema can tolerate angiotensin-receptor
discontinued? blockers (ARBs).
How is the cause of If the C4 level is normal during an episode of
angioedema angioedema, there is no problem with C 1 INH because
established? C4 is used up in this process. If the C4 level is low or
if a person is seen in an asymptomatic period, C 1 INH
level and functional activity should be measured (to
determine if it is HAE I or II), as should the C1q level.
C1q levels are normal in hereditary angioedema and
decreased in acquired C 1 INH deficiency. C2 is reduced
during acute episodes. Acquired C 1 INH is associated
with malignancy, particularly B-cell lymphomas.

What is the first-line H1 antihistamines (preferably long-acting; e.g.,

therapy for urticaria cetirizine, fexofenadine). If control is not achieved,
and angioedema not H2 antihistamines (e.g., ranitidine) can be added or
related to C 1INH
doxepin can be used, which has both H1 and H2
deficiency?
antihistaminic activity.

Where do steroids fit Daily steroids are to be avoided as they provide only
in the treatment of short-term relief.
urticaria and
angioedema not
related to C 1INH
deficiency?

What other agents Leukotriene modifiers (montelukast, zileuton) can also

can also be used for be used. A short course of cyclosporine for those with
the treatment of autoimmune urticaria that is refractory to their
urticaria and medications may be beneficial. Epinephrine 1:1,000 IM
angioedema not is used if angioedema is threatening the airway.
related to C 1INH
deficiency?

What is the treatment C 1 INH deficiency is treated with attenuated

for urticaria and androgenic steroids, which increase the production of
angioedema C 1 INH. This is effective in patients with deficient
secondary to C 1INH
production, deficient activity, and increased
deficiency? catabolism of C 1 INH. Epinephrine may not work in a
crisis, and a tracheostomy is indicated for laryngeal
edema. Antifibrinolytics (epsilon-aminocaproic acid or
tranexamic acid) may be helpful.

P.22
P.23
Mastocytosis
What is Mastocytosis is a disease of excess mast cells; it can be
mastocytosis? localized to the skin or may occur in systemic form.

How common Approximately 1 in 5000 patients seen in dermatology clinics

is has mastocytosis. It is slightly more common in men than in
mastocytosis? women (1.5:1).

What is the Urticaria pigmentosa (UP)

most
common
lesion found
on skin
examination
in
mastocytosis?

What are Symptoms: pruritus, flushing, abdominal pain, fatigue,

symptoms musculoskeletal pain, recurrent anaphylaxis
and signs of Signs: skin lesions (UP), hepatosplenomegaly, ascites, bone
mastocytosis? lesions

What are the 1. Cutaneous: includes UP, nodular or telangiectasia

features of macularis, eruptive persistent, diffuse cutaneous
the seven 2. Indolent systemic mastocytosis: involving skin and bone
categories of marrow only (UP and diffuse cutaneous) and systemic
mastocytosis? (marrow, gastrointestinal, and UP)
3. Systemic: associated with a hematologic nonmast cell
disorder (dysmyelopoietic syndrome, acute nonlymphocytic
leukemia, myeloproliferative disorders, malignant
lymphoma, chronic neutropenia)
4. Aggressive systemic: lymphadenopathy and eosinophilia
5. Mast cell leukemia
6. Mast cell sarcoma
7. Extracutaneous mastocytoma

How is the One major diagnostic criterion + one minor criterion or three
diagnosis of minor criteria
mastocytosis Major criteria:
made? Bone marrow biopsy and aspirate with dense infiltrates of mast
cells
Minor criteria:
1. Spindle-shaped mast cells
 2. Detection of 816 c-kit mutation
3. Flow cytometry with CD2, CD25, and CD117 expression
4. Serum tryptase >20 "g/mL

What is the H1 antihistamines for pruritus, flushing, and tachycardia.

treatment for H2 antihistamines for gastric hypersecretion.
mastocytosis?
Epinephrine.
Cromolyn (200 mg before meals and at bedtime) may help with
gastrointestinal symptoms.
Tricyclic antidepressants for headaches.
Avoidance of ethanol, NSAIDs, opiates, friction, and physical
exertion.

What is the Those with the cutaneous form usually have high rates of
prognosis for spontaneous remission. The indolent form is usually associated
mastocytosis? with a normal life expectancy. The prognosis of patients with
systemic disease and an associated hematologic nonmast cell
disorder is determined by the hematologic abnormality.
Aggressive systemic disease is the rarest and has the most
fulminant course. Mast cell leukemia is rapidly progressive over
1 to 2 years.

What are the Constitutional symptoms, anemia, thrombocytopenia, abnormal

poor liver function tests, lobulated mast cell nucleus, low
prognostic percentage of fat cells in the marrow, associated hematologic
indicators for disorder, absence of UP, male gender, absence of skin and
mastocytosis? bone symptoms, hepatosplenomegaly, and normal bone films

What IFN-# (controversial), hydroxyurea (may reduce mast cell

therapies are progenitors in type III disease), and other chemotherapy for
available for leukemic forms (types II and IV)
more severe
forms of
systemic
mastocytosis?

P.24
P.25

Drug Allergies
How common Allergies account for 6% to 10% of all adverse drug
are immune- reactions. The rest are commonly known, predictable
mediated drug- pharmacologic actions of the drug.
induced allergic
reactions?

Is skin testing Penicillin skin testing with penicillin major and minor is
helpful for reliable for the diagnosis of immediate hypersensitivity. A
patients with a negative test has a 99% negative predictive value, whereas
history of hives a positive skin test indicates a high risk for immediate
to antibiotics? hypersensitivity reactions.

How common is The history of a reaction to penicillin carries a 5% to 15%

antibiotic cross- risk of immediate hypersensitivity to first-generation
reactivity in cephalosporins (4% to second and 1% to 3% to third and
penicillin- fourth) and increases the risk of an adverse response to
sensitive other, unrelated drugs eightfold. A positive penicillin skin
patients? test increases the risk of a reaction to cephalosporins (and
probably imipenem).

What drugs Most antihistamines if used within 3 days of the test

interfere with (astemizole, 6 weeks) and tricyclic antidepressants
immediate skin
tests?

Are there skin Clinically proven skin tests have not been developed for
tests for other other pharmacologic agents. Testing is sometimes
antibiotics? performed for other drugs, but a negative test must be
interpreted with caution (poor negative predictive value).
Nonirritating doses are available for testing which, if
positive, suggest IgE-mediated sensitization. There are no
prospective challenges published other than for beta
lactams.

What if there is Desensitization protocols decrease the risk of uncontrolled

no alternative anaphylaxis. Once therapy is initiated, it cannot be
agent than the interrupted without resuming the risk of anaphylaxis.
drug allergen?

How does It is not known for certain, but there may be a gradual
desensitization cross linking of IgE by antigen, causing a controlled
work? anaphylaxis.

Are drug rashes Penicillin skin testing predicts only immediate IgE-mediated
possible with a hypersensitivity. With a negative penicillin skin test, it is
negative still possible for a nonIgE-mediated drug rash, serum
penicillin skin sickness, mucocutaneous syndrome, or other adverse side
test? effects to develop.
 Which reactions A history of serum sickness, Stevens-Johnson
are syndrome/toxic epidermal necrolysis, erythroderma,
contraindications hemolytic anemia, interstitial nephritis, or exfoliative
to drug use? dermatitis

P.26

Atopic Dermatitis (See Chapter 12, Dermatology)

Contact Hypersensitivity (See Chapter 12,

Dermatology)

Rhinitis and Sinusitis

What is the differential 1. Allergic
diagnosis of chronic 2. Nonallergic
rhinitis?
A. Inflammatory [infectious, NARES, nasal
polyps (NSAID allergy), atrophic rhinitis]
B. Noninflammatory
1. Vasomotor
2. Systemic disease (hypothyroidism,
diabetes)
3. Rhinitis medicamentosa (oral
contraceptives, topical decongestants,
cocaine, ACE inhibitors)
4. Chronic sinusitis
5. Structural defects
(trauma/cerebrospinal fluid rhinorrhea,
tumor, foreign body)
6. Pregnancy

What is chronic sinusitis? Symptoms $12 weeks

Requires two or more of the following:
1. Anterior or posterior mucopurulent drainage
2. Congestion
3. Facial pain/pressure
4. Decreased sense of smell
5. Objective documentation:
Rhinoscopy
X-ray (sinus CT preferred)
 How is the diagnosis of Radiographically by sinus CT scan (plain films not
chronic sinusitis made? very sensitive)

What is the treatment for Antibiotics that cover beta lactamasepositive

acute sinusitis? organisms for 10 to 21 days
Promotion of nasal drainage
Topical nasal decongestants for 3 to 5 days

What is the treatment for Nasal steroids

chronic sinusitis? Short course of oral steroids
FESS (in certain patientsi.e., nasal polyps)

What are potential Somnolence and a theoretical thickening of mucus,

adverse effects of therefore possibly reducing clearance
antihistamines?

P.27

Asthma (See Also Chapter 10, Pulmonology)

What is the 1. Asthma
differential 2. Pulmonary edema
diagnosis for 3. Airway obstruction (laryngospasm, tracheomalacia, vocal
wheezing? cord dysfunction, tracheal web, foreign body)
4. Chronic obstructive pulmonary disease (COPD)
5. Congestive heart failure
6. Pulmonary embolus
7. Primary eosinophilic lung disease (hypereosinophilic
syndrome, eosinophilic pneumonia, Churg-Strauss
syndrome)
8. Secondary eosinophilic lung disease [allergic
bronchopulmonary aspergillosis (ABPA), hypersensitivity
pneumonitis, drugs, malignancy, collagen vascular
disease, sarcoid]
9. Bronchiolitis obliterans
10. Interstitial lung disease

Gastroenterology
What is eosinophilic An eosinophilic infiltrate of the bowel potentially
esophagitis/gastroenteritis? involving all layers of the gut; symptoms include
nausea, vomiting, diarrhea, malabsorption,
weight loss, and dysphagia

How is the diagnosis of Biopsy shows >15 to 20 eosinophils per high-

 eosinophilic power field. Involvement is sporadic, so multiple
esophagitis/gastroenteritis biopsy samples may be required. Usually, about
made? half of patients have a peripheral eosinophilia
and some have high levels of IgE. IgE testing
(skin test may be more sensitive than serum
immunoassays) to foods should be performed.
Patch testing is still experimental.

What is the treatment for Treatment of coexisting acid reflux may relieve
eosinophilic symptoms. Swallowed metered-dose-inhaler
esophagitis/gastroenteritis? steroids; a trial of strict avoidance of any
identified offending foods in esophagitis; an
elemental diet in gastroenteritis or severe
esophagitis; oral glucocorticoids in very severe
cases.

P.28
P.29

Transplantation Immunology
Are all grafts Although matching for intrafamilial transplants of all
matched? types is performed, nonfamilial cardiac, lung, and liver
grafts are not MHC-matched because other factors such
as size, location, and availability limit the transplants
much
more. Kidney transplantation, for which there is the
potential for living related and unrelated donors, allows
for matching. Bone marrow transplants must be matched,
whereas matching in liver transplants may actually
decrease survival.

What is hyperacute Rejection mediated by preformed complement-fixing

rejection? antibodies. It occurs in <24 hours and is irreversible.

What is Rejection mediated by preformed but not complement-

accelerated fixing antibodies. Onset is 3 to 5 days.
rejection?

How is accelerated Treatment is with antithymocyte or antilymphocyte

rejection treated? globulin or newer antimonoclonal antibodies against T-
cell surface antigens (e.g., CD3). Treatment is successful
in approximately 60% of cases.

What is acute Rejection mediated by recipient T cells and antibodies as

rejection? a primary response. It occurs 6 to 90 days after
 transplantation and is thought to be directed at
passenger APCs. There is prominent infiltration of CD8
cells and polymorphonuclear neutrophils.

How is acute Immunosuppression with pulse steroids and agents used

rejection treated? in accelerated rejection is successful 80% to 90% of the
time.

What is chronic Mostly antibody deposition leading to hyperplasia and

rejection? endothelial necrosis >60 days posttransplant. It is slowly
progressive and does not respond well to treatment.

What is graft- Graft-versus-host disease is an immune response of the

versus-host donor T cells against the recipient usually 6 or more days
disease? after transplant. It is a problem only when transplanting
hematopoietic tissue (bone marrow, nonirradiated blood
transfusions).

Why not purge the Sometimes the donor marrow is purged of T cells before
T cells from transplant, but without T cells, engraftment is less often
marrow before successful and the incidence of leukemia increases.
transplantation?

What 1. Antithymocyte globulin, antilymphocyte globulin, and

immunosuppressive antimonoclonal antibody to T-cell antigens (CD3,
drugs specifically OKT3), which, in part, bind with the activation sites
target T cells? of T cells via foreign proteins (horse, rabbit, or
mouse) and are then selectively cleared by the host's
immune system
2. Calcineurin inhibitors (cyclosporine, tacrolimus) and
antiIL-2 receptor antibodies, which decrease IL-2
and interfere with growth and function

Should blood Yes, for persons likely to need a bone marrow

transfusion be transplant; however, it may enhance renal and cardiac
avoided? allograft survival by selecting for patients who are
hyporesponsive for antibody production. Transfusions
with irradiated or filtered blood are usually safe,
however.

P.30

Tumor Immunology
What are common 1. Increased activity of proto-oncogenes
alterations that lead
alterations that lead 2. Decreased activity of suppressor genes
to cancer? 3. Alterations in genes that regulate apoptosis
4. Defect in genes that regulate DNA repair

What are causes of 1. Chemical carcinogens and ionizing radiation may

antigenic alter protein synthesis.
differences between 2. Viruses may introduce new DNA or RNA into cells.
normal and tumor 3. Malignant cells may revert to synthesis of fetal
cells? markers such as alpha fetoprotein,
carcinoembryonic antigen, or other fetal proteins.
4. Genetic mutation may lead to expression of
inappropriate antigens such as ABO.

Why are antigenic If differences between normal cells and malignant cells
differences can be found, immunotherapy may be effective in
potentially curing patients.
important?

What Interleukins and interferons, monoclonal antibodies, and

immunotherapeutic antitumor vaccines
agents are currently
under investigation?

What are potential 1. To direct action against tumors through antibody-

uses for monoclonal or complement-dependent cytotoxicity
antibodies? 2. To carry cytotoxic substances such as radiolabeled
compounds, chemotherapeutic agents (e.g.,
methotrexate or doxorubicin), naturally existing
toxins, or immunoconjugates (e.g., ricin)
Editors: Bergin, James D.
Title: Advanced Medicine Recall, 1st Edition
Copyright 2009 Lippincott Williams & Wilkins

> Table of Contents > Section II - The Specialties > Chapter 3 - Cardiology

Chapter 3
Cardiology

P.32
P.33
P.34
P.35

Abbreviations
A2 Second heart sound, aortic valve component

AAA Abdominal aortic aneurysm

ABI Ankle brachial index

ACE Angiotensin-converting enzyme

ACE-I Angiotensin-converting enzyme inhibitor

ACS Acute coronary syndrome

ADP Adenosine diphosphate

AF Atrial fibrillation

AI Aortic insufficiency

AIVR Accelerated idioventricular rhythm

ALCAPA Anomolosis left coronary artery originating from the pulmonary

artery

AMI Acute myocardial infarction or anterior myocardial infarction

APB Atrial premature beat

aPTT Activated partial thromboplastin time

ARB Angiotensin-receptor blocker

AS Aortic stenosis
ASA Acetylsalicylic acid

ASD Atrial septal defect

AST Aminotransferase

AV Atrioventricular

AVNRT AV node reciprocating tachycardia

AVRT AV reciprocating tachycardia

BBB Bundle branch block

BCLS Basic cardiac life support

bNP b-type natriuretic peptide

BP Blood pressure

BiVD Biventricular ICD

BiVP Biventricular pacemaker

BSA Body surface area

CABG Coronary artery bypass grafting

CAD Coronary artery disease

CCU Cardiac care unit

CEA Carotid endarterectomy

CHB Complete heart block

CHD Congenital heart disease

CHF Congestive heart failure

CI Cardiac index

CK Creatine kinase

CKMB Creatine kinase, MB isoform

CO Cardiac output

COPD Chronic obstructive pulmonary disease

CMRI Cardiac magnetic resonance imaging

CTA CT angiogram

cTn Cardiac troponin (either cTnI or cTnT)

CVA Cerebrovascular accident

CVP Central venous pressure (also RA pressure)

DCA Directional coronary atherectomy

DCM Dilated cardiomyopathy

DM Diabetes mellitus

DORV Double-outlet right ventricle

DP Dipyridamole

EBCT Electron beam CT

ECG Electrocardiogram

EECP External enhanced counterpulsation

EF Ejection fraction

EP Electrophysiology

ESR Erythrocyte sedimentation rate

GPIIb/IIIa Glycoprotein IIb/IIIa

GXT Graded exercise test

HF Heart failure

HDL High-density lipoprotein

HIT (or HITT) Heparin-induced thrombocytopenia (with thrombosis)

HMG-CoA 3-Hydroxy-3-methylglutaryl coenzyme A

HOCM Hypertrophic obstructive cardiomyopathy (also IHSS)

HR Heart rate

hsCRP Highly sensitive C-reactive protein

HTN Hypertension
IABP Intra-aortic balloon pump

ICD Implantable cardioverter-defibrillator

ICU Intensive care unit

IE Infective endocarditis

IHD Ischemic heart disease

IHSS Idiopathic hypertrophic subaortic stenosis (also HOCM)

IMA Internal mammary artery

IMI Inferior myocardial infarction

INR International normalized ratio

IVC Inferior vena cava

IVNC Isolated ventricular noncompaction

IVUS Intravascular ultrasound

JVD Jugular venous distension (also JVP)

JVP Jugular venous pressure (also JVD)

LA Left atrium

LAD Left anterior descending artery or left axis deviation

LAFB Left anterior fascicular block

LBBB Left bundle branch block

LCx Left circumflex artery

LDH Lactate dehydrogenase

LDL Low-density lipoprotein

LIMA Left internal mammary artery (also abbreviated LITA for left
internal thoracic artery)

LMCA Left main coronary artery

LMWH Low molecular weight heparin

LPFB Left posterior fascicular block

LV Left ventricle

LVED Left ventricular end-diastolic

LVEDP Left ventricular end-diastolic pressure

LVEF Left ventricular ejection fraction

LVES Left ventricular end-systolic

LVH Left ventricular hypertrophy

LVOT Left ventricular outflow tract

MAP Mean arterial pressure

MAT Multifocal atrial tachycardia

MET Metabolic equivalent

MI Myocardial infarction

MIBI Methoxyisobutyl isonitrile

MR Mitral regurgitation

MRI/A Magnetic resonance imaging/angiography

MS Mitral stenosis

MUGA Multigated acquisition

MVP Mitral valve prolapse

NCEP National Cholesterol Education Program

NSTEMI Non-ST-elevation MI

NSVT Nonsustained ventricular tachycardia

NTprobNP N terminal pro-b-type natriuretic peptide

NYHA New York Heart Association

P2 Second heart sound, pulmonic valve component

PA Posteroanterior or pulmonary artery

PAD Peripheral arterial disease

PAF Paroxysmal atrial fibrillation

PAOD Peripheral arterial occlusive disease

PAOP Pulmonary artery occlusion pressure

PCI Percutaneous coronary intervention

PCWP Pulmonary capillary wedge pressure (also PAOP)

PDA Posterior descending artery or patent ductus arteriosus

PE Pulmonary embolism

PEA Pulseless electrical activity

PI Pulmonic insufficiency

PMI Posterior myocardial infarction or point of maximal impulse

PND Paroxysmal nocturnal dyspnea

PS Pulmonic stenosis

PTCA Percutaneous transluminal coronary angioplasty

PTCI Percutaneous transluminal coronary intervention

PVC Premature ventricular contraction

PVD Peripheral vascular disease

PVE Prosthetic valve endocarditis

PVR Pulmonary vascular resistance

PVRI Pulmonary vascular resistance index

RA Right atrium

RAD Right axis deviation

RBBB Right bundle branch block

RCA Right coronary artery

RV Right ventricle

RVEF Right ventricular ejection fraction

RVH Right ventricular hypertrophy

RVR Rapid ventricular response

saECG Signal-averaged ECG

SR Sinus rhythm

STEMI ST-elevation MI

SK Streptokinase

SVR Systemic vascular resistance

SVRI Systemic vascular resistance index

SVT Supraventricular tachycardia

TAA Thoracic aortic aneurysm

TEE Transesophageal echocardiogram

TG Triglycerides

TGA Transposition of the great arteries

TIA Transient ischemic attack

TIMI Thrombolysis in Myocardial Infarction

TNK-tPA Tenecteplase-tPA

tPA Tissue plasminogen activator

TR Tricuspid regurgitation

TS Tricuspid stenosis

TTE Transthoracic echocardiogram

UFH Unfractionated heparin

UA or USA Unstable angina

VF Ventricular fibrillation

VLDL Very low density lipoprotein

[V with dot Oxygen consumption

above]o2

VPB Ventricular premature beat (also PVC, VPC)

 VPC Ventricular premature contraction

VSD Ventricular septal defect

WPW Wolff-Parkinson-White

P.36
P.37

ICU
What are the potential Bleeding, infection, pneumo- or hemothorax,
complications of placing a arrhythmias, death
pulmonary artery (PA)
catheter?

What arrhythmias occur during VT and heart block

placement of PA catheters?

What group of patients are Those with a LBBB

prone to developing heart
block?

When do the arrhythmias When the catheter passes through the RV

usually occur?

What are the normal filling

pressures?

RA pressure or CVP 0 to 8 mm Hg (mean)

RV pressure 15 to 30/0 to 8 mm Hg (systolic/diastolic)

PA pressure 15 to 30/3 to 12 mm Hg (systolic/diastolic)

PCWP 3 to 12 mm Hg (mean)

What is the PCWP? Approximation of the LA and LV pressure

during ventricular filling (LVEDP)

What is the danger of PA rupture, which can be fatal

overinflating the balloon while
measuring the PCWP?

What are three sources of 1. Zeroing error

error encountered when 2. Deterioration in frequency response
measuring pressures with a check for air in the catheter or
fluid-filled catheter (e.g., transducer
arterial line, Swan-Ganz 3. Catheter impactcatheter impact is
catheter)? caused by a valve or other structure
hitting the catheter
4. Catheter whipas the catheter is hit by
 the pulse wave and motion is generated,
increasing systolic pressures and lowering
diastolic pressures (i.e., the mean
pressure is unaltered)

How can you test for catheter In arterial lines, by inflating a BP cuff
whip? proximal to the line; as the cuff is deflated,
the pressure that corresponds to the first
pressure wave recorded on the arterial line
is the true systolic pressure.

What is the normal CO? 5 1 L/min

What is the normal CI? 3 0.5 L/min/m 2

How is SVR calculated? SVR = {[systemic BP (mean) RA

(mean)]/CO} ! 80 dyne " cm " sec -5

What is the normal SVR? 1200 300 dyne " cm " sec -5

How is the SVRI calculated? SVRI = SVR ! BSA

What is the normal SVRI? 2100 500 dyne " cm " sec -5 ! m2

How is the PVR calculated? PVR = [(PA mean PC mean)/CO] ! 80 dyne

" cm " sec -5

What is the normal PVR? 100 50 dyne " cm " sec -5

How is the PVRI calculated? PVR ! BSA

What is the normal PVRI? 170 70 dyne " cm " sec -5 ! m2

How are Wood units PVR = [PA (mean) PCWP (mean)]/CO

calculated?

What is the appropriate value <4

for PVR in Wood units?

P.38

Determination of Cardiac Output

Name five 1. Low outputs (outputs <2.5 L/min average a 35%
pitfalls of the overestimation)
thermodilution 2. Tricuspid regurgitation
method. 3. Improper technique (i.e., slow injection, incorrect volume)
4. Intracardiac shunts (VSD)
5. Extracardiac shunts (AV fistula)
6. Cold patients
7. Distal tip of the catheter in the main PA
 8. Changes in blood viscosity (anemia or polycythemia)
9. Invasive insertion

What is the CO = [oxygen consumption ! 10]/[(AoO2 sat PAO2 sat) !

Fick equation? (Hgb ! 1.36)]

What is the 110150 mL/kg/min (110 for stable patients; 150 for ICU
estimated patients)
value for
oxygen
consumption?

Name at least 1. Intracardiac shunts

three pitfalls 2. Difficult measurement of oxygen consumption (generally
of the Fick estimated)
equation. 3. Incorrect data
4. Invasive insertion
5. PA sample drawn too quickly, which pulls pulmonary
capillary (oxygenated) blood into the sample, thus
overestimating the PA saturation

In general, A PAO2 saturation of >65% and <80% is consistent with a

what PA normal CO. A PAO2 saturation >80% is consistent with some
saturation
types of left-to-right shunting, and <65% is consistent with a
levels would
reduced cardiac output.
be in a normal
range?

How can The SVR, PVR, and so on are calculated numbers, and errors
errors in CO in pressure or CO measurements affect these numbers. For
determination example, a patient with a normal CO of 6.0 L/min and
affect SVR? significant tricuspid regurgitation may have a measured CO of
3.0 L/min. This would double the calculated SVRI and may
result in inappropriate treatment.

P.39
P.40
P.41
P.42
P.43

History and Physical Examination

History
What seven historical features of Think PQRST: Precipitating factors,
chest pain must be identified to Quality, Radiation and location, Relief,
differentiate cardiac pain from Risk factor, Symptoms, and Time and
noncardiac pain? duration

Physical Examination
What causes an S 1? Closure of the mitral and tricuspid valves

What causes a loud Sometimes with MVP, sometimes MS and ASD

S 1?

What causes a soft MR (rheumatic or calcific), severe acute AI (valve

S 1? closes prematurely)

What causes a widely TS, Ebstein's anomaly, VT, RBBB, LV pacing

split S 1?

What causes an S 2? Closure of the aortic and pulmonic valves

What is the first Aortic valve closure

sound of a split S 2?

What is on the Pulmonary hypertension, LBBB, aortic stenosis, HOCM,

differential of patent ductus arteriosus (left-to-right shunt), TR
paradoxical splitting?

What causes a single Either absence of A 2 or P2 (i.e., single ventricle,

S 2? pulmonary atresia), or very soft P2 (Tetralogy of
Fallot), or fusion in VSD or PA HTN

What causes a loud Thin chest wall, systemic HTN, aortic coarctation, and
A 2? corrected TGA

What causes a soft Either AS (decreased mobility) or AI (fails to coapt)

A 2?

What causes a loud PA HTN

P 2?

What causes a soft Valvular or infundibular PS

P 2?

What is in the LVH (HTN, AS, HOCM), RVH, IHD, hyperdynamic

differential when an circulation, acute valvular regurgitation, and restrictive
S 4 is noted? cardiomyopathy

When is the click Usually midway through systole

heard in MVP?

What maneuvers can Things that shrink the ventricle push the click closer to
affect the click? S2 (sitting up, part of Valsalva).

What is an ejection A click usually heard during systole due to a

click? congenitally abnormal aortic or pulmonic valve
What is an opening An early diastolic sound associated with abnormal
snap? mitral or tricuspid valve opening. Heard with MS or TS.

When does cyanosis When the concentration of deoxyhemoglobin in the

occur? blood is >5 mg/dL

What are the two Central and peripheral

main categories of
cyanosis?

What are the general Decreased arterial oxygen saturation caused by right-
causes of central to-left shunting, impaired ability of hemoglobin to bind
cyanosis? oxygen (e.g., in methemoglobinemia or abnormal
hemoglobin variants), or impaired pulmonary function

What causes Cutaneous vasoconstriction due to low CO or exposure

peripheral cyanosis? to cold

What are the causes Chronic venous insufficiency

of peripheral edema? Venous obstruction
Lymphatic obstruction
Thrombosis
Heart failure (high- and low-output)
Constrictive pericarditis
Nephrotic syndrome
Hepatic cirrhosis
Angioneurotic edema
Myxedema

What is the formula cm H2 O ! 0.75 = mm Hg

for converting cm
H 2O to mm Hg?

In the jugular venous 1. a wave

tracing below,* 2. c wave
identify the various 3. v wave
numbered 4. x descent
waveforms. 5. y descent
 Passive ventricular filling

What is the An increase in JVP of >3 cm H2 O with 10 to 30 seconds

abdominaljugular of periumbilical pressure
(also called
hepatojugular)
reflux?

When does It is associated with RV or LV failure, TR, or any cause

abdominaljugular of elevated CVP or PCWP.
reflux occur?

How high is the JVP >15 cm H2 O

if the earlobes have a
bobbing motion while
the patient is sitting?

What is the Constrictive pericarditis, restrictive cardiomyopathy, RV

differential diagnosis infarction or failure
of Kussmaul's sign?

What is the Pericardial tamponade, constrictive pericarditis,

differential diagnosis restrictive cardiomyopathy, COPD (exacerbation),
of pulsus paradoxus? asthma (exacerbation), superior vena cava obstruction,
pulmonary embolus, hypovolemic shock, pregnancy, and
obesity

What is the Severe HF, anything causing rapid respiratory rates,

differential diagnosis pericardial tamponade
of pulsus alternans?

What is a bisferiens A pulse waveform with two upstrokes

pulse?

List five causes of a AI, HOCM, exercise, fever, PDA

bisferiens pulse.

With what are the following findings associated?

Pulsus tardus Obstruction to LV outflow (valvular AS or nonvalvular

AS)

Pulsus parvus Reduced LV stroke volume

Pulsus parvus et Severe AS

tardus

Bisferiens pulse Conditions in which a large stroke volume is ejected

(both peaks in rapidly from the LV (aortic regurgitation, combined AS
systole) and AI), hypertrophic cardiomyopathy, hyperkinetic
circulation, normal variant

Dicrotic pulse (first Hypotension, fever with decreased SVR, tamponade,

peak in systole, severe heart failure, hypovolemic shock
second peak in
diastolebased on
the relation to S 2)

Pulsus alternans Severe LV dysfunction and a regular rhythm

What is the pulse The systolic BP minus the diastolic BP; index = (systolic
 pressure? BP diastolic BP)/(systolic BP)

What are causes of a Aortic regurgitation, PDA, truncus arteriosus, CHB,

wide pulse pressure? sinus bradycardia, fever, anemia, strenuous exercise,
thyrotoxicosis, AV fistulas, and hot weather

*Modified from Fuster et al: Hurst's The Heart, 10th ed. New York: McGraw-Hill,
2001:64.

P.44

Cardiovascular Procedures

Chest Radiography
See Medicine Recall, 3rd ed.

Table 3-1. Calculating the Heart Rate on the ECG

Number of Large Boxes Time Rate (bpm)

1 200 ms 300

2 400 ms 150

3 600 ms 100

4 800 ms >75

5 1s 60

6 1.2 s 50

Electrocardiogram
What is the normal size of #120 ms (3 boxes)if longer, consider LA
the P wave measured in enlargement
II? #0.25 mV (2.5 boxes)if taller, consider RA
enlargement

What is the 300, 150, 100 The 300, 150, 100 rule is used to quickly
rule? calculate the rate on the ECG. The HR =
150/(number of small boxes between R waves) or
300/(number of large boxes between R waves)
What is the normal range 120 to 200 ms (3 to 5 boxes)
for the PR interval?

List three causes of a 1. Accelerated AV conduction

short PR interval. 2. Tachycardia
3. Accessory AV pathway (e.g., WPW syndrome)

List five causes of a long 1. High vagal tone

PR interval. 2. AV conduction system degenerative disease
3. IHD
4. Drugs that impair AV conduction (e.g., beta-
adrenergic blockers and digoxin)
5. Dual AV node physiology using the slow
pathway

What is the normal range 60 to 119 ms (1.5 to 3 boxes). A conduction

for the QRS interval? delay is present if the QRS is $110 ms, and a BBB
is present if the QRS is $120 ms.

What is the QTc? The corrected QT interval (corrects for the HR)

Why is it important to The measurement allows determination of blocks

measure intervals? (e.g., first-degree or RBBB).

What prolongs the PR AV blocks

interval?

What prolongs the QRS BBBs

interval? Premature ventricular beats
LVH
Preexcitation syndromes (e.g., WPW syndrome)
Electrolyte abnormalities (e.g., hyperkalemia)
Paced beats
Medications (e.g., amiodarone, procainamide,
tricyclic antidepressants)

What prolongs the QT Medications [tricyclic antidepressants,

interval? antiarrhythmics (e.g., quinidine, procainamide,
amiodarone, sotalol, dofetilide), methadone,
antipsychotics, terfenadine plus macrolide
antibiotics (e.g., erythromycin)]
Electrolyte deficiencies (e.g., potassium,
magnesium, calcium)
Congenital long QT
IHD
Hypothermia
MVP
Intracranial events (e.g., subarachnoid
hemorrhage)

What is the I, aVF rule? From the previous example, if leads I and aVF
are both more positive than negative, the axis is
 normal.

What is a significant Q 40 ms or one third the height of the QRS

wave?

What does the Q wave A previous MI

represent?

Does the absence of a Q Some infarctions tend to lose Q waves over time:
wave mean that no inferior infarctions lose Q waves 50% of the time;
infarction has occurred? anterior infarctions lose Q waves <10% of the
time.

Describe the QRS complex in the following:

RBBB QRS $120 ms

rSR% pattern in V 1
Deep slurred S wave in V 6 , I

LBBB QRS $120 ms

All negative in V 1
All positive in V 6 , I

LAFB QRS <120 ms (unless associated with an RBBB)

LAD (>30 degrees)
Small Q waves in I, aVL
R waves in II, III, aVF (i.e., no IMI)

LPFB QRS <120 ms (unless associated with an RBBB)

RAD (>120 degrees)
Small Q waves in II, III, aVF
R waves in I, aVL (i.e., no lateral MI)

If an RBBB pattern is Septal perforation by the wire, a high RV septal

observed with paced beats location (the impulse crosses to the LV side) and
(transvenous), what should biventricular pacing
be considered?

Name the causes of ST AMI, ventricular aneurysm, pericarditis,

elevation. Prinzmetal's angina, myocardial contusion,
hypothermia (Osborne or J wave), hyperkalemia,
early repolarization, and artifact. ST elevation is
also occasionally seen with LBBB, LVH,
myocardial neoplasms, hypertrophic
cardiomyopathies, and after VT.

Name the causes of ST Acute posterior MI, ischemia, digitalis, LVH, and
depression. BBB

What does the S 1S 2S 3 Acute pulmonary embolus causing acute RV strain

pattern (i.e., S waves in
 leads I, II, and III) or the
S 1Q 3T 3 pattern (i.e., S
wave in lead I and Q wave
and inverted T wave in
lead III) suggest?

How frequently is this ECG In 10% of cases

abnormality seen?

What is electrical Alternating ECG voltage beat by beat

alternans?

P.45
P.46
P.47
P.48
P.49
P.50
P.51
P.52
P.53
P.54
P.55
P.56

ECG Case Studies

The following ECGs, on pages 47 through 49, are those of a 74-year-old man with chest pain. He was
admitted to the CCU.

What is the rate, rhythm, and axis Rate = 80 bpm; rhythm = sinus; axis = ()10
of the ECG below?

What is the other important finding? A LBBB

 With the chest pain and a new Emergent PCI or thrombolysis
LBBB, what therapy should be
considered?

You are then called for tachycardia Rate = 120 bpm; rhythm = atrial fibrillation; axis = 0
and hypotension. What is the rate,
rhythm, and axis on the ECG below?

What else is demonstrated on the The same LBBB

ECG?

What is the clue that this rhythm The rhythm is irregularly irregular.
isn't VT?

You treat the rhythm with a beta Rate = 33 bpm; rhythm = complete heart block (3rd degree AV
blocker and the patient's symptoms block) axis = ()80
resolve. You are then called a few
hours later for bradycardia and
dizziness. What is the rate, rhythm,
and axis of the ECG on page 49?
 What are the other findings on the An atypical RBBB, RVH, and LVH. There is likely a recent
ECG? anterior infarction (Q waves in V 1 through V 3 with ST
elevation), although that can sometimes be related to LVH.

Is it odd that the patient does not Yes, and very concerning. He now shows severe conduction
have the same LBBB? system disease with an alternating BBB.

What therapy should be considered An emergent temporary pacemaker.

for this man?

The ECG on below is that of a 42-year-old man who has been referred for the evaluation of heart
failure.

What is the rate, rhythm, and axis? Rate = 76 bpm; rhythm = sinus; axis = (+)120

What is the conduction abnormality? He has an isolated LPFB.

What are the features of this The right axis, lack of evidence of a lateral MI (no Q waves
conduction abnormality? noted in I or aVL), and the small Q waves in leads II, III, and
aVF

The ECG below is that of a 47-year-old man involved in a head-on crash. The car did not have airbags
and he was not wearing a seat belt.

What is the rate, rhythm, and axis? Rate = 64 bpm; rhythm = sinus; axis = ()45

He complains of chest pain. Did he There are Q waves in II, III, and aVF, consistent with an IMI;
have an MI? however, an MI is unlikely owing to other findings.

What other findings are there? The PR interval is short (100 ms). Delta waves are present in all
leads but best seen in V1 through V3, also I and aVL. The delta
waves are also noted in II, III, and aVF, explaining the IMI
pattern.

What is the cause of the ECG WPW syndromean abnormal connection between the atrium
findings? and ventricle, allowing conduction to pass to the ventricle
outside the AV node

The ECG below is that of a 60-year-old man in the CCU.

 What is the rate, rhythm, and axis? Rate = 79 bpm; rhythm = Wenckebach; axis = (+)130. The PR
interval is shortest at the start and end of the tracing with the
longest PR right at the transition to leads V 4 through V 6 with
the dropped beat at V 4 through V 6 .

What else is demonstrated on this There is a RBBB. Possibly LA enlargement and diffuse STT
ECG? changes suggesting ischemia.

What do the T waves in the chest The T inversions in those leads could be consistent with
leads suggest? ischemia or an evolving MI (now age-indeterminate). Usually,
age-indeterminate MIs do not have as deep a T-wave inversion.

The ECG below is that of a 75-year-old woman.

What is the rate, rhythm, and axis? Rate = 49 bpm; rhythm = 2:1 AV block; axis = ()45. The extra P
waves are best noted in leads V 1 and V 2 .
 How is it possible to tell whether It isn't absolutely possible. The PR interval on the conducted
this is Wenckebach or Mobitz 2? beats does not change consistent with the 2:1 cycle. If the
patient has other cycles, like a 3:1 or 4:1 with a constant PR,
this would likely be Mobitz 2. An exercise test can be helpful in
that patients with Wenckebach tend to improve their
conduction (or at least not worsen).

What else is noted on this ECG? An LAFB and inferior T changes that may represent ischemia.
The anterior T waves are also quite broad, suggesting
hypokalemia, hypomagnesemia, or hypocalcemia.

The ECG on page 53 is that of a 74-year-old man who presents to your clinic complaining of
palpitations.

What is the rate, rhythm, and axis? Rate = 130 bpm; rhythm = atrial flutter with predominant 2:1
conduction; axis = ()43. This has a fairly typical sawtooth
appearance, although the rate is a little slower than the usual
150 bpm.

The ECG below is that of a 70-year-old man complaining of dyspnea.

 What is the rate, rhythm, and axis? Rate = 75 bpm, rhythm = atrial fibrillation, axis = (+)165

What is the major finding? The RBBB and the left posterior fascicular block

Is there anything of concern about The voltage is quite high, suggesting pulmonary hypertension.
the RBBB configuration?

Of interest, the image below shows Rate = 80 bpm; rhythm = atrial fibrillation; axis = (+)100
the ECG of the same man 2 years
earlier. What is the rate, rhythm, and
axis?

What does the axis and taller R RVH

wave suggest?

The ECG below is that of a 70-year-old man with a dilated cardiomyopathy. He is admitted to
Neurology owing to a change in mental status and you are called to assess VT.
 What is the rate, rhythm, and axis? Rate = 130 bpm at the beginning and 140 bpm from the middle
of the strip onward. The rhythm begins as paced. The VT is
actually sinus rhythm with his baseline LBBB as P waves seen on
the shoulder of the T wave. The axis cannot be determined as
it is just a single lead.

The ECG below is that of a 65-year-old man with chest pain.

What is the rate, rhythm, and axis? Rate = 84 bpm; rhythm = sinus; axis = ()40

What is the reason for the chest This is a classic inferior posterior lateral MI, given the anterior
pain? ST depression with the inferior and lateral ST elevation.

What noninvasive test should be There are a couple options, but an ECG with right-sided chest
considered next? leads would give prognostic information (looking for RV
infarction). An echocardiogram could help to look at RV and LV
function but would take longer to obtain.

This patient is given aspirin and This would be a typical scenario for an RV infarction with
nitroglycerin and nitropaste is applied. hypotension secondary to the nitropaste. If the paste is removed
The patient then becomes and some volume given, the hypotension is likely to resolve.
hypotensive. What should be
considered?

The ECG below is that of a 61-year-old man with chest pain.

 What is the rate, rhythm, and axis? Rate = 75 bpm; rhythm = sinus rhythm; axis = (+)30

If this patient presented 30 minutes Thrombolysis for the very large anterolateral MI
into chest pain, what therapy should
be considered?

If this patient presented 2 hours Direct PCI

into pain and did not have
contraindications, what could be
considered?

P.57

Signal-Averaged Electrocardiography
What is signal- An ECG technique used to look for late depolarizations
averaged ECG from the ventricle (small depolarizations that occur
(saECG)? after the QRS complex)

What are late Late ventricular afterdepolarizations

depolarizations
called?

What is the They can be a substrate responsible for some VTs.

significance of late
afterdepolarizations?

When is saECG When you suspect that a patient's symptoms are caused
helpful? by VT and you want to risk-stratify that patient for risk
of VT and sudden death. A patient with a low LVEF and
 an abnormal saECG has a higher risk of VT and sudden
death (approximately 30% at 1 year of follow-up).

P.58

Holter Monitoring, Long-Term Event Recorders

What is the Allows the evaluation for symptomatic and asymptomatic
advantage of a rhythm disturbances (such as silent PAF). Allows the
Holter monitor? evaluation for cardiac and noncardiac causes of
palpitations.

What is the It can be cumbersome to wear and can be used for only
disadvantage of a 24 to 48 hours.
Holter monitor?

What are two types Continuous looping and noncontinuous recording

of recording modes
for an event
recorder?

What is the It does not have to be worn continuously. It is placed in

advantage of a contact with the skin only during symptoms.
nonlooping device?

What are the It is not helpful for patients with syncope or brief
disadvantages of a symptoms.
nonlooping device?

What is the When the event is tagged by the patient, the ECG
advantage of a recording immediately prior to the event is saved,
looping device? allowing the triggering event to be studied.

What is another An implantable device.

type of long-term
ECG recorder?

How is this device Much like a single-lead pacemaker. The device is

placed? implanted under the skin (usually the left shoulder) and
a lead is placed into the ventricle.

How are data from Much like the interrogation of a pacemaker.

the device
obtained?

How long can these Usually over a year.

devices be used?

Tilt Table
What is the tilt table test To look for vasovagal syncope
used for?
 How is a tilt table test The patient is strapped to a table, and the table
performed? is tilted to 70 degrees from horizontal for 45
minutes with continuous ECG and arterial BP
monitoring.

What medication can be Isoproterenol.

added to tilt table testing
to bring out autonomic
instability?

P.59

Echocardiography
What Doppler Peak instantaneous gradients >50 mm Hg
findings correspond
to significant aortic
valve stenosis?

What equation is The continuity equation

used during the
Doppler exam to
calculate the aortic
valve area?

What Doppler Gradients >10 to 15 mm Hg

findings correspond
to significant mitral
valve stenosis?

What equation is The pressure half-time formula

used during the
Doppler exam to
calculate the mitral
valve area?

What Doppler A simplified Bernoulli equation: 4v 2 + RA pressure. If

technique is used to
the Doppler velocity is 3 m2 and you estimate the RA
estimate the PA
pressure at 10 mm Hg, then the PA pressure (assuming
pressure?
no PS) is 4 ! (3) 2 + 10 = 46 mm Hg.

How is the RA By evaluating the size and dispensability of the IVC.

pressure estimated?

How are shunts Color-flow and pulsed Doppler sonography can identify
detected? abnormal flows (e.g., ASD and VSD). Agitated saline or
Albunex, a contrast agent, can be rapidly injected into
a peripheral vein while the heart is imaged.

What are the echo If there is an ASD, contrast can be seen flowing from
findings when there the RA to the LA. Often, shunts are bidirectional and
is a shunt at the flow into the RA of noncontrasted blood, which creates
atrial level? a contrast-negative jet.
 P.60

Stress Testing
What are some Uncontrolled HTN
contraindications to Decompensated CHF
exercise stress AMI or unstable angina
testing (i.e., a Critical AS
GXT)? Severe idiopathic subaortic stenosis
Known severe LMCA disease
Uncontrolled arrhythmia or heart block
Inability to walk on treadmill because of neurologic or
musculoskeletal abnormalities or vascular disease
Acute myocarditis or pericarditis
Acute systemic illness

What are Significant asthma or COPD (due to stimulation of

contraindications to adenosine a2b receptors, causing bronchospasm), and
DP testing? recent CVA. Caffeine and theophylline compounds must
be withheld before testing.

What are Significant HTN, known catechol-induced arrhythmias,

contraindications to and a large AAA (i.e., $6 cm)
dobutamine testing?

What variables Inability to exercise or poor exercise performance (<5

indicate a high-risk METs) because of a cardiac reason
GXT? Significant ECG changes within the first 3 to 6 minutes
Extensive ischemic changes (>2-mm ST depression, many
leads involved)
Decrease in BP or flat BP response to exercise
Significant arrhythmias

What ECG findings ST depression (usually the lateral leads)

are noted during a ST elevation (usually the anterior leads when it occurs)
positive but not a Heart block or VT
high-risk test?

How much should 10 bpm/stage

the HR increase
during a GXT?

When is a delay in May be noted in athletes and patients taking beta-

HR acceleration adrenergic blockers
commonly noted?

How much should 10 mm Hg/stage (a delay may be noted in athletes and

the BP increase fit individuals)
during a GXT?

What is the 65% and 65%

sensitivity and
 specificity of GXT
for detecting CAD?

List the causes of Female gender, hyperventilation, MVP, LVH, digitalis

false-positive GXT
results.

What is the 1:10,000

mortality rate for a
stress test?

P.61

Cardiopulmonary Exercise Testing

What is Measurement of the body's oxygen consumption during
cardiopulmonary peak exercise.
exercise testing?

How is During a standard treadmill or bicycle stress test, snorkel-

cardiopulmonary like equipment or a mask is attached to the patient so
testing that all the inspired O 2 and expired CO 2 can be measured
performed? by the machine.

In general terms, Age, gender, and size all affect the peak [V with dot
what affects the above]o2 . Severe lung disease, anemia, beta blockers,
peak [V with dot and deconditioning will also affect the results.
above]o2 a patient
can achieve?

In general, when To determine the prognosis in patients who have LV

is dysfunction
cardiopulmonary
testing used?

What peak [V with A peak [V with dot above]o2 <14 mL/kg/min or <50% of
dot above]o2 level the predicted value for a given patient is associated with
is associated with poor long-term survival. A peak [V with dot above]o2 <10
a poor long-term mL/kg/min or <35% predicted carries an abysmal 1-year
prognosis? survival rate.

What peak [V with [V with dot above]o2 >20 mL/kg/min

dot above]o2 level
is associated with
a good long-term
prognosis?

Stress Echocardiography
What is the stress- echocardiographic Normal wall motion at rest that
appearance of ischemia? becomes abnormal (asynergic) during
stress
 What is the stress- echocardiographic Generally asynergic segments of
appearance of infarcted myocardium? myocardium that are thinned

What is the stress- echocardiographic Asynergic regions that improve with

appearance of hibernating stress (treadmill or dobutamine)
myocardium?

P.62

Radionuclide Imaging
Why does It behaves like potassium; that is, it is taken up by viable
thallium provide cells, and thallium uptake is directly proportional to
useful coronary blood flow.
information?

How does MIBI MIBI is a lipophilic compound that diffuses across intact cell
work? membranes (cells with working mitochondria).

Why is it Hibernating myocardium improves function after

important to revascularization.
determine
viability?

What are A rest study is used to assess LVEF with or without RVEF.
indications for
radionuclide
ventriculography
(MUGA)?

How does a Red blood cells are removed from the body and labeled
MUGA scan with pyrophosphate. The labeled cells are then returned to
work? the patient and technetium is injected into the patient.
The technetium binds to the pyrophosphate-labeled cells.
The gamma rays are then tracked. LVEF = (LVED counts
LVES counts)/LVED counts. This provides an accurate means
of monitoring the LVEF.

Positron Emission Tomography

What is PET imaging? Imaging with the use of positrons.

What is the advantage of PET over Less tissue attenuation (better

other imaging techniques? imaging of all body types)
Can be used to study metabolism
(e.g., fatty acid, glucose)

What are the disadvantages of PET? Requires a linear accelerator to

manufacture the positrons.
The equipment is expensive.

P.63
Electrophysiologic Procedures
What general rhythm SA node modification for inappropriate sinus
disturbances can be treated tachycardia
by catheter ablation? Atrial flutter
Pulmonary vein modification for atrial
fibrillation
Ablation of preexcitation pathways
Ablation of ventricular tachycardia

How do the EP physicians Either through the coronary sinus, through a

gain access to the left side transseptal approach (right atrium into the left
of the heart for evaluation? atrium), or retrograde across the aortic valve

Pacemakers and Internal Defibrillators

What do the The first letter is the chamber or chambers paced (i.e., A, V,
letters in a or D). The second letter is the chamber or chambers sensed
three-letter (i.e., A, V, or D). The third letter is the mode of response to
pacemaker a sensed event (i.e., T, I, or D). The fourth letter refers to
code the rate response or not (i.e., R or blank)
represent?

In a rate- Changes in respiratory rate, CO 2 level/minute ventilation, or

responsive motion
pacemaker (R),
what are the
triggering
modes?

How is the LV By threading a pacemaker lead through the coronary sinus up

paced with a to the great cardiac vein (drains the LAD territory) or down a
biventricular lateral wall vein. Can also be implanted on the LV directly
pacemaker? with surgery.

What are the Patients with NYHA class II to III/IV heart failure despite
indications for medical therapy with EF <35% who are in sinus rhythm and
biventricular have evidence of LV dyssynchrony with a QRS >130 msec
pacing?

What are the Antitachycardia pacing, defibrillation, and single- or dual-

capabilities of chamber pacing
a three-zone
ICD?

What is Termination of VT by pacing the ventricle at a rate 10% or so

antitachycardia faster than the tachycardia, which results in shifting the
pacing? tachycardia circuit to a new location. When the pacing is
terminated, the tachycardia is also terminated.

What is a The tachycardia speeds up to the paced rate and does not
potential terminate.
complication
 of
antitachycardia
pacing?

What is the Painless termination of the VT

advantage of
antitachycardia
pacing?

P.64
P.65

Cardiac Catheterization
What is the A branch from the LMCA (in between the LAD and
ramus circumflex)
intermedius?

How common is This occurs in 90% of cases. The other 10% of the time, the
right PDA comes from the LCx (left dominant).
dominance?

Which artery The RCA in 55%, the LCx in 45%

supplies the SA
node?

Which artery The RCA if dominant (85% to 90%); the LCx otherwise.
supplies the AV
node?

What are the Allergic contrast reaction, bleeding, infection, renal failure,
important 1/1000 incidence of stroke, MI, arrhythmias, cardiac
complications of perforation, and death
cardiac
catheterization?

What are the It provides a map of all vessel stenoses, distal vessels,
benefits of collaterals, and LV function. It also provides information as
cardiac to the severity of valvular regurgitation, allows calculation
catheterization? of stenotic valve areas, and directly measures intracardiac
pressures.

What are the Absence of any antegrade coronary blood flow

coronary flow
findings for TIMI
0 flow?

What are the Faint filling beyond the coronary stenosis but not to the
coronary flow distal portion of the artery
findings for TIMI
1 flow?

What are the Complete filling of the artery with delayed or sluggish flow
coronary flow
findings for TIMI
2 flow?

What are the Normal coronary blood flow

coronary flow
findings for TIMI
3 flow?

How can Redilatation, stenting, brachytherapy, atherectomy, and

restenosis be CABG
treated?

What common Sirolimus and paclitaxel

drugs are used
in the drug-
eluting stents?

What factors of A smaller stent diameter and a longer stent length

a stent are
associated with
a higher
restenosis rate?

What is subacute A platelet-mediated phenomenon that occurs before

stent reendothelialization of the stent
thrombosis?

When does Typically early after intracoronary stent implantation,

subacute stent usually within the first 30 days. However, this can also
thrombosis occur late out.
occur?

How does Patients present with chest pain and ST elevation.

subacute
thrombosis
present?

How is subacute Cotreatment with ASA (325 mg for the first month; 81 mg
stent thrombosis thereafter) and clopidogrel (75 mg every day) has been
prevented? shown to limit its occurrence to about 2%.

What are the Usually crushed or kissing stents.

options for
bifurcation
lesions?

What is Intracoronary radiation (beta or gamma).

brachytherapy?

What is the Candy wrapper restenosis. Stenosis that occurs at the

downside of proximal and distal margins of the brachytherapy field.
 brachytherapy?

What are the A bridge for patients with AS who require noncardiac
indications for surgery. May be helpful to determine if the AS is the cause
aortic of LV dysfunction prior to valve replacement in very ill
valvuloplasty? patients. Can be a lasting therapy for patients with
congenital noncalcific AS.

How do you time The device inflates during diastole (the dicrotic notch),
an IABP? augmenting coronary blood flow, and deflates during systole
(just prior to the aortic pressure upstroke), causing a
reduction in afterload. This can be timed off the aortic
pulsation or the ECG tracing.

What are three 1. Significant aortic regurgitation

contraindications 2. Aortic dissection
to an IABP? 3. Severe peripheral vascular disease

P.66

Coronary Artery Bypass Grafting

What are the Restoration of blood flow to the myocardium, MI during
mechanisms of surgery, placebo effect, and denervation.
chest pain reduction
after CABG?

What is an OPCAB? Off-pump coronary bypass

What is an Since it is done off pump, there is the theoretical

advantage of an advantage of less neurologic complications due to the
OPCAB? bypass machine and less manipulation of the aorta.

What is a It can be difficult to revascularize all areas of the

disadvantage of an heart.
OPCAB?

What is robotic Using human-controlled robotic hands to perform

surgery? heart surgery

What is a potential It can be done remotely. For example, a technician

advantage of the could place the cannulae and the surgeon could operate
robotic surgery? from thousands of miles distant.

What is hybrid Using a combination of percutaneous (i.e., stents) and

surgery? operative procedures.

P.67
P.68
P.69

Coronary Artery Disease

What is the incidence of On an annual basis in the United States, 5.4
CAD? million people are diagnosed with CAD, and CAD
is responsible for in excess of 500,000 deaths per
year.

What is the coronary Mean arterial pressure LVEDP

perfusion pressure?

What factors can lower Coronary perfusion pressurehypotension,

perfusion pressure? coronary stenosis
High LVEDPhypertrophy (HTN <AS), HF, MR, and
AR

How is coronary flow Coronary flow = (perfusion pressure)/(vascular

determined? resistance)

How are the different Type I: increased chylomicrons, normal

types of cholesterol, increased triglycerides
hyperlipoproteinemia Type IIA: increased LDL and cholesterol; may
classified (Fredrickson and have increased triglycerides; normal VLDL
Lee)? Type IIB: increased LDL, VLDL, and triglycerides
Type III: floating beta lipoprotein; increased
cholesterol and triglycerides
Type IV: increased VLDL and triglycerides; normal
to increased cholesterol
Type V: increased chylomicrons, VLDL, and
cholesterol; greatly increased triglycerides;
reduced LDL and HDL

What LDL should be the <100 mg/dL, consider <70 mg/dL in high-risk
goal (based on NCEP III patients
guidelines) in patients
with known CAD or CAD
equivalent (i.e., DM)?

How much cardiovascular About 20%

mortality benefit do you
get for lowering the LDL
by 40 mg/dL?

How much fat is in the 35% to 40% of all calories ingested

average American diet?

How much can dietary Reducing ingested fat to 20% to 25% of the total
modification lower LDL calories taken in can lead to a 15% reduction in
cholesterol? LDL cholesterol.

What HMG-CoA reductase Fluvastatin, lovastatin, pravastatin, simvastatin,

inhibitors are available atorvastatin, and rosuvastatin
for the treatment of
hyperlipidemia?
 What bile-acid Cholestyramine [Questran], colestipol [Colestid],
sequestrants are available and colesevelam [Welchol]
for the treatment of
hyperlipidemia?

What fibric acid Gemfibrozil [Lopid] and fenofibrate [Tricor]

derivatives are available
for the treatment of
hyperlipidemia?

What cholesterol Ezetimibe [Zetia], Benecol, Take Control, and B-

absorption inhibitors are sitosterol
available for the
treatment of
hyperlipidemia?

What else is available for Nicotinic acid and fish oil. Garlic may also have a
the treatment of mild benefit.
hyperlipidemia?

Besides CAD, what is a Pancreatitis

potential complication of
elevated TG?

What are the side effects of:

HMG-CoA reductase Constipation, rhabdomyositis (<1%; more frequent

inhibitors? with drug combinations such as gemfibrozil and
cyclosporine and potentiated by large quantities
of grapefruit juice), hepatitis (<3%), myopathy,
and transaminitis

Bile-acid resins? Gastrointestinal complaints (e.g., constipation,

bloating)

Niacin? Flushing, pruritus, hepatitis, hyperglycemia,

hyperuricemia, gout

Fibric acid derivatives? Gastrointestinal complaints, hepatitis, and

myopathy/myositis

What is LP(a)? A derivative of LDL that is substantially more

atherogenic than LDL alone

What are the features of Waist >40 inches [men], >35 inches [women],
the metabolic fasting glucose >110 mg/dL, BP $130/85 mm Hg,
syndrome? HDL <40 mg/dL, TG $150 mg/dL

P.70
P.71

Biomarkers in Acute Coronary Syndromes

Name seven causes of AMI, myocarditis, rhabdomyolysis (trauma, status
CK elevation. epilepticus, surgery, severe prolonged exercise),
polymyositis or muscular dystrophy, devastating
brain injury, familial elevation, renal injury

Name four causes of CK- Acute MI, cardiac surgery, muscular dystrophy, and
MB elevation. myocarditis

Name four causes of CK- Brain injury or Reye's syndrome, uremia, malignant
BB elevation. hyperthermia, and small intestine necrosis

Name six causes of LDH Acute MI, hemolytic anemia, pernicious anemia or
elevation. sickle cell crisis, large pulmonary embolus, renal
infarction, prosthetic heart valves, hepatic injury,
and myoglobin

What are the Some patients with heart failure may leak
circumstances where troponin at all times. Patients with renal failure
troponin I and T may may have prolonged elevations due to decreased
remain elevated for clearance.
prolonged periods?

What else causes a rise Hepatic congestion/ischemia, skeletal muscle injury

in AST? (including IM injections), PE, and during shock

When does the LDH Elevation at 24 to 48 hours, peak at 3 to 6 days,

elevate, peak, and and resolution at 8 to 14 days
resolve in AMI?

What else causes LDH to Hemolysis, megaloblastic anemia, leukemia, liver

elevate? disease, hepatic congestion/ischemia, renal
disease, some neoplasms, PE, myocarditis, skeletal
muscle disease, and shock

In the figure below, label the curves for the appropriate enzyme:
 Troponin
CK
LDH

What is hsCRP? A biomarker of inflammation

What is b-type A peptide released by the myocardium in response

natriuretic peptide? to stretch

What are the two bNP and NTproBNP

commonly used b-type
natriuretic peptides?

What conditions elevate Congestive heart failure, acute MI, PE

b-type natriuretic
peptide levels?

Acute Coronary SyndromesGeneral Considerations

What is the 1.5 million people per year; accountable for 25% of all
incidence of AMI? deaths in the United States

P.72
P.73
P.74

Treatment of Acute Coronary Syndromes

If argatroban Patients are usually treated to an INR of 6 and then the
and warfarin are argatroban is withdrawn. If the INR falls below 2, the
used in patients argatroban is restarted.
with HITT, when
is the argatroban
discontinued?

Which of the Abciximab (30 minutes versus 120 to 150 minutes for the
GPIIb/IIIa other two)
inhibitors has
the shortest
half-life?

What is the onset of action of

Abciximab 120 minutes

Tirofiban 5 minutes

Eptifibatide 60 minutes

What is the duration of action of the GPIIb/IIIa inhibitors on the platelet

function?

Abciximab? 48 hours

Tirofiban? 4 to 6 hours

Eptifibatide? 4 to 6 hours

Are any of the Yes, tirofiban and eptifibatide (theoretically abciximab is

GPIIb/IIIa also if you give enough platelets)
inhibitors
reversible?

Name the direct Lepirudin, bivalirudin, argatroban

thrombin
inhibitors.

What are the Cost and late subacute thrombosis

disadvantages of
drug-coated
stents compared
with bare metal
stents?

How is subacute Full deployment of the stent and at least a year of

thrombosis thienopyridine use following placement of a drug-eluting
prevented? stent

List five of the Age >65 years, >3 CAD risk factors, known prior CAD, ASA
seven risk use last 7 days, >2 anginal events in <24 hours, ST
factors in the deviation, and elevated troponin or CK
TIMI risk score
for patients with
UA or NSTEMI.

How is the risk If the TIMI score is $3, the outcome is worse, suggesting a
score used? more aggressive approach (GPIIb/IIIa inhibitors and early
catheterization) in these patients.

What are the ST elevation in two contiguous ECG leads in patients with
indications for pain onset within 6 hours who have been refractory to
thrombolysis? sublingual nitroglycerin (with or without heparin), who
cannot have primary PCI within 90 minutes of first medical
contact, and who have no contraindications; therapy may
also be beneficial in patients
presenting at 6 to 12 hours and perhaps at 12 to 24 hours.
Also, new LBBB with typical pain.

When is When the patient presents early after symptom onset

thrombolysis When PCI is not an option
generally When there would be a prolonged transport time
preferred over When the door to balloon time would exceed 1 hour
PCI?

What are seven 1. Any prior intracranial hemorrhage

absolute 2. Known structural cerebral vascular lesion (e.g., AVM)
contraindications 3. Significant closed head or facial trauma within 3
to thrombolysis? months
4. Ischemic CVA in the past 3 months (excludes an
ischemic CVA in the past 3 hours)
5. Malignant intracranial neoplasm (primary or metastatic)
6. Known bleeding disorder or active bleeding not
including menses
7. Suspected aortic dissection

What are nine 1. Active peptic ulcer disease or internal bleeding within
relative the last 2 to 4 weeks
contraindications 2. A history of uncontrolled or poorly controlled HTN
to thrombolysis? 3. Severe uncontrolled HTN on presentation: systolic
pressure >180 mm Hg, diastolic pressure >110 mm Hg
4. Traumatic CPR or CPR >10 minutes
5. Ischemic or embolic CVA more than 3 months ago,
dementia or other known intracranial process
6. Use of warfarin or other anticoagulants
7. Significant trauma or major surgery <3 weeks
8. Pregnancy
9. Noncompressible vascular punctures

When is primary When an invasive lab is available

PCI generally When the expected door to balloon time is <90 minutes
preferred over When the (door to balloon) (door to needle) <1 hour
thrombolysis? For high-risk patients (shock and heart failure)
When there are contraindications to lysis
 When patients present late out from the event
When the diagnosis of STEMI is in question

What is rescue Patients who fail thrombolysis at 90 minutes are taken

PCI? urgently to PCI.

What is Patients who receive thrombolysis are then brought to the

facilitated PCI? catheterization laboratory for immediate PCI. This is
generally not pursued owing to higher complication rates.

What are the Warm and dry (good CO and low PC)
four Warm and wet (good CO and high PC)
hemodynamic Cold and dry (poor CO and low PC)
classes Cold and wet (poor CO and high PC)
(Forrester) for
post-MI patients?

P.75
P.76

Mechanical Complications of Myocardial Infarction

List six Left ventricular aneurysm or rupture, papillary muscle
mechanical rupture or dysfunction, thromboembolism, reinfarction or
complications that extension, pericardial effusion or tamponade, and heart
may follow an failure
AMI.

What is the 1% to 5% in patients who die of AMI

incidence of
ruptured papillary
muscle in patients
who die after AMI?

When does a 2 to 10 days after the MI. Primarily, the posterior

ruptured papillary papillary muscle is involved.
muscle typically
occur?

When does a VSD 9 to 10 days after MI, although it may occur earlier after
typically occur? revascularization

What is the More common than VSD or papillary muscle rupture;

incidence of left accountable for up to 25% of fatal AMIs
ventricular
rupture after AMI?

When does left 50% of cases within 5 days of AMI; 90% within 2 weeks
ventricular
rupture typically
occur?

What is the >95%

 mortality rate for
left ventricular
rupture?

What are the risk Female gender, hypertensive patients, usually larger
factors for LV infarct size (at least 20% of the free wall), treatment
rupture? with lytic therapy.

How can acute MR caused by papillary muscle rupture be differentiated from

an acute VSD?

By history? Patients with VSDs have little or no orthopnea early after

the event, whereas patients with acute MR often have
severe orthopnea.

By auscultation? The VSD murmur is heard best over the sternum. The MR
murmur can be heard at the apex but frequently radiates
superiorly in posterior leaflet papillary muscle ruptures
and posteriorly in anterior leaflet papillary muscle
ruptures.

Echocardiogram Probably the best wayallows direct visualization of the

and Doppler? defect or flow.

Right heart An increase in oxygen saturation by more than 5%

catheterization between chambers is consistent with a shunt (i.e., VSD).
with measurement For example, RAO 2 saturation, 61%; RVO 2 saturation,
of the oxygen 75%; PAO2 saturation, 78%; arterial O 2 saturation, 95%.
saturation?

How is an LV By a resting dyskinetic region

aneurysm
recognized on
imaging
procedures?

What is a A ventricular free wall rupture contained by a section of

pseudoaneurysm? pericardium (commonly a scarred section that prevents
tamponade)

How is a A narrow neck feeding into a nontrabeculated sac

pseudoaneurysm
recognized on
imaging?

What is Abnormal reshaping of the ventricle at sites not involved

ventricular in the initial injury owing to abnormal loading conditions
remodeling?

P.77

Other Care After Myocardial Infarction

 How are high- Highest risk is seen with thrombi that project into the LV
embolic-risk cavityi.e., that are not layered.
LV thrombi
recognized?

What is the None

prognostic
significance of
VF early after
an AMI (within
48 hours)?

What is the The mortality rate significantly increases owing to recurrent

prognostic VF, which requires evaluation and long-term treatment.
significance of
VF late after
an AMI (longer
than 48
hours)?

Are ICDs No. A study (Defibrillator After Acute Myocardial Infarction

indicated Trial DINAMIT) has suggested a higher death rate within the
early after MI first 40 days.
associated
with LV
dysfunction
(LVEF <35%)?

When are ICDs In patients with sustained or symptomatic VT, otherwise in

indicated those >40 days post MI with LV dysfunction and mild to
post-MI? moderate symptoms of heart failure. One study [Multicenter
Automatic Defibrillator Implantation Trial (MADIT) II] also
suggested a benefit in patients post-MI with LVEF <30% and no
symptoms.

Besides First-, second- and then third-degree heart block

VT/VF, what
rhythm is
seen after
some IMIs?

P.78

Arrhythmias

Common Arrhythmias
List the common SVTs Sinus tachycardia, AV node reentry, atrial
tachycardia, AV reciprocating tachycardia
(accessory pathway), atrial flutter with rapid
ventricular response, AF, and MAT

How is sinus tachycardia Always search for the underlying cause and
 treated? treat that.

How is atrial tachycardia treated?

With evidence of block? Digitalis intoxication should be high on the

list of causes and treated appropriately
(Digibind if needed).

Without evidence of block? AV nodeblocking agents like diltiazem, beta

blockers, and digoxin.

What is inappropriate sinus A rhythm from the region around the sinus
tachycardia? node that inappropriately accelerates
periodically. It is an atrial tachycardia.

What are the ECG indicators P waves not connected to the QRS (AV
to look for to determine if a dissociation), fusion beats, complexes >140
patient is in VT? ms, and common-looking BBB complexes.

What is a fusion beat? A combination of a normal QRS and a VT

beat, so it is more narrow than the VT beats.

What is the name of the wide AIVR (accelerated idioventricular rhythm)

complex rhythm at 100 to 120 often associated with reperfusion
bpm seen in patients with MI
undergoing treatment?

What is the best question to Have you had a heart attack? If the answer
ask to determine whether a is yes, the rhythm is most likely VT; if the
patient has an SVT with answer is no, consider SVT.
aberrancy or VT?

What is torsades de pointes? A polymorphic VT where the axis shifts up

and down as if it were turning about a point.

P.79

Atrial Fibrillation
What is the yearly risk for CVA for 5%, depending on the risk group
the average patient in AF on ASA?

What is the yearly risk for CVA for About 1%

the average patient in AF on
warfarin?

Considering all patients with AF, what factors place patients at:

High risk for CVA? Prior CVA/TIA, mitral stenosis,

prosthetic valves (metal)

Intermediate risk for CVA? Age >75 years, hypertension, heart

failure, LVEF #35%, diabetes mellitus
 Low risk for CVA? Female gender, age 65 to 74 years,
CAD, and thyrotoxicosis

What are the factors that place a Prior CVA/TIA

patient at high risk for CVA with Age >75 years
nonvalvular AF? Hypertension
Diabetes
Heart failure

Do all patients with AF require No. Those with minimal risk or none
anticoagulation with warfarin? of the risk factors above may just
require ASA.

In patients who are on warfarin for 1.8 to 2.5

atrial fibrillation, what is the goal
INR?

What else can be done for patients Ablation of the regions around the
with AF and symptoms? pulmonary veins

Antiarrhythmic Medications
Name the antiarrhythmics Class Ia (quinidine, procainamide,
according to the Vaughan disopyramide)
Williams classification. Class Ib (lidocaine, mexiletine)
Class Ic (flecainide, propafenone)
Class II (beta-adrenergic blockers)
Class III (amiodarone, bretylium, sotalol (also
a beta-adrenergic blocker), propafenone,
dofetilide, and ibutilide)
Class IV (nondihydropyridine calcium channel
blockers)

What causes quinidine Torsades de pointes

syncope?

What is a cause of arthritis in Drug-induced lupus reaction

patients taking procainamide?

P.80

Emergent TreatmentProtocols
What is the presumptive diagnosis VT
in a patient with a wide-complex,
regular tachycardia, and no pulse?

What is your first intervention? Cardioversion

What is the diagnosis in a patient VT or SVT with a BBB

with a wide-complex, regular
tachycardia who is comfortable,
 awake, and has a pulse?

What is your first intervention? Intravenous amiodarone, lidocaine,

beta blockers, or possibly procainamide

If the monitor shows sinus rhythm Pulseless electrical activity [formerly

but the patient is unresponsive and known as electromechanical
has no pulse, what is the diagnosis? dissociation (EMD)]

In a patient with no blood pressure, Epinephrine (1 mg) and vasopressin (40

what agents should be used? IU)

What are the reversible causes of Hypoxemia, hypovolemia, hypothermia,

PEA pneumothorax, pulmonary embolism,
acidosis, coronary thrombosis, and
cardiac tamponade

In patients with torsades de Cardioversion, treatment of electrolyte

pointes, what therapies should be disarray, Magnesium 1 to 2 g IV,
considered? isoproterenol, pacing

What are some of the common Disopyramide, procainamide, quinidine,

medication causes of torsades? dofetilide, ibutilide, and sotalol

What antibiotics can cause Clarithromycin, erythromycin, and the

torsades? fluoroquinolones

P.81

Syncope
What percentage of syncope cases are:

Cardiovascular? 10% to 25% (mortality rate at 12 months = 30%)

Noncardiovascular? 40% to 60% (mortality rate at 12 months = 12%)

Unknown? 50% to 70% (mortality rate at 12 months = 6%)

List 10 noncardiac Vasovagal, orthostatic, hypovolemic (includes

causes of syncope. bleeding), CVA/TIA (rare), seizure, psychogenic,
hypoglycemic, hyperventilation, pulmonary embolus

List six AS, CAD catastrophic event (e.g., ventricular free wall
cardiovascular rupture or acute VSD), dissecting aortic aneurysm,
causes of syncope. congenital lesions, dysrhythmias (including long QT and
heart block), neurocardiogenic

Valvular Heart Disease

What are AS, MR, and VSD
the
common
 systolic
murmurs?

What are HOCM, MVP, supravalvular aortic stenosis, RV outflow obstruction,

the pulmonic stenosis, tricuspid regurgitation
uncommon
systolic
murmurs?

What are Aortic regurgitation and MS

the
common
diastolic
murmurs?

What are Tricuspid stenosis, left atrial myxoma, left-to-right shunts, Austin
the Flint murmur, pulmonic regurgitation
uncommon
diastolic
murmurs?

What are PDA and the combination of AS and AI

the
common
continuous
murmurs?

What are Surgically created systemic-to-pulmonary shunts, venous hums

the
uncommon
continuous
murmurs?

What are Screening criteria for the diagnosis of acute rheumatic fever.
the Jones Patients with two major or one major and two minor criteria have
criteria? a high probability of acute rheumatic fever.

What are Carditis, erythema marginatum, chorea (St. Vitus' dance),

the major polyarthritis, subcutaneous nodules
Jones
criteria?

What are Fever, arthralgia, elevated ESR or positive C-reactive protein,

the minor previous rheumatic fever or rheumatic heart disease, and
Jones prolonged PR interval. There is also supporting evidence for a
criteria? preceding streptococcal infectionthat is, history of recent
scarlet fever, positive throat culture for group A streptococcus, or
increased ASO titers or titers for other streptococcal antibodies.

P.82

Valvular Surgery
 Name some of the Porcine, bovine, pericardial, and human (cadaveric)
sources of
bioprosthetic valves.

What are the common Hancock, Carpentier, and homograft (human valve
names of the tissue)
bioprosthetic valves?

Why is The valves are fixed in glutaraldehyde; there is no

immunosuppression active surface protein.
not required for tissue
valves?

How long do tissue There is a 30% failure rate at 15 years.

valves last?

Which are the two Younger patients and those with chronic kidney
groups at higher risk disease.
of tissue valve failure?

Name some of the St. Jude's, Medtronic-Hall, Star-Edwards, Lillehei-

mechanical valves Kaster. Bjork-Shiley valves are uncommon.
available.

What medication is Warfarin with or without aspirin

required after
placement of a metal
valve?

In whom should Young children, older persons (especially those prone

anticoagulation be to falling), young women who desire to bear
avoided? children, and patients with a history of peptic ulcer
disease or bleeding diathesis (in whom a tissue valve
would be required)

In patients undergoing It helps maintain normal ventricular geometry.

mitral valve surgery,
why is it important to
maintain the
subvalvular apparatus?

P.83

Aortic Stenosis
What is the 2 to 3 cm2
normal aortic
valve area?

What valve <0.7 cm2 (<0.5 cm2 /m 2 )

area is
considered to
be critically
 narrowed?

What are the Sustained apical impulse

nonauscultatory Low pulse pressure
findings of Delayed pulse peak and low amplitude (pulsus parvus et
severe AS? tardus; best appreciated at the brachial artery)

What are the Diamond-shaped systolic murmur (the later the peak, the
auscultatory tighter the valve) heard at the base with radiation to the
findings of carotids
severe AS? S4 ; S3 if in CHF
Ejection click
Reduced (or absent) A 2
Delayed A 2 closure (or paradoxic splitting of A 2 P2 )
Mild AI (severe AS and severe AI cannot occur together)

What is an easy
formula to
calculate the
aortic valve
area?

Why isn't The average patient obtains only 6 months of relief prior to
percutaneous restenosis of the valve.
aortic balloon
valvuloplasty
the standard of
care for severe
AS?

P.84

Aortic Regurgitation
What connective tissue Marfan's syndrome, Ehlers-Danlos syndrome,
and arthritic syndromes Reiter's, rheumatoid arthritis, systemic lupus
are associated with AI? erythematosus, Takayasu's aortitis

Why is acute AI difficult The murmur is soft because of the rapid

to diagnose? equalization of the aortic diastolic pressure and the
LVEDP.

What are the common Wide pulse pressure (If pulse pressure is <50 mm Hg
nonauscultatory or aortic diastolic pressure is >70 mm Hg, the AI is
physical findings of probably not severe.)
chronic severe AI?

What is the description Midfrequency decrescendo diastolic murmur

of the murmur in AI?

Name the common signs Corrigan's pulse (rapid increase and decrease)
associated with AI. DeMusset's sign (head bob with pulsations)
Pistol-shot pulses
 Duroziez's murmur (femoral artery systolic and
diastolic murmur)
Mueller's sign (uvular bobs)
Quincke's sign (nail-bed pulsation)
Hill's sign (augmented femoral artery systolic and
diastolic pressure)

What is the Austin-Flint It occurs in severe AI. The regurgitant jet strikes
murmur? the anterior leaflet of the mitral valve, causing it to
move into the mitral inflow and resulting in relative
MS.

When is surgery needed Some studies have shown improved survival when
for patients with AI? the LV is >70 mm at end diastole or >50 mm at end
systole.

P.85

Mitral Stenosis
What is the normal mitral 4 to 6 cm2
valve area?

At what valve area and valve Mitral valve area <2 cm2 and gradients >20 mm
gradient do symptoms Hg
commonly begin?

What are some nonvalvular Atrial myxoma, LA thrombus, and cor

causes of LV inflow triatriatum
obstruction?

What is cor triatriatum? A congenital abnormality where the left atrium

remains a septated chamber

What are the common Malar flush.

nonauscultatory physical Peripheral cyanosis.
findings of MS? Elevated JVD (when right heart failure occurs).
Augmented v wave on jugular inspection.
All signs increase with exercise and pregnancy.

What is the description of A diastolic rumble that increases with exercise

the murmur in MS? and is heard best in the left lateral decubitus
position

What are the other Increased S1

auscultatory findings in Opening snapthe closer the A 2 opening snap
patients with MS?
interval, the tighter the valve
Presystolic augmentation of the rumble

When patients present with Atrial fibrillation

symptoms of MS, what is the
usual ECG finding?
 Why does atrial fibrillation Loss of the atrial kick to fill the ventricle
cause symptoms in patients
with MS?

What features of the valve If the valve is not heavily calcified or the
determine whether the valve submitral apparatus is not too severely
can be repaired? thickened, the valve can be repaired.

P.86
P.87

Mitral Regurgitation
How does LV cavity It results in a stretch of the mitral annulus and
dilatation cause MR? consequent leaflet noncoaptation. Enlargement of
the ventricle also causes malposition of the
papillary muscle structure and leaflet
malcoaptation.

How does CAD cause Recurrent MIs lead to LV dilatation.

MR? MIs involving the inferior or inferoposterior walls
can tether the leaflet and prevent full closure.
Papillary muscle infarction causes papillary muscle
dysfunction or disruption, leading to leaflet
malcoaptation.

What connective tissue Marfan's syndrome, Ehlers-Danlos syndrome,

diseases cause MR? osteogenesis imperfecta, and systemic lupus
erythematosus

How does HOCM cause As the column of blood accelerates across the
MR? obstruction in the LVOT, the anterior mitral leaflet
is pulled into the LV cavity (SAM: systolic anterior
movement of the mitral valve).

What are some examples Corrected transposition, endocardial fibroelastosis,

of congenital heart partial AV canal, and cleft leaflet
diseases with MR?

What populations are Older women and patients with renal failure
most commonly affected
by mitral annular
calcification?

Where does the murmur The regurgitant jet (and murmur) is reflected to
of acute MR radiate if the back below the scapula.
the anterior papillary
muscle or leaflet is
injured?

Where does the murmur The regurgitant jet (and murmur) is reflected
of acute MR radiate if superiorly to the clavicular region.
the posterior papillary
 muscle or leaflet is
injured?

What is the common Holosystolic murmur radiating to the apex

auscultatory finding of
chronic MR?

What are the common Loud holosystolic murmur, S3 gallop, rales, JVD,
physical examination liver distension, and edema
findings of chronic
severe MR?

What maneuvers cause Any maneuver that shrinks the LV cavitythat is,
the click and murmur of decreases the preload or afterload (e.g., by sitting
MVP to move early into or standing up) causes the click and murmur to
the systolic cycle? occur earlier.

What maneuvers cause Any maneuver that increases the cavity sizethat
the click and murmur of is, increases preload or afterload (e.g., by raising
MVP to move late into the legs up or gripping the hands) causes the click
the systolic cycle? and murmur to occur later.

What is the typical body Pectus excavatum, asthenic features, and straight
habitus for patients with back
MVP?

P.88
P.89
P.90
P.91

Infective Endocarditis
What organisms It is caused by more virulent organisms, such as
are frequently Staphylococcus aureus, Streptococcus pneumoniae, and
seen in patients Streptococcus pyogenes.
with acute
endocarditis?

What historical It is more common in patients with prior valvular disease.

feature is more
common in
patients
presenting with
subacute
endocarditis?

What congenital Patent ductus, VSD, coarctation of the aorta, bicuspid aortic
heart defects valve, tetralogy of Fallot, and pulmonary stenosis
are risk factors
for IE?

What are some Rheumatic heart disease

of the other Degenerative cardiac lesions (aortic sclerosis and mitral
risk factors for calcification)
IE? Some MVP with regurgitation
Intracardiac pacemakers or intracardiac prostheses
Intravascular access procedures in ill, hospitalized patients
Intravenous drug use

What are the Almost any organ can be involved. Symptoms and signs
symptoms and include fever, constitutional symptoms, heart murmur,
signs of IE? peripheral manifestations (see below), musculoskeletal
symptoms, HF, emboli, and neurologic symptoms.

How often is a In >85% of cases

heart murmur
heard in IE?

How often is a In <10% of cases

new or a
changing
murmur heard
with IE?

How often are In <50% of cases

peripheral
findings of IE
seen?

What are the Infectious process on the valve

signs and Bland or septic embolization
symptoms of IE Sustained bacteremia
due to? Circulating immune complexes

What are the Splinter hemorrhages, Roth's spots, petechiae, Osler's nodes,
peripheral and Janeway lesions
manifestations
of IE?

What else They may also occur with trauma and are more suggestive of
causes splinter IE if they are close to the nail matrix.
hemorrhages
and how are IE
splinters
differentiated
from them?

How often is 90% to 100% of cases

the ESR
elevated?

What are the Proteinuria, hematuria, and red blood cell casts
typical findings
on urinalysis
with IE?
How should Three sets of specimens should be drawn within 24 hours,
blood cultures but no more than two vials should be drawn from one site at
be drawn in one time. Cultures should be held for 21 days (for fastidious
patients with organisms).
suspected IE,
and how many
should be
drawn?

In patients with In two thirds of patients, all blood cultures are positive.
culture-positive
IE, how
commonly are
all the blood
cultures
positive?

How often are If the patient has not been exposed to antibiotics, the first
the first two two blood cultures yield a pathogen more than 90% of the
blood cultures time.
positive in
culture-positive
IE?

What findings A vegetation, valvular dysfunction, or the presence of an

are seen on abscess.
TTE in patients
with IE?

How much TEE is more sensitive (95%) than TTE (65%). Consider TEE
more sensitive when TTE is negative and there is suspicion of IE.
is TEE than TTE
for the
evaluation of
IE?

How often are Streptococci and staphylococci cause approximately 90% of

strep and staph all cases of IE.
species the
cause in IE?

What are the Streptococci (viridans, mutans, or bovis and enterococci,

pathogens among others)
involved in IE? Staphylococci (S. aureus; coagulase-negative)
Gram-negative bacilli (uncommon, high mortality rate)
Fungi
Miscellaneous bacteria
Culture-negative causes [including the HACEK organisms:
Haemophilus species (H. parainfluenzae, H. aphrophilus,
and H. paraphrophilus), Actinobacillus
actinomycetemcomitans, Cardiobacterium hominis,
Eikenella corrodens, and Kingella species]
How likely is endocarditis if a blood culture is positive for the following:

Streptococcus 15 cases of IE for every one case of bacteremia without

mutans? valvular involvement

Streptococcus Three cases of IE for every one case of bacteremia without

sanguis? valvular involvement

Enterococci? Equal likelihood of IE or bacteremia without valvular

involvement

Group A Only one case of IE for every seven cases of bacteremia

streptococcus? without valvular involvement

Why does Possible explanations include subacute right-sided

culture- endocarditis, mural endocarditis, timing [cultures drawn at
negative the end of a chronic course (>3 months)], prior antibiotic
endocarditis use, slow-growing fastidious organisms (HACEK, nutritionally
occur? variant streptococci), fungal infection, obligate intracellular
pathogens, noninfectious endocarditis, or the wrong
diagnosis.

What are the Positive blood cultures (typical microorganisms and

major Duke persistently positive cultures)
criteria to Evidence of endocardial involvement (mass, abscess, valve
define IE? dehiscence, worsening murmur)

What are the Predisposing heart condition or IV drug use

minor Duke Fever ($38.0C)
criteria to Vascular phenomenon (arterial embolism, septic pulmonary
define IE? infarcts, mycotic aneurysms, intracranial hemorrhage,
Janeway lesions)
Immunologic phenomenon (Roth spots, Osler's nodes,
glomerulonephritis)
Microbiologic (positive cultures not meeting the major
criteria)

Using the Duke criteria, what is:

Definite Two major criteria

evidence of IE? One major and three minor criteria
Five minor criteria

Possible Evidence short of definite but not rejected

evidence of IE? One major and one minor criterion
Three minor criteria

Evidence of Firm alternative diagnosis

IE rejected? Resolution of IE syndrome with #4 days of antibiotic therapy
No pathologic evidence of IE at surgery or autopsy with
antibiotic therapy #4 days
 What is the Parenteral antibiotics with sustained bactericidal activity,
general shown on susceptibility testing, should be selected and used
principle of the for a prolonged course (6 to 8 weeks).
antibiotic
treatment?

Why should the To watch for heart block due to a ring abscess.
patients with
suspected IE
have
continuous
monitoring?

Why are repeat To document clearing, therefore response to treatment.

blood cultures
drawn after
starting
therapy?

Should these Anticoagulation is associated with bleeding complications

patients be and should be avoided.
anticoagulated?

What are the Refractory CHF, uncontrolled infection, significant valvular

indications for dysfunction, repeated systemic embolization, large
surgery in a vegetation size (>1 to 2 cm), ineffective antimicrobial
patient with IE? therapy (against, e.g., fungi), mycotic aneurysm, most cases
of prosthetic valve endocarditis and local (cardiac)
suppurative complications with conduction abnormalities

P.92
P.93
P.94

Prosthetic Valve Endocarditis

Are mechanical or bioprosthetic valves Probably about the same
more prone to develop PVE ?

Are prosthetic aortic and mitral valves Aortic valves are about twice as
similar in rates of PVE? likely to develop PVE.

Antibiotic Prophylaxis
Is transient bacteremia Extremely. With tooth extraction, this occurs
common with dental 10% to 100% of the time. In periodontal surgery,
manipulation? it occurs 40% to 90% of the time, and with teeth
cleaning up to 40%.

Does bacteremia occur Yes. With tooth brushing and flossing, up to 70%
during common tasks? of the time; with toothpicks, up to 40% of the
time; and with water irrigation devices, up to
 50% of the time. Chewing food causes
bacteremia up to 50% of the time.

How high is the risk of The estimation is 1 case of IE per 14 million

endocarditis with dental dental visits.
procedures?

Is the risk of IE higher in Yes. The estimate is 1 case of IE per 1.1 million
patients with valvular heart dental visits in patients with MVP; 1 per 475,000
disease? dental visits in patients with congenital heart
disease; 1 per 140,000 in patients with
rheumatic heart disease; 1 per 115,000 visits in
patients with prosthetic valves; and 1 per 95,000
visits in patients with previous IE.

How common are fatal Estimated at 15 to 25 individuals per 1 million

anaphylactic reactions in patients
patients receiving
penicillin?

Based on the 2007 guidelines, which of the patient groups below should
receive endocarditis prophylaxis?

Patients with prosthetic Yes

heart valves?

Patients with a history of Yes

IE?

Patients with unrepaired Yes

congenital heart disease?

Patients with completely Yes for the first 6 months

repaired congenital defects
with prosthetic material or
devices?

Patients with repaired Yes

congenital disease but
residual defects?

Patients who have had a Yes

heart transplant and some
valvulopathy?

An isolated ASD No
(secundum) or patients >6
months out from a repair
of an ASD, VSD, or PDA
(surgical or percutaneous)

Innocent or functional No
murmur or echo evidence
of MR but a normal valve

Aortic valve sclerosis No

with a mild gradient (<2
m/s) and good leaflet
motion

Physiologic TR or PI with No
normal valves

Give examples of procedures that do or do not require antibiotic prophylaxis

in selected patients:

Skin and musculoskeletal Doany procedure where the skin or

tissue musculoskeletal tissue is infected

Respiratory Doany procedure with an incision or biopsy of

mucosal tissue
Do notET intubation, flexible bronchoscopy
without biopsy

Gastrointestinal DoEsophageal dilatation or sclerosing

therapies, any procedure of the biliary tree, any
operation involving the intestinal mucosa
Do notTEE and endoscopic procedures

Genitourinary Dourethral, prostate, or cystoscopic procedures

only if the GU tract is infected
Do notcesarean and vaginal deliveries, vaginal
hysterectomy, and procedures on uninfected
uterine tissues

Dental Doany procedure involving the manipulation of

gingival tissue or the periapical tooth region or
breaking of the mucosal barrier in the selected
patient groups above
Do notrestorations, orthodontic adjustments,
fluoride treatments, and loss of primary teeth

In patients with the Amoxicillin: adults, 2.0 g (children, 50 mg/kg)

appropriate indications given by mouth 1 hour before the procedure
who are able to take oral Penicillin allergicclindamycin: adults, 600 mg
medications, what (children, 20 mg/kg) given by mouth 1 hour
antibiotics are indicated as before the procedure OR
prophylaxis against Cephalexin or cefadroxil: adults, 2.0 g (children,
bacterial endocarditis (non- 50 mg/kg) by mouth 1 hour before procedure OR
GI/GU procedures)? Azithromycin or clarithromycin: adults, 500 mg
(children, 15 mg/kg) by mouth 1 hour before the
procedure
Antistaphylococcal coverage should be added if
indicated.
 In patients with the Ampicillin: adults, 2.0 g (children, 50 mg/kg)
appropriate indication who given IM or IV within 30 minutes before
are unable to take oral procedure)
medications, what Penicillin allergicclindamycin: adults, 600 mg
antibiotics are indicated as (children, 20 mg/kg) given IV 30 minutes before
prophylaxis against procedure OR
bacterial endocarditis (non- Cefazolin or ceftriaxone: adults, 1.0 g (children,
GI/GU procedures)? 25 mg/kg) IM or IV 30 minutes before procedure
Antistaphylococcal coverage should be added if
indicated.

In patients with the Amoxicillin 2.0 g orally (adults) or 50 mg/kg

appropriate indication, orally (children) 1 hour before procedure or
what antibiotics are ampicillin 2 g IM or IV (adults) or 50 mg/kg
indicated as prophylaxis for (children) IM or IV 30 minutes before procedure
GU and GI procedures? Or vancomycin 1 g IV (adults) or 20 mg/kg
(children) IV 1 to 2 hours before procedure in
penicillin-allergic patients

P.95

Athletes and Cardiovascular Disease

What are the common ECG Owing to the high vagal tone: sinus
findings in athletes? bradycardia, junctional rhythms, first-
degree AV block, and Wenckebach (Mobitz
1)

What are the three most Hypertrophic cardiomyopathy, commotio

common cardiovascular causes cordis, and coronary artery anomalies
of sudden death in young
athletes?

What is commotio cordis? VT/VF following a blow to the chest

Why does commotio cordis The blow hits at the time of the T-wave
occur? vulnerable period, causing and R-on-T
initiation of VT/VF.

What is the survival rate for About 15%

victims of commotio cordis?

For all athletes, what four Football, soccer, basketball,

sports are associated with the running/orienteering
highest number of sudden
deaths?

P.96
P.97
P.98
P.99

Cardiomyopathies
General Cardiomyopathies
What are the three classic Dilated, hypertrophic, and restrictive
types of cardiomyopathy?

What is an ischemic Recurrent MIs cause abnormal loading conditions

cardiomyopathy? and consequent ventricular remodeling.

Do all patients with heart No. There is a large group, perhaps 40% of the
failure have poor systolic heart failure population, with normal ejection
function? fractions.

Do all patients with heart No. Patients with volume overload due to renal
failure and normal failure and those with pericardial constriction
ejection fractions have are examples of patients with heart failure and
diastolic dysfunction? normal diastolic function.

Compared to NYHA class Metabolic exercise testing (determination of

assignment, what is a more oxygen consumption)
accurate way to determine
prognosis in patients with
advanced heart failure?

What are the four stages Stage Ahigh risk for developing heart failure
of heart failure? Stage Basymptomatic heart failure
Stage Csymptomatic heart failure
Stage Drefractory end-stage heart failure

What are the classic Distended neck veins, lateral PMI, S3 and/or S4
cardiovascular physical gallop, murmurs of mitral or tricuspid
signs of heart failure? regurgitation, and a narrow pulse pressure

What is the significance of A pulse pressure index of <25% is associated with

a narrow pulse pressure in a CI of <2 L/min/m 2 .
a patient with
cardiomyopathy?

List the common chest Cardiomegaly, Kerley B lines, venous congestion

radiograph features of or cephalization, and pulmonary edema
heart failure.

From the above list, what Cardiomegaly

is the most common chest
radiograph finding in
patients with HF?

List some of the Alcoholic cardiomyopathy, hypocalcemia,

potentially reversible hypokalemia, hypophosphatemia,
causes of a dilated hemochromatosis (also casuses restrictive),
cardiomyopathy. pheochromocytoma, myocarditis, sarcoid heart
disease, lead poisoning, selenium deficiency,
uremic cardiomyopathy, and ischemic
 cardiomyopathy

What are some of the Coxsackie A and B, influenza B and A, echovirus,

viruses that can cause hepatitis, and HIV, among others.
myocarditis?

What is the most common Chagas' disease [a parasitic infection caused by a

cause of myocarditis and trypanosomal infection after the bite of a
the most common cause of reduviid bug (bedbug)]
HF worldwide?

What are some classic Adriamycin (doxorubicin) and cyclophosphamide

medication-induced forms cardiotoxicity
of myocarditis?

What other drugs can Cocaine, methamphetamine, alcohol, and

cause myocarditis? arsenic.

What are some of the Wasp, bee, and scorpion stings. Snake and spider
causes of myocarditis that bites.
occur secondary to things
in the environment?

Why is the muscle injured It is uncertain, and likely heterogenous, but

in myocarditis? there may be a close HLA match between viral
proteins and the myocardium, or autoimmune, or
direct induction of apoptosis.

How common is It shows up on 0.5% of all autopsies.

myocarditis?

What elements predict Short time interval between disease onset and
recovery in virally induced presentation as well as fairly low filling
myocarditis? pressures (e.g., PCWP <20 mm Hg)

Do steroids help in the There are no good studies to answer this

treatment of virally question.
induced myocarditis?

How often does LV Improvement in LV function occurs about 50% of

function improve in the time.
patients with viral
myocarditis, alcohol-
induced myocarditis, or
peripartum myopathies?

What are the restrictive Impairment of myocardial relaxation (i.e.,

cardiomyopathies? diastolic dysfunction)

What are some examples Amyloidosis, eosinophilic infiltration, and

of restrictive hemochromatosis
cardiomyopathies?
What is a hypertrophic Impaired relaxation due to disordered
cardiomyopathy? hypertrophy of the myocardium

Do all hypertrophic The classic is HOCM, but there are variations,

cardiomyopathies have including progressive apical thickening and
impairment to LV outflow? generalized myocardial thickening.

What is IVNC? An ill-defined cardiomyopathy thought to result

from an arrest in the normal compaction of the
loose myocardial meshwork during fetal
development

What are the characteristic Isolated regions of thickened myocardium with

findings of IVNC on deep myocardial trabeculations
echocardiography?

What is Takotsubo's An apical ballooning syndrome (also called

cardiomyopathy? broken heart)

What group of people are It usually occurs in women under stressful

more prone to this situations.
cardiomyopathy?

What is the natural history 90% or more of affected individuals recover over
of this cardiomyopathy? time.

What is the standard ACE-I plus a beta-adrenergic blocker.

therapy for patients with
systolic dysfunction?

What are some potential Hypotension, renal failure (in patients with
side effects of ACE-Is? bilateral renal artery stenosis), hyperkalemia,
allergic reactions (the most serious of which is
angioedema), and cough

Are ARBs as good as ACE-Is Probably. They can also be used as add-on
in reducing mortality in therapy to ACE-Is.
patients with LV systolic
dysfunction?

If ACE-Is and ARBs are Hyperkalemia, hypotension, and renal failure

used together, what are
the potential
complications?

If ACE-Is or ARBs are not Hydralazine and isosorbide

tolerated, what drug
combination is generally
used?

Is there a specific group of African Americans

patients to whom
 hydralazine and isosorbide
may offer a mortality
benefit in addition to ACE-
I and beta-adrenergic
blockers?

If an aldosterone inhibitor The potassium level. It is suggested that labs

is added onto a regimen of should be drawn at 1 week, 1 month, and then
a beta-adrenergic blocker every 3 months.
and ACE-I, what must be
followed?

What are potential Arrhythmias (e.g., sinus tachycardia, VT, VF),

cardiovascular side effects hypotension (all vasodilate), and tolerance
of inotropic medications? secondary to beta-adrenergic receptor
downregulation

What is the cardiorenal Worsening renal function noted in patients with

syndrome? heart failure.

How is this diagnosed? A $0.3 mg/dL rise in serum creatinine

Why is the cardiorenal It is associated with a longer stay in the hospital,

syndrome an issue? more days in the ICU, more rapid readmission
rates, and worse in- and out-of-hospital
prognosis.

P.100

Transplant
What medications lower Dilantin, phenobarbital, rifampin, and isoniazid
cyclosporine or
tacrolimus levels?

What medications Macrolides (e.g., erythromycin), ketoconazole,

increase cyclosporine or itraconazole, diltiazem, and amiodarone
tacrolimus levels?

What medications may Aminoglycosides, amphotericin, nonsteroidal anti-

potentiate renal inflammatory agents
dysfunction when used
with cyclosporine or
tacrolimus?

Besides cyclosporine and Sirolimus

tacrolimus, what is a
third IL-2 inhibitor
approved for use?

What are some of the Marrow suppression, lymphoma, nonlymphoma

side effects of malignancies, diarrhea, and hyperlipidemia
mycophenolate mofetil?
 Name six side effects of Glucose intolerance, adrenal insufficiency if
steroids. acutely withdrawn, cataracts, osteoporosis,
cushingoid appearance, and skin fragility

What medications should Adenosine and digoxin. A transplanted heart is

not be used to treat SVT more sensitive to adenosine and adenosine may
after heart cause prolonged and/or fatal asystole. Digoxin is
transplantation? ineffective due to lack of vagal innervation.

Does reinnervation of the Yes; 75% of heart recipients show some

transplanted heart ever sympathetic reinnervation after 1 year. A smaller
occur? number show parasympathetic innervation.

Does reinnervation have Yes; patients with reinnervation have improved

any practical implication? exercise performance (faster HR response), and
some recipients in whom CAD develops complain
of chest pain.

What noninfectious Transplant-associated B-cell lymphoma, which

process can masquerade occurs in 1% to 5% of patients over time
with fever and an (frequency depends on the organ transplanted).
infiltrate after organ
transplantation?

P.101

Assist Devices
What is the IABP
most common
assist device
used in
treatment of
HF?

What are the Limb ischemia of the leg where they are inserted. Limited
disadvantages mobility due to insertion in the femoral artery and infection.
of balloon The level of support is only moderate.
pumps?

What two types Continuous and pulsatile

of flow
patterns are
associated with
LV assist
devices?

What is the It closely mimics the natural pumping of the human heart.
advantage of
pulsatile flow?

What are the The devices tend to be more complex to insert, must be
disadvantages larger than the continuous-flow devices because of the
 of pulsatile obligatory size of the pumping chamber, and must vent to
flow? the outside or into some other chamber because of the
displaced air.

P.102
P.103

Pericardial Disease

Acute and Chronic Pericarditis

What are some The common ones are systemic lupus, rheumatoid arthritis,
of the and scleroderma. Others include Sjgren's syndrome,
autoimmune dermatomyositis, ankylosing spondylitis, Reiter's syndrome,
causes of Wegener's granulomatosis, Felty's syndrome, and serum
pericarditis? sickness.

What other Temporal arteritis, inflammatory bowel disease, Kawasaki's

autoimmune- disease, Familial Mediterranean fever, Whipple's and Behet's
type illnesses diseases.
can have
associated
pericarditis?

What are Viral (Coxsackie B, echovirus, influenza, herpes simplex

infectious virus)
causes of Bacterial (S. aureus, S. pneumoniae, and Histoplasma
pericardial capsulatum), commonly from a pleuropulmonary focus from
disease? trauma, surgery, or local spread of an abscess. Also Acute
rheumatic fever
Fungal or other infections, such as toxoplasmosis and Lyme
disease

What are some Sarcoidosis and amyloidosis

of the
inflammatory
disease causes
of pericarditis?

What are some Hydralazine and procainamide. Odd causes include penicillin,
of the common cromolyn sodium, minoxidil, dantrolene sodium, and
medications methylsergide.
that can cause
acute
pericarditis?

What is the Pericardial friction rub, which is heard best at the apex with
most important the patient leaning forward
physical finding
of pericarditis?

When does During ventricular systole, ventricular diastole, and atrial

each occur in systole. Commonly at least two components are heard.
 the cardiac
cycle?

What does the There is diffuse ST elevation and PR depression

ECG show in
patients with
acute
pericarditis?

What else Atrial infarction, which is uncommon

causes PR
depression?

How is chronic There is chronic and generally relapsing pain after a bout of
pericarditis acute pericarditis
recognized?

What are the Pleuritic chest pain and often a rub

symptoms and
signs of
chronic
pericarditis?

What is the Search for an underlying cause (e.g., infection). NSAIDs and
treatment for colchicines are the mainstays of treatment. Steroid use
chronic should be avoided if possible. Other agents, such as
pericarditis? azathioprine, and other immunosuppressants may be helpful.
Pericardial resection has also been reported.

P.104

Effusions and Tamponade

What is a A drop of $12 mm Hg in the systolic blood pressure during
pulsus inspiration.
paradoxus?

How is a The BP cuff is inflated and lowered to the first Korotkoff sound
pulsus (which is audible initially only during expiration). The cuff is
paradoxus then slowly deflated until the first Korotkoff sound is heard
exam throughout the entire respiratory cycle. The difference in
performed? systolic pressure between the first Korotkoff sound occurring in
expiration and then the Korotkoff sounds occurring throughout
the respiratory cycle is the pulsus paradoxus.

What else is Beck's triad: Decreased systolic BP, distended neck veins (with
found on rapid x descent and attenuated y descent), and distant heart
physical sounds. Sinus tachycardia is seen in most patients.
examination
of
pericardial
tamponade?
Constrictive Pericarditis
What are the physical Clear lungs (usually)
examination signs of Kussmaul's sign (elevation of JVP with inspiration)
constrictive pericarditis? Rapid y descent on jugular venous pulsations
Hepatic congestion

What procedures are MRI, CT, echocardiogram, and cardiac

helpful in making a catheterization
diagnosis of constrictive
pericarditis?

What is seen on MRI in Demonstrates pericardial thickening and adhesion

pericardial constriction? to the epicardium

What is seen on the Can sometimes demonstrate pericardial adhesions,

echocardiogram in stranding, or thickening. The atria are commonly
pericardial constriction? enlarged with normal-sized ventricles.

What is seen on CT in The same as the echocardiogram. Sometimes the

pericardial constriction? pericardial thickness can be exaggerated by
tangential cuts.

What is seen on the Elevation of all the diastolic filling pressures,

hemodynamic portion of similar to tamponade. In contrast to tamponade,
a cardiac however, there is an exaggerated y descent and the
catheterization in PA systolic pressure is almost never >50 mm Hg.
constrictive pericarditis?

P.105
P.106
P.107

Central and Peripheral Vascular Disease

What is the definition of Dilatation to >50% of the normal vessel size
an aneurysm?

What is the diameter of 3 cm

a normal ascending
aorta?

Where are most 50% ascending, 10% arch and 40% descending
thoracic aortic
aneurysms found?

When should you When it is around 4.5 cm

consider operating on a
patient with Marfan's
syndrome who has an
aortic aneurysm?

When should you 4.5 to 5 cm

consider operating on a
patient with a bicuspid
aortic valve?

What is Takayasu's Also called pulseless disease, Takayasu's disease is

disease? inflammation and then scarring of the aorta, major
branches, and pulmonary arteries, leading to
occlusion (hence pulselessness) or pulmonary HTN if
the pulmonary arteries are involved.

What is the cause of Thought to be secondary to an autoimmune

Takayasu's disease? process. It affects women 9:1 over men.

What are the causes of Marfan's syndrome and other connective tissue
aortic dissections? abnormalities (Ehlers-Danlos)
Cystic medial necrosis (without overt Marfan's
syndrome)
Bicuspid aortic valves and aortic coarctation
(predisposing factors to dissection)
Pregnancy (with 50% of dissections occurring in
women younger than 40 years of age during the last
trimester of pregnancy; often associated with
coronary dissection)
Trauma, possibly causing a tear in the aorta at the
isthmus

What are the common Shock, although, initially 50% of patients are
physical examination hypertensive
features of a dissecting Pulse deficits (right-to-left difference; occurs in
aorta? 50% of proximal dissections and may occur in distal
dissection secondary to compression of the
subclavian artery)
Aortic regurgitation (50% of patients with proximal
events; may cause severe, rapid-onset CHF)
Neurologic deficits

What are the causes of Cardiac tamponade

hypotension during an Intrapleural or intraperitoneal rupture
aortic dissection? Pseudohypotension (impingement on the
brachiocephalic vessels by the dissecting hematoma
interfering with BP measurement)
RV failure (IMI)
Bradycardia (IMI rhythms)

What is the mortality 50%; roughly 1% mortality/hour

rate for medical
treatment in patients
with type A dissections
in the first 48 hours?

What are the indications Evidence of continued dissection (pain) or organ or

to operate on a type B limb ischemia.
dissection?
What is the surgical 10% to 20% if uncomplicated and up to 60% if
mortality rate for a type complicated
B dissection?

What is the diameter of <2 cm

a normal descending
aorta (at the level of
the renal arteries)?

What percentage of the 1% to 4%

general population has
an AAA?

What percentage of 50% (the larger the aneurysm, the greater the
abdominal aneurysms percentage); 80% if symptomatic
larger than 6 cm will
rupture by 1 year?

How is an aortic rupture Patients complain of severe back and abdominal

recognized? pain and present with hypotension or the
appearance of frank hemorrhagic shock. Most
patients have a palpable pulsatile abdominal aorta.

What is the mortality 50% to 80%

rate for a recognized
rupture of an AAA?

How common is Symptomatic in 2% of adults and asymptomatic in

peripheral vascular 10%
disease?

How common are 25% of patients with PAD require an amputation at

amputations in patients 1 year and only 50% are alive with two legs at 5
with PAD? years

In patients with PAD, 20% iliac arteries, 40% femoral arteries, 20% lower
where are the stenoses limb arteries, and 20% diffusely
located?

What are the six Ps of Pain, paresthesias, paralysis, pallor, pulselessness,

acute arterial occlusion? poikilothermy

What should you think Small vessel disease (DM) and spinal stenosis
of in a patient who
complains of
claudication symptoms
but has good distal
pulses or good ABIs?

Where are the common Superficial femoral artery, popliteal artery, and
arterial entrapment thoracic outlet
 sites?

How is the diagnosis of When the arm is abducted to 90 degrees and

thoracic outlet externally rotated, paresthesias and numbness
syndrome made? occur, a bruit is heard over the supraclavicular
fossa, and symptoms resolve when the arm is
returned to baseline position.

What dermatologic clues Patients with venous disease usually have thick,
suggest venous rather scaly skin; those with arterial disease usually have
than arterial disease? thin, shiny skin.

Where are venous ulcers The medial malleolar area; these ulcers usually
usually seen, and what resolve and recur.
is their usual course?

P.108
P.109

Congenital Heart Disease

What are the causes of CHD with each of the following:

Left-to-right shunts ASD (secundum type)

with cyanosis? Atrioventricular septal defects (primum type)
Complete AV canal defect
VSD
Patent ductus arteriosus (PDA)
Truncus arteriosus
Tricuspid atresia with a VSD

Right-to-left shunts Tetralogy of Fallot

(cyanosis)? Ebstein's anomaly
Tricuspid atresia
PA atresia with intact ventricular septum
Transposition of the great arteries
Total anomalous pulmonary venous return
Double-outlet right ventricle with pulmonary
stenosis or atresia (DORV will have a VSD)

Obstructive valvular Hypoplastic left heart syndrome

or vascular lesions (with Congenital valvular AS or AI, MS or MR
or without cyanosis)? Pulmonary vein atresia
Cor triatriatum (the left atrium fails to become a
common chamber)
Peripheral pulmonary artery stenosis (with or with a
VSD)
Tetralogy of Fallot

Transpositions? Transposition of the great arteries

Congenitally corrected transposition of the great
arteries (the aorta and pulmonary arteries are
transposed, but the RV and LV are also transposed
 leading to a functionally normal circulation)

What are some of the The left coronary artery originating from the PA
other congenital heart (ALCAPA)
defects? Atrial septal and sinus of Valsalva aneurysms
AV fistula
Double-outlet right ventricle without pulmonary
stenosis
Congenital heart block

What is Eisenmenger's Any CHD with consequent pulmonary HTN and

syndrome? reversal of flow to right to left (e.g., ASD, VSD,
patent ductus, and AP window)

What is a Blalock- A connection created between the systemic

Taussig shunt? circulation and the PA (e.g., the subclavian artery
and PA)

Why is this performed? To establish or improve blood flow to the lung (and
hence oxygenation)

What is a Fontan Anastomosis of the IVC or right atrium to the

procedure? pulmonary artery. A bidirectional Glenn adds the
SVC to PA anastomosis.

What are the acyanotic Bicuspid aortic valve, supra-aortic or subaortic

forms of CHD seen in valvular stenosis, aortic coarctation, valvular PS,
adults? ASD, patent ductus unless associated with
Eisenmenger's syndrome, and corrected TGA

What are the cyanotic Tetralogy of Fallot; VSD, some ASDs, and some PDAs
forms of CHD seen in when associated with Eisenmenger's syndrome;
adults? atrioventricular septal defect (formerly AV canal
defect); pulmonary atresia with a VSD, and Ebstein's
anomaly

What are the VT, atrial fibrillation, RV failure due to obstruction,

complications seen in and pulmonary hypertension
adult patients who have
had a TOF repair?

For the long-term care Endocarditis prophylaxis

of patients with CHD,
what else is important
to remember prior to
procedures?

P.110

Neoplasms
What is the location of most myxomas? LA (75%). Myxomas in children
are found in increased
 frequency in the ventricle.

What is the classic examination feature of A tumor plop (occurs when the
a myxoma? patient shifts position)

What percentage of metastatic tumors 5%

affect the myocardium?

What percentage of metastatic tumors 10%

affect the pericardium?

What metastatic tumors most frequently Bronchogenic carcinoma, breast

involve the heart (endocardium, cancer, leukemias, and
myocardium, and pericardium)? lymphomas

Major Trials in Cardiology

The following is a list of the pivotal trials in cardiology, with references.

Primary Prevention Studies

WOSCOPS: Pravastatin versus placebo was studied in 6595 men with hyperlipidemia
(average cholesterol 272 mg/dL, average LDL 192 mg/dL) followed for a mean of 4.9
years; 31% relative risk (RR) reduction in MI or death (1.6% versus 2.3%, P < 0.001),
similar reduction in nonfatal MI (31%) and cardiovascular death (28%) with
pravastatin. N Engl J Med 1995;333:13011307.

P.111

Secondary Prevention
CAPRIE: Clopidogrel versus ASA was studied in 19,185 patients with known
atherosclerotic disease (CVA/MI/PVD) followed for a mean of 2 years; 9.4% RR
reduction in death/MI/CVA (5.32% versus 5.83%, P = 0.043) in the clopidogrel group.
Lancet 1996;348:13291339.

PROVE IT-TIMI 22: High-dose atorvastatin (80 mg) versus standard therapy
(pravastatin 40 mg) was compared in 4162 patients with ACS with a mean follow-up
of 24 months. The composite triple endpoint of death, myocardial infarction, and
rehospitalization for recurrent ACS was assessed at 30 days (3.0% of atorvastatin
patients versus 4.2% of pravastatin patients, P < 0.046) and demonstrated a hazard
reduction of 24% after the mean of 24 months (15.7% versus 20.05%, P = 0.0002).
There was also a highly significant difference in LDL between the atorvastatin and
pravastatin groups (60 mg/dL versus 88 mg/dL). J Am Coll Cardiol. 2005;46:1405
1410.

Asymptomatic CAD
ASTEROID Trial: A total of 507 patients with coronary artery disease were treated
with rosuvastatin 40 mg after a baseline IVUS study and followed up at 24 months
with a repeat IVUS. There was a 53% reduction in LDL (130.4 mg/dL to 60.8 mg/dL,
P < 0.001). The mean reduction in atheroma volume for the group was 0.98% for the
entire vessel; for the most diseased 10 mm, there was a 6.8% median reduction (P <
0.001 compared to baseline). 1.2% of patients had a CK elevation of >5 times the
upper limit of normal, but only 0.2% had elevation on two sequential visits. There
were no occurrences of rhabdomyolysis. Likewise, 1.8% of patients had an elevation
in ALT >3 times the upper limit of normal, with 0.2% having an elevation on two
sequential visits. JAMA 2006;295:15561565.

COURAGE Trial: Optimal medical treatment was compared with PCI in 2287 patients
with stable angina. All patients were treated to an LDL of 60 to 85 mg/dL; 95% of
patients had ischemia and 69% of those with multivessel disease. At 5 years, the
primary endpoint of death occurred in 18.5% of the medical treatment patients and
19.0% of the PCI group (P = 0.62). No difference was noted for the secondary
endpoint of death, MI or stroke. At 3 years, the PCI group averaged $5295 higher
than the medical treatment group (P <0.0001).

Stents
RAVEL: A total of 238 patients with primary native single coronary lesions were
randomized to sirolimus coated (2.5 to 3.5 mm and <18 mm length) or bare metal
stents. At 6 months, late lumen loss was significantly less in the sirolimus group
compared with the bare metal stent group (0.01 mm versus 0.9 mm, P < 0.001).
Stent restenosis was 26.6% in the bare metal
P.112
group versus 0% in the sirolimus group at 6 months (P < 0.001). N Engl J Med
2002;346:17731780.

TAXUS I NIRx: A total of 61 patients with de novo or restenotic lesions with vessel
diameter 3.0 to 3.5 mm and <15 mm in length were randomized to paclitaxel versus
bare metal stents. Major adverse events had occurred in 3% of the paclitaxel group
and 10% of the control group at 12 months. Minimal lumen diameter, diameter
stenosis, and late lumen loss were all significantly less in the paclitaxel group (P <
0.01 for all three categories). Circulation 2003;107:3842.

REPLACE-2: A total of 6010 patients undergoing urgent or elective PCI were

randomized to IV bivalirudin (0.75 mg/kg bolus + 1.75 mg/kg/hr during the PCI)
IIb/IIIa versus heparin IIb/IIIa inhibitor. Patients were followed for 30 days for the
primary endpoint of death, MI, urgent repeat revascularization, or in-hospital
bleeding and the secondary endpoint of death, MI, or urgent repeat
revascularization. The primary endpoint occurred in 9.2% of those receiving
bivalirudin and 10.0% of the heparin group (P = 0.32). The secondary endpoint
occurred in 7.6% of the bivalirudin group and 7.1% of the heparin patients. In-
hospital bleeding occurred less often in the bivalirudin group (2.4% versus 4.1%; P <
0.001). JAMA 2003;289:853863.

USA/NSTEMI
ESSENCE: Enoxaparin versus heparin was studied in 3171 patients with USA/NSTEMI
followed for 30 days; the result was 16% and 15% RR reduction in death/MI/recurrent
ischemia at 14 days (16.6% versus 19.8%, P = 0.019) and 30 days (19.8% versus 23.3%,
P = 0.016) in the enoxaparin-treated patients N Engl J Med 1997;337:447452.

TIMI 18 (TACTICS): In a comparison of early invasive versus early conservative

strategy, 2220 patients with NSTEMI were treated with ASA/heparin/tirofiban and
randomized to catheterization within 4 to 48 hours versus early conservative
strategy and followed out to 6 months; the result was a 22% RR reduction in
death/MI/rehospitalization in the early invasive strategy (15.9% versus 19.4%, P =
0.025) at 30 days and a 26% RR reduction in death/MI at 6 months (7.3% versus 9.5%,
P <0.05) N Engl J Med 2001;344:18791887.

PURSUIT: Eptifibatide/heparin versus ASA/heparin was studied in 10,948 patients

with USA/NSTEMI followed for 30 days; the result was an 11% RR reduction in
death/MI (14.2% versus 15.7%, P = 0.04) for the eptifibatide group. N Engl J Med
1998;339:436443.

SYNERGY: This was a safety and efficacy trial of enoxaparin compared with UFH in
high-risk ACS patients treated with an early invasive strategy. The primary endpoint
of death or nonfatal MI at 30 days occurred in 14% (enoxaparin) versus 14.5% (UFH)
and met the noninferiority criteria.
P.113
However, in the patients not pretreated with antithrombotic therapy or those who
were pretreated but continued on the same therapy postrandomization, there was a
lower rate of death or MI with enoxaparin. JAMA 2004;292:4554.

ACUITY: A total of 9207 patients with moderate- to high-risk ACS undergoing an

invasive strategy were randomized to IIb/IIIa use as an initial strategy (upstream use)
versus deferred/selective use in the catheterization lab. At 30 days, death, MI, or
unplanned revascularization for ischemia occurred in 7.1% of patients in the
upstream use group versus 7.9% of patients in the selective use group (P = 0.044 for
noninferiority). Selective/deferred use was associated with less major bleeding (4.9%
versus 6.1%, P < 0.001 for noninferiority and P = 0.009 for superiority) JAMA
2007;297:591602.

STEMI
ExTRACT-TIMI 25: Fibrinolysis followed by randomization to UFH or enoxaparin was
studied in 20,506 patients. Patients were given 7 days of SQ enoxaparin versus at
least 48 hours of UFH. At 30 days, death or nonfatal recurrent MI outcome was
significantly less frequent in the enoxaparin group (9.9% versus 12%; P < 0.001). At
30 days, major bleeding was slightly more frequent in the enoxaparin group (2.1%
versus 1.4%, P < 0.001). All 4676 patients in the cohort were treated with PCI with
similar results (death + nonfatal MI; 10.7% with enoxaparin versus 13.8% with UFH, P
= 0.001) with no difference in major bleeding (1.4% enoxaparin versus 1.6% UFH, P =
0.56). N Engl J Med 2006;354:14771488.

OASIS-5: A total of 20,078 patients with acute coronary syndromes received either
fondaparinux (2.5 mg daily) or enoxaparin (1 mg/kg/bid) for a mean of 6 days. At 9
days, 579 patients treated with fondaparinux and 573 patients treated with
enoxaparin experienced the primary endpoint of death, MI, or refractory ischemia (P
= NS). At 30 days, there was a trend favoring the fondaparinux group (805 patients
versus 864 patients; P = 0.13), and also at 6 months (1222 patients versus 1308
patients; P = 0.06). Major bleeding occurred less often in the fondaparinux group at
all time points (9 days: F 217, E 412; 30 days: F 313, E 494; 180 days: F 417, E 569;
p = NS). N Engl J Med 2006;354:14641476.

SHOCK trial (follow-up): A total of 302 patients who presented with STEMI and
cardiogenic shock within 36 hours of admission were randomized to early invasive
therapy versus initial medial stabilization. Among patients randomized to early
revascularization, there was no difference between CABG and PCI. At 1, 3, and 6
years there was a 13% to 13.2% absolute reduction in mortality in the early invasive
group (P < 0.05 at all three time points). JAMA 2001;285:190192; JAMA
2006;295:25112515.

P.114

Heart Failure
MERIT-HF: Metoprolol CR/XL versus placebo was studied in 3991 patients (on ACE-I)
with class II to IV CHF followed for an average of 1 year; the study was terminated
early because of a 34% RR reduction in mortality (7.2% versus 11.0%, P < 0.0062) in
the metoprolol group. Lancet 1999;353:20012007.

REMATCH: A total of 129 patients with severe heart failure not eligible for cardiac
transplantation were randomized to device therapy with the HeartMate LVAD versus
optimal medical therapy (OMT); 68 patients received LVAD and 61 OMT. At 1 year,
survival was 52% in the LVAD patients and 25% in the OMT group (P = 0.002). At 2
years, survival was 23% in the LVAD group and 8% in the OMT group (P = 0.09). A
serious adverse event (infection, bleeding, or device malfunction) was 2.35 times
more likely to occur in LVAD-treated patients. N Engl J Med 2001;345:14351443.

COMET: Carvedilol versus immediate release metoprolol was studied in 3029

patients with primarily class II to III CHF with an average daily dose of 42 mg
carvedilol and 85 mg metoprolol. Patients were followed for a mean of 58 6 (SD)
months. The primary endpoint of all-cause mortality was improved in the carvedilol
group (33.9% versus 39.5% in the metoprolol group, P = 0.0017). The coprimary
endpoint of all-cause mortality or all-cause hospitalization did not have statistical
significance. Lancet 2003;362:713.

CARE-HF: A total of 813 patients were followed for 29.4 months and randomized to
biventricular pacing or medical therapy. The primary endpoint of death from any
cause or cardiovascular hospitalization occurred in 39% of the biV group (159
patients) and 55% of the medical therapy group (224 patients; P < 0.001). Other
findings included reduction in LV end-systolic volume, MR jet, ejection fraction, and
quality of life (P < 0.01). N Engl J Med 2005;352:15391549.

Atrial Fibrillation/Sudden Death Trials

AFFIRM: A total of 4060 patients with atrial fibrillation were randomized to rate
versus rhythm control and followed for a mean of 3.5 years; 26% had a reduced
ejection fraction, 39% were women, 70.8% had hypertension, and 38.2% had CAD. In
the rate-control group, 21.3% of patients died; 23.8% died in the rhythm-control
group (P = 0.08). In addition, 77 patients experienced strokes in the rate-control
and 80 in the rhythm-control group. Most patients experienced strokes when
warfarin was discontinued or when the warfarin was subtherapeutic. More patients
in the rhythm-control group were hospitalized with drug-related side effects. N Engl
J Med 2002;347:18251833.

MADIT-II: ICD versus conventional therapy was studied in 1232 patients with CAD and
LVEF <30% who had had a least one MI. The study was
P.115
stopped early owing to a 31% RR reduction in mortality in the ICD arm (P = 0.016)
when followed for an average of 2 years. The survival benefit was seen after 9
months. N Engl J Med 2002:346:877883.

SCD-HeFT: ICD versus amiodarone or placebo when added to standard medical

therapy was studied in 2521 patients with class II to III CHF due to ischemic and
nonischemic causes and LVEF <35%. After a median follow-up of 45 months, ICD
patients had a reduction in all-cause mortality of 23% when compared with placebo
(17.1% versus 22.3%, P = 0.007). N Engl J Med 2005;352:225237.

Postinfarction
AIRE: Ramipril versus placebo was studied in 2006 patients with therapy initiated on
day 3 to 10 after STEMI with clinical evidence of CHF at any time after the MI and
followed for an average of 15 months; a 27% RR reduction in all-cause mortality was
found in the ramipril-treated patients (17% versus 23%, P = 0.002). Lancet
1993;342:821827.

TOAT: A total of 223 patients approximately 1 month following a LAD related STEMI
with no evidence of ischemia were randomized to elective PCI versus medical
therapy. The PCI group had an increase in LV volume (systolic:diastolic; 106.6
37.5/162.0 51.4) compared to the medical treatment group (79.7 34.4/130.1
46.1), P < 0.01 for both. The PCI group did show an increase in exercise time
compared with the medical treatment group (P = 0.05). Quality of life (impact on
lifestyle) was reduced in the medical treatment arm and remained stable in the PCI
group (P = 0.025). J Am Coll Cardiol 2002;40:869876.
Editors: Bergin, James D.
Title: Advanced Medicine Recall, 1st Edition
Copyright 2009 Lippincott Williams & Wilkins

> Table of Contents > Section II - The Specialties > Chapter 4 - Endocrinology

Chapter 4
Endocrinology

Abbreviations
ACTH Adrenocorticotropic hormone

ADH Antidiuretic hormone

AI Adrenal insufficiency

BMD Bone mineral density

BUN Blood urea nitrogen

CRH Corticotropin-releasing hormone

CT Computed tomography

DCCT Diabetes Control and Complications Trial

ddAVP 1-desamino-8-d-arginine vasopressin

DHEA-S Dehydroepiandrosterone-sulfate

DI Diabetes insipidus

DKA Diabetic ketoacidosis

DTR Deep tendon reflex

FSH Follicle-stimulating hormone

GFR Glomerular filtration rate

GH Growth hormone

GLP Glucagon-like peptide

GnRH Gonadotropin-releasing hormone

GHRH Growth hormonereleasing hormone

hCG Human chorionic gonadotropin

HHS Hyperglycemic hyperosmolar states

IDDM Insulin-dependent diabetes mellitus

IGF Insulin-like growth factor

ITT Insulin tolerance test

IVF Intravenous fluids

LH Luteinizing hormone

MEN Multiple endocrine neoplasia

MRI Magnetic resonance imaging

MSH Melanocyte-stimulating hormone

NIDDM Noninsulin-dependent diabetes mellitus

NPH Neutral protamine Hagedorn

PCOS Polycystic ovary syndrome

PO By mouth

PPI Protein pump inhibitor

PRL Prolactin

PTH Parathyroid hormone

PTHrP Parathyroid hormone related protein

 PTU Propylthiouracil

RAI Radioactive iodine

SERM Selective estrogen receptor modulators

SIADH Syndrome of inappropriate ADH

T3 Triiodothyronine

T 3RU T3 resin uptake

T4 Thyroxine

TB Tuberculosis

TBG Thyroxine-binding globulin

TPO Thyroid peroxidase antibody

TRH Thyrotropin-releasing hormone

TSH Thyroid-stimulating hormone (thyrotropin)

TSS Transsphenoidal surgery

UKPDS United Kingdom Prospective Diabetes Study

UTI Urinary tract infection

VIPoma Vasoactive intestinal peptide (oma)

P.118

Endocrine Emergencies
Name five endocrine 1. Pituitary apoplexy or sudden loss of
emergencies. pituitary function
2. Thyrotoxic crisis (thyroid storm)
3. Myxedema coma
4. Addisonian crisis/acute adrenal insufficiency
5. Hyperglycemic crisesDKA and HHS
Pituitary Emergencies
What is pituitary The clinical syndrome that occurs after a sudden
apoplexy? infarction or hemorrhage into the pituitary gland

What are some causes Hemorrhagic infarction of a pituitary tumoroften an

of pituitary apoplexy? adenoma, which is a neurosurgical emergency
Head trauma, skull base fractures, stalk compression.
Hypertension, sickle cell, diabetes, and acute
hypovolemic shock/hypoperfusion can precipitate this
as well.

What are the most Sudden onset severe headache (frontal or retro-
common presenting orbital) and visual field defects
features of pituitary
apoplexy?

What are some Neck stiffness, nausea, vomiting, progressive cranial

additional presenting nerve dysfunction
features of pituitary Hypotension, visual disturbances, hypoglycemia, fever,
apoplexy? and altered consciousness; even coma can occur

How is it diagnosed? CTfavored in acute setting (MRI in the subacute

setting) with evidence of bleed, mass, pituitary
trauma

How is pituitary Urgent neurosurgical consultation for possible

apoplexy managed? transsphenoidal surgery. Indicated for failure of optic
tract pressure to resolve or progressive pituitary
compression.
Stress-dose corticosteroids (100 mg hydrocortisone IV
q8h or 4 mg dexamethasone IV q8h) until stability is
achieved.
Most patients will require long-term cortisol, thyroid,
and gonadal steroid replacement.

What features suggest Hypernatremia, polyuria, and polydipsiafrom central

posterior pituitary diabetes insipidus (loss of vasopressin secretion)
trauma or loss of occur in ~4% of cases of pituitary apoplexy.
function?

P.119
P.120
P.121
Thyroid Emergencies
What is thyroid Clinically severe or accelerated thyrotoxicosis that
storm? results in multiorgan and multisystem dysfunction

What are some High fever and profuse sweating

characteristic Altered mental statusdelirium, psychosis, seizures; if
features of thyroid untreated, coma can develop
storm? Hyperreflexia, hyperkinesis
Tachycardia or arrhythmia, systolic hypertension, wide
pulse pressure
High-output heart failure and pulmonary edema
Gastrointestinal hypermotility, nausea, vomiting

What is the most Graves' disease most commonly, and less commonly
common underlying multinodular goiter
medical condition in
which thyroid storm
occurs?

What are the Most often a thyroid event in a patient with preexisting
precipitants of thyroid disease:
thyroid storm? Thyroid manipulationsurgery, radioiodine therapy,
iodinated contrast or withdrawal of antithyroid
medication
Systemic insult/stress:
Infection, MI, trauma, surgery, DKA, parturition

Do thyroid hormone No, and they are often not significantly greater than
levels correlate with those in clinically milder forms of thyrotoxicosis.
illness severity?

In general terms, 1. Supportive care usually in the ICU: oxygen,

how is thyroid storm mechanical ventilation if needed, BP control, fluids,
managed? cooling blankets, antipyretics.
2. Treat thyrotoxicosis.
3. Search for and treat the underlying cause and
precipitant if possiblee.g., infection, MI.

How is thyroid Propylthiouracil (PTU) is the preferred drug (600- to

hormone synthesis 1000-mg load, then 200 to 300 mg PO q6h). An
blocked? alternative is methimazole (60- to 100-mg load, then
30 to 60 PO mg q8h).

How is the release Inorganic iodine 2 hours after giving PTU/methimzole

of preformed (e.g., saturated solution of potassium iodide, 5 drops
thyroid hormone PO q6h)
blocked?

What do steroids do Steroids block the release of thyroid hormone, decrease

in the treatment of conversion of T4 to T3 , and cause immunomodulation in
thyrotoxicosis? Graves' cases (dexamethsone 2 mg PO q6h or
hydrocortisone 100 mg IV q6h to q8h).

How are beta Propranolol (40 to 80 mg PO q6h), labetalol, esmolol

blockers used? drip, oppose beta-adrenergic effects and reduce
conversion of T4 to T3 (propranolol).

Why is PTU At high doses it inhibits conversion of T4 to T3 .

advantageous over
methimazole in
thyroid storm?

Which drug is safer PTUit is less likely to cross the placenta and enter
to use in pregnancy breast milk, but it should still be used with caution.
and lactationPTU
or methimazole?

What is myxedema The term is used to describe progressive dysfunction of

coma? the cardiovascular, respiratory, and central nervous
systems as a result of critical hypothyroidism; however,
patients do not usually present in myxedema or coma.

What is myxedema? Generalized skin and soft tissue swelling characterized

as harder, generally nonpitting edema, sometimes
associated with periorbital edema, macroglossia, and
ptosis.

What causes Decreased clearance of glycosaminoglycans in

myxedema? interstitial fluid as a result of severe hypothyroidism.

What are the Hypothermia and altered mental status

systemic Delayed relaxation phase of deep tendon reflexes
manifestations of Bradycardia, hypotension, pericardial effusion
myxedema coma or Hypoventilation
severe Constipation, ileus, megacolon
hypothyroidism? Decreased GFR and hyponatremia

Who is at greatest The elderly with preexisting hypothyroidism during the

 risk for myxedema winter months
coma?

What are some Cold exposure

precipitants of Trauma, burns, surgery
myxedema coma? Infection, sepsis
MedicationsCNS depressants, anesthetics, narcotics

What are the 5 H's Hypothermiapassively rewarm (blanket, warm room)

of myxedema coma Hypoventilationoxygen, mechanical ventilation
and their supportive HypotensionIsotonic IVF, blood if anemia
treatments? Hyponatremiafree water restriction and saline
infusion
HypoglycemiaIV dextrose with isotonic fluid

Why is active It can result in vascular collapse from vasodilatation.

rewarming
contraindicated?

What is the 1. Thyroid replacementT 4 500 !g IV loading dose,

hormonal therapy
followed by 50 to 100 !g daily thereafter
for myxedema
2. Empiric steroidshydrocortisone 100 mg IV q8h or
coma?
dexamethasone (2 to 4 mg IV q8h) until adrenal
insufficiency is ruled out

What initial TSH, free T4 , and random cortisol (if <25, continue
hormone levels steroids; if >25, can discontinue steroid replacement)
should be checked?

Once therapy for Improvement is usually seen within hours.

myxedema coma is
started, what is the
time course for
improvement?

P.122
P.123
P.124
P.125
P.126
P.127

Adrenal Emergencies
How does acute Acute circulatory failure and hypotension
adrenal insufficiency Fever, nausea, vomiting, and abdominal pain
or Addisonian crisis
present?

Who is at greatest Patients with preexisting Addison's disease or adrenal

risk for adrenal insufficiency subjected to sudden stress or those who
crisis? omit glucocorticoid therapy

What are some precipitants of adrenal crisis

In patients with Omission of steroid therapy, failure to increase dose in

known adrenal stressful settings, or undiagnosed disease in the setting
insufficiency? of an illness or systemic stressor
Infection, surgery, trauma, burns

In patients without Bilateral adrenal hemorrhage or infarction

known adrenal Pituitary apoplexy
insufficiency?

What lab tests Simultaneous ACTH and cortisol, plasma electrolytes,

should be ordered if and blood glucose
acute adrenal
insufficiency is
suspect?

What electrolyte In primary adrenal insufficiency aldosterone secretion is

abnormalities will be also deficient, so hyponatremia and hyperkalemia are
present in primary usually both present.
adrenal
insufficiency?

What electrolyte In secondary adrenal insufficiency, aldosterone is

abnormalities will be intact, so potassium and salt regulation will be
present in secondary relatively normal, although hyponatremia will still
(pituitary) adrenal occur from glucocorticoid absence.
insufficiency?

What stress A random cortisol of >25 !g/dL in the setting of

cortisol level significant stress is generally accepted as adequate,
suggests an although there is some controversy about what
appropriate constitutes a normal cortisol response to stress.
response?

What doses of Hydrocortisone 100 mg IV or IM q6h (or dexamethasone

steroids are used to 4 mg IV q12h if unable to draw blood samples for
treat an adrenal cortisol prior to treatment).
crisis?

During an adrenal 1 L of D5 0.9% saline immediately, then 3 to 4 L in the

crisis, what other next several hours with continued fluids as per patient's
treatment is condition and needs (electrolytes, volume status)
needed?

What is the next Evaluate and treat the underlying illness (e.g.,
critical step in the infection, adrenal hemorrhage).
treatment of an
adrenal crisis?

What defines Blood glucose >250 mg/dL

diabetic ketoacidosis Arterial pH <7.3
(DKA)? Serum bicarbonate <15 meq/L
Moderate ketonemia or ketonuria

What defines the Blood glucose >600 mg/dL

hyperosmolar Serum total osmolality >330 mOsm/kg
hyperglycemic state Arterial pH "7.3
(HHS)? Serum bicarbonate >18 meq/L
Mild ketonemia or ketonuria

What types of Type 1 and type 2 diabetics can present with either
diabetics present depending on the relative degree of insulin deficiency
with DKA and HHS? and counterregulatory hormone excess.
Type 1 classically associated with DKA.
Type 2 classically associated with HHS.

What are the Altered mental status, variable degrees of lethargy,

general features of a dehydration, polyuria and polydipsia
hyperglycemic
crisis?

What features are Abdominal pain, sweet acetone breath, rapid and
more characteristic deep Kussmal respirations
of DKA?

What features are More severe dehydration and hypovolemia; also

more characteristic electrolyte disturbances
of HHS? Focal neurologic deficits, movement disorders, and
seizures

What are the three Infections (30% to 50% of which are pneumonias or
most common UTIs)
precipitants of Omission of, or inadequate, insulin therapy
hyperglycemic crises Myocardial ischemia or infarction
(DKA and HHS)?

What are the typical ~6 L in DKA

total body water ~9 L in HHS
deficits in DKA and
HHS?

What are the five Volume replacement

major components Insulin replacement
of management for Potassium and electrolyte management
DKA and HHS? Acidosis/bicarbonate management
Treatment of precipitating event or cause

How are the following managed in both DKA and HHS?

Volume replacement:

First hour Give 1 L of NS within first hour of treatment prior to

starting insulin.

Hours 2 to 4 Continue IVF at 500 to 1000 mL/hr of 0.45% or 0.9%

saline depending on hydration and volume statusavoid
exceeding 50 mL/kg in the first 4 hours.

Why should 50 To reduce risk of cerebral edema

mL/kg be the limit
in the first 4 hours?

Insulin therapy: IV bolus of regular insulin (0.15 U/kg), then

0.1 U/kg/hr IV infusion until resolution of DKA or HHS

What is the general Goal is a fall in blood glucose of 50 to 70 mg/dL/hr. If

goal of insulin this does not occur, either fluid resuscitation or insulin
therapy with regard dosing is inadequate. If fluids are adequate, double the
to the fall in blood amount of infused insulin.
glucose?

When should Add dextrose to fluid when blood glucose is #250

dextrose be added mg/dL in DKA and #300 mg/dL in HHS.
to the fluid
resuscitation?
What signs signal the No gap, pH >7.3, HCO 3 - >18 meq/L
resolution of DKA?

What signs indicate Total serum osmolality <315 mOsmol/kg and good
the resolution of mental status
HHS?

Potassium:

What is the first Hold insulin therapy and replace K+ with 40 meq K+
step if the (2/3 as KCL + 1/3 as Kphos or Kacetate)/L IVF until K+
potassium is < 3.3 >3.3 meq/L. Then initiate insulin.
meq/L?

What is the first Check q2h and replace when K+ <5.5 meq/L.
step if the
potassium is > 5.5
meq/L?

What is the first Replace with 20 to 30 meq K+/L IVF to maintain serum
step if the K+ at 4 to 5 meq/L.
potassium is 3.3 to
5.5 meq/L?

Phosphate:

When does Phosphate usually does not need to be replaced unless

phosphate need to it goes below 1 mg/dL.
be replaced?

How is phosphate Can give 20 to 30 meq/L fluid over several hours and
replaced? must monitor calcium levels

Sodium bicarbonate:

When is it When arterial pH is <7.0

reasonable to use
sodium bicarbonate?

How should If pH is 6.9 to 7.0, give 1 amp HCO 3 - in 250 mL sterile

bicarbonate
water + 15 meq KCl over ~1 hour
replacement be
If pH is <6.9, give double the amount over 2 to 3 hours
given?
(with total 30 meq KCl).
 How is the corrected Not all sodium levels need to be corrected; however,
sodium calculated? add 1.6 to 2.4 meq Na+ to measured sodium for every
100 mg/dL of glucose over 100 mg/dL (e.g., for blood
glucose 300 mg/dL and Na+ 134, corrected Na+ is
~137.2 to 138.8).

How is the water (0.6 $ weight in kg) $ [(Na+ /140) 1] = water deficit
deficit calculated? (in L). This formula uses corrected sodium.

How is the water Restore volume status first with 0.9% saline during the
deficit repleted? first 6 to 8 hours, then 0.45% saline can be used over
the next 24 hours to correct any remaining water
deficit.

How is total plasma 2 (Na + ) + (glucose/18) + (BUN/2.8), with the normal

osmolality range being 285 to 295 mOsm/kg
calculated?

How is effective 2 (Na + ) + (glucose/18)

osmolality Urea is an ineffective osmolar agent and passes in and
calculated? out of cells; true tonicity is reflected by effective
osmolality.

Anterior Pituitary

Diseases of the Anterior Pituitary

What six Prolactin, GH, TSH, ACTH, FSH, and LH. The secretion of
hormones are those hormones is controlled by both releasing hormones
produced in the from the hypothalamus and feedback from target-organ
anterior products.
pituitary?

P.128

Prolactinomas
How common They account for ~40% of pituitary tumors.
are
prolactinomas?

What are the Symptoms include amenorrhea (90%), galactorrhea (80% in

symptoms of women and rarely in men), infertility, and impotence in men
prolactin (75%).
excess?
 How do Women tend to present with microadenomas (<1 cm) and
prolactinomas signs of prolactin excess, most commonly amenorrhea,
present in galactorrhea, and infertility, but rarely with neurologic
women? signs.

How do Men tend to present with macroadenomas (>1 cm) and signs
prolactinomas of mass effect such as headache, visual loss, crainial nerve
present in men? dysfunction, and hypopituitarism.

How is a Elevated serum prolactin level and the absence of secondary

prolactinoma causes, with confirmation by gadolinium-enhanced MRI of
diagnosed? the pituitary. A serum prolactin >200 ng/dL is almost always
indicative of a prolactinoma.

What are Hypothyroidism, pregnancy, ovarian tumors, medications

secondary (including estrogens, phenothiazides, amitriptyline,
causes of metoclopramide, calcium channel blockers, histamine H2
elevated blockers), renal failure, stress, cirrhosis, drugs (cocaine,
prolactin levels? opioids)

What is the First-line therapy is medical with dopamine agonist

medical bromocriptine or cabergoline. Medical therapy is successful
treatment for a in decreasing tumor size and prolactin levels in the majority
prolactinoma? of cases (>70%).

What is the TSS

surgical therapy
for a
prolactinoma?

What are the If medical therapy fails, if the tumor is rapidly growing, if
indications for symptoms such as headache or vision changes persist or
surgery in worsen despite medical therapy. Radiation therapy is rarely
patients with a indicated.
prolactinoma?

What are the Nausea, fatigue, nasal stuffiness, postural hypotension

side effects of
bromocriptine?

P.129
P.130
P.131

GH/ACTH-Secreting Tumors
What percent of ~15% each
pituitary tumors
secrete GH and
ACTH?

What causes GH excess after closure of the epiphyseal plates

acromegaly?

What does GH Elevated GH stimulates secretion of IGF-1, which results in

stimulate? the insidious onset of symptoms (unfortunately, slow onset
of symptoms often delays diagnosis for years).

What symptoms Arthralgias, jaw enlargement and pain, macroglossia,

are associated sleep apnea, glucose intolerance, prominent forehead,
with acromegaly? increased hand and shoe sizes, carpal tunnel syndrome,
cardiomegaly, increased sweating, hypogonadism and
impotence, acanthosis/skin tags, and increased colon
polyps

How are GH- Check IGF-1 levels. A level >3 U/mL suggests adenoma.
secreting Confirm with glucose suppression test.
adenomas
diagnosed?

How is a glucose Measure growth hormone levels during a 2-hour period

suppression test after a standard 75-g oral glucose load. A positive test is
performed? failure to adequately suppress GH levels (GH nadir of
>0.05 !g/L after glucose load is abnormal).

What are the Transsphenoidal surgery

first-line Conventional pituitary radiation (4500 cGy), is also
therapies for a effective and has been shown to decrease GH levels to <5
GH adenoma? ng/mL in 50% of cases after 5 years.
Gamma knife radiation focused to pituitary gland

What medical Carbergoline, a dopamine agonist, may cause clinical

therapeutic improvement with a decline in IGF-1 levels in 50% of
options are patients, but this is a temporary effect.
available for GH Octreotide, a synthetic somatostatin analog, reduces GH
adenomas? secretion in most patients but has variable effects on
tumor size. Generally second line in patients who cannot
undergo surgery or radiation and were unable to tolerate
bromocriptine or cabergoline.
Pegvisomant, a GH receptor antagonist, has been
 approved for treatment of acromegaly that has not
responded to other treatments. This medication is
administered as a subcutaneous daily injection.

What is the cure The cure rate for TSS is 75% if the preoperative GH level
rate for TSS of a is <40 ng/mL and 35% if the preoperative GH level is >40
GH adenoma? ng/mL. These results vary with the experience of the
neurosurgeon.

What is the Patient's with Cushing's syndrome manifest symptoms and

difference signs attributable to excess glucocorticoid exposure
between Cushing's regardless of originexogenous versus endogenous.
syndrome and In Cushing's disease, the cause of Cushing's syndrome is
Cushing's disease? pituitary-dependent (e.g., adenoma).

What are the 1. Establish the presence of Cushing's syndrome with the
three major steps measurement of 24-hour urinary free cortisol (values
in the diagnosis of >250 !g/24 hr are diagnostic) or a low-dose
Cushing's disease? dexamethasone suppression test.
2. Determine the origin of hypercortisolismeither ACTH
dependent or independentby measuring an ACTH
level.
3. Differentiate between a pituitary and ectopic source
of ACTH. An inappropriately elevated ACTH level
should be followed up with a high-dose
dexamethasone suppression test; serum cortisol will
be suppressed by >50% in those with pituitary tumors
but not in those with ectopic ACTH production.

What is the best Between 11 P.M. and 1 A.M. This is the time of day when
time of day to ACTH secretion is at its lowest.
measure an ACTH
level in
evaluating for
causes of
Cushing's
syndrome?

What ACTH values Values above 5 pmol/L in the setting of hypercortisolism

are significant? confirm an ACTH dependent cause.

What test can be Inferior petrosal sinus sampling (IPSS)

done if the high-
dose
dexamethasone
test is
inconclusive?

How is IPSS done? A catheter is placed in each inferior petrosal sinus, an IV

bolus of CRH (100 !g) is given, and simultaneous samples
of bilateral inferior petrosal sinus blood and one
peripheral venous site are collected at regular intervals.

How is IPSS A petrosal sinus/peripheral ACTH ratio of >3.0 has a

interpreted? sensitivity of 97% and specificity of 100% in diagnosing
Cushing's disease; a ratio of <1.4 is found in patients with
ectopic ACTH syndromes.

What is the cure 90% for patients with microadenomas, 50% for those with
rate for TSS in macroadenomas.
Cushing's disease?

How is cure With cortisol levels every 6 hours for 24 hours after
assessed after surgery. If cure has been achieved, the patient's cortisol
TSS? will be <5 !g/dL. Normal levels may indicate a surgical
failure.

What are three Repeat TSS, pituitary irradiation, and medical or surgical
options for adrenalectomy
treatment in
patients who are
not cured after
TSS?

What is the TSS, with a cure rate of 80% to 90%. If TSS is unsuccessful,
treatment for treatment includes adjuvant conventional pituitary
ACTH LH, FSH, radiation or gamma knife radiation.
and TSH
adenomas?

What is Nelson's Progressive enlargement of an ACTH-producing pituitary

syndrome? tumor after bilateral adrenalectomy due to lack of
cortisol-mediated pituitary suppression

What is Sheehan's A postpartum infarct of the pituitary that results in a

syndrome? decrease in all anterior pituitary hormones and is often
accompanied by the onset of DI

P.132
P.133
Posterior Pituitary Gland

Physiology
What hormones are Vasopressin (or ADH) and oxytocin. Hormone release
released by the is controlled by direct nerve stimulation from the
posterior pituitary? hypothalamus.

What are the Osmolality (increases dramatically at plasma

physiologic stimuli for osmolality >285 to 290 mOsmol/kg)
the release of ADH? Nonosmotic factors: BP and volume status, nausea,
angiotensin II, acute hypoxia and/or hypercapnia, and
hypoglycemia

What defines SIADH? 1. Decreased effective plasma osmolality (<275

mOsmol/kg)
2. Inappropriate urinary concentration at some level
of hypoosmolality (urine osmolality >100
mOsmol/kg)
3. Clinical euvolemia with absence of signs of hypo-
or hypervolemia
4. Elevated urinary sodium (usually >40 meq/L) with
a normal salt and water intake
5. Absence of another cause like hypothyroidism,
adrenal insufficiency, diuretics, or pituitary ACTH
deficiency

What are the Bronchogenic carcinoma, lymphoma, sarcoma, and

neoplastic causes of cancer of the duodenum, pancreas, brain, prostate,
SIADH? or thymus

What are the Pneumonia, TB, lung abscess, viral pneumonitis,

nonmalignant empyema, chronic obstructive pulmonary disease,
pulmonary causes of asthma, pneumothorax, and positive-pressure
SIADH? ventilation

What are the Stroke, trauma, anterior pituitary diseases,

intracranial causes of hemorrhage, infections, brain tumors, and
SIADH? hydrocephalus or other pathology that increases
intracranial pressure

What medications can Chlorpropamide, vincristine, vinblastine,

cause SIADH? cyclophosphamide, carbamazepine, oxytocin,
narcotics, selective serotonin reuptake inhibitors,
 clofibrate, thiazides

What is the treatment Correction of the underlying cause of SIADH.

for SIADH? Water restriction to 800 to 1000 mL/day.
Demeclocycline (interferes with renal action of ADH).
If severe symptomatic hyponatremia is present, 3%
saline can be administered slowly over several hours
and is generally given with a loop diuretic.
Conivaptan, an ADH inhibitor that works at both
isotypes of the vasopressin receptor (V1a and V2).

At what rate should Rate of correction should not exceed 10 meq/L in the
the sodium be first 24 hours or 18 meq in the first 48 hours.
corrected?

What is the indication Treatment of hospitalized patients with euvolemic

to use conivaptan? hyponatremia resulting from inappropriate or
excessive secretion of ADH

What is cerebral salt A syndrome resulting from salt loss that is similar to
wasting (CSW)? SIADH based on laboratory measures and has most
commonly been described after subarachnoid
hemorrhage or other CNS insult

How can one 1. Clinical history or status with evidence of

differentiate SIADH hypovolemia
from CSW? 2. Trial of isotonic saline infusion

How can isotonic In CSW, isotonic saline will normalize the serum
saline infusion help sodium because it will restore volume status, suppress
differentiate the physiologic ADH, and result in the excretion of excess
cause of hyponatremia water as dilute urine.
in CSW versus SIADH? In SIADH, saline will not improve serum sodium and
instead will likely make it worse.

What are the Autosomal dominant familial inheritance, CNS injury,

neurogenic (central) infection, cancer, and vascular (Sheehan's syndrome)
causes of DI?

How is neurogenic DI DDAVP is the drug of choice in most cases (either SQ,
treated? intranasally, or orally). Worse cases are occasionally
treated with chlorpropamide.

How is the release of Through neuroregulation by the hypothalamus, which

 oxytocin controlled? is stimulated by estrogen or manipulationor distension
of breasts or the female genital tract

What is the function It acts on membranes of myometrial cells to increase

of oxytocin? the force of contraction, exerts contractile effects on
the myometrium postpartum, and contracts the
myoepithelial cells of mammary alveoli to cause
expulsion of milk.

What are the clinical For induction of labor and control of hemorrhage
uses of oxytocin? after delivery.

P.134
P.135

Hypopituitarism
What are the symptoms and signs of the following:

GH deficiency? In children, decreased linear growth; in adults, fine

wrinkling around eyes and mouth, decreased muscle
mass, increased fat mass

Gonadotropin Amenorrhea, infertility, altered libido, decreased facial

deficiency? hair growth in men

TSH deficiency? Hypothyroidism with fatigue, cold intolerance, and

constipation in the absence of goiter

ACTH deficiency? Cortisol deficiency manifest by fatigue, decreased

appetite, weight loss; abnormal response to stress
characterized by fever, hypotension, hyponatremia; and
a high mortality rate

How is the diagnosis Insulin tolerance test (ITT). Insulin is injected and GH
of GH deficiency measured at specific time intervals thereafter.
made?

What is a normal GH should normally rise to >9 ng/mL after insulin

response of GH to injection.
insulin?

What other Oral L-dopa and arginine infusion for adults and oral
stimulation studies clonidine and intramuscular glucagon for children
are available to
 detect GH
deficiency?

How is the diagnosis ITT

of ACTH deficiency
made?

What is the normal The cortisol level should be >20 !g/dL after adequate
cortisol response to hypoglycemia.
the ITT?

What is empty sella The sella has little if any obvious normal pituitary tissue
syndrome? and is filled with cerebrospinal fluid.

What are the causes This is likely either the result of a prior pituitary tumor
of the empty sella (that spontaneously regressed) or is congenital.
syndrome?

What is the pituitary In most cases, normal pituitary function is observed, but
function in empty some patients do have pituitary hormone deficiencies.
sella syndrome?

Adrenal Gland

Cushing's Syndrome
How is the Dexamethasone, 1 mg, is taken at 11 P.M., and a serum
dexamethasone cortisol is measured at 8 A.M. the next morning. Normal
suppression test response is suppression of cortisol to <5 !g/dL.
performed?

What are the Pathologic hypercortisolism, noncompliance, stress, obesity,

causes of depression, alcoholism, increased metabolism of
abnormal dexamethasone by anticonvulsants or rifampin
screening tests?

How is Low-dose dexamethasone suppression test

pathologic
hypercortisolism
confirmed?

How is a low- After measuring basal 24-hour urine free cortisol, 8 A.M.
dose plasma cortisol, and ACTH, dexamethasone 0.5 mg is given
dexamethasone PO every 6 hours for 48 hours. A 24-hour urine for free
suppression test cortisol is collected during the second day, and serum
 performed? cortisol is measured at 48 hours. In patients with pathologic
hypercortisolism, urine free cortisol and cortisol levels are
not suppressed.

A suppressed Primary adrenal tumor or nodular dysplasia

ACTH (<5
pg/mL) suggests
what causes of
endogenous
Cushing's
syndrome?

How is a high- Dexamethasone (2 mg) PO is taken every 6 hours for 48

dose hours. Urine is collected for free cortisol on the second
dexamethasone day, and serum cortisol is drawn 6 hours after the final
suppression test dose of dexamethasone is given.
performed?

Why is a chest Some ACTH-secreting bronchial carcinoid tumors can be

CT obtained in suppressed with dexamethasone, thereby mimicking
some cases in Cushing's disease.
which there is
suppression of
cortisol by high-
dose
dexamethasone?

Name four 1. Aminoglutethimideblocks side-chain cleavage enzyme

adrenal needed for conversion of cholesterol to pregnenolone
inhibitors and 2. Metyraponeinhibits 11%-hydroxylase, which catalyzes
their site of the final step in cortisol and aldosterone syntheses
inhibition. 3. Ketoconazoleblocks both side-chain cleavage enzyme
and 11%-hydroxylase
4. Mitotanea cytotoxic drug that preferentially destroys
cells of the zona fasciculata and zona reticularis

P.136
P.137
P.138
P.139

Adrenal Insufficiency
What are some differences in For primary failure aldosterone is lost as
how patients with primary well and ACTH levels are usually elevated,
versus secondary adrenal resulting in salt wasting, hyperkalemia,
insufficiency (AI) present? hypotension and hypovolemia, and
hyperpigmentation.
For secondary failure or a pituitary lack of
ACTH, aldosterone is intact and potassium
and volume status is usually normal. There is
also no associated hyperpigmentation.

How much adrenal function >90%

must be lost for primary AI to
develop?

How much cortisol is normally ~8 to 15 mg/day

produced at baseline?

How much cortisol is normally 75 to 200 mg/day

produced under stressful
situations such as major
surgery?

When should plasma cortisol 8 A.M.

and ACTH be collected in
evaluation of AI?

What levels of cortisol suggest 8 A.M. value of <3 !g/dL or <6 !g/dL under
primary AI? stress, with an elevated ACTH in this setting

What AM cortisol level virtually "20 !g/dL

excludes AI?

What diagnostic test is The high-dose cosyntropin stimulation test

commonly used to diagnose or
exclude primary AI?

How is this test performed? Injection of 250 !g of synthetic ACTH, IV or

IM, measure cortisol at baseline, at 30
minutes, and at 60 minutes

What constitute normal and A plasma cortisol at 30 or 60 minutes of "18

abnormal results? !g/dL excludes adrenal cortisol deficiency.
An 8 A.M. ACTH should be collected to
confirm the diagnosis (one would expect
ACTH to be high).

How can a stimulated A postcosyntropin aldosterone level of <18

aldosterone measurement be suggests deficiency.
helpful?

What is the most common Exogenous glucocorticoid use and abrupt

cause of ACTH deficiency? withdrawal of chronic glucocorticoids can
precipitate acute AI.

What happens to the adrenal It atrophies.

gland when ACTH is chronically
suppressed or absent?

For patients who stop long- It can take up to a year or more. The
term (>1 year) glucocorticoids individual response is variable, and the
or those with a history of effect will depend on the total dose over
treated Cushing's disease, how time as well.
long does it take for the
function of the HPA axis to
return to normal?

How is secondary AI evaluated? A morning ACTH level, cosyntropin

stimulation test, and then an insulin
tolerance test if deficiency is still suspected
despite a normal cosyntropin-stimulation
test

How is an insulin tolerance 0.1 to 0.15 U of insulin per kilogram of body

test done? weight is given as an IV bolus; baseline and
serial cortisol levels are measured along with
blood glucose.
A blood glucose of <40 mg/dL and signs of
neuroglycopenia should be achieved.

What cortisol level excludes A peak cortisol of "18 !g/dL excludes

secondary AI? deficiency.

What test differentiates The CRH stimulation test

secondary from tertiary
adrenal insufficiency?

What is the expected ACTH Patients with secondary adrenal insufficiency

response to CRH in secondary have little or no ACTH response to CRH.
AI?

What is the expected ACTH Patients with tertiary adrenal insufficiency

response to CRH in tertiary AI? have an exaggerated ACTH response to CRH.
How should AI be treated? Evaluate underlying cause and treat if
possible.
Replacement cortisol doses range from ~10
to 20 mg in the A.M. and 5 to 10 mg in the
P.M., to try to mimic physiologic secretion.
Fludricortisone at 0.05 to 0.2 mg/day, but
this is not needed if ACTH deficiency is the
cause.
DHEA 50 mg/day for women.

How should cortisol dosing be Mild illness like a cold or a dental procedure
adjusted for mild stress? no adjustment.

How should cortisol dosing be Moderate illness such as fever, minor

adjusted for moderate stress? trauma, or minor surgerydouble daily dose.

How should cortisol dosing be Severe stresshydrocortisone 150 to 200 mg

adjusted for severe stress? divided in q6h to q8h dosing, then taper by
50% per day when stress is no longer
present.

How is relative AI defined in By failure to increase cortisol by >9 !g/dL

septic shock? after a 250-!g cosyntropin stimulation test

What time of day should Any time; it loses diurnal variation in the
cortisol be measured in septic setting of severe stress and should be
shock and other critical elevated.
illness?

How should patients be Begin with baseline cortisol: If <15 !g/dL,

selected for steroid treatment initiate treatment; if 15 to 34 !g/dL, do
in septic shock? cosyntropin stimulation test and treat if
there is a failure to increase cortisol level
by "9 !g/dL; if >34 !g/dL, it is reasonable
not to treat as cortisol response is likely
adequate.

How is relative AI treated in Hydrocortisone 50 mg IV q6h and

septic shock? fludrocortisones 0.5 mg once daily, both for
7 days

What are the clinical Adrenal insufficiency, hypoparathyroidism,

manifestations of polyglandular and mucocutaneous candidiasis
autoimmune syndrome type I?
 What is the inheritance Autosomal recessive
pattern of polyglandular
autoimmune syndrome type I?

What are the clinical Adrenal insufficiency, autoimmune thyroid

manifestations of polyglandular disease (Hashimoto's or Graves' disease),
autoimmune syndrome type II? autoimmune diabetes, gonadal failure, and
alopecia

P.140

Aldosterone
What aldosterone A ratio of plasma aldosterone to plasma renin activity
and renin levels are >30 along with an aldosterone level >20 ng/dL is
suggestive of an suggestive of either an aldosteronoma or bilateral
adrenal cause of adrenal hyperplasia and warrants further investigation.
hyperaldosteronism? Also, secondary hyperaldosteronism is dependent on
volume status. Renin secretion and levels of aldosterone
should decline with saline infusion or blockade of
converting enzyme (i.e., with captopril).

How do After 4 hours of upright posture, plasma aldosterone

aldosterone- increases significantly in bilateral hyperplasia.
secreting adenomas Aldosterone does not rise in patients with adenomas and
and bilateral may even paradoxically decrease.
hyperplasia differ in
their response to
upright posture?

What diagnostic CT or MRI and adrenal venous sampling

procedures can aid
in localization of an
aldosterone-
secreting adenoma?

What is the 1%
incidence of
nonsecretory
incidental adrenal
masses detected on
abdominal CT scan?

How is adrenal Both adrenal veins and a peripheral site are

venous sampling catheterized. A continuous infusion of ACTH is
performed? administered while samples for aldosterone and cortisol
are obtained from all three sites.

What results would The concentration of aldosterone from the adenoma-

be expected with an containing adrenal gland is typically 10 times greater
adenoma? than that of the opposite adrenal.

What medical Spironolactone (200 to 400 mg/day), amiloride, and

therapies can be calcium channel blockers
used in primary
aldosteronism that
has failed surgical
management or in
the nonsurgical
candidate?

P.141
P.142

Pheochromocytoma
What are the classic Paroxysmal episodes of severe headache, palpitations,
and most common and diaphoresis; >90% of cases present with at least
presenting features two of these three features.
of
pheochromocytoma?

How common are 0.1% to 0.6% in some studies

pheochromocytomas
in hypertensive
patients?

What is the rule of 10% of pheochromocytomas are extra-adrenal, 10%

10s? bilateral, 10% familial, 10% malignant, 10% recurrent,
10% incidental.

Which patients with 1. Patients with severe, sustained, or paroxysmal

hypertension should hypertension or grade 3 or 4 retinopathy
be screened for 2. Patients with MEN 2 syndromes and their first-
pheochromocytoma? degree relatives
3. Patients with hypertension during labor, anesthesia,
or receipt of radiographic contrast
4. Patients with worsening hypertension on beta-
adrenergic blockers, guanethidine, or ganglionic
blockers
5. Patients with unexplained pyrexia and hypotension
 6. Patients with supra-adrenal masses

What special diet or Products containing vanilla and caffeine,

medication acetaminophen (Tylenol) and beta-adrenergic blockers
adjustments are must be withheld for 72 hours.
necessary before
urinary
catecholamines are
measured?

How are plasma The patient should be supine and resting in a

catecholamines comfortable setting. Plasma is best drawn from an
measured? indwelling catheter, as the stress of venipuncture may
elevate catecholamines in some patients.

What factors affect Anxiety, pain, dehydration, congestive heart failure,

plasma smoking, and beta-adrenergic blockers
catecholamine
levels?

What is the clonidine Plasma catecholamine levels may be elevated in both

suppression test? essential hypertension and with pheochromocytomas.
Clonidine (0.3 mg PO) suppresses the blood pressure in
both groups and brings the plasma catecholamine
levels back to the normal range in patients with
essential hypertension but not in those with
pheochromocytoma.

What is the Surgical removal of the tumors. All patients should be

treatment for given alpha-adrenergic blocking agents. Calcium
pheochromocytomas? channel blockers may also be helpful, and beta-
adrenergic blockers should be considered before
surgery.

Why should Administration of beta-adrenergic blockers before

alphaadrenergic alpha-adrenergic blockade may precipitate a
blockade be hypertensive crisis.
established before
the use of beta-
adrenergic blockers
in patients with
pheochromocytoma?

P.143
P.144
 P.145
P.146
P.147
P.148

Thyroid Gland
What is the Thyrotoxicosis encompasses all causes of thyroid hormone
difference excess; hyperthyroidism is a form of thyrotoxicosis that
between occurs from increased thyroid hormone production.
thyrotoxicosis
and
hyperthyroidism?

How can one By doing a 24-hour radioiodine uptake scan

separate
hyperthyroidism
from other forms
of
thyrotoxicosis?

What conditions Diffuse uptake: Graves' disease, TSH-producing pituitary

will result in adenomas, trophoblastic disease (from hCG-mediated
increased uptake thyroid stimulation)
suggestive of More focal uptake: Toxic adenoma, toxic multinodular
hyperthyroidism? goiter (usually mildly increased uptake)

What conditions Subacute thyroiditis, radiation thyroiditis, amiodarone

result in low toxicity, exogenous thyroid intake, metastatic follicular
radioiodine thyroid cancer, and struma ovarii (thyroid tissue in an
uptake? ovarian tumor, often teratoma)

What is the most Graves' disease

common cause
of
hyperthyroidism?

What forms of 1. Postpartum thyroiditisusually develops 3 to 6 months

thyrotoxicosis after delivery, then goes through a hypothyroid phase
are postpartum and finally returns to normal
women at 2. Graves' disease 3 to 9 months postpartum, in some
greatest risk for? cases transient, some recurrent, and some new

How is Graves' Evidence of thyrotoxicosis, goiter, and infiltrative

disease orbitopathy are enough to make the diagnosis.
diagnosed? When the diagnosis is in question, an uptake scan should be
performed, and one can test for TSH receptor antibodies.

What is the There is buildup of glycosaminoglycans in the extraocular

pathogenesis of and adipose tissues as a result of cytokine-stimulated
Graves' fibroblast activation. The immune system, via T cells and
orbitopathy? antibodies, appears to recognize a common antigen, most
likely the TSH receptor, present in retro-orbital tissues.

What are the strategies for treatment of the following:

Graves' disease? PTU or methimazoleit will take 2 to 6 weeks to see

improvements, but larger doses may be needed for more
severe disease. These drugs block the synthesis of new
thyroid hormone but will not inhibit the release of hormone
already present. Beta blockers can be used for symptoms,
along with iodine for more severe cases.
Surgery.
Radioiodine ablationmost often recommended.

Subacute NSAIDs or corticosteroids for more severe disease

thyroiditis?

Postpartum Observation beta blockers for symptoms, and then many

thyroiditis? will need thyroid replacement during the hypothyroid phase

Toxic Radioiodine therapy; surgery if mass effects from the goiter

multinodular itself
goiter?

Toxic adenoma? Radioiodine versus surgery, depending on symptoms and

nodule size

When should a At <0.1 U/mL the risks of cardiac dysfunction, dementia,

low TSH be osteoporosis, and fractures is increased.
treated in the
setting of mild
thyrotoxicosis?

Why is PTU and methimazole therapy results in ~20% to 30%

radioiodine success in long-term treatment of Grave's disease; however,
ablation there are rare but serious side effects of agranulocytosis
preferred for and hepatotoxicity.
Graves' disease?
What is the most Hashimoto's thyroiditis
common cause
of
hypothyroidism?

What are some Iodine deficiency, drugs such as lithium, sulfonamides, and
other causes of large doses of iodine in patients with preexisting thyroid
hypothyroidism? disease and cystic fibrosis infiltrative disease (sarcoid,
hemochromatosis, scleroderma, amyloid), postablation or
surgery, central (hypothalamic or pituitary), and congenital
causes

What is It is seen in an asymptomatic patient with a slightly

subclinical elevated TSH (5 to 15 mU/mL).
hypothyroidism?

When is it Some suggest if TSH is >10 mU/mL; others recommend

reasonable to checking for TPO and antithyroglobulin antibodies first. If
treat based on these are positive or the patient has goiter, the risk of
TSH alone? developing overt hypothyroidism is great enough to treat
empirically. If negative, it may be reasonable to follow
TSH every 6 to 12 months.

How may lipid For persistently elevated or increasing lipid levels, it would
levels be helpful be reasonable to treat subclinical hypothyroidism.
in evaluating the
need to treat
subclinical
hypothyroidism?

What is the In elderly patients or patients with cardiac disease, a low

starting dose of dose is given to start, then the dose is increased very
levothyroxine? gradually (e.g., a 25-!g dose is increased by 25 to 50 !g
every 4 weeks until thyroid function tests normalize, which
usually occurs at a dose of 125 !g/day).
In younger patients, a dose of 1.6 !g/kg/day is reasonable
to start with.

What is the They occur in up to 5% of the population, with a female-

incidence of to-male ratio of 4:1.
solitary thyroid Incidence increases with age.
nodules?

What percent of 2% to 5%
thyroid nodules
are malignant?

How are thyroid 1. Determine thyroid status by history, exam, and labs.
nodules 2. If normal or hypothyroid, a fine needle aspiration or
evaluated? biopsy should be done; most often an ultrasound is
done for guidance as well as determination of size and
consistency.
3. If hyperthyroid, an iodine uptake scan is done to
evaluate for hyperfunction.

What are the Papillarymost common

two most Follicularsecond most common
common thyroid
cancers?

What three Papillary, follicular, and medullary carcinoma

cancers of the
thyroid present
as solitary, cold
nodules?

What cancers of Anaplasticrapidly enlarging mass, 90% present with

the thyroid metastases
present as Thyroid lymphomarapidly enlarging goiter
rapidly enlarging
masses or
goiter?

What are the risk factors for the following cancers:

Papillary Radiation exposure of the head and neck, especially as a

child.

Follicular Iodine deficiency

Medullary 80% sporadic, other associated with MEN2 A and B.

carcinoma

Anaplastic Previous (20%) or coexisting (20% to 30%) differentiated

thyroid cancer (often papillary)

Thyroid Chronic Hashimoto's thyroiditis (~50%) and history of

lymphoma hypothyroidism with goiter (~10% to 20%)
What are the approximate 10-year survivals for the following cancers:

Papillary 98%

Follicular 92%

Medullary 80%

Anaplastic 13%

What are For follicular and papillary cancers, debate continues as to

therapies for the most effective therapies. Patients with small lesions
thyroid cancer? usually undergo partial or near-total thyroidectomies,
depending on the preference of the surgeon. The larger
malignant lesions, follicular cancers and medullary
carcinoma, likely need near-total thyroidectomies, as they
are more likely advanced or multifocal. For metastatic
disease, radioactive iodine can be used.

What is the A range of thyroid hormone abnormalities encountered in

nonthyroidal critical illness or starvation
illness (NTI)
syndrome?

What are the Abnormalities progress with more severe illness through
typical thyroid several stages:
function tests in 1. With mild illness, there is a decrease in T3 and no
the NTI
change in other parameters.
syndrome?
2. With progressive illness, T3 is further reduced, T4 is
increased from reduced clearance, and TSH is normal.
3. With more severe illness, normal TSH secretion is lost
and all parameters decrease.

What lab test rT 3 . Reverse T3 will be elevated in the first two stages but
may be useful in may begin to decrease in the most severe stage.
diagnosing this
syndrome?

What two drugs Dopamine and high-dose corticosteroids

commonly used
in ICUs directly
suppress TSH
release?
 What are the It provides a high iodine loadit is 37% iodine by weight.
physical and It resembles T4 structurally and inhibits T4 deiodination to
chemical T3 ; this results in higher T4 levels, lower T3 , and a rise in
features of
TSH. These effects usually resolve in a few weeks.
amiodarone that
It may compete for the T3 receptor in tissues.
result in its
ability to alter It has direct toxic effects on the thyroid gland.
thyroid function
and action?

Who is likely to In areas of iodine sufficiency, it most often causes

become hypothyroidism; in areas of iodine deficiency, it most often
hypothyroid causes thyrotoxicosis.
versus thyrotoxic
on amiodarone?

Multiple Endocrine Neoplasia Syndromes

What gene is mutated in The MEN1 gene is believed to be responsible
MEN1? with a loss-of-function mutation.

What are the most common Parathyroid, pancreatic, pituitary

endocrine tumors in MEN1?

What gene is mutated in The RET oncogenewith a gain-of-function

MEN2? mutation

What are the most common Medullary thyroid carcinoma,

endocrine tumors in MEN2 A? pheochromocytoma, and parathyroid

What distinguishes MEN2 B? Medullary thyroid carcinoma,

pheochromocytoma, and multiple mucosal
neuromas

P.149
P.150

Bone and Mineral Disorders

Hypocalcemia
What are the Predominantly neuromuscular irritability, which is manifest as
clinical tetany, perioral paresthesias, tingling in the hands and feet,
manifestations and muscle cramps. If severe it can cause seizures,
of acute generalized tonic muscle spasm, laryngospasm, papilledema,
hypocalcemia? emotional instability, and psychosis.
What are Chvostek's sign: tetany of the ipsilateral facial muscles elicited
Chvostek's by tapping on the facial nerve anterior to the ear. Contraction
and is seen in the corner of the mouth, the nose, and the eye.
Trousseau's Trousseau's sign: carpal spasm after 3 minutes of occluding
signs? arm blood flow with a blood pressure cuff. Often the spasm is
painful.

What is the Prolonged QT interval

classic ECG
finding in
hypocalcemia?

What is the differential diagnosis for hypocalcemia if

It is PTH- Postparathyroid, thyroid, or radical neck surgeries

related? Congenital absence of PTH glands, DiGeorge's syndrome,
autoimmune polyglandular syndrome I
Hypomagnesemia, respiratory alkalosis
Hemochromatosis, Wilson's disease, metastatic disease
Pseudohypoparathyroidism types I and II

Vitamin D Deficiency, fat malabsorption syndromes

related? Liver disease/failure (impaired 25-hydroxylation)
Renal failure (hyperphosphatemia and impaired 1 alpha-
hydroxylation)
Vitamin Ddependent rickets types I and II

Other causes? Critical illness (sepsis, pancreatitis, toxic shock)

Chelation (phosphate infusion, citrated blood products)
HIV infection (drug therapy and vitamin D deficiency)

How does There is a decrease in total serum calcium of ~0.8 mg/dL for
serum every 1 g/dL decrease in albumin.
albumin relate
to total
calcium
measurement?

What is the Ionized calcium

best test for
calcium in
acute or
critical
illness?
 What is Severe and prolonged hypocalcemia after parathyroid removal
hungry bone in a patient with preexisting hyperparathyroidism and bone
syndrome? disease. Thought to result from sudden increase in bone
calcium uptake upon withdrawal of excessive PTH.

What is the Calcium gluconate 100 mg IV (~10 mL of 10% solution) over 15

treatment for to 20 minutes, then 100 mg over 24 hours if symptoms persist.
acute Once symptoms resolve, replacement is with oral calcium
symptomatic carbonate (1.5 to 3.0 g of elemental calcium) in three to four
hypocalcemia? divided doses daily, usually along with vitamin D (400 to 800
IU/day).

P.151

Hypercalcemia
What are the clinical Nausea, vomiting, abdominal pain, and constipation
manifestations of Fatigue, weakness, altered mental status.
hypercalcemia? Polyuria and polydipsia.
In severe or acute cases it can lead to lethargy and
coma.

What is the classic Shortened QT interval

ECG finding in
hypercalcemia?

What are the most 1. Hyperparathyroidism (mainly outpatients).

common causes of 2. Malignancy (most common in inpatient setting). Can
hypercalcemia? be related to osteolytic disease from metastases,
PTHrP, or excess 1, 25(OH) 2 -vitamin D (B-cell
lymphoma).

What are some other Vitamin Dmediated:

causes of Sarcoid and granulomatous disease (excess 1&-
hypercalcemia? hydroxylation of vitamin D by macrophages)
Vitamin D intoxication
Other:
Hyperthyroidism, adrenal insufficiency
Rhabdomyolysis, immobilization (e.g., after spinal cord
injury, calcium peaks at ~4 months)
Drugsthiazides in the setting of hyperparathyroidism,
chronic lithium, milk-alkali syndrome, excess vitamin A
Paget's disease
 What are some PTHrP, PTH, and 1, 25(OH) 2 -vitamin D levels.
important lab tests
in hypercalcemia of
malignancy?

What is milk-alkali Hypercalcemia, metabolic alkalosis, and renal failure

syndrome? after ingestion of large amounts of calcium and alkali

What is a common Ingestion of excessive calcium carbonate (up to several

cause of this grams a day)
syndrome?

What are the 1. Normal saline (0.9%) at 2 to 4 L/day initially.

treatments for acute 2. IV Pamidronate 60 to 90 mg once a day over 4 to
symptomatic 24 hours (restores calcium to normal in 2 to 3 days)
hypercalcemia? 3. Calcitonin (human) 0.5 mg SQ every 12 hours
(reduces calcium in hours but the effect lasts for
only a few days)

1. Lasixif vigorous hydration fails to improve

hypercalcemia or volume overload occurs.
Otherwise it risks volume contraction and
aggravation of renal failure.

P.152
P.153

Osteoporosis
How does osteoporosis Osteoporosis is characterized by the disruption of
differ pathologically normal bone architecture; there are fewer,
from osteomalacia? thinner, and less connected trebeculae as well as
thinned and more porous cortices. There is no gross
defect in collagen structure or mineralization.
Osteomalacia is characterized by a lack of mineral
in newly formed bone matrix as well as a reduced
rate of bone growth. There are obvious defects of
increased osteoid and decreased mineralization.

What is a T score? The standard deviation (SD) from the bone mineral
density (BMD) of a young normal population.

What is a Z score? The SD away from an age- and gender-matched

group.
How is osteoporosis T score <2.5
defined?

What defines normal Normal is T score >1

and low bone mass? Low is T score 1 to 2.5

When is treatment for T score <2.0

osteoporosis generally T score <1.5 and risk factors
indicated? Women over age 70 with multiple risk factors

What is the most Corticosteroid usebone loss after 1 year

common cause of approaches 20%.
secondary osteoporosis?

What is the incidence of 30% to 50%

fractures in patients on
corticosteroids for
greater than 6 months?

How can steroid-induced Calcium (1500 mg/day elemental), vitamin D (800

osteoporosis be IU/day), bisphosphonates, teriparatide, calcitonin
prevented or treated?

What is the lifetime risk 13%

of osteoporosis in a man
over age 50?

How is the action of Estrogen-like drugs, such as SERMs, have estrogen-

selective estrogen agonist activities at bone but antagonist actions at
receptor modulators breast and uterus. The single agent in this class is
(SERMs) different from raloxifene (Evista).
that of hormone
replacement therapy?

How do bisphosphonates Bisphosphonates inhibit bone resorption; they

work and how are they include etidronate (cyclic therapy), alendronate
dosed? (continuous or weekly therapy), risedronate
(continuous or weekly therapy) and ibandronate
(monthly or given IV every 3 months).

What is an added Calcitonin can stabilize bone mass and may have
benefit of calcitonin? additional beneficial actions on reducing bone pain
from fractures.

How is human PTH Daily SQ injections of recombinant human PTH can

 administered? increase BMD and reduce spine fractures; it is
approved for the treatment of postmenopausal
osteoporosis.

What are some causes of Vitamin D deficiency with resulting calcium and
osteomalacia? phosphate deficiency caused by malabsorption
syndromes, hepatic disease with fat malabsorption,
pancreatic disease with exocrine insufficiency, and
renal disease

P.154

Paget's Disease
What is the Paget's disease is most common in persons above 50 years of
epidemiology age, with a slight male predominance. There may be a genetic
of Paget's component in that 15% to 30% of patients have a family history
disease? of Paget's disease.

How is the Biochemically, Paget's disease is characterized by an increase in

diagnosis of markers of bone turnover, including increased urinary excretion
Paget's of hydroxyproline, an elevated serum alkaline phosphatase, and
disease osteocalcin.
made?

What are the Affected bones show cortical thickening, expansion, and areas
radiographic of mixed lucency and sclerosis. The skull of affected patients is
findings in often described as having a cotton-wool appearance.
Paget's
disease?

What is the Therapy is directed at suppressing the activity of the

therapy for osteoclasts. These medications include calcitonin, etidronate,
Paget's alendronate, risedronate, and plicamycin. Calcitonin is given as
disease? a subcutaneous injection. Unfortunately tachyphylaxis has been
reported. Etidronate is very effective but may alter normal
mineralization and must be given on an intermittent regimen.
Plicamycin is a very potent inhibitor of resorption but has a
number of toxicities and should be reserved for refractory
cases.

P.155

Reproductive Endocrinology

Female
What disorders cause or Genotype disorder (e.g., testicular feminization
present as primary and 5-& reductase deficiency)
amenorrhea? Anatomic defect [e.g., Mllerian agenesis,
Asherman's syndrome (intrauterine adhesions),
and imperforate hymen]
Ovarian failure (e.g., gonadal dysgenesis and
autoimmune disease)
Metabolic (e.g., weight loss and chronic illness)
Hormonal (e.g., polycystic ovary disease,
congenital adrenal hyperplasia,
hyperprolactinemia, and hypopituitarism)

What is the first test that A pregnancy test

should be done in
evaluating secondary
amenorrhea?

What are some causes of Pregnancy, Asherman's syndrome (outflow

secondary amenorrhea? obstruction as a result of uterine
instrumentation), premature ovarian failure,
hyperprolactinemia, hypothalamic causes

What other diseases are Autoimmune diseases such as Hashimoto's

associated with premature thyroiditis, type 1 diabetes, and Addison's
ovarian failure? disease

Why does hypothyroidism Because of increased levels of TRH, which

cause elevated prolactin? directly stimulate prolactin production

What is hypothalamic It results from impaired GnRH release, which

amenorrhea? occurs in the setting of stress, severe weight
loss, fat loss, and excessive exercise.

Women with amenorrhea Generally, no. Women with PCOS are generally
are often at risk for overweight and have high androgen levels, both
osteoporosis; is this true of which appear to protect bone mass.
for women with PCOS?

What are some of the 26% higher rate of cardiac events during the first
adverse effects that have 5 years (Women's Health Initiative), increased
been associated with breast cancer risk (RR 1.2 to 1.3), increased risk
postmenopausal hormone of dementia in women over age 65 (hazard ratio
replacement therapy? of 2.0)

What hormones have these Estrogen-progesterone combination therapy

adverse effects been
associated with?

What are the Nonestrogen therapy for osteoporosis and the

recommendations for shortest duration and lowest doses of estrogen
treating osteoporosis, for menopausal symptoms
vasomotor symptoms, and
vaginal dryness?

P.156
P.157

Male
What are the features of Puberty is delayed or does not occur.
childhood hypogonadism?

What are some symptoms Decreased libido, energy, and infertility

and signs of adult male
hypogonadism?

What are some physical Soft, smooth skin, loss of body hair,
features of adult male gynecomastia, and a decrease in size of prostate
hypogonadism? and testesthese signs are usually detectable if
androgen deficiency has been present for years.

How should the cause of Measure a morning serum testosterone; if low,

hypogonadism be then check LH and FSH to separate central
evaluated? versus primary gonadal disease.

What are the feedback Testosterone, estradiol, and inhibin-B

signals for LH and FSH?

What hormone will be FSHregulated by inhibin-B from the Sertoli

elevated in milder forms cells; they are more sensitive to damage than
of gonadal failure? the Leydig cells, which secrete testosterone and
estradiol.

What is the most common Klinefelter's syndrome: 47 XXY

congenital cause of
primary testicular failure?

How frequently does it 1 in 500 to 1000 men

occur?
How is it diagnosed? Usually in teenagers with incomplete pubertal
development, gynecomastia, or small testes

What malignancies afflict Testicular or extragonadal germ cell tumors

men with Klinefelter's particularly in the mediastinim
syndrome?

What immune diseases Lupus, systemic sclerosis, thyroiditis

afflict men with
Klinefelter's syndrome?

What psychiatric disorders Depression, anxiety, poor verbal skills

afflict men with
Klinefelter's syndrome?

What vascular disorders Varicose veins and leg ulcers

afflict men with
Klinefelter's syndrome?

What are some other Cryptorchidism, orchitis, chemotherapy

causes of primary
testicular failure?

What is hypogonadotropic Hypothalamic or pituitary dysfunction resulting in

hypogonadism? abnormal LH secretion and hypogonadism

What is the key laboratory Testosterone, because LH is secreted in pulses

test in hypogonadal men?

What lab abnormalities Low serum testosterone and low to low-normal

would be expected in LH
hypogonadotropic
hypogonadism?

What are some causes of Congenitalsporadic (75%) and familial.

hypogonadotropic Mutations in LH and FSH beta subunits, GnRH
hypogonadism? receptor gene, and mutations of transcription
factors PROP-1 or HESX1
Acquiredpituitary or suprasellar tumor
(craniopharyngioma), illnesses such as cancer and
AIDS as a result of low GnRH

What lab test(s) should be Prolactinbecause prolactinomas are the most

ordered if common functional pituitary tumors. Other
hypogonadotropic pituitary hormones should be checked as well.
 hypogonadism is found?

What disorder is associated Kallmann's syndrome

with anosmia or other
midline defects and
hypogonadotropic
hypogonadism?

When should free In obesity and hyperinsulinemic states

testosterone be measured?

Why are those two Because these states are associated with low sex
conditions associated with hormonebinding globulin levels, which will result
low testosterone? in low total testosterone and mimic
hypogonadotropic hypogonadism.

P.158
P.159

Endocrine Tumors of the Pancreas and Gut

What are the 1. Insulinoma
various 2. Glucagonoma
pancreatic and 3. Gastrinoma
gut endocrine 4. Somatostatinoma
tumors? 5. VIPoma
6. Carcinoid

What are the Most often postexercise hypoglycemia and sometimes

symptoms of an hypoglycemia after overnight fasting
insulinoma?

Besides imaging, Inappropriately high insulin and C-peptide in the setting of

how is an spontaneous or induced (72-hour fast) hypoglycemia (blood
insulinoma glucose <50 mg/dL) and the absence of other precipitants,
diagnosed? such as sulfonylurea therapy or insulin antibodies

What are the Necrolytic migratory erythemaa raised erythematous rash

symptoms of a beginning at the groin and perineum with occasional bullae
glucagonoma?

Besides imaging, Pancreatic mass and a glucagon level >1000 pg/mL are
how is a virtually diagnostic; most have >500 pg/mL. However, the
glucagonoma classic syndrome can rarely manifest with high-normal
diagnosed? glucagon levels.
What are the Abdominal pain, diarrhea, and heartburn; refractory peptic
symptoms of a ulcers leading to perforation and hemorrhage.
gastrinoma?

Besides imaging, Fasting gastrin >200 pg/mL and gastric acid secretion of
how is a >15 meq/h in the absence of antisecretory therapy (ppi/H2
gastrinoma blockers). Most have gastrin >500 pg/mL. Diagnosis can be
diagnosed? confirmed with a secretin stimulation test for levels 200 to
500 pg/mL. A rise in serum gastrin >200 pg/mL from
baseline or doubling in 15 minutes after a bolus of IV
secretin.

What are the Mild diabetes, steatorrhea, and cholelithiasis. Arises in

symptoms of a pancreas and duodenum.
somatostatinoma?

In addition to Found as either a pancreatic or duodenal mass or, if

imaging, how is a suspected based on symptoms, a somatostatin level >160
somatostatinoma pg/mL is suggestive.
diagnosed?

What are the Intermittent watery diarrhea, hypokalemia, and

symptoms of a achlorhydria
VIPoma?

Besides imaging, History of severe, recurrent, diarrhea and fasting plasma

how is a VIPoma VIP >200 pg/mL
diagnosed?

What are the Flushing, diarrhea, right heart fibrosis and failure, and
symptoms of a less commonlybronchial constriction
carcinoid?

Besides imaging, Clinical features and urinary 5-HIAA >100 !mol in 24 hours.
how is a Not elevated in hindgut carcinoid, and a number of
carcinoid foods/substances may result in false positives. Avoiding
diagnosed? certain foods prior to testing and using multiple less
specific markers may be needed (chromogranin A, fasting
blood serotonin, plasma substance P, hCG-&).

P.160
P.161
P.162
Diabetes Mellitus
How is diabetes diagnosed? Any of the following:
1. Symptoms of polyuria, polydipsia, and
unexplained weight loss, plus a random
plasma glucose of "200 mg/dL
2. Fasting plasma glucose of "126 mg/dL (no
food intake of "8 hours)
3. A 2-hour plasma glucose concentration
"200 mg/dL after a 75-g oral glucose
tolerance test

What ethnic groups have a Hispanic Americans, African Americans, Asians,

high risk of developing Pacific Islanders, and Native Americans
diabetes?

What defines the metabolic Abdominal obesity (waist circumference >102

syndrome? cm in men and >88 cm in women)
Triglycerides "150 mg/dL
HDL <40 mg/dL in men and <50 mg/dL women
Blood pressure "130/85
Fasting blood glucose "110 mg/dL

What are five general forms 1. Type 1 diabetessplit into types 1A and
of diabetes mellitus? 1Bboth characterized by severe insulin
deficiency.
1A refers to autoimmune-mediated
diabetes and is the most common of this
type.
1B refers to other forms of severe insulin
deficiency (e.g., pancreatitis associated
insulin deficiency).
2. Type 2 diabetes accounts for ~90% of cases
globally and is characterized by insulin
resistance, obesity, and impaired
pancreatic insulin secretion.
3. Latent autoimmune diabetes of adulthood
patients can be thin or phenotypically
appear like type 2 diabetics but have
autoimmune beta-cell destruction and
diabetes diagnosed as adults.
4. MODY (maturity-onset diabetes of youth)
five forms due to impaired %-cell function
resulting from genetic defects.
5. Gestational diabetesglucose intolerance
 with onset at or first recognized during
pregnancy.

What are the major 1. Anti-GAD65 (The 65-kDa form of glutamic

autoantibodies in acid decarboxylase)
autoimmune (Type 1A or 2. Islet-cell autoantibodies (ICA512)
LADA) diabetes? 3. Insulin autoantibodies (less common in
adults)
4. Autoantibodies to tyrosine phosphatases
IA-2, IA-2B (less common in adults)

What is the 10-year risk of For "2 antibodies, 90%

diabetes among first-degree For 1, only ~20%
relatives of type 1 diabetics
based on number of
antibodies present?

What is the function of It is the enzyme involved in the synthesis of

GAD65? GABA from glutamic acid. Beta-cell GABA may
play a role in the regulation of insulin and/or
glucagon secretion.

What rare neurologic Stiff-man syndromeas a result of GAD

syndrome is associated with autoantibodies to neuronal epitopes, these
anti-GAD65 antibodies? patients also have a higher incidence of type
1A diabetes.

Are there genetic linkages in HLA haplotypes (e.g., DR3 and DR4) are
type 1A diabetes mellitus? associated with a higher incidence of type 1
diabetes mellitus. There is a 50% concordance
in identical twins.

Are there genetic linkages in There is nearly a 100% concordance in

type 2 diabetes mellitus? identical twins. There are no HLA markers.

What are the two most MODY 3 is the most common (25% to 50%).
common forms of MODY and The defect is in hepatic nuclear factor 1&,
their causes? resulting in defective insulin synthesis and
beta-cell function.
MODY 2 is the second most common (10% to
40%) and is due to defects in glucokinase, a
rate-limiting step in beta-cell glucose sensing.

How common is gestational 5% to 10% of pregnancies

 diabetes?

How is gestational diabetes Oral glucose tolerance test, random blood

diagnosed? glucose "200 mg/dL, or fasting glucose "126
mg/dL. The latter two should be confirmed on
a subsequent day.

What is the risk of ~50% at 10 years after delivery

developing diabetes in
patients with a history of
gestational diabetes?

P.163

Hyperglycemia in the Hospital

What is stress Hyperglycemia that may occur in both
hyperglycemia? nondiabetics and diabetics as a result of the
stress hormone response (catecholamines,
cortisol, etc.) to a severe systemic stressor.

What is the physiologic role To maintain a constant supply of glucose to the

of increased glucose CNS under conditions where nutrient intake and
production and insulin tissue delivery may be impaired
resistance in acute stress?

What are some conditions Hypoxia (PaO 2 <30 to 40 mm Hg),

that cause stress hypotension/shock, recovery from hypoglycemia,
hyperglycemia? hypothermia, surgery, trauma, burns, sepsis,
myocardial infarction

How should stress When CNS perfusion is in question (hypotension,

hyperglycemia be managed hypoxia, cerebrovascular occlusive disease), one
when CNS perfusion is in should be careful to avoid hypoglycemia and
question? correct the underlying pathology before
measures for tight glycemic control are
initiated.

How should stress When CNS glucose delivery is not in question or

hyperglycemia be managed in cases of surgery, burns, cold stresswhen
when CNS perfusion is not nutrient requirements are increasedthe use of
in question? insulin to control glucose should be initiated as
needed.

What levels of Blood glucose levels >200 to 250 mg/dL. These

 hyperglycemia are require prompt treatment and control.
associated with adverse
effects on wound healing
and the vascular,
hemodynamic, and immune
systems?

When should a hemoglobin For known diabetics, on admission to assess

A 1C be measured in recent control and intervention needs
hospitalized patients? For hyperglycemic patients without a previous
diagnosis of diabetes, to assess for the presence
of undiagnosed diabetes

What level of hemoglobin >7%

A 1C suggests previously
undiagnosed diabetes?

What are the blood glucose As close to 110 mg/dL as possible and <180
goals for patients in the mg/dL overall
ICU?

What are the blood glucose As close to 90 to 130 mg/dL as possible and
goals for patients on a <180 mg/dL after meals
general medical ward?

What are some benefits of Fewer bloodstream infections, shorter duration

tight glucose control in the of mechanical ventilation and ICU stay, less
ICU? antibiotic use, and less critical-illness
polyneuropathy, renal failure, and need for
hemodialysis (This is from surgical ICU data.)

What mortality benefit has 10% absolute risk reduction in mortality for
been shown with tight those treated in the ICU >5 days (This is from
glucose control in the ICU? surgical ICU data.)

P.164
P.165

Hypoglycemia
How is The most reliable method is Whipple's triad: Low plasma
hypoglycemia most glucose concentration, symptoms of hypoglycemia, and
reliably diagnosed? relief of symptoms with restoration of normal glucose
concentration.
What blood <50 mg/dL after an overnight fast indicates
glucose level postabsorptive hypoglycemia. However, it is not possible
defines to define an exact number below which symptoms occur,
hypoglycemia? as patients with chronically elevated blood glucose may
experience symptoms at levels that would be considered
normal for others.

What are the two Autonomic/neurogenic, which can be divided further into
major groups of adrenergic symptoms and paresthesias
hypoglycemic Neuroglycopenic
symptoms?

What are the Palpitations, tremor, and anxiety, and cholinergic

adrenergic symptoms of sweating, and hunger
symptoms?

What are the A direct result of glucose deprivation resulting in altered

neuroglycopenic mental status, dizziness, confusion, visual changes,
symptoms? fatigue, headache, weakness, and seizures

What diabetics are Type 1 diabetics, the elderly, and those with acute renal
at greatest risk of failure or on hemodialysis
hypoglycemia?

What are some Drugs: Insulin, sulfonylurea, alcohol, sulfonamides

causes of Critical illness: Sepsis, renal failure, liver failure
hypoglycemia? Hormonal deficiency: Adrenal, growth hormone, glucagon,
epinephrine
Tumor: Insulinoma, large non-insulin-secreting tumor
burden
Autoimmune: Insulin antibodies, insulin receptor
antibodies

What is the classic A supervised 72-hour fast: Fast until blood glucose <45
diagnostic test for mg/dL with symptoms or signs of hypoglycemia. Measure
hypoglycemia? baseline and hypoglycemic parameters.

What are the 1. Insulin level (may be falsely elevated if insulin

three standard antibodies are present)
tests to order in 2. C peptide
the setting of 3. Sulfonylurea level
acute
hypoglycemia or
after a 72-hour
fast?
 What results would Elevated insulin, low C peptide, and negative sulfonylurea
one expect from level
exogenous insulin
administration?

What results would Elevated insulin and C peptide but negative sulfonylurea
one expect from level
an insulinoma?

What results would All three elevatedinsulin, C peptide, and sulfonylurea

one expect from
sulfonylurea
ingestion?

What are the 1. Oral glucose if able to eat (4 to 8 oz fruit juice or 2

treatments for to 3 glucose tablets)
acute 2. IV glucose D5% infusion or 50 mL of D50% IV push
hypoglycemia? 3. IM glucagon (0.5 to 1 mg for one dose, can repeat in
25 minutes)

P.166
P.167
P.168

Treatment of Diabetes
What are the Premeal glucose, 80 to 120 mg/dL
daily glycemic 2-hour postmeal glucose, <160 mg/dL
goals in type 1 Bedtime glucose, 100 to 140 mg/dL
diabetes?

What does A long-acting insulin such as glargine to mimic basal

intensive insulin pancreatic insulin secretion, and then rapid-acting insulin
therapy include? to mimic prandial insulin secretion with or without a
correction dose for premeal hyperglycemia. This type of
regimen requires more frequent monitoring and injections
but allows for greater flexibility in dietary intake and
glucose correction.

What are the 1. Basal insulin such as glargine

three components 2. Meal-based insulin depending on body weight or
of intensive carbohydrate counting
insulin therapy? 3. Correction doses or sliding scale that can be given
along with meal based doses to adjust for premeal
 hyperglycemia

How are the The total amount of insulin required for most patients
morning and with type 1 diabetes mellitus is 0.5 to 1.0 U/kg/day and,
evening doses for patients with type 2, 1 to 2 U/kg/day (or more). Two
calculated in a thirds of the total is given in the morning and one third in
split-mixed the evening. Of the morning dose, two thirds is given as
regimen? NPH (or Lente) and one third as regular insulin. In the
evening, the amounts of regular and NPH are usually even.
If using a glargine-based regimen in type I DM,
approximately 40% to 50% of the total daily dose is given
as glargine and the remainder as rapid-acting insulin.

When should type When lifestyle modification fails to maintain a hemoglobin

2 diabetics begin A 1 C of <7%
pharmacotherapy?

What drug is the Metforminthe major action of which is to reduce hepatic

only agent shown glucose output/hepatic insulin resistance
to reduce both
microvascular
(e.g.,
retinopathy) and
macrovascular
(e.g., MI and
death) diabetic
complications?

When should For creatinine "1.5 mg/dL in men and "1.4 mg/dL in
metformin not be women; a better estimate would be a calculated
used? creatinine clearance of <50 mL/min (by Cockroft-Gault
equation).
Alcoholics
Patients with symptomatic heart failure
24 to 48 hours prior to IV contrast (it can be resumed 48
hours or later after contrast)

What drugs act The thiazolidinedionespioglitazone and rosiglitazone

predominantly as
peripheral insulin
sensitizers?

What are some Edema and weight gain; there is some suggestion they
potential side may increase cardiac events and mortality.
effects of these
 drugs?

What drugs The sulfonylureas (glyburide, glipizide, glimepiride),

stimulate insulin meglitinides (repaglinide), and nateglinide, a derivative of
secretion phenylalanine
(secretagogues)?

How are the Glipizide and glimepiride are long-acting and can be taken
different once daily.
secretagogues Repaglinide and nateglinide are rapid-acting and are
used? taken with meals.

What are the new Mimetics: Exenatide (Exendin-4), a GLP-1 receptor agonist
incretin mimetics Enhancers: DPP-IV (dipeptidyl peptidase) inhibitors, which
and enhancers? block the breakdown of GLP-1. These include sitagliptin
and vildagliptin.

What are the GLP-1 is a gut-derived hormone that enhances glucose-

effects of GLP-1? induced insulin secretion, reduces glucagon secretion,
slows gastric emptying, and may preserve and promote
beta-cell life and growth.

How is Subcutaneously twice per day; it is approved for the

exenantide used? treatment of type II DM in conjunction with sulfonylurea
and or metformin therapy.

When should type Upon failure to maintain a hemoglobin A 1 C of <7% on two

2 diabetics oral agents and lifestyle modifications. Addition of a third
initiate insulin agent may reduce A 1 C by 0.9% to 1.3%; therefore an A 1 C
therapy?
of >8.3% on two agents will require insulin.

How should Starting with a single daily dose (most often bedtime) of
insulin therapy long-acting insulin may reduce hemoglobin A 1 C to <7%;
for type 2 however, as beta-cell failure progresses, the insulin
diabetics be regimen may progress toward that of a typical regimen in
initiated? type 1 diabetes.

P.169

Diabetic Nephropathy
How many Five
stages are
there in the
progression
 of diabetic
nephropathy?

What happens in the kidney at each stage of diabetic nephropathy and what
is the timing of the occurrence?

Stage 1 Glomerular hyperfiltration, increased GFR (up to 140% normal),

and renal enlargement

Stage 2 Early glomerular lesions. Expansion of the glomerular

mesangium and thickening of the glomerular basement
membrane occurs from 4 or 5 years to 15 years after onset of
diabetes mellitus.

Stage 3 Incipient diabetic nephropathy. Microalbuminuria (defined as

urinary protein excretion between 30 and 200 mg/day)
develops and precedes later nephropathy and the development
of
end-stage renal disease. GFR begins to decline once the
microalbuminuria exceeds 70 !g/min. Hypertension often is
noted.

Stage 4 Clinical nephropathy with proteinuria and declining GFR. GFR

declines below normal, and proteinuria >300 mg/day develops.
Signs of reduced oncotic pressure (e.g., anasarca) become
evident. Hypertension is universal. Overt nephrotic syndrome
with proteinuria, hypoproteinemia, and hyperlipidemia can
develop. Nearly all patients with azotemia from diabetic
nephropathy have coincident retinopathy. End-stage renal
disease usually develops within 5 years of clinical proteinuria.

Stage 5 End-stage renal disease. Uremic signs and symptoms are

apparent and renal replacement therapy is necessary.

P.170

Major Trials in Endocrinology

The following is a list of the pivotal trials in endocrinology with references.

Diabetes
DCCT: The Diabetes Control and Complications Trial evaluated the importance of
strict glycemic control. Groups were divided into intensive therapy (average blood
glucose of 155 mg/dL) versus conventional therapy on long-term microvascular
complications in type 1 diabetes mellitus. Compared with conventional therapy: the
risk of development of retinopathy declined by 76%; the risk of progression of
retinopathy declined by 54%; the occurrence of microalbuminuria declined by 39%;
the occurrence of overt proteinuria declined by 54%; and the risk of development of
neuropathy declined by 60% in the intensive therapy group. The major adverse event
was a twofold to threefold increase in severe hypoglycemia. N Engl J Med
1993;329:977986.

UKPDS: Like the DCCT, the United Kingdom Prospective Diabetes Study investigated
the incidence of complications in patients with type 2 diabetes receiving intensive
therapy versus conventional therapy. The intensive therapy group had a significant
25% decrease in incidence of microvascular complications. Lancet 1998;352:837852.
Editors: Bergin, James D.
Title: Advanced Medicine Recall, 1st Edition

Copyright 2009 Lippincott Williams & Wilkins

> Table of Contents > Section II - The Specialties > Chapter 5 - Gastroenterology

Chapter 5
Gastroenterology

P.172

Abbreviations
ALF Acute liver failure

AFP Alpha-fetoprotein

AIDS Acquired immunodeficiency syndrome

AMA Antimitochondrial antibody

ANA Antineutrophil antibodies

ANCA Antineutrophil cytoplasmic antibody

Anti- Antibodies to hepatitis C

HCV

APACHE Acute Physiology and Chronic Health Evaluation II test

II

ARDS Adult respiratory distress syndrome

ATP Adenosine triphosphate

Anti- Antibodies to hepatitis B core antigen

HBc

Anti- Antibodies to hepatitis B e antigen

HBe

ASMA Antismooth muscle antibody

AVM Arteriovenous malformation

BMI Body mass index

BRBPR Bright red blood per rectum

BUN Blood urea nitrogen

CBC Complete blood count

CBD Common bile duct

CD Crohn's disease
CEA Carcinoembryonic antigen

CLO Campylobacter-like organism

CMV Cytomegalovirus

CRC Colorectal cancer

CREST Calcinosis, Raynaud's, esophageal dismobility, sclerodactyly, and

telangectasia

CT Computed tomography

DES Diffuse esophageal spasm

DIC Disseminated intravascular coagulopathy

DILI Drug-induced liver injury

EGD Esophagogastroduodenoscopy

ELISA Enzyme-linked immunosorbent assay

ERCP Endoscopic retrograde cholangiopancreatography

EUS Endoscopic ultrasound

FAP Familial adenomatous polyposis

GB Gallbladder

GERD Gastroesophageal reflux disease

GI Gastrointestinal

HAV Hepatitis A virus

HBV Hepatitis B virus

HBcAg Hepatitis B core antigen

HBeAg Hepatitis B e antigen

Anti- Antibodies to hepatitis B surface antigen

HBs

HBsAg Hepatitis B surface antigen

HCC Hepatocellular carcinoma

HCV Hepatitis C

HDV Hepatitis delta virus

HIDA Hepatobiliary iminodiacetic acid

HIV Human immunodeficiency virus

HLA Human leukocyte antibody

HNPCC Hereditary nonpolyposis colon cancer

HPS Hepatopulmonary syndrome

HRS Hepatorenal syndrome

H2RA H2-receptor antagonist

IBD Inflammatory bowel disease

IBS Irritable bowel syndrome

INR International normalized ratio

LES Lower esophageal sphincter

LGI Lower gastrointestinal (distal to ligament of Treitz)

MALT Mucosal-associated lymphoid tissue

MEN Multiple endocrine neoplasia

MRCP Magnetic resonance cholangiopancreatography

MRI Magnetic resonance imaging

NAC N-acetyl cysteine

NAFLD Nonalcoholic fatty liver disease

NAPQI N-acetyl-p-benzoquinoneimine

NSAID Nonsteroidal anti-inflammatory drug

OCP Oral contraceptive pills

PBC Primary biliary cirrhosis

PCR Polymerase chain reaction

PPHTN Portopulmonary hypertension

PPI Proton pump inhibitor

PSC Primary sclerosing cholangitis

PSE Portosystemic encephalopathy

PT Prothrombin time

PTT Partial thromboplastin time

PUD Peptic ulcer disease

PVT Portal vein thrombosis

RBC Red blood cell

 RDA Recommended daily allowance

SBP Spontaneous bacterial peritonitis

SLE Systemic lupus erythematosus

SRMD Stress-related mucosal disease

TIPS Transjugular intrahepatic portosystemic shunt

UC Ulcerative colitis

UGI Upper gastrointestinal (proximal to ligament of Treitz)

VIP Vasoactive intestinal peptide

VOD Veno-occlusive disease

WBC White blood cell

ZES Zollinger-Ellison syndrome

P.173
P.174
P.175
P.176

Nutrition
What is Adults require 25 to 30 kcal/kg body weight per day (i.e., 2100
normal kcal/day in a 70-kg person). A typical American derives 40% to
energy 45% of calories from carbohydrates, 40% to 45% from lipids,
metabolism? and 10% to 15% from protein.

What Macronutrients, the major part of the diet, include proteins,

nutrients do carbohydrates, lipids, water, and electrolytes.
humans Micronutrients, which are often used in minute amounts,
require? include trace elements and vitamins.

What are the Emaciation, growth retardation, wasting of subcutaneous fat,

clinical severe constipation, dry skin, and thin, sparse hair
consequences
of marasmus?

What are the Decreased protein synthesis with muscle atrophy and normal or
clinical increased body fat. Accompanying are anorexia, anasarca,
consequences edema, moon face, distended abdomen as a result of dilated
of bowel loops and hepatomegaly, dry skin, and hypopigmented,
kwashiorkor? dry hair. Edema may mask true malnutrition.

What is the The recommended daily allowances are different for men and
RDA and how women and vary with age. In addition, although the RDA
has it nomenclature has been used for several decades to define a
changed? set of standards for nutrient and energy intake, a major
revision occurred in 1997 to create a broader set of dietary
guidelines than the RDA. The revised nomenclature is known as
the dietary reference intakes (DRI).

What are the Folate, calcium (duodenum and jejunum), magnesium (ileum
most and jejunum), vitamin B12 (terminal ileum), zinc
common
deficiencies
associated
with
intestinal
disease?

What Low serum albumin, prealbumin, carotene, transferrin, total

laboratory lymphocyte count, negative nitrogen balance, and delayed
tests suggest hypersensitivity skin response to common antigens are useful
malnutrition? indices for visceral protein status.

How much 20 to 25 kcal/kg, 0.8 to 1.0 g protein/kg

should
healthy
adults be
fed?

How much 20 to 25 kcal/kg, 1.0 to 1.5 g protein/kg

should obese
adult patients
or patients
adapted to
starvation
be fed?

How much 25 to 30 kcal/kg, 1.3 to 1.5 g protein/kg

should adult
patients
experiencing
mild to
moderate
stress be
fed?

How much 30 to 35 kcal/kg, 1.6 to 2.5 g protein/kg

should adult
patients
experiencing
moderate to
severe stress
be fed?

What is the If the gut works, use it.

general rule
of thumb for
nutrition?

Clinical pearl Recovery is slow. It is much easier to prevent malnutrition

than to treat it.

How are By depleting the intracellular stores of these minerals.

potassium, Phosphorus levels are maintained by mobilization of bone
magnesium, stores and enhanced renal resorption.
and
phosphorus
levels
maintained
during
starvation?
What causes On refeeding, metabolism increases as the body attempts to
the mineral replenish its stores of ATP and increase protein synthesis, body
depletion cell mass, and glycogen synthesis. Phosphate, magnesium, and
seen in potassium are retained by cells during these processes; thus
refeeding the corresponding serum level may fall. Also, after
syndrome? carbohydrate
ingestion, the resulting increase in serum insulin can cause
intracellular shifts of potassium and phosphate, contributing to
the low serum levels.

What factors With chronic starvation, cardiac mass, end-diastolic volume,

contribute to and stroke volume all decrease. Bradycardia and fragmentation
the fluid of cardiac myofibrils may occur. In addition, increased insulin
overload and levels (resulting from carbohydrate ingestion) lead to sodium
cardiac and water retention. Ventricular arrhythmias, often preceded
insufficiency by a prolonged QT interval, may result from hypokalemia and
in some hypomagnesemia.
patients with
refeeding
syndrome?

What GI Decreased mucosal epithelial cell mass and regeneration,

changes decreased digestive pancreatic enzymes, and impaired
occur with absorption of amino acids. Diarrhea is not uncommon.
chronic
starvation
and
subsequent
refeeding
syndrome?

How long They usually reverse within 1 to 2 weeks on refeeding.

does it take
for the
changes to
reverse?

What BMI is Between 18.5 and 24.9 kg/m 2

considered
normal?

What BMI 30 kg/m 2

defines a
person as
being obese?

How many Dietary changes must be individualized, ideally with the

calories guidance of a nutritionist or other trained professional. A low-
should calorie diet (1000 to 1500 kcal/day) can produce an 8% weight
overweight loss over 4 to 6 months. Very low calorie diets have greater
and obese initial yield but are associated with more complications (e.g.,
people electrolyte abnormalities, gallstones, and arrhythmias) and
exclude from greater rates of weight regain.
their diet to
lose weight?

How much of On average, a 7500-kcal deficit is needed to lose 1 kg of

an energy adipose tissue (the average adult expends approximately 3500
deficit is kcal after walking 35 miles).
needed to
lose weight?
 What are Appetite suppressants (e.g., amphetamines, fenfluramine,
some phentermine, sibutramine, selective serotonin reuptake
examples of inhibitors), phenylpropanolamine, opioid antagonists, dietary
medications fat substitutes (e.g., Olestra, Simplesse), carbohydrase
that have inhibitors (e.g., Acarbose), lipase inhibitors (e.g., orlistat),
been used to thermogenic agents (e.g., thyroid hormone, ephedrine), and
treat obesity? other hormones (e.g., human chorionic gonadotropin,
cholecystokininoctapeptide). Currently, only sibutramine and
orlistat are approved for long-term use.

For which Patients with a BMI >40 kg/m 2 or a BMI >35 kg/m 2 with
patients is medical comorbidities. Patients should have failed nonsurgical
surgical weight-loss strategies.
treatment of
obesity
considered?

P.177
P.178
P.179
P.180

Gastrointestinal Bleeding
What are symptoms Hemodynamic instability (i.e., tachycardia, tachypnea,
and signs of acute, orthostatic hypotension, angina, mental status change
severe GI bleeding? or coma, and cold extremities)

What additional signs Hepatic encephalopathy or HRS

may be present in a
cirrhotic patient with
GI bleeding?

What are the more Peptic ulcer (related to Helicobacter pylori or NSAID
common causes of use), hemorrhagic gastritis, Mallory-Weiss tear, erosive
UGI bleeding? esophagitis, and varices. Also consider neoplasm,
angiectasia (formerly known as angiodysplasia),
Dieulafoy's lesion, gastric vascular ectasia, aortoenteric
fistula, and hemobilia.

What are the more Hemorrhoids and fissures (rarely require

common causes of hospitalization), AVMs, diverticulosis, ischemia,
LGI bleeding? neoplasms, IBD, infectious colitis, radiation colitis, and
Meckel's diverticulum

How much blood At least 100 mL of blood must be present in the GI

must be present to tract for melena to occur. Note: Iron, bismuth, and
produce melena? some foods can cause black stools.

Does bright red Bright red blood per rectum usually indicates a LGI
blood per rectum source, but 10% to 15% of cases result from vigorous
always indicate a LGI UGI bleeding.
bleed?

How much bleeding Need 1000 mL blood for hematochezia

from the UGI is
necessary to cause
BRBPR?

Is NG aspiration In all patients with GI bleeding, NG aspiration and

necessary in LGI lavage should be considered. Some 10% to 15% of
bleeding? patients presenting with hematochezia will have UGI
sources.

How is NG aspiration Continuous bright red blood demonstrates active,

helpful? vigorous bleeding, whereas coffee grounds are more
consistent with bleeding that is slower or has stopped.

Is there a false- There is a 16% false-negative rate for NG lavage (even

negative rate with if bile is visualized) in patients with endoscopically
NG aspiration? active UGI bleeding.

Is a rectal Yes; character and color of stool can help determine

examination needed the severity and source of bleeding.
for UGI bleeding?

Why might the BUN The BUN becomes elevated due to the digestion of
be elevated in the blood proteins and absorption of nitrogenous
setting of an UGI compounds in the small intestine.
bleed?

What additional For UGI sources, consider urgent endoscopy.

testing should be
considered in
patients with a UGI
source of bleeding?

What is the Medical therapy includes supportive care, transfusions

treatment for when needed, correction of any coagulopathy, and acid
bleeding associated suppression (with PPIs or H2 RAs). An intravenous PPI
with PUD? should be initiated in the acute setting; it acts to
minimize further PUD progression and promote more
effective coagulation.

What is the medical For intermediate- and high-risk lesions, endoscopic

treatment for acute thermal coagulation, with or without preceding
esophageal varices epinephrine injections, is frequently performed.
that are causing GI Intravenous octreotide is used to decompress the
bleeding? portal venous system without the significant
cardiovascular side effects of vasopressin and
nitroglycerin.
Broad-spectrum antibiotics are indicated (generally
ciprofloxacin is used), as there is increased morbidity
and mortality directly attributable to infectious
complications of variceal bleeding in a cirrhotic
patient.

What percent of Approximately 40%

patients with
compensated
cirrhosis develop
esophageal varices?

What percent of Approximately 85%

patients with
decompensated
cirrhosis develop
esophageal varices?

What is the mortality Approximately 30%

associated with an
esophageal variceal
bleed?

What is a TIPS Transjugular intrahepatic portosystemic shunt

procedure?

(From Yamada T, Alpers DH, Laine L, Owyang C, Powell DW: Textbook of

Gastroenterology, 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 1999:723.)

What oral Beta-adrenergic blockers. Nitrates are sometimes used.

medications may
decrease the risk of
variceal bleeding?

How are beta Propranolol or nadolol is started at a relatively low

blockers titrated? dose and then titrated to achieve a 25% reduction in
resting heart rate or a resting heart rate of 50 to 60
bpm.

Do beta blockers No, they only decrease the incidence of bleeding from
decrease the existing esophageal varices by reducing the hepatic
incidence of the venous pressure gradient.
development of
esophageal varices in
patients with portal
hypertension?

Which factors predict A higher Child-Pugh score, alcohol as an etiology of the

the progression of varices, and the presence of red wale marks
esophageal varices?

Are gastric varices Unlike esophageal varices, gastric varices do not

treated the same as respond optimally to band ligation; novel therapies for
esophageal varices? gastric varices, such as the injection of various glue-
like materials into the varices, are being investigated.

How are They neutralize pathogenic gastric acid after UGI

antisecretory agents bleeding. Maintaining intragastric pH >4.0 reduces the
H 2 antagonists, direct harmful effects of acid and pepsin on the
PPIs, and antacids bleeding lesion and allows platelets to aggregate.
useful in GI
 bleeding?

What is a simple rule Tachycardia = 10%

for quantifying the Orthostatic hypotension = 20%
amount of blood loss Hypotension = 30%
a patient has
experienced?

What are the adverse Severe persistent bleeding.

prognostic factors for Onset of bleeding after admission or rebleeding in the
GI bleeding? hospital (>30% mortality in some series).
Mortality doubles in patients >60 years of age and in
those with concomitant central nervous system,
hepatic, pulmonary, or neoplastic disease. It triples in
patients with renal disease, and it increases several-
fold in patients with cardiac or pulmonary disease.
Urgent surgery for UGI bleeding carries a 25% mortality
compared to 2% for elective surgery.

Should an adherent Recent studies demonstrate decreased recurrences of

clot be removed or bleeding and better outcomes with removal of
left alone? adherent clots and subsequent thermal coagulation or
epinephrine injection.

Name a medication Octreotide, which decreases splanchnic blood flow and

that could be of decreases acid secretion.
benefit in stabilizing
a bleeding ulcer
prior to definitive
therapy.

P.181

Esophagus

Dysphagia, Reflux, and Motility

What does dysphagia Solid food > liquid suggests structural abnormality.
with solid foods
suggest?

What does dysphagia Solids = liquids suggests neuromuscular (motility)

with either suggest? origin.

Does the location of No, particularly for distal esophageal lesions

the patient's symptoms
accurately predict the
location where the
food or liquid is getting
stuck?

Name the disorder

from these defining
characteristics:

Intermittent Schatzki's ring

dysphagia

Progressive Scleroderma or achalasia

dysphagia for solids
and liquids
 Regurgitation of Achalasia or Zenker's diverticulum
undigested food

Patients often have Nutcracker esophagus or diffuse esophageal spasm

undergone workup for
angina

What is the Bird's beak appearance

characteristic
appearance of
achalasia on barium
swallow?

What is the treatment Achalasia can be treated with pneumatic balloon

for achalasia? dilation of the LES or surgical myotomy. Injection of
botulinum toxin into the LES can be utilized for
patients who are not good surgical candidates, but
repeat injections are generally required every 6
months.

What is A tumor in the distal esophagus producing findings

pseudoachalasia? similar to those of achalasia on imaging and
manometry

How are DES and Manometry demonstrates >20% simultaneous

nutcracker esophagus contractions in DES and high-amplitude contractions
diagnosed? in nutcracker esophagus. Barium swallow may
demonstrate a corkscrew esophagus in DES
(although this is not diagnostic).

What is the treatment These motility disorders can be difficult to treat,

for DES and nutcracker and antidepressants (including tricyclic
esophagus? antidepressants), calcium channel blockers, nitrates,
and antispasmodics are often used to attempt to
alleviate symptoms.

P.182
P.183
P.184

Gastroesophageal Reflux
How common is Common. More than 33% of Americans have intermittent
esophageal symptoms; 10% have daily heartburn.
reflux?

What is the Lifestyle changeselevation of the head of the bed (6 to 8

nonpharmacologic inches), weight loss, avoidance of tight-fitting clothes,
treatment of smoking cessation, decreased caffeine consumption,
GERD? avoidance of foods and medications that decrease LES
pressure, minimizing oral intake for a few hours before
lying supine, and consumption of frequent small, high-
protein meals

What is the PPIs, H2 receptor antagonists, and prokinetics.

pharmacologic Metoclopramide increases LES pressure and improves
treatment of esophageal and gastric emptying.
GERD?

What are the Open or laparoscopic Nissen fundoplication, which is

interventional usually reserved for patients who have failed medical
treatments for therapy. Endoscopic suturing and radiofrequency treatment
GERD? are newer, less invasive techniques.

Clinical pearl The character of the pain does not help to differentiate
cardiac from noncardiac sources. Pain of esophageal origin
may radiate to the neck, arm, or jaw and can be
aggravated by stress and exercise. Therefore an adequate
cardiac evaluation is often first required to exclude
potentially life-threatening processes.

What type of Adenocarcinoma

cancer may arise
in Barrett's
esophagus?

How frequent is Dysplasia and adenocarcinoma have a prevalence of 3% to

dysplasia and 9%. The risk of developing adenocarcinoma is about 0.5%
adenocarcinoma to 0.8% per year in patients with Barrett's esophagus.
in the setting of
Barrett's
esophagus?

How should Patients without evidence of dysplasia should undergo

Barrett's endoscopy with multiple biopsies every 2 to 3 years.
esophagus be Patients with evidence of low-grade dysplasia should have
followed up? more frequent surveillance.

What is the Surgical esophagectomy is often recommended. If a

treatment for patient is not a surgical candidate, endoscopic ablation
Barrett's with photodynamic therapy can be considered.
esophagus with
severe or high-
grade dysplasia?

What additional Male gender, Caucasian race, obesity, chronic GERD, and
risk factors exist smoking (possibly)
for development
of
adenocarcinoma
of the esophagus?

What is tylosis? A rare autosomal dominant disease associated with

hyperkeratosis of the palms and soles of the feet

How is the CT and endoscopic ultrasound (EUS) with fine needle

staging of aspiration. EUS is particularly good at determining depth
esophageal of invasion and local lymph node metastases.
carcinoma
performed?

What is the typical EGD appearance of esophageal infection with each of the
following?

Candida Confluent or nodular white-yellow plaques

Herpes Vesicles and ulcers

CMV Diffuse ulceration or a giant esophageal ulcer

What is the treatment of esophageal infection with each of the following?

 Candida? Fluconazole, ketoconazole, nystatin, or amphotericin B

Herpesvirus? Acyclovir. Foscarnet can be used for resistant herpes

infections.

CMV? Ganciclovir or foscarnet

What are the risk Poor esophageal motility, large pills, gelatin capsules, and
factors for advanced patient age.
developing pill
esophagitis?

Which class of Bisphosphonates, because of their potential to produce

medications is severe esophageal erosion.
associated with
high-risk pill
esophagitis?

What is the Patients should be in an upright position to take the pills,

treatment for pill and a full glass of liquid should be taken with them.
esophagitis? Viscous lidocaine or sucralfate may be tried for
symptomatic relief.

P.185

Stomach

Gastritis, Gastroparesis, and Dumping Syndrome

What 50% to 70%
percentage of
gastric ulcers
are related to
H. pylori?

What are Bacterial infections (e.g., tuberculosis, syphilis, phlegmonous

infectious or emphysematous gastritis caused by systemic bacterial
causes of infections), viral infections (e.g., CMV, herpesviruses), fungal
gastritis? infections (e.g., Candida, histoplasmosis, mucormycosis), and
parasitic infections (e.g., anisakiasis, Cryptosporidium)

What are CD, eosinophilic gastritis, graft-versushost disease,

noninfectious sarcoidosis, pernicious anemia, and Mntrier's disease
causes of
gastritis?

How is the The diagnosis is largely clinical, but clinicians generally utilize
diagnosis of the confirmation of a gastric emptying study. This study can
gastroparesis define the degree of delayed emptying; however, it is
made? difficult to standardize. A half-life >90 minutes suggests
delayed gastric emptying.

Clinical pearl An exacerbation of gastroparesis may be caused by severe

hyperglycemia that then resolves when the blood sugar is
adequately controlled.

Can No, patients develop tachyphylaxis within weeks.

erythromycin
be used for
long-term
 treatment of
gastroparesis?

Does gastric No, it is thought to reduce symptoms by feedback to the

pacing central nervous system, reducing symptoms of fullness and
normalize nausea.
gastric
motility?

What occurs Approximately 1 hour after eating, dumping of hyperosmolar

during the food draws water into the small bowel lumen, stimulating
early intestinal motility and release of vasoactive peptides.
(hyperosmolar) Hypotension, dizziness, and tachycardia result.
phase of
dumping
syndrome?

What occurs in Approximately 1 to 3 hours after eating, rapid absorption of

the late large amounts of glucose stimulates excessive insulin release.
(hypoglycemic) This causes hypoglycemia, which results in tachycardia, light-
phase of headedness, and diaphoresis.
dumping
syndrome?

P.186
P.187
P.188
P.189
P.190
P.191

Peptic Ulcer Disease

What are Dyspepsia, nausea, bloating, and belching
symptoms of
PUD?

What causes The vast majority of PUD is related to H. pylori (70% to 90%)
PUD? or NSAID use (15% to 30% of gastric ulcers). ZollingerEllison
syndrome, malignancy, CD, radiation, and infectious etiologies
(e.g., CMV and TB) account for <10% of cases.

What if a Gastric ulcers (but not duodenal ulcers) should be reassessed

gastric ulcer with a repeat EGD after 8 weeks of therapy because of the
is found by potential for an underlying gastric malignancy. If H. pylori is
EGD? present, the treatment of PUD should include H. pylori
eradication.

What medical Gastritis (both acute and chronic forms), intestinal metaplasia
conditions of the gastric mucosa, gastric adenocarcinoma, and MALT
have been lymphoma (thus H. pylori is classified as a class I definite
associated gastric carcinogen in humans). The contribution of H. pylori to
with H. dyspepsia in the absence of PUD remains controversial. It may
pylori, other be a cause of unexplained iron-deficiency anemia.
than PUD?

What is the It is the most common chronic bacterial infection throughout

epidemiology the world, with at least 50% of the world's population affected.
of H. pylori? Prevalence increases with age, and H. pylori is more common
in blacks and Hispanics, owing to socioeconomic and possibly
genetic factors. In the United States, about 50% of people >60
 years of age have serologic evidence of infection. In developing
nations, >80% of those >50 years of age test seropositive. Most
infections are acquired during childhood. Incidence is 0.1% to
1% per year for adults in developed countries.

What is the Typically, it is a chronic lifelong infection unless medically

natural eradicated. The majority of people with H. pylori remain
history of H. asymptomatic and never develop PUD or cancer.
pylori
infection?

Are all H. Probably not. Some H. pylori organisms have a cytotoxin-

pylori associated gene A (CagA strains). Compared with CagA()
infections strains, CagA(+) strains appear to result in more severe
the same? inflammation and epithelial injury,
are more likely to be associated with gastric or duodenal
ulcers, and may impart a greater risk of gastric
adenocarcinoma.

Which Patients with active PUD, a documented history of PUD, or

patients gastric MALT lymphoma
should
undergo
testing for H.
pylori?

Should In general, asymptomatic patients should not undergo testing.

asymptomatic Consider it for patients with a family history, particularly
patients descendants of high-risk populations, such as Japanese, Korean,
undergo H. or Chinese patients or those with a personal fear of gastric
pylori carcinoma.
testing?

Should Although many physicians are testing the utility of this

patients with approach, it is controversial.
functional
dyspepsia
undergo H.
pylori
testing?

What are the H. pylori serology (ELISA), 13 C bicarbonate assay, CLO test
diagnostic
(rapid urease test), histology, breath tests ( 13 C, 14 C), H. pylori
tests for H.
culture, and stool assays. Note: PPI therapy may affect the
pylori?
results of the noninvasive tests.

What are the uses and advantages of the most common tests?

H. pylori IgG antibody against H. pylori is detected. The test is

serology noninvasive and inexpensive.
(ELISA)

Stool ELISA assayuseful for initial diagnosis of H. pylori and

antigen documentation of eradication after treatment
assays

Breath It is safe, noninvasive, and involves very low radiation

tests ( 13C, exposure. It is the test of choice to document successful
14C) eradication of H. pylori but should be performed at least 4
weeks after completion of the eradication regimen and after
 PPI discontinuation.

CLO test Results are available within hours.

(rapid urease
test)

Histologic study

H. pylori Useful when antimicrobial resistance is suspected to allow

culture sensitivities to be determined

PCR of Excellent sensitivity and specificity; can be performed even if

mucosal biopsy specimen is not fresh
biopsies

What are the disadvantages of each?

H. pylori Titers remain high for a year or more, so it cannot accurately

serology confirm recent H. pylori eradication. May be less accurate in
(ELISA) patients >50 years of age and in those with cirrhosis.

Stool Limited availability. Sensitivity may be reduced in patients

antigen taking PPIs or bismuth-containing products. May not be
assays accurate in evaluating for successful H. pylori eradication,
particularly if performed 1 month after treatment.

Breath Require minimal amounts of radiation exposure if 14 C (but not

13
tests ( C, 13 C) is used. Sensitivity is reduced in patients taking PPIs or
14C) H2 RAs.

CLO test Requires EGD. Sensitivity is reduced in patients with recent GI

bleeding and in patients taking PPIs, H2 RAs, antibiotics, or
bismuth-containing products.

Histologic Requires EGD. Sensitivity is reduced in patients taking PPIs or

study H2 RAs.

H. pylori Technically complex and requires strict transport conditions

culture because of H. pylori's fastidious nature. An academic toolnot
widely available.

PCR of Limited availability, and not practical for routine use. False
mucosal positives may occur from contamination of specimen at the
biopsies laboratory (given the high sensitivity of PCR).

What is the Bismuth, metronidazole, and tetracycline. Noncompliance with

current this regimen is common (owing to side effects and the number
standard of pills). One common easier regimen involves a 2-week course
therapy for of twice-daily amoxicillin, clarithromycin, and a PPI.
H. pylori? Antimicrobial resistance is an emerging problem.

What is the 35% to 40% resistance to metronidazole and 10% to 12%

current resistance to clarithromycin
resistance
pattern of H.
pylori in the
United
States?
What About 75%
percentage
of patients
who are
treated with
triple
therapy have
eradication
of their H.
pylori?

What should Eradication (cure) of H. pylori should be attempted, as 1-year

be done if H. ulcer recurrence rates are 6% to 80% without and <10% with
pylori is eradication of H. pylori. Eradication should be confirmed in
detected in patients with a history of bleeding ulcers because 30% may
the setting of develop recurrent bleeding ulcers.
PUD?

Should Confirmation of H. pylori cure is not mandatory in

eradication uncomplicated PUD.
of H. pylori
always be
confirmed?

Does H. H. pylori in the stomach can inhibit acid secretion and may
pylori offer offer some protection against esophagitis.
any
protective
effects?

What are the Hypochlorhydric and achlorhydric conditions (e.g., pernicious

causes of anemia, H. pylori infection, gastric atrophy, and medications
elevated such as PPIs)
gastrin? Hypersecretory conditions (e.g., ZES, retained antrum
syndrome, antral G-cell hyperplasia, gastric outlet obstruction,
short bowel syndrome, systemic mastocytosis, basophilic
granulocytic leukemia)
Decreased clearance (e.g., renal failure)

List some Multiple ulcers, ulcers in unusual locations, recurrence after

distinguishing treatment, or MEN 1 features. Close to 40% of patients will
features of have accompanying diarrhea.
ZES.

What is the Majority of patients between 30 to 50 years old. Occurs in men

epidemiology more frequently than women. May be sporadic or associated
of ZES? with MEN I (genetic defect in chromosome 11).

What is the Defined by the junctions of the CBD and cystic duct, the
gastrinoma second and third portion of the duodenum, and the neck and
triangle? body of the pancreas

Are 60% to 90% are malignant, typically determined by the tumor's

gastrinomas behavior (e.g., metastases) rather than histology.
in ZES Approximately 30% will have metastases (generally to liver or
considered bone). Sporadic gastrinomas tend to be malignant more often
malignant? than those associated with MEN I.

How is the Elevated fasting gastrin (most patients have levels >150 pg/mL;
diagnosis of some have levels >1000 pg/mL, which is virtually diagnostic in
ZES made? the correct clinical setting).
 Elevated basal acid output (98% of cases).
If the gastrin level is equivocal, a secretin stimulation test can
confirm the diagnosis.
After intravenous administration of 2 U/kg of secretin, there is
an increase in serum gastrin of >200 pg/mL above the basal
gastrin level.
Calcium stimulation test may also be useful (as intravenous
calcium stimulates gastrin secretion).

What are Bone, liver, and lung

common
metastatic
sites for
gastrinomas?

What is the High-dose PPIs should be used to decrease gastric acid

treatment of hypersecretion. When feasible, surgical excision of the primary
ZES? gastrinoma should be attempted, as this is the only curative
option. Rarely, more radical surgeries, such as antrectomy with
vagotomy or total gastrectomy, are required. Surgery for ZES in
the setting of MEN 1 is controversial. Other interventions
including octreotide, chemotherapy, and embolization of
tumorshave not yet been shown to have consistent benefit.

What is the Up to a 30% surgical cure rate may be achieved with an

prognosis for aggressive approach to tumor localization. ZES tends to be
ZES after indolent and survival can be quite long. Octreotide or hepatic
surgical artery embolization can be utilized for metastases.
excision?

P.192

Small and Large Intestine

Diarrhea
List the most Infectious, IBD, ischemic, and radiation
common
etiologies of
inflammatory
diarrhea.

What are Escherichia coli, Salmonella, Giardia lamblia, and

common causes Entamoeba histolytica
of traveler's
diarrhea?

What are the Giardia, E. histolytica (people in institutions),

infectious Mycobacterium tuberculosis, Clostridium. difficile
causes of (pseudomembranous colitis), and Cryptosporidium,
chronic Microsporidium, or Isospora (most common in people with
diarrhea? AIDS)

What are the UC, CD, microscopic colitis, and ischemia

inflammatory
causes of
chronic
diarrhea?

Which Think CHESS:

infectious Campylobacter
 agents are a Hemorrhagic E. coli (serotype 0157:H7)
common cause E. histolytica
of bloody Salmonella
stool? Shigella

Clinical pearls Avoid antibiotic therapy in enteric Salmonella infection

because a prolonged carrier state may be induced.
Antimotility agents must be used with caution in patients
with inflammatory diarrhea (e.g., IBD, pseudomembranous
colitis, Shigella, Salmonella).

What chronic Microscopic colitis is not usually apparent on gross

diarrheal state examination of colonic mucosa and requires random biopsies.
may be missed
on
colonoscopy?

P.193
P.194
P.195

Malabsorption
What is celiac T cellmediated inflammatory reaction to dietary gluten
sprue? (wheat, barley, rye, oats) that causes injury to the small
bowelgenetic predisposition. Also known as gluten-
sensitive enteropathy.

Who is affected by Can occur at any age. Serologic testing of blood donors
celiac sprue? suggests a prevalence of 1:250 in the United States. HLA
DQ II is found in 95%.

What dermatologic Dermatitis herpetiformis

manifestation is
associated with
celiac sprue?

What diseases are Type 1 diabetes, autoimmune thyroiditis, PBC, sclerosing

associated with cholangitis, and IgA nephropathy
celiac sprue?

What serologic IgA antiendomysial antibodies (sensitivity >90%,

markers should be specificity >95%) or ELISA for tissue transglutaminase
checked for? (sensitivity >90%, specificity >95%), which is the antigen
for the antiendomysial antibody. Antigliadin antibodies
can also be measured.

Are these markers These markers are not sensitive for diagnosis if the
helpful during patient has already initiated a gluten-free diet; they can
treatment? be used to assess response to or compliance with a
gluten-free diet.

Clinical pearl 2% to 3% of patients with celiac sprue have IgA

deficiency. Thus, IgA levels should be obtained to
minimize false-negative serologies.

What does a small Biopsy is the gold standard for diagnosis, showing
bowel biopsy show blunt, flattened villi and an inflammatory infiltrate in
in celiac sprue? the lamina propria, with intraepithelial lymphocytes.

What else confirms Response to gluten-free diet. Small bowel biopsies

the diagnosis of should be repeated after 4 to 6 months of a gluten-free
celiac sprue? diet. If no histologic improvement is seen, the diagnosis
should be questioned.

What vitamin Folic acid, iron, calcium, and vitamin D

deficiencies are
most commonly
seen?

What other risks Lymphoma, esophageal cancer, melanoma, splenic

are associated with atrophy, liver function test abnormalities, and sequelae
celiac sprue? of vitamin deficiencies (e.g., anemia, coagulopathy,
osteomalacia, or osteoporosis)

What is the Lifelong gluten-free diet and nutritional supplementation

treatment of celiac as needed (calcium/vitamin D, iron, and folate). These
sprue? interventions can decrease the risk of cancer, infertility,
and osteoporosis associated with celiac sprue.

What is the Dapsone, in addition to a gluten-free diet

treatment of
dermatitis
herpetiformis?

On treatment, how Can take up to a year for improvement in symptoms

long should it take
for dermatitis
herpetiformis to
resolve?

What is tropical An acquired form of sprue of unclear etiology but

sprue? thought to be bacterial in nature, infrequently
encountered in the continental United States. It often
improves with antibiotic therapy.

What vitamin Folic acid

deficiency is often
seen in tropical
sprue?

What is Whipple's Systemic disorder typically affecting middle-aged men.

disease? Protean manifestations include diarrhea, weight loss,
abdominal pain, and arthralgias. There may also be
anemia, fevers, myalgias, intra-abdominal
lymphadenopathy, serositis, and central nervous system
involvement.

What are other CD, lymphoma, parasitic infection, radiation enteritis,

causes of intrinsic abetalipoproteinemia, and ischemia
small bowel
disease that result
in malabsorption?

What are the Chronic pancreatitis, pancreatic resection, pancreatic

causes of cancer, and cystic fibrosis
pancreatic
exocrine
insufficiency?

What nutrients are Fat, protein, and carbohydrates

not absorbed
properly with
exocrine
insufficiency?

What are the Any disorder of bile acid enterohepatic circulation (e.g.,
causes of bile acid severe intrinsic liver disease, biliary obstruction, and
insufficiency? disorders of the terminal ileum)

How does Insufficient bile acids impair the formation of

malabsorption intraluminal micelles.
occur in bile acid
insufficiency?

What nutrients are Fat and fat-soluble vitamins (A, D, E, K).

not absorbed
properly in bile
acid insufficiency?

Why does Bile salt deconjugation occurs, resulting in impaired

malabsorption of micelle formation.
fat and fat-soluble
vitamins occur
with small bowel
bacterial
overgrowth?

What vitamin Low vitamin B12, elevated folic acid (due to bacterial
B12/folate levels production)
are characteristic
of bacterial
overgrowth?

What are the Steatorrhea

symptoms and Weight loss
signs of Bone pain or tetany (calcium deficiency)
malabsorption? Glossitis or stomatitis (iron and riboflavin deficiency)
Edema (hypoalbuminemia)
Bleeding and easy bruisability (vitamin K deficiency)
Night blindness (vitamin A deficiency)

What is the bile To establish the presence of small bowel bacterial

acid breath test overgrowth
used for?

How is the test 14 C-glycocholate is ingested. Normally, 95% is absorbed

performed? in the terminal ileum and 5% enters the colon and is
deconjugated by bacteria to 14 CO 2 , which is absorbed
and exhaled in expired air.

How is a positive With bacterial overgrowth, earlier bacterial

test determined? deconjugation occurs and a larger amount of 14 CO 2 is
measured.

What is the Therapy is directed at the specific cause of

treatment for malabsorption.
malabsorption? Dietary modification is frequently necessarylow-fat
diets (restriction of long-chain fatty acids) or ingestion
of medium-chain triglycerides (which do not require bile
 acids for absorption) may be used.
Bile acid binders (cholestyramine) may improve bile salt
induced diarrhea but can significantly worsen
steatorrhea.

P.196

Irritable Bowel Syndrome

What key Diarrhea does not awaken the patient from sleep, the patient
symptoms denies weight loss, and symptoms related to stress.
are
virtually
diagnostic
for IBS?

What are Constipation-predominant, diarrhea-predominant, and

the alternating diarrhea/constipation.
subgroups
of IBS?

What Lactase deficiency, IBD, colon cancer, microscopic colitis, enteric

organic infections, and endometriosis. In a recent study of 300 patients
conditions with newly diagnosed IBS, 5% were found to have celiac sprue.
can cause
symptoms
similar to
IBS?

In addition 1. Medicationstegaserod (constipation and bloat predominant)

to and alosetron (diarrhea-predominant) are the only two
emotional specific therapies for IBS. Other therapies aimed at
and dietary controlling symptoms include antispasmodics when abdominal
therapy, pain and constipation predominate, antidiarrheals
what (loperamide) when diarrhea predominates, laxatives when
medications constipation predominates, and antidepressants (e.g.,
can be used tricyclics).
to treat 2. AntibioticsRecent studies show that a 10-day course of
IBS? rifaximin produces a significant improvement in symptoms for
at least 6 months.

Clinical Some patients with IBS report a past history of physical or sexual
pearl abuse in childhood. In some cases this can be correlated with the
severity of symptoms.

P.197
P.198

Ischemic Bowel
What is the Ischemic colitis (i.e., colonic ischemia)
most
common
region
affected in
ischemic
bowel?

What age Most cases (>90%) of noniatrogenic ischemic colitis occur in

group is patients >60 years of age.
typically
affected with
ischemic
colitis?

What are the In the majority of cases, no specific cause or trigger is

causes of identified. Potential causes include mesenteric artery or vein
ischemic occlusion, vasospasm, vasculitis, systemic circulatory
colitis? insufficiency, trauma, medication-induced (e.g., digoxin may
cause mesenteric vasospasm; also vasopressors, psychotropic
drugs, danazol, gold, estrogens), hematologic disorder,
volvulus, and strangled intestinal hernias.

What is the In the absence of gangrene or evidence of perforation,

treatment for management is conservative. This usually includes intravenous
acute fluid, bowel rest, and broad-spectrum antibiotics.
ischemic
colitis?

What is the In uncomplicated cases, symptoms resolve in 24 to 48 hours

usual and the colon heals itself in 1 to 2 weeks; however, it can
prognosis for progress to chronic colitis and stricture formation.
patients with
ischemic
colitis?

What is acute Acute ischemia of the mesentery and small bowel. It may lead
mesenteric to intestinal perforation if not diagnosed and treated early.
ischemia?

What are Hypovolemia, sepsis, congestive heart failure, recent

some myocardial infarction, arrhythmias; mesenteric ischemia has
nonocclusive also been seen after cardiac surgery or dialysis.
conditions
that can
result in
acute
mesenteric
ischemia?

What Factors that predispose to thrombotic (e.g., polycythemia or

conditions hypercoagulable states) or embolic disease (e.g., atrial
may cause fibrillation or endocarditis)
occlusive
vascular
disease and
subsequent
acute
mesenteric
ischemia?

What are Pain out of proportion to exam (20% to 30% are painless).
symptoms Decreased or absent bowel sounds.
and signs of Occult blood that rapidly progresses to frankly bloody stool.
acute Hypotension, tachycardia, fever, elevated WBC count, and
vascular acidosis may occur if transmural infarction occurs and
occlusion? peritonitis develops.

What serum Lactic acid (causing an anion gap acidosis) can point to the
markers are diagnosis. However, an elevated lactic acid indicates that
available? infarction is already occurring.

What are the Portal venous gas or pneumatosis intestinalis may occur late.
 CT findings? CT angiography or magnetic resonance angiography may be
helpful.

What is the Potential options include surgical revascularization,

treatment for percutaneous angiographyguided revascularization, intra-
acute arterial infusion of thrombolytic or vasodilator agents, or
mesenteric systemic anticoagulation. In patients with nonocclusive disease,
ischemia? attempts to optimize blood flow are important.

What venous Mesenteric venous thrombosis causes approximately 10% of

disorder can cases of intestinal ischemia. Predisposing factors include
cause hypercoagulable states and cirrhosis. It may present as acute
intestinal or chronic disease.
ischemia?

What is the If there is no evidence of complication, anticoagulation is

treatment for preferred.
mesenteric
venous
thrombosis?

What causes Atherosclerosis is the most common cause. The pain is usually
chronic postprandial because of the increased blood flow required for
mesenteric digestion.
ischemia?

How is the Doppler ultrasounds, magnetic resonance angiography, or spiral

diagnosis of CT may be helpful. If these are abnormal or if clinical
chronic suspicion is very high, angiography should be performed.
mesenteric
ischemia
made?

What does Complete or near-complete occlusion of at least two of the

abdominal three major splanchnic arteries
angiography
show in
patients with
chronic
mesenteric
ischemia?

What are Percutaneous transluminal angioplasty or arterial bypass or

treatment endarterectomy
options for
chronic
mesenteric
ischemia?

P.199

Diverticular Disease
What is the Colonic diverticula are common, occurring in approximately
incidence of 50% of patients >60 years of age.
diverticular
disease?

Where do In the proximal duodenum, near the ampulla of Vater

small bowel
diverticula
 most
commonly
arise?

How common Common, occurring in approximately 20% of the population

are small
bowel
diverticula?

What is A persistent omphalomesenteric ductthe most common

Meckel's congenital abnormality of the GI tract
diverticulum?

What is the Meckel's diverticulum occurs in 2% of the population, it is

rule of 2s? found approximately 2 feet from the ileocecal valve, and it is
approximately 2 cm long.

What is Approximately 50% of all Meckel's diverticula contain

unusual about heterotopic tissue (e.g., functional gastric mucosa, pancreatic
the tissue, colonic epithelium, and even biliary epithelium).
composition
of the
Meckel's
diverticulum?

What are the Those containing gastric mucosa can cause ileal ulceration
most common with bleeding. Other complications include diverticular
complications inflammation, perforation, or obstruction.
of a Meckel's
diverticulum?

How is the A Meckel's scan (with technetium-99m) may help if gastric

diagnosis of a mucosa is present, particularly in children with bleeding.
Meckel's However, this test is less helpful in adults, even if they
diverticulum present with bleeding. Small bowel follow-through is rarely
made? diagnostic. Angiography may be helpful.

Clinical pearl 90% of patients with colonic diverticula are asymptomatic.

P.200

Diverticulitis1
What is the Sigmoid colon, secondary to increased intraluminal pressures
most
common
location for
diverticulitis
to occur?

How is the Often based on symptoms and physical examination alone.

diagnosis of Abdominal CT scan may be useful. Colonoscopy should be
diverticulitis avoided because of the risk for perforation.
made?

What CT Characteristic findings include fat stranding, bowel wall

findings are thickening, and air seen in the diverticula.
characteristic
of
diverticulitis?
 What is the Patients with mild disease may be managed with a liquid diet
treatment for and broad-spectrum antibiotics with anaerobic coverage
diverticulitis? (generally ciprofloxacin and metronidazole), whereas patients
with more severe disease will require bowel rest and
intravenous fluids in addition to broad-spectrum antibiotics.

What if a Patients generally begin to improve within 48 hours. If no

patient improvement is noted, complicated diverticulitis (e.g., abscess,
doesn't perforation, or fistula) should be suspected.
respond to
adequate
therapy?

P.201

Diverticular Bleeding
How does Bleeding is usually painless. Some 70% of diverticular bleeds
diverticular are localized in the right colon. Bleeding stops spontaneously
bleeding in 80% of cases.
usually
present?

How are A tagged red blood cell scan helps localize the site,
bleeding angiography allows for the option of embolization if a bleeding
diverticula source is found. Colonoscopy allows for localization and
localized and therapy with epinephrine injection if the bleeding does not
treated? obscure visualization of the colon. Surgical resection of
involved areas may be required. Long-term therapy involves
prevention of progression of disease with a stool-softening
regimen.

What are Spastic diverticular diseaseepisodic or constant constipation,

some other crampy lower quadrant abdominal pain, and postprandial
complications abdominal distension
of colonic Stricturessecondary to chronic inflammation
diverticular
disease?

P.202

Inflammatory Bowel Disease

What is the Incidence rates for IBD show geographic variation, with
geographic higher rates in northern countries (e.g., United States,
distribution of United Kingdom, Norway, and Sweden) than in southern
IBD? countries. Within the United States, rates are greater in
northern states.

What The highest incidence is in developed countries. Greater

socioeconomic incidence in higher socioeconomic groups.
classes and Whites are affected more than nonwhites.
ethnicities are More frequent in Jewish populations.
commonly
affected?

Which genders Overall, men and women are affected equally. However, CD
are more itself (excluding UC) is slightly more common in women.
frequently
affected?

What is the age Peak incidence is between ages 15 and 30 years, with a
distribution for second smaller peak between ages 60 and 80 years
IBD? (particularly CD).

What are some Genetic susceptibility: with CD, the risk of IBD for first-
risk factors for degree relatives is about 4%, which is 13-fold higher than in
IBD? control populations. Children of a person with CD have a
10% risk of developing CD.
Smoking appears to increase the risk of CD but may actually
decrease the risk of UC.
Oral contraceptives may increase risk of IBD, particularly
CD.
Dietary and infectious factors may also contribute.

What are the UC: typically involves the rectum, continuous inflammation
bowel of the mucosal layer
differences CD: affects any segment of the GI tract, often discontinuous
between CD and and transmural inflammation
UC?

What are the extraintestinal manifestations of IBD (see Table 5-1)?

What Uveitis
manifestations Episcleritis
occur Erythema nodosum
concurrently Arthritis/arthropathies (peripheral)
with intestinal
disease activity?

What Ankylosing spondylitis

manifestations Pyoderma gangrenosum
occur PSC
independently Other extraintestinal manifestations include gallstones,
of intestinal kidney stones, and demineralizing bone diseases.
disease activity?

P.203

Table 5-1. Differences between CD and UC

Crohn's Disease Ulcerative Colitis

GI tract Mouth to anus Colon

involvement

Gross Skip lesions Continuous from

inflammation rectum

Rectal Rectal sparing 99%

involvement

Histologic Transmural Mucosal or

inflammation submucosal

Histology Focal inflammation and Diffuse

granulomas inflammation
 Fistulae Common Rare

Ulcers Linear or transverse Diffuse or

superficial

Bleeding 20% 98%

Abdominal pain Common Uncommon

Perianal disease 80% 25%

Abdominal mass Common Uncommon

Carcinoma Uncommon Common

Toxic megacolon Rare More likely

Postsurgical Frequent (70%) Rare

recurrence

Smoking Exacerbates CD May be

protective

P.204

What is the Therapy of IBD depends on the severity of inflammation

medical treatment and the site of involved bowel. Mild disease may be
for IBD? treated with the 5-acetylsalicylic acid derivatives.
Immunosuppressive therapy (e.g., azathioprine, 6-
mercaptopurine, cyclosporine, and methotrexate) and
biologic therapies (e.g., infliximab) are utilized as
chronic therapy for moderate to severe disease.
Corticosteroids are generally used for acute flares but
may be required as chronic therapy in more refractory
cases.

What supplement Folic acid, because the 5-acetylsalicylic acid derivatives

should be given in inhibit folic acid absorption
prescribing 5-
acetylsalicylic acid
derivatives?

How can the side Many of the side effects of the 5-acetylsalicylic acid
effects of the 5- derivatives arise from the sulfa group, so newer
acetylsalicylic acid formulations that lack the sulfa group may be tolerated
derivatives be better.
minimized?

What is A corticosteroid that undergoes extensive first-pass

budesonide? hepatic metabolism after it is absorbed in the gut and
thus has a lower incidence of systemic manifestations
than conventional steroids.
 How should They are useful for fistulas or perianal disease as well as
antibiotics be used colitis. Antibiotics used include ciprofloxacin and
in treatment of metronidazole.
IBD?

How should They may be used for treating patients with active
immunosuppressive disease who have not responded to corticosteroids, for
therapies be used maintenance of remission, and as steroid-sparing agents.
in treatment of However, because of their delayed onset of action, they
IBD? have limited usefulness in treating severe acute disease.

How is infliximab May be useful as a steroid-sparing agent or as a bridge

used in treatment to other immunosuppressive medications because it can
of CD? result in rapid improvement. It is also useful for
fistulizing CD and in some cases for maintenance of
disease remission. Overall, approximately two thirds of
patients respond to therapy.

What are Infliximab should not be used in stricturing CD. Also, it

contraindications may result in disseminated tuberculosis; thus all patients
to using should be screened prior to initiation.
infliximab?

Does diet affect No specific diet has been consistently shown to change
disease activity in outcomes in CD. However, initiation of total parenteral
patients with CD? nutrition or elemental tube feeds may actually induce
remission in some patients. Unfortunately, relapse is the
rule on resuming a normal diet.

P.205

Crohn's Disease
What are the causes in CD of:

Diarrhea? Fat malabsorption, bile salt malabsorption, decreased

absorptive surface area, bacterial overgrowth, and decreased
fluid and electrolyte absorption.

Gallstones? Impaired ileal resorption of bile salts (gallstones occur in 15%

to 30% of patients)

Kidney These occur due to reduced intraluminal concentrations of free

stones calcium (because the calcium is bound by free fatty acids,
(oxalate) which are poorly absorbed in patients with small bowel CD),
allowing more unbound oxalate to be absorbed by the colon
into the systemic circulation.

How is the The clinical symptoms and signscombined with endoscopic or

diagnosis of radiographic evidence of ulcerations, strictures, and skip areas
CD made? suggest CD. A biopsy demonstrating noncaseating granulomas
and chronic inflammation also supports the diagnosis.
Anti-Saccharomyces cerevisiae antibodies, or ASCA, may help
make the diagnosis in patients with unclear histology; they are
found in >60% of patients with CD.

When is Surgery may be required in symptomatic obstruction, fistulous

surgical disease, abscess, toxic megacolon, and for patients who
treatment experience intolerable drug toxicity. The goal is to preserve as
used for CD? much bowel as possible. Postoperative recurrence in CD is high
(approximately 70%).
 P.206

Ulcerative Colitis
What are the Rectal bleeding and tenesmus. Systemic symptoms are
clinical features usually absent, and diarrhea is variably present. Extension
of proctitis or of disease can occur but is uncommon. There is little or no
left-sided colitis? malignant potential.

What are the Fewer than four bowel movements per day with minimal
clinical features blood; mild anemia but no fever or tachycardia
of mild UC?

What are the Six or more bloody stools per day, with fever, tachycardia,
clinical features and significant anemia
of severe UC?

What are the Severe bloody diarrhea (at least 10 episodes per day).
clinical features Fever, hypovolemia, and anemia are common, and occur
of fulminant in 5% to 15% of UC patients.
colitis?

What are possible Barium enemas, colonoscopy, medications (e.g.,

precipitating antidiarrheals, anticholinergics, and opiates), and rapid
factors for toxic tapering of corticosteroids in patients with colitis
megacolon?

What is the Complete bowel rest, NG tube suction, stress ulcer

medical prophylaxis, electrolyte replacement, and corticosteroids
treatment of (if active, noninfectious colitis is present)
toxic megacolon?

When is surgery If resolution does not occur within 24 to 72 hours

considered?

How should colon Annual colonoscopy with random mucosal biopsies to look
cancer screening for dysplasia is recommended after 8 to 10 years of UC.
be done in
patients with UC?

When is If significant dysplasia or carcinoma is found

colectomy
recommended?

What is the The goal of surgery in UC is cure; it is indicated for

surgical medical failure and complications such as perforation or
treatment for toxic megacolon.
UC?

P.207

Microscopic Colitis
What is Includes collagenous colitis and lymphocytic colitis, considered
microscopic variants of IBD. Findings include either a thickened collagen
colitis? basement membrane in the colonic epithelium or a lymphocytic
infiltrate in the mucosa. Often the gross appearance on
endoscopy is normal.

Who is It predominately affects middle-aged women.

affected by
 microscopic
colitis?

What is the There is no curative therapy. Medications, to varying degrees,

treatment include 5-ASA products, steroids, antidiarrheal agents,
for antibiotics, fiber, or cholestyramine. Minimizing caffeine, NSAIDs,
microscopic dietary fats, and lactose may help some patients.
colitis?

Appendicitis
What are Poorly localized periumbilical pain (secondary to visceral
symptoms irritation) is followed within several hours by a more steady,
and signs of localized right-lower-quadrant pain (secondary to parietal
appendicitis? peritoneal irritation). Anorexia, nausea, and vomiting usually
ensue.

What Perforation is suggested by fever >38C and leukocyte count

indicators >15,000/mL.
suggest
appendiceal
perforation?

What is the Generally, emergent appendectomy is desirable.

treatment of
acute
appendicitis?

What is the 25% by 24 hours after the onset of symptoms

risk of 50% by 36 hours
perforation 75% by 72 hours
in acute
appendicitis?

P.208
P.209
P.210

Colorectal Polyps, CRC, and Colonic Polyposis

Syndromes
Describe the In most cases of CRC, an area of normal mucosa first
adenomacarcinoma undergoes a genetic mutation
model. (mutations in the APC gene, which is a tumor
suppressor gene, account for approximately 80% of first
hits). When this occurs, the previously normal mucosa
may, as aberrant clones accumulate, develop into an
early adenomatous polyp. The adenomatous cells then
experience additional mutations, leading to various
molecular abnormalities, such as loss of heterozygosity,
deletions/mutations of other tumor suppressor genes
(such as K-ras, p53, or the deleted in colon cancer
gene, or DCC), methylation abnormalities, and/or
mismatch repair genes abnormalities. Over time, these
changes may cause progression from benign adenomas
to frank CRC.

Clinical pearl If a polyp is found at flexible sigmoidoscopy, there is a

10% to 15% chance of finding a more proximal
synchronous polyp; therefore colonoscopy is
recommended.
What is the Endoscopic surveillance should be performed regularly.
treatment if a Hyperplastic polyps do not progress to CRC and should
resected polyp is not affect screening parameters.
benign?

What are the screening recommendations for the following patients?

An average-risk Begin screening at age 50 with colonoscopy every 10

patient with no years or fecal occult blood testing annually with
family history of sigmoidoscopy every 5 years.
CRC?

An average-risk A 3- to 5-year interval between colonoscopies is

patient found to commonly recommended. This may change as we learn
have a few benign more about the natural history of adenomatous polyps
adenomatous polyps and their progression into CRC.
that were
successfully
removed?

A patient with a Begin screening at age 40 or 10 years before the age

first-degree relative of onset of the involved relative (normal intervals
with CRC? between colonoscopy for one involved relative, 5-year
intervals if two first-degree relatives are affected).

A patient with IBD? Initiate annual colonoscopy 8 years after onset of

pancolitis or 15 years after left-sided colitis. Random
biopsies must be performed.

A patient at risk Annual sigmoidoscopy starting at 10 years of age.

for familial
adenomatous
polyposis?

When can screening When a patient has a life expectancy of <10 years.
colonoscopy be
discontinued?

After a person has Presence of preexisting high-risk factors (e.g., personal

adenomatous polyps or family history of CRC or hereditary CRC syndromes),
removed, what are number of polyps identified on previous endoscopic
some factors that studies, and adequacy of previous attempts at
influence the removing polyps
frequency with
which surveillance
colonoscopies should
be performed?

How common is It is the second most common cancer overall in the

colon cancer? United States, with a 6% lifetime risk in the general
population.

How does age affect The incidence doubles every decade from 40 years of
the risk of colon age to 80 years of age.
cancer?

What other factors Personal history of colorectal adenomas or colon

may be associated cancer (relative risk = 2 to 4)
with an increased Personal or family history of polyposis syndrome
risk of CRC? Familial cancer syndromes (see below)
 First-degree relatives with colon cancer
Personal history of IBD (particularly UC)
Personal history of gynecologic cancers

If a person has One first-degree relative with CRC: two- to threefold

family members with increased risk
a history of Two first-degree relatives with CRC: three- to six fold
adenomatous polyps increased risk
or CRC, how much One first-degree relative with CRC at an early age (<50
greater is his or her years): three- to sixfold increased risk
personal risk of One first-degree relative with adenomatous polyp:
adenomatous polyps about twofold increased risk
or CRC?

What other factors High-red-meat diet, high-fat diet, pelvic irradiation,

might increase the alcohol, cigarette smoking, and obesity
risk for CRC?

What are factors that High-fiber diet with fruits and vegetables, exercise,
might protect against NSAIDs, high calcium and folate intake, and
CRC? postmenopausal hormone replacement therapy

Are any serum tumor CEA is a nonspecific tumor antigen associated with
markers useful in colon cancer. It is not diagnostic and is used only to
CRC? monitor for recurrence after treatment or metastatic
spread.

What is the About one third of tumors and polyps are missed,
disadvantage to particularly if smaller than 1 cm in size.
barium enema?

What are the 5-year survival rates of colon cancer by Dukes' staging?

Dukes' A 95% to 100%

Dukes' B1 67%

Dukes' B2 50%

Dukes' C1 40%

Dukes' C2 20%

Dukes' D 0%

How much has Survival rates have changed little in the last 20 years.
survival changed
over the last 20
years?

What is the Radiographs, including a chest radiograph, and liver CT

presurgical scan (particularly with an abnormal hepatic panel)
evaluation of CRC
patients with
potentially
resectable disease?

P.211
P.212
P.213
 P.214

Hereditary CRC Syndromes

What is the HNPCC is an autosomal dominant condition with incomplete
genetic basis for penetrance. It is caused by inherited or germ-line
HNPCC? mutations in various DNA mismatch-repair genes.

What is the >80%. As with most colon cancers, HNPCC tumors arise from
lifetime risk of adenomatous precursors (see adenoma-carcinoma model).
colon cancer in
HNPCC patients?

Is HNPCC a No. Although HNPCC predisposes people to CRC, they

polyposis typically have relatively few adenomatous polyps.
syndrome?

Where are the About 60% to 70% are proximal to the splenic flexure.
CRCs located in
patients with
HNPCC?

What There is a 40% to 60% lifetime risk of developing an

extracolonic extracolonic malignancy. Common sites include the small
cancers are intestine, stomach, ovaries, genitourinary tract, and
associated with pancreas.
HNPCC?

What are the The criteria, referred to as the Amsterdam criteria, are as
clinical features follows:
required for the 1. At least three first-degree relatives with cancer of the
diagnosis of colorectum, endometrium, small bowel, ureter, or renal
HNPCC? pelvis
2. At least two successive generations affected
3. At least one case diagnosed before 50 years of age
When these criteria are met, 50% of families are found to
have a disease-causing mutation.

How often At least every 2 years starting at age 25 years (or 10 years
should screening earlier than the youngest family member found to have a
colonoscopies be CRC)
performed in
patients with an
HNPCC
mutation?

What is the Colectomy is recommended when cancer or an adenomatous

treatment for polyp with advanced histologic features is found.
patients with Prophylactic colectomy for carriers of HNPCC associated
HNPCC found to mutations remains controversial.
have
adenomatous
polyps or CRC?

What are the FAP, Gardner's syndrome, Turcot's syndrome, Peutz-Jeghers

major syndrome, juvenile polyposis, neurofibromatosis, Cowden's
hereditary syndrome, and Cronkhite-Canada syndrome
polyposis
syndromes?

What are the modes of inheritance and the genes involved in these polyposis
syndromes?

FAP and Autosomal dominant; disorders result from mutations in the

Gardner's APC gene on the long arm of chromosome 5. However, both
syndrome? APC alleles must be mutated to result in expression of the
syndrome (i.e., two-hit hypothesis).

Turcot's Usually results from APC mutations (autosomal dominant),

syndrome? but some cases result from mutations in mismatch-repair
genes (autosomal recessive).

Peutz-Jeghers Autosomal dominant with incomplete penetrance; involves

syndrome? mutations in the STK gene on chromosome 19.

Cowden's Autosomal dominant; juvenile polyposis syndrome involves

syndrome? mutations in the PTEN gene on chromosome 10.

Cronkhite- A noninherited syndrome (it is acquired)

Canada
syndrome?

What is FAP and Hereditary polyposis syndromes in which numerous

Gardner's adenomatous polyps develop and there is a very high risk of
syndrome? cancer

What is the Once believed to be separate diseases, FAP and Gardner's

difference syndrome are caused by mutations in the same gene (the
between FAP APC gene) and have similar GI manifestations. Patients with
and Gardner's Gardner's syndrome tend to have more prevalent
syndrome? extraintestinal manifestations (dental abnormalities,
osteomas, thyroid cancer, and desmoid tumors) than do
patients with classic FAP.

What types of Adenomas of the colon, stomach, and small bowel. Benign
polyps are found fundic gland polyps may also be seen in the stomachs of
in FAP and these patients.
Gardner's
syndrome?

How is the There are specific tests to evaluate for the presence of the
diagnosis of FAP abnormal mutated APC protein (i.e., protein truncation
and Gardner's testing) or the mutated gene itself.
syndrome made?

What is the risk 100% (adenocarcinoma)

of colon cancer
in FAP and
Gardner's
syndrome?

Are there any NSAIDs (e.g., sulindac, celecoxib) have been shown to
medical decrease the size and number of polyps in FAP patients.
therapies that However, polyps and cancer still develop; thus surgery
are effective in remains the only definitive treatment.
treating the
colonic polyps in
FAP and
Gardner's
syndrome?
What is Turcot's A syndrome of familial polyposis associated with primary
syndrome? central nervous system tumors (e.g., brain tumors)

What types of Adenomas, similar to those seen in FAP and Gardner's

polyps are seen syndrome
in Turcot's
syndrome?

What is the risk 100% (adenocarcinoma), as in FAP. Proctocolectomy is

of CRC for recommended for patients who have developed multiple
patients with colonic polyps or for people who are found to have the
Gardner's and genetic defect.
Turcot's
syndrome?

What is Peutz- A syndrome involving mucocutaneous pigmentation (buccal

Jeghers mucosa, hands, feet, and perianal skin) with bladder, nasal
syndrome? and GI polyposis

What types of Hamartomatous polyps (mostly small bowel, but also colon
polyps are seen and stomach)
in Peutz-Jeghers
syndrome?

What Polyps can cause intussusception or obstruction. They can

complications also infarct, causing bleeding and abdominal pain.
are associated
with Peutz-
Jeghers
syndrome?

What is the risk <3% risk of cancer

of CRC in
patients with
Peutz-Jeghers
syndrome?

What is juvenile A rare syndrome resulting in nonneoplastic, hamartomatous

polyposis GI tract polyps (mostly colonic, some gastric and small
syndrome? bowel) usually occurring in children between 4 and 14 years
of age

What is the risk At least 10%, possibly higher. They arise from adenomatous
of colon cancer changes within the hamartomatous polyps. Other cancers
with juvenile such as gastric, duodenal, and pancreaticcan also occur.
polyposis
syndrome?

What is An acquired, nonfamilial syndrome, involving GI polyposis

Cronkhite- and cutaneous hyperpigmentation, hair loss, nail atrophy,
Canada diarrhea, weight loss, abdominal pain, and malnutrition in
syndrome? middle-aged patients

What is the It develops in 15% as a result of adenomatous changes

cancer risk in within hamartomatous polyps.
Cronkhite-
Canada
syndrome?

P.215
P.216
 P.217

Pancreas

Diseases of the Pancreas

Acute Pancreatitis
How frequently is an The most sensitive indicator of pancreatitis, it is
elevated serum present in 75% of patients with acute pancreatitis.
amylase seen in
patients with acute
pancreatitis?

How quickly does Within 24 hours; it resolves in 3 to 5 days in the

the amylase absence of ongoing pancreatic injury.
elevate?

What are other Renal insufficiency, salivary gland disorders, acidemia,

causes of and macroamylasemia (amylase binds to proteins and
hyperamylasemia? cannot be filtered), as well as other pancreatic, biliary,
or intestinal processes (pseudocyst, trauma, obstruction
or ischemia)

When are falsely low With hypertriglyceridemia or a history of chronic

amylase levels seen? pancreatitis

How specific is an The most specific indicator of pancreatitis, it is

elevation of serum elevated in 70% of patients with acute pancreatitis. It
lipase? remains elevated longer than amylase.

What complications Shock, ARDS, acute renal failure, hypocalcemia, and GI

are seen with acute hemorrhage can all be seen in severe pancreatitis.
pancreatitis?

How is abdominal CT It can be used to determine the size and appearance of

helpful in acute the pancreas (i.e., diffuse inflammation, necrosis, fluid
pancreatitis? collections), spread of inflammation, and presence of
biliary abnormalities. CT is far superior to
transabdominal ultrasound in visualizing the pancreas.

How is the severity The Balthazar score:

of pancreatitis Grade A: Normal appearance
graded on CT? Grade B: Focal or diffuse enlargement of the pancreas
Grade C: Grade B plus peripancreatic inflammation
Grade D: Single peripancreatic fluid collection
Grade E: Two or more collections of fluid or gas in the
pancreas or retroperitoneum

What is the NPO, fluid resuscitation (often requiring large volumes

treatment for acute secondary to third spacing), and provision of analgesia
pancreatitis? while determining the cause

What are the Ranson Prognostic indicators determined at presentation and

criteria? within 48 hours of admission (see Table 5-2).

What is the 1 to 2 risk factors, <1%

predicted mortality 3 to 5 risk factors, 10% to 20%
rate based on the 6 to 7 risk factors, nearly 100%
Ranson criteria?
What is another APACHE II is a scoring system that ranks various clinical
model for parameters and may be more accurate than the Ranson
calculating severity criteria, but it is more complex and requires computer
of pancreatitis? calculation.

What structures are Bile duct, duodenum, mesenteric vessels, spleen,

potentially affected posterior mediastinum, and diaphragm
in the inflammatory
process?

What is the most Fluid collections occur in approximately 30% of cases;

frequent however, 50% of these respond without intervention.
complication of
pancreatitis?

What are Accumulations of necrotic tissue, pancreatic juice,

pseudocysts? blood, and fat within or near the pancreas, which
occur several weeks after the onset of acute
pancreatitis. They have an organized wall of fibrinous
material without an epithelial lining.

When are empiric The carbapenems have been shown to decrease the
broad-spectrum incidence of infection when pancreatic necrosis is
antibiotics used in identified.
acute pancreatitis
and what antibiotic
is preferred?

What sites are Pericardium, pleura, and synovial surfaces. Alveolar

involved when capillary membranes may also be disrupted, leading to
polyserositis noncardiogenic pulmonary edema or ARDS.
develops in the
setting of
pancreatitis?

What is the cause of Circulating pancreatic enzymes

pancreatitis-induced
DIC?

What causes It is usually caused by hypovolemia or circulating

cardiovascular shock vasodilators.
in pancreatitis?

What is the etiology Splenic vein thrombosis may result from the surrounding
of gastric varices in inflammation.
acute pancreatitis?

Table 5-2. Ranson Criteria for Severity of Acute

Pancreatitis

At Presentation Within 48 Hours

Age >55 years Base deficit >4 meq/L

WBC >16,000/:L BUN increase >5 mg/dL

 Glucose >200 mg/dL Fluid sequestration >6 L

AST >250 IU/L Serum calcium <8 mg/dL

LDH >350 IU/L Hct decrease >10%

PO2 <60 mm Hg

Note: Amylase level is not one of the Ranson criteria!

AST, aspartate transaminase; LDH, lactate dehydrogenase; Hct,
hematocrit.

P.218

Chronic Pancreatitis
Describe An autoimmune process, most common in Asian populations,
autoimmune that causes pancreatic ductal irregularities and pancreatic
pancreatitis. enlargement. Laboratory testing reveals
hypergammaglobulinemia with elevated
IgG4 levels, with the frequent finding of other autoimmune
markers (ANA). Can be associated with other autoimmune
diseases such as Sjgren's or SLE.

What is the Steatorrhea, calcification of pancreas on radiographs or CT, and

classic triad diabetes (<25% of cases)
of chronic
pancreatitis?

What are Abdominal pain, malabsorption, diabetes, and jaundice

symptoms The abdominal pain is typically steady, boring, achy, in the
and signs of midepigastrium, upper quadrants, or periumbilical area,
chronic radiating to the back; worse when supine, better when sitting
pancreatitis? up and leaning forward. The pain is worst in the first 5 years
after diagnosis, then may diminish or resolve in two thirds of
patients.

What are Normal or slightly elevated amylase and lipase; elevated liver
possible function tests (suggests concomitant liver disease, and biliary
laboratory obstruction), elevated glucose (diabetes mellitus), elevated
findings in alkaline phosphatase (osteomalacia), and elevated PT (vitamin K
chronic malabsorption)
pancreatitis?

What One-third show diffuse pancreatic calcifications. CT scans can

radiographic identify calcifications in three quarters of patients.
finding may
be seen on
plain films
in chronic
pancreatitis?

What does ERCP is the gold standard to demonstrate pancreatic ductal

ERCP anatomy. Ductal dilatation, cystic changes, strictures, and
demonstrate calculi may be visualized and potentially treated. Brushings to
in chronic rule out pancreatic carcinoma can also be done.
pancreatitis?
 What other EUS is the most sensitive modality for diagnosing chronic
modality is pancreatitis.
useful in
identifying
changes
consistent
with chronic
pancreatitis?

What Abstinence from alcohol, use of narcotics (addiction is

measures common), celiac ganglion blockade with EUS or fluoroscopic
are taken to guidance, use of ERCP for removal of ductal stones, dilatation
manage pain and stenting of strictures, and providing duct drainage. Surgical
in chronic resection or drainage procedures (e.g., pancreaticojejunostomy,
pancreatitis? or Puestow procedure) may be needed. Pancreatic enzyme
replacement is useful in some but not all patients.

P.219
P.220

Pancreatic Neoplasia
What are the Smoking, African heritage, family history, chronic
risk factors for pancreatitis, exposure to carcinogens, increased age, and a
pancreatic history of diabetes
adenocarcinoma?

What genetic Mutations in the K-ras oncogene occur in 90% and

mutations are mutations in the tumor suppressor genes p16 and p53 occur
associated with in 95% and 50% to 75% respectively.
pancreatic
adenocarcinoma?

What are the Painless jaundice is classically associated with a pancreatic

clinical mass, but symptoms such as abdominal discomfort,
manifestations of anorexia, nausea, and weight loss occur more commonly.
pancreatic Symptoms usually are nonspecific or present late, such that
adenocarcinoma? the diagnosis is generally delayed until late in the disease
process.

What imaging Helical CT scan of the abdomen is the preferred modality

modalities are for diagnosis and to evaluate for metastases. EUS is more
useful in the accurate than CT for evaluating tumor size and nodal
diagnosis of involvement. EUS also allows for biopsy if the diagnosis
pancreatic remains in question.
adenocarcinoma?

What tumor CA-19-9 levels can be useful in monitoring status during

marker can be treatment. CA-19-9 should not be used for diagnostic
used for purposes as its specificity is too low.
following the
status of
pancreatic
adenocarcinoma?

What is the Whipple procedure (resection of the pancreatic head,

current optimal duodenum, first portion of jejunum, and gallbladder with
therapy for CBD) followed by chemotherapy with 5-fluorouracil
pancreatic
adenocarcinoma?

What parameters No evidence of metastases, no involvement of the celiac or

 delineate a superior mesenteric arteries, and patent superior
resectable mesenteric and portal veins.
pancreatic
adenocarcinoma?

What is the Chemotherapy with 5-fluorouracil in combination with x-

treatment of ray therapy is the preferred treatment for locally advanced
choice for disease. Gemcitabine is the preferred chemotherapeutic
unresectable agent for metastatic disease.
pancreatic
adenocarcinoma?

What is the The prognosis is dismal, as even resectable cancer has a 2-

prognosis of year survival rate of only 20%.
pancreatic
adenocarcinoma?

What are the Mucinous cystadenoma, serous cystadenoma, and

three main types intraductal papillary mucinous tumor
of pancreatic
cystic
neoplasms?

Describe A mucin-producing neoplasm that occurs most commonly in

characteristics of the main pancreatic duct in older men. Mucin production
the intraductal may cause obstruction leading to pancreatitis. The risk of
papillary invasive cancer is high and surgical resection should be
mucinous tumor. performed.

Describe Mucinous cystadenomas usually occur as large macrocystic

characteristics of cysts that do not communicate with the pancreatic duct.
the mucinous Aspirates generally demonstrate elevated CEA levels with
cystadenoma. low amylase/lipase levels. Their malignant potential is high
and surgical resection should be performed.

Describe Serous cystadenomas usually occur as a collection of

characteristics of multiple microcystic cysts that do not communicate with
the serous the pancreatic duct. Their malignant potential
cystadenoma. is low, and small, asymptomatic cystadenomas can be
observed.

P.221

Liver and Biliary Tract

What happens to It decreases because bilirubin cannot get into the bowel
the amount of to be metabolized into urobilinogen by the gut bacteria.
urobilinogen in the Thus, in a patient with cholestatic liver enzymes and a
setting of CBD large amount of urinary urobilinogen, it is less likely
obstruction? that CBD obstruction will be the cause of the
cholestasis.

What are the Increased bilirubin productionhemolytic anemia,

causes of ineffective erythropoiesis, blood transfusions, resolving
unconjugated hematomas, defective conjugation (Gilbert's disease,
hyperbilirubinemia? Crigler-Najjar types I and II), and drugs

What is Gilbert's A benign, common cause of mild unconjugated

disease? hyperbilirubinemia, resulting from an autosomal
dominant inherited partial deficiency in bilirubin
glucuronyl transferase activity. Serum bilirubin is usually
 1.3 to 3.0 mg/dL (rarely >5 mg/dL).

What are specific Hereditary disorders (e.g., Dubin-Johnson syndrome,

causes of Rotor's syndrome)
conjugated Hepatocellular diseases
hyperbilirubinemia? Infiltrative diseases (e.g., sarcoidosis, Hodgkin's
lymphoma, tumor, infection, tuberculosis, and abscess)
Extrahepatic cholestasis (e.g., choledocholithiasis, PSC,
biliary stricture or tumor, and obstructive pancreatic
processes)
Intrahepatic cholestasis (e.g., pregnancy, sepsis,
postoperative jaundice, PBC, and medicationsthiazides,
OCPs, NSAIDs)

P.222
P.223

Cholelithiasis
What is the They are formed when the GB becomes supersaturated
pathogenesis of with cholesterol, leading to nucleation and stone
cholesterol formation.
gallstones?

What is the There is no straightforward correlation.

correlation
between serum
cholesterol levels
and gallstones?

What are the The majority occur as multiple, mixed (>70% cholesterol)
characteristics of stones, whereas <10% occur as pure cholesterol (generally
cholesterol single stones).
gallstones?

What are risk Think four Fs:

factors for Female
cholesterol Fat
gallstones? Fertile
Forty

What are some of Diabetes

the other risk Dietrapid weight loss or fasting, cholesterol-lowering
factors for diets
cholesterol Drugsestrogen, clofibrate, octreotide, ceftriaxone
gallstones? Hyperlipidemia
Heredityespecially Pima Indian women
Bile salt malabsorptionpancreatic insufficiency, cystic
fibrosis, ileal disease, ileal bypass or resection

What are the two Black and brown

types of
pigmented
gallstones?

What are the risk Chronic hemolysis, advancing age, long-term total
factors for black parenteral nutrition, and cirrhosis
pigmented
gallstones?

What are the risk Seen mostly in biliary stasis associated with bacterial
 factors for brown infection in bile ducts (e.g., E. coli)
pigmented
gallstones?

What is biliary Relatively, rapid onset of steady epigastric or right-

colic? upper-quadrant pain, which may radiate to the
interscapular area or the right shoulder and may be
associated with nausea and vomiting. Episodes usually last
1 to 6 hours and may follow ingestion of a heavy meal or
occur at night.

How is the Most commonly by ultrasound, which has a sensitivity and

diagnosis of specificity of >90%. CT scan is less reliable.
cholelithiasis
made?

How is the Ultrasound has a sensitivity of only 50%. Elevations in

diagnosis of AST, alkaline phosphatase, and bilirubin to greater than
choledocholithiasis twofold normal values has a greater sensitivity but lower
made? specificity than ultrasound. EUS and MRCP can be useful
diagnostic tools if the clinical picture is unclear. ERCP
should be utilized as both a diagnostic and therapeutic
intervention in those patients with complications such as
cholangitis or pancreatitis.

What are other Biliary stricture formation, gallstone ileus, fistulization,

complications of sepsis, perforation, and peritonitis
cholelithiasis?

P.224
P.225

Acute and Chronic Cholecystitis

What are Approximately 90% of cases are associated with
causes of acute cholelithiasis.
cholecystitis?

How is the The triad of sudden onset of right-upper-quadrant

diagnosis of tenderness, fever, and leukocytosis is highly suggestive.
acute Ultrasound reveals a stone in >90% of cases.
cholecystitis Cholescintigraphy or HIDA scan is the most sensitive imaging
made? modality.

What Thickened GB wall, pericholecystic fluid, and elicitation of

ultrasound Murphy's sign with the ultrasound probe applying direct
findings are pressure over the GB. Sonographic Murphy's sign has a
suggestive of positive predictive value >90%.
acute
cholecystitis?

What is the Conservative therapy includes nothing by mouth, NG tube

treatment of placement if the patient has been vomiting, IV fluids,
acute parenteral analgesics, and IV antimicrobial agents.
cholecystitis? Cholecystectomyopen or laparoscopicis the only definitive
therapy.
Cholecystotomymay be required in severe cases in which
surgery is contraindicated.

What is the 1%
mortality rate
 of acute
cholecystitis?

What is Inflammation of the GB in the absence of gallstones. It is

acalculous associated with a high incidence of complications (e.g.,
cholecystitis? necrosis, gangrene, and GB perforation).

How common is It represents 5% to 10% of all cases of acute cholecystitis.

acalculous
cholecystitis?

What is the 50%; most affected patients are elderly or debilitated with
mortality rate coexisting disease or trauma.
of acalculous
cholecystitis?

How is the Requires a high index of suspicion because symptoms (e.g.,

diagnosis of abdominal pain, nausea, and fever) and laboratory results
acalculous (e.g., leukocytosis and elevated liver enzymes) are not
cholecystitis always present and the disorder may present as an isolated
made? fever in a ventilated patient.
Ultrasound or CT findings of a thickened GB wall,
pericholecystic fluid, intramural gas, sloughed mucosal
membranes, and sonographic Murphy's sign are supportive of
the diagnosis.
Hepatobiliary scintigraphy (e.g., HIDA scan) has sensitivities
ranging from 70% to 90%; false-positive results are frequent.

What is the Urgent cholecystectomy is required in those patients who are

treatment for surgical candidates. Cholecystostomy may be utilized for
acalculous high-risk surgical candidates.
cholecystitis?

What is Infection of the GB by gas-producing organisms including

emphysematous anaerobes such as Clostridium welchii or C. perfringens.
cholecystitis?

What is a Diabetes
predisposing
factor for
emphysematous
cholecystitis?

What is the Imaging via ultrasound or CT can demonstrate characteristic

evaluation and changes. Patients generally derive symptom relief with
treatment of cholecystectomy. If chronic acalculous cholecystitis is
chronic suspected, evaluation with cholescystokinin (CCK)
cholecystitis? scintigraphy to determine GB ejection fraction can be
helpful. Manometry via ERCP can confirm biliary dyskinesia
and allows for stent placement.

Cholangitis
What are Sepsis, hepatic abscess, biliary strictures
complications
of
cholangitis?

What is the Relief of obstruction is essential (via ERCP, percutaneous

treatment for transhepatic cholangiography, or surgery) and intravenous
 cholangitis? antibiotics with coverage for enteric organisms

Acute Hepatitis
What are the causes of The differential can generally be limited to viral,
acute hepatitis that toxic ingestion, or ischemic causes. More rarely,
generate transaminases autoimmune hepatitis can present in this manner.
>1000?

Viral Hepatitis
What virusesother than HAV, HBV, Several, including herpes simplex
and HCVcan cause acute hepatitis? viruses, Epstein-Barr virus, and CMV

P.226

Hepatitis A
What is the mode of Fecaloral
transmission for
HAV?

Why is parenteral Because the viremic phase is short

transmission of HAV
rare?

In the illustration below, the curves mark the appearance of the HAV,
symptoms and signs, various antibodies, and laboratory tests. What antibody
time course is illustrated by:

(From Hoofnagle JH, DiBisceglie AM. Serologic diagnosis of acute and chronic
viral hepatitis. Semin Liver Dis. 1991;11:73.)

Curve 1? Anti-HAV IgG

Curve 2? Anti-HAV IgM

How is the diagnosis Transaminitis (or cholestatic hepatitis) and the

of acute HAV presence of anti-HAV IgM in the serum during acute
infection made? illness. HAV IgG denotes previous infection and
recovery or vaccination. It is present after 3 weeks of
disease and persists indefinitely.
 What complication Aplastic anemia
other than fulminant
hepatic failure can
rarely be seen in
acute HAV infection?

Who should receive Travelers to endemic areas, patients with chronic liver
the HAV vaccine? disease and persons at high risk, such as day-care and
health-care workers

P.227
P.228
P.229
P.230
P.231

Hepatitis B
What happens to The virus is not cytopathic, but it generates a host immune response, resulting in lysis of
hepatocytes after infected hepatocytes.
infection with HBV?

What is the epidemiology In low-prevalence areassuch as the United States, western Europe, Australia, and New Zealand
of HBV infection? the HbsAg carrier rates are 0.1% to 2%. In high-prevalence areas, including Southeast Asia and
sub-Saharan Africa, HbsAg carrier rates are 10% to 20%. HBV accounts for 35% to 70% of all
cases of viral hepatitis worldwide and nearly all cases of virus-induced fulminant hepatic
failure.

What is the risk Approximately 1 in 63,000, mostly because of the window period.
associated with blood
transfusion?

What is the rate of Approximately 90% in HbeAg-positive mothers, while only 30% in HbeAg negative mothers.
perinatal transmission? Breast-feeding does not appear to be a risk factor and cesarean section is not protective.

What is the rate of HBV Approximately 30% (in an unvaccinated health-care worker)
transmission after an
occupationally related
needle-stick injury?

What is the incubation 1 to 6 months

period for acute HBV
(time from exposure to
jaundice)?

In the illustration on the following page, the curves mark the appearance of the HBV symptoms and signs, various
antibodies, and laboratory tests. What antibody time course is illustrated by:
 (From Hoofnagle JH, DiBisceglie AM. Serologic diagnosis of acute and chronic viral hepatitis. Semin Liver Dis. 1991;11:73.)

Curve 1? HbsAg

Curve 2? Anti-HBc IgG

Curve 3? Anti-HBc IgM

Curve 4? Anti-HBs IgG

What happens to markers Serum becomes positive for HbsAg and HBV DNA. HbeAg is detected in patients with high
of HBV during acute HBV circulating levels of HBV; it signals active viral replication and infectivity.
infection?

What happens to the HbsAg persists for >6 months. Over time, anti-HBc IgM wanes and anti-HBc IgG develops.
serologic markers in
chronic HBV infection?

What are the two main Replicative and nonreplicative phases

phases of chronic HBV
infection?

Describe the replicative There is usually HbeAg and HBV DNA in serum, active liver disease (elevated transaminases),
phase of chronic HBV and features of both active and chronic hepatitis on liver biopsy. Spontaneous seroconversion to
infection acquired in a nonreplicative phase occurs at a rate of 10% to 20% per year. This is manifest by clearance of
adults. HbeAg and the development of anti-Hbe.

Describe the replicative These patients are more likely to have chronic HBV, but they often develop immune tolerance
phase of chronic HBV to the virus. When this happens, ongoing viral replication may occur with minimal hepatitis. A
infection acquired in similar rate of seroconversion to a nonreplicative phase is seen (10% to 20% per year); but when
infancy or childhood. it occurs, it is often heralded by a flare of hepatitis.

Describe the During this phase, patients are HbeAg-negative and anti-Hbepositive. Many of these patients
nonreplicative phase of have undetectable HBV DNA by PCR testing, and no
chronic HBV infection. evidence of active liver disease, and they may remain in remission for years.

What happens to HbsAg In a minority of patients, the HbsAg titer may become undetectable over time.
after converting from a
replicative to a
nonreplicative phase?

What are extrahepatic Circulating antigenantibody complexes can result in various conditions, including serum sickness
manifestations of chronic (fever, rash, arthralgia, and arthritis), glomerulonephritis, essential mixed cryoglobulinemia,
HBV infection? papular acrodermatitis (Gianotti-Crosti syndrome), aplastic anemia, and polyarteritis nodosa
 (systemic vasculitis).

What percentage of all 10% to 50%

patients with
polyarteritis nodosa are
HbsAg-positive?

What can cause a flare of Reactivation of active liver disease can occur spontaneously. Also, cessation of
hepatitis in chronic HBV- immunosuppressive medications (e.g., chemotherapeutics or corticosteroids) can lead to
infected patients whose reactivation of hepatitis (due to reconstitution of the immune system).
liver disease has been
quiescent?

How common is cirrhosis Develops in 10% to 30% without treatment

in chronic HBV infection?

What factors are The risk increases with long-standing viral replication. Unlike many other causes of cirrhosis,
associated with increased HBV can lead to HCC even without the development of cirrhosis because of the integration of
risk of HCC in chronic HBV DNA into host DNA.
HBV?

What is lamivudine and A nucleoside analog, reverse transcriptase inhibitor, which has suppressive activity against HBV
how is it used in patients replication. Initially, HBV replication is suppressed in >90% of patients. However, loss of HbsAg
with chronic HBV? is rare, and viral replication often resumes once therapy is discontinued. This may be
associated with a flare of hepatitis.

What happens with Over time, some patients convert back to the replicative phase even while continuing
continued treatment with lamivudine. HBV mutants, such as the YMDD mutant, appear to develop more commonly with
lamivudine? lamivudine therapy.

What is the YMDD mutant A genetic variant of HBV that develops in approximately 30% of patients receiving lamivudine.
of HBV? These mutants continue to replicate. Fortunately, they seem to be less virulent than the wild-
type HBV.

What treatment options Adefovir and entecavir, both nucleoside reverse transcriptase inhibitors, can be used in
are available for resistant cases but are more expensive than lamivudine and have a slower onset of action.
lamivudine resistant Entecavir may also be used as an initial therapy.
HBV?

What could explain a This suggests the presence of a mutant strain of the HBV virus, known as a precore mutant.
negative HbeAg but a This strain of HBV has a genetic mutation that makes the virus incapable of producing HbeAg
PCR test that reveals even though the virus is still actively replicating.
moderate levels of
viremia?

What does superinfection Infection with other hepatotropic viruses (e.g., HAV, HCV, HDV, and CMV) after acquiring HBV,
in an HBV patient mean? which may lead to worsening hepatitis or decompensated liver disease

Who should receive the Members of high-risk groups, all infants, travelers at risk, and people with cirrhosis or chronic
hepatitis B vaccine? liver disease that is not caused by HBV
After sexual exposure to HBV, both hepatitis B immune globulin and the first of three hepatitis
vaccines should be administered within 14 days of exposure. Follow-up doses are given at 1 and
6 months.

P.232
P.233
P.234

Hepatitis C
Are there Six distinct genotypes with multiple subtypes have been identified worldwide.
different Subtypes 1a and 1b are most common in the United States and western Europe (and
subtypes of HCV? are the most difficult to eradicate), followed by genotypes 2 and 3. Genotypes 4, 5,
and 6 are rarely seen in the United States.

What is the <1 in 1 million

current risk of
HCV infection
from an HCV
antibody-negative
blood donation?

What is the risk Approximately 3% (as high as 10%). The risk associated with a stick from a hollow
of HCV infection needle is much higher than that with a solid needle.
for a health-care
worker after a
needle-stick
injury?

What is the rate Sexual transmission of HCV is much less efficient than that of HBV or HIV. Although
of sexual the risk is increased in persons with high-risk sexual practices, persons in monogamous
transmission of relationships with HCV-infected partners appear to have 0.1% annual risk of infection.
HCV?

How often does Approximately 80% will progress to chronic infection. Once this occurs, spontaneous
chronic HCV clearance is uncommon.
develop?

What is the rate Approximately 25% of patients progress to cirrhosis, generally after at least 20 years
of progression to of chronic HCV.
cirrhosis in
chronic HCV?

What is the In patients with cirrhosis, the incidence is approximately 1% to 4% per year. HCC only
incidence of HCC rarely develops in cases of HCV without cirrhosis; thus routine screening is not
in HCV? warranted unless cirrhosis or fibrosis is present on biopsy.

What is essential Although most HCV patients with measurable cryoglobulins are asymptomatic, some
mixed develop a systemic disorder that can manifest with signs and symptoms of a vasculitis,
cryoglobulinemia? such as arthralgias, weakness, purpura, petechiae, peripheral neuropathy, and
Raynaud's phenomenon. In severe cases, glomerulonephritis may occur.

In the illustration below, the curves mark the appearance of the symptoms and signs, various
antibodies, and laboratory tests of a patient with chronic active HCV.

What antibody Anti-HCV IgG

time course is
illustrated by
curve 1?
What conditions Immunocompromised conditions, renal failure, and cases associated with essential
can cause a false- mixed cryoglobulinemia
negative HCV
antibody test?

What is the Supportive care

treatment for
acute HCV
infection?

Which patients Patients with significant extrahepatic manifestations (e.g., glomerulonephritis) and
should be those with persistent viremia, transaminitis, and significant necrosis, inflammation, or
considered fibrosis on liver biopsy (because these patients are at high risk of disease
candidates for progression). Patients with normal transaminases and no significant histologic evidence
treatment of of disease are at less risk of disease progression. In such cases, the decision to treat
chronic HCV? must be tailored to the individual.

When should Treatment should be initiated at 8 to 12 weeks following infection. Patients initiated
treatment be on therapy at 8 weeks have a higher rate of sustained response, but early treatment
initiated after a leads to treatment of more patients who would have spontaneously cleared the
patient contracts infection.
acute HCV?

How is response HCV viral load is evaluated at week 12 of treatment for genotype 1 and week 4 of
to treatment of treatment for genotypes 2 and 3. One should expect at least a 1-log decrease in viral
HCV assessed? load at this time if there is to be an eventual meaningful response. If a 1-log
decrease in viral load is not met, it is reasonable to discontinue therapy to avoid
unnecessary side effects.

In attempting to Approximately 24 weeks for genotypes 2 and 3

eradicate the Approximately 48 weeks for other genotypes
HCV virus, what
are the usual
durations of
treatment?

Of patients who Approximately 95% for at least 5 years. Many of these patients will also have
attain a sustained improvement in their health-related quality-of-life scores and normal or improved
virologic histology on subsequent liver biopsies.
response, how
many will remain
 PCR-negative?

P.235
P.236

Hepatitis D
What is the Its prevalence in an area correlates with that of HBV.
epidemiology of Approximately 5% of HBV carriers have concomitant HDV
HDV? infection. It is rare in Western countries, where most cases
involve high-risk groups (e.g., intravenous drug users and
those who have had multiple previous transfusions).

What is the Like that of HBV. Perinatal transmission is rare. The most
mode of important factor influencing transmission of HDV is the
transmission of presence of an already established HBV infection.
HDV?

What are Superinfection often results in a flareup of hepatitis, often

clinical severe. Of the survivors, >90% will progress to chronic HDV
manifestations with HBV. Less commonly, the HDV infection may resolve
of acute HDV (while the HBV persists), or the HDV superinfection may
superinfection result in clearance of HbsAg. Fulminant hepatitis is not
in patients with uncommon.
chronic HBV?

What is the Variable. In most cases, the disease causes more rapid
course of histologic progression to cirrhosis. Approximately 80% will
chronic HDV progress to cirrhosis in 5 to 10 years. However, many of
infection? these patients remain clinically stable for many years before
decompensated liver disease occurs. In a minority of
patients, a rapidly progressive course to liver failure over
months to years can occur; in another subset of patients, a
benign, nonprogressive course may ensue.

During the During the early period of chronic HDV, the HDV may inhibit
early time HBV replication, making HBV DNA undetectable.
period of
chronic HDV,
what may
happen to the
HBV?

How is the Detection of HDV RNA or HDV antigen in the serum or liver
diagnosis of is the most accurate. Serologic tests to detect antibodies to
HDV made? HDV are commonly used. In the acute phase of coinfection,
antibodies to HDV might not be detectable; repeat serology
in several weeks may be needed to confirm the diagnosis.

What is the Overall, cirrhosis develops in approximately 80% of cases

prognosis of during a 5- to 10-year period. In a minority of patients, the
HDV? flareup of hepatitis caused by HDV superinfection can result
in clearance of the HBV.

What is the Reinfection of the graft liver with HBV, and the severity of
outcome of such recurrences, may actually be decreased by the
HDV and HBV presence of HDV. In some cases, a third form of HDV can
after liver occurHDV can infect the transplanted hepatocytes but HBV
transplantation? reinfection is initially prevented by posttransplant use of
HBV intravenous immune globulin; thus the HDV remains
latent. However, over time, the HBV evades neutralization
 and reinfects the hepatocytes, allowing HDV to replicate.
Clinical hepatitis can then occur.

What is the 15% mortality over 3 years

mortality
associated with
HDV?

Hepatitis E
What serologic HEV IgM is diagnostic of acute infection, whereas HEV IgG
markers suggest occurs months to years after infection.
infection with
HEV?

How long does it Biochemical markers usually normalize over 1 to 6 weeks

take to recover after symptoms manifest.
from HEV
infection?

How is HEV No vaccine is clinically available at this time. HEV

prevented? intravenous immune globulin, for postexposure
prophylaxis, has not shown consistent clinical benefit.

P.237

Hepatitis G
What is An RNA virus currently being studied
HGV?

How is it By blood transfusions. Approximately 2% of eligible donor

transmitted? samples contain HGV RNA.

How is HGV By detection of HGV RNA by PCR, or detection of antibodies by

infection enzyme immunoassays. Presence of antibodies suggests
detected? clearance of infection and also immunity.

What is the The significance of HGV infection is uncertain. There is

clinical conflicting literature regarding the pathogenicity of HGV
significance infection. In cases of chronic liver disease in which HGV RNA is
of HGV? present, it is unclear whether the HGV is causative or not.

Drug-Induced Liver Injury

What is the It accounts for 10% of cases of adult hepatitis (40% of cases
epidemiology of in patients >50 years of age) and 25% of all cases of
DILI? fulminant hepatic failure.

What is the In most cases, the drug or drug metabolites cause direct
pathophysiology hepatocellular injury and necrosis. In other cases, DILI arises
of DILI? from injury to the biliary epithelium, vascular endothelium,
and autoimmune damage via hapten production on the
surface of hepatocytes. Often the reactions are idiosyncratic
(i.e., not dose dependent, and may occur long after the drug
was started).

What are some Ethanol, acetaminophen, certain NSAIDs, methotrexate,

drugs that azathioprine, 6-mercaptopurine, intravenous tetracycline,
cause liver and L-asparaginase
injury via
 direct toxicity?

What are some Phenytoin, sulfonamides, amoxicillin-clavulanate, halothane,

drugs that dapsone, isoniazid, ketoconazole, amiodarone, and
cause liver propylthiouracil
injury via
idiosyncratic
reactions?

What are some Jin bu huan, ma huang, valerian, germander, skullcap,

common herbal chaparral leaf, comfrey, mistletoe, and herbal teas
remedies that containing toxic alkaloids
may cause liver
injury?

Is liver biopsy Liver biopsy obtained early may be helpful in identifying the
helpful in the type and extent of injury. However, histologic findings are
diagnosis of often not specific to DILI and may be seen in hepatitis from
DILI? other causes.

What is the Supportive care and avoidance or discontinuation of

treatment of suspected agents. Most cases resolve.
DILI?

P.238
P.239

Acetaminophen Hepatotoxicity
What happens to After ingestions of therapeutic doses, most (>90%) is
acetaminophen conjugated to glucuronide or sulfates into nontoxic
when ingested, and metabolites. Approximately 4% is metabolized by the
what causes the cytochrome P-450 system, resulting in N-acetyl-p-
hepatic injury? benzoquinoneimine (NAPQI), a toxic intermediate that
normally is rapidly inactivated by conjugation to
glutathione and then renally excreted. However, after
large ingestions of acetaminophen, more NAPQI is
produced and the stores of glutathione are overwhelmed,
resulting in decreased clearance of the NAPQI, which
causes hepatocyte injury.

What is the effect Increases the risk of toxicity by the same mechanisms
of malnutrition on
the effect of
acetaminophen
hepatotoxicity?

How is the Clinical suspicion and history, verified by laboratory

diagnosis of testing
acetaminophen
hepatotoxicity
made?

What are the initial Manifestations in the first 24 hours include nausea,
symptoms of vomiting, malaise, and diaphoresis.
acetaminophen
toxicity?

What are the lab Liver enzyme abnormalities begin to appear at 24 hours
findings of and usually peak at 72 hours (transaminitis may be
acetaminophen severe and evidence of hepatic synthetic dysfunction
 toxicity and when may develop).
are they seen? Evidence of renal failure, hypoglycemia, and
encephalopathy develops maximally at this stage.

How is the Serum acetaminophen levels should be drawn 4 hours

potential risk of and 24 hours after ingestion. These values should be
hepatotoxicity evaluated using the Rumack-Matthews nomogram. This
after nomogram applies only to acute ingestions with an
acetaminophen accurate, established time of ingestion.
ingestion
determined?

What is considered Ingestion of >7.5 to 10 g (250 mg/kg) of acetaminophen

to be a toxic over a 24-hour period
acetaminophen Ingestion of >4 g over a 24-hour period in a person with
dose? increased susceptibility to acetaminophen

What prognostic The King's College Criteria and the APACHE II score (see
indicators are discussion of acute liver failure, below)
available for
acetaminophen
overdose?

What is the In one study, hyperphosphatemia was seen exclusively in

significance of nonsurvivors; signifying lack of hepatocyte regeneration
hyperphosphatemia (hepatocyte regeneration requires phosphate, generally
in acetaminophen leading to hypophosphatemia) and renal failure.
overdose?

What is the Early on, it decreases the risk of severe hepatotoxicity by

mechanism of limiting the formation of NAPQI, increasing glutathione
action for N- stores (which facilitate detoxification of NAPQI), and
acetyl-cysteine? enhancing sulfation of acetaminophen to nontoxic
metabolites. Once hepatotoxicity develops, N-acetyl-
cysteine may be beneficial because it has antioxidant
and anti-inflammatory activities. It may also improve
blood and oxygen delivery to the liver.

P.240

Acute Liver Failure

What are the main Acetaminophen is the leading cause (40%). Many other
causes of ALF? drugs (as outlined in the discussion of DILI) as well as
toxins (Amanita) may cause ALF. Viral causes include
HAV, HBV, HCV, HEV in pregnancy, HSV, EBV,
adenovirus, and CMV. Autoimmune hepatitis, acute
fatty liver of pregnancy and inherited disorders
(Wilson's) along with vascular disease (VOD and Budd-
Chiari) can also cause ALF.

What are the King's The King's College Criteria are indicators of poor
College Criteria? prognosis without liver transplantation. They have
good specificity but relatively poor sensitivity.

What are the poor Arterial pH <7.3 following volume resuscitation or the
prognostic indicators combination of PTT >100 with creatinine >3.4 with at
of the King's College least grade III encephalopathy
Criteria
(immunosuppression)?
 What are the poor PTT >100 or any three of the following: drug toxicity,
prognostic indicators age <10 or >40, jaundice preceding coma by >7 days,
of the King's College PT >50, total bilirubin >17.5
Criteria
(nonacetaminophen)?

What other prognostic The APACHE II score has similar specificity to the
indicators are King's College Criteria but better sensitivity.
available for Unfortunately the APACHE score requires larger
evaluating ALF and amounts of data, requires the use of a computer
the need for program, and thus is not as easily accessible.
transplantation?

What is the main Early mortality is most often related to cerebral

cause of death in edema. Once patients have survived the early stages
ALF? of ALF, infection becomes the leading cause of death.

What lab markers Correction of transaminases does not necessarily imply

signify recovery and recovery; it may only indicate a burned-out liver.
hepatocyte Recovery of
regeneration? synthetic function is essential to determine improving
liver status. Hypophosphatemia is a marker of
hepatocyte regeneration, as phosphate is required for
cellular activity. Elevated AFP levels are also markers
of hepatocyte regeneration.

P.241

Other Hepatobiliary Disorders

Primary Sclerosing Cholangitis

What are usual Elevated alkaline phosphatase (>2 times normal), elevated
laboratory serum transaminases (<5 times normal), and fluctuating
findings at the bilirubin levels
time of Elevated serum IgM in 40% to 50% of cases
diagnosis? Positive p-ANCA in 65% of cases

What diseases 70% have UC, but CD, autoimmune diseases, and infiltrating
have been seen disorders can also be risk factors.
in association
with PSC?

What is the No medical therapy has yet consistently improved outcomes

medical therapy in PSC patients, including immunosuppressive medications,
for PSC? colchicine, and ursodeoxycholic acid.
Medical therapies directed at the manifestations of the
disease include:
Antibiotics for ascending cholangitis
Cholestyramine, antihistamines, and ursodeoxycholic acid,
which may improve pruritus
Replacement of fat-soluble vitamins

What is the Liver transplantation is the only lifesaving treatment for

surgical therapy end-stage PSC. The 5-year survival is 85% to 90%.
for PSC?

What is the Up to 20% of transplanted patients experience recurrence.

recurrence rate
of PSC
following liver
 transplantation?

Clinical pearls PSC can precede UC symptoms by several years, so

colonoscopy should be performed despite the absence of
bowel symptoms. In patients with known UC, do not be
fooled by quiescent bowel symptoms, because PSC is not
related to IBD disease activity.

P.242
P.243

Primary Biliary Cirrhosis

What is PBC? An autoimmune destruction of intrahepatic bile ducts,
leading to chronic cholestasis and cirrhosis. It may be in
the spectrum of autoimmune liver disease.

What other Sjgren's syndrome and keratoconjunctivitis sicca are each

conditions are found in up to 75% of patients. Scleroderma, CREST
associated with syndrome, and Hashimoto's thyroiditis are also seen.
PBC?

What symptoms Insidious fatigue and pruritus, with jaundice developing

and signs may be months or years later, occurs in 50% to 65% of cases.
seen on Hyperpigmentation, hepatosplenomegaly, hirsutism, and
presentation of xanthomata may be present.
PBC? 25% of patients are diagnosed owing to asymptomatic
elevations in alkaline phosphatase and other liver enzymes.

What are Elevation of alkaline phosphatase is the most characteristic

laboratory abnormality (usually 2 to 20 times normal).
findings in PBC? Transaminases are mildly elevated (1 to 5 times).
Hyperbilirubinemia is not common at diagnosis (only 10%),
but significant rises may occur with progression of disease
(and serve as a prognostic indicator).
Cholesterol and triglycerides are often elevated.

What are other Antimitochondrial antibody in 90% to 95% of cases (the

laboratory subtype M2 is most specific for PBC).
findings in PBC? Elevated serum IgM (4 to 5 times normal). These patients
often fail to convert IgM to IgG following immunizations.
Other autoantibodies (ANA, antihistone, antithyroid) may
also be present.

What is seen on Granulomas are classic, but, more commonly there is

liver biopsy in inflammatory destruction of bile ducts, a paucity of bile
PBC? ducts, and portal fibrosis.

What is the Ursodeoxycholic acid may delay progression of disease or

medical therapy the need for transplantation and may improve survival free
specifically for of transplant. Colchicine or methotrexate have also been
PBC? shown to improve survival.

How is Ursodeoxycholic acid and other cholesterol-lowering

hyperlipidemia in medications may help. However, there does not appear to
PBC treated? be an increased risk of atherosclerosis in PBC patients.

How are fat With replacement of fat-soluble vitamins and medium-

malabsorption chain triglycerides as well as a low-fat diet
and steatorrhea
in PBC treated?
 How is pruritus in It may respond to ursodeoxycholic acid, antihistamines,
PBC treated? cholestyramine, or naloxone.

What is the With proper immunosuppression, there is no recurrence of

recurrence rate disease following transplant.
of PBC following
liver
transplantation?

What is the Survival is 10 to 15 years in asymptomatic patients but

prognosis for PBC only 7 years in symptomatic patients.
patients without
transplantation?

What are the They include patient age, level of hepatic function
poor prognostic (bilirubin, PT, albumin), and histologic scores. AMA levels
indicators for do not affect prognosis.
PBC?

P.244

Autoimmune Hepatitis
What are the Type Iclassic autoimmune hepatitis, typically characterized
main forms by positive ANA (80%) or ASMA (70%). The majority have
of elevated levels of IgG.
autoimmune Type IIdefined by the presence of antibodies to liver and
hepatitis and kidney microsomes, which typically develops in girls or young
what groups women.
do they Overlap syndromesconditions in which the histologic features
affect? and serologic markers of both autoimmune hepatitis and PBC
(or, less commonly, PSC) coexist.

What are the Transaminitis is usually greater than alkaline phosphatase or

typical liver bilirubin.
enzyme
abnormalities
seen in cases
of
autoimmune
hepatitis?

What is seen Portal inflammation with lymphocytes and plasma cells, erosion
on liver of the limiting plate, piecemeal necrosis, and rosette formation
biopsy in
autoimmune
hepatitis?

What are Corticosteroids are the mainstay of treatment and are generally
treatment given with a very gradual taper over a 2-year period. Other
options for immunosuppressive medications, such as azathioprine, are
autoimmune sometimes used in addition to a steroid agent. Note:
hepatitis? Decompensated liver disease is not an absolute
contraindication to therapy; many of these patients will
respond with significant clinical improvement.

What is the Remission is achieved in approximately 80% of cases, usually

response within several months. Up to 50% of cases remain in remission
rate to or have only mild inflammation for several months to years
treatment of after discontinuation of therapy. However, over time, most
autoimmune patients will require repeat therapy as well as chronic
 hepatitis? maintenance immunosuppressive therapy.

What is the The overall survival, including patients with cirrhosis, is >90%.
prognosis of
autoimmune
hepatitis?

P.245

Wilson's Disease
What is An autosomal recessive disorder of chromosome 13 resulting
Wilson's in progressive copper accumulation affecting the brain, liver,
disease? eyes, heart, kidneys, and hematopoietic cells. Normal
hepatocyte elimination of copper into the bile is impaired.

What are There are several different manifestations, ranging from

hepatic asymptomatic liver enzyme abnormalities to cirrhosis or even
manifestations fulminant hepatic failure. Common biopsy features include
of Wilson's macrosteatosis, chronic hepatitis, and fibrosis or cirrhosis.
disease?

What are some Kaiser-Fleischer rings (slit lamp) and sunflower cataracts,
ophthalmologic which are especially prevelant in patients with
manifestations neuropsychiatric manifestations
of Wilson's
disease?

What are some Fanconi syndrome, renal tubular acidosis, kidney stones, and
renal proteinuria
manifestations
of Wilson's
disease?

How is the Elevated serum copper, low serum ceruloplasmin (<20

diagnosis of mg/dL), elevated 24-hour urinary copper (>100 g/day), and
Wilson's elevated quantitative measurement of copper in a liver
disease made? biopsy specimen

P.246

Hereditary Hemochromatosis
What are the Most cases are inherited in an autosomal recessive
genetics of fashion. The most commonly identified HFE mutations are
hereditary the C282Y and H63D mutations. Although uncommon,
hemochromatosis? African American people do develop hemochromatosis,
and current gene testing is often unrevealing, suggesting
that mutations in other, yet unidentified loci exist. People
who are compound heterozygotes (e.g., one C282Y
mutation and one H63D mutation) may develop some
degree of hemochromatosis.

What tests may Elevated fasting serum transferrin saturation (>50% to

be used in 55%), ferritin (may be >1000 ng/mL), and iron. HFE gene
attempting to testing. Imaging studies, particularly MRI, are not
diagnose diagnostic but may suggest the existence of hepatic iron
hereditary overload.
hemochromatosis?

What is the The hepatic iron content of a dry liver biopsy specimen is
hepatic iron divided by the person's age (in years). Most normal
 index? subjects have a hepatic iron index of <1.0. An index >1.9
supports the diagnosis of iron overload. Note: Up to 15% of
hemochromatotic patients will have an index <1.9,
particularly if they are asymptomatic.

Is a liver biopsy Not necessarily. Some clinicians defer liver biopsies in

required in all people thought to be at lower risk.
patients with
hereditary
hemochromatosis?

What are HCC: 20- to 30-fold increased risk (even patients without
potential life- cirrhosis are at increased risk)
threatening Increased risk of certain infections, such as Listeria,
complications of Yersinia enterocolitica, and Vibrio vulnificus (thus
hereditary patients should avoid processed meats, high-risk dairy
hemochromatosis? products, and undercooked seafood)

P.247

Nonalcoholic Fatty Liver Disease

Who is affected Classic risk factors include female gender, obesity, diabetes,
by nonalcoholic and hyperlipidemia. However, it may be seen in patients who
steatohepatitis? have few or none of these characteristics. Children may also
be affected.

What are Most patients are asymptomatic, although they may have
symptoms and fatigue or right-upper-quadrant discomfort. Hepatomegaly is
signs of often seen.
steatohepatitis?

What are There are no specific diagnostic laboratory tests. Modest

laboratory transaminitis (two to three times normal) is common.
findings of Alkaline phosphatase and bilirubin elevation may occur (in
steatohepatitis? <50% and 10% to 15% of cases, respectively).

How is the Presence of typical liver enzyme abnormalities, without

diagnosis of another explanation despite reasonable evaluation for other
steatohepatitis causes. Imaging studies may suggest fatty infiltration but
made? cannot differentiate between simple fatty liver versus
steatohepatitis. Liver biopsy, although not always absolutely
required, is the gold standard.

What is the Although this is usually an indolent disease, some patients

natural history develop progressive fibrosis with eventual cirrhosis and portal
of nonalcoholic hypertension.
steatohepatitis?

Cirrhosis
What is the Child- A scoring system that predicts prognosis and helps
Turcotte-Pugh in pretransplantation risk stratification.
classification?

P.248

Table 5-3. Modified Child-Turcotte-Pugh

Classification
 1 Point 2 Points 3 Points

Albumin >3.5 2.83.5 <2.8

Bilirubin <2.0 2.03.0 >3.0

Encephalopathy None Grade I or II Grade III or IV

Ascites None Mild Difficult to control

PT (sec/control) <4 46 >6

What is the Child's class A = score 5 to 6

Child-Turcotte Child's class B = score 7 to 9
scoring criteria? Child's class C = score 10 to 15

What are the 1- and 3-year survivals for a Child-Turcotte:

Class A? 85%, 60%

Class B? 60%, 35%

Class C? 40%, 25%

What other In 2002 the United Network for Organ Sharing (UNOS)
classification adopted the Model for End-stage Liver Disease (MELD)
systems are Score for determination of organ allocation. The MELD
available to score provides an accurate assessment of 3-month survival
prognosticate and is superior to the Child classification.
patients with
cirrhosis?

What are the It incorporates bilirubin, creatinine, and INR into a log
components of scale.
the MELD score?

P.249

Varices
When do Varices form when the pressure gradient between the portal
varices form? and hepatic system reaches >12 mm Hg (normal <5 mm Hg).

What is the Greater than one third of compensated cirrhotics will develop
risk of varices. The risk is higher with cirrhosis from alcohol, higher
developing Child classification, and evidence of thrombocytopenia.
varices?

What is the Risk of bleeding is increased with variceal size and

prognosis for characteristics (red wale marking) as well as worsening liver
varices? function. Overall mortality from bleeding varices is 30%.

What is the Acute treatment is aimed at stabilizing the patient with IV

acute fluid, blood transfusion as needed, and an octreotide drip.
treatment for The patient can then be taken for endoscopic band ligation.
esophageal Studies have shown that antibiotic coverage during
 varices? hospitalization for an acute hemorrhage (usually
ciprofloxacin) decreases infection and mortality.

What is a final A Sengstaken-Blakemore tube can be used to control bleeding

option if until the patient is stabilized and definitive therapy can be
bleeding provided. Blakemore tubes pose a high risk of esophageal
cannot be perforation and infarction.
controlled?

What is the Prophylaxis is based on directly treating visible esophageal

chronic varices with banding along with medical management aimed
therapy for at decreasing portal hypertension. Portal pressure should be
esophageal reduced with propranolol, with a target dose based on a 25%
varices to reduction in heart rate (or a goal of resting HR 50 to 60) with
reduce the the addition of a long-acting nitrate if tolerated. TIPS may be
rebleeding risk necessary for continued variceal bleeding episodes with
in patients optimal management.
who have had
prior
bleeding?

What is the As opposed to esophageal varices, gastric varices do not

treatment of respond as well to band ligation or sclerotherapy. TIPS or
bleeding transplantation have been used in this setting. Studies are
caused by being performed to evaluate the efficacy of obliterating
gastric gastric varices by injecting them with rapidly polymerizing
varices? glue-like compounds.

P.250

Table 5-4. Serum to Ascites Albumin Gradient

SAAG !1.1 SAAG <1.1

Pre-liver portal hypertension: Inflammation: tuberculous

PVT, SVT, schistosomiasis peritonitis, secondary
peritonitis, pancreatitis, bowel
infarct

Liver portal hypertension: Low oncotic pressure: nephrotic

cirrhosis, acute liver failure, syndrome, protein-losing
massive hepatic malignancy enteropathy

Post-liver portal hypertension: Malignancy: peritoneal

Budd-Chiari, congestive carcinomatosis, Meig's syndrome
hepatopathy, tricuspid
regurgitation

Ascites
How is the A gradient of >1.1 implies that the ascites is a result of portal
serum-to- hypertension (with 97% accuracy). Most commonly this implicates
ascites cirrhosis. Preliver causes of an elevated SAAG include portal vein
albumin thrombosis and splenic vein thrombosis, while postliver causes
gradient include CHF and Budd-Chiari.
 (SAAG)
useful?

P.251

Spontaneous Bacterial Peritonitis

What is the Translocation of bacteria through the gut wall into lymphatics
pathogenesis or bloodstream, with subsequent seeding of the ascitic fluid.
of SBP? Decreased opsonizing activity within the ascitic fluid also
contributes.

What are the Most commonly aerobic gut flora (e.g., E. coli, Klebsiella, and
most common less commonly Streptococcus and Staphylococcus species).
organisms Anaerobic infections are rare.
involved in
SBP?

Why is Gram's Since organisms average one per milliliter of ascitic fluid,
staining of Gram's staining of fluid is almost always negative for
ascitic fluid organisms.
usually a low- Therefore, inoculation of blood culture bottles, instead of
yield sending a sample in a syringe or empty tube, can increase the
procedure? culture-positivity rate from 50% to 80% in patients with >250
polymorphonuclear cells per cubic millimeter in the ascitic
fluid.

What if Consider secondary peritonitis (e.g., bowel perforation,

multiple abscess)
organisms are
cultured?

What ascitic Ascitic fluid glucose <50 mg/dL, total protein >1 g/dL, lactate
fluid dehydrogenase greater than the upper normal limit for serum
characteristics lactate dehydrogenase, and elevated amylase are suggestive
can help of secondary bacterial peritonitis.
differentiate
SBP from
secondary
peritonitis?

What are risk Ascitic fluid total protein <1 g/dL

factors for Prior history of SBP
SBP? Serum bilirubin >2.5 mg/dL
Variceal hemorrhage

What is the Intravenous cefotaxime should be used for hospitalized

treatment for patients, while an oral fluoroquinolone can be used as an
SBP? outpatient therapy for uncomplicated cases. Recent data
suggest that intravenous albumin on hospital days 1 and 3 may
decrease the incidence of renal failure (which occurs in 30% to
40% of patients with SBP) and decrease overall mortality.

What is the The incidence of death owing to infectious complications

prognosis for (e.g., shock) has decreased dramatically as a result of early
patients with detection and treatment of SBP. In-hospital mortality from
SBP? other causes approaches 20% to 40%; 1- and 2-year mortality
rates remain high (70% and 80%, respectively). Future risk is
reduced with appropriate antibiotic prophylaxis and proper
diuresis.

P.252
Hepatorenal Syndrome
What are the Type 1the more acute and severe form, manifest by a
clinical precipitous decline in renal function (usually to glomerular
manifestations filtration rate <20 mL/min) within a 2-week period, often
of HRS? with oliguria or anuria
Type 2a more insidious, gradual decline in renal function,
without other etiologies (e.g., nephrotoxic medications,
dehydration), in a patient with advanced liver disease (often
with diuretic refractory ascites)

How is the Progressive azotemia with creatinine >2.5 mg/dL, over days to
diagnosis of weeks, in patients with acute or chronic liver failure
HRS made? Urine volume <500 mL/day
Urine sodium <10 meq/L (off diuretics) and urine osmolarity
greater than serum
Benign-appearing urinalysis
Failure to respond to a fluid challenge to exclude prerenal
azotemia and exclusion of other causes of renal failure

What is the >90% mortality

prognosis of Type IMean survival 2 weeks
HRS? Type IIMean survival 6 months

Portosystemic Encephalopathy
What is the One-year survival is only 40%.
mortality of
patients
diagnosed
with PSE?

What are the Increased ammonia level is a marker of PSE (elevated in up to

laboratory 90% of cases). However, the degree of elevation does not
findings in correlate with stage of PSE.
PSE?

Once PSE is Once a patient is determined to have PSE, there is little

diagnosed, benefit from measuring serial ammonia levels.
should
ammonia
levels be
followed?

What are the Ingestion of animal-derived proteins should be sharply

dietary minimized in the acute setting but only modest restriction
changes should be utilized for chronic therapy.
needed to
minimize PSE?

What are the Correction of precipitating causes and use of medications to

other general reduce the load of nitrogenous products absorbed from the GI
treatments for tract are the mainstays of treatment.
PSE?

What are the Lactulosea nonabsorbable disaccharide, which is

main types of metabolized by gut bacteria, leading to acidification of the
medical intestinal contents, resulting in conversion of absorbable
therapies for ammonia (NH3 ) into nonabsorbable ammonium (NH4 + ) and a
PSE, and how
change in gut flora causing a decrease in NH 3 producing
 change in gut flora causing a decrease in NH 3 producing
do they work?
organisms.
Antibiotics (e.g., neomycin, metronidazole)decrease the
numbers of ammonia-producing gut flora.
Zinc supplementationincreases the conversion of NH 3 to NH 4
and can be useful in refractory cases.

P.253

Hepatopulmonary Syndrome
What is HPS? Hypoxemia and frequently platypnea (dyspnea upon
standing) and orthodeoxia (oxygen desaturation with
upright position) caused by pulmonary vascular dilation and
arterialvenous shunts

What else may Portopulmonary syndrome and ventilationperfusion

cause dyspnea mismatch (caused by diaphragmatic elevation from ascites,
and hypoxia in resulting in atelectasis)
patients with
chronic liver
disease?

How is the Contrast echocardiogram (e.g., bubble studies) is the

diagnosis of HPS initial study of choice.
made?

How is contrast A contrast material (e.g., bubbles within agitated saline) is

echocardiography injected into a peripheral vein. Bubbles normally appear
useful in HPS? in the right heart but are filtered by the pulmonary
capillaries, so they never reach the left heart. When a
right-to-left shunt exists, bubbles are seen in the left
heart. If the shunt is an intracardiac shunt, bubbles appear
in the left heart within three cardiac cycles, whereas
intrapulmonary shunts, such as in HPS, take longer (3 to 7
cardiac cycles).

How is Although not routinely obtained, angiography may reveal

pulmonary abnormalities supporting the diagnosis of HPS, and it helps
angiography used exclude other causes of hypoxemia, such as pulmonary
in HPS? emboli. Contrast may cause issues, however.

What is the Liver transplantation for patients with significant hypoxia.

treatment for Case reports suggest benefit from medications such as
HPS? aspirin and methylene blue.

Why is it Severe pulmonary hypertension is a contraindication to

important to liver transplant.
differentiate HPS
from pulmonary
hypertension?

P.254
P.255

Portopulmonary Hypertension
What is PPHTN? Pulmonary hypertension associated with portal hypertension
in the absence of secondary causes of pulmonary
hypertension

What is the Unknown, but may involve humoral mediators from the gut
 pathophysiology entering the systemic circulation rather than being
of PPHTN? metabolized by the liver, leading to the pulmonary
vasoconstriction, remodeling of the muscle layer within the
pulmonary arterial walls, and in situ thrombosis. Genetic
factors may play a role.

What are Symptoms, which may initially be subtle, include dyspnea on

clinical exertion, fatigue, chest pain, syncope, orthopnea, or
(symptomatic) hemoptysis.
manifestations
of PPHTN?

What are the Examination may reveal an accentuated P2 , tricuspid

physical signs regurgitation murmur and edema. Most patients have
of PPHTN? manifestations of portal hypertension.

How is the Echocardiography shows evidence of pulmonary hypertension.

diagnosis of Pulmonary angiography is the gold standard. If pulmonary
PPHTN made? hypertension is identified, tests to exclude other secondary
causes should be performed.

What is the Like treatments used for primary pulmonary hypertension,

treatment for including anticoagulants to prevent in situ thrombosis of
PPHTN? pulmonary arteries and vasodilators (e.g., epoprostenol,
nitrates). Both types of therapy must be used cautiously in
patients with chronic liver disease.
Transplantation is considered for mild to moderate PPHTN
but may be associated with poor outcomes with severe
PPHTN.

What is the Poor, especially without treatment. Major causes of death

prognosis for include right heart failure and infections.
PPHTN?

Hypersplenism
Why does hypersplenism It results from portal hypertension, causing
occur with cirrhosis? sequestration and destruction of blood cells.

Should patients with Surgical splenectomy is not routinely

hypersplenism undergo recommended.
splenectomy?

Tumors of the Liver

How are hemangiomas recognized? They are often found
incidentally.

What is the treatment for hepatic adenomas? Surgical resection

What are the most common malignancies Metastases from other

affecting the liver? sources

P.256
P.257

Hepatocellular Carcinoma
What is the Prevalence varies worldwide, being highest in sub-Saharan
epidemiology Africa, China, Hong Kong, and Taiwan. Although the United
of HCC? States is a low-prevalence region, the incidence has increased
 during the last two decades.

What are Cirrhosis of any cause. Others include race (e.g., Asian and
predisposing Eskimo), male gender, environmental carcinogens (e.g.,
factors for tobacco, aflatoxin, and betel nut chewing), viral infection
HCC? (especially HBV), hereditary hemochromatosis, and Clonorchis.

Does HCC Yes. Approximately 20% of cases occur in noncirrhotic livers,

occur in whereas 80% occur in the setting of cirrhosis.
noncirrhotic
patients?

What is the Approximately 3% to 4% per year

annual
incidence of
HCC in
patients with
compensated
cirrhosis?

What are Many patients do not have symptoms directly attributable to

clinical HCC. Manifestations may include abdominal pain, weight loss,
manifestations early satiety, palpable mass, obstructive jaundice,
of HCC? intraperitoneal bleeding caused by rupture, and bone pain
caused by metastases. Rarely, HCC may cause paraneoplastic
syndromes, causing hypoglycemia, watery diarrhea,
erythrocytosis, or hypercalcemia.

Clinical pearl HCC should always be considered when a previously stable

cirrhotic patient decompensates with worsening
encephalopathy or ascites (often as a result of PVT).

What is the Seeding the needle track with tumor cells, resulting in
concern about extrahepatic disease
liver biopsy
for HCC
besides
bleeding?

What is the Most cases are found late in the course of chronic liver
prognosis for disease, resulting in median survivals of 6 to 20 months after
HCC? diagnosis.

What factors Hepatic function, tumor size, and the presence of metastases.
determine Fibrolamellar HCC occurs more commonly in young patients
prognosis for without underlying liver disease and has a much better
HCC? prognosis.

For which Those with adequate liver function reserve, smaller tumors
patients (e.g., >5 cm), and no evidence of metastases.
should tumor
resection be
considered?

What factors Single tumors <5 cm, !3 tumor nodules each >3 cm, and
indicate that absence of metastases or local invasion into blood vessels or
liver lymphatics. In carefully selected patients, 5-year survivals of
transplant is a 70% to 80% may be achieved.
viable option
for cure?
 P.258
P.259

Liver Transplantation
Clinical pearl Thomas Starzl performed the first human liver
transplantation in 1963.

What are the Advanced cardiopulmonary disease, active sepsis,

absolute extrahepatic malignancy, active alcohol or substance abuse,
contraindications anatomic abnormalities precluding transplantation, and
to liver inability of the patient to understand or accept the
transplantation? procedure and subsequent immunosuppressive medications

What are the Advanced age (>65 years), inadequate social or family
relative support, intrahepatic tumor >5 cm, or SBP. In some
contraindications transplant centers, cholangiocarcinoma and HIV are also
to liver contraindications.
transplantation?

What is the <10 units packed RBCs. No transfusions are needed in up to

usual number of 30% of cases.
blood
transfusions
required during
cadaveric liver
transplantation?

What is the Immunosuppressive regimens vary but usually include

postoperative corticosteroids, cyclosporine or tacrolimus, and
medical therapy azathioprine or mycophenolate.
after
transplantation?

What are the postoperative complications after transplantation at the

following times:

Immediate Procurement injury (graft dysfunction as a result of

postoperative inadequate preservation), thrombosis or stenosis of vascular
period? anastomoses, biliary complications in 5% to 10% of cases,
and hyperacute rejection (usually as a result of preformed
antibodies). The most frequently encountered technical
complications result from damage to the biliary tree.

Early Acute cellular rejection (usually after the fifth day

postoperative postoperatively); bacterial, viral, or fungal infection, renal
period? insufficiency

Late Chronic rejection (e.g., vanishing bile duct syndrome)

postoperative and recurrence of primary disease
period?

When do Patients are at highest risk for bacterial and fungal

infections most infections in the first 2 months following transplant. If they
commonly occur are on standard-dose immunosuppressants, their risk of
posttransplant? infection approaches that of the normal population at 6
months. The standard use of trimethoprim sulfamethoxazole
and acyclovir, for Pneumocystis jirovecii and herpes
prophylaxis respectively, has lowered the incidence of
these infections.
What is the 1- Between 85% and 90% for most liver diseases
year survival for
patients who
undergo liver
transplantation
in the United
States?

What is the 3- >70%. Survivors usually have a good quality of life. Some
year survival for 85% return to their previous occupation; women have had
patients who subsequent normal pregnancies.
undergo liver
transplantation
in the United
States?

What long-term Hypertension as a result of immunosuppressants occurs in

medical 50% of patients. Hyperlipidemia occurs in approximately
problems occur 25% of patients and is generally treated with statins.
after liver Diabetes develops in more than 30% of patients and
transplantation? generally requires insulin for control. Patients are also at
increased risk for osteoporosis and skin cancer.
Editors: Bergin, James D.
Title: Advanced Medicine Recall, 1st Edition
Copyright 2009 Lippincott Williams & Wilkins

> Table of Contents > Section II - The Specialties > Chapter 6 - Hematology

Chapter 6
Hematology

Abbreviations
ACT Activated clotting time

APC Activated protein C

aPPT Activated partial thromboplastin time

ATIII Antithrombin III

BMT Bone marrow transplantation

CKD Chronic kidney disease

CLL Chronic lymphocytic leukemia

CML Chronic myelogenous leukemia

CMML Chronic myelomonocytic leukemia

CVA Cerebrovascular accident

DDAVP 1-desamino-8-D-arginine vasopressin (desmopressin acetate)

DIC Disseminated intravascular coagulation

DTI Direct thrombin inhibitor

ELISA Enzyme-linked immunosorbent assay

ET Essential thrombocytosis
G-CSF Granulocyte colony-stimulating factor

GFR Glomerular filtration rate

HELLP Hemolysis, elevated liver enzymes, and low platelets

syndrome

HIT Heparin-induced thrombocytopenia

HITT Heparin-induced thrombocytopenia and thrombosis

Hgb Hemoglobin

HUS Hemolytic uremic syndrome

ITP Idiopathic or immune thrombocytopenic purpura

IVF Intravenous fluid

LAP Leukocyte alkaline phosphatase

LDH Lactate dehydrogenase

MCV Mean cell volume

MDS Myelodysplastic syndrome(s)

MI Myocardial infarction

PCR Polymerase chain reaction

PNH Paroxysmal nocturnal hemoglobinuria

PT Prothrombin time

PV Polycythemia vera

RA Refractory anemia

RAEB-1 Refractory anemia with excess blasts (<5%)

RAEB-2 Refractory anemia with excess blasts (519%)

 RARS Refractory anemia with ringed sideroblasts

RCMD Refractory cytopenia with multilineage dysplasia

RCMD-RS Refractory cytopenia with multilineage dysplasia and ringed

sideroblasts

RDW Red cell distribution width

RI Reticulocyte index

RPI Reticulocyte production index

MDS-U Myelodysplastic syndrome, unclassified

MDS 5q- Myelodysplastic syndrome associated with isolated chromosome

5q deletion

RAEB-T Refractory anemia with excess blasts in transformation

SLE Systemic lupus erythematosus

TIBC Total iron-binding capacity

TSH Thyroid-stimulating hormone

TTP Thrombotic thrombocytopenic purpura

VTE Venous thromboembolism

vWD von Willebrand's disease

vWF von Willebrand factor

P.261
P.262

Red Blood Cells

What is hemoglobin Hemoglobin A 2 is a tetramer of two alpha and two
A 2? delta chains. Hemoglobin A 2 constitutes
approximately 2% of normal adult hemoglobin.

When are teardrop In disorders that result in infiltration of the bone

cells seen? marrow space, resulting in crowding out of normal
bone marrow components. These disorders are known
as myelophthisic disorders.

Give examples of Examples include malignant infiltration of the bone

myelophthisic marrow; myeloproliferative disorders, especially
disorders: myeloid metaplasia with myelofibrosis; and infections
such as in tuberculosis.

What type of blood Myelophthisic disorders are commonly associated with

smear is commonly a leukoerythroblastic blood smear.
associated with
myelophthisic
disorders?

What is a The presence of nucleated RBCs, early myeloid

leukoerythroblastic precursors (metamyelocyte and younger), and giant
blood smear? platelets on the smear

What is an An RBC with a few irregular spiny projections

acanthocyte? unevenly distributed on the membrane of a cell with
a reduced volume

When are In spur cell anemia, severe liver disease, and

acanthocytes seen? abetalipoproteinemia

What is a burr cell? Also called echinocytes, burr cells are characterized
by numerous regular scalloped projections that are
evenly distributed on the RBC surface.

When are echinocytes In patients with severe renal disease or liver disease
seen?

What is a target cell? An RBC with a bull's-eye appearance, with

hemoglobin color in the center and periphery of the
cell

What causes the The cells have an increased ratio of surface area to
target appearance? volume; the redundant cell membrane causes the
target appearance.

When are target cells In thalassemia or other hemoglobinopathies, liver

seen? disease, or disorders of splenic function

What is a An RBC with a slitlike central pale area. These cells

stomatocyte? are also referred to as fish-mouth cells.

When are In ethanol abuse and in an inherited disorder called

stomatocytes seen? hereditary stomatocytosis

P.263

Anemias
How may anemias A useful formulation is to think of anemias as arising
be categorized? from RBC underproduction, destruction or loss, or
sequestration.

What tests should The MCV can be used to categorize the anemia as
be ordered in the microcytic, normocytic, or macrocytic. Measuring the
initial workup of reticulocyte count, checking renal function, and
anemia? reviewing the peripheral smear are also integral parts of
the initial workup.

What is a corrected One that is corrected for the baseline hematocriti.e.,

reticulocyte count? an adequate reticulocyte count in someone with a
severe anemia should be higher than that in a
nonanemic person.

What is a normal !5%

(nonanemic)
corrected
reticulocyte count?

What methods can 1. The absolute reticulocyte count equals the

be used to percentage of reticulocytes multiplied by the RBC
determine the count.
reticulocyte count? 2. The corrected reticulocyte count is determined by
multiplying the percentage of reticulocytes by the
patient's hematocrit and dividing by the normal
hematocrit.

What absolute An absolute reticulocyte count >100,000/"L usually

reticulocyte count suggests an adequate bone marrow response to blood
suggests an loss or hemolysis.
adequate marrow
response to anemia
or blood loss?

What is the A correction factor

 reticulocyte index?

How is the Take the corrected reticulocyte count divided by (1 +

reticulocyte x), where x = 0.5 for every 10% decrease in Hct.
production index
calculated?

How is the Under conditions of severe anemia, reticulocytes are

reticulocyte count released from the marrow prematurely and finish their
useful? maturation in the peripheral circulation, giving a falsely
high estimate of daily RBC production.

What does an An appropriately elevated reticulocyte count suggests

elevated that the anemia is secondary to acute blood loss or a
reticulocyte count hemolytic process.
suggest?

What does a low An inappropriately low reticulocyte count suggests that

reticulocyte count the process is at least partly caused by decreased bone
suggest? marrow production. So a RI <2 for a Hct of 10% to 35%
indicates a hypoproliferative anemia. Very frequently,
mixed pictures are present.

P.264

Microcytic Anemias
What are the causes of Iron deficiency, thalassemias, sideroblastic
microcytic anemia? anemia, and sometimes anemia of chronic
disease

In a patient with an elevated Thalassemia. To confirm this suspicion,

reticulocyte count and microcytic the peripheral smear should be reviewed
anemia, what diagnosis is and a hemoglobin electrophoresis ordered.
suggested?

In a patient with a microcytic A serum ferritin level

anemia and a low reticulocyte
count, what test should be
ordered?

What does a low ferritin level If the ferritin is low, the patient likely
indicate? suffers from iron deficiency anemia, at
least in part.

How sensitive and specific is a A ferritin <15 ng/mL has a specificity of

 low ferritin level with regard to 99% for iron deficiency anemia but a
the diagnosis of iron deficiency? sensitivity of only 60%. Note: A cause of
blood loss must be identified.

If the ferritin is normal with a Serum creatinine

low reticulocyte count, what test
should be ordered next?

What does an elevated creatinine If the patient has an elevated creatinine

and normal ferritin suggest? with a normal ferritin, the likely cause of
anemia is renal insufficiency.

What other lab test should be In patients with mild-to-moderate

considered in patients with mild abnormalities of renal function, it is
to moderate renal dysfunction? useful to check an erythropoietin level for
confirmation.

In a patient with a low TIBC or transferrin

reticulocyte count, normal
ferritin, and normal renal
function, what blood test should
be done?

What do low TIBC or transferrin A low TIBC or transferrin suggests a

levels indicate? diagnosis of anemia of
inflammation/chronic diseases.

What is the most common cause Thalassemia

of significant microcytosis
without anemia?

P.265
P.266

Iron Deficiency
Does a normal serum No. Inflammatory states and liver disease can
ferritin rule out iron elevate the serum ferritin level into the normal
deficiency anemia? range (ferritin is an acute-phase reactant). In these
cases, the anemia is usually multifactorial.

What is the gold Prussian blue stain for iron stores in a bone marrow
standard for the aspirate
diagnosis of iron
deficiency?
 After making the Finding the reason for the iron deficiency which is
diagnosis, what is the commonly blood loss from the GI tract
next critical step?

When should the iron Ferrous sulfate is best absorbed away from meals;
be taken? however, it is better tolerated with food.

Is there anything that Simultaneous administration of vitamin C facilitates

can be done to iron absorption.
improve the iron
absorption?

What are some of the Gastrointestinal upset, constipation, and nausea.

side effects of oral iron Stool softeners should always be used with iron
therapy? therapy.

What is done for IV iron formulations are sometimes needed if the

patients who do not patient cannot tolerate oral iron or does not absorb
absorb iron well or it.
cannot tolerate the
medication?

How long does it take The reticulocyte count peaks in 5 to 10 days. It

for oral iron to begin usually takes 2 to 3 months of continuous iron
to increase the therapy to reestablish the body's iron stores.
reticulocyte count?

P.267

Thalassemias
What is the Normal. A low MCV with normal ferritin without
hemoglobin evidence for beta thalassemia or a hemoglobinopathy
electrophoresis are clues to the diagnosis. PCR analysis can now be
pattern with alpha done to confirm the diagnosis of alpha thalassemia.
thalassemia trait?

What is hydrops Deletion of all four alpha-globin genes. This is

fetalis in relation to incompatible with life and the fetus usually dies in
thalassemia? utero.

What is hemoglobin H Three of the four alpha-globin genes are

disease? dysfunctional. Hemoglobin H forms as a result, a
tetramer of beta chains. This is the most severe form
of alpha-thalassemia that is compatible with life.
 How does hemoglobin As significant anemia in early childhood
H disease present?

What are the common Hemolysis, hypersplenism, and anemia. Iron overload
consequences of (secondary to transfusions) leading to end-organ
hemoglobin H damage is relatively uncommon.
disease?

How is the diagnosis By demonstration of microcytic anemia with target

of beta thalassemia cells and ovalocytes, moderate poikilocytosis,
minor made? basophilic stippling, and reticulocytosis. Hemoglobin
electrophoresis shows an elevated percentage of
hemoglobin A 2 .

What is beta Abnormalities of both beta-globin genes with markedly

thalassemia major? reduced-to-absent beta-chain synthesis. This disorder
is also referred to as Cooley's anemia.

How does beta With severe anemia within the first 6 months of life
thalassemia major resulting in growth retardation unless the patients are
present? transfused

What are the Transfusion-related infections and iron overload

predominant medical secondary to massive transfusion requirements.
problems in patients
with beta thalassemia
major due to?

What is beta Both beta-globin genes are abnormal, but one of the
thalassemia genes is partially functional and can still synthesize a
intermedia? small amount of normal beta-globin chain.

What are the signs Usually, patients do not require transfusions and have
and symptoms of beta mild splenomegaly. However, cardiomegaly and
thalassemia osteoporotic fractures can develop.
intermedia?

P.268

Sideroblastic Anemia
What is a An erythroid precursor with increased iron granules in the
sideroblast? cytoplasm

What are ringed Erythroid precursors with large iron granules within
 sideroblasts? mitochondria ringing the nucleus. Normal erythroid
precursors have a few small punctate iron granules
scattered throughout the cytoplasm.

What is the An enzymatic defect of heme synthesis does not allow iron
defect that to be incorporated into the heme molecule. There are
results in the both hereditary and acquired causes. When this is a
accumulation of lifelong process, however, it is likely due to hereditary
iron within the sideroblastic anemia.
mitochondria in
ring sideroblasts?

What are the Idiopathic, MDS, lead poisoning, and drug use (e.g., use of
acquired causes isoniazid, hydralazine, chloramphenicol, and ethanol)
of sideroblastic
anemia?

What is the Phlebotomy or chelation. Pyridoxine (vitamin B6 ) may lead

treatment for to an increase in the hematocrit in some patients with the
sideroblastic hereditary forms. Removal of offending drugs/toxins is
anemia? vital for acquired causes. Supportive care is the mainstay
in the MDS variety. Some idiopathic forms respond to
erythropoietin and G-CSF.

Hemoglobinopathies
How are acute IVF and pain management with opioids. Avoid
painful episodes meperidine (the metabolite accumulates and can
(vaso-occlusive crisis) cause seizures). Give supplemental oxygen if patient is
in sickle cell patients hypoxic.
managed?

What is sickle cell Hypoxia, infiltrate on CXR, pain, and dyspnea

chest syndrome
characterized by?

What are the causes May be due to infection, thrombosis, or fat emboli
of sickle cell chest
syndrome?

How is sickle cell Transfusions to decrease the percentage of Hb S

chest syndrome
managed?

What causes aplastic Parvovirus B19 infection, which is usually self-limited

 anemia in sickle cell in immunocompetent patients.
patients?

What is hemoglobin A heterozygous condition in which one allele for the

SC disease? beta chain is hemoglobin S and the other allele is
hemoglobin C

How is hemoglobin Patients with hemoglobin SC disease usually have

SC disease different fewer symptoms, but they may be equally affected.
from sickle cell Patients with SC disease have a higher frequency of
anemia? avascular necrosis of the femoral head and
proliferative retinopathy.

What is sickle beta One of the beta-chain alleles has hemoglobin S and
thalassemia disease? the other allele has dysfunctional beta-chain synthesis.

How does the course Even though the disease is usually less severe than
of sickle beta sickle cell anemia, the clinical course can be identical.
thalassemia disease The amount of normal hemoglobin A present usually
compare to that of correlates with the severity of the disease.
sickle cell anemia?

P.269
P.270

Normocytic Anemias

Anemia of Inflammation
What is seen on bone Staining the bone marrow reveals normal or
marrow staining in increased iron stores, but iron within the
anemia of inflammation? erythroblasts is decreased or absent.

How is the diagnosis of The diagnosis should be considered in a patient

anemia of inflammation with a systemic illness, a hypoproliferative
made? anemia, and normal iron stores. A low TIBC or
transferrin is highly suggestive of anemia of
inflammation.

When differentiating iron

deficiency anemia from
anemia of inflammation,
what is seen with regard
to:
 The RDW? In iron deficiency anemia, the RDW is high; in
patients with anemia of inflammation, the RDW is
normal.

The serum ferritin In iron deficiency anemia, the ferritin is low

level? (unless there is a concomitant inflammatory
process, recent blood transfusion, or liver injury).
In patients with anemia of inflammation, the
serum ferritin level is normal or elevated.

The TIBC and In iron deficiency anemia, the TIBC or transferrin

transferring level? level is elevated. In patients with anemia of
inflammation, the TIBC is decreased.

If you still cannot figure In some situations, an iron stain of the bone
it out, what else can be marrow is required to differentiate these
done to differentiate iron disorders. Especially in hospitalized patients, both
deficiency anemia and may coexist.
anemia of chronic
disease?

How do you treat anemia Ideally, the underlying disorder is treated and the
of inflammation? anemia resolves. If a patient requires transfusions,
alternative causes for the anemia should be
considered. If necessary, erythropoietin can
increase the hematocrit in many patients.

Anemia of Renal Failure

At what GFR do Particularly in patients with a GFR <50 mL/min.
erythropoietin levels
usually drop?

What Hgb level should Evaluation in patients with CKD should begin when
prompt further the Hgb is <12 mg/dL in females and <13.5 mg/dL in
evaluation? males.

P.271

Hemolytic Anemias
What are the broad Thalassemias, hemoglobinopathies, autoimmune
categories of hemolytic anemia, RBC membrane disorders,
hemolytic anemias? microangiopathic hemolytic anemias, and enzyme
deficiencies of the hexose monophosphate shunt and
the Embden-Meyerhof pathway (i.e., glycolysis)
What is the In an extravascular hemolytic anemia, RBCs are
difference between removed by the reticuloendothelial system, primarily in
an extravascular the spleen. Intravascular hemolytic anemias result from
hemolytic anemia destruction of RBCs within the vasculature, as happens
and an intravascular with the microangiopathies (TTP/HUS, DIC, etc.).
hemolytic anemia?

Is the reticulocyte Yes, unless the bone marrow is simultaneously affected

count usually by a hypoproliferative process such as iron deficiency,
elevated in vitamin B12 deficiency, anemia of inflammation, or a
hemolytic anemia? primary marrow disorder.

What biochemical Elevated LDH, unconjugated bilirubin, and urine

abnormalities urobilinogen with a decreased haptoglobin or, with
suggest a hemolytic severe cases of intravascular hemolysis, hemoglobinuria
anemia?

What disorders are Lymphoproliferative disorders, Mycoplasma

associated with cold pneumoniae, infectious mononucleosis, and syphilis
antibody
autoimmune
hemolytic anemia?

What are cold Antibodies whose affinity for their antigen is increased
antibodies? at relatively low (<37C) temperatures, usually but not
always of the IgM type

What is the Avoidance of cold. Can consider cytotoxic agents

treatment of cold particularly if associated with lymphoproliferative
antibody disorder. For acute, severe hemolysis, can consider
autoimmune apheresis.
hemolytic anemia?

What disorders are Idiopathic, autoimmune (SLE), viral, lymphoproliferative

associated with disorders (CLL), and numerous drugs
warm antibody
autoimmune
hemolytic anemia?

What are the warm IgG antibodies that react with RBC membrane proteins
antibodies? at room temperature

What is the Steroids are the mainstay to reduce the antibody

treatment of production. In refractory cases, cytotoxic drugs or
 autoimmune splenectomy may be successful. Transfusion of RBCs is
hemolytic anemia? imperative in patients with circulatory collapse and
symptoms associated with heart disease.

What is the difficulty Finding compatible blood

in transfusing these
patients?

What are the RBC PNH, hereditary spherocytosis, hereditary elliptocytosis,

membrane disorders and spur cell anemia of severe liver disease
associated with
hemolysis?

What are the causes Mechanical heart valves, infected heart valves,
of microangiopathic TTP/HUS, malignant hypertension, DIC, preeclampsia or
hemolytic anemia? eclampsia, HELLP syndrome, connective tissue diseases,
and malignancy

What is the Mechanical heart valves may directly shear the RBCs. In
pathophysiologic other disorders, fibrin strand formation in the
process in microcirculation traps and shears the RBCs.
microangiopathic
hemolytic anemia?

P.272

Macrocytic Anemias
What is Macrocytic anemia associated with delayed nuclear
megaloblastic maturation and with normal to increased cytoplasmic
anemia? maturation, producing large erythroid precursors. This type
of anemia is caused by disorders affecting DNA or RNA
synthesis or repair.

What are the Vitamin B12 or folate deficiency, chemotherapy,

causes of antiretroviral therapy, and other disorders of DNA synthesis
megaloblastic
anemia?

What should be Reticulocyte count, serum B12 and folate levels, TSH, and
the first tests peripheral blood smear
ordered for the
evaluation of a
patient with
macrocytic
anemia?
 A patient with an Hemolytic anemia
elevated
reticulocyte
count and
macrocytic
anemia suggests
what diagnosis?

What are the Anemia of inflammation, iron deficiency secondary to

causes of anemia gastrointestinal blood loss, vitamin B12 and folate
associated with deficiency, hypersplenism, and mild hemolysis
liver disease?

What peripheral Macrocytosis with target cells. In severe liver disease,

smear findings markedly abnormal RBC shapes (spur cells) can be seen.
suggest liver These abnormalities appear to be caused by cholesterol
disease? synthesis abnormalities in the liver.

What laboratory Cytopenias of two or more lineages (WBC, RBC, platelets)

and peripheral are suspicious. RBCs are usually large, with
smear findings macroovalocytes. Coarse basophilic stippling can be seen.
suggest a MDS? Hypogranulation, nuclear sticks, and hypo- or
hypersegmentation of neutrophil nuclei are highly
suggestive.

What test is done Examination of the bone marrow aspirate and biopsy are
to confirm the required to make a definitive diagnosis of an MDS.
diagnosis of an Dysplastic changes of hematopoietic precursors, an
MDS? increased percentage of blasts, pathologic and ringed
sideroblasts, and clonal cytogenetic abnormalities are all
suggestive of an MDS.

P.273

Erythrocytosis
What three mechanisms 1. Decreased plasma volume (unknown
produce the increased mechanism).
hematocrit seen in 2. Underlying lung disease causing hypoxemia.
cigarette smokers? 3. Lower oxygen delivery to tissues. Carbon
monoxide from smoke has a higher affinity for
hemoglobin than oxygen, resulting in the
lower oxygen delivery.

P.274
Pancytopenia
What are the causes Disorders involving infiltration of the bone marrow,
of pancytopenia? hypersplenism, vitamin B12 or folate deficiency,
myelodysplasia, aplastic anemia, PNH, and
medications

What is the Leukoerythroblastosis

characteristic finding
on peripheral smear
in infiltrative
disorders of bone
marrow?

What are the Congestive splenomegaly (e.g., cirrhosis and portal

disorders of the vein thrombosis), lymphomas, Gaucher's disease,
spleen that result in Niemann-Pick disease, Letterer-Siwe disease, and
pancytopenia? infectious diseases (e.g., kala-azar, miliary
tuberculosis, and syphilis)

Aplastic Anemia
What is the differential Toxin effects, viral infection, hypoplastic MDS,
diagnosis of aplastic hypoplastic acute leukemia, PNH, and
anemia? myelofibrosis

Pure RBC aplasia may be Parvovirus B19

caused by what infectious
agent?

What tumor may be Thymoma

associated with pure RBC
aplasia?

What are treatment options Immunosuppression with antithymocyte globulin

for aplastic anemia? and/or cyclosporine plus steroids, or allogeneic
BMT

P.275

Leukocytes

Leukopenia
Below what neutrophil 0.5 # 10 9 /L
 count is the patient at
significantly increased
risk of serious bacterial
infection?

What are some common Clozapine, thioamides,

drug-related causes of trimethoprimsulfamethoxazole, phenytoin,
neutropenia? chemotherapy, phenothiazine, procainamide, and
beta lactams

What are some of the Bone marrow disorders (e.g., tumor infiltration,
other causes of fibrosis, leukemia, aplastic anemia), megaloblastic
neutropenia? disorders, sepsis, autoimmune neutropenia, collagen
vascular diseases, and hypersplenism

What is seen on the No myeloid activity. Patients are at extremely high

bone marrow risk of infection and sepsis.
examination of patients
with agranulocytosis?

What is the treatment Immediate discontinuation of all drugs associated

for agranulocytosis? with agranulocytosis and administration of
antibiotics for signs or symptoms of infection.
Should granulocyte activity not reestablish itself, G-
CSF may be started.

Leukocytosis
What is a leukemoid An increase in the WBC count to >25 # 109 /L secondary
reaction? to another condition

What are causes of Leukemia and reactive states, such as infection,

leukocytosis? extreme stress, trauma, and cancer

Neutrophilia
What are An increase in intensity of staining and number of
toxic myeloperoxidase granules within neutrophils
granulations?

In whom are In patients with active infection or bone marrow stress,

toxic including that caused by G-CSF
granulations
seen?
 How can a In CML, the spleen is usually enlarged, the LAP level is very
leukemoid low, and there is often basophilia, none of which characterize
reaction be a leukemoid reaction. If in doubt, the presence of the
differentiated Philadelphia chromosome is pathognomonic for CML.
from CML?

P.276

Lymphocytosis
What are the causes of Infectious mononucleosis, pertussis infection,
marked lymphocytosis chronic lymphocytic leukemia, and acute
(>15 ! 10 9/L)? lymphocytic leukemia

Eosinophils
What are causes of Think NAACP: Neoplasm (acute leukemia or chronic
peripheral myeloid disorders), allergic reactions, autoimmune,
eosinophilia? collagen vascular/cortisol insufficiency, and parasitic
infections

What is the Rare disease with persistent eosinophilia (>1.5 #

hypereosinophilic 10 9 /L for more than 6 months) in the absence of an
syndrome? identifiable underlying cause and with organ
involvement

What organs are Heart (endomyocardial fibrosis), liver, skin, lungs, and
commonly involved in central nervous system
the hypereosinophilic
syndrome?

What is the standard Corticosteroids

first-line therapy for
hypereosinophilic
syndrome?

Platelets
What are some of Calcium, serotonin, and adenosine diphosphate
the platelet dense
granule contents?

What are some of Platelet factor 4, alpha-thromboglobulin, factor V,

the platelet alpha vWF/FVIII, plasminogen activator inhibitor (PAI), FXIII,
granule contents? and transforming growth factor beta
 P.277

Thrombocytopenia
At what Platelet counts >50 # 10 9 /L are usually sufficient to prevent
platelet count major bleeding from surgical procedures and trauma. The
is there a more severe the trauma and the larger the
significantly operation, the greater the risk of bleeding; neurosurgical
increased risk procedures generally require a platelet count closer to 100 #
of bleeding
10 9 /L, but rigorous studies supporting this requirement have
from trauma or
not been performed.
surgery?

At what Ecchymoses and petechiae usually do not occur until the

platelet count platelet count is <50 # 10 9 /L.
does
spontaneous
hemorrhage
become a risk?

At what <5 # 10 9 /L for children and <10 # 10 9 /L for adults

platelet count
does
spontaneous
life-threatening
hemorrhage
become a
distinct
possibility?

When should At a platelet count of <100 # 109 /L when there is life-

platelets be threatening or clinically significant bleeding. Prophylactic
transfused? platelet transfusion is routinely given to patients with
platelet counts <10 # 10 9 /L when they have decreased
platelet production (<20 # 10 9 /L if there is concomitant
infection, fever, uremia, or other additional bleeding risk).

What is the Drugs, liver injury, sepsis, myelophthisic disorders, acute

differential leukemia, myelodysplasia, aplastic anemia, viral infections,
diagnosis of AIDS, vitamin B12 and folate deficiency, or splenomegaly
decreased
platelet
production?
 What are the ITP, TTP/HUS, and DIC
causes of
increased
destruction or
consumption?

Immune Thrombocytopenic Purpura

What diseases are Chronic lymphocytic leukemia, Hodgkin's disease, non-
associated with Hodgkin's lymphoma, SLE, rheumatoid arthritis, Hepatitis C
ITP? and HIV

What are some Intravenous immunoglobulin, which gives a rapid but

alternative transient increase in platelet count, anti-D immunoglobulin
treatments for (for Rh-positive patients), B-cell depletion with rituximab,
steroid-refractory splenectomy, danazol, and rarely, cytotoxic chemotherapy
patients with ITP? agents

P.278

Thrombotic Thrombocytopenic Purpura and Hemolytic

Uremic Syndrome
What is Fever, hemolytic anemia with schistocytes, thrombocytopenia,
the pentad neurologic changes, and renal dysfunction
of TTP?

What two The presence of microangiopathic hemolytic anemia and

of the five thrombocytopenia without apparent cause is sufficient to begin
criteria treatment for TTP.
above are
sufficient
to prompt
treatment
of TTP?

What is A triad of thrombocytopenia, hemolytic anemia with schistocytes,

HUS? and renal failure

What are HUS is associated with a greater degree of renal failure and, less
the often, with other end-organ damage (e.g., heart, brain, lungs,
differences gastrointestinal tract, and retinal vessels). Thrombocytopenia and
between hemolysis are more profound in TTP than in HUS. It is often
TTP and difficult to distinguish between TTP and HUS owing to clinical
HUS? overlap, so many consider them as a continuum of disease. HUS
as a distinct entity is more frequent in children.
 What is DIC, preeclampsia, and eclampsia, HELLP syndrome, malignant
the hypertension, and severe vasculitis; or multiple simultaneous
differential comorbidities (e.g., sepsis causing renal failure, altered mental
diagnosis status, and DIC) mimicking its clinical picture
of
TTP/HUS?

What are Infection, pregnancy, immune disorders, allogeneic BMT, and

some drugs (including chemotherapy)
inciting
factors for
TTP/HUS?

Which Cyclosporine, ticlopidine (Ticlid), clopidogrel (Plavix), and

drugs are mitomycin C
associated
with TTP
and HUS?

What is Daily apheresis of 3 to 4 L leads to improvement in many patients

the within 1 week. Before the institution of apheresis therapy, TTP
treatment was nearly universally fatal. Steroids are sometimes used as an
for TTP? adjunct to plasma exchange. HUS is treated similarly but may
respond more poorly.

Should In both disorders, platelet transfusions are contraindicated.

platelets
be
transfused
in patients
with TTP
or HUS?

P.279

Thrombocytosis
What two laboratory tests Fibrinogen and C-reactive protein levels, which
may help differentiate are often elevated with reactive thrombocytosis
reactive thrombocytosis because many of the reactive disorders cause
from essential elevation of acute-phase reactant protein levels
thrombocythemia?

Myeloproliferative Disorders
 What are the four PV, essential thrombocythemia, CML, and
myeloproliferative myelofibrosis with myeloid metaplasia
disorders?

P.280

Polycythemia Vera
Is only the No. The leukocyte count is elevated in two thirds of patients
hematocrit and the platelet count is elevated in 50%.
elevated in
PV?

What are the Elevated RBC mass (Hgb >18.5 g/dL for men and Hgb >16.5
major criteria g/dL for women), oxygen saturation >92%, splenomegaly
making the
diagnosis of
PV?

What are the Leukocytosis, thrombocytosis, elevated LAP, and elevated B12
minor criteria binding proteins
making the
diagnosis of
PV?

How is the The presence of the three major criteria or the first two
diagnosis of major criteria and two of the minor criteria are sufficient to
PV made? make the diagnosis.

What is key in The key issue is distinguishing PV from other causes of

making the reactive erythrocytosis, which is why the serum erythropoietin
diagnosis of level is tested; it is usually markedly decreased in PV.
PV?

What is the 10 years with phlebotomy

median
survival of
patients with
PV?

What is the Thrombosis; less often, hemorrhage

major cause
of death in
PV?

Is there an Yes. This risk is not nearly as high as that seen with MDS, and
 increased risk it is often associated with attempts to treat the condition
for with alkylating agents or radioactive phosphorus.
development
of acute
leukemia in
PV?

What is the Phlebotomy to a hematocrit of !42% to 45%. Aspirin is

treatment for recommended for all patients who do not have a
PV? contraindication. Hydroxyurea is indicated if the patient's age
is >40 years and there is a history of thrombosis or platelet
count >400,000/"L. Anagrelide may be used to decrease the
platelet count without the (debated) potential leukemogenic
potential of hydroxyurea.

What is the The development of myelofibrosis with associated low cell

spent phase counts and possible transfusion dependence. This state is
of indistinguishable from agnogenic myeloid metaplasia.
polycythemia?

When is the The onset averages 10 years from diagnosis and occurs in
spent phase approximately 15% of patients with PV. Increasing
seen, and splenomegaly, anemia, and bone marrow fibrosis with
how common associated leukoerythroblastic blood smear marks this phase.
is it?

How often is Acute leukemia eventually develops in 25% to 50% of patients

acute with this complication.
leukemia
seen in
patients in
the spent
phase?

P.281

Essential Thrombocythemia
What is essential A myeloproliferative disorder with persistent
thrombocythemia? thrombocytosis (platelet count >600 # 10 9 /L) that is not
reactive to another disorder and is not caused by another
myeloproliferative disorder. Bone marrow biopsy shows
megakaryocyte hyperplasia and clustering.

What are some of Arterial or venous thrombosis and hemorrhage (CVA, MI,
the common digital ulceration, VTE, epistaxis, and gastrointestinal
clinical problems bleeding). Also headache, visual symptoms, and livedo
in patients with reticularis.
essential
thrombocythemia?

What abnormalities Thrombocytosis, often with very large platelets;

are seen in the leukocytosis (30% of cases); leukoerythroblastic blood
peripheral blood in smear (25% of cases); eosinophilia; and basophilia
essential
thrombocythemia?

What is the Other myeloproliferative disorders, MDS (e.g., 5q-), and

differential reactive thrombocytosis
diagnosis for
essential
thrombocythemia?

What is the typical It is usually not seen until the sixth or seventh decade of
age of onset of life, but a cohort of young women in the fourth and fifth
essential decades of life occasionally present with the condition.
thrombocythemia?

What is the acute For acute thrombosis: plateletpheresis is followed by

treatment for administration of platelet-lowering drugs (hydroxyurea or
essential anagrelide). For hemorrhage: platelets, then platelet-
thrombocythemia? lowering drugs.

What defines a Age >60 years or history of thrombosis

high-risk patient
with essential
thrombocytosis?

What defines a Age <60 years, no history of thrombosis, and platelet

low-risk patient count < 1,500,000/"L
with essential
thrombocytosis?

What is the It is somewhat controversial for asymptomatic patients.

chronic treatment Low-risk patients may not need therapy. In patients at
for essential high risk for thrombosis, the platelet count should be
thrombocythemia? lowered into the normal range with hydroxyurea or
anagrelide.

How does Hydroxyurea nonspecifically interferes with DNA

hydroxyurea work? synthesis.
 How does Anagrelide specifically blocks platelet production and
anagrelide work does not have the (debated) leukemogenic potential of
hydroxyurea.

Should aspirin be Low-dose aspirin is also recommended in symptomatic or

used in these high-risk patients.
patients?

P.282

Chronic Myelogenous Leukemia

How is a leukemoid The LAP is characteristically very low in CML and is
reaction distinguished markedly elevated in a leukemoid reaction.
from early CML?

What is the usual 3 to 5 years

length of the chronic
phase of untreated
CML?

What is imatinib A tyrosine kinase inhibitor that specifically targets

mesylate (Gleevec)? the ABL tyrosine kinase

What is its effect in It has shown dramatic effectiveness in restoring

chronic phase CML? normal blood counts, causing loss of the Philadelphia
chromosome as well as major reductions in BCR-ABL
transcripts as measured by PCR DNA.

What brings about the Likely accumulation of additional genetic errors: new
progression from the nonrandom cytogenetic abnormalities have been
chronic phase to the found in up to 80% of patients in the blast phase.
accelerated phase to
the blast phase in
CML?

What changes occur at An elevated leukocyte count, persistent

the onset of the thrombocytosis, increase in percent blasts and
accelerated phase of promyelocytes in blood and bone marrow, increased
CML? splenomegaly, development of myelofibrosis and
development of chloromas (focal leukemic tumors)

What is the clinical Usually, over a period of several months,

course of the transformation into the blast phase occurs.
accelerated phase of
 CML?

What indicates the >20% blasts in the peripheral blood or bone marrow
onset of the blast
phase of CML?

What is the usual Usually myeloid but occasionally lymphoid.

phenotype of the CML Treatment for each phenotype is different.
blasts?

What is the treatment Same as for de novo acute leukemia. With

of the blast phase of chemotherapy, some patients can be converted back
CML? into the chronic phase. The duration of partial or
complete remission is usually short.

P.283

Myelofibrosis with Myeloid Metaplasia

What is A neoplastic hematopoietic stem cell disorder
myelofibrosis with characterized by bone marrow fibrosis, marked
myeloid splenomegaly, extramedullary hematopoiesis,
metaplasia? pancytopenia, and a leukoerythroblastic blood smear

What are some of Teardrop RBCs with nucleated RBCs, early myeloid forms
the findings on including blasts, and large platelets
peripheral smear
in myelofibrosis
with myeloid
metaplasia?

What is the Other myeloproliferative disorders, metastatic carcinoma,

differential lymphoma, hairy cell leukemia, MDSs, disseminated
diagnosis for tuberculosis, and histoplasmosis
myelofibrosis with
myeloid
metaplasia?

What is the Supportive care with transfusions, growth factors, and

treatment for antibiotics as needed. A trial of thalidomide and steroids
myelofibrosis with may be offered to improve anemia and platelet counts.
myeloid Hydroxyurea, splenectomy, and radiation therapy can
metaplasia? palliate symptomatic splenomegaly.

What are the MI or heart failure (30%), hemorrhage (25%), acute

common causes of leukemia (20%), and infection (10%)
 death attributable
to agnogenic
myeloid
metaplasia?

P.284

Myelodysplastic Syndromes
How does MDS Symptoms are attributable to cytopenias. Anemia results
commonly present? in weakness and congestive heart failure, for example,
neutropenia results in infection, and thrombocytopenia
results in bleeding.

What is the median From approximately 6 years to 4 to 5 months.

survival of patients
with MDS?

What are the causes Acute leukemia in 30% and cytopenias in 30%. The
of death in patients remainder die of unrelated comorbid conditions, as MDS
with MDS? is usually a disease of the elderly.

What are the most Percentage of blasts in the bone marrow, presence of
important particular chromosomal abnormalities (e.g., deletions of
prognostic factors chromosome 7, complex karyotypes), and presence of
for MDS? pancytopenia are the strongest predictors of a poor
prognosis.

What clonal 5q-: the 5q-syndrome is classically seen in elderly

cytogenetic women with transfusiondependent anemia,
abnormality can thrombocytosis, and a normal leukocyte count.
portend a good
prognosis for MDS?

What is the In patients with the 5q- abnormality with or without

treatment of MDS other chromosomal abnormalities, treatment with the
for patients with immunomodulator lenalidomide may be offered.
the 5q-
abnormality?

What other Hypomethylating agents such as 5-azacytidine or

chemotherapy may decitabine
be offered for
patients with a
good performance
status?
 When should BMT In young patients requiring frequent transfusions or with
be considered? excess blasts

What therapies can Induction chemotherapy may be considered, but

be offered when complete response rates are considerably less than in de
the MDS transforms novo acute leukemia and the overall prognosis is very
to an acute poor.
leukemia?

P.285

Spleen and Lymph Nodes

If the spleen is palpable, About 2.5 times
how much bigger than
normal is it?

What infections commonly Epstein-Barr virusmediated mononucleosis, viral

cause splenomegaly? hepatitis, malaria, and rickettsial infections

What are the common Reactive to a systemic process: e.g., viral and
causes of certain bacterial infections (Epstein-Barr virus,
lymphadenopathy? HIV, syphilis)
Direct infiltration by pathogens: e.g.,
mycobacterial, fungal, or staphylococcal
infections
Neoplasia: e.g., lymphomas, leukemias, and
locally advanced or metastatic cancer
Miscellaneous: e.g., sarcoidosis or nonneoplastic
lymphoid conditions

P.286

Transfusion Medicine
Transfusion of 1 Approximately 3% per unit transfused, but this relationship
unit of packed may not hold for extremely large or small patients
RBCs should
increase the
patient's
hematocrit by
how much?

When after the 2 to 10 days

transfusion do
 delayed
hemolytic
transfusion
reactions usually
occur?

What is the An anamnestic increase in previously formed antibodies or

cause of delayed the formation of new antibodies to minor antigens on the
hemolytic transfused RBCs
transfusion
reactions?

What types of IgG. These antibodies are directed against blood group
antibodies cause antigens other than the A and B antigens. These reactions
delayed are predominantly seen in individuals who were previously
hemolytic transfused.
transfusion
reactions?

What kind of Extravascular. The decrement in hematocrit is generally

hemolysis occurs less than in an immediate transfusion reaction mediated by
in a delayed ABO incompatibility, which is intravascular.
transfusion
reaction?

What is the Rh-positive patients have an immunogenic D antigen on

importance of their RBCs. After exposure to Rh-positive RBCs,
the Rh RBC approximately 50% of Rh-negative individuals produce anti-
antigen system? D antibodies with resultant delayed transfusion reaction on
subsequent transfusion of Rh-positive (D antigenpositive)
blood.

Hemostasis and Thrombosis

Is FXII a Not in vivo, but to make blood clot in vitro where tissue factor is
necessary not available, FXII is a necessary protein. Patients with FXII
enzyme in deficiency do not bleed spontaneously and are at no higher risk
the for bleeding during surgical procedures.
cascade?

P.287
P.288

Approach to Bleeding Disorders

What are the four broad Disorders arising from platelet dysfunction, clotting
categories of bleeding factor deficiency or dysfunction, vascular
disorders? dysfunction (e.g., connective tissue diseases), or
hyperfibrinolysis

What is platelet-type Bleeding at mucocutaneous sites, multiple small

bleeding? bruises, and immediate bleeding after trauma or
surgery

What disorders are Thrombocytopenia, platelet function defects, and

associated with vWD
plateletrelated
bleeding?

What is clotting factor Soft tissue bleeding with occasional large bruises or
type bleeding? hematomas and delayed bleeding after trauma or
surgery

What are the causes of Hemophilia A (FVIII deficiency), hemophilia B (FIX

clotting factortype deficiency), hemophilia C (FXI deficiency), and
bleeding? other rare deficiencies of FII, FV, FVII, FX, and
fibrinogen

What factor deficiency FXIII

is associated with
delayed bleeding and
poor wound healing and
normal PT and PTT?

How is bleeding Cryoprecipitate

associated with FXIII
deficiency treated?

What suggests the Spontaneous bruising (i.e., bruising not associated

presence of a true with trauma), bruising located on the trunk or in
bleeding disorder in other areas not typically prone to ordinary trauma,
patients with easy large size of bruises, and long period of time for
bruisability? bruising to resolve

What bleeding disorders FVII and vitamin K deficiencies, warfarin use, and
may be associated with liver dysfunction. Deficiencies of FII, FV, FX, and
an isolated prolonged fibrinogen are usually associated with prolongation
PT? of both the PT and aPTT.

What bleeding disorders Deficiencies of FVIII, FIX, and FXI, and vWD (due to
may be associated with coexistence of FVIII deficiency)
 an isolated prolongation
of the aPTT?

What bleeding disorders Simultaneous deficiency of multiple factors, as seen

may be associated with with liver disease, vitamin K deficiency,
a prolongation of the PT malnutrition, and DIC. Rarer causes include isolated
and aPTT? deficiencies or acquired inhibitors of factors II, V,
and X, or fibrinogen.

What does the ACT The clotting time of whole blood in the presence of
assay measure? an activating substance. This allows for a quick
bedside assessment of anticoagulant (typically
heparin) adequacy.

What are some vWD, platelet function defects (e.g., Bernard-

disorders that can Soulier syndrome), essential thrombocythemia,
prolong the bleeding paraproteinemias, microangiopathic hemolytic
time? anemias, uremia, and dysfibrinogenemia

What is cryoprecipitate? A concentrate of plasma enriched in vWF/FVIII,

FXIII, and fibrinogen

What is the treatment Fresh-frozen plasma; FXI concentrates are available

for acute bleeding in a in some other countries.
patient with FXI
deficiency?

What are the common Thrombocytopenia, coagulation factor deficiencies

causes of bleeding in (both from impaired synthetic function and vitamin
patients with cirrhosis? K deficiency), platelet dysfunction, low-grade DIC,
and increased fibrinolysis

P.289
P.290

von Willebrand's Disease

What is the function of vWF mediates adhesion of platelets to the
vWF? vessel wall basement membrane after vascular
injury, and is the carrier protein for FVIII.

What laboratory tests are vWF and FVIII antigen levels, ristocetin cofactor
used in testing for vWD? activity, and vWF multimer testing

What does the ristocetin It is an approximation of vWF function.

cofactor activity measure?
What are the 4 types of Type 1
vWD? Type 2
Type 3
Platelet type

Describe the abnormality Quantitative decrease in levels of functionally

with type 1 vWD: normal vWF

How common is type 1 This subtype is the most common, comprising

vWD? 70% to 80% of cases.

Describe the abnormality of Qualitative abnormalities of vWF

type 2 vWD:

How common is type 2 This subtype comprises 15% to 30% of vWD

vWD? cases. There are several subtypes of type 2.

Describe the abnormality of Absence of vWF

type 3 vWD:

How common is type 3 This is a rare form and may be associated with
vWD? profound bleeding problems.

Describe the abnormality of The platelet receptor for vWF (glycoprotein Ib)
platelet type vWD: has increased affinity for vWF, resulting in
increased clearance of plasma vWF.

Why is it important to Because administration of DDAVP can cause

distinguish type 2B vWD thrombocytopenia in patients with these
and platelet type vWD from subtypes
all other types of vWD?

How is vWD inherited? Usually autosomal dominant, but patients with

type 3 may be autosomal recessive or doubly
heterozygous. In contrast, hemophilia A and B
are X-linked.

What is the treatment of Desmopressin (DDAVP)

bleeding in patients with
type 1 vWD?

How is bleeding treated in FVIII concentrates. For major operations or life-

patients who cannot threatening hemorrhage, these concentrates
 receive or do not respond should be given to all subtypes.
to DDAVP?

When should In an emergency when DDAVP is not appropriate

cryoprecipitate be used to and when no virally inactivated intermediate-
treat vWD? purity factor VIII product is available

What are the adverse DDAVP may be contraindicated in certain

effects of DDAVP? subtypes of vWD. DDAVP can cause
hyponatremia, facial flushing, minor alterations
in blood pressure, nausea, and headache.

What is the most common FVIII deficiency. FVIII circulates attached to

cause of aPTT prolongation vWF. In the absence of vWF, the half-life of
in severe vWD? FVIII is shortened.

P.291

Thrombotic Disorders
Under what Thrombosis without a precipitating risk factor, thrombosis
circumstances at a young age, recurrent thromboses, thrombosis in an
should a unusual location (e.g., upper extremity, portal vein,
hypercoagulable mesenteric vein, cerebral vein), a family history of
state be thrombosis, and resistance to anticoagulation with heparin
suspected? or warfarin

What are the APC resistance (FV Leiden mutation), prothrombin (FII)
known common gene mutation, protein C deficiency, protein S deficiency,
inherited AT III deficiency, dysfibrinogenemia, and
hypercoagulable hyperhomocysteinemia. More than 30% of patients who
states? clinically appear to have an inherited hypercoagulable
state currently have no identifiable abnormality.

What are the two APC resistance (FV Leiden mutation), and prothrombin (FII)
most common gene mutation
inherited
disorders
associated with
an increased risk
of venous
thrombosis?

How is APC Patient plasma demonstrates decreased prolongation of

resistance the aPTT compared with that of normal subjects after the
diagnosed? addition of APC. Alternately, genetic studies can be
 ordered to screen for the FV Leiden mutation.

What acquired Malignancy, myeloproliferative disorders, PNH, connective

conditions are tissue diseases (e.g., SLE, rheumatoid arthritis, etc.) and
associated with a other inflammatory conditions, antiphospholipid antibody
hypercoagulable syndrome, hyperviscosity states (e.g., paraproteinemia
state? and untreated PV), HITT, TTP/HUS, DIC

How is protein C After binding to endothelial cell thrombomodulin,

activated? thrombin cleaves protein C, generating APC.

What does protein Protein S is a cofactor to APC.

S do?

P.292

Antiphospholipid Antibody Syndrome

What is the A disorder where the patient has a history of
antiphospholipid thromboembolic events or pregnancy mishapse.g.,
antibody recurrent spontaneous abortionsas well as autoantibodies
syndrome? to complexes of phospholipids and plasma proteins

What is lupus Autoantibodies against phospholipidprotein complexes. Their

anticoagulant? presence is inferred from abnormalities in various
phospholipid-dependent clotting tests (e.g., aPTT).

What are Antibodies measured in serum with specificities toward a

anticardiolipin specific phospholipid, cardiolipin, or to beta-2-glycoprotein-
or beta-2- 1.
glycoprotein-1
antibodies?

When are In the setting of a thromboembolic event or recurrent

antiphospholipid miscarriage, they are suggestive of a hypercoagulable state;
antibodies if the antiphospholipid antibody persists, long-term
clinically anticoagulation should be considered.
meaningful?

How do you The American College of Rheumatology classification

diagnose involves one clinical (vascular thrombosis or frequent
antiphospholipid miscarriages) and one lab criterion listed above.
syndrome?

Disseminated Intravascular Coagulation

 What is DIC is a syndrome in which diffuse activation of coagulation factors
DIC? overwhelm the body's normal anticoagulant regulatory systems,
leading to excessive fibrin formation and platelet activation,
followed by depletion of clotting factors and platelets.

What is Diffuse microvascular clot formation with organ damage and

the dysfunction, followed by clinical hemorrhage. Sequentially, the
clinical fibrinolytic system becomes activated, lysing thrombi and
result of exacerbating hemorrhage.
DIC?

What Sepsis, head trauma, cancer, abruptio placentae, amniotic fluid

are the embolism, fat embolism, eclampsia, snake bites, viral and rickettsial
common infections, and collagen vascular diseases
causes
of DIC?

How is In the appropriate clinical setting, prolongation of the PT, elevation

the of the D-dimer titer with thrombocytopenia, and
diagnosis hypofibrinogenemia. Serial measurements of the variables listed are
of DIC usually helpful.
made?

P.293
P.294

Anticoagulation
What are the most Heparin, low-molecular-weight heparins (enoxaparin,
commonly used dalteparin, tinzaparin), and warfarin. In the inpatient
anticoagulants in setting, direct thrombin inhibitors (argatroban, lepirudin,
the United States? bivalirudin) are commonly used. The pentasaccharide
fondaparinux is becoming more commonly used, and oral
DTIs are in development.

How is low- Smaller fragments of heparin interact with ATIII to have

molecular-weight greater inhibition of FXa and lesser inhibition of
heparin different thrombin. Their pharmacokinetics are more predictable
from standard than that of unfractionated heparin.
heparin?

How are the They are dosed in a weight-based fashion and normally
effects of low- do not need monitoring. If necessary, inhibition of FXa
molecular-weight may be assayed.
heparins or
fondaparinux
monitored?

Why should the To monitor for the development of HITT

platelet count be
monitored if a
patient is receiving
heparin or low-
molecular-weight
heparins?

What platelet A platelet count drop of >50% from baseline

counts should
signal the
consideration of
HIT/T?

Why is HITT such This is a disorder in which limb- or life-threatening

an important thrombosis can occur. If HIT/T is suspected then all
illness to diagnose? heparin and/or low molecular weight heparin must be
stopped

In patients with The patient must be covered with a DTI until the
HITT, how is platelet count begins to rise. After the acute risk of
anticoagulation thrombosis has passed, the DTI may be transitioned to
handled? warfarin.

What is the risk of 30% or higher

thrombosis in
patients with HITT?

How long should At least 4 weeks even if no thrombosis is evident

patients remain on
warfarin once
diagnosed with
HITT?

What laboratory 14
C-serotonin release assay has a positive predictive
tests can be done value near 100%, but a negative predictive value of only
to confirm the 20%. The use of ELISA assays for antiplatelet factor 4
diagnosis of HITT? (PF4) antibodies has a positive predictive value of 93%
for a definitive diagnosis and a negative predictive value
of 95%.

How can the effect Administration of vitamin K orally or intravenously. For

of warfarin be bleeding, plasma or a concentrate of vitamin K
reversed? dependent clotting factors may be given. Recombinant
FVIIa can be given, which in pharmacologic doses directly
activates factor X to bypass the need for clotting factors
higher in the cascade.

How do the direct ATIII is not a necessary cofactor: thrombin inhibitors

thrombin inhibitors inactivate thrombin and only thrombin.
differ from
heparin?

How are the direct By aPTT or ACT

thrombin inhibitors
monitored?

How are the None of the currently available thrombin inhibitors are
effects of direct reversible. If a patient is bleeding he or she must be
thrombin inhibitors supported with fluids and/or blood products until the
reversed? drugs have been cleared from the body.
Editors: Bergin, James D.
Title: Advanced Medicine Recall, 1st Edition
Copyright 2009 Lippincott Williams & Wilkins

> Table of Contents > Section II - The Specialties > Chapter 7 - Infectious Disease

Chapter 7
Infectious Disease

P.296

Abbreviations
AIDS Acquired immune deficiency syndrome

ALT Alanine aminotransferase

APH Acute pulmonary histoplasmosis

AST Aspartate aminotransferase

BSI Bloodstream infection

CAP Community-acquired pneumonia

CBC Complete blood count

CMV Cytomegalovirus

CNS Central nervous system

CoNS Coagulase-negative staphylococcus aureus

CPH Chronic pulmonary histoplasmosis

CPK Creatine phosphokinase

CSF Cerebrospinal fluid

CT Computed tomography

DEET Diethyltoluamide
EBV Epstein-Barr virus

ELISA Enzyme-linked immunosorbent assay

ESR Erythrocyte sedimentation rate

FTA-ABS Fluorescent treponemal antibody, absorbed

FUO Fever of unknown origin

GC Gonococcus

GU Gonococcal urethritis

HIV Human immunodeficiency virus

HPF High-power field

HSV Herpes simplex virus

Ig Immunoglobulin

INH Isoniazid

IVDAs Intravenous drug abusers

KOH Potassium hydroxide

LFT Liver function test

MAC Mycobacterium avium complex

MHA-TP MicrohemagglutinationTreponema pallidum

MRI Magnetic resonance imaging

MRSA Methicillin-resistant Staphylococcus aureus

NGU Nongonococcal urethritis

NK Natural killer
 PCP Pneumocystis jiroveci pneumonia

PCR Polymerase chain reaction

PDH Progressive disseminated histoplasmosis

PET Positron emission tomography

PID Pelvic inflammatory disease

PMN Polymorphonuclear neutrophil

PZA Pyrazinamide

RMSF Rocky Mountain spotted fever

RPR Rapid plasma reagin

SBP Spontaneous bacterial peritonitis

SIRS Systemic inflammatory response syndrome

SLE Systemic lupus erythematosus

STD Sexually transmitted disease

TSS Toxic shock syndrome

UTI Urinary tract infection

VDRL Venereal Disease Research Laboratory

VRE Vancomycin-resistant enterococcus

VZV Varicella zoster virus

WBC White blood cell

P.297

Diagnostic Methods
What is Polymerase chain reaction. It uses the enzyme DNA polymerase to
PCR? increase (amplify) the number of copies of DNA or RNA in a sample.
 PCR is very sensitive because only a few copies of genetic material
(and not whole organisms) need to be present. It is useful for
organisms that are difficult to culture (including HIV).

What is To diagnose infection when the pathogen cannot be cultured. It

serologic measures acute and convalescent sera to detect a fourfold increase
testing in titer (synonymous with recent infection). Diagnosis can be made
used only retrospectively.
for?

P.298

Antimicrobial Therapy

General Principles
In which diseases is Meningitis, endocarditis, brain abscess,
bactericidal therapy osteomyelitis, and neutropenia
mandatory?

What are reasons for Development of resistance in vivo, superinfection,

antimicrobial treatment decreased activity at the site of infection (e.g.,
failure? necrotic tissue, foreign body, and lack of
penetration into abscess), impaired immune host
defenses, improper dosing, and altered
pharmacokinetics secondary to drug interactions

What is Pharmacodynamics describes the biochemical and

pharmacodynamics? physiologic effects of the drug and its mechanism of
action.

What makes an It is bacteriostatic if it inhibits growth and

antimicrobial agent replication.
bacteriostatic?

What makes an It is bacteriocidal if it causes bacterial cell death.

antimicrobial agent
bacteriocidal?

What determines The antimicrobial concentration at the site of

whether a drug is action
bacteriostatic or
bacteriocidal?

What is the MIC90? The minimum concentration of an antimicrobial that

is inhibitory for 90% of all isolates of a bacterial
 species

What is Antibiotics that develop high concentrations at the

concentrationdependent bacteria binding site have concentration-dependent
killing of bacteria? killing where peak/MIC ratio is critical.

What are the Fluoroquinolones, aminoglycosides, macrolides,

concentration- azalides, ketolides, and metronidazole
dependent killing
agents?

What is time-dependent Antibiotics that spend an extensive amount of time

(concentration- bond to a bacteria. Therefore, the time the
independent) killing of antibiotic is bound to the bacteria at greater than
bacteria? MIC is critical.

What are the time- Penicillins, cephalosporins, aztreonam, vancomycin,

dependent killing carbapenams, linezolid, and clindamycin
agents?

P.299
P.300

Antibacterial Agents
Note: General statements regarding antimicrobial susceptibilities are difficult owing
to changing resistance patterns. Consideration of individual organism and local
resistance patterns is needed in selecting appropriate antimicrobial therapy.

What is the Inhibition of bacterial cell wall synthesis

mechanism of
action of penicillins
and other beta
lactams?

What are the other Cephalosporins, carbapenems, and monobactams

beta-lactam
antimicrobials?

What is the only Aztreonam

monobactam?

What is the most Beta-lactamase production

common method of
resistance to
penicillins and
other beta lactams?

How do beta They covalently react with the beta lactam ring and
lactamases work? hydrolyze it, causing destruction of the activity of the
drug.

What are the three Clavulanate, sulbactam, and tazobactam

beta-lactamase
inhibitors?

What are the Amoxicillin-clavulanate (Augmentin), ticarcillin-

combination beta- clavulanate (Timentin), ampicillin-sulbactam (Unasyn),
lactam/beta- pipercillin-tazobactam (Zosyn)
lactamase inhibitor
antimicrobials?

What is the Allergic reactions from penicillins occur with a frequency

incidence of of 7 to 40 of every 1000 penicillin treatment courses.
hypersensitivity
reactions with
penicillins?

Name the four Type 1 (IgE)urticaria, angioedema, anaphylaxis. Occurs

types of penicillin in 4 to 15 of every 100,000 penicillin treatment courses;
hypersensitivity fatality occurs once in every 32,000 to 100,000
reactions. treatment courses.
Type 2 (IgG, cytotoxic antibodies)hemolytic anemia
Type 3 (immune complexes)serum sickness
Type 4 (cell-mediated)contact dermatitis, idiopathic
maculopapular rash, interstitial nephritis, drug fever,
eosinophilia, exfoliative dermatitis, Stevens-Johnson
syndrome

Through what Vancomycin is effective in systemic infections only if

routes is given intravenously. The oral form does not have
vancomycin significant systemic absorption; it is effective only
absorbed? against Clostridium difficile, since the site of action is
in the GI tract.

What is the A lipopeptide antibiotic with broad gram-positive

antimicrobial activity including MRSA and VRE. Currently approved for
activity of skin infections, bacteremia, and endocarditis.
daptomycin?

What is the It is a glycylcycline antibiotic (related to the

 antimicrobial tetracyclines) with activity against gram positives
activity of (including MRSA and VRE), enteric pathogens, and
tigecycline? anaerobes. It is bacterostatic and not active against
Pseudomonas.

Antimycobacterial Agents
What is the If transaminase levels increase to more than five times
management of upper limits of normal, INH, rifampin, and PZA should be
antimycobacterial discontinued in favor of an alternative regimen. Possible
drug induced hepatotoxic drugs are reintroduced one at a time to
hepatotoxicity? identify the offending agent.

P.301

Antifungal Agents
What toxicities are Dose-dependent decrease in glomerular filtration rate,
associated with potassium and bicarbonate wasting (renal tubular
amphotericin B? acidosis), decreased erythropoietin production, nausea,
vomiting, phlebitis, and acute reactions

What acute reactions Chills, fever, tachypnea, hypoxemia, and hypotension

are associated with may occur 30 minutes after beginning infusion.
amphotericin B
infusions?

What premedication Premedication with acetaminophen, hydrocortisone, or

regimen may reduce meperidine may diminish reactions.
these side effects?

What is the Most Candida species, C. neoformans, and

antimicrobial coccidioidomycoses
spectrum of
fluconazole?

What is the Blastomycosis and histoplasmosis. Itraconazole may

antimicrobial have a role for Aspergillus infections when
spectrum of amphotericin B fails or cannot be administered.
itraconazole?

What is the Histoplasmosis and blastomycosis. Ketoconazole is not

antimicrobial used commonly because of its side effects. Itraconazole
spectrum of is equally or more effective and less toxic. Newer
ketoconazole? triazoles with activity against Aspergillus sp. are in
development.
 What is the Refractory invasive Aspergillus infection. It also has
indication for significant activity against Candida sp.
echinocandin
caspofungin?

What is the In vitro and in vivo activity has been shown against
antimicrobial Aspergillus spp. as well as other molds; also active
spectrum of against most Candida spp.
voriconazole?

What are the In general, candidemia and esophageal candidiasis.

indications for the Caspofungin also indicated for febrile neutropenia and
echinocandins refractory invasive Aspergillus.
(caspofungin,
micafungin, and
anidulafungin)?

Antiviral Agents
What are the Treatment and chronic suppression of invasive CMV disease
indications for (e.g., retinitis, pneumonia, and gastroenteritis) in
ganciclovir? immunocompromised patients

What are the Progressive CMV disease caused by ganciclovir-resistant

indications for strains. It is used most often in AIDS patients with refractory
foscarnet? CMV retinitis.

What are the Refractory CMV retinitis. Its role in the treatment of other
indications for CMV diseases and other viral infections is being evaluated.
cidofovir?

What is the CMV retinitis is currently the only indication.

indication for
valganciclovir?

P.302
P.303
P.304
P.305
P.306
P.307

Pathogens
Bacteria
What are the two main Toxic shock syndrome toxin-1 (TSST-1)
superantigens asscociated with and staphylococcal enterotoxins
staphylococcal toxic shock
syndrome?

What are the clinical signs and Fever, hypotension, diffuse macular rash
symptoms associated with that subsequently desquamates, with
staphylococcal toxic shock three of the following organ involvements:
syndrome? liver, blood, renal, mucous membranes,
GI, muscular, central nervous system

What is the treatment for staph Antibiotics, usually nafcillin or vancomycin

TSS? if MRSA; IVIg (to help neutralize the
superantigen activity of the staphylococcal
toxins), intravenous fluids and
vasopressors if needed

What groups of patients are at Hemodialysis, peritoneal dialysis, HIV-

increased risk for S. aureus infected, IVDAs, diabetics, and alcoholics
infections?

What is the pyogenic staph Hidradenitis suppurativa

infection of the apocrine sweat
glands?

S. aureus accounts for what S. aureus is responsible for approximately

percentage of infective 30% of native valve endocarditis; 70% of
endocarditis? endocarditis in IVDAs, and about 20% of
those with early or late prosthetic valve
endocarditis.

What percentage of CAP or S. aureus is responsible for less than 10%

hospital-associated pneumonias of CAP but accounts for around 30% of
are due to S. aureus? hospital-associated pneumonias.

What percentage of osteomyelitis Osteomyelitis due to S. aureus accounts

is caused by S. aureus? for 50% to 70% of cases.

What are some of the major Bacteremia, osteomyelitis, native valve

infections caused by coagulase- endocarditis, infections of indwelling
negative staph? foreign devices such as prosthetic valve
endocarditis and central venous catheters
What drug is most commonly Because CoNS is usually resitant to
used to treat CoNS infections? multiple antibiotics, vancomycin is the
drug of choice

What species of Streptococcus is Strep. pyogenes

Lancefield group A?

What is the hemolytic reaction Beta hemolysis

associated with group A strep?

Strep. pyogenes is associated Pharyngitis, skin/soft tissue and

with what major clinical respiratory infections
syndromes?

What species of Streptococcus is Strep. agalactiae

Lancefield group B?

What is the hemolytic reaction(s) Beta and gamma hemolysis

associated with group B strep?

Strep agalactiae is associated Chorioamnionitis, puerperal sepsis,

with what major clinical bloodstream infections in nonpregnant
syndromes? adults

What species are included in the This includes the anginosus, bovis,
viridans streptococcal group? mutans, salivarius, and mitis species
groups.

Streptococcus pneumoniae is Otitis media, sinusitis, meningitis,

associated commonly with what community-acquired pneumonia
clinical syndromes?

Enterococcus species often have Nonhemolysis (or gamma hemolysis)

what effect on blood agar?

Enterococci are commonly found As a part of the normal gut flora

where in humans?

What are some common clinical Urinary tract infections (most common),
syndromes associated with bacteremia and endocarditis, intra-
Enterococcus species? abdominal/pelvic infections, and rarely,
wound and tissue infections, meningitis,
or respiratory tract infections
Infection with Listeria Ingestion of organisms in a contaminated
monocytogenes occurs most food source
commonly how?

Why are pregnant women at Because of to a mild impairment of cell-

increased risk for Listeria mediated immunity that occurs during
bacteremia? pregnancy

During which trimester are they The third trimester

most at risk?

What clinical syndromes other Meningitis, brain abscess, and endocarditis

than bacteremia are associated
with Listeria?

What is the most common cause Escherichia coli

of UTI?

What are the E. coli pathogens ETEC (enterotoxigenic E. coli), EPEC

that cause diarrhea? (enteropathogenic E. coli), EHEC
(enterohemorrhagic E. coli), EAEC
(enteroaggregative E. coli), EIEC
(enteroinvasive E. coli), DAEC (diffuse
adhering E. coli)

What are zoonoses? Infections caused in humans by a variety

of pathogens that usually infect nonhuman
animals

What zoonosis is commonly Brucellosis

transmitted from ingestion of
unpatsteurized dairy products?

What pathogen is commonly Pasteurella

isolated from humans bitten by
cats or dogs?

What is the etiologic agent of the Yersinia pestis

plague?

What are some of the common Rats, ground squirrels, prairie dogs, and
animal reservoirs for Yersinia? field mice

What disease is characterized by Cat scratch disease

the development of a primary
cutaneous papule or pustule at
the site of inoculation along with
regional ipsilateral
lymphadenopathy?

What is the causative agent of Bartonella henselae

cat scratch disease?

What is the etiologic agent of Borrelia burgdorferi

Lyme disease?

What is the time of onset to the Stage I (early): up to a month

three stages of Lyme disease Stage II (disseminated): weeks to months
after the initial exposure? Stage III (late): years

What is the classic skin finding in Erythema migrans

localized stage I Lyme disease?

What are the classic findings in Cardiac (myocarditis, heart block),

stage II Lyme disease? neurologic (aseptic meningitis, Bell's palsy,
encephalitis), and dermatologic (many
annular skin lesions)

What are the classic findings in Arthritis and neuroborreliosis

stage III Lyme disease?

Approximately how long must a Tick attachement for greater than 24 to

tick be attached to a human in 36 hours is usually needed to cause
order to cause an infection? infection.

How is Lyme disease diagnosed? The combination of clinical picture,

exposure history in an endemic area, and
positive antibody response to B.
burgdorferi (ELISA and if positive,
checking a confirmatory Western blot)

What are the two types of human Human monocytic ehrlichiosis (Ehrlichia
ehrlichisosis infections? chaffenesis infects monocytes)
Human granulocytic ehrlichiosis
(Anaplasma phagocytophilum infects
granulocytes)

Human ehrlichiosis is transmitted The Lone Star tick (human monocytic

by what tick? ehrlichiosis caused by E. chaffeensis)
 The tick Ixodes scapularis (human
granulocytic ehrlichiosis caused by A.
phagocytophilum)

What is seen on peripheral blood Morulae (cytoplasmic vacuoles containing

smear in 1% to 2% of circulating Ehrlichia organisms)
leukocytes in those with human
ehrlichiosis?

What is the causative agent of Rickettsia rickettsii

Rocky Mountain spotted fever
(RMSF)?

What are the prominent clinical Fever, headache, rash

symptoms of RMSF?

Where on the body does the rash It usually begins around the wrists and
associated with RMSF usually ankles.
appear?

When does the rash usually 3 to 5 days after the onset of fever
appear with RMSF?

How is the diagnosis of RMSF Treatment decisions are based on clinical

made? grounds and history consistent with
possible tick exposure in an endemic area.
Serologic testing can check for acute and
convalescent antibody titers.

What is a vector-borne disease Babesiosis

found in New England that is
screened for in blood donor
samples from endemic areas?

What is babesiosis caused by? Babesia microti

How is babesiosis treated? Clindamycin plus quinine or atovaquone

plus azithromycin

What bacilli commonly stain Mycobacterial species and Nocardia

acid fast?

What is the most common mode Airborne droplets

of transmission of Mycobacterium
tuberculosis?
The tubercle bacilli transmitted Terminal air spaces
in airborne droplets begin
multiplication where in the
lungs?

The initial pulmonary focus or The initial focus is unsually solitary and
tuberculosis is where? found in the subpleura and in the midlung
zone (lower upper lobe or
upper/lower/middle lobes)

How are the types of Primary

tuberculosis infections classified? Superinfection
Reactivation

How does the primary infection Occurs as part of the initial infection
present? (when the mycobacteria are not contained
by the host's defense mechanisms) and
presents as pneumonia or miliary disease.

What is the TB superinection? Occurs when a patient is already infected

with TB but is reexposed to a high
quantity of mycobacteria. Pulmonary
cavitary disease is seen.

What is TB reactivation? Occurs years after the initial infection

when there is a decline in cell-mediated
immunity (as seen with normal aging,
malignancy, and HIV)

How long from exposure does the 3 to 8 weeks

tuberculin skin test turn
positive?

What treatment regimen should An initial four-drug regimen including

be started for TB infection? isoniazid, rifampin, pyrazinamide, and
ethambutol or streptomycin. Once the
resistance pattern of the TB isolate is
known, the therapy can be tailored more
specifically.

What is the most common Mycobacterium avium complex (MAC)

atypical mycobacterial lung
infection in the United States?
 P.308

Viruses

Herpesviruses
Name the herpesviruses. HSV-1 and 2, VZV, CMV, EBV, human herpesviruses
6, 7, and 8, and herpesvirus simiae

What are the clinical Mucocutaneous infections (oral-facial and genital),

syndromes associated CNS infection, and rarely, visceral organ
with HSV 1 and HSV 2? involvement

What are the clinical HSV encephalitis (typically HSV-1) is characterized

manifestations of HSV by the acute onset of fever and focal neurologic
encephalitis? (esp. temporal lobe) symptoms.

What is herpetic HSV infection of the finger

whitlow?

Varicella Zoster Virus

What diseases are associated with Primary infectionvaricella (chickenpox)
VZV? Recurrent infectionherpes zoster
(shingles)

P.309

Cytomegalovirus
What are the clinical Congenital infectionthree fourths of patients are
manifestations of asymptomatic. Symptoms include jaundice,
congenital CMV hepatosplenomegaly, petechiae, and CNS involvement.
infection?

What are the clinical CMV mononucleosislike EBV-related mononucleosis,

manifestations of with fever, mild lymphadenopathy, lymphocytosis,
CMV mononucleosis? increased liver enzymes, and splenomegaly

What are the Interstitial pneumonitis, hepatitis, Guillain-Barr

potential syndrome, meningoencephalitis, myocarditis,
complications of thrombocytopenia and hemolysis, retinitis, and
CMV infection? gastrointestinal disease

Papillomaviruses
 What are routes of transmission Close personal contact; anogenital warts
for papillomaviruses? are the most common STDs.

Influenza
What are the In uncomplicated influenza, incubation is 1 to 2 days followed
clinical by abrupt onset of fever, chills, headache, myalgias, malaise,
manifestations dry cough, and anorexia.
of influenza
virus
infection?

What are the Primary influenza pneumonia

two primary Secondary bacterial pneumonia
pulmonary
complications
of influenza?

Rapid Immunologic detection of viral antigens on respiratory

diagnostic secretions including nasal/throat swab specimens or from a
tests for nasal wash
influenza are
based on
what?

What other Other pulmonary processes, myositis, TSS, Guillain-Barr

complications syndrome, and Reye's syndrome
of influenza
can occur?

What is the For uncomplicated influenza A, amantadine or rimantadine.

treatment for Oseltamivir and zanamivir are available for treatment of
influenza? influenza A and B.

Who should Persons at increased risk of complications from influenza,

receive the including persons above 50 years of age, residents of chronic
influenza care facilities, and persons with underlying chronic pulmonary
vaccine? or cardiovascular disease, significant metabolic disorders,
hemoglobinopathies, renal dysfunction, or immunosuppression.
Health-care workers and other persons who provide care to
individuals at risk should also be immunized.

Enteroviruses
Name the enteroviruses. Coxsackieviruses, echoviruses, and enteroviruses
 P.310
P.311

Hepatitis Viruses

Hepatitis A
What type of RNA picornavirus
virus is
associated with
hepatitis A
infection?

How is hepatitis Fecaloral route, person-to-person contact, and

A transmitted? contaminated food or water

How can Avoiding contaminated food/water.

hepatitis A Vaccination is effective if given 2 weeks before travel,
infection be otherwise, if possible exposure is anticipated in less than 2
prevented? weeks, serum immune globulin can be given to prevent
infection.

Hepatitis B
How is hepatitis B transmitted? Parenterally (IVDAs, blood transfusions),
sexual contact, and perinatally. It is not
transmitted by the fecaloral route.

What is the incubation period 1 to 4 months

after exposure to hepatitis B?

Which transaminase is usually ALT

higher in acute hep B: AST or
ALT?

What is the best indicator of PT (prothrombin time)

prognosis in those with acute
hep B?

Acute hep B is diagnosed by The detection of HBsAg, anti-HBc IgM,

evidence of elevation of what HBe Ag (hepatitis B e antigen), and HBV
viral markers?
DNA

What viral markers indicate past Presence of anti-HBsAg, and anti-HBcAg

 infection with hepatitis B IgG
(immunity through infection)?

What viral markers indicate Anti-HBsAg

immunity through vaccination?

What defines chronic hepatitis The presence of HBsAg for more than 6
B? months

What is the seroconversion rate Greater than 90%

for healthy adults and children
to the hepatitis B vaccine?

P.312

Hepatitis C
What are the hepatitis C 1b, 1a, 3a, 2b, 2a, 3, 4a, 2, 2c, 4, 1, 5a, other
genotypes? (in order of decreasing frequency)

What are the most common 60% to 70% of genotypes are of types 1a or 1b
genotypes of hepatitis C in
the United States?

What is the average 7 weeks

incubation period for acute
hepatitis C?

What are the ways hepatitis By IVDAs, sexual contact, and perinatal
C is transmitted? transmission

What percentage of those 50% to 85%

with acute hepatitis C
develop chronic infection?

How is the diagnosis of Enzyme immunoassay measuring antibodies to

hepatitis C infection made? recombinant HCV polypeptides, HC viral load to
evaluate for persistent infection

How are genotypes used in As a predictor to response to therapy

the treatment of hepatitis
C?

Hepatitis D
 What is the mode of Primarily the parenteral route, less often by
transmission of hepatitis D? sexual contact, and rarely perinatally

Fungi

Candida
What are the Candida albicans, glabrata, and parapsilosis are the three
major Candida main pathogens for both bloodstream and mucosal
species? infections.

Aspergillus
Who is most at risk for Neutropenic patients, recipients of organ or bone
infections with marrow transplantation, those with chronic
Aspergillus species? immunosuppression and acquired or congenital
immunodeficiency syndromes

Infection or Allergic bronchopulmonary aspergillosis (allergic

colonization with response to the Aspergillus colonization of airways in
Aspergillus species patients with asthma or cystic fibrosis), pulmonary
may result in what aspergilloma, and invasive aspergillosis
types of diseases?

P.313

Cryptococcus
What types of Invasive fungal infection due to Cryptococcus
cryptococcal neoformans, which most
infections affect

immunocompromised commonly causes meningoencephalitis or pneumonia.

patients (in However, cryptococcal infections have been reported in
particular AIDS most organ systems.
patients or solid
organ transplant
recipients)?

In addition to Monitoring the opening pressure recorded on the

starting antifungal lumbar puncture. It is often elevated in cryptococcal
therapy for AIDS meningoencephalitis. The goal opening pressure should
patients with be less than 200 mm water. Daily lumbar punctures
cryptococcal may be needed and can be discontinued once the
meningoencephalitis, opening pressure is within the normal range for several
what else should be days.
 done?

Histoplasma
Name the APH (acute pulmonary histoplasmosis), CPH (chronic
three clinically pulmonary histoplasmosis), and PDH (progressive disseminated
important histoplasmosis)
histoplasmosis
syndromes.

What are the Patients are asymptomatic in 90% of cases. Symptoms include
clinical fever, headache, malaise, and nonproductive cough after a 3-
features of to 21-day incubation period.
acute
pulmonary
histoplasmosis?

What are the Persistent cough, weight loss, malaise, low-grade fevers, and
symptoms of night sweats over several weeks. Symptoms may mimic those
CPH? of tuberculosis.

What are the Severity of PDH ranges from acute illness to more chronic
clinical disease lasting for months to years. Manifestations may
manifestations include hepatosplenomegaly with abnormal LFTs,
of PDH? gastrointestinal mucosal ulcerations, oropharyngeal ulcers,
adrenal insufficiency, anemia, interstitial pneumonitis, and
renal involvement. More rarely, CNS disease, lytic bone
lesions, and lymphadenopathy occur.

P.314

Blastomyces
What are the pulmonary
manifestations of the
following:

Acute pulmonary Typically influenza-like with fevers, arthralgias,

blastomycosis? myalgias, and cough

What are the Chest radiograph is nonspecific, often with

radiographic findings of localized consolidation; hilar adenopathy is rare.
acute pulmonary
blastomycosis?
 Chronic pulmonary Cough, sputum production, weight loss,
blastomycosis? hemoptysis, dyspnea, pleuritic chest pain

What are the Nonspecific radiographic findings

radiographic findings of
chronic pulmonary
blastomycosis?

How is the diagnosis of Culture of fungus. A presumptive diagnosis can be

blastomycosis made? made from some histopathologic specimens based
on morphology and staining characteristics.

Sporothrix
What are the Primarily cutaneous. A papule, chancre, or subcutaneous
clinical nodule develops at the site of a traumatic inoculation.
manifestations Secondary nodules, which often ulcerate and drain, develop
of along regional lymphatics. Osteoarticular involvement is the
sporotrichosis? most common extracutaneous manifestation.

What hobbies Gardening and farming

and
occupations
put individuals
at risk for
sporotrichosis?

Host Defenses

Humoral Immunity
What are the Increased risk of respiratory infections with Streptococcus
consequences of pneumoniae,
antibody H. influenzae, Neisseria meningitidis (encapsulated
deficiencies? pathogens), and mycoplasma, and increased incidence of
sinusitis, otitis, and gastrointestinal infections

P.315

Complement
How is Antigens and antibodies activate the classic pathway;
complement polysaccharides, lipopolysaccharides, and teichoic acid activate
activated? the alternative pathway.
 What is the The result depends on which component is deficient and
result of whether that component is absent or reduced. The most
complement common pathogen seen is meningococcus, which is responsible
deficiency? for 80% of infections.

Phagocytosis
What pathogens occur in Staphylococci, gram-negative bacilli, and fungi
neutropenic patients? (Candida, Aspergillus, Mucor)

Cell-Mediated Immunity
What is cell- Part of the immune response that is carried out by T
mediated lymphocytes, NK cells, and mononuclear phagocytes
immunity?

What are Proteins or glycoproteins secreted by cells that act as

cytokines? signals between cells of the immune system and
mediators of response to infection

What are NK cells? Closely related to T lymphocytes, NK cells can lyse target
cells without major histocompatibility complex restriction
or presensitization.

What are Bone marrow progenitors, circulating monocytes, and

mononuclear tissue macrophages
phagocytes?

What are the Primarygenetic

kinds of defects in Secondarydrug therapy (immunosuppressive medications
cell-mediated including corticosteroids), radiation therapy, organ
immunity? transplantation, lymphoreticular malignancies,
malnutrition, and infections (viral, most notably HIV
infection)

What are the Think intracellular organisms including mycobacteria,

pathogens that Legionella, Salmonella, Chlamydia, Brucella, Yersinia,
result from Nocardia, Rickettsia, Listeria, fungi (Histoplasma,
defects in cell- Candida, Cryptococcus) protozoa, and viruses.
mediated
immunity?

P.316

Major Clinical Syndromes

Fever of Unknown Origin
What are criteria A temperature >38C for >3 weeks, or >2 visits or 3
for defining classic days in the hospital with evaluation of the cause.
FUO?

What are the major Infection (30% to 40% of cases), neoplasms (20% to 30%
causes of FUO? of cases), collagen vascular diseases (10% to 15% of
cases), and miscellaneous (10% to 20% of cases)

What is included in History (including travel), repeated physical exams, CBC

the initial diagnostic with differential, UA, CXR, blood cultures, ESR,
evaluation for FUO? rheumatoid factor, ANA, HIV, tuberculosis skin test

What additional CT of chest, abdomen, and pelvis if initial workup

diagnostic tests negative. If negative, PET scan may be useful.
should be ordered
for FUO?

What invasive tests Always attempt symptom-directed workups. Biopsy of

should be ordered bone marrow, liver, and involved organs should be
for FUO? considered in all patients with FUO.

P.317

Fever and Rash

What history questions Drug ingestion, travel history, occupational or sun
are important to ask in exposure, recent immunizations, STD/HIV exposure,
a patient with fever exposure to another with similar symptoms/signs,
and rash? pets and hobbies

What are the common HIV, CMV, varicella zoster, RMSF, Lyme, Ehrlichia,
organisms that can Neiserria meningitidis
cause fever and rash?

Community-Acquired Pneumonia
What laboratory Leukopenia
abnormality is associated
with a poorer prognosis?

What is the most common Streptococcus pneumoniae

bacterial pathogen in CAP?
 What are some of the Staphylococcus aureus, Haemophilus influenzae,
other typical bacterial Legionella
pathogens in CAP?

What are some of the Mycoplasma pneumoniae, Chlamydophilia

atypical bacterial pneumoniae, and Legionella pneumophila
pathogen in CAP?

What diagnostic tests Blood cultures, sputum culture, CXR

should be perfomed?

What is the empiric A respiratory flouroquinolone alone or an

therapy for CAP in a non- advanced macrolide plus a beta lactam
ICU hospitalized patient?

What is the duration of The literature on the optimum duration of

therapy? therapy for CAP is still evolving. On average the
treatment course is 7 to 14 days.

Pleural Effusion and Empyema

What are the three most common causes of Pneumonia, thoracotomy,
pleural space infections? and trauma

P.318

Urinary Tract Infections

What are the classic symptoms of Dysuria, frequency/urgency, hematuria
lower UTI?

What are the classic symptoms of Fever (with occasional chills), flank pain,
upper UTI? along with lower tract symptoms

What constitutes pyuria? Presence of leukocytes at least 10/mm3

of midstream urine specimen

What are the accepted methods Midstream clean catch, catheterization,

for urine collection? and suprapubic aspiration

What should the initial evaluation Urinalysis, urine culture, blood cultures,
include in a hospitalized patient CBC with differential, and a basic
with cystitis/pyelonephritis? chemistry panel

What pathogens are associated E. coli, S. saprophyticus, K. pneumoniae,

 with uncomplicated cystitis? P. mirabilis

What are the empiric therapy Trimethoprim-sulfamethoxazole (where

choices for treatment of UTIs? local area resistance rates are less than
10% to 15%) or a fluoroquinolone

Generally, what is the duration of 3 days

therapy for uncomplicated
cystitis?

What is the most common risk An indwelling Foley catheter

factor for Candida UTIs?

P.319

Sepsis
What is SIRS? Systemic inflammatory response syndrome defined as two
or more of the following:
Temperature >38C or <36C, Heart rate >90
Respiratory rate >20, WBC count >12 or <4 or >10% bands

What is sepsis? The systemic response to infection (SIRS associated with

suspected or proven infection)

What is severe Sepsis associated with organ dysfunction away from the
sepsis? site of infection, hypoperfusion, or hypotension

What is in the Trauma, burns, adrenal insufficiency, pacreatitis,

differential for pulmonary embolus, myocardial infarction, dissecting or
sepsis? ruptured aortic aneurysm

What A broad-spectum, intravenous regimen that will cover

antimicrobials most gram-positive and gram-negative bacteria
should be used
for empiric
therapy for
sepsis?

What are some Depending on the suspected source of infection,

choices for possibilities include a carbapenem or cefepime plus
empiric vancomycin or a beta-lactam/beta-lactamase inhibitor
antimicrobial combination agent such as pipercillin-tazobactam.
therapy for
sepsis?
 P.320

Intraperitoneal Infections
What is primary Also known as SBP (spontaneous bacterial peritonitis), it
peritonitis? is an infection of the peritoneal cavity without an evident
source.

What population Patients with cirrhosis and ascites

of patients is SBP
most commonly
seen?

What microbes are Enteric organisms such as E.coli (most common), K.

usually seen in pneumoniae, S. pneumoniae; anaerobes are reported
SBP? infrequently.

What are the An acute febrile illness with abdominal pain, nausea,
clinical vomiting, and diarrhea. However, some cirrhotic patients
manifestations of with SBP will present only with encephalopathy or vague
SBP? abdominal pain and malaise.

How is the By evaluation of the ascitic fluid obtained by

diagnosis of SBP paracentesis. This should be sent for Gram's stain,
made? aerobic/anerobic culture, cell count with differential,
protein and albumin. A PML count >250/mm 3 is
diagnositic (even in the absence of positive Gram's stain
and culture).

What drugs are A third-generation cephalosporin or a fluoroquinolone

commonly used
for empiric
therapy for SBP?

What potential Intraperitonel abscess

complication of
SBP should be
evaluated for in
those not
responding to
therapy?

P.321

Infections of the Liver and Biliary System

What are the two Amebic and pyogenic
main categories
of liver abscess?

What is the cause Entamoeba histolytica

of amebic liver
abscess?

In what group is Travelers returning from endemic areas

amebic liver
abscess most
commonly seen in
the United
States?

What are the Fever and a dull, aching rightupper-quadrant pain; usually
clinical without jaundice. Only up to one third of patients have
manifestations of concurrent gastrointestinal symptoms.
amebic liver
abscess?

What is the Medical management alone is usually successful; treatment

therapy for with metornidazole 750 mg three times a day for 7 to 10
amebic liver days.
abscess?

What are the E. coli, Klebsiella spp., Enterococcus spp., Streptococcus

common anginosus group, Bacteroides spp.
etiologies of
pyogenic liver
abscess?

What is the most Infection of the biliary tree

common route of
infection in
pyogenic liver
abscess?

What is the Fever, jaundice, and right-upper-quadrant pain (seen in

classical triad only 1 in 10)
seen in pyogenic
liver abscess?

What is the most An elevated alkaline phosphatase

frequently
 abnormal liver
function test in
pyogenic liver
abscess?

What is the usual Ceftriaxone plus metronidazole

empiric regimen
for suspected
pyogenic liver
abscess?

What is the Ultrasound or CT-guided drainage of lesion

mainstay of
treatment of
pyogenic liver
abscess in
addition to
antibiotics?

What infections Cholecystitis, acalculous cholecystitis, and cholangitis

are associated
with the biliary
tract?

What is the Right-upper-quadrant pain; possibly a Murphy's sign

typical (inhibition of inspiration by pain when the area of the
presentation of gallbladder fossa is palpated); fever, tachycardia; with
biliary tract cholangitis, Charcot's triad of fever, right-upper-quadrant
disease? pain, and jaundice may be seen.

P.322

Infective Endocarditis
What is infective Infection of the endocardial surface of the heart
endocarditis (IE)? with the physical presensce of microorganisms in the
lesion

What is the 1 case per 1000 hospital admissions

approximate incidence
of IE?

Which heart valve is Mitral (30% to 45%), aortic (5% to 35%), mitral and
involved in IE, from the aortic (0% to 35%), tricuspid (0% to 5%), pulmonary
most common to the (<1%)
least?
 What is the 85%, but it may be absent in right-sided disease.
approximate The classic changing murmur or new regurgitant
percentage of those murmur occurs only 5% to 10% and 3% to 5%,
with IE who have a respectively.
murmur?

What are some of the Fever, heart murmur, skin manifestations (such as
common clinical petechiae), embolic phenomenon
manifestations of IE?

What are some of the Anemia, elevated ESR, abnormal UA (proteinuria,

common laboratory microscopic hematuria), leukocytosis
findings in IE?

How should blood Three sets of blood cultures from different sites
cultures be collected in should be collected in the first 24 hours.
suspected cases of IE?

What other diagnostic Transthoracic and sometimes transesophogeal

measure is important in echocardiography
the diagnosis of IE?

What are the most Streptococcus, Staphylococcus, Viridans streptococci,

common bacterial Enterococcus
pathogens associated
with IE?

What is the empiric Vancomycin plus gentamicin

therapy for native
valve IE?

What is the duration of Approximately 6 weeks of intravenous therapy

therapy for left-sided
IE?

See Chapter 5
(Cardiology) for
more discussion of
endocarditis.

P.323

Acute Meningitis
What are the Enteroviruses, herpesviruses, HIV
leading
causes of
viral or
aseptic
meningitis?

What does A pleocytosis, with the WBC count 100 to 1000/mm 3

evaluation of (predominately leukocytes), mildly elevated or normal protein,
the CSF show normal or mildly decreased glucose
in viral
meningitis?

What is the Supportive care

treatment for
most cases of
viral
meningitis?

What is the Treatment with intravenous acyclovir benefits patients with

specific HSV meningitis and focal neurologic findings.
therapy for
herpes
meningitis?

What are the H. influenzae, N. meningitides, S. pneumoniae

three most
common
pathogens
associated
with bacterial
meningitis?

What are the Headache, fever, meningismus, altered sensorium

symptoms
and signs of
bacterial
meningitis?

What does Pleocytosis with WBC 1000 to 5000/mm 3 (neutrophil

the CSF show predominant), glucose !40, elevated protein (100 to 500
in bacterial mg/dL), positive Gram's stain 60% to 90%, positive culture of
meningitis? CSF (70% to 85%)

When should With focal neurological deficits on exam (including altered

a CT scan be consciousness), in the immunocompromised, history of CNS
 performed disease, new-onset seizures, or papilledema. Blood cultures
before a and antibiotics should be started while awaiting imaging.
lumbar
puncture?

What is the Dexamethasone reduces the inflammation in the subarachnoid

role of space following the antibiotic-mediated lysis of bacteria. A
steroids in meta-analysis evaluated the role of adjunctive dexamethasone
the treatment given before or at the time of antibiotics and found improved
of bacterial outcomes (most clearly seen for children with pneumococcal
meningitis? meningitis).

What is the Vancomycin and a third-generation cephalosporin. Depending

empiric on the clinical situation, acyclovir and/or ampicillin can be
antimicrobial started as well to treat for HSV and Listeria respectively.
therapy for
bacterial
meningitis?

P.324

Epidural Abscess
What is an epidural abscess? An epidural abscess is a localized collection of
pus between the dura mater and the overlying
skull or vertebral column.

What are the two main ways Hemotogenous spread from a different foci of
epidural abscesses are infection or by direct extension from vertebral
formed? osteomyelitis

What is the most common S. aureus

organism isolated from
those with an epidural
abscess?

What are the four clinical 1. Backache and focal vertebral pain
stages associated with 2. Nerve root pain, manifest by radiculopathy
thoses presenting with an or paresthesias
epidural abscess? 3. Spinal cord dysfunction, manifest by defects
in motor, sensory, or sphincter function
4. Complete paralysis

What is the treatment for A combined medical/surgical approach. Emperic

spinal epidural abscess? antimicrobials should be given while the
 patient is planned for surgical decompression
and drainage.

What is the empiric therapy A regimen that contains coverage for S. aureus,
for spinal epidural abscess? including resistant organisms and for aerobic
gram negative bacilli

Gastroenteritis
What is the Oral rehydration therapy. Therapy with a fluoroquinolone
empiric treatment (e.g., ciprofloxacin) may shorten the duration of
for inflammatory symptoms if C. difficile and E. histolytica are not
diarrhea? suspected.

What is the Discontinuation of the offending antibiotic if possible

treatment for C. Therapy with oral metronidazole or oral vancomycin if
difficile diarrhea? patient is refratory or intolerant to metronidazole

What are the Rotavirus, Norwalk virus, Giardia, Cryptosporidium, S.

causes of aureus, Bacillus cereus, Clostridium perfringens, Vibrio
noninflammatory cholerae, and enterotoxigenic E. coli
diarrhea?

P.325

Genitourinary Infections

Vulvovaginal Candidiasis
What organisms are most Candida albicans (80% to 90%). Candida
commonly associated with tropicalis, and Candida glabrata also
vulvovaginal candidiasis? cause vaginitis.

What is the sensitivity of the KOH Approximately 50% to 75%

prep in vulvovaginal candidiasis?

Trichomoniasis
What risk factor is associated with Having an increased number of
trichomoniasis? sexual partners

What is the sensitivity of the wet mount 60% to 80% in symptomatic

in trichomoniasis? women

Bacterial Vaginosis
 What is seen on wet Clue cells and the absence of leukocytes,
mount in bacterial trichomonads, and the normal flora of rods
vaginosis?

What are clue cells? Squamous epithelial cells with ragged borders and
stippling caused by colonization with bacteria

Mucopurulent Cervicitis
What are the etiologic agents Chlamydia trachomatis and N. gonorrhoeae
of mucopurulent cervicitis?

What are complications of PID; in pregnant women, preterm delivery

mucopurulent cervicitis? and premature rupture of membranes

P.326

Pelvic Inflammatory Disease

What are the sequelae Infertility, ectopic pregnancy, chronic pelvic pain, and
of PID? recurrent episodes of PID

What is the Ectopic pregnancy, acute appendicitis, ruptured

differential diagnosis ovarian cyst, endometriosis, and ovarian torsion
for PID?

Urethritis
What other pathogens should be treated Chlamydiae
empirically in patients with gonorrhea?

What is the incidence of Chlamydia 10% to 30% in heterosexual

coinfection with GC? men; 40% to 60% in women

Herpes Genitalis
What is the role of Frequent recurrences may be controlled with daily
suppressive therapy in suppressive therapy, but this does not prevent
herpes infection? viral shedding.

Syphilis
What are the Primarychancre
stages of Secondarydisseminated (mean of 6 weeks after contact)
syphilis? Latentdiagnosed only by serologic testing; early and late
 stages
Tertiarymay or may not be clinically apparent; develops in
30% of untreated patients and involves the aorta and CNS

What are the One or more chancres (ulcerated lesions with heaped-up
manifestations margins), which are minimally painful, and nontender
of primary regional adenopathy
syphilis?

What are the Maculopapular, symmetric, generalized rash primarily

features of involving the oral mucous membranes and genitalia but often
secondary with involvement of palms and soles; generalized
syphilis? lymphadenopathy; sometimes alopecia

What are the Lymphocytic meningitis, dementia, tabes dorsalis (posterior

major spinal column and ganglion disease), aortic disease, or
manifestations destructive lesions of skin and bone
of tertiary
syphilis?

What are the Acute viral illnesses, collagen-vascular diseases, pregnancy,

causes of false- intravenous drug use, and leprosy, among others
positive
nontreponemal
tests?

P.327

Soft Tissue, Bones, and Joints

Cellulitis
What is the Because it is difficult to distinguish clinically between
presumptive staphylococcal and streptococcal skin infections, initial
therapy for therapy should adequately cover both organisms.
cellulitis in Penicillinase-resistant penicillins or first-generation
penicillin cephalosporins are antibiotics of choice.
nonallergic
patients?

What is the Erythromycin, clindamycin, and vancomycin are alternatives

presumptive for mild and severe infections, respectively, in penicillin-
therapy for allergic patients.
cellulitis in
penicillin-
allergic patients?
 What is the There has been an increased prevalence of community-
therapy for acquired MRSA skin infection in patients presenting with
suppurative suppurative cellulitis. These infections can be treated with
cellulitis? clindamycin, trimethoprim-sulfamethoxazole, or rifampin.

What is the Surgical debridement and antibiotics, which are ultimately

therapy for guided by bacteriologic data. Depending on clinical
necrotizing circumstances, presumptive therapy may include
fasciitis? combinations of the following:
Ampicillin, gentamicin, and clindamycin
Ampicillin, gentamicin, and metronidazole
Ampicillin-sulbactam and gentamicin

What are the Clostridium perfringens type A and other Clostridium sp.
principal agents
that cause gas
gangrene?

What is the Emergent surgical debridement

treatment for Penicillin and additional agents to cover possible anaerobic
gas gangrene? and Gram-negative copathogens

P.328

Osteomyelitis
How can the Early bone biopsy for culture and histopathology not only
diagnosis of establishes the diagnosis but also often provides the etiologic
osteomyelitis agent.
definitively be
made?

What is the Plain films are insensitive for diagnosing osteomyelitis. MRI is
role of a very sensitive (98%) and specific (93%) tool for diagnosing
radiologic vertebral osteomyelitis and diskitis.
studies in
diagnosing
osteomyelitis?

What other CT with contrast

imaging studies Radionuclide studies (bone scan or indium labeled WBC scan)
are useful in can also be performed although there may be false positives
osteomyelitis? with the radionuclide scans due to inflammation.

Are cultures of These cultures reflect colonization of the tract and do not
 sinus tracts correlate with the underlying bone infection. However, if S.
useful in aureus is isolated from an open sinus tract, the likelihood is
osteomyelitis? high (>80%) that S. aureus is also present in bone.

What is the 1. Debridement of necrotic, avascular infected bone

treatment for 2. Removal of all foreign objects
osteomyelitis? 3. Pathogen-specific antimicrobial therapy

What is the Acute4 to 6 weeks intravenous therapy

duration of Chronic6 weeks intravenous therapy, then several months
therapy for of oral therapy
osteomyelitis?

P.329

Infectious Arthritis
What is included in Gout, pseudogout, rheumatoid arthritis, SLE, Reiter's
the differential for syndrome, other infectious but nonbacterial causes
pyogenic arthritis?

How is the Identification of bacteria from synovial fluid obtained

diagnosis of through arthrocentesis
infectious arthritis
made?

What are the A swollen, painful, erythemetous joint, usually with a

clinical symptoms visible effusion; usually accompanied by moderated
and signs of fevers, chills
infectious
arthritis?

What does the Mild leukocytosis, elevated ESR, synovial fluid usually
laboratory findings contains an elevated number of WBC/mm 3 (as high as
in infectious 50,000 to 100,000 in gonoccocal arthritis), a neutrophil
arthritis? predominance

P.330

Acquired Immunodeficiency Syndrome

What is HIV? Retrovirus that causes progressive dysfunction of the
immune system

What is AIDS? Acquired immunodeficiency syndrome is caused by

infection with HIV.
What is the CD4 cell count of less than 200/mm 3 , a percentage of CD4
definition of cells below 14%, or 1 or more of 26 different
advanced opportunistic diseases (occurring when at least moderate
immunodeficiency suppression of cell-mediated immunity is present).
in AIDS?

What is the More than 40 million people worldwide; the number of

prevalence of HIV newly infected in 2005 estimated at 4.9 million.
infection?

What is the In 2007, the number of people living with HIV/AIDS

prevalence of worldwide was 33.2 million. As of 12/2005, an estimated
AIDS? 1.1 million persons in the United States were living with
HIV/AIDS, with 25% of those undiagnosed or unaware.
Currently more than 2.5 million new infections occur
yearly, with more than 2.1 million deaths, making
HIV/AIDS the leading cause of death as a result of
infection.

What is acute HIV The time right after infection before there is an immune
seroconversion? response.

What are the An acute mononucleosis-like illness (fever, headache,

symptoms of arthralgias, myalgias, malaise, oral ulcers, weight loss,
acute pharyngitis, rash, gastrointestinal symptoms, and,
seroconversion? occasionally, aseptic meningitis) develops. Almost all
patients have anti-HIV antibodies by 6 months.

When should CD4 count <200/"L

combination AIDS-defining illness
antiretroviral HIV-related constitutional symptoms
treatment be Asymptomatic patients with CD4 count between 200 to
initiated in HIV 350/"L; depends on the viral load
infection?

What are the Candidal esophagitis, PCP, MAC, CMV, toxoplasmosis,

most common cryptococcal meningitis, and M. tuberculosis
opportunistic
infections in HIV
infected persons?

What is MAC? Mycobacterium avium complex is an atypical

mycobacterium that produces disseminated disease in
patients with advanced AIDSthe CD4 cell count is usually
 <50/mm 3 . Patients have fever (to 40C), night sweats,
and weight loss, and they may have abdominal pain or
diarrhea. Diagnosis is made by blood culture. Treatment is
clarithromycin plus ethambutol.

What is the most CMV; it develops late, when CD4 cell counts are
common cause of <100/mm 3 .
retinitis in AIDS
patients?

How does CMV Initially, patients may be asymptomatic (disease begins

retinitis present? peripherally), but progressive visual loss develops. CMV
retinitis has the appearance on funduscopy of cottage
cheese and ketchup.

How is CMV Patients with CMV retinitis require therapy with

retinitis treated? ganciclovir or foscarnet.

What is the most Kaposi's sarcoma

common
malignancy in
AIDS?

What is the most Toxoplasmosis

common cause of
a focal CNS lesion
in AIDS?

What are the PCP, bacterial pneumonia, tuberculosis, fungi

most common (Cryptococcus, Histoplasma)
causes of
pneumonia in
AIDS?

P.331

Nosocomial Infections
What is the incidence of Occurs in more than 5% of patients admitted
nosocomial infection? to acute care hospitals

Nosocomial Bloodstream Infection

What are the risk Indwelling venous catheters, extremes of age, underlying
factors for disease, malnutrition, increased length of hospital stay,
 nosocomial BSI? invasive procedures, ICU stay

What pathogens Coagulase-negative staphylococci, S. aureus,

are associated with enterococci, Candida, E. coli, Enterobacter, Proteus,
nosocomial BSI? Klebsiella, and other bacteria (less commonly)

Nosocomial Pneumonia
What is the incidence More than 250,000 episodes per year. It is the second
of nosocomial leading cause of nosocomial infection and the number
pneumonia? one cause of death as a result of nosocomial
infection in the United States.

How long does a 48 hours, assuming that he or she was not incubating
patient need to be a pneumonia prior to admission
hospitalized to be at
risk for hospital
acquired pneumonia?

What are the main S. aureus, Pseudomonas aeruginosa, and mutidrug-

pathogens in resistant pathogens in addition to the regular CAP
hospitalacquired or etiologies
health careassociated
pneumonia?

What are the risk Hospitalized for at least 2 days within the past 90
factors for health days, long-term-care facility resident, has received
careassociated intravenous antibiotics or chemotherapy within the
pneumonia? past 30 days, or has regular visits to an outpatient
clinic

P.332

Nosocomial Urinary Tract Infection

What is the incidence of 400,000 to 1 million infections per year; 40% of
nosocomial UTI? all nosocomial infections

Surgical Wound Infection

What is the Because skin pathogens are most common, consider nafcillin or
treatment for vancomycin. Cover gram-negative anaerobes if there is deep
surgical wound infection or if the patient is at risk. Surgery is often
wound needed for deep infection.
infection?
Nosocomial Gastrointestinal Infections
What pathogens Bacteria cause more than 90% of episodes, and C. difficile
are associated causes 90% of episodes in which a pathogen is identified.
with nosocomial Rotavirus is the second most common pathogen and is seen
diarrhea? in 1 of 20 infections.

What is the Hydration, supportive care, and, if possible, stop antibiotics.

treatment for Treat with metronidazole (oral route is preferred to
nosocomial intravenous therapy if the pathogen is C. difficile).
diarrhea?

P.333

Traveler's Syndromes
In what percentage of persons 30% to 50%
traveling to underdeveloped countries
does traveler's diarrhea develop?

What is the predominant microbial Enterotoxigenic E. coli

pathogen in traveler's diarrhea?

What are the contraindications for High fever, bloody stools, or other
antimotility agents in traveler's evidence of an inflammatory colitis
diarrhea? or dysentery

Why are antimotility agents avoided Toxic megacolon has been reported
with these symptoms? with the use of antimotility agents
with inflammatory diarrhea.

What are the most common causes of Malaria, enteric fever, hepatitis, and
febrile illness in returning travelers? amebic liver abscess

What are the major causes of Helminthic, including filariasis,

eosinophilia in travelers? schistosomiasis, and strongyloidiasis
Editors: Bergin, James D.
Title: Advanced Medicine Recall, 1st Edition
Copyright 2009 Lippincott Williams & Wilkins

> Table of Contents > Section II - The Specialties > Chapter 8 - Nephrology

Chapter 8
Nephrology

P.335
P.336

Abbreviations
ACE Angiotensin-converting enzyme

ACEI Angiotensin-converting enzyme inhibitor

ADPKD Autosomal dominant polycystic kidney disease

AG Anion gap

AIN Acute interstitial nephritis

AKI Acute kidney injury

ANA Antinuclear antibody

ANCA Antineutrophil cytoplasmic antibody

APA Antiphospholipid antibody syndrome

ARB Angiotensin receptor blocker

ARF Acute renal failure

ATN Acute tubular necrosis

AVP Arginine vasopressin

BP Blood pressure
BUN Blood urea nitrogen

CBC Complete blood count

C3, C4 Complement components 3 and 4

CHF Congestive heart failure

CIN Chronic interstitial nephritis

CK Creatine kinase

CKD Chronic kidney disease

CLL Chronic lymphocytic leukemia

CMV Cytomegalovirus

CNS Central nervous system

CrCl Creatinine clearance

CRI Chronic renal insufficiency

CSW Cerebral salt wasting syndrome

CT Computed tomography

CVA Cerebrovascular accident

CXR Chest x-ray

DI Diabetes insipidus

DKA Diabetic ketoacidosis

DM Diabetes mellitus

DNA Deoxyribonucleic acid

dsDNA Double-stranded DNA

ECF Extracellular fluid

EM Electron microscopy

ESR Erythrocyte sedimentation rate

ESRD End-stage renal disease

FENa Fractional excretion of sodium

FMD Fibromuscular dysplasia

FSGS Focal segmental glomerulosclerosis

GBM Glomerular basement membrane

GFR Glomerular filtration rate

GI Gastrointestinal

GN Glomerulonephritis

HCO3- Bicarbonate

HD Hemodialysis

HELLP Hemolysis, elevated liver enzymes, low platelet count

HF Heart failure

HIV Human immunodeficiency virus

HLA Human leukocyte antigens

HSP Henoch-Schnlein purpura

HRS Hepatorenal syndrome

HTN Hypertension

HUS Hemolyticuremic syndrome

IF Immunofluorescence
IgA, G, M Immunoglobulin A, G, M

IV Intravenous(ly)

IVP Intravenous pyelogram

LM Light microscopy

MARS Molecular absorbent recirculating system

MCD Minimal change disease

MDRD Modification of diet in renal disease (study)

MIDD Monoclonal immunoglobulin deposition disease

MM Multiple myeloma

MMF Mycophenolate mofetil

MPGN Membranoproliferative glomerulonephritis

MRI Magnetic resonance imaging

MRA Magnetic resonance arteriography

NDL Nephrogenic diabetes lusipidus

NKF National Kidney Foundation

NSAIDs Nonsteroidal anti-inflammatory drugs

PAN Polyarteritis nodosa

PAS Periodic acidSchiff

PCP Pneumocystic carinii pneumonia

PCT Proximal convoluted tubule

P Cr Plasma creatinine

PK Plasma potassium
PKD Polycystic kidney disease

P Na Plasma sodium

P osm Plasma osmolality

PT Proximal tubule

PTH Parathyroid hormone

PTRA Percutaneous renal angioplasty

PVD Peripheral vascular disease

RAS Renal artery stenosis

RBC Red blood cell

RBF Renal blood flow

RF Rheumatoid factor

RPGN Rapidly progressive glomerulonephritis

RPN Renal papillary necrosis

RTA Renal tubular acidosis

RTC Renal tubular cell

SIADH Syndrome of inappropriate antidiuretic hormone

SLE Systemic lupus erythematosus

SPEP Serum protein electrophoresis

TB Tuberculosis

Tc Technetium

TIPS Transjugular intrahepatic portosystemic shunt

 TTKG Transtubular potassium gradient

TTP Thrombotic thrombocytopenic purpura

UAG Urine anion gap

U Cr Urine creatinine

UK Urine potassium

U Na Urine sodium

U osm Urine osmolality

UPEP Urine protein electrophoresis

UTI Urinary tract infection

VUR Vesicourethral junction

WBC White blood cell

P.337
P.338
P.339
P.340

Evaluation of Kidney Function

What is the best GFR
measurement of
kidney function?

How is GFR GFR is not measured directly. Urinary clearance of inulin

estimated? (a substance that appears in the urine only by filtration)
is the gold standard for measuring filtration. However,
the test is difficult to do. The best estimate of GFR is to
use the equation of the MDRD study:
GFR = 186 ! (Pcr) -1.154 ! (age)0.203 ! (0.742 if female) !
(1.210 if black)

How is creatinine 1. Based on a 24-hour urine collection: CrCl = [U cr

clearance
(mg/mL) ! Uvol (mL/24hr)]/[Pcr (mg/mL) ! 1440
assessed?
assessed?
(min)]
2. Estimation using Cockcroft and Gault: {[140 age (yr)]
! wt (kg)]/[Pcr (mg/dL) ! 72]} ! (0.85 in women)

Why is GFR a 1. Creatinine clearance overestimates GFR because

better measure of creatinine is secreted by the proximal tubule.
kidney function 2. Secretion of creatinine can be affected by medications
than creatinine (both trimethoprim and cimetidine decrease
clearance? secretion).
3. The generation of serum creatinine also varies with
age, race, gender, diet, amputation.

What are some 1. Ketotic states and hyperglycemia (if the Jaffe method
factors that can of determination of creatinine is utilized)
increase the 2. Cephalosporins (Jaffe method)
serum creatinine 3. Flucytosine (enzymatic method of determination of
but not affect creatinine)
clearance? 4. Cimetidine, trimethoprim (inhibit secretion of
creatinine)
5. Vigorous exercise
6. Ingestion of cooked meat

What are some of Gender: GFR approximately 8% higher in males

the causes of Body size: GFR conventionally factored by 1.73 m2
interpatient Ethnicity
variability in GFR? Age: age-related decline in GFR, 0.75 to 1.0 mL/min/1.73
m2 (0.01 to 0.02 mL/s/1.73 m2 ) per year
Pregnancy: GFR elevated as much as 50% in first trimester
and onward; returns toward normal by 4 to 8 weeks
postpartum
Protein intake: GFR higher in patients on high-protein diet
Diurnal variation: values tend to be about 10% higher in
afternoon than at night
Antihypertensive therapy: secondary to lowering of blood
pressure; variable effect not directly predictable
States associated with hyperfiltration: diabetes, obesity,
acromegaly

For which patient Age <18 and >70 years, pregnant women, ethnic subgroups
populations has other than African Americans and Caucasians
the MDRD-
estimated GFR not
been validated?
What is the major Failure to calibrate creatinine assay to the laboratory that
drawback for the developed the estimating equation can introduce error in
use of the MDRD estimating GFR, especially at higher GFR values.
equation?

What is a normal Normal GFR has a wide variation. Ages 13 to 21 years

GFR? (males) 140 30; (females) 126 22.

How does GFR Declines by 1 mL/min/1.73 m2 per year approximately

change with after 20 to 30 years
aging?

Why is urea not a 1. It is freely filtered but reabsorbed in the proximal and
good marker of distal nephron.
GFR? 2. Urea production is highly variable and greatly
influenced by diet and hydration status.

What is cystatin 1. Cysteine protease inhibitor produced at a constant

C? rate by all nucleated cells.
2. Freely filtered and then completely reabsorbed by the
tubules.
3. Most studies demonstrate that serum levels of cystatin
C are a better marker of GFR than creatinine.

What urine 1. Urinalysis with + protein + blood

findings are 2. Microscopy with oval fat bodies, fatty casts (nephrotic
markers for syndrome); WBCs, WBC casts, tubular casts, granular
kidney disease? casts (tubulointestinal process), dysmorphic RBCs, RBC
casts (glomerular process)

Why is 1. It is a marker of CKD if it persists "3 months

measurement of 2. It is associated with accelerated progression of
proteinuria cardiovascular and kidney disease.
important? 3. It is usually a sign of significant glomerular or tubular
damage.

What is the Urine albumin is 10 mg protein per day

normal rate of Urine total protein is 50 mg protein per day
protein excretion?

On a urine Proteinuria: >300 mg/day on 24-hour collection or >200

collection, what mg/g on urine spot
defines
proteinuria?

On a urine Microalbuminuria: 30 to 300 mg/day on 24-hour collection

collection, what or 30 mg/g on urine spot
defines
microalbuminuria?

On a urine Albuminuria: >300 mg/day on 24-hour collection or >300

collection, what mg/g on urine spot
defines
albuminuria?

What is the Albumin

recommended
protein to assess
for proteinuria?

Does proteinuria Yes. Higher levels of proteinuria are associated with

aid in determining glomerular disease and diabetic kidney disease.
the etiology of
CKD?

What are common Hematuria, UTI, exercise, dehydration

causes of false-
positive
proteinuria?

Can a single spot Yes, the ratio of protein or albumin to creatinine in a

urine be used to single early-morning specimen is acceptable.
quantitate
proteinuria?

What proteins are Only albumin. Thus this method is useful only as a
detected by the screening test and will not detect light chains or
urine dipstick nonalbumin proteins in the urine.
analysis?

What is the first Rule out pigmenturia.

step in evaluating
hematuria?

How do you rule By centrifuging the urine sample. If the sediment is red,
out pigmenturia? there is hematuria. If the supernatant is red, there is
pigmenturia.
 What are common Myoglobinuria, hemoglobinuria, beeturia, porphyria
causes of
pigmenturia?

Once hematuria is Glomerular hematuria: >70% dysmorphic cells, erythrocyte

determined, how casts, other cellular casts, proteinuria >1 g/day
is the site of Nonglomerular: <30% dysmorphic cells, no casts, absent or
disease localized? minimal proteinuria

P.341
P.342
P.343
P.344
P.345
P.346

AcidBase Disorders
What is the typical Initial blood buffering of newly formed acid by
response of the bicarbonate and creation of CO 2
body to an acid Less efficient buffering of acid by hemoglobin in RBCs
load or acid
and by Ca 2+ exchange in bones
generation?
Renal handling of acid load

What is involved H+ excretion by PT into lumen leads to reclamation of

with the renal bicarbonate.
handling of the H+ also combines with HPO 4 2 or HSO4 (titratable acids)
acid load?
or NH 3 in tubular lumen.
Kidney varies NH 3 production to allow for more acid
excretion.

What are the Increased acid load

causes of Lactic acidosis
metabolic acidosis? Ketoacidosis (starvation, diabetic, alcoholic)
Ingestions: salicylates, methanol, ethylene glycol,
toluene, metformin, ammonium chloride,
hyperalimentation fluids)
Extrarenal acidosis
Bicarbonate loss through GI tract: diarrhea, intestinal
fistula, ureterosigmoidostomy
Renal acidosis
Defect in bicarbonate reclamation: type 2 RTA
Defect in bicarbonate regeneration:
Diminished NH 4 + production (type IV RTA)
 Diminished H+ secretion (type I RTA)

What is the Winter's formula:

expected Pco 2 = (1.5 ! bicarbonate) + 8 (2)
respiratory
compensation with
a metabolic
acidosis?

How do you AG = (Na + ) [(Cl -) + (HCO 3 -)]: normal 8 to 11 meq/L

calculate the anion
gap?

What is the utility Buffering of HA (proton-anion) by bicarbonate in setting

of the plasma of increased acid load leads to increased unmeasured
anion gap? anions (A-) and increased anion gap.

What are the Unmeasured anions in the plasma, with the major
determinants of constituent being albumin. Thus the normal anion gap
the normal anion varies directly with the serum albumin level. A
gap? correction equation to use with estimating the normal
anion gap in the setting of hypoalbuminemia is 3 times
serum albumin.

What are the Methanol

typical causes of Uremia/renal failure
an increased anion Ketoacidosis (starvation, diabetic, alcoholic)
gap? Ethylene glycol
Lactic acidosis
Toluene
Salicylates
Metformin (lactic acidosis)
Tylenol (pyroglutamic acid)

How is ethylene Competitive inhibition of alcohol dehydrogenase with

glycol or methanol either ethanol or fomepizole decreases production of
ingestions treated? toxic by-products and hemodialysis.

What are some Volume depletion (hyperalbuminemia)

causes of an Metabolic or respiratory alkalosis
increased anion Severe hyperphosphatemia
gap not associated Presence of anionic paraprotein (often IgA)
with a metabolic
acidosis?
What are some Hypoalbuminemia (most common)
causes of an Hypermagnesemia
abnormally low or Hypercalcemia
even negative Lithium intoxication
anion gap? IgG paraprotein or polyclonal gammopathy
Bromide intoxication

How do you UAG = [(Na+ ) + (K + )] (Cl -)

calculate the urine
anion gap?

What is the utility In the setting of metabolic acidosis with a normal AG,
of the urine anion UAG is helpful to determine extra-renal versus renal
gap? acidosis. With normal renal compensation, NH 4 +
production increases in response to the acidosis and the
UAG becomes more negative (higher Cl- concentration).

How is the UAG UAG >0 suggests failure to produce NH 4 + and thus a
interpreted? renal (RTA) cause.
UAG <0 suggests normal renal response and extrarenal
bicarbonate loss (usually diarrhea).

What is a type I Defect in H+ secretion in the distal tubule

RTA?
Defect in H+ -ATPase pump which secretes acid
(Sjgren's syndrome)
Back diffusion of H+ due to increased tubular
permeability to H+ (amphotericin B)
Decreased distal delivery of Na+ (volume depletion)
Decreased cortical reabsorption of Na+ with net
increase in luminal charge and inhibition of H+ and K+
secretion (hyperkalemic type I) (urinary tract obstruction
and sickle cell disease)

What are the Urine pH >5.3

diagnostic features Plasma K+ usually low or normal
of a type I RTA? Plasma bicarbonate low (<14 meq/L)
Nephrocalcinosis

How is a type I Bicarbonate supplementation (in the form of potassium

RTA treated? or sodium/potassium citrate)

What is a type II Decreased ability to reabsorb bicarbonate in the PTnew

RTA? absorptive threshold
Injury to Na+/H+ antiporter or basolateral Na-K-ATPase
(myeloma, Fanconi's syndrome, ifosfamide)
Deficient/inhibited carbonic anhydrase (cystinosis,
acetazolamide)

What are the Urine pH >5.3 is serum bicarbonate level above

diagnostic features reabsorptive threshold; in steady state usually <5.3.
of a type II RTA? Plasma K+ usually low
Bicarbonate low (14 to 20 meq/L)
Often associated with other PT defects (glycosuria,
amino aciduria, phosphaturia)

How is a type II Bicarbonate supplementation (nearly impossible to

RTA treated? completely correct serum level). Can add a thiazide
diuretic which induces mild volume depletion, causing
increased proximal Na+ and bicarbonate resorption.

What is a type IV Due to decreased activity of the renin-angiotensin-

RTA? aldosterone system at any level. The acidosis is
worsened by hyperkalemia which inhibits renal
ammoniagenesis.

What are some of Diabetes, adrenal insufficiency, heparin, ACEI, ARB,

the causes of type potassium sparing diuretics, HIV infection, and primary
IV RTA? adrenal insufficiency

What are the Urine pH <5.3

diagnostic features Elevated plasma K
of a type IV RTA? Bicarbonate low (14 to 20 meq/L)

How is a type IV Remove offending medications; often acidosis improves if

RTA treated? hyperkalemia is treated; bicarbonate supplementation
and steroid replacement if primary adrenal insufficiency

At what GFR does At GFR less than 40 mL/min, total ammonium excretion
renal ammonia begins to fall and a non-gap acidosis may appear.
production begin Generally, the bicarbonate is stabilized at a level from
to fall? 12 to 20 meq/L through bone buffering of acid.

What are the Factors that generate a metabolic alkalosis include:

common causes of Gastric suction
a metabolic Vomiting
alkalosis? Antacid therapy
Chloride-losing diarrhea
 Diuretics
Mineralocorticoid excess
Hypercalcemia/milk-alkali syndrome
Low chloride intake
Hypokalemia (shift of H+ into cells)
Refeeding (shift of H+ into cells)
Massive blood transfusions
Bicarbonate administration

What are the Normally, the kidney can efficiently excrete bicarbonate
factors that permit and rapidly correct a metabolic alkalosis. Thus the
maintenance of following factors must occur to maintain a metabolic
metabolic alkalosis:
alkalosis? Decreased GFR (volume depletion or renal failure)
Increased tubular reabsorption of bicarbonate
(hypokalemia, hyperaldosteronism, chloride depletion)

In the diagnosis of
metabolic alkalosis,
what are the
diagnostic
possibilities if the
urine chloride is:

<10 meq/L? Vomiting or nasogastric suction; diuretics

>10 meq/L with Cushing's syndrome, hyperaldosteronism, hypokalemia,

hypertension? conditions of apparent mineralocorticoid excess

>10 meq/L and Bartter's or Gitelman's syndrome

normal or low
blood pressure?

How is a metabolic
alkalosis treated:

With a low urine Normal saline

chloride?

With a high urine Treatment of underlying disorder

chloride?

What are common Inhibition of respiratory drive (drugs, sleep apnea, CNS
causes of a lesions)
respiratory Disorders of respiratory muscles (myasthenia, spinal cord
acidosis? injury)
Upper airway obstruction (aspiration, sleep apnea)
Lung disease (pneumonia, asthma, etc.)

What is the renal

compensation for a
respiratory
acidosis:

If it develops Bicarbonate increases by about 1 for every 10 mm Hg

acutely? rise in PaCO 2 .

If it is a chronic Bicarbonate increases by about 4 for each 10 mm Hg rise

problem? in PaCO 2 .

Should bicarbonate Perhaps beneficial in severely acidemic patient. Use with

be given to extreme caution.
patients with a
respiratory
acidosis?

What are the Associated with hypoxemia (pulmonary diseases, HF,

common causes of anemia)
a respiratory Stimulation of medullary respiratory center (sepsis, liver
alkalosis? disease, salicylates, CNS diseases)
Mechanical ventilation

What is the renal

compensation for a
respiratory
alkalosis:

If it develops Bicarbonate decreases by about 1 for every 10 mm Hg

acutely? rise in PaCO 2 .

If it is a chronic Bicarbonate decreases by about 4 for each 10 mm Hg rise

condition? in PaCO 2 .

What are the most Mixed respiratory acidosis and metabolic alkalosis (COPD
common mixed and diuretic therapy)
acidbase Mixed metabolic acidosis and metabolic alkalosis
disorders? (ketoacidosis and vomiting)
Mixed respiratory alkalosis and metabolic acidosis
(salicylate intoxication)
 What is the ! anion #AG = measured AG normal AG
gap?

How is it used? Used to determine if a mixed acidbase disturbance is

present
Most useful to distinguish concomitant metabolic
alkalosis and AG metabolic acidosis

What if the !AG is Then next look at the measured bicarbonate. Add the
+? #AG to the measured bicarbonate.

What if the !AG + There is no concomitant metabolic alkalosis.

measured
bicarbonate is in
the normal range
for bicarbonate?

What if the sum of There is a concomitant metabolic alkalosis.

the !AG +
measured
bicarbonate is
greater than the
normal range for
bicarbonate?

P.347
P.348
P.349

Water Balance Disorders

Hyponatremia
What are the factors This is due to the finely controlled excretion or
that control the serum retention of water by the kidneys and control of
sodium concentration? thirst. Thus, disorders of sodium concentration are
disorders of water balance.

What are the factors 1. GFR

that control renal 2. Delivery of filtrate to the diluting segments of
water excretion? the kidney
3. A hypertonic medullary interstitium
4. AVP
What are the Usually related to the CNS: lethargy, obtundation,
symptoms of acute confusion, seizures, coma, nausea, vomiting
hyponatremia?

What is the They are due to cerebral edema.

pathogenesis of the
symptoms of acute
hyponatremia?

What is Normal plasmal osmolality with an artificially low

pseudohyponatremia? measured serum sodium

When does In states of hyperproteinemia or hyperlipidemia when

pseudohyponatremia there is an increase in the mass of the nonaqueous
occur? components of serum and when sodium is measured
using flame photometry

What are some Urea, ethanol, ethylene glycol, isopropyl alcohol,

substances that can methanol. These substances are lipophilic and
increase osmolality partition in all body compartments.
without changing the
serum sodium
(ineffective osmoles)?

What is cerebral salt In patients with acute CNS injury (such as

wasting syndrome subarachnoid bleeds), there is excessive renal loss of
(CSW)? sodium (mechanisms unknown), leading to volume
depletion and thus a secondary baroreceptor
mediated stimulation of AVP secretion.

How can CSW be Patients with SIADH are euvolemic while patients
differentiated from with CSW are hypovolemic.
SIADH?

How is CSW treated? Vigorous repletion of salt and volume

How do thiazide They lead to mild volume depletion with secondary

diuretics cause AVP secretion; they also cause potassium depletion,
hyponatremia? which leads to intracellular movement of sodium.
Furthering this is the possibility that thiazides may
also increase thirst.

What is the correct Initial rapid correction of serum sodium at a rate of

therapy of acute 1.5 to 2 meq/L/hr until the patient is asymptomatic.
symptomatic Often requires the use of hypertonic (3%) saline. The
hyponatremia? serum sodium should not be increased more than 8
to 10 meq/L in the first 24 hours.

How can you estimate Change in serum sodium (per L infused) = [Infusate
the change in serum (Na + ) Serum (Na + )]/[Total body water + 1 (liter
sodium with the infused)]
infusion of an IV fluid?

How does potassium Since potassium and sodium can exchange across cell
influence the membranes, infusion of potassium can lead to an
correction of increase in serum sodium; thus, if potassium is given,
hyponatremia? it should be included in the above equation.

What are the Given that there is time for adaptation of the brain,
symptoms of chronic cerebral edema is minimized and most patients are
hyponatremia? minimally impaired with slight confusion, gait
difficulties, or no discernible symptoms.

What is the definition Inappropriately elevated urine osmolality in the

of the syndrome of setting of a low serum osmolality. Urine osm >100
inappropriate ADH mOsm/L
(AVP) secretion Clinical euvolemia
(SIADH)? Decreased extracellular osmolality
Normal renal, pituitary, adrenal, cardiac, and
hepatic function

What is the most Selective serotonin receptor uptake inhibitors (SSRIs)

common drug that
causes SIADH?

What other diseases HIV, carcinomas, pulmonary disorders, CNS disorders

are associated with
SIADH?

How is SIADH treated? 1. Removal of all possible causes

2. Water restriction
3. Diuretics to decrease urinary concentrating
ability
4. Demeclocycline
5. Vasopressin receptor antagonists

What are vasopressin Oral (tolvaptan) or IV (conivaptan) agents that

receptor antagonists? selectively antagonize the action of ADH at the
collecting duct and thus lead to an increase in free
 water excretion by the kidney

What is the proper If symptoms are acute, some immediate correction is

therapy for chronic needed, generally not more than a 10% correction in
hyponatremia? the first 24 hours.
Frequent measurement of urine and serum
electrolytes is mandatory. Do not exceed correction
rate of 1 to 1.5 meq/L/hr or more than 12 meq/day.

What is the potential Osmotic demyelination syndrome (ODS)

risk of correcting
chronic hyponatremia
too quickly?

What is the Patients often show initial improvement in mental

presentation of ODS? status with correction of hyponatremia with
subsequent development of motor abnormalities,
pseudobulbar palsy and mental status changes

How is ODS diagnosed? Hyperintense lesion on T2-weighted MRI

What is the Excessive water ingestion in the setting of high AVP

pathogenesis of levels and concomitant salt loss in sweat
exercise-associated
hyponatremia?

P.350
P.351

Hypernatremia
What are the The ability of the kidney to excrete a concentrated urine
mechanisms (retain water) and thirst
that defend
the body
against
hypernatremia?

What is the 1. Impaired thirst (elderly, altered level of consciousness,

pathogenesis of inadequate access to water)
hypernatremia? 2. Inability of the kidney to retain water (diabetes insipidus)
3. Rarely, sodium gains (hypertonic IV solutions)

What are the Usually of a neurologic nature due to cellular dehydration:

signs/symptoms lethargy, hyperreflexia, coma, seizures
of
hypernatremia?

What is the In adults above age 60, the mortality may be as high as 40%
mortality and often reflects the severity of the underlying
associated with comorbidities.
acute
hypernatremia?

What is the The primary goal is restoration of serum tonicity. The

therapy for specific approach depends upon the patient's extracellular
hypernatremia? volume status. First correct any significant hypovolemia with
the best volume expander such as normal (0.9%) saline, then
correct the water deficit.

How do you Water deficit (L) = 0.6 ! body wt(kg) ! [(plasma Na+ /140)
calculate the 1]
water deficit?

What is the There is no need to rapidly correct a serum [Na] below 150
proper rate of meq/L. Generally, in patients with acute hypernatremia,
correction? correction of 1 meq/L/hr can be safely achieved. In patients
with chronic hypernatremia, the rate should be considerably
slower (0.5 meq/L/hr or less).

What is the risk Cerebral edema

for rapid
correction of
hypernatremia?

What are the Central and nephrogenic

forms of
diabetes
insipidus?

What are the Brain tumors, histiocytosis, trauma, cerebral hemorrhage or

causes of infarct, infectious, idiopathic, and metastatic tumors
central
diabetes
insipidus?

How is central Desmopressina synthetic, long-acting vasopressin analog

diabetes with minimal vasopressor activity. It can be given
insipidus intranasally, subcutaneous or IV.
treated?
 What are the 1. X-linked mutations in the vasopressin receptor in the
causes of collecting duct
nephrogenic 2. Autosomal dominant and recessive mutations in the
diabetes aquaporin 2 (water channel) gene
insipidus (NDI)? 3. Acquired causes

What are the Chronic kidney disease, drugs (lithium, colchicine, glyburide,
common causes amphotericin, foscarnet), sickle cell disease, amyloidosis,
of acquired Sjgren's syndrome, sarcoidosis. All associated with
NDI? impairment in the functioning of the distal tubule and
insensitivity to AVP. Also consider hypokalemia and
hypercalcemia.

How is NDI Low-sodium diet, hydrochlorothiazide and/or amiloride,

treated? indomethacin (only for short periods of time)

How do these They lead to contraction of the extracellular volume and

agents work? increase proximal tubular fluid reabsorption. This decreases
the amount of water that is presented to the distal tubule.

P.352

Electrolyte Disorders

Potassium
What are the 1. Acid-base status: acidosis leads to shift of potassium out
major factors of cells, alkalosis shifts potassium into cells.
involved in 2. Insulin: shifts potassium intracellularly.
potassium 3. Tonicity: high osmolality shifts potassium out of cells.
balance? 4. Beta-2 adrenergic receptor: catecholamines shift
potassium intracellularly.
5. Renal excretion (see below).
6. Dietary potassium intake.
7. Small losses in stool.

What are the The distal tubule is the major site of potassium excretion and
factors regulation, mediated by sodium reabsorption through specific
involved in sodium channel in exchange for potassium excretion into
renal tubular lumen. Factors controlling this process are:
excretion of
1. Angiotensin II: increase K+ excretion
potassium?
2. Aldosterone: increase K+ excretion
3. Distal delivery of sodium and filtrate: more sodium and
 filtrate delivered to distal tubule, more K+ that can be
excreted

P.353
P.354
P.355

Hypokalemia
What are the common Alkalemia
causes of hypokalemia Insulin excess
with normal total body Stress states (acute MI, asthma attacks, etc.)
potassium (transcellular Hypokalemic periodic paralysis
shift)? Thyrotoxicosis
Refeeding syndromes

What are the common Decreased intake of K+ or increased K+ losses

causes of hypokalemia (renal or GI)
with decreased total
body potassium?

What diagnostic tests are Determination of urine potassium excretion: either

useful in determining spot urine concentration, transtubular potassium
the cause of gradient, or 24-hour potassium excretion
hypokalemia?

In the setting of Extrarenal K+ losses are more likely, usually from

hypokalemia, what does the GI tract
+
a low urine K (<20
meq/day) signify?

In the setting of Signifies that K+ losses are derived from the

hypokalemia, what does kidney. The next step is to look at the acidbase
+
a high urine K (>20 status and whether the patient is hypertensive to
meq/day) signify? determine the specific etiology.

What are the most Most commonly due to diuretics or vomiting. Can
common causes of be easily determined by measuring the urine
hypokalemia occurring in chloride, which should be <10 meq/L. However, if
combination with a the patient is hypertensive, see below.
metabolic alkalosis?

In a patient with Can be determined by measuring the renin and

hypertension, aldosterone levels. Generally, these patients have
hypokalemia and either an excess of aldosterone or an aldosterone-
metabolic alkalosis, how like substance that leads to sodium retention and
do you determine the K+ wasting.
potential etiologies?

What if it is a high- RAS, malignant hypertension

renin/high-aldosterone
state?

What if it is a low- Primary aldosteronism, glucocorticoid remediable

renin/high-aldosterone aldosteronism
state?

And the low- Liddle's syndrome, Cushing's syndrome, certain

renin/low-aldosterone forms of congenital adrenal hyperplasia, apparent
condition? mineralocorticoid excess syndrome

What is A rare disease where there is a translocation of

glucocorticoidremediable the promoter (regulatory) elements of the
aldosteronism (GRA)? glucocorticoid gene to the aldosterone synthase
gene. Thus aldosterone production is now under
the control of ACTH and can be shut down with
dexamethasone therapy.

What is Liddle's A rare mutation that leads to overactivity of the

syndrome? distal sodium channel, leading to inappropriate
sodium retention and K+ -wasting

What is the syndrome of Normally, the aldosterone receptor can be

apparent activated by cortisol, but this does not occur owing
mineralocorticoid to the presence of 11-$-OH steroid dehydrogenase,
excess? which converts cortisol to the inactive cortisone. In
this syndrome, the inactivating enzyme is
nonfunctional while the aldosterone receptor
responds to both cortisol and aldosterone and is
overactive.

What are the causes of Bartter's syndrome: a group of mutations affecting

hypokalemia, metabolic the ascending limb of the loop of Henle and
alkalosis, and an leading to impaired Na+ /K + /Cl - reabsorption.
elevated urine chloride Similar to the effects of a loop diuretic.
with a normal BP? Gitelman's syndrome: a mutation in the distal
tubule Na+ /Cl - cotransporter that impairs Na+ and
Cl- reabsorption. Effects similar to a thiazide
diuretic.
What are the causes of RTA type I and II (see acidbase section)
hypokalemia associated
with metabolic acidosis?

What are some causes of Magnesium deficiency

hypokalemia associated Anionic drugs, which are delivered to the distal
with a variable pH? tubule and obligate K+ losses (such as penicillins)

What is hypokalemic Can occur as either autosomal dominant or

periodic paralysis? associated with thyrotoxicosis.
Rapid intracellular shift of K+ into cells leading to
muscle weakness.

Besides potassium Treatment with beta blockers

correction, what can
help minimize symptoms
in periodic paralysis?

What are the clinical Cardiac arrhythmias, digitalis intoxication

manifestations of Ileus
hypokalemia? Skeletal muscle weakness, rhabdomyolysis
Glucose intolerance
AVP resistance (polyuria)
Increased renal ammonia production and metabolic
alkalosis
Renal cysts
Chronic renal interstitial fibrosis

What is the therapy for If possible, correct the initiating problem.

hypokalemia? K+ deficit can only be approximated.
In general, a reduction in K+ from 4.0 to 3.0 meq/L
requires loss of 200 to 400 meq K+ .
KCl should be the preferred form of replacement
except in the presence of an RTA (K + -citrate).

What is the maximum 10 to 20 meq/hr

+
rate of K IV infusion?

What are the K +-sparing Amiloride, triamterene, and spironolactone

diuretics?

When should they be Useful to block K+ excretion in states of

used?
 used? aldosterone excess (diuretic therapy, primary
hyperaldosteronism)

P.356
P.357

Hyperkalemia
What are the causes Exercise, especially in the presence of beta blockers
of hyperkalemia due Metabolic acidosis
to transcellular Insulin deficiency
shifts? Tissue breakdown or ischemia (rhabdomyolysis, tumor
lysis)
Succinylcholine

What are causes of Thrombocytosis

spurious Leukocytosis
hyperkalemia? Prolonged tourniquet application (ischemia)

What are the causes Low GFR (<20 mL/min)

of hyperkalemia due Decreased distal sodium delivery (volume depletion)
to impaired renal K + Hypoaldosteronism
excretion? Type I RTA, hyperkalemic form
Drugs that impair K+ secretion (ACEI, ARB, K+ -sparing
diuretics)

What are some Hyporeninemic hypoaldosteronism (type IV RTA,

common causes of common in diabetics)
hypoaldosteronism? NSAIDs
ACEIs, ARBs
AIDS
Adrenal insufficiency
Congenital adrenal hyperplasia (21-OHase deficiency)
Heparin
Cyclosporine

What are the Muscle weakness

common clinical Cardiac arrhythmias (especially alterations in T-wave
manifestations of configuration)
hyperkalemia? Metabolic acidosis (reduced renal ammonia production)

What is an indirect Transtubular potassium gradient (TK + KG):

method of
[K + /(Uosm/Posm)]/Pk
determining the
This equation reflects the gradient of K+ between the
level of aldosterone
distal tubular lumen and the plasma. In the setting of
action on the distal
 action on the distal
tubule? hyperkalemia with adequate mineralocorticoid activity,
the value should be high (>7). If low (generally <4), it
reflects hypoaldosteronism of some sort.

What should be the Emergent ECG. If there are any T-wave changes, IV
first step in deciding calcium should be given immediately. The effect begins
the appropriate within a minute and is short-lived.
therapy for
hyperkalemia?

What other IV insulin and glucose: shifts K+ into cells

therapies are
Sodium bicarbonate: shifts K+ into cells (less effective
available for the
in patients with advanced CKD)
treatment of
Beta-2 adrenergic agonists: shifts K+ into cells
hyperkalemia?
Diuretics: increase renal excretion (takes time and less
effective with advanced CKD)
Sodium polystyrene sulfonate (cation-exchange resin):
increases GI excretion of K+
Dialysis: achieves the greatest reduction in K+ the
fastest

What medication Fludrocortisone, a synthetic mineralocorticoid, can

can be utilized to restore K+ balance, but often at the expenses of Na+
treat patients with retention and volume overload
hyporeninemic
hypoaldosteronism
(type IV RTA)?

What are potential Low-potassium diet

treatments for Removal of drugs that inhibit K+ secretion
chronic Loop or thiazide diuretics
hyperkalemia? Low-dose sodium polystyrene sulfonate
Oral bicarbonate

P.358

Regulation of Calcium and Phosphorus

What are the PTH and 1,25(OH) vitamin D acting on the effector organs:
major hormones bone, intestine, and kidney
involved in
calcium and
phosphorus
homeostasis?
 How is PTH PTH is released in response to lowering of ionized serum
secretion calcium (via Ca 2+ sensing receptor inactivation). 1,25(OH)
regulated? vitamin D inhibits PTH secretion. Hyperphosphatemia and
hypomagnesemia also stimulate PTH secretion.

What are the Increases calcium reabsorption from kidney

activities of PTH? Decreases phosphorus reabsorption from kidney
Increases bone resorption with release of calcium and
phosphorus
Indirectly increases intestinal absorption of calcium by
stimulating conversion of 25(OH) vitamin D to 1,25(OH)
vitamin D

How is vitamin D Sources of vitamin D are diet and skin via conversion by
metabolized? UV light to cholecalciferol, which is metabolized by the
liver to 25(OH) vitamin D. The active 1,25(OH) vitamin D
is formed through the action of a 1-alpha hydroxylase in
the kidney.

How is vitamin D 1-alpha hydroxylase (rate-limiting step) is increased by

synthesis low phosphorus, low calcium, and increased PTH. The
regulated? activity is decreased by 1,25(OH) vitamin D and by kidney
failure.

What is the Acts on intestine to increase calcium and phosphorus

activity of absorption
vitamin D? Acts on bone to increase mineralization
Inhibits PTH secretion

P.359
P.360

Calcium
In what ways is 1. 99% stored in bone; 0.9% intracellular, and 0.1%
calcium stored and extracellular
transported in the 2. Extracellular calcium: 50% free (ionized and
body? physiologically active), 10% bound to anions, and
40% bound to albumin

How do you correct [(Normal albumin concentration patient's albumin

total serum calcium concentration) ! 0.8] + patient's calcium concentration
for low albumin?

How is calcium 60% to 70% absorbed in proximal tubule; 20% to 30% in

handled by the thick ascending limb of Henle; 10% in distal tubule
kidney?

What stimulates 1. Volume depletion

calcium 2. PTH
reabsorption in the 3. PTH related peptide (PTHrp)
kidney? 4. Hypocalcemia

What are the signs Nausea, constipation, abdominal pain, decreased

and symptoms of mentation, lassitude, thirst, dehydration, reduced urine
hypercalcemia? output, nocturia, polyuria, volume depletion

What are the causes 1. Primary hyperparathyroidism (55%)

of hypercalcemia? 2. Malignancy (35%)
a. Humoral due to PTHrp (lung, esophagus, head
and neck, renal cell, ovary, bladder)
b. Local osteolytic: breast, multiple myeloma
3. Hematologic malignancy (lymphoma) with ectopic
1,25(OH) vitamin D (also seen in granulomatous
diseases)
4. Misc (10%): drugs (thiazides, lithium, vitamin D);
immobilization, pheochromocytoma, thyrotoxicosis,
milk-alkali syndrome

What initial Calcium, phosphorus, PTH, PTHrp, 25(OH) and 1,25(OH)

diagnostic tests vitamin D, SPEP, UPEP
should be obtained
in a patient with
hypercalcemia?

What is the acute 1. Volume repletion with IV saline.

treatment for 2. Once volume is repleted, loop diuretics can be
hypercalcemia? added (must avoid volume depletion to be
effective).
3. Bisphosphonates or calcitonin.
4. Corticosteroids if associated with granulomatous
disorder.
5. Cinacalcet (calcimimetic) for hyperparathyroidism
(binds to calcium receptor to activate it and
decreases PTH secretion).

What are the signs Carpal pedal spasm, perioral numbness, tetany,
and symptoms of dyspnea, stridor, wheezing, seizures, bone pain, muscle
hypocalcemia? weakness, cataracts (chronic), bone deformities
 (rickets)

What is Chvostek's Elicited by tapping on the face just anterior to the ear
sign? and just below zygomatic bone. A positive response is
twitching of the ipsilateral facial muscles due to
neuromuscular irritability.

What is Trousseau's Elicited by inflating BP cuff over systolic pressure for

sign? several minutes. A positive response is flexion of the
wrist and metacarpophalangeal joints, hyperextension
of the fingers, and flexion of the thumb.

What is the 1. Low albumin

differential diagnosis 2. Hypoparathyroidism (surgical, postradiation,
of hypocalcemia? congenital, or autoimmune)
3. Vitamin D deficiency (renal failure, poor nutrition,
malabsorption)
4. Pancreatitis
5. Pseudohypoparathyroidism
6. Hypomagnesemia
7. Increased phosphorus (binds calcium):
rhabdomyolysis, tumor lysis, renal failure
8. Hungry bone syndrome (postparathyroidectomy)

What diagnostic Calcium, albumin, ionized calcium, phosphorus, PTH,

tests should be 25(OH) vitamin D and 1,25(OH) vitamin D
ordered for the
evaluation of
hypocalcemia?

What is the 1. Severe: parenteral calcium (calcium chloride or

treatment of gluconate)
hypocalcemia? 2. Chronic: oral calcium supplement and vitamin D
3. If magnesium is depleted, it must be replaced as
well.

P.361
P.362

Phosphorus
How is phosphorus 1. 85% in bone, 14% intracellular, 1% extracellular
stored and 2. Extracellular phosphorus is bound to albumin and
transported in the cations, but lab measures only physiologically active
body? form (unlike calcium)
How is phosphorus 85% reabsorbed in the proximal tubule through a Na/P
handled by the cotransporter, remainder taken up in distal segments.
kidney? Uptake is stimulated by volume contraction,
hypophosphatemia. Excretion stimulated by PTH, PTHrp
and diuretics.

What are the signs Muscle weakness, hypoventilation, confusion, seizures,

and symptoms of osteomalacia
hypophosphatemia?

What are the causes Antacids, malabsorption, chronic diarrhea, vitamin D

of deficiency, starvation, anorexia, alcoholism
hypophosphatemia
due to decreased
intestinal
absorption?

What are the causes Primary hyperparathyroidism, postrenal transplant,

of volume expansion, glucosuria, resolving ATN, Fanconi's
hypophosphatemia syndrome, X-linked and vitamin Ddependent rickets,
due to increased oncogenic osteomalacia
urinary loss?

What are the causes Respiratory alkalosis, alcohol withdrawal, burns, TPN,
of refeeding syndrome, leukemic blast crisis
hypophosphatemia
due to transcellular
shifts?

How is Phosphate comes in either Na- or K-salts: choice

hypophosphatemia dictated by other illnesses and electrolyte levels. Oral
treated? repletion can also be accomplished with milk. Treat
underlying condition.

What are the signs Usually asymptomatic unless hypocalcemia occurs due
and symptoms of to precipitation of insoluble CaPO 4 complexes. Chronic
hyperphosphatemia? hyperphosphatemia in CKD is associated with vascular
calcification and increased mortality.

What are the causes Occurs almost exclusively with decreased GFR. Other
of rare causes include hypoparathyroidism, acromegaly,
hyperphosphatemia? thyrotoxicosis, tumor lysis, rhabdomyolysis, vitamin D
overdose, phosphate-containing enemas.
What is the acute Dialysis is the most effective, also volume repletion.
therapy of
hyperphosphatemia?

What is the chronic Dietary restriction and use of phosphate binders

therapy of (calcium acetate, calcium carbonate, sevelamer) with
hyperphosphatemia? meals

P.363

Magnesium
How is magnesium 66% in bone, 33% intracellular and 1% extracellular. Serum
stored and levels are not reflective of body stores. Extracellular
transported in the magnesium can be measured as total magnesium, of
body? which 55% is ionized and physiologically active, 15% bound
to anions, and 30% bound to albumin.

How is magnesium 40% reabsorbed in the proximal tubule, 50% in ascending

handled by the limb of Henle, 5% reabsorbed actively in distal tubule.
kidney? Renal tubule reabsorption increased by volume
contraction, hypomagnesemia and PTH.

What are the signs Lethargy, nausea, confusion, hypoventilation,

and symptoms of hypotension, arrhythmias, muscle weakness, decreased
hypermagnesemia? deep tendon reflexes

What are the Most often occurs with depressed GFR

causes of 1. Increased intake: antacids, laxatives, enemas,
hypermagnesemia?
treatment of preeclampsia with Mg ++ salts
2. Decrease renal function
3. Cellular shifts: pheochromocytoma, acidosis

What is the If symptomatic, IV calcium salts reverse neuromuscular

treatment for and cardiac effects. Hemodialysis is the most effective
hypermagnesemia? way to remove excess Mg ++ , especially if GFR decreased.

What are the signs Tremors, myoclonic jerks, positive Chvostek and
and symptoms of Trousseau signs, tetany, generalized muscle weakness
hypomagnesemia? (particularly respiratory muscles), vertigo, nystagmus,
coma. There is an increased incidence of ventricular
arrhythmias, PVCs, ventricular tachycardia, torsades de
pointes, ventricular fibrillation. Also increased
susceptibility to digitalis-related arrhythmias.
 What are the 1. Reduced intake: starvation, alcoholism, prolonged
causes of postoperative state
hypomagnesemia? 2. Redistribution from extracellular to intracellular
fluids: insulin, hungry-bone syndrome,
postparathyroidectomy, catecholamine excess, alcohol
withdrawal, acute pancreatitis
3. Reduced GI absorption: malabsorption syndromes,
postbowel resection, chronic diarrhea, laxative abuse

What diagnostic Two available tests to determine total body Mg

tests are useful deficiency:
for
1. Retention of >75% of Mg ++ after IV Mg ++ loading
hypomagnesemia?
2. Low urine fractional excretion of Mg + is indicative of
deficiency

Very low (<1 mg/dL) levels of Mg ++ in the serum always

reflect significant deficiency, as do neuromuscular
symptoms.

What is the 1. Symptomatic or severe: IV magnesium sulfate slowly

therapy for infused
hypomagnesemia? 2. Asymptomatic: oral repletion with magnesium salts:
may be limited by diarrhea

P.364

Acute Kidney Injury

What is the incidence of Approximately 5% of all patients.
acute kidney injury (AKI) Approximately 15% to 20% of intensive care
in the hospital setting? patients. The majority of AKI occurs in the
hospital setting.

What is the mortality risk Substantial; in one large study, the mortality rate
associated with AKI? of patients who had a rise in SCr >0.5 mg/dL
while hospitalized increased by 6.5-fold.

What are the major Prerenal azotemia and acute tubular necrosis
causes of acute kidney
injury in the hospital
setting

What are the renal Prerenal azotemia: hypoperfusion

anatomic sites that can Renal artery and vein
be involved in AKI? Small renal vessels
 Glomerular disease
Acute tubular necrosis
Acute interstitial nephritis
Intratubular obstruction
Postrenal obstruction

What are the etiologies of Intravascular volume depletion

prerenal acute kidney Distributive shock (early sepsis, third-spacing)
injury? Low cardiac output
Renal artery hypoperfusion: NSAIDs, contrast-
induced, cyclosporine/tacrolimus, ACEIs/ARBs

What diseases cause Renovascular (renal artery or vein thrombosis,

acute intrinsic kidney atheroembolic disease, large vessel vasculitis)
injury? Diseases of small vessels and glomeruli
(glomerulonephritis, TTP/HUS, malignant
hypertension)
Tubulointerstitial diseases (acute tubular necrosis
(ischemic or toxic), acute interstitial nephritis,
acute bilateral pyelonephritis)

What are etiologies of Ureteral obstruction: must be bilateral or

postrenal acute kidney unilateral in a patient with single kidney
injury? Neurogenic bladder
Cervical/uterine/ovarian cancer
Prostate disease

P.365

Acute Tubular Necrosis

What two types of Ischemic
injury can lead to Nephrotoxic
acute tubular necrosis
(ATN)?

What are high-risk Sepsis, pancreatitis, burns, postcardiac surgery,

clinical settings for patients with baseline CKD
ATN?

What are the Restoration of kidney perfusion.

nonelectrolyte Removal of nephrotoxic agents.
management strategies Treat volume overload with IV diuretics,
for the treatment of ultrafiltration if refractory.
ATN? Protein restriction to 0.8 to 1.0g/kg/day,
carbohydrate 3 to 5 g/kg/day.
 GI ulcer prophylaxis with histamine antagonist or
proton-pump inhibitor.
There are no specific treatments for ATN (controlled
trials do not support IV diuretics, dopamine,
endothelin-1, atrial naturetic peptide, insulin-like
growth factor, mannitol).

What are the Restriction of potassium to <40mmol/day, dialysis if

electrolyte related K+ >6.5 or 5.5 to 6.5 with ECG changes.
management strategies Phosphate restriction to <800 mg/day, phosphate
for the treatment of binding agents for phosphorus >5.
ATN? Dialysis if phosphorus (mg) ! calcium (mg) >70.
Sodium bicarbonate to maintain serum levels
between 15 and 20 mmol/L and pH>7.2
Hypocalcemia treatment with calcium gluconate

What is the typical time Highly variable and dependent upon the other
course for the comorbidities. If a single insult in a relatively
resolution of ATN? healthy patient, should resolve within days to a
week.

P.366
P.367

Acute Interstitial Nephritis

What are the Drugs
etiologies of AIN? Infections
Systemic disease
Idiopathic

What are the Antimicrobial (penicillin G, ampicillin, methicillin,

common classes ciprofloxacin, rifampin, and sulfonamides, including
of drugs that cotrimoxazole)
cause acute NSAIDs (aspirin, ibuprofen, fenoprofen, naproxen,
interstitial indomethacin)
nephritis (AIN)? Anticonvulsants (phenytoin)
Diuretics (furosemide)
Antiulcer (omeprazole, cimetidine)
Allopurinol

How does drug- In 80% of patients, onset of symptoms is 3 weeks but

induced AIN range is from 1 day to 2 months.
present? Clinical findings of flank pain (distension of renal capsule),
oliguria, hematuria, pyuria, WBC casts, mild proteinuria,
fever, rash, eosinophilia may be present.
 What is the 1.5 months
average recovery
of renal function
from drug-
induced AIN?

What is the best Renal biopsy. The presence of urine eosinophils is

way to diagnose suggestive, but the finding is very insensitive.
drug-induced
AIN?

What biopsy Interstitial inflammatory infiltrates (T cells, macrophages,

findings are plasma cells, eosinophils)
consistent with Interstitial edema
drug-induced Tubulitis
AIN? No vascular or glomerular lesions

Are steroids Perhaps. There are no controlled trials but many case
effective in reports demonstrating the benefit in select cases. Should
treating drug- be considered in cases that do not have spontaneous
induced AIN? improvement in creatinine after 3 to 7 days of
withdrawing the offending agent.

What microbes Bacteria: Staphylococcus, Streptococcus, Escerichia coli,

are associated Campylobacter jejuni, Chlamydia, Mycoplasma,
with AIN? Leptospira, Legionella, Mycobacterium tuberculosis,
Salmonella, Yersinia
Viruses: CMV, EBV, hepatitis B virus HSV, HIV, rickettsia
Parasites: Toxoplasma

What systemic Systemic lupus erythematosus (SLE)

diseases are Sjgren's syndrome
associated with Sarcoidosis
AIN?

P.368

Pigment-Induced Acute Kidney Injury

In what two Rhabdomyolysis and hemolysis
clinical settings
does heme
pigment
nephropathy
occur?
 How does 1. Fluid sequestration into injured muscle leading to
rhabdomyolysis profound volume depletion
lead to acute 2. Cytokine and toxins leading to renal vasoconstriction
kidney injury? and tubular injury
3. Myoglobin, freely filtered at the glomerulus, causing
tubular cast obstruction and direct tubular injury

What are the CK usually >10,000 U/mL

clinical features Red-brown discoloration of the urine
of Urine analysis with positive heme but negative RBCs on
rhabdomyolysis- microscopy
induced acute Low fractional excretion of sodium
kidney injury?

What are the Muscle injury: burns, trauma, electric shock, seizures,
etiologies of heat exhaustion
rhabdomyolysis? Drugs: statins, fibrates, neuroleptic malignant syndrome
Toxins: alcohol, cocaine, ecstasy, amphetamines
Familial: McArdle's disease, malignant hyperthermia

What are the Incompatible blood transfusion, autoimmune hemolytic

etiologies of anemia, paroxysmal nocturnal hemoglobinuria, glucose 6-
hemoglobinuria? phosphate dehydrogenase deficiency

What are the Aggressive fluid repletion: 1 to 2 L/hr IV normal saline

management with goal urine output 300 mL/hr.
strategies to [Less clear role for alkalinization of urine to prevent cast
prevent heme formation with % normal saline + 75 meq HCO 3 titrated
pigment
to urine pH >6.5. There is no definitive evidence that the
nephropathy?
alkaline diuresis is more effective than saline diuresis.]
Monitor serum iCa++ and serum bicarbonate closely while
using bicarbonate.
Consider loop diuretic or mannitol to increase urine
output if not at goal.
If acute kidney injury developed, discontinue mannitol and
bicarbonate.

P.369

Contrast Nephropathy
What are the risk factors for Renal impairment
developing radiocontrast Rarely seen in patient with normal renal
induced nephropathy (RCIN)? function
 Creatinine >2.0 mg/dL
Diabetes
Heart failure
Volume depletion, NSAIDs, ACEIs/ARBs

What is the clinical course for Elevation of creatinine 24 to 48 hours

RCIN? postexposure, peak creatinine 4 to 5 days,
return to baseline 7 to 10 days
If no full recovery, likely concomitant
kidney insult (sepsis, hypotension,
atheroemboli)

What are the mechanisms for Direct tubular toxicity:

RCIN? Reactive oxygen species causing proximal
tubular injury
Kidney vascular hemodynamic changes:
Renal vasoconstriction by renin-
angiotensin system (RAAS), endothelin,
adenosine
Osmotic diuresis, thereby increasing NaCl
delivery to macula densa and consequent
activation of RAAS

How can one minimize the risk Alternative choice of imaging in high-risk
for RCIN? patients
Use of low osmolar or iso-osmolar contrast
Hydration with NS 1 mL/kg/hr 12 hours
before and after contrast exposure
Avoidance of loop diuretics, NSAIDsS, ACEIs
prior to contrast
Some studies support N-acetylcysteine 600
q12h ! 48 hours prior to procedure
Some studies support bicarbonate or
vitamin C prior to procedure
Combination of N-acetylcysteine and
bicarbonate with IV fluids may be the best
preventive strategy

P.370

Atheroembolic Acute Kidney Injury

When does Usually after arterial manipulation:
atheroembolic kidney vascular surgery, angioplasty and stenting,
disease typically arteriography.
occur? It can also occur without manipulation: either
 spontaneously or after administration of
anticoagulants or thrombolytics.

How does acute Nonoliguric or oliguric ATN with a high FeNa (intrinsic
atheroembolic kidney kidney injury): usually with systemic signs of
disease clinically embolization elsewhere (CNS, confusion; skin, livedo
present? reticularis; feet, ischemic digits)

What is the subacute Slow progressive kidney disease with mild proteinuria,
clinical presentation hematuria, possible eosinophiluria, labile
of atheroembolic hypertension. Low-grade fevers may be present.
kidney disease?

What laboratory Elevated sedimentation rate, low C3, low C4, elevated
abnormalities may liver and muscle enzymes, anemia, eosinophilia,
support a diagnosis of leukocytosis
atheroembolic
disease?

What is the Cholesterol clefts with giant-cell reaction on light

characteristic kidney microscopy
biopsy finding of
atheroembolic
disease?

What is the therapy Generally supportive care. In the setting of AKI, some
for atheroembolic small case series suggest a role for steroids.
disease?

P.371

Hepatorenal Syndrome
In what patients can Acute liver disease (severe alcoholic hepatitis)
hepatorenal Chronic liver disease (cirrhosis of any etiology)
syndrome (HRS) Advanced hepatic failure
occur? Portal hypertension

What are the two Type I: Doubling of serum creatinine to >2.5 mg/dL or
clinical presentations 50% reduction in creatinine clearance in 2 weeks.
of HRS? Severely jaundiced and coagulopathic
Type II: Slow progressive deterioration in renal
function. Less jaundiced and with refractory ascites.

What clinical findings Serum creatinine >1.5 mg/dL, absence of shock and GI
support HRS? fluid losses, persistence of AKI after withdrawal of
 diuretics and fluid challenge (1.5 L isotonic saline or
100 g albumin in 500 mL saline); oliguria <500 mL,
urine sodium <10 mmol/L, urine osmolarity > plasma
osmolarity, urine red blood cells <50/hpf, and urinary
protein <500mg/L, serum sodium concentration <130
mmol/L, no evidence of obstruction by ultrasound

What is the 1-year: 20%

probability of 5-year: 40%
cirrhotic patients
developing HRS?

What is the prognosis Between 80% and 95%

of HRS?

What is the only Orthotopic liver transplantation

established
treatment for HRS?

What Vasopressin analogs: theoretical reversal of splanchnic

pharmacotherapeutic vasodilation
agents are used in Ornipressin 2 IU/hr !15 days + albumin 1 g/kg first
the treatment of day and then 20 to 40 g daily
HRS? Terlipressin + albumin
Splanchnic vasoconstrictors:
Octreotide
Vasoconstrictors: increase mean arterial pressure
Midodrine
Volume expanders:
Albumin

What interventional Paracentesis of 2 L to reduce intra-abdominal pressure

procedures can be TIPS to reduce portal hypertension
considered for MARS (molecular adsorbent recirculating system) to
management of HRS? remove toxic metabolites using an albumin-containing
dialysate and charcoal and anion-exchanger columns
Renal replacement therapy

P.372

Acute Kidney Injury in the Setting of Cancer

What are common Prerenal: dehydration, hypercalcemia
etiologies of acute kidney Vascular: renal vein thrombosis from
injury in patients with hypercoagulable state, disseminated intravascular
cancer? coagulation (acute promyelocytic leukemia),
 thrombotic microangiopathy
Acute tubular necrosis: sepsis, hypercalcemia,
drugs (cisplatin, iphosphamide)
Acute interstitial nephritis: antibiotics, interferon-
alpha, IL-2
Malignant infiltration: acute lymphoblastic
leukemia, lymphoma
Intraluminal obstruction: tumor lysis syndrome,
myeloma cast nephropathy
Postrenal obstruction: ureteral compression from
tumor or retroperitoneal fibrosis, bladder cancer

Which patients should be Patients with leukemias and lymphomas

suspected of having Oligoanuric kidney injury
tumor lysis syndrome? Elevated lactate dehydrogenase levels
Elevated potassium, phosphate, uric acid

What therapies can High dose allopurinol 600 to 900 mg/day prior to
prevent tumor lysis chemotherapy
syndrome? Intravenous fluid loading to have urine output
>100 mL/hr
Early continuous dialysis for hyperuricemia and
hyperphosphatemia
Urine alkalinization for a pH >7.0 is not
recommended because of increased risk of
calcium-phosphate precipitation

What are the etiologies of Acute kidney injury:

acute reversible kidney Hypercalcemia
injury in patients with Dehydration
myeloma? Contrast nephropathy
Cast nephropathy
Infiltration of plasma cells

What is the clinical Slow development of nonoliguric acute kidney

presentation of direct injury with benign sediment and enlarged kidneys
kidney infiltration by on ultrasound
lymphoma or leukemia?

P.373
P.374

Obstructive Nephropathy
What are the Drugs such as acyclovir, methotrexate, sulfonamides,
common causes of indinavir, trimethoprim, which can crystallize in the
intraluminal tubules
(tubular) Uric acid in tumor lysis
obstruction? Extrarenal intraluminal obstruction can be caused by
stones, blood clots, or papillary necrosis

What medications Any anticholinergic medication and levodopa

are associated
with the
development of
urinary tract
obstruction due to
bladder
dysfunction?

What medical Diabetes mellitus, multiple sclerosis, Parkinson's disease,

conditions are and strokes can all lead to bladder dysfunction.
associated with
the development
of urinary tract
obstruction due to
bladder
dysfunction?

What infection Schistosoma haematobium can infect the bladder wall and
can lead to distal ureter, leading to obstruction.
urinary tract
obstruction?

What are the Women: gravid uterus, cervical cancer, ovarian cancer or
common causes of masses, pelvic inflammatory disease
extrinsic Males: prostatic hypertrophy or cancer
obstruction of the Both genders: retroperitoneal fibrosis, lymphadenopathy,
urinary tract? diverticulosis, Crohn's disease, aortic aneurysms

What is the Pain

typical clinical Decreased urinary output or change in character of
presentation of urinary stream
obstructive If bladder outlet obstruction: painful, distended bladder
nephropathy? Urinary tract infections
Uremic symptoms

What are the GFR: falls quickly and then resolves as obstruction is
changes in GFR relieved. The extent of GFR recovery is dependent on the
and tubular duration of obstruction.
function that Tubular function: impaired ability of kidney to
 occur with concentrate urine (polyuria), development of distal RTA.
obstructive
nephropathy?

What is the test Ultrasonography is the quickest and safest method for
of choice for diagnosisdemonstrates hydronephrosis. Other tests such
diagnosing as CT, MRI, or retrograde pyelography may be useful for
obstructive localization of the site of obstruction.
nephropathy?

What is the Depends upon the cause and site of obstruction. Insertion
treatment of of nephrostomy tubes is generally the appropriate
choice for emergency treatment for upper urinary tract obstruction.
obstructive
nephropathy?

What is a Polyuria is common after the relief of obstruction. This is

postobstructive due to salt and water retention during AKI, tubular
diuresis? damage to the kidney preventing urinary concentration,
and the buildup of osmotic particles such as urea, which
can act like a diuretic. Aggressive attention to volume
status and IV hydration is required to avoid volume
depletion.

P.375

Glomerular Disease
What are the Asymptomatic proteinuria (150 mg to 3 g/day), hematuria
clinical (>2 RBCs per high-power field or RBC casts),
presentations of hypoalbuminemia, edema, hypercholesterolemia,
glomerular lipiduria, oliguria, hypertension, may have
disease? signs/symptoms of underlying multisystem disease

What glomerular Minimal change disease

diseases present Focal segmental glomerulosclerosis
as nephrotic Membranous nephropathy
syndrome? Membranoproliferative glomerulonephritis (MPGN)
Cryoglobulinemic MPGN
Amyloidosis
Diabetic nephropathy

What are the Volume depletion leading to prerenal failure or acute

mechanisms for tubular necrosis
acute renal failure Renal vein thrombosis (hypercoagulable state)
in patients with Transformation to crescentic type glomerulonephropathy
 nephrotic Acute allergic nephritis from diuretics
syndrome? Hemodynamic response to ACEI

What are the Nephrotic edema: dietary sodium restriction (60 to 80

therapies for mmol/24 hr), oral loop diuretics albumin for gradual
treating the fluid removal.
complications of Proteinuria: reduction of afferent arteriolar dilation with
nephrotic low-protein diet or dipyridamole. Or blocking efferent
syndrome? arteriolar vasoconstriction with ACEI or ARB.
Hypercoagulability: prophylactic anticoagulation is
controversial.
Hyperlipidemia: statin therapy for goal LDL 100 to 129
mg/dL.
Infections: some advocate prophylactic antibiotics,
especially for children.
HTN goal: 125/75; first line to consider is ACEI or ARB.

P.376
P.377

Minimal Change Disease and Focal Segmental

Glomerulosclerosis
What diseases are Malignancies: Hodgkin's, mycosis fungoides, CLL.
associated with the Drugs: NSAIDs, interferon-alpha, gold.
development of MCD? Allergy: insect stings, pollens.
Most cases are idiopathic.

What are the More common in children.

epidemiologic, clinical, More common in South Asians and Native Americans.
and pathologic features Hypertension at the time of diagnosis is less likely.
of MCD? Microscopic hematuria is rare.
Light microscopy and immunohistology: normal.
Electron microscopy: podocyte foot process
effacement.
Does not progress to renal failure.

What are the More common in adults.

epidemiologic, clinical, More common in African Americans.
and pathologic features Hypertension common at the time of diagnosis.
of primary FSGS? Microscopic hematuria more common.
Light microscopy: segmental glomerular scarring with
adhesions to Bowman's capsule.
Immunohistology: +IgM and C3 deposited in the
mesangium.
Electron microscopy: Foot process fusion.
 Progresses to renal failure in 50% of patients; degree
of proteinuria determines risk.

How is adult MCD First episode: steroids (prednisone for up to 6

treated? months).
For frequent relapses and steroid-dependent
patients, cyclophosphamide can be added.

What is the response Nearly 100% of children and 75% of adults achieve
rate of MCD to remission. Relapses are common (up to 30% to 40%).
therapy?

How is primary FSGS Steroids (prednisone for at least 6 months).

treated? Nonresponders or relapsers: cyclosporine.
Other potential treatments include
cyclophosphamide, tacrolimus, mycophenolate.

What is the response 40% of nephrotic patients achieve complete remission

rate of FSGS to and the responders have renal survival >95%.
therapy?

What factors are Viruses: HIV, hepatitis B, parvovirus

associated with Drugs: pamidronate, heroin
secondary FSGS? Malignancies: lymphomas
Reduced renal mass: solitary kidney, renal allograft,
vesicoureteral reflux

What are the Collapsing form

histological variants of Cellular variant
FSGS? Mesangial hypercellularity
FSGS with glomerular tip lesions

What is the prognosis Severe nephrotic syndrome on presentation, steroid

for the collapsing form resistance, rapid development of ESRD (median time
of FSGS? of 13 months compared with 65 months in other
forms of FSGS)

What factors are Idiopathic, heroin, HIV, pamidronate, parvovirus

associated with
collapsing FSGS?

HIV-Associated Nephropathy
What is HIV- It is HIV-associated FSGS-variant characterized by a syndrome of
associated massive proteinuria, microhematuria, and azotemia with rapid
nephropathy progression to ESRD. The collapsing form of FSGS is seen on
(HIVAN)? light microscopy.

When does Usually when CD4 cells <200 ! 10 6 /L. It can also occur during
HIVAN acute HIV infection.
occur?

How is No prospective controlled trial has been done. Retroviral

HIVAN therapy may be efficacious. High-dose ACEI/ARB therapy delays
treated? the progression of kidney disease. Improvement in renal function
correlates with reduction in plasma viral load.

P.378
P.379
P.380

Membranous Nephropathy
What is Glomerular disease as a consequence of IgG deposition
membranous on the capillary subepithelial surface. Glomerular
nephropathy? permeability is increased, causing nephrotic syndrome.
Over time, leads to tubular atrophy and renal failure.

What is the most Idiopathic; over 60% of cases have unknown etiology.
common cause of
membranous
nephropathy?

What conditions are Systemic diseases: diabetes mellitus, SLE, solid tumors
associated with Drugs: NSAIDs, penicillamine, gold
membranous Infections: hepatitis B and C
nephropathy? Carcinomas: breast, lung, colon, ovarian, prostate (may
be presenting symptom of a carcinoma)

What are the Insidious onset

clinical Women affected > men
manifestations of Bimodal distribution (ages 30 to 40) and (50 to 60)
membranous Weeks to months of nonnephrotic range proteinuria and
nephropathy? then nephrotic range
50% patients with microscopic hematuria
Unusual to have hypertension, red blood cell casts,
macroscopic hematuria

What studies should Assessment of kidney function: serum creatinine and

constitute the creatinine clearance
initial workup for Assessment of proteinuria: ratio of urine protein to
 membranous urine creatinine
nephropathy? Serum albumin, cholesterol, urinalysis
Kidney biopsy to determine exact pathology
Evaluate for associated diseases: hepatitis B surface
antigen, hepatitis C antibody or PCR, antinuclear
antibody, antidouble-stranded DNA, complements
Consider renal vein angiography depending on
probability of renal vein thrombosis (flank pain,
hematuria, thromboembolic events)
Age-appropriate cancer screening, particularly if
patient's age is >55

What are the 30% spontaneous remission

outcomes for 30% partial remission
untreated 30% persistent nephrotic range proteinuria with
membranous progressive decline in GFR
nephropathy?

How is idiopathic Treatment depends on proteinuria and renal function.

membranous If nonnephrotic and normal GFR: treat proteinuria (ACEI
nephropathy and/or ARB), lipid management, blood pressure control.
treated? If proteinuria is 3.5 to 10 g and normal GFR: treatment
as above.
If proteinuria is 3.5 to 10 g and reduced GFR: first treat
as above. If proteinuria persists on the order of 4 to 8
months, consider cytotoxic agents and steroids.
If urine protein >10 g, regardless of GFR, treat with
cytotoxic therapy and steroids.

If patients are on Antiulcer medications

cytotoxic/steroid Bone-stabilizing agents: calcium, vitamin D,
treatment, what bisphosphonates
types of prophylaxis PCP prophylaxis with trimethoprim/sulfamethoxazole
is needed?

P.381
P.382

Membranoproliferative Glomerulonephritis
What are the clinical Microscopic hematuria
manifestations of Nonnephrotic-range proteinuria or nephrotic
MPGN? syndrome
Progressive glomerulonephritis
Rapidly progressive glomerulonephritis
What are the etiologies Idiopathic
of Secondary: hepatitis C, chronic hepatitis B, HIV,
membranoproliferative malaria, chronic liver disease, chronic lymphocytic
glomerulonephritis? leukemia, lymphoma, thymoma, renal cell
carcinoma, SLE, Sjgren's syndrome, hereditary
complement deficiency, acquired complement
deficiency, bacterial endocarditis

What are the different MPGN type I (with mixed cryoglobulinemia or

histological types of without cryoglobulinemia)
MPGN? MPGN type II (associated with C3 nephritic factor or
associated with factor H defect)
MPGN type III (associated with or without terminal
complement nephritic factor)

What is the C3 An autoantibody formed against the C3 convertase

nephritic factor? component of the complement cascade. This leads to
continuous complement activation and is associated
with the development of MPGN.

What types of MPGN MPGN type I with and without cryoglobulinemia

are associated with MPGN type III
hepatitis C?

In which setting is In conditions with chronic generation of immune

MPGN type I likely to complexes (HIV, HCV, HBV, malaria, SLE, chronic
occur? lymphocytic leukemia)
In conditions with a patient's inability to clear
immune complexes (hereditary complement
deficiencies of classic pathway)
In conditions with continuous complement activation
(C3 nephritic factor or factor H deficiency)

Where are immune Mesangium and subendothelial space

complexes deposited in
MPGN type I?

Where are immune Subendothelial space

complexes deposited in
MPGN type II?

Where are immune Mesangium and subendothelial space, but deposition

complexes deposited in may occur in subepithelial space.
MPGN type III?
 What are findings for
MPGN on:

Light microscopy? Hypercellularity of the glomerulus and prominent

lobes of the glomerulus because of mesangial
proliferation

Immunofluorescence? Granular staining of glomerular capillary wall

Electron microscopy? Subendothelial deposits mesangial deposits

subepithelial deposits with duplicated basement
membrane (tram-tracking)

What are Immunoglobulins that are precipitated in the cold

cryoglobulins?

What diseases are Lymphoproliferative disorders, monoclonal

cryoglobulins gammopathies (myeloma, Waldenstrm's), HCV, HBV,
associated with? poststreptococcal glomerulonephritis, endocarditis
SLE
Chronic liver disease

What are the systemic Artralgias, purpura, Raynaud's phenomenon, digital

manifestations of necrosis, painful skin lesions
cryoglobulinemia?

How is MPGN treated? Normal GFR and nonnephrotic: observation

Impaired GFR or nephrotic: steroids
If HCV or cryoglobulin associated and normal GFR:
interferon-alpha and ribavirin
If HCV or cryoglobulin associated and reduced GFR:
interferon-alpha, ribavirin, steroids
If HCV or cryoglobulin associated and RPGN:
methylprednisolone, cyclophosphamide, and
cryofiltration (plasmapheresis)

What is the prognosis Renal replacement therapy needed in >50% at 10

for MPGN? years

Does MPGN recur in Yes

kidney transplants?

P.383

Nephritic SyndromeGeneral
 What is the nephritic Development of deterioration in GFR
syndrome? associated with:
Active urine sediment: dysmorphic RBCs, RBC
casts, white blood cells, granular casts
Hypertension
Systemic symptoms of the underlying disease
(such as SLE)

What glomerular diseases Immune complex: poststreptococcal

present as nephritic glomerulonephritis, SLE, endocarditis, IgA
syndrome? nephropathy
Vasculitis (usually ANCA-positive)
Associated with anti-GBM antibodies

P.384

IgA Nephropathy
What is the most Hematuria during upper respiratory illness
common clinical (synpharyngitic hematuria) or isolated asymptomatic
presentation of IgA microscopic hematuria.
nephropathy? IgA nephropathy is the most common pattern of
glomerular disease in the world.

How is Henoch- The kidney pathology is the same, with diffuse

Schnlein purpura mesangial deposition of IgA. However, in HSP, there are
(HSP) differentiated extrarenal manifestations, including vasculitis of the
from IgA skin, gut, and joints.
nephropathy?

What is the Likely due to abnormal glycosylation of IgA and

pathogenesis of IgA formation of circulating IgA, circulating immune
nephropathy? complexes that deposit in the mesangium, leading to
glomerular injury.

What are the clinical Asymptomatic hematuria and proteinuria

presentations of IgA Macroscopic hematuria often with a concomitant upper
nephropathy? respiratory tract infection
Nephrotic syndrome
Acute kidney injury with crescent formation
Chronic kidney disease

What are clinical Palpable purpuric rash

presentations of Abdominal pain/bloody diarrhea from intestinal
HSP? vasculitis
Polyarthralgias
 Acute renal failure

What is the Observation

treatment for IgA
nephropathy
associated with
hematuria and
stable kidney
function?

What is the Biopsy to evaluate for crescentic IgA nephropathy. If

treatment for IgA crescents form, begin prednisone and
nephropathy cyclophosphamide.
associated with
acute kidney injury?

What is the If evidence of minimal change on biopsy, begin

treatment for IgA prednisone. If proteinuria >1 g/24 hr, use ACEI. For
nephropathy persistent proteinuria on ACEI, consider steroids,
associated with azathioprine, or fish oil. Combination of ACEIs and ARBs
proteinuria? appears to be particularly beneficial.

What is the role of Advocated by some, but the data are inconclusive.
tonsillectomy in the
treatment of IgA
nephropathy?

Does IgA Yes

nephropathy recur
in kidney
transplants?

P.385

Rapidly Progressive Glomerulonephritis

What glomerular diseases Goodpasture's disease
present as rapidly Vasculitis: Wegener's granulomatosis,
progressive microscopic polyangiitis, Churg-Strauss
glomerulonephritis? Immune complex: SLE, poststreptococcal
glomerulonephritis, IgA/HSP, endocarditis,
membranoproliferative glomerulonephritis

What is the diagnostic Serologic studies: ANA, anti-dsDNA,

workup for a patient with complement levels (C3, C4), ANCA, anti-GBM
RPGN? antibodies.
 Most patients will be biopsied for definitive
diagnosis.

Goodpasture's Disease
What is the clinical Rapidly progressive glomerulonephritis (RPGN) and
presentation of hemoptysis. A renal-limited form of the disease is
Goodpasture's disease? termed anti-GBM disease.

What is the etiology of Autoimmunity to a common antigen found on lung

Goodpasture's disease? and kidney basement membrane

What is the antigen in The noncollagenous domain of the alpha-3 chain of

Goodpasture's disease? type IV collagen: alpha-3(IV)NC1

What precipitating Cigarette smoking

factors may uncover Hydrocarbon exposure
basement membrane Infections
epitopes and Pulmonary edema
precipitate the
disease?

What information can Degree of necrosis and crescent formation

be gained by kidney Degree of tubular loss and chronic scarring
biopsy to determine
prognosis?

What immunohistologic Linear staining of immunoglobulin along the basement

finding on kidney membrane (reacting to the type IV collagen in the
biopsy is basement membrane)
pathognomonic for
anti-GBM or
Goodpasture's disease?

What therapies are Plasma exchange (most effective if initiated early

available for acute with serum creatinine <6 mg/dL), plus prednisone and
Goodpasture's disease? cyclophosphamide

What factors predict Presenting creatinine <6 mg/dL

kidney recovery? Nonoliguric

Which patients should Patients who do not have lung hemorrhage and are
be considered for dialysis-dependent at onset and with high percentage
supportive treatment of crescents, glomerulosclerosis and tubular loss.
(i.e., no These patients do not appear to benefit from
 immunosuppression)? aggressive immunosuppression.

Does anti-GBM or Yes.

Goodpasture's disease
recur in kidney
transplants?

What is the optimal Anti-GBM antibodies should be undetectable for at

timing for kidney least 6 months to minimize recurrence in transplant.
transplant in
Goodpasture's disease?

P.386
P.387

Vasculitis
What diseases present with Giant-cell arteritis
vasculitis involving large vessels? Takayasu's arteritis

What diseases present with Polyarteritis nodosa

vasculitis involving medium-sized Kawasaki's disease
vessels?

What diseases present with Wegener's granulomatosis

vasculitis involving small vessels? Churg-Strauss syndrome
Microscopic polyangiitis
Henoch-Schnlein purpura
Cryoglobulinemic vasculitis
Leukocytoclastic angiitis

What are the clinical RPGN

manifestations of ANCApositive Fever, malaise, anorexia, weight loss,
(small vessel) vasculitis? myalgias, arthralgias
Palpable purpura
Upper and lower respiratory involvement
(most common in Wegener's)
Peripheral neuropathy

What are the two antigens Proteinase 3 (cANCA): Wegener's

associated with ANCA diseases? Myeloperoxidase (pANCA): microscopic
polyangiitis

What is the sensitivity of ANCA >90%

for small-vessel vasculitis?
 What is seen pathologically in Focal necrotizing lesions in the glomerulus
ANCA diseases? and vasculature
Crescent formation
Termed pauci-immune secondary to lack
of immune deposits and negative
immunohistochemistry

How is ANCA-associated RPGN High-dose methylprednisone IV followed

treated? by high-dose oral prednisone
Oral cyclophosphamide daily for 6 to 12
months
Plasma exchange is controversial but likely
beneficial if patients have concomitant
hemoptysis

What is the percentage of ANCA 25% to 50%

disease relapse?

P.388

Systemic Lupus Erythematosus (SLE)

What are the immunologic Anti-dsDNA and anti-ssDNA antibodies. They
findings in patients with SLE also usually have antibodies against C1q and
nephritis? depressed levels of C3 and C4.

For the following features,

what percentage of patients
have the findings?

Proteinuria 100%

Microscopic hematuria 80%

Tubular abnormalities 6080%

Nephrotic syndrome 4565%

Reduced renal function 4080%

Nephritis 30% to 50%

Granular casts 30%

RPGN 30%
 Hypertension 15% to 50%

How is SLE nephritis By the World Health Organization (WHO)

classified? system: based on light microscopy:
WHO class I: normal
WHO class II: mesangial disease
WHO class III: focal proliferative GN
WHO class IV: diffuse proliferative GN
WHO class V: membranous GN

How common are each of Class I: <5%

the types of SLE nephritis? Class II: 10% to 25%
Class III: 20% to 35%
Class IV: 35% to 60%
Class V: 10% to 15%

What are the different Class I: hematuria, mild proteinuria

presentations of the SLE Class II: hematuria, proteinuria
nephritis subtypes? Class III: hematuria, proteinuria, HTN, possibly
decreased GFR
Class IV: hematuria, proteinuria, HTN,
decreased GFR, possibly RPGN
Class V: nephrotic-range proteinuria

How is SLE nephritis For mild nephritis (WHO class II): prednisone
treated? alone
For severe disease (WHO classes III and IV):
prednisone plus either cyclophosphamide or
mycophenolate
For class V disease: same at classes III and IV
or may try cyclosporine as well

What percent of patients 10% to 15%

with lupus nephritis
progress to ESRD?

P.389

Collagen Vascular Disease

What are the Membranous nephropathy
renal Rheumatoid vasculitis
manifestations Amyloidosis
of rheumatoid Mesangial proliferative GN
arthritis?
 What are the Mesangial proliferative GN
renal Scleroderma renal crisis: AKI associated with severe
manifestations hypertension, renal vasoconstriction, microangiopathic
of hemolytic anemia. Leads to ischemic injury of the glomerulus
scleroderma? and tubules. Treated with high-dose ACEI.

P.390

Immunoglobulin Deposition Diseases

What are the two 1. Organized
categories of glomerular Fibrillar (amyloid)
disease caused by Microtubular (cryoglobulinemia, immunotactoid
immunoglobulin glomerulonephritis)
deposition as seen by 2. Nonorganized (monoclonal immunoglobulin
electron microscopy? deposition disease)

What is amyloidosis? Amyloidosis is defined by the ability of a variety

of proteins to form beta-pleated sheets and for
these proteins to deposit in a variety of organs
(kidney, heart, blood vessels, nerves), leading to
end-organ dysfunction.

What two types of Primary amyloid (AL, AH)

amyloidosis have kidney Secondary amyloid (AA)
involvement?

How are the two diseases By the precursor proteins:

distinguished? Both AL and AH amyloid have light-or heavy-chain
immunoglobulin deposition.
AA amyloid has SAA apolipoprotein deposition.

What are the main Nephrotic syndrome

clinical manifestations of Peripheral neuropathy
AL and AH amyloid? Restrictive cardiomyopathy and congestive heart
failure
Orthostatic hypotension

What are the light Mesangial expansion, tubular and glomerular

microscopy findings of AL basement membrane thickening, and Congo red
amyloid? staining, seen as apple-green birefringence under
polarized light

What are the Staining for immunoglobulin molecules

 immunofluorescent
findings of AL amyloid?

What are the electron Organized fibrils deposited within or alongside

microscopy findings of AL capillary basement membrane
amyloid?

What is the median Median survival: 16 months

survival for AL amyloid Negative prognostic factor: symptomatic heart
and what is the most failure (median survival 5 months)
significant negative
prognostic factor?

What are treatment Melphalan, prednisone, autologous stem cell

options for AL amyloid? transplant

What is monoclonal Deposition of monoclonal immunoglobulins in a

immunoglobulin nonorganized distribution, depicted as granular
deposition disease deposits on electron microscopy. Deposits can be
(MIDD)? of light chains (LCDD), heavy chains (HCDD), or
heavy and light chains (LHCDD)

What is the most common Nephrotic syndrome with progressive decline in

renal presentation of GFR
MIDD?

What are the light Nodular glomerulosclerosis in 30% to 100% of

microscopy findings of patients, 10% may have positive Congo red
MIDD? staining

What are the Positive for deposition of immunoglobulin

immunofluorescent molecules
findings of MIDD?

What are the electron Dense granular deposits along glomerular

microscopy findings of basement membrane
MIDD?

What hematologic Multiple myeloma (MM), Waldenstrm's

diseases occur with MIDD? macroglobulinemia, or chronic lymphocytic
leukemia

P.391

Multiple Myeloma
 What kidney Prerenal azotemia (volume depletion), often associated with
diseases occur hypercalcemia
in patients ATN
with multiple Interstitial nephritis
myeloma? Myeloma kidney (cast nephropathy)
AL amyloid
LCDD
Plasma cell infiltration

What is the Over 40% of patients with MM have serum creatinine >1.5
incidence of mg/dL. Of these, most cases are caused by cast nephropathy.
renal
insufficiency
in MM?

What are Melphalan/dexamethasone or vincristine, doxorubicin

treatment (Adriamycin), dexamethasone, and consideration of stem cell
options for MM transplant and plasmapheresis
and renal
failure
secondary to
myeloma
kidney?

Does Unknown. To date there is one positive trial and several

plasmapheresis negative trials regarding the efficacy of plasmapheresis in
lengthen renal decreasing death and dialysis and improving renal recovery.
survival in The biological limitation is that plasmapheresis can remove
patients with only those proteins in the intravascular space. IgGs and light
myeloma chains are distributed 50% in intravascular and 50% in
kidney, AL extravascular space.
amyloid, or
LCDD?

P.392
P.393

Thrombotic Microangiopathy (TMA)

What are clinical Thrombotic thrombocytopenic purpura (TTP)
presentations of TMA? Hemolytic-uremic syndrome (HUS)
Antiphospholipid antibody syndrome (APA)

What features can HUS tends to affect children, have higher

distinguish HUS from TTP? association with kidney injury and less
neurological involvement than TTP. HUS also
 associated more often with shiga-toxin producing
E. coli that leads to bloody diarrhea.

What is the clinical Thrombocytopenia

pentad for TTP? Microangiopathic hemolytic anemia
Acute kidney injury
Neurologic deficits
Fever

What laboratory values Thrombocytopenia

support TTP? Hemolytic anemia: high LDH, low haptoglobin,
high indirect bilirubin, schistocytes on peripheral
smear, negative Coombs' test
Normal coagulation tests
Acute kidney injury

What is in the differential Malignant hypertension, vasculitis, disseminated

diagnosis for intravascular coagulation, APA
thrombocytopenia,
microangiopathic
hemolytic anemia, acute
kidney injury?

What are some potential Infections: HIV, Shiga toxin from E. coli (0157:H7)
causes of TTP/HUS? Drugs: clopidogrel, ticlopidine, rifampin,
metronidazole, penicillin, quinine, some
antineoplastic drugs or immunosuppressants
(cyclosporine, tacrolimus)
Autoimmune disease: SLE, scleroderma
Pregnancy: HELLP syndrome, postpartum HUS
Idiopathic
Malignancy: metastatic gastric cancer

What is the pathogenesis Low levels or activity of a protease (ADAMTS13)

of idiopathic TTP? that normally cleaves von Willebrand factor
multimers

How is HUS secondary to Plasma exchange can be considered (adults)

Shiga toxin treated? Supportive care, hydration, electrolyte repletion
Dialysis for volume or uremic clearance
No antibiotics for E. coli (0157:H7) or antimotility
agents

How is idiopathic TTP Plasma exchange and fresh frozen plasma as

treated? replacement fluid
 Cryoprecipitate can be considered for relapsing
TTP
Exchange is done until platelets and LDH
normalize
Other therapies include steroids, vincristine,
cyclophosphamide, azathioprine, splenectomy

How is TTP in pregnancy Plasma exchange and delivery

treated?

P.394
P.395
P.396
P.397

Tubulointerstitial Disease
What are the Collagen vascular diseases (sarcoidosis, SLE, Sjgren
different types of syndrome, Behet's), infectious diseases (EBV,
diseases affecting tuberculosis, Brucella, Toxoplasma, fungi), drugs
the tubules and (Lithium, tacrolimus, Chinese herbs), VUR, heavy
interstitium that can metals, MM, hypokalemia, and hypercalcemia
lead to chronic
interstitial disease?

What are the clinical Decrease in GFR, polyuria and nocturia due to
hallmarks of chronic incomplete nephrogenic diabetes insipidus, renal
interstitial kidney tubular acidosis, Fanconi's syndrome due to proximal
disease? tubular injury, anemia out of proportion to fall in GFR,
proteinuria <1.5 g/day

What percentage of Varies widely, from ~3% to 8% in the United States to

patients with ESRD 42% in Scotland, depending on diagnostic precision and
have CIN as their geographical factors.
primary diagnosis?

What are the 1. Immune-mediated, involving antibodies directed

mechanisms by against tubular epithelial antigens (as in
which collagenvascular disease).
tubulointerstitial 2. Direct cytotoxic exposures, as in lead poisoning or
structures are analgesic nephropathy.
injured? 3. Idiosyncratic reactions, as in cytokine-mediated
damage from tacrolimus.
4. The final pathway for all these injuries is
interstitial fibrosis, glomerulosclerosis, and tubular
atrophy.
What is the Acutely, interstitial edema with a leukocytic (usually
histologic lymphocytic) infiltrate; CIN is marked by tubular
appearance of atrophy and interstitial fibrosis lymphocytic
tubulointerstitial infiltrate. The degree of tubular atrophy and
nephritis? interstitial fibrosis is one of the best predictors of long-
term renal outcome.

What are the renal Calcitriol is synthesized at a high rate by macrophages

manifestations of in granulomas; this results in hypercalciuria,
sarcoidosis? hypercalcemia, and nephrocalcinosis (the most common
cause of CKD in sarcoid). Sarcoid can also cause a
granulomatous interstitial nephritis. Rarely, sarcoid can
cause GN or retroperitoneal fibrosis causing obstructive
uropathy.

What is the Granulomatous interstitial nephritis often responds well

treatment of CKD to high-dose corticosteroids; hypercalcemia often
associated with responds to a low dose of steroids but is more likely to
sarcoidosis? recur after treatment.

What are the renal CIN that predominantly affects the distal tubule,
manifestations of leading to type 1 RTA. Rarely, associated with
Sjgren's syndrome? glomerulonephritis.

What is the Corticosteroids or cytotoxic drugs; CIN typically

treatment of CKD responds well, although tubular dysfunction is usually
associated with permanent.
Sjgren's syndrome?

What is chronic Interstitial fibrosis secondary to sodium urate crystal

urate nephropathy? deposition in the interstitium of medullary cells; usually
seen in patients with tophaceous gout.

Who develops reflux Children and adults with congenital vesicoureteral

nephropathy? (VUR) junction abnormalities that predispose to reflux
of urine into the kidney during bladder contraction

What is the Recurrent reflux of infected urine is thought to cause

pathogenesis of renal scarring. Progressive loss of nephron mass leads
reflux nephropathy? to glomerular hyperfiltration and in some cases
development of FSGS. As VUR is often associated with
hypoplastic kidneys, this population may also be more
susceptible to any form of kidney damage and CKD.
What are the Recurrent urinary infections, heavy proteinuria (often
characteristics of due to FSGS), slowly progressive decline in GFR
reflux nephropathy?

What is A rare complication of chronic urinary inflammation,

xanthogranulomatous where granulomatous tissue replaces nearly all renal
pyelonephritis? parenchyma

Aside from reflux Many cases of documented TIN have occurred with
nephropathy, what is infections such as HIV, tuberculosis, leptospirosis,
the role of infectious fungi, and others and remitted after treatment. These
agents in causing cases are typically rare. Several investigators have
TIN? found EBV DNA and antigens in renal biopsies with
otherwise unexplained TIN.

What is BK virus An acute or chronic interstitial nephritis occurring in

nephropathy? Who is postrenal transplant patients caused by BK (or JC)
at risk and how is it virus. Intranuclear viral inclusions are found on kidney
treated? biopsy. Treatment with lowering of immunosuppression
or antiviral medications is attempted but often not
successful, leading to eventual failure of the kidney
transplant.

What is myeloma A form of TIN that occurs more often with kappa-light
cast nephropathy? chain immunoglobulins. Tubular injury and cast
formation are caused by light chain precipitation in
renal tubules, causing both obstruction and
inflammatory damage. Can progress rapidly to ESRD.
Hypovolemia plays a prominent role in promoting cast
formation.

What are other Proximal tubular dysfunction leading to Fanconi's

tubular abnormalities syndrome; urate or calcium stones
in kidney function
caused by MM?

Which heavy metals Lead, cadmium, and mercury; very rarely, gold,
have been uranium, arsenic, zinc, and others
implicated in CKD?

What are the Proximal tubular dysfunction, hyporeninemic

manifestations of hypoaldosteronism, hyperuricemia resulting from
lead nephropathy? decreased uric acid excretion and causing gout,
hypertension, progressive renal failure
 What is saturnine Recurring gout, usually tophaceous, that occurs as a
gout? result of lead-induced hypouricosuria and resultant
hyperuricemia

How is the diagnosis As >90% of total body lead is in bone, an EDTA

of lead nephropathy mobilization test is necessary. After administration of
made? EDTA, a 72-hour collection of urine is measured for
lead; >600 &g is diagnostic of high lead burden.

How is lead EDTA chelation of lead to decrease progression of CKD

nephropathy
treated?

What is renal RPN is an uncommon complication of CIN; medullary

papillary necrosis ischemia caused by a variety of diseases can result in
(RPN)? infarction and subsequent necrosis of the renal
papillae.

What disorders have Any cause of CIN; diabetes mellitus, analgesic

been known to cause nephropathy, renal vein thrombosis, pyelonephritis,
RPN? sickle cell disease, obstructive uropathy, and many
others. Transplanted kidneys, especially cadaveric, are
more susceptible to RPN.

What is the As the renal medulla has a relatively poor blood

mechanism by which supply, it is especially vulnerable to hypoperfusion. In
RPN occurs? most cases of RPN, inflammation of the interstitium
results in vasoconstriction and subsequent ischemia
leading to infarction. Ischemia may also be due to
other causes, such as obstruction of blood flow in
sickle cell nephropathy.

How is the diagnosis Imaging studies such as CT or ultrasound suggest the

of RPN made? diagnosis.

What is the RPN may result in progressive CKD, tubular defects

significance of RPN? with electrolyte wasting or concentrating difficulties
(polyuria/nocturia); sloughing of necrotic papillae can
lead to acute urinary obstruction. Management of RPN
is that of the underlying process.

P.398
P.399

Renovascular Disease
What are the Fibromuscular dysplasia (FMD)
various forms of Atherosclerotic disease
renal artery
stenosis (RAS)?

What are the Ischemic renal disease (progressive renal failure)

clinical syndromes ACEI/ARB-induced AKI
secondary to Flash pulmonary edema
atherosclerotic Renovascular hypertension
renovascular Acute renal infarction
disease? Asymptomatic

What constitutes >70% stenosis

hemodynamically
significant RAS?

What are the Occurs more often in young females and diffusely involves
clinical the renal arteries and other arteries as well with a
characteristics of characteristic appearance on angiography (rosary
FMD? beading). Most often presents as isolated hypertension.

What are the Older patients with hypertension, other risk factors for
clinical atherosclerotic disease such as smoking, hyperlipidemia,
characteristics of family history. Atherosclerotic disease tends to be
atherosclerotic restricted to the ostia of the renal arteries. Can present
renal vascular in more varied fashion: hypertension, renal insufficiency,
disease? etc.

Can renal artery Yes, often renal artery lesions are found incidentally and
stenosis be are not functionally significant. In fact, up to 60% of
asymptomatic? patients age >70 years who die from cardiovascular causes
are found to have RAS on autopsy that was not clinically
suspected.

What are the Holosystolic with a short diastolic component heard best
characteristics of in the flank regions or just lateral to the umbilicus
a bruit due to
RAS?

What diagnostic MRA

tests have the Spiral CT scan with IV contrast
highest sensitivity Duplex ultrasonography (highly operator-dependent)
and specificity for Angiography (the gold standard)
making the
diagnosis of RAS?
 What are the Contrast nephropathy
complications Cholesterol emboli
associated with Renal artery or aortic dissection
renal Retroperitoneal hematoma
angiography? Pseudoaneurysm formation

What is a common The studies detect only the presence of a stenotic lesion;
problem with all they do not predict functional significance (either in
imaging studies causing progressive renal insufficiency or hypertension).
for RAS?

What is the Fibromuscular dysplasia: 100% technical success with 50%

success rate for hypertension cure rate and 50% hypertension improved
percutaneous rate.
transluminal renal Atherosclerotic RAS: >70% technical success with the
angioplasty majority of ostial lesions requiring stent placement. Cure
(PTRA)? of hypertension is rare (0% to 15%) with improved BP
control in 50% to 85% of patients.

What are the Long-standing hypertension

clinical clues that Small (<8 cm) kidneys
suggest a poor Creatinine >3 mg/dL
outcome from Bilateral RAS
PTRA? Diabetes or other causes of progressive kidney disease
Poor LV function

Can patients with Yes. Three randomized clinical trials have looked at this
RAS be managed and suggest that a majority of patients can be managed
medically? with medical therapy. However, this may be at the
expense of additional medications. A larger study (CORAL)
is now reinvestigating this question.

P.400
P.401

Genetic Kidney Diseases

What is the Autosomal dominant polycystic kidney disease (ADPKD); it is
most common the fourth most common cause of ESRD.
inherited
renal disease?

What are the Types I and II

various forms
of ADPKD?
How do these Type I: accounts for 80% to 90% of cases with ESRD occurring
forms differ? by age 50 to 60
Type II: accounts for 10% to 20% of cases with milder disease
and ESRD occurring by age 70

What is the The mutations occur in proteins named polycystins, which are
gene involved expressed in the renal tubules and are important in cell
in ADPKD? signaling and proliferation.

What are the Hematuria, nocturia (loss of renal concentrating ability), flank
renal pain, nephrolithiasis, cyst rupture, cyst bleeding and cyst
manifestations infections
of ADPKD?

What are the Liver cysts, pancreatic cysts, cerebral aneurysms, colonic
extrarenal diverticula, mitral valve prolapse
manifestations
of ADPKD?

How is ADPKD Either by ultrasonographic findings of an abnormal number of

diagnosed? renal cysts or through genetic testing

What are the Early age onset with severe renal abnormalities and early
features of progression to ESRD. May cause neonatal death and associated
autosomal with progressive hepatic fibrosis.
recessive
PKD?

What are the Autosomal dominant.

features of Hamartomas develop in multiple organs.
tuberous 80% have seizures.
sclerosis? 50% have mental retardation.
Skin manifestations are common.
Renal lesions include renal cell carcinoma, cysts, and
angiomyolipomas.

What are the Autosomal dominant

features of Predisposition for tumors of the eyes, brain, spinal cord,
von Hippel adrenals, and pancreas
Lindau Pheochromocytomas in 20%
disease? Associated with renal cysts and development of bilateral renal
cell carcinoma

What is X-linked disease (in a minority of patients, it is an autosomal

 Alport's recessive disorder) characterized by hematuria, progressive
syndrome? renal failure, and hearing difficulties. It is caused by defective
production of type IV collagen in the glomerular basement
membrane.

What is thin Also a defect in type IV collagen which presents as isolated

basement glomerular hematuria with a very low risk of progressive renal
membrane disease.
disease?

What are the Hereditary deficiency of alphagalactosidase A

features of Results in intracellular accumulation of glycosphingolipids
Fabry's Leads to involvement of the heart, CNS, skin, and kidneys
disease? Leads to proteinuria and progressive renal failure
Treated with human recombinant enzyme

What are the Impaired renal concentrating ability with nocturia (due to
renal medullary injury)
manifestations Hematuria
of sickle cell Papillary necrosis
disease? Distal renal tubular acidosis with hyperkalemia
Focal segmental glomerulosclerosis
Hypertension
ESRD (2% to 5%)

P.402

Drugs and the Kidney

NSAIDs
What effects do NSAIDs have NSAIDs inhibit renal prostaglandin synthesis
on the kidney at typical (PGE 2 and PGI 2 ), leading to afferent arteriolar
therapeutic doses? constriction.

Which patients are most at Patients with preexisting CKD, AKI,

risk for NSAID-induced hypovolemia, HF, liver disease
nephrotoxic effects?

How do NSAIDs cause:

Prerenal azotemia? PGI 2 inhibition causing vasoconstriction of

afferent arteriole. NSAIDs may also precipitate
HRS via a similar mechanism.
 Edema and hypertension? PGE 2 inhibition causes sodium retention via
local and ADH-mediated mechanisms.

ATN? PGI 2 keeps renal blood flow constant in

ischemic conditions; its inhibition can increase
the risk of ATN.

Type 4 RTA? Prostaglandin-mediated reduction in renin

secretion

AIN? Typically seen with chronic use

Acute papillary necrosis? Vasoconstriction, often with hypovolemia

Nephrotic syndrome? Minimal change disease; less commonly,

membranous nephropathy

P.403

Aceis and ARBs

What is the Reduced levels of angiotensin II, reducing
mechanism of ACEI- vasoconstriction of the efferent arteriole and reducing
induced decrease in vasodilation of the afferent arteriole, thereby
GFR? decreasing glomerular capillary pressure and filtration

In which conditions All causes of CKD (except for bilateral renal artery
have ACEIs been stenosis)
shown beneficial for
retardation of
kidney damage?

How do ACEIs Reduction of intraglomerular (as well as systemic)

reduce progression pressure, decreasing glomerular permeability and
to ESRD and glomerulosclerosis. Reduction of proteinuria has the
proteinuria? added benefit of decreasing protein-dependent
inflammation and damage.

Are ACEIs As of 2007, the NKF considers ACEIs and ARBs to be

equivalent to ARBs interchangeable for treatment of CKD.
in treatment of
chronic kidney
disease?

Are ACEIs and ARBs Multiple trials, such as COOPERATE, have demonstrated
 complementary in reduced progression to ESRD and reduced proteinuria
treatment of CKD? with combined ACEIARB therapy.

How do ACEIs and Aldosterone deficiency, especially with some degree of

ARBs cause reduction in GFR
hyperkalemia?

How can ACEIs and Synergistically (in the presence of other factors such as
ARBs cause AKI? nephrotoxins or hypoperfusion) or by excessive efferent
arteriolar vasodilation in bilateral renal artery stenosis

P.404

Trimethoprim/Sulfamethoxazole
What are the Impair secretion of creatinine causing falsely elevated SCr;
adverse effects hyperkalemia, occasional hyponatremia, normal AG
of trimethoprim metabolic acidosis
(TMP) that affect
the kidneys?

What is the TMP is structurally similar to amiloride; it inhibits the

mechanism of ENaC ion channel in the CT, decreasing the electrochemical
TMP-induced gradient driving K+ and H+ transport. This leads to a distal
electrolyte tubular acidosis similar to type 4 RTA, causing
abnormalities? hyperkalemia and occasional hyponatremia and metabolic
acidosis. This is usually seen in high-dose TMP (e.g.,
treatment of PCP).

Who are most at Patients with preexisting CKD, type 4 RTA, hyponatremia
risk for TMP- (e.g., SIADH); any patient receiving high-dose TMP/SMX,
induced critically ill patients
electrolyte
abnormalities?

What are the AIN, crystalluria leading to tubular obstruction; rarely,

adverse effects rhabdomyolysis
of
sulfamethoxazole
that affect the
kidneys?

Lithium
What are the NDI (by down regulating aquaporin 2), nephrotic syndrome
effects of (MCD or FSGS), chronic interstitial nephritis, CKD
lithium on the
kidney?

How common 10% to 20% have at least some degree of concentrating

is NDI in impairment.
patients
receiving
lithium
chronically?

What other Nausea, delirium, hypo/hyperthyroidism, hypercalcemia,

effects are aplastic anemia, long-QT syndrome, seizures, arrhythmias
seen in acute
or chronic
lithium
toxicity?

Which Preexisting renal dysfunction, use of ACEIs, chronic lithium

conditions use
predispose to
a higher risk
of lithium
toxicity?

At what serum Toxic levels >1.5 meq/L chronically, higher levels in acute
lithium levels intoxication
are these
effects seen?

At what point Any serum level >4 meq/L, >2.5 meq/L with renal
is dialysis insufficiency or neurologic symptoms, increasing levels after
indicated to admission, or any level in ESRD with symptoms. Dialysis should
remove be extended to account for tissue redistribution and prevent
lithium? rebounding levels post-HD.

What other Amiloride (blocks lithium reuptake in the collecting tubules);

treatments for thiazides and NSAIDs
lithium-
induced NDI
exist besides
dialysis?

P.405
Anti-Infective Drugs
How do various
anti-infective
agents cause AKI:

Beta lactams? AIN; several cephalosporins and carbapenems are toxic to

proximal tubular cells and can cause ATN

Aminoglycosides? Dose-related proximal tubular toxicity; may cause ATN.

Vancomycin? AKI due more to the vehicle vancomycin is suspended in,

which is substantially less nephrotoxic than in the past.
Vancomycin alone rarely causes AKI these days; AKI is
usually seen in combination with other drugs (e.g.,
aminoglycosides).

HIV protease Accumulate in proximal tubular cells (reuptake by

inhibitors (adefovir organic anion transport channels) leading to proximal
and tenofovir) and tubular toxicity (ATN and Fanconi's syndrome)
cidofovir?

Acyclovir and Crystalluria causing obstructive nephropathy, TIN, ATN

indinavir?

Foscarnet? Direct tubulotoxic causing AKI, hypocalcemia,

nephrogenic diabetes insipidus (DI)

Amphotericin B? Intrarenal vasoconstriction plus direct toxicity to

proximal tubular cells

P.406

Cytotoxic and Immunosuppressive Drugs

What effects do Both tacrolimus and cyclosporine nephrotoxicity result from
tacrolimus and calcineurin inhibition. Reversible, dose-dependent
cyclosporine reduction in RBF (due to afferent arteriole constriction) is
have on renal mediated by increased endothelin and angiotensin II
function? Which activity and decreased nitric oxide activity. Irreversible
effects are interstitial fibrosis is thought to be cytokine-mediated and
reversible and dose-independent.
which are not?

What is the Suppression of mineralocorticoid synthesis

mechanism of
 tacrolimus-
induced
hyperkalemia?

What is the Suppression of plasma renin activity and renal tubular

mechanism of aldosterone resistance
cyclosporine-
induced
hyperkalemia?

Compared to Sirolimus likely has some nephrotoxicity. However,

tacrolimus, does sirolimus can increase CyA nephrotoxicity by raising tissue
sirolimus have CyA levels. Also, both tacrolimus and sirolimus can cause
similar effects on TTP-HUS.
the kidney?

Is mycophenolate No
mofetil
nephrotoxic?

How can Tubulotoxicity and precipitation of MTX crystals in tubules

methotrexate
(MTX) cause AKI?

What are specific Prevention with hydration and urinary alkalinization has
treatments for greatly reduced AKI.
MTX-induced
AKI?

What are the Tubular toxicity causing Fanconi's syndrome and

nephrotoxic occasionally AKI
effects of
ifosfamide?

What effects can Tubulotoxicity causing progressive renal failure, magnesium

cisplatin have on wasting; with bleomycin, can cause TTP-HUS
the kidney?

P.407

Miscellaneous Drugs and Herbs

What is the danger of Severe lactic acidosis in patients with overdose or
metformin in patients impaired renal function; unclear mechanism
with reduced GFR?
 What are potential Some opioids (especially meperidine and morphine)
adverse effects of have metabolites with significantly prolonged half-
opioids in CKD or AKI? lives and/or adverse effects (e.g., seizures with
meperidine)

How can ATN, collapsing FSGS

bisphosphonates cause
AKI?

How do drugs that Osmotic nephrosis (uptake of substances into PCT

expand plasma volume cells leading to swelling and resultant tubular
(IV immunoglobulin, obstruction)
hetastarch, mannitol,
dextran) cause AKI?

Which herbs and Aristolochia sp. causes TIN and chronic interstitial
alternative medicines fibrosis (Chinese herb nephropathy); licorice
have been implicated (mineralocorticoid activity causes HTN, hypokalemia,
in kidney disease? Fanconi's syndrome in chronic use); many traditional
African herbal therapies cause ATN.

P.408
P.409

Diabetic Kidney Disease

What percentage of Type I: 25% to 30% after 25 to 40 years
patients with type I Type II: 25% after 20 years
and type II diabetes
develop
nephropathy?

What are the risk Ethnicity (African Americans and Mexican Americans at
factors for the highest risk)
development of Hypertension
diabetic Higher levels of proteinuria
nephropathy? Poor glycemic control

What is the Nodular glomerular lesions (KimmelsteilWilson) are

pathologic lesion of located in the central regions of the glomerulus and
diabetic have a hard, eosinophilic appearance. There is also
nephropathy? expansion of the mesangium with capillary wall and
basement membrane thickening.

What are the stages Stage 1: renal hypertrophy and hyperfiltration

of diabetic Stage 2: development of pathological changes with
nephropathy? normal GFR
Stage 3: development of microalbuminuria (usually 6 to
15 years after development of diabetes)
Stage 4: worsening proteinuria, development of
hypertension, decline in GFR begins
Stage 5: ESRD (develops on average 7 years after the
development of persistent proteinuria)

What are the Type I: yearly after 5 years of diabetes or over age of 12
screening Type 2: yearly after diagnosis
recommendations Screening can be done with a spot albumincreatinine
for ratio. If elevated, three timed overnight urine
microalbuminuria in collections should be obtained to verify.
diabetics?

What is the Evidence of incipient diabetic nephropathy with high risk

significance of for both progressive nephropathy as well as CV disease
microalbuminuria?

What other forms Membranous nephropathy

of kidney disease Renal papillary necrosis
are diabetics Renovascular disease
susceptible to? Obstruction due to autonomic neuropathy of the bladder
Higher risk for UTIs and pyelonephritis
Higher risk for contrast nephropathy

What clinical Quantitate proteinuria

evaluation should Renal ultrasound
be done in Rule out UTI
diabetics with Urine microscopy
proteinuria? Serology if glomerulonephritis suspected: complements,
ANCA, anti-DNA antibodies

Does tight glycemic Yes. Good glycemic control can slow progression of
control prevent nephropathy, especially in the early stages. In the DCCT
diabetic (Diabetes Control and Complications Trial), those with
nephropathy? lower HgBA1C values had a lower risk for development
of microalbuminuria.

In patients with It has been more difficult to show that tight glycemic
nephropathy, does control slows progressive nephropathy.
tight glycemic
control slow the
progression?
What is the goal BP 130/80 in the absence of proteinuria.
for a diabetic The exact goal BP for diabetic patients with proteinuria
patient? is not clear, however a goal of 125/75 has been
suggested.

What are the ACEIs or ARBs. ACEIs have been most studied in type 1
preferred diabetes and ARBs in type 2 diabetes. These drugs have
antihypertensive specific antiproteinuric effects and slow renal
drugs for diabetic progression above their antihypertensive effects.
patients with
microalbuminuria?

Do ACEIs prevent Yes

the development of
microalbuminuria?

What other Statins

therapies are Smoking cessation
important in Low-protein diets
slowing the
progression of
diabetic
nephropathy?

Is there a role for Probably. Small trials have shown a synergistic fall in
combined use of proteinuria with both drugs, but no long-term outcome
ACEIs and ARBs in studies looking at renal function are available as yet.
treatment of
diabetic
nephropathy?

What are the Angioedema (ACEIs ARBs)

complications Cough (ACEIs)
associated with Hyperkalemia
ACEIs or ARBs in Worsening GFR
diabetic patients?

Can ACEIs be used Yes. ACEIs have been safely used in patients with Cr up
in patients with to 3.0 mg/dL. Need to monitor for hyperkalemia and
elevated increase in serum Cr >30% from baseline.
creatinine?

How can you Low-potassium diet

manage Addition of diuretic
 hyperkalemia and Sodium bicarbonate
continue the ACEI
or ARB?

P.410
P.411
P.412
P.413

Chronic Kidney Disease

What is chronic For "3 months, a GFR <60 mL/min/1.73 m2 or GFR >60
kidney disease
mL/min/1.73 m2 with a marker of kidney damage
(CKD)?
(proteinuria, hematuria, HTN related to kidney
disease)

What are the stages Stage 1: GFR "90 mL/min with kidney damage
of CKD? Stage 2: GFR "60 to 89 mL/min with kidney damage
Stage 3: "30 to 59 mL/min
Stage 4: "15 to 29 mL/min
Stage 5: <15 mL/min

What are the

management
strategies for:

Stages 1 and 2 Avoidance of nephrotoxic drugs, lifestyle modifications

CKD? to reduce cardiovascular disease, yearly monitoring of
renal function, aggressive treatment of hypertension,
hyperlipidemia

Stage 3 CKD? Interventions as above. Nutrition counseling.

Evaluation for secondary hyperparathyroidism and
anemia associated with CKD.

Stages 4 and 5? As above, and preparation for renal replacement

therapy. Referral to nephrologist is recommended.

What are the Hypertension, normocytic anemia, hyperphosphatemia,

complications of hypocalcemia, secondary hyperparathyroidism,
CKD? increased risk of cardiovascular disease, malnutrition

What is done to slow General measures include antihypertensive therapy,

the progression of especially with ACEIs or ARBs, hyperlipidemia therapy,
CKD? smoking cessation, anemia treatment. Specific
 therapies depend upon the underlying disease.

What is end-stage Medicare ESRD program definition: patients on dialysis

renal disease (ESRD)? or transplant regardless of GFR. Other definitions: all
patients with GFR <15 or patients restarting dialysis
after failed transplant.

What is the According to USRDS data from 2004, the prevalence of

prevalence of ESRD? ESRD is over 335,000.

What is the annual >20%.

mortality rate of
patients with ESRD?

What guidelines are The NKF's K/DOQI: Kidney Disease Outcomes Quality
available for Initiative, found at http://www.kidney.org/
management of
patients with CKD?

What is uremia? The constellation of symptoms due to renal failure.

These include: fatigue, nausea, vomiting, anorexia,
volume overload, encephalopathy, peripheral
neuropathy, pericarditis, and in very late stages,
coma.

What are the Uremic symptoms, which can be very subjective, or

indications to start GFR <15 mL/min or life-threatening electrolyte
patients with CKD on imbalances such as hyperkalemia
dialysis?

What is the Loss of erythropoietin production by the kidney as GFR

pathogenesis of falls <60 mL/min
anemia due to CKD?

Why is treating Anemia is associated with increased hospitalizations,

anemia in CKD cognitive and functional impairment, and increased
patients important? cardiovascular disease, especially left ventricular
hypertrophy.

When should anemia GFR ' 60; Hgb <11 (Hct 33% in premenopausal women);
workup be initiated? Hgb <12 in postmenopausal women and in men

What is the initial Hgb/Hct, reticulocytes, RBC indices, serum iron, total
workup? iron-binding capacity,% transferrin saturation, fecal
occult blood testing, vitamin B12 and folate levels
What therapies are Erythropoietin SC for goal of Hgb 11 to 12 g/dL or Hct
available and what 33% to 36%
are treatment Iron IV or oral for goal of % transferrin saturation >20%
targets? and ferritin >100 ng/mL

What is the As GFR falls, hyperphosphatemia and decreased

pathogenesis of production of 1,25 vitamin D occurs. This leads to
secondary hypocalcemia and increased levels of PTH.
hyperparathyroidism?

How is secondary 1. Control serum phosphorus levels: achieved by using

hyperparathyroidism oral phosphate binders (calcium carbonate, calcium
treated? acetate, or sevelamer) with meals
2. Low-phosphorus diet
3. Replace active 1,25 vitamin D to suppress PTH
production

What are the 1. Osteitis fibrosa cystica (increased risk of fractures)

consequences of 2. Tertiary hyperparathyroidism
untreated secondary 3. Increased risk of cardiovascular disease
hyperparathyroidism?

What are dietary and Low-protein (no more than 0.8 g/kg/day), low-
nutritional goals for potassium, low-phosphorus diet
patients with CKD?

What are the daily <0.6 to 0.75 g/kg/day for patients with GFR <25, as
protein intake goals reduced protein intake is correlated with slower
for patients with progression to ESRD.
CKD? For patients on dialysis, goal is 1.2 g/kg.

What is the etiology Non-gap acidosis due to reduced ammoniagenesis by

of metabolic acidosis tubular cells; anion gap acidosis due to acidic uremic
in patients with CKD? toxins (phosphates, etc.)

Should metabolic Yes. Correction of acidemia has been associated with

acidosis in patients reductions in hypoalbuminemia and metabolic bone
with CKD be treated? disease. Goal is [HCO3-] of at least 22 meq/L,
achieved with oral NaHCO3.

What is the leading Cardiovascular disease

cause of death in
patients with stages
 3 to 5 CKD?

What are the risk Typical risk factors such as diabetes, hypertension,
factors for hyperlipidemia, smoking, family history, age account
cardiovascular for only 40% to 50% of attributable risk. Other
disease in this nontraditional risk factors include inflammation,
population? secondary hyperparathyroidism, vascular calcification,
and numerous unidentified risk factors.

What is the typical Low HDL, low to normal LDL, high triglycerides
lipid profile for a
patient with stage 4
to 5 CKD?

What is nephrogenic More recently termed nephrogenic systemic fibrosis. A

fibrosing rare fibrosing condition that occurs in patients with
dermopathy? advanced CKD (stages 3 to 5). The dominant clinical
manifestations involve
the skin. Leads to progressive restriction in joint
movement and functional incapacity. Associated with
the exposure to the MRI contrast agent gadolinium.

P.414
P.415
P.416

Hemodialysis
What are the 1. Diffusion: solute moves from the side of higher
mechanisms concentration to the side of lower concentration.
governing the 2. Ultrafiltration: movement of solvent (water) across a
clearance of semipermeable membrane from a region of high pressure
toxic solutes to one of low pressure.
from the blood 3. Convection: as solvent moves down a pressure gradient,
during dialysis? dissolved solutes are dragged across the membrane.

How are these 1. Diffusion: removal of small molecules such as electrolytes

mechanisms and urea
utilized in 2. Ultrafiltration: removal of body water
dialysis? 3. Convection: removal of larger molecules and protein-
bound molecules

What is the This is the critical part of the dialysis machine where the
dialyzer? exchange of molecules and water occurs. It consists of
thousands of hollow capillary fibers composed of a
 biocompatible semipermeable membrane. Blood flows
through these fibers, whereas the outer surface is bathed in
the dialysate solution.

How is dialysis The amount of solute removed is measured in terms of

therapy clearance. Clearance reflects the volume of blood or plasma
monitored? cleared of a given solute in a unit time. Dialysis therapy is
prescribed to give each patient a minimum acceptable
clearance, and this is closely monitored.

What solute Blood urea nitrogen serves as the marker for clearance.
clearances are
monitored?

What are These are a group of ill-defined molecules that lead to the
uremic toxins? symptoms of uremia. These molecules include urea, beta-2
microglobulin, and many others. One goal of dialysis is to
remove these toxic substances.

What is KT/V? This is a measure of dialysis adequacy that incorporates:

1. K: clearance of urea
2. T: time on dialysis
3. V: total body water
A goal KT/V of 1.2 is set for all patients.

What are signs Malnutrition (low serum albumin), weight loss, anorexia,
and symptoms nausea, vomiting, declining functional status,
of inadequate encephalopathy, peripheral neuropathy, pericarditis,
dialysis? persistent volume overload, KT/V <1.2

Which is the AV fistula: longest life span and fewest complications. AV

preferred form grafts typically develop stenotic lesions at the venous
of AV access? anastomosis.

How is an AV A surgeon forms an anastomosis between an artery and vein

fistula created? usually in the forearm of the nondominant arm. Arterial
pressure is transmitted to the vein, which dilates, becomes
thickened, and then can be used to cannulate for access to
the bloodstream.

How is an AV A tubular graft (polytetrafluoroethylene) is interposed

graft created? between an artery and vein and tunneled beneath the skin.

What are the Infections, clotting, low blood-flow rates, and poor dialysis
problems clearances
associated with
central venous
dialysis
catheters?

What are the Hypotension, cardiac arrhythmias, muscle cramps, nausea,

complications vomiting, headaches. Complications due to machine-related
associated with issues include air embolism, hemolysis
a dialysis (usually due to exposure of blood to contaminants in the
session? dialysis water), and hypersensitivity reactions to the dialysis
membrane.

What is dialysis An uncommon reaction that usually occurs during the first
disequilibrium dialysis treatment. Symptoms include headaches, nausea,
syndrome? vomiting, disorientation, seizures, obtundation, or coma.

What is the It is believed that the rapid removal of extracellular solute

cause of this leads to movement of water into the CNS and the
syndrome? development of cerebral edema.

What is the The life expectancy of ESRD patients is only one-fourth to

mortality one-sixth that of the age-matched general population.
associated with
chronic
hemodialysis?

What is the Cardiovascular disease

leading cause
of death in
these patients?

Do statins Observational studies suggest decreased CV mortality;

lower the risk however, the one randomized control trial (RCT) failed to
of CV mortality show a statistically significant benefit. Further studies are
in patients on needed.
hemodialysis?

What is Modality of hemodialysis utilized in the ICU for critically ill,

continuous hemodynamically unstable patients. CRRT uses lower blood
renal flow rates and lower dialysate flow rates along with a slower
replacement removal of body fluid to maximize stability of blood
therapy pressure. Since the flow rates are lower, CRRT needs to run
(CRRT)? continuously to ensure removal of toxins.
 What do the
following terms
mean for the
various forms
of CRRT:

CVVH? Continuous venovenous hemofiltration. Here there is no

dialysate solution and removal of toxins and body water is
through ultrafiltration only.

CVVHD? Continuous venovenous hemodialysis. Here there is a dialysis

solution that is used to remove solutes via diffusion.

CVVHDF? Continuous venovenous hemodiafiltration. This modality

combines dialysis and hemofiltration to maximize solute and
water removal.

What is SLED? SLED is slow, low-efficiency dialysis. This is another form of

slower dialysis similar to CRRT that runs for 6 to 12 hours
during the day and not continuously.

Is there a No. Clinical trials have not conclusively determined that one
preferred modality is superior to another.
modality of
hemodialysis
therapy in the
ICU?

P.417

Peritoneal Dialysis
How is fluid A hypertonic solution of dextrose is used as the dialysate.
removed from Water from the vascular space enters the peritoneal cavity
the body with down the osmotic gradient, and then this excess ultrafiltrate
PD? is drained out by the patient.

What are the 1. Peritonitis

common 2. Failure of the peritoneal membrane to act as an
complications effective dialyzer
of PD? 3. Catheter malfunction
4. PD fluid leaks (either internal or external)
5. Hernia development

What are the Abdominal pain, fever, cloudy dialysate

 symptoms/signs
of peritonitis?

How is Finding of WBCs >100/mm 3 in a dialysate sample.

peritonitis
diagnosed?

What are the Staphylococcus aureus, Staphylococcus epidermidis,

most common enterococci, gram-negative organisms including Pseudomonas
organisms spp.
associated with
peritonitis?

What is the First-generation cephalosporin (cefazolin) or vancomycin in

correct empiric combination with either an aminoglycoside or third- or
therapy for PD- fourth-generation cephalosporin. Generally, antibiotics
associated should be given intraperitoneally to maximize efficacy.
peritonitis?

P.418
P.419
P.420
P.421
P.422

Kidney Transplantation
How does the cost The average yearly cost of hemodialysis is $50,000. The
of a kidney cost of a kidney transplant is $100,000 for the first year
transplant compare and then approximately $10,000 per year after this.
with that of After 4 years, the overall costs of successful kidney
hemodialysis? transplantation are lower than those of dialysis.

How does the Overall, after 100 days posttransplant, a mortality

survival of patients advantage is seen in patients receiving a transplant. The
receiving a kidney magnitude of the survival benefit of transplantation
transplant compare varies according to patient age and comorbidities and is
with that of those greatest in young diabetics.
remaining on
dialysis?

What are the There are at least two different signals:

events required for 1. Binding of the foreign antigen presented by the HLA
T-cell activation? antigen to the T-cell receptor.
2. Interaction of accessory molecules on T-cells and
 antigen-presenting cells (such as between CD28 and
B7).
3. A third signal is due to elaboration of cytokines
(especially IL-2), which leads to T-cell activation,
cell division, and clonal expansion.

How are these 1. With agents that target signal 1: these include
events utilized to monoclonal (OKT3) and polyclonal (thymoglobulin)
design agents targeted to the T-cell receptor complex. The
immunosuppressive drugs tacrolimus and cyclosporine inhibit IL-2
therapy? production through blockade of calcineurin.

1. Agents that block this step are in development.

2. The humanized monoclonal antibodies basiliximab
and daclizumab are targeted against the IL-2
receptor. Sirolimus acts on the signaling pathway
downstream from the cytokine receptor.
Mycophenolate mofetil and azathioprine impair de
novo nucleotide synthesis and cell division.

What HLA antigens HLA A (class 1), B (class 1) and DR (class 2). Since we
are routinely inherit one allele from each parent, six potentially
tested for prior to unique antigens can be present in an individual. Blood
transplantation? group antigens are also tested, and while transplants can
be undertaken across mismatched ABO blood types,
there is an extremely high likelihood of rejection and
special protocols are required.

At what GFR can a GFR of 20 mL/min

person be placed
on the waiting list
for a kidney
transplant?

What are the 1. Cadaveric versus live donor: superior outcomes with
factors that live donation
determine the 2. HLA-matching: superior outcomes with five- or six-
outcome of kidney antigen matched kidneys.
transplantation? 3. Race: poorer outcomes in blacks
4. Recipient age: worse outcomes in the very young and
old
5. Donor age: worse outcome with increasing age
6. Comorbidities: worse outcome in diabetics, hepatitis
C-positive
 7. Rejection: worse outcome with prior episodes of
rejection

What is the typical Tacrolimus or cyclosporine plus mycophenolate mofetil

immunosuppressant (MMF) plus prednisone
protocol utilized
posttransplant?

What are This class of medications includes tacrolimus and

calcineurin cyclosporine. These drugs block the expression of critical
inhibitors? cytokine genes such as IL-2

What are the major Nephrotoxicity including chronic kidney disease,

side effects of hypertension, hyperkalemia, hypomagnesemia,
calcineurin hypertrichosis (cyclosporine), alopecia (tacrolimus),
inhibitors? gingival hyperplasia (cyclosporine), hyperlipidemia
(cyclosporine), glucose intolerance, (tacrolimus),
neurotoxicity (taciolimus), infections and malignancy

What is the risk of Increased risk of rhabdomyolysis with all statins (lower
using a statin with likelihood with pravastatin)
a calcineurin
inhibitor?

What is the MMF inhibits the production of de novo purine synthesis

mechanism of which is required for cell division of lymphocytes.
action of
mycophenolate
mofetil (MMF)?

What are the side The major side effects are GI: diarrhea, nausea,
effects of MMF? vomiting. Other side effects are leukopenia,
thrombocytopenia, and increased risk for infections.

What is sirolimus? Immunosuppressant that blocks the downstream effects

of IL-2 to inhibit cytokine-mediated cellular
proliferation. It can be exchanged for calcineurin
inhibitors when toxicity of these drugs warrants a switch.

What is It is made by immunization of rabbits with human

thymoglobulin? lymphoid tissue and is a polyclonal antibody preparation
used at the time of transplantation (induction therapy)
to deplete peripheral lymphocytes.

How is acute Rise in serum creatinine or rarely, pain over the

rejection allograft. Rejection is diagnosed with a biopsy of the
manifested? allograft.

What do biopsies in The biopsy typically reveals an acute inflammatory

acute rejection infiltrate surrounding the renal tubules and occasionally
show? (in more severe cases) involving the vasculature or
glomerulus.

How is acute 1. Pulse high-dose corticosteroids

rejection treated? 2. If severe, thymoglobulin may also be used
3. Intensification of immunosuppression

What are the 1. Better short- and long-term results

advantages of 2. Lower incidence of delayed graft function
living kidney 3. Avoidance of long wait for cadaveric transplant
donation? 4. Capacity to optimally time transplant procedure

What are the 1. Donor operative mortality (less than 1 in 2000)

potential risks to 2. Operative and post-op morbidity and recovery time
the donor? 3. Post-op complications
4. Increased risk of long-term hypertension and perhaps
proteinuria

What is the 1. Education

evaluation process 2. ABO blood type and cross-match
for a potential 3. Complete history and physical
donor? 4. Comprehensive lab screening (CBC, chemistries, HIV,
lipids, hepatitis B, C, CMV, glucose tolerance test)
5. Urine for creatinine clearance, proteinuria
6. CXR, ECG, and possibly stress test
7. CT or MRI of the kidney

What are the 1. Age <18 or >70 years (differs across programs)
exclusion criteria 2. Hypertension
for living donation? 3. Diabetes
4. Proteinuria
5. Abnormal GFR
6. Hematuria

1. Significant medical illness

2. Obesity
3. Strong family history of renal disease, hypertension,
or diabetes
 4. Psychiatric contraindications

What are the 1. Chronic kidney disease

contraindications 2. Age >70 years (relative)
for cadaveric 3. Potentially metastasizing malignancy
transplantation? 4. Severe hypertension
5. Sepsis
6. IV drug abuse
7. HIV-positive
8. Hepatitis B surface antigenpositive
9. Oliguric acute kidney injury

Is there a higher Yes, the risk for non-skin malignancies is 3.5-fold higher.
incidence of
malignancy in renal
transplant
patients?

What malignancies Lymphomas as well as malignancies related to viral

are noted? etiologies, such as posttransplant lymphoproliferative
disease (EBV) and cervical cancer (HPV)

What is chronic This is a common cause of late graft failure and is due
allograft to both immunological factors (rejection) and
nephropathy? nonimmunological factors (diabetes, hypertension,
hyperlipidemia).

What is the most CMV; thus prophylaxis with an antiviral agent such as
common viral ganciclovir is recommended.
infection after
transplantation?

How does CMV Most commonly as fever, malaise, leukopenia, and

infection present? transaminitis. More severe presentations include
pneumonitis, gastritis, esophagitis, and hepatitis.

What other TMP/SMX to prevent PCP and oral nystatin to prevent

prophylactic thrush
antimicrobials are
given to kidney
transplant
patients?

P.423
Major Trials in Nephrology
1. Prevention of Diabetic Nephropathy: Role of Angiotensin Blockade

a. Type 1 diabetes: Lewis et al. (N Engl J Med 1993;329:1456) demonstrated

that the ACEI captopril significantly slowed the progression of renal disease
in type I diabetics as compared to a group of patients treated with other
agents to an equivalent blood pressure.

b. Type 2 diabetes: Two studiesRENAAL ( N Engl J Med 2001;345:861) and IDNT

(N Engl J Med 2001;345:851)in type 2 diabetic patients with nephropathy
have demonstrated that the ARBs losartan and irbesartan, respectively,
significantly slowed the progression of renal disease as measured by either
the doubling of serum creatinine or development of ESRD.

2. Prevention of Diabetic Nephropathy: Role of Glycemic Control

a. The Diabetes Control and Complication Trial demonstrated that intensive

glycemic control could lessen the risk of development and slow the
progression of diabetic nephropathy. There was no clear threshold value of
HgBA1C but progression was slow, with values less than 7.5% (N Engl J Med
1993;329:977).

b. The UKPDS (United Kingdom Prospective Diabetes Study) demonstrated that

blood pressure control had a much larger effect on slowing progression of
nephropathy than glycemic control (Br J Med 1998;317:693).

3. Prevention of Progressive Chronic Kidney Disease

a. The role of blood pressure control: The Modification of Diet in Renal Disease
(MDRD) study evaluated whether lower blood pressure targets gave greater
renoprotection. Recommendations based upon a secondary analysis of this
trial were that in patients with proteinuria of >1 g/day, blood pressure below
125/75 mm Hg was associated with a slower rate of renal disease progression
(Ann Intern Med 1995;123:754).

b. The role of angiotensin blockade: In the REIN study, 352 patients with
nondiabetic CKD randomized to either ACE-inhibitor or placebo with equal
blood pressure in both groups. The ACE-inhibitor group had a much slower
rate of progressive CKD, especially in those patients with urine protein >3
g/day (Lancet 1997;349:1857).

c. The role of dihydropyridine calcium channel blockers: In the African

American Study of Kidney Disease (AASK), patients with CKD and hypertension
were randomized to either an ACEI, a dihydropyridine calcium channel
blocker (amlodipine), or a beta blocker. The amlodipine arm of the trial was
stopped early due to more rapid progression of CKD in this arm, especially in
those patients with proteinuria >1 g/day (JAMA 2001;285:2719).

d. The role of protein-restricted diets: The MDRD study (above) randomized

 patients to either 1.3 g/kg/day (usual) or 0.58 g/kg/day (low) protein diets.
A second arm of the study added a very low (0.28 g/kg/day)
P.424
arm. Primary analysis of the results demonstrated no significant
renoprotection associated with the low-protein diet. Secondary analysis
revealed benefit from the low-protein diet in those patients with a greater
initial decline in renal function, and extrapolation of the trends in decline in
GFR predicted a benefit if the trial had been extended in length.

4. Prevention of Contrast Nephropathy

a. While no trials of deliberate hydration have been tested in a randomized trial

versus no therapy, the study by Solomon et al. (N Engl J Med 1994; 331:1416)
demonstrated that a protocol of IV hydration with 0.45% saline led to a lower
incidence of contrast nephropathy (defined as a 0.5 mg/dL or greater rise in
serum creatinine within 48 hours of the procedure) as compared with saline
plus either mannitol or furosemide.

b. Aspelin et al. (N Engl J Med 2003;348:491) demonstrated that the iso-

osmolar contrast agent iodixanol led to fewer instances of contrast
nephropathy as compared to low-osmolar contrast agents in patients at high
risk for developing AKI.

c. Tepel et al. (N Engl J Med 2000;343:180) demonstrated that oral N-

acetylcysteine 600 mg twice a day in addition to 0.45% saline before and
after the procedure led to a significant reduction (2% versus 21%) in the
development of contrast nephropathy in high-risk patients. Subsequently,
Marenzi et al. (N Engl J Med 2006;354:2773) demonstrated the superiority of
a regimen of N-acetylcysteine (1200-mg IV bolus before angioplasty followed
by 1200 mg orally twice daily for 48 hours) over either a 600-mg dose of N-
acetylcysteine or IV fluids alone.

d. Merten et al. (JAMA 2004;291:2328) demonstrated in a prospective

randomized trial of 119 patients at high risk for the development of contrast
nephropathy that IV hydration with an isotonic solution of sodium bicarbonate
was superior to that of saline (1.7% versus 13.6% developed contrast
nephropathy in each group respectively).

5. Renal Artery Stenosis

Three randomized controlled trials have investigated the blood pressure

outcomes of medical therapy versus percutaneous transluminal renal angioplasty
in patients with renal artery stenosis. Webster et al. (J Hum Hypertens
1998;12:329) studied 55 patients and showed no difference in blood pressure,
renal function, or survival in either group. Plouin et al. (Hypertension
1998;31:822) studied 49 patients and showed no difference in blood pressure but
slightly fewer antihypertensive medications in the angioplasty group. In the
largest study, van Jaarsveld et al. (N Engl J Med 2000;342:1007) studied 106
 patients and once again showed no difference in blood pressure between the
groups at 12 months. However, 44% of the patients in the medical therapy arm
crossed over to receive subsequent angioplasty.

P.425
6. Hemodialysis

a. The National Cooperative Dialysis Study (NCDS) (N Engl J Med 1981; 305:1176
1181) set the initial guidelines for dosing of hemodialysis and demonstrated
that focusing on a minimum amount of urea clearance was important to
ensure good outcomes.

b. The HEMO Study (N Engl J Med 2002;347:2010) evaluated the potential

benefits of increasing the dialysis dose above currently recommended target
levels. There was no significant difference in mortality between the high and
standard dialysis dose groups.

7. Continuous Renal Replacement Therapy:

Mehta et al. (Kidney Int 2001;60:1154) conducted the only randomized

controlled trial of CRRT (84 patients) versus standard intermittent hemodialysis
(82 patients) in patients with acute renal failure in the intensive care unit.
Intermittent hemodialysis resulted in a lower mortality (41.5%) than occurred
with CRRT (59.5%). However, despite the randomization process, patients
allocated to CRRT had more severe illness. Several other trials have not shown a
significant benefit of CRRT over conventional intermittent dialysis (Lancet
2006;368:379).

8. Hepatorenal Syndrome

Angeli et al. (Hepatology 1999;29:1690) demonstrated significant benefit of

combined therapy with IV albumin, octreotide, and midodrine in patients with
hepatorenal syndrome. Those patients treated with these drugs demonstrated
improved renal function and urine output. This has recently been confirmed in
another study with a larger number of subjects (Dig Dis Sci 2007;52:742).
Editors: Bergin, James D.
Title: Advanced Medicine Recall, 1st Edition
Copyright 2009 Lippincott Williams & Wilkins

> Table of Contents > Section II - The Specialties > Chapter 9 - Oncology

Chapter 9
Oncology

P.427

Abbreviations
ACS American Cancer Society

AFP Alpha-fetoprotein

AIDS Acquired immunodeficiency syndrome

ALL Acute lymphocytic leukemia

AML Acute myeloid leukemia

CBC Complete blood count

CLL Chronic lymphocytic leukemia

CML Chronic myelogenous leukemia

CNS Central nervous system

CT Computed tomography

DCIS Ductal carcinoma in situ

DIC Disseminated intravascular coagulation

EBV Epstein-Barr virus

EGGCT Extragonadal germ-cell tumor

ERCP Endoscopic retrograde cholangiopancreatography

5-FU 5-Fluorouracil

GCT Germ-cell tumor

GRFoma Gastrin-releasing factorproducing tumor

Beta-HCG Beta-human chorionic gonadotropin

H&P History and physical examination

HPV Human papillomavirus

HTLV 1 Human T-cell lymphotrophic virus type 1

ITP Idiopathic thrombocytopenic purpura

LCIS Lobular carcinoma in situ

LGL Large granular lymphocyte

MGUS Monoclonal gammopathy of undetermined significance

MRI Magnetic resonance imaging

NHL Non-Hodgkin's lymphoma

NK Natural killer

NSCLC Nonsmall cell lung cancer

NSGCT Nonseminomatous germ-cell tumor

PDA Poorly differentiated adenocarcinoma

PDC Poorly differentiated carcinoma

PP Pancreatic polypeptide

PPoma Pancreatic polypeptideproducing tumor

PSA Prostate-specific antigen

 PSC Primary sclerosing cholangitis

PT Prothrombin time

PTC Percutaneous transhepatic cholangiogram

PTT Partial thromboplastin time

RPLN Retroperitoneal lymph node

RPLND Retroperitoneal lymph node dissection

RTIO Radical transinguinal orchiectomy

SCLC Small cell lung cancer

SLL Small lymphocytic lymphoma

SMA Superior mesenteric artery

SVC Superior vena cava

TNM Tumor, node, metastasis

VIPoma Vasoactive intestinal polypeptideproducing tumor

WBC White blood cell

WDLL Well-differentiated lymphocytic lymphoma

P.428
P.429

Oncologic Emergencies

Spinal Cord Compression

What are the most Lung, breast, prostate, lymphoma, and multiple
common myeloma. Other more unusual cancer causes are
malignancies colorectal, melanoma, sarcoma, and renal cell
involved in spinal carcinoma.
cord compression?

In a cancer patient Plain radiographs of the affected area.

with back pain and
no neurologic
symptoms, what is
the first study that
should be done?

What should be If the plain films show evidence of metastatic cancer, an

done if the plain MRI should be done on an outpatient basis.
films show
metastatic
changes?

What should be If the plain films are negative, a bone scan should be
done if the plain done.
films are negative
for metastatic
changes?

Can a patient have Yes. Therefore, if neurologic symptoms are present, an

spinal cord MRI of the spine to rule out cord compression should be
compression with done.
normal plain
radiographs?

What is the A CT myelogram is probably the most specific and

radiographic study sensitive study. However, MRI has virtually supplanted
of choice to rule the myelogram as the initial study because it is nearly as
out spinal cord accurate, noninvasive, and quicker.
compression?

What is the Poor. Few patients with paraplegia regain neurologic

prognosis for function. Most patients (80%) who are ambulatory at the
regaining lost time of treatment are ambulatory after treatment. As
neurologic many as one third of patients with mild to moderate
function? neurologic dysfunction have improvement of symptoms
with treatment.

Who should receive Patients with a known radiation-sensitive tumor and no

radiotherapy for spinal instability, those with spinal involvement without
the treatment of spinal instability or neurologic deficit, or for palliation in
spinal cord patients who are poor candidates for surgery
compression?

Who should receive Patients with a pathologic fracture with spinal instability
surgery followed by or compression of the spinal cord by bone, patients with
radiation in radiation-resistant tumors with neurologic deficits, and
 treatment of spinal patients with an unknown tissue diagnosis
cord compression?

Who should receive Patients whose tumors relapse or fail to respond to

surgery alone in radiation
treatment of spinal
cord compression?

Who should receive Pediatric patients with responsive tumors, adults with
chemotherapy responsive tumors, and patients whose tumors relapse at
alone in treatment a site of radiation and surgery
of spinal cord
compression?

Increased Intracranial Pressure

When is surgery indicated in 1. To make a diagnosis
cases of increased intracranial 2. If symptoms are refractory or
pressure presumed to be progressive after medical or radiation
related to cancer? therapy
3. If the patient has had good performance
status with a single metastasis and a
long disease-free interval

What are the usual LP results The glucose level is usually less than 45
regarding glucose and protein mg/dL, the protein level is generally
levels? increased.

What is the treatment for Whole brain radiation therapy. Intrathecal

carcinomatous meningitis? chemotherapy is occasionally successful for
a short time, depending on the underlying
tumor type.

What is the prognosis for Generally poor, with median survival in the
patients with carcinomatous 4- to 6-month range
meningitis?

P.430

Superior Vena Cava Syndrome

What are Malignant causes (80% to 90% of cases)most commonly, lung
the causes cancer, lymphoma, thymoma, GCTs, and breast cancer
of SVC Nonmalignant causes (10% to 20% of cases)histoplasmosis with
syndrome? mediastinal fibrosis, syphilis, tuberculosis, and thrombosis,
 usually as a result of an indwelling central venous catheter

Hypercalcemia
What is the Aggressive hydration is the mainstay. Diuretics after
treatment for aggressive intravenous hydration can enhance kaliuresis but
hypercalcemia? should not be initiated until the patient has been generously
hydrated. Bisphosphonates are effective and are commonly
used after rehydration.

Hyperuricemia
What Acute leukemias, high-grade lymphomas, and
malignancies myeloproliferative disorders (including CML)
are commonly
associated with
hyperuricemia?

What is the Prophylactic measures need to be undertaken before

management cytotoxic chemotherapy. Medications that lead to an
of elevated serum uric acid or that acidify urine are
hyperuricemia? discontinued. Allopurinol is started, intravenous hydration is
begun to maintain good urine output, and urine is alkalinized
with sodium bicarbonate to a pH of 7.0 to 7.5.

Tumor Lysis Syndrome

Which labs need to be Serum uric acid, phosphate and uric acid. These
monitored for tumor lysis are released from the breakdown of malignant
syndrome? cells.

How is tumor lysis Hydration and alkalinization of the urine (the

syndrome treated? urinary pH is maintained at 7.0 to 7.5)

What prophylactic therapy Allopurinol. The dose often needs to be

should be used in patients adjusted for renal insufficiency in this setting.
with a large tumor burden Rasburicase, a recombinant urate oxidase
who are at risk for tumor enzyme, is indicated as prophylaxis in pediatric
lysis syndrome? patients at high risk for tumor lysis syndrome.
Its use in adults has not been studied in
randomized controlled trials.

P.431

Neutropenic Fever
 Which patients with Those with prolonged neutropenia and those with
neutropenia are at immunodeficiencies as a result of their primary
greatest risk for disease or therapy (e.g., leukemias and lymphomas)
infection?

Are there cases where Consider additional coverage for gram-positive

additional coverage organisms for severe mucositis or any indwelling
should be considered? catheters.

What should be done If fevers persist after 2 to 5 days, agents that are
if fevers persist effective against fungi should be considered.
despite antibiotics?

Acute Leukemia
What are urgent Neurologic findings including altered mental status,
clinical findings in seizures, headache, and cranial nerve palsies or other
acute leukemia? focal neurologic signs, suggesting leukemic meningitis,
leukostasis, or bacterial meningitis
Pulmonary edema secondary to leukostasis
Tumor lysis
Hemorrhage (CNS, visceral, or gastrointestinal)
Infection or fever with or without neutropenia

What are the Leukophoresis and hydroxyurea acutely, with initiation of

treatment options induction chemotherapy as soon as possible
for leukostasis with
neurologic
findings?

How do you RBC and platelet transfusion to maintain platelet count

manage >20,000/mm 3 and hematocrit >25 to 30 mg/dL. Check
hemorrhage in for evidence of DIC with PT, PTT, fibrinogen, and D-
acute leukemia? dimer.

P.432

Acute Lymphoid Leukemia

What cytogenetic groups t(9;22), the Philadelphia chromosome; t(4;11);
convey a poor prognosis trisomy 8; and hypodiploidy
in adult ALL?

What is the long-term 30% to 40%. In contrast, nearly 80% of children are
disease-free survival rate long-term disease-free survivors.
 in adults?

What is the standard Vincristine, prednisone, l-asparaginase, and an

induction regimen for anthracycline. The complete remission rate in
ALL? adults is 80% to 90%.

What are the good Hyperdiploidy and complete response to induction

prognostic factors for chemotherapy
ALL?

What are the bad Adverse cytogenetics, WBC >50,000/mm 3 , age

prognostic factors for older than 60 years, and time to complete
ALL? response of >4 to 6 weeks

P.433

Acute Myeloid Leukemia

What is the basis for Cytogenetics, molecular genetics, therapy related
WHO reclassification AMLs, and biphenotypic leukemias (with features of
of AML? AML and ALL)

Which subtype of Promyelocytic

AML is commonly
associated with DIC?

What vitamin Transretinoic acid

induces a complete
remission in 90% of
patients with
promyelocytic
leukemia?

What percent of AML 50% to 70%

patients achieve
complete remission
with induction
chemotherapy?

What is the standard Cytarabine (100 mg/m 2 ) by continuous infusion over 24

induction regimen
hours for 7 days and daunorubicin (45 mg/m 2 )
for AML patients?
intravenously for 3 days (commonly abbreviated as 7 +
3)

How many patients None. They all need some form of consolidation
 are cured if they go chemotherapy.
into complete
remission?

What is the 5-year Varies dramatically with underlying cytogenetics: 60%

survival rate in for good cytogenetics t(15;17), t(8;21), and inv(16);
patients who 40% for normal cytogenetics; 20% or less for poor
undergo treatment cytogenetics [such as del(5), del(7) and complex
for AML? karyotypes]

What are good De novo leukemia (i.e., leukemia that is not preceded
prognostic factors by a myelodysplastic syndrome), young age, and
for AML? presence of specific cytogenetic abnormalities,
including t(15;17), t(8;21), and inv(16)

What are poor Leukemia evolving out of a prior myelodysplastic

prognostic factors syndrome or associated with prior alkylating
for AML? chemotherapy, advanced age, high peripheral WBC
count, and the presence of the following cytogenetic
abnormalities: 5, 5q, 7, +8

Lymphoproliferative Disorders
What are the CLL, hairy cell leukemia, LGL leukemia, lymphoma (e.g.,
lymphoproliferative Hodgkin's disease and NHL), and plasma cell dyscrasias
disorders? (e.g., multiple myeloma and Waldenstrm's
macroglobulinemia)

P.434

Chronic Lymphocytic Leukemia

Patients with Both bacterial and viral infections secondary to
CLL are hypogammaglobulinemia and defects in cell-mediated immunity
susceptible
to what
types of
infections?

Do patients Yes. Autoimmune hemolytic anemia occurs in 10% to 25% of

with CLL cases. ITP and pure red blood cell aplasia are also more
have an common in CLL.
increased
incidence of
autoimmune
diseases?
With regard Frequently, there is lymphadenopathy and splenomegaly.
to the
diagnosis of
CLL, what
are the usual
physical
exam
features?

With regard An increase in the absolute number of lymphocytes in the

to the peripheral blood, which, on the peripheral smear, appear
diagnosis of morphologically as small, mature lymphocytes
CLL, what is
seen on
peripheral
blood smear?

With regard Flow cytometry shows a monoclonal population that

to the coexpresses CD19 and CD5.
diagnosis of
CLL, what is
seen on flow
cytometry?

What is the Lymphoproliferative disorders such as the leukemic phase of

differential follicular lymphoma, monocytoid B-cell lymphoma, mantle cell
diagnosis for lymphoma, SLL, LGL syndrome, lymphoplasmacytic lymphoma,
CLL? Szary cell lymphoma, hairy cell leukemia, splenic lymphoma
with villous lymphocytes, and Waldenstrm's
macroglobulinemia. A few of the nonmalignant causes of
lymphocytosis include tuberculosis, mononucleosis, and
pertussis infection.

What is the Varies dramatically with stage and cytogenetics. With low-risk
median cytogenetics (isolated 13q deletion), median survival is >10
survival years; with high-risk cytogenetics (17p deletion, p53 gene),
expectation median survival is 4 to 5 years.
for a person
with CLL?

What is the Stage 0: lymphocytosis alone; 15 years

Rai staging Stage I: lymphocytosis with lymphadenopathy; 9 years
system for Stage II: lymphocytosis with spleen or liver involvement; 5
CLL and years
 survival for Stage III: lymphocytosis with anemia; 2 years
each stage? Stage IV: lymphocytosis with anemia and thrombocytopenia; 2
years

What is the Observation if the patient is asymptomatic

treatment for
asymptomatic
patients with
CLL?

What is the Oral alkylating agents or fludarabine are commonly used in

treatment for symptomatic patients.
symptomatic
patients with
CLL?

P.435

Hairy Cell Leukemia

What is The bone marrow is often difficult to aspirate, resulting in a
often noted dry tap.
on bone
marrow
aspiration?

How is the By the appropriate clinical scenario and by hairy cells seen on
diagnosis of peripheral smear or bone marrow examination. A special stain
hairy cell called TRAP (tartrate-resistant acid phosphatase) is
leukemia confirmatory, as is flow cytometric data.
made?

Large Granular Lymphocyte Syndrome

What is an On peripheral smear, an LGL appears as a large lymphocyte
LGL? with abundant pale cytoplasm with prominent azurophilic
granules.

What is the Chronic, sometimes severe neutropenia with frequent bacterial

presentation infections. Infiltration of the spleen, bone marrow, and liver are
of T-cell not uncommon. Interestingly, 25% of cases are associated with
LGL? rheumatoid arthritis, making it difficult to distinguish from
Felty's syndrome.

What is the Usually, an acute clinical course involving fever and B symptoms
presentation (e.g., fever, drenching night sweats, anorexia, weight loss).
 of NK-cell Anemia and thrombocytopenia are more common than with T-
LGL? cell LGL. Massive hepatosplenomegaly, lymph node involvement,
and gastrointestinal symptoms are common.

P.436

Lymphoma
What are B symptoms? Fever, drenching night sweats, anorexia, and
weight loss

What are typical physical Lymphadenopathy and hepatosplenomegaly are

findings in lymphoma? the most predominant findings.

Hodgkin's Disease
What are the WHO Nodular lymphocyte predominant and classic
histologic subtypes of Hodgkin's lymphoma (classic further divided into
Hodgkin's disease? nodular sclerosing, mixed cellularity, lymphocyte
rich, and lymphocyte-depleted)

What are the stages in the Stage I: involvement of a single lymph node
Modified Ann Arbor staging region or single extralymphatic site (IE); 90%
system and the Stage II: involvement of two or more lymph
corresponding 5-year node regions on the same side of the diaphragm
survival rates? or localized extranodal extension plus one or
more nodal regions (IIE); 80% to 90%
Stage III: involvement of lymph node regions on
both sides of the diaphragm, may be
accompanied by localized extralymphatic
extension (IIIE) or splenic involvement (IIIS); 60%
to 85%
Stage IV: diffuse or disseminated involvement of
one or more extralymphatic organs or tissues
with or without associated lymph node
involvement; 50% to 60%

What are the dominant Stage, presence of extranodal disease, bulk of

factors that determine disease, and the presence of B symptoms.
therapy in Hodgkin's Histologic subtype has little or no bearing on
disease? choice of therapy.

How is bulky disease Bulky disease within the chest is defined as

defined? lymphadenopathy greater than one third of the
diameter of the chest. Bulky disease elsewhere
is defined as lymphadenopathy >10 cm.
 What are late Acute leukemia and myelodysplasia as a result of
complications of treatment alkylating agent chemotherapy
of Hodgkin's disease? Solid tumors within and adjacent to the
radiation port
Cardiac disease as a result of radiation and
doxorubicin (Adriamycin) exposure
Sterility and hypothyroidism

P.437

Non-Hodgkin's Lymphoma
What is the staging The Modified Ann Arbor staging system; see under
system for NHL? Hodgkin's disease above

What monoclonal Rituximab targets the CD20 receptor and is being

antibody therapy is investigated as initial therapy, in chemotherapy
used in the treatment combinations, and as single agent maintenance
of NHL? therapy.

Plasma Cell Dyscrasias

What are the MGUS, multiple myeloma, Waldenstrm's
major plasma macroglobulinemia, and amyloidosis
cell dyscrasias?

What are the An MGUS must have:

diagnostic Serum M protein <3.5 g/dL (IgG) or <2 g/dL (IgA) <10%
criteria for an plasma cells in the bone marrow
MGUS? Urine light chains <1 g/24 hr
No lytic bone lesions

Does an MGUS Yes. 1% to 2% per year progression to myeloma. Recently

transform into a the serum-free light chain has been used to help determine
plasma cell risk of progression in a single patient and is gaining wider
dyscrasia? use.

P.438

Multiple Myeloma
Do all patients No. Only 80% of patients have an M protein in serum; 20%
with multiple have only light chains, which must be measured in a 24-
myeloma have a hour urine collection, or with the new serum light chain
monoclonal assay. Approximately 1% of patients with multiple myeloma
protein in the are termed nonsecretors and have no identifiable
 serum? monoclonal protein.

In nonsecretors, On staining of the plasma cells, the protein is shown to be

where is the within the cytoplasm, but the plasma cells cannot excrete
immunoglobulin? the immunoglobulin molecule.

What are some Thalidomide analogs and bortezomib, a proteasome

of the newer inhibitor. Allogeneic bone marrow transplantation can cure
treatments for the disease, but its use is limited because multiple
multiple myeloma is a disease of the elderly. Nonmyeloablative
myeloma? transplantation is being investigated. High-dose
chemotherapy with peripheral stem cell rescue has been
shown to lengthen time to relapse compared with standard
therapy; however, long-term disease-free survival is
limited.

What is the Untreated, 6 months; treated, 2 to 3 years; 5-year survival

median survival? is <10%

P.439

Waldenstrm's Macroglobulinemia
What are the
differences between
Waldenstrm's
macroglobulinemia
and

multiple myeloma in
respect to the
following?

Physical findings Patients with Waldenstrm's macroglobulinemia

commonly have lymphadenopathy with
hepatosplenomegaly and rarely have bone lesions.

Paraproteins By definition, Waldenstrm's macroglobulinemia must

involve a monoclonal IgM paraprotein, whereas in
multiple myeloma, IgG and IgA are the most common
immunoglobulins involved.

Neoplastic cells Waldenstrm's macroglobulinemia shows

lymphoplasmacytic morphology, and the neoplastic
cell in multiple myeloma is a plasma cell.
 Symptom complex Hyperviscosity is a more common problem in
Waldenstrm's macroglobulinemia.

What are common Weakness, fatigue, oral and nasal mucocutaneous

presenting symptoms bleeding, symptoms attributable to splenomegaly, and
of Waldenstrm's symptoms attributable to hyperviscosity
macroglobulinemia?

What is the median 3 to 5 years, but expected to improve with newer,

survival for patients more effective therapies
with Waldenstrm's
macroglobulinemia?

P.440

Head and Neck Cancer

What percent of patients 30%, but this amount varies with tumor
present with localized location
disease?

When a patient is first seen, Supraglottic larynx, oropharynx, and

at which anatomic locations is hypopharynx
disease more commonly
advanced?

What are the staging criteria Each site has its own specifics. The four
for head and neck cancer? general stages are (I) local, (II) locally
advanced but resectable, (III) locally
advanced but unresectable, and (IV)
metastatic.

What is the general treatment Local diseaseradiation or surgery with

approach for head and neck curative intent. Radiation chosen when organ
cancer? preservation is important, as in laryngeal
cancer
Resectable locally advanced diseasesurgery
followed by radiation with concurrent
chemotherapy
Unresectable locally advanced disease
concurrent chemotherapy and radiation
Metastatic diseasepalliative chemotherapy
and or palliative radiation

What is the surgical procedure Wide local excision with ipsilateral radical
 for head and neck cancer? neck dissection. Contralateral radical neck
dissection is performed if clinical or
radiologic evidence of disease is present
within the contralateral neck.

What is the 5-year survival

rate for the following:

Local disease? 60% to 90%

Locally advanced disease? 30%

Metastatic disease? <5%

What is the incidence of new Each year, a new cancer of the aerodigestive
aerodigestive cancers arising epithelium develops in 3% to 7% of patients.
in a patient previously This effect is referred to as field
rendered disease-free from a cancerization.
head and neck cancer?

P.441

Breast Cancer
What inherited It is estimated that 5% to 10% of all cases of breast
genetic cancer in the United States are related to inherited
abnormalities are genetic abnormalities.
associated with Genes involved include BRCA1, BRCA2, PTEN (associated
breast cancer? with Cowden syndrome), TP53 (associated with Li-
Fraumeni syndrome), and STK11 (associated with Peutz-
Jegher's syndrome)

What percentage 6%
of patients with
breast cancer
present with
metastatic
disease?

Is lumpectomy plus Yes. This has been confirmed by seven studies. About 25%
radiation of women require mastectomy because it is necessary for
equivalent to complete excision or because radiation is contraindicated
mastectomy in the in the patient.
primary
management of
breast cancer?
 What is the role of Stem cell transplantation had shown initial promise in
bone marrow patients with locally advanced or metastatic disease;
transplantation in however, subsequent randomized controlled trials showed
the management no survival benefit for autologous bone marrow
of breast cancer? transplantation.

What monoclonal Herceptin targets the HER2/neu antigen and is available

antibody therapy is to individuals with tumors that overexpress HER2/neu. It
available to is most effective when combined with cytotoxic therapy,
individuals with and its use was recently expanded to the adjuvant
breast cancer? setting.

What is the 5-year Roughly 80% to 85% for all stages. For women with
survival rate for cancers localized to the breast, the 5-year survival rate
women with breast is 96%. Women with regional metastases (positive axillary
cancer? node involvement) have a 75% 5-year survival rate. Those
with distant metastases have a 20% 5-year survival rate.

P.442
P.443

Lung Cancer
What are the chest
radiograph findings
for the following
histologies?

Squamous cell A central lesion with hilar involvement and frequent

carcinoma? cavitation

Adenocarcinoma? A peripheral lesion, which can also cavitate

Bronchoalveolar Peripheral, sometimes multifocal, ground-glass opacity

carcinoma?

Large cell Usually a peripheral lesion, which can cavitate

carcinoma?

Small cell A central lesion with hilar mass and early mediastinal
carcinoma? involvement, which does not cavitate

How is SCLC Limited and extensive.

staged?
What is limited In limited-stage SCLC, all disease is within a single
SCLC disease? radiation port within the chest and supraclavicular fossa

What is the cure There is a 15% to 20% cure rate in limited SCLC with
rate for limited combined radiation and chemotherapy.
SCLC?

What is Extensive-stage SCLC extends outside a single radiation

extensive SCLC port within the chest.
disease?

What is the Combination chemotherapy offers a 60% to 90% response

treatment of rate with a median survival for all patients of 9 to 11
extensive-disease months. In untreated disease, the median survival is 6
SCLC? weeks.

What is the current Cisplatin or carboplatin and etoposide

chemotherapy
standard for SCLC?

What is the staging Stage I: negative nodal involvement and an easily

of NSCLC? resectable tumor
Stage II: resectable tumor with ipsilateral peribronchial
or hilar node involvement
Stage IIIA: potentially resectable tumor with positive
ipsilateral mediastinal and/or subcarinal lymph node
involvement
Stage IIIB: any tumor with contralateral lymph node or
supraclavicular lymph node metastases. Any tumor,
regardless of lymph node status, that invades the
mediastinum, heart, great vessels, trachea, esophagus,
vertebral body, or carina, or has a malignant pleural
effusion. Not surgically resectable.
Stage IV: distant metastases

What is the Stages I and II: surgical resection. Role for adjuvant
treatment of chemotherapy under investigation. Some trials show
NSCLC? benefit for stage II.
Stage IIIA: neoadjuvant chemotherapy radiation
followed by surgery in resectable patients. Patients who
are found to have stage IIIA after surgical resection
(microscopic N2 involvement) benefit from adjuvant
chemotherapy. Unresectable patients are treated with
radiation and concurrent chemotherapy.
Stage IIIB: radiation with concurrent chemotherapy.
 Stage IV: combination chemotherapy for patients with
good performance status improves survival and quality of
life.

What are the Carboplatin, cisplatin, paclitaxel, gemcitabine, navelbine

commonly used in combination for first-line therapy. Bevacizumab, an
chemotherapy antibody against vascular endothelial growth factor
drugs for NSCLC? (VEGF) in combination with carboplatin and paclitaxel
has resulted in the best survival, with median survival
reported around 12 months. Docetaxel, pemetrexed, and
erlotinib as single agents in the second-line setting.

What is the
approximate 5-
year survival rate
of NSCLC for the
following:

Stage I 50%

Stage II 30%

Stage IIIA 20%

Stage IIIB 15%

Stage IV <5%

P.444

Gastrointestinal Cancer

Esophageal Cancer
What are the most Squamous cell and adenocarcinoma
common
histologies of
esophageal
cancer?

What has occurred Adenocarcinoma has been increasing in frequency over

with the histologic the past four decades. In the 1960s, some 10% of
frequency of esophageal cancers were adenocarcinomas. Currently
esophageal nearly 50% of cases are adenocarcinoma.
cancer?
 What is the most The middle third (55%). The esophagus is divided into
common location three portions: upper third, cervical (15%); middle third,
of cancer of the upper and midthoracic (55%); and lower third, lower
esophagus? thoracic (35%).

P.445

Gastric Cancer
What are the Intestinal and diffuse
two histologic
presentations of
gastric
adenocarcinoma?

Where do the Intestinal manifestations arise from precancerous lesions,

intestinal such as gastric atrophy or intestinal metaplasia.
manifestations
arise from?

What is the Intestinal gastric cancer is found in epidemic areas (e.g.,

epidemiology of the Far East). There is a male predominance.
intestinal
cancer?

What are the Diffuse manifestations occur as symptoms of early satiety

symptoms of secondary to the diffuse involvement of the stomach wall.
diffuse gastric
adenocarcinoma?

What is the The name commonly given to this histologic subtype is

common name linitis plastica, which refers to poor distensibility of the
for this entity? stomach as seen on an upper gastrointestinal series.

Where does Local nodal metastases within the wall of the stomach
gastric extending to the duodenum and esophagus and direct
adenocarcinoma extension to adjacent organs are the most common areas
metastasize? of involvement.

How commonly As many as 75% of lesions have spread in this fashion by the
are gastric time of diagnosis.
carcinomas
found to be
metastatic?
 What are the The liver is the most common site of distant metastases.
most common At autopsy, disease involves the liver in 50% of patients,
sites of distant the peritoneum in 25%, the omentum in 20%, and the lungs
metastasis? in 15%.

What is the Because most diagnoses are made late, the prognosis is
prognosis for poor: the 5-year survival rate is approximately 10%. Early
gastric gastric cancer confined to mucosa and submucosa with no
adenocarcinoma? metastases or lymph node involvement has a 90% 5-year
survival rate.

Does adjuvant Intergroup 0116 is the largest of three randomized trials to

therapy improve show a survival benefit for patients who received
survival in postoperative chemoradiotherapy after complete surgical
locally resected resection of their primary gastric carcinoma. Chemotherapy
gastric cancer? was 5-fluorouracil plus leucovorin. Current trials are under
way to determine the optimal chemotherapy.

What is the Palliation of symptoms. Gastric bypass and debulking

treatment for procedures are sometimes useful. Combination
advanced gastric chemotherapy can produce response in 30% of patients, but
cancer? many of those responses are of short duration. Drugs used
include 5-FU, leucovorin, doxorubicin (Adriamycin),
methotrexate, cisplatin, and etoposide.

P.446

Small Bowel Neoplasm

What is a carcinoid Tumor of neuroendocrine cells90% are located in
tumor? the gastrointestinal tract. Midgut carcinoid tumors
are most common.

Where are carcinoid Appendix: 35% to 45%

tumors located? Ileum: 10% to 15%
Right colon: 5%
Other gastrointestinal locations include the rectum
(10% to 15%), duodenum, stomach, gallbladder,
pancreas, esophagus, biliary tract, and Meckel's
diverticulum.

What is the treatment Surgical resection can cure small carcinoids, but
and prognosis for cure is not possible with metastatic disease.
carcinoid tumors of the Somatostatin analog controls the vasomotor
small bowel? symptoms and diarrhea.
 P.447
P.448

Colorectal Cancer
What is the There are approximately 148,610 new cases diagnosed in
incidence and the United States each year and approximately 55,000
death rate of deaths due to colorectal cancer each year.
colorectal
cancer?

What are risk Age: 90% of cases are diagnosed after the age of 50 years.
factors for Genetic factors: familial adenomatous polyposis (FAP) and
developing hereditary nonpolyposis colorectal cancer (HNPCC)
colorectal Inflammatory bowel disease: ulcerative colitis or Crohn's
cancer? disease

Is there anything Diets high in fruits and vegetables and low in animal fats
that will reduce Regular physical activity
the risk of Nonsteroidal anti-inflammatory drugs (NSAIDs) and
developing acetylsalicylic acid (ASA) have been associated with
colorectal reduced risk.
cancer?

How do the two Stage I (T12, N0, M0) = Duke's A

staging systems Stage IIA (T3, N0, M0) = Duke's B
of colorectal Stage IIB (T4, N0, M0) = Duke's B
cancer compare? Stage IIIA (T12, N1, M0) = Duke's C
Stage IIIB (T34, N1, M0) = Duke's C
Stage IIIC (any T, N2, M0) = Duke's C
Stage IV (any T, any N, M1)

For the above T1 = tumor invades submucosa.

staging system, T2 = tumor invades muscularis propria.
what do T1, T2, T3 = tumor invades through the muscularis propria into the
T3, and T4 subserosa or into nonperitoneal or perirectal tissues.
mean? T4 = tumor directly invades other organs or structures
and/or perforates visceral peritoneum.

For the staging N0 = no regional nodal metastases

system, what do N1 = metastasis in 1 to 3 regional lymph nodes
N0, N1, and N2 N2 = metastasis in 4 or more regional lymph nodes
mean?

What do M0 and M0 = no distant metastasis

 M1 mean? M1 = distant metastasis

How is colorectal Surgical resection is the primary modality of therapy for

cancer treated? stages I to III. For select cases of metastatic disease such
as those with a solitary liver metastasis or lung
metastasis, resection of the colorectal primary as well as
the metastatic lesion can result in long-term survival.

What is the 5- Stage I = 93%

year survival for Stage IIA = 85%
colorectal Stage IIB = 72%
carcinoma? Stage IIIA = 83%
Stage IIIB = 64%
Stage IIIC = 44%
Stage IV = 8%

In what stage of Stage III or Duke's C. Randomized trials evaluating

colorectal cancer adjuvant chemotherapy in patients with stage II or Duke's
has adjuvant B have not consistently shown significant survival benefit
chemotherapy in this group of patients; it is therefore not recommended.
been shown to
prolong survival?

Does treatment Median survival of patients with metastatic colorectal

of metastatic cancer who received best supportive care alone is 5 to 6
colorectal cancer months. Median survival of patients with metastatic
improve survival colorectal cancer who are treated with irinotecan or
of these patients? oxaloplatin in combination with 5-FU have a median
survival around 20 to 24 months.

What are the 5FU-based therapy has been the standard for decades.
chemotherapeutic Several new drugs have recently been approved, including
options for irinotecan, oxaliplatin, cetuximab [which is an antibody
patients with against epidermal growth factor receptor (EGFR)],
metastatic bevacizumab [which is an antibody against
colorectal vasculoendothelial growth factor (VEGF)], and
carcinoma? panitumumab (which is also an EGFR inhibitor).

P.449
P.450

Pancreatic Cancer
What is the most Ductal adenocarcinoma comprises >80% of pancreatic
common carcinoma.
histologic
subtype of
pancreatic
carcinoma?

Where in the 70% arise in the head of the pancreas (possibly resulting in
pancreas are biliary obstruction).
most ductal
adenocarcinomas
found?

Besides ductal Many other histologic subtypes are seen and have a better
adenocarcinoma, prognosis. These include carcinoid, lymphoma, sarcoma,
what other cell nonfunctioning islet cell carcinomas, malignant and benign
types are found? insulinomas, gastrinomas, and glucagonomas.

What tumor Gastrin, carcinoembryonic antigen, AFP, beta-2

markers are microglobulin, CA-125, and CA 199. None of these,
used in however, is sensitive or specific enough to be used
pancreatic routinely.
cancer?

What are the Porta hepatis, liver, peritoneum with malignant ascites,
most common penetration into the splanchnic nerves, and local lymph
sites of nodes. Less commonly, lung and bone are affected.
metastatic
disease in
pancreatic
cancer?

Pancreatic Tumors arising in the tail of the pancreas and those >4 cm
carcinomas at are rarely resectable.
what location
and of what size
are generally
unresectable?

What percent of <20%

patients who
undergo a
resection are
alive at 5 years?

Are there any One prospective controlled study demonstrated an

proven adjuvant improvement in survival (21 months versus 11 months) with
treatments that use of postoperative 5-FU and radiation therapy versus
improve survival surgery alone.
in resectable
pancreatic
cancer?

What surgical Palliative and prophylactic biliary bypass surgery. Biliary

approaches stent placement either transhepatically or via ERCP is an
should be alternative. Relief of gastric outlet obstruction and
considered for duodenal obstruction can be useful. Prophylactic gastric
locally bypass procedures are useful in some scenarios. Splanchnic
unresectable and celiac ganglion nerve blocks may relieve pain.
disease?

Are radiation Radiation therapy alone can improve pain and possibly
and prolong survival. Combined-modality therapy with 5-FU and
chemotherapy radiation therapy in one study showed an improvement in
useful in the survival from 5 to 10 months.
treatment of
locally advanced
pancreatic
cancer?

What is the most Palliation of symptoms

important
treatment for
patients with
metastatic
pancreatic
cancer?

What standard 5-FU is associated with a response rate of <20% and does
treatments are not improve the survival rate. Gemcitabine was approved
there for for metastatic pancreatic cancer because of its ability to
metastatic improve quality of life. Combination chemotherapy such as
pancreatic 5-FU or gemcitabine plus cisplatin or oxaliplatin or
cancer? irinotecan, for example, typically yield higher response
rates; however, little or no difference in survival has been
observed.

What other Novel targeted therapies such as erlotinib (an oral

novel therapies epidermal growth factor inhibitor) or bevacizumab [an
are available for intravenous monoclonal antibody targeted against vascular
the treatment of endothelial growth factor (VEGF)] have been investigated in
metastatic pancreatic cancer. A recent randomized phase III trial
pancreatic comparing gemcitabine erlotinib has recently been
 cancer? reported, showing improvement in survival for the patients
treated with gemcitabine plus erlotinib. Another trial
comparing gemcitabine bevacizumab was recently
completed and no benefit was noted in the treatment
group.

P.451

Pancreatic Islet Cell Tumors

What are the types Endocrine tumors of the pancreas are classified
of pancreatic islet according to the type of clinical syndrome present:
cell tumors? insulinoma, gastrinoma (Zollinger-Ellison syndrome),
somatostatinoma, VIPoma (e.g., pancreatic cholera,
Verner-Morrison syndrome), glucagonoma, PPoma,
GRFoma, and nonfunctioning tumors.

How is the Tumor localization

diagnosis of
pancreatic islet cell
tumor made?

What is the
sensitivity of the
following tests in
localizing islet cell
tumors?

Ultrasound 10% to 20%

Abdominal CT 20% to 40%

Selective 80% to 90%

angiography

Intraoperative 90%
ultrasound

OctreoScan 40% to 100% (OctreoScan is indiumlabeled pentetreotide

used in a nuclear medicine study that is noninvasive;
results depend on tumor type)

What is the Only 10% of insulinomas are malignant; at least 50% of

malignant potential all other histologic subtypes are considered malignant.
of pancreatic islet
cell tumors?
 What is the All patients should be considered for possible surgical
treatment for resection of the tumor. Medical treatment may be useful
pancreatic islet cell in unresectable or incompletely resectable tumors.
tumors?

What is the specific

medical treatment
for the following:

Insulinoma? Diazoxide and frequent small meals

Gastrinoma? Omeprazole

Glucagonoma? Streptozocin chemotherapy

Somatostatinoma? Streptozocin has worked in a few cases.

VIPoma, Octreotide
glucagonoma,
GRFoma,
insulinoma,
Zollinger-Ellison
syndrome?

What is the Islet cell tumors have a far more favorable prognosis
prognosis for than ductal adenocarcinomas because they grow slowly
pancreatic islet cell and cause physical symptoms early. Survival is directly
tumors? related to tumor extent: if no
tumor is found at surgery, the 5- to 10-year survival
rate is 90% to 100%; if there is complete tumor
resection, the 5- to 10-year survival rate is 90% to
100%; if there is incomplete resection, the 5-year
survival rate is 15% to 75%; in unresectable cases, the 5-
year survival rate is 20% to 75%.

P.452

Cholangiocarcinoma
What is a Klatskin Cholangiocarcinoma arising at the bifurcation of the
tumor? right and left hepatic ducts

How is the diagnosis Ultrasound, abdominal CT, ERCP, and angiography may
of be useful in localizing the tumor and staging the
 cholangiocarcinoma disease.
made?

Are serum AFP No

levels elevated in
patients with
cholangiocarcinoma?

What is the Surgery is the only definitive therapy. Resectable

treatment for tumors of the distal bile duct are associated with a 60%
cholangiocarcinoma? 1-year survival rate. Arterial or portal vein involvement
precludes resection. ERCP with stent placement and
PTC with drainage may be useful palliative procedures
to relieve biliary obstruction.

What For patients with advanced cholangiocarcinoma and

chemotherapeutic good performance status, improved survival has been
options are there observed with 5-FU or gemcitabine based regimens.
for patients with
cholangiocarcinoma?

P.453

Genitourinary Cancer

Renal Cell Carcinoma

What are the Some of the more common findings are pyrexia,
paraneoplastic syndromes cachexia, anemia, nonmetastatic liver dysfunction,
associated with renal cell amyloidosis, polycythemia, and hypercalcemia.
carcinoma?

How is renal cell Stage I: within kidney

carcinoma staged? Stage II: within Gerota's fascia
Stage IIIA: involvement of the renal vein or
inferior vena cava
Stage IIIB: involvement of hilar lymph nodes
Stage IV: metastatic disease

What is the treatment of Radical nephrectomy with lymphadenectomy. Two

localized renal cell thirds of patients with stage I and stage II disease
carcinoma? survive 5 years.

Can patients with Yes. Occasionally, patients with isolated

metastatic renal cell pulmonary or brain metastasis can be cured with
carcinoma be cured? surgical resection of the metastatic foci.
Bladder Cancer
What percentage of 50%
individuals with invasive
tumors have distant
metastatic disease at the
time of diagnosis?

What are some of the Major prognostic factors include the depth of
prognostic factors? invasion and degree of differentiation.

What are the treatment

options for:

Carcinoma in situ or Transurethral resection. Intravesicular therapy

superficial tumors? with BCG is used for high-risk patients.

Muscle invasive tumors? Radical cystectomy with bilateral pelvic lymph

node dissection

Metastatic disease? Typically treated with combination

chemotherapy with regimens including
methotrexate, cisplatin, doxorubicin, and
vinblastine. Newer treatment agents include
gemcitabine and the taxanes.

What are the 5-year

survival rates for:

Superficial disease? 95%

Regional disease? 50%

Metastatic disease? 6%

P.454

Prostate Cancer
What is the The proximal ducts of the prostate give rise to 98% of all
most common prostate cancers, of which the most common histologic
histologic subtype is adenocarcinoma.
subtype of
prostate
 cancer?

What other They include mucinous carcinoma, adenoid cystic carcinoma,

histologic carcinoid tumors, and undifferentiated cancers. The distal
subtypes of ducts give rise to 2% of cancers of the prostate, including the
prostate following histologic subgroups: transitional cell carcinoma,
cancer are squamous cell carcinoma, papillary carcinoma, and ductal
there? cancer.

How are The Gleason grade is used to provide additional prognostic

prostate information for prostate cancer.
cancers
graded?

How is the Tumors are graded from 1 to 5 based on the degree of

Gleason grade glandular differentiation and structural architecture seen on
determined? the pathologic sample, 1 being small uniform cells and 5 being
poorly differentiated cells. The final score is the sum of the
two prominent cell types seen and ranges from 2 (best
prognosis) to 10.

What test is Serial measurement of PSA

effective in
following up
prostate
cancer
patients after
treatment?

P.455
P.456

Testicular Cancer
Do all GCTs arise No. As many as 5% of GCTs are termed extragonadal.
within the testicle? Extragonadal GCTs arise as a result of malignant
transformation of
residual midline germinal elements, usually in the
mediastinum and retroperitoneum but occasionally
within the pineal gland and sacrococcygeal area.

What is the most Seminoma comprises 40% of GCTs. The other

common GCT? histologic subtypes are referred to as
nonseminomatous germ-cell tumors (NSGCTs).

What percent of 70%

seminomas are
confined to the
testicle at
presentation?

What percent of 30% to 40%

NSGCTs are confined
to the testicle at
presentation?

Which GCT typically Choriocarcinoma. Seminomas can have an elevated

results in elevation of beta-HCG, but it is usually <100 !/L. Embryonal
beta-HCG? carcinoma can also have an elevated beta-HCG.

Which GCT typically Yolk sac and embryonal carcinoma. Pure

has an elevated AFP? choriocarcinoma and seminoma do not have an
elevated AFP.

What other conditions Cancer of prostate, bladder, kidney, and ureter; also
can elevate beta- marijuana use and pregnancy
HCG?

What other conditions Pregnancy, hepatocellular carcinoma, and gastric

can elevate the AFP? cancer

How are GCTs staged? Stage I (A): tumor confined to the testicle
Stage IIA (B1): minimally bulky RPLNs
Stage IIB (B2): moderately bulky RPLNs
Stage IIC (B3): bulky RPLN
Stage III (C): supradiaphragmatic or visceral disease

How is stage I RTIO with 25- to 35-Gy radiation therapy to RPLNs.

seminoma managed? RTIO followed by close observation is a reasonable
alternative, probably with an equivalent 5-year
survival rate.

How is stage I NSGCT RTIO with RPLND. Surveillance in lieu of RPLND is an

managed? alternative but is not standard.

What is the Radiation therapy

management of stage
II seminoma?

What is the Stages IIA and B: RPLND and chemotherapy

management of stage Stage IIC: chemotherapy
 II NSGCT?

What is the Chemotherapy

management of all
stage III GCTs?

What chemotherapy is Cisplatin, etoposide, and bleomycin

used?

What is the 5-year

survival rate of
seminoma for the
following:

Stage I >95%

Stage II >95%

Stage III 80%

What is the 5-year

survival rate of NSGCT
for the following:

Stage I >95%

Stage II 90% to 95%

Stage III 70%

What is the treatment Chemotherapy

of EGGCT?

P.457
P.458
P.459

Ovarian Cancer
Under what The patient is premenarchal or postmenopausal.
circumstances The mass is >8 cm.
should a patient Complex cysts are shown on ultrasound.
with an adnexal There is an increase in size or persistence of the cyst
mass warrant through two to three menstrual cycles.
consideration for The masses are solid and irregular, fixed, or bilateral.
surgical There is pain associated with the mass.
exploration? There is ascites.

Do all patients No. However, 80% of patients with advanced disease and
with ovarian 50% of patients with early-stage disease have elevated
cancer have CA125 levels.
elevated CA125
levels?

What are the most Serosal surfaces of intra-abdominal tissues and RPLNs are
common sites of the most common sites of metastases. Pelvic lymph
metastases for nodes, liver, lung, bone, and brain metastases can occur.
ovarian cancer?

What are the Stage I: tumor limited to the ovaries

components of Stage IA: one ovary, intact capsule, no ascites
stage I ovarian Stage IB: both ovaries, intact capsule, no ascites
cancer? Stage IC: ruptured capsule, capsular involvement,
positive peritoneal washings, or malignant ascites

What are the Stage II: ovarian tumor with pelvic involvement
components of Stage IIA: pelvic extension to the uterus or tubes
stage II ovarian Stage IIB: pelvic extension to other pelvic organs
cancer? (bladder, rectum, or vagina)
Stage IIC: pelvic extension and positive findings in stage
IC

What are the Stage III: tumor outside the pelvis or positive nodal
components of involvement
Stage III ovarian Stage IIIA: microscopic seeding outside the pelvis
cancer? Stage IIIB: gross deposits "2 cm
Stage IIIC: gross deposits >2 cm or positive nodal
involvement

What are the Distant organ involvement including the liver or pleural
components of space
stage IV ovarian
cancer?

What are the Epithelial carcinomas comprise 85% of cases and all are
histologic subtypes approached in essentially the same way. GCTs and sex
of ovarian cancer? cord stromal tumors are the predominant nonepithelial
tumors and are managed differently.

What is the Bilateral salpingo-oophorectomy, omentectomy with

surgical treatment careful examination of all serosal surfaces, biopsy of
for ovarian cancer? suspicious and grossly involved areas, collection of
ascites and peritoneal washings, and debulking of all
gross disease. If the disease is limited to the ovary, an
RPLND is performed for additional staging.

What Hypercalcemia, cerebellar degeneration (pancerebellar

paraneoplastic dysfunction associated with extensive Purkinje cell loss),
syndromes are sign of Leser-Trlat (sudden increase in the size and
seen in ovarian number of seborrheic keratosis), and Trousseau's sign
carcinoma? (migratory thrombophlebitis)

What is the For stage IA and IB good-risk patients (well- or

postoperative moderately well-differentiated histologic grade), no
management of further treatment is indicated. In poor-risk stage I and II,
stage I and II postoperative adjuvant chemotherapy with a cisplatin-
patients? based regimen is the standard.

What is the After an optimal surgical procedure, adjuvant

management of chemotherapy is with cisplatin or carboplatin and
stage III and IV paclitaxel or cyclophosphamide for six cycles.
(advanced) ovarian Intraperitoneal chemotherapy is a consideration in
cancer? optimally debulked stage IIIA and IIIB patients.

What are the

survival rates for
the following:

Stage IA and IB >90% cure rate with surgery alone

with good
prognostic factors

Stage II patients 60% cure rate with surgery plus adjuvant chemotherapy
or stage I patients
with poor
prognostic factors
and stage IC

Stage IIIA and 25% to 40% cure rate with surgery and adjuvant
IIIB chemotherapy

Stage IIIC and IV <10% cure rate with surgery and adjuvant chemotherapy

P.460
Carcinoma of Unknown Primary Site
What are the Adenocarcinoma, 70%; poorly differentiated carcinoma,
potential histologic 15% to 20%; poorly differentiated adenocarcinoma, 10%;
diagnoses? squamous cell and neuroendocrine are uncommon.

In whom should a In a young patient with predominantly midline disease

GCT variant be (mediastinal and retroperitoneal lymphadenopathy).
suspected? However, in any patient with a good performance status
with the diagnosis of PDA or PDC, it is not unreasonable
to obtain an AFP and beta-HCG and treat with
chemotherapy for an extragonadal GCT.

What is the This is usually the result of a head and neck primary
management of and can be cured with a radical neck dissection,
squamous cell radiation therapy, or both. A careful head and neck
carcinoma in an examination should be undertaken.
isolated cervical
lymph node?

What is the Careful evaluation of the anorectum, vagina, cervix,

management of and penis. These malignancies are potentially curable
squamous cell with surgery, chemoradiotherapy, or both.
carcinoma in an
inguinal lymph
node?

What is the A mammogram should be performed, followed by a

management of modified radical mastectomy with axillary node
adenocarcinoma in dissection. Adjuvant chemotherapy, radiotherapy, or
an isolated axillary both should be offered according to the final pathologic
lymph node in a stage.
woman?

What is the Laparotomy with consideration of a debulking procedure

management of as in patients with ovarian carcinoma. Postoperative
peritoneal chemotherapy is recommended if, after the debulking
carcinomatosis and procedure, ovarian cancer is suspected.
pathologic findings
demonstrating
adenocarcinoma in
a woman?
Editors: Bergin, James D.
Title: Advanced Medicine Recall, 1st Edition

Copyright 2009 Lippincott Williams & Wilkins

> Table of Contents > Section II - The Specialties > Chapter 10 - Pulmonology

Chapter 10
Pulmonology

P.462
P.463

Abbreviations
A-a Alveolararterial gradient

ABG Arterial blood gas

ABPA Allergic bronchopulmonary aspergillosis

AFB Acid-fast bacillus

AHI Apnea hypoxia index

AIDS Acquired immunodeficiency syndrome

AIP Acute interstitial pneumonitis

ANCA Antinuclear cytoplasmic antibodies

ARDS Adult respiratory distress syndrome

ASD Atrial septal defect

BAL Bronchoalveolar lavage

BiPAP Bilevel positive airway pressure

BO Bronchiolitis obliterans (also obliterative

bronchiolitis)

BOOP Bronchiolitis obliterans with organizing

pneumonia

CAP Community-acquired pneumonia

CF Cystic fibrosis

CMV Cytomegalovirus

CNS Central nervous system

COP Cryptogenic organizing pneumonia

COPD Chronic obstructive pulmonary disease

CPAP Continuous positive airway pressure

CSA Central sleep apnea

C-T Connective tissue

CT Computed tomography

CTPA Computed tomographic pulmonary

angiogram

CXR Chest x-ray

DLco Diffusion capacity for carbon monoxide

DVT Deep venous thrombosis

EDS Excessive daytime sleepiness

FEV 1 Forced expiratory volume in 1 second

FIO2 Fraction inspired oxygen

FVC Forced vital capacity

HAP Hospital-acquired pneumonia

HF or CHF Heart failure or congestive heart failure

HIV Human immunodeficiency virus

HRCT High-resolution CT

HSP Hypersensitivity pneumonitis

HTN Hypertension
ICU Intensive care unit

ILD Interstitial lung disease

INH Isoniazid

INR International normalized ratio

IPF Idiopathic pulmonary fibrosis

IPG Impedance plethysmography

KS Kaposi's sarcoma

LDH Lactate dehydrogenase

LFT Liver function test

MAC Mycobacterium avium complex

NIPPV Noninvasive positive-pressure ventilation

NSAID Nonsteroidal anti-inflammatory drug

OP Organizing pneumonia

OSA Obstructive sleep apnea

PA Pulmonary artery

PA gram Pulmonary artery angiogram

PAH Pulmonary arterial hypertension

PC Pressure control

PCP Pneumocystis jiroveci pneumonia

PE Pulmonary thromboembolism

PEEP Positive end-expiratory pressure

PEF Peak expiratory flow

PFT Pulmonary function test

PMN Polymorphonuclear leukocytes

 PPD Purified protein derivative

PPH Primary pulmonary hypertension

P-R Pulmonaryrenal

PS Pressure support

PSG Polysomnogram

PSI Pneumonia severity index

PTT Partial thromboplastin time

PZA Pyrazinamide

RAST Radioallergosorbent test

RDI Respiratory disturbance index

RERA Respiratory effort-related arousal

RV Right ventricle (ventricular)

SaO2 Oxygen saturation

SIMV Synchronized intermittent mandatory

ventilation

SIRS Systemic inflammatory response syndrome

SLE Systemic lupus erythematosus

TB Tuberculosis

TLC Total lung capacity

UARS Upper airway resistance syndrome

VATS Video-assisted thoracoscopic surgery

[V with dot above][Q with dot Ventilation/perfusion scan

above]scan

WBC White blood cell

History and Physical Examination

 What findings in someone with Respiratory rate >30 breaths per minute
obstructive lung disease suggest and the use of accessory muscles of
that his or her FEV 1 is decreased respiration; there may be evidence of
to 30% or less? CO 2 retention on ABG.

P.464
P.465

Obstructive Lung Disease

Chronic Obstructive Pulmonary Disease

What causes Decreased elastic recoil of the lung, increased airway
the airflow resistance or dynamic airway collapse
obstruction
in patients
with COPD?

Is clubbing a No, it is a feature of pulmonary fibrosis, among other things.

feature of
COPD?

What is the Alpha-1 antitrypsin levels

first
laboratory
test to check
when looking
for a genetic
cause of
COPD?

What is the The threshold level is 80 mg/dL (11 !mol/L), which is 35% of
normal value predicted. Below this level, patients have increased risk of
for alpha-1 emphysema.
antitrypsin?

When should Emphysema in the absence of a known risk factor (in a minimal
one order an or nonsmoker, no occupational dust exposure); early-onset
alpha-1 emphysema ("45 years old); emphysema favoring the lower
antitrypsin lobes; symptomatic adult with emphysema; COPD or asthma
level? with incompletely reversible airflow obstruction despite
aggressive treatment; clinical findings or history of unexplained
liver disease; bronchiectasis of unknown etiology; clinical
findings or history of necrotizing panniculitis; antiproteinase 3
positive vasculitis [C-ANCA (anti-neutrophil cytoplasmic
antibody)-positive vasculitis]; family history of emphysema,
liver disease, bronchiectasis, or panniculitis

What are the High-risk phenotype [PiZZ, PiZ(null), PiZ(null)] (normal is MM;
indications SZ and MZ rarely have evidence of clinical pulmonary disease),
for obstructive lung disease (FEV 1 <80% predicted), serum alpha-1
replacement antitrypsin levels <80 mg/dL (11 !mol/L), and smoking
therapy with abstinence
alpha-1
proteinase
inhibitor
[human]
(Prolastin)?

Are No. Mucolytics such as acetylcysteine may be irritants and

mucolytics worsen cough and bronchospasm, especially if inhaled.
useful in Excessive intravenous hydration is not helpful either.
patients with
COPD?

What are the In order of most to least important: [V with dot above][Q with
mechanisms dot above] mismatch (increased dead-space ventilation), the
whereby Haldane effect, decreased hypoxic drive
supplemental
oxygen
causes
hypercarbia
in a patient
with COPD?

What is the The exact mechanism of action remains controversial.

mechanism Theophylline is a phosphodiesterase inhibitor and increases
of action and levels of intracellular cyclic adenosine monophosphate.
effect of Antagonism of adenosine receptors is another proposed
theophylline? mechanism. Theophylline may affect eosinophilic infiltration
into bronchial mucosa as well as decrease T-lymphocyte
numbers in the epithelium. Theophylline has numerous effects
including bronchodilation, enhancement of mucociliary
clearance, stimulation of the respiratory drive, increased
cardiac function, pulmonary arteriole vasodilation, and
augmentation of diaphragmatic contractility.

Which Macrolide antibiotics (erythromycin, clarithromycin),

medications cimetidine, ticlopidine, and quinolones (e.g., ciprofloxacin)
increase
theophylline
levels?

Which Phenobarbital, phenytoin, carbamazepine, and rifampin

medications
decrease
theophylline
levels?

What factors Hypoxia, cirrhosis, heart failure, systemic febrile viral illness,
or medical and advanced age
conditions
increase
theophylline
levels?

Why can Intake of increased carbohydrate calories may lead to

overly increased oxygen consumption and increased CO 2 production,
aggressive leading to increased ventilatory requirements. Replacing
nutritional carbohydrates with lipids will remedy this situation. However,
therapy be not overfeeding the patient is probably more important than
detrimental the relative percentage of carbohydrates and lipids in the diet.
in patients
with severe
COPD?

What is the 50% 1-year mortality rate

long-term
prognosis for
COPD
patients
hospitalized
on
mechanical
ventilation
who are
discharged to
home?

What is lung Lung volume reduction surgery removes emphysematous lung

volume tissue.
reduction
surgery?

What are the Improved pulmonary mechanics (increased lung recoil,

physiologic decreased resistance, decreased hyperinflation, decreased air
effects of trapping), respiratory muscle strength (by making the
lung volume diaphragms less flat), and gas exchange (decreased Paco 2 ,
reduction? increased PaO 2 ).

What Improved [V with dot above][Q with dot above] mismatch and
improves the dead-space ventilation are the etiologies of the improved gas
gas exchange exchange.
in these
patients?

Which Patients with predominantly upper lobe emphysema and low

patients are (<40% of predicted) maximum exercise capacity after
best pulmonary rehabilitation
 candidates
for lung
volume
reduction
surgery?

P.466
P.467
P.468
P.469

Asthma1
Which allergens should Indoor allergens, including dust mite, animal
be tested for? dander, and cockroach antigens. Other important
allergens include Alternaria, which is associated
with an increased risk of fatal and near-fatal
asthma attacks in the Midwest, and Aspergillus
because of the syndrome of ABPA.
Pollen and other seasonal allergies are usually
more obvious to the patient and therefore less of a
problem.

What are the criteria for Requires normal lung function, PEF variability
mild intermittent <20%, using a beta-2 adrenergic agonist <2 times a
asthma? week, and waking up <2 times a month

What are the criteria for PEF variability 20% to 30%, using a beta-2
mild persistent asthma? adrenergic agonist >2 times a week but <1 per day,
and waking up >2 times a month

What are the criteria for PEF variability >30%, using a beta-2 adrenergic
moderate persistent agonist daily, and waking up >1 times a week
asthma?

What are the criteria for PEF variability >30%, continual daily symptoms and
severe persistent frequent nocturnal symptoms
asthma?

In a patient uncontrolled Adding a long-acting beta-adrenergic agonist is

on inhaled superior to doubling the dose of inhaled
corticosteroids alone corticosteroids or adding a leukotriene modifying
(400 !g or greater), agent.
what is the most
appropriate next step?

What agents have been Methotrexate, gold, cyclosporine, antitumor

used as corticosteroid- necrosis factor-alpha agents, macrolides. Studies
sparing? have failed to show a benefit of corticosteroid-
sparing agents over steroids, but in selected
 patients, these agents may be useful to minimize
corticosteroid side effects.

What are the Contraindications also include initiation during

contraindications to pregnancy and beta-adrenergic blocker therapy.
allergen testing?

How is aspirin sensitivity Sensitivity is generally tested by challenging the

testing performed? patient with escalating concentrations of aspirin.
Because such testing is dangerous, it should be
done in a monitored unit. Similarly, aspirin
desensitization is performed using graduating doses
and is similarly dangerous.

Is aspirin desensitization Yes. Desensitization is effective in controlling

effective? asthma in some sensitized patients. There is little
evidence to suggest that aspirin desensitization is
effective for urticaria. Leukotrienemodifying agents
may be useful in this population. However, aspirin
and NSAIDs should still be avoided.

Is cromolyn useful in No. Cromolyn is not a bronchodilator; rather, it

acute asthma? works by inhibiting histamine release from mast
cells and neurogenic mechanisms. It works as an
NSAID and can take several weeks for improvement
to occur. Although very safe, it is no longer
frequently used even for stable asthma because it
is a weak anti-inflammatory agent and must be
taken three or four times a day.

What are the indications Incomplete response to emergency room therapy

for hospital admission? defined as persistence of mild to moderate
symptoms and signs, hypoxemia, FEV1 and PEF
<50% to 70% (see findings in severe asthma)

What are the indications Asthmatics are very difficult to ventilate

in acute asthma for mechanically because of hyperinflation and airway
initiating noninvasive resistance. Intubate for drowsiness or confusion,
(via nasal or oronasal fatigue, progressive hypercapnia, refractory
mask) and invasive (via hypoxemia, or bradycardia. Paradoxical
endotracheal tube) thoracoabdominal movement and absence of
ventilatory support? wheezing are also ominous.

What should a peak flow To provide an objective measure of a patient's

meter be used for? condition at home (a patient may have a
decrement in airflow and be unaware of the
change) and objective information about a patient's
response to therapy in the emergency room
Do short-acting beta- Although some studies suggest that high doses of
adrenergic agonists short-acting beta-adrenergic agonists may be
increase the risk of associated with increased mortality, their increased
death? use was more likely a sign of uncontrolled asthma
than a direct cause.

Do long-acting beta- Long-acting beta-adrenergic agonists appear to be

adrenergic agonists safe as long as they are utilized when needed for
increase the risk of uncontrolled asthma and with an inhaled
death? corticosteroid.

What are some areas of Laboratory work; work in the pharmaceutical and
work associated with food industries; sawmill, plastic, and metal work;
immunologically farming; cosmetology (e.g., beauticians);
mediated occupational longshoring; and clothing manufacturing. One
asthma? should take a careful occupational and
environmental history in all patients with asthma.

What symptoms should

suggest a diagnosis of:

Work-aggravated A history of asthma symptoms occurring in the

asthma? workplace and improving when away from work
(i.e., at night, on weekends, vacation).

Irritant-induced asthma? For irritant-induced, either the exposure is massive

and obvious or many workers are affected.

Immunologically For immunologically mediated, few workers are

mediated asthma? affected. Symptoms progressively worsen as the
work week progresses.

What are the similarities Both diseases are characterized by cough and
and differences between shortness of breath, but HSP also causes systemic
HSP and immunologically symptoms such as fever as well as pulmonary
mediated occupational infiltrates and restrictive PFTs (decreased TLC,
asthma? DLco). HSP is not IgE-mediated, whereas
occupational asthma generally is.

What are the three Acute, subacute, and chronic.

types of HSP?

How does acute HSP Acute HSP presents similarly to community-

present? acquired pneumonia with the acute onset of both
respiratory and systemic symptoms occurring 4 to 8
hours after exposure.

How does subacute HSP Subacute HSP presents with a several-week to

present? many-month history of respiratory and mild
 systemic symptoms.

How does chronic HSP Chronic HSP presents more indolently over months
present? to years, often without systemic symptoms.

What are the major 1. Exposure to a known offending agent (history,

criteria to diagnose HSP? serum precipitating antibodies, or
environmental analysis)
2. Compatible symptoms (i.e., recurrent episodes
of symptoms occurring 4 to 8 hours after
exposure)
3. Infiltrates on CXR

What are the minor 1. Crackles on physical examination

criteria to diagnose HSP? 2. Decreased PaO 2 , lung volumes, or DLco
3. Lung biopsy that demonstrates loosely formed
granuloma and a lymphocytic alveolitis around
airways
4. Positive challenge test
5. BAL may also be helpful, because there is an
increase in CD8+ T cells, as opposed to the
increase in CD4+ T cells seen in sarcoidosis.

What is required to Requires all major and two minor criteria

diagnose HSP?

P.470

Bronchiectasis2
What is the Perform skin prick test to Aspergillus; if negative, perform
first step in intradermal injection. If both are negative, ABPA is ruled out. If
the positive, one must go on to the next step, because 20% to 30% of
diagnostic asthmatics may have a positive response.
evaluation
for ABPA?

What is the Measure total IgE and serum precipitating antibodies (IgG) to
second step Aspergillus (serum precipitans).
in the
diagnostic
evaluation
for ABPA?

What is the If total IgE >1000 ng/mL and serum precipitans is positive, check
third step specific IgE to Aspergillus (e.g., by RAST) and HRCT; a positive
in the specific IgE to Aspergillus or an HRCT demonstrating central or
diagnostic proximal bronchiectasis clinches the diagnosis of ABPA.
evaluation Other diagnostic criteria for ABPA include an eosinophil count
 for ABPA? #8%.

Which All the criteria with the exception of positive RAST testing may
criteria be absent when patients are in remission. Also, peripheral
above may eosinophilia and elevated total IgE may be absent in patients
be affected who are being treated with oral prednisone, although the total
by IgE level rarely returns entirely to normal.
remission
or therapy?

P.471
P.472

Interstitial Lung Disease

Which Usual interstitial pneumonitis (UIP), desquamative interstitial
disorders are pneumonitis (DIP), respiratory bronchiolitisassociated
included in interstitial lung disease (RB-ILD), nonspecific interstitial
the idiopathic pneumonitis (NSIP), AIP, and COP. COP is the new term for
fibrosing idiopathic BOOP. IPF is synonymous with usual interstitial
interstitial pneumonitis from an unknown cause.
pneumonia
group?

Which C-T SLE, rheumatoid arthritis, ankylosing spondylitis, progressive

diseases systemic sclerosis, Sjgren's syndrome, and polymyositis
cause ILD? dermatomyositis

Which P-R Goodpasture's syndrome, Wegener's granulomatosis,

syndromes microscopic polyangiitis, allergic angiitis, and granulomatosis
cause ILD? (Churg-Strauss syndrome)

Which Inorganic dusts, fibers, and metals: asbestos, silica, coal, and
environmental beryllium
substances Organic dusts: cotton (byssinosis)
cause ILD? Toxic gases and fumes: nitrogen dioxide

Which ILDs Known causes: HSP, beryllium, silica, and medications (e.g.,
are associated methotrexate)
with Unknown causes: sarcoidosis, Langerhans cell granulomatosis
granulomas? (eosinophilic granuloma), granulomatous vasculitides
(Wegener's, Churg-Strauss), and bronchocentric granulomatosis

Which Tuberous sclerosis, HermanskyPudlak syndrome,

inherited neurofibromatosis, metabolic storage disorders (e.g.,
diseases Gaucher's, NiemannPick), and hypocalciuric hypercalcemia
cause ILD?

Which BO with or without organizing pneumonia (BOOP/COP),

miscellaneous eosinophilic pneumonia, drugs, radiation,
 diseases lymphangioleiomyomatosis, alveolar proteinosis, veno-
cause ILD? occlusive disease, lymphangitic carcinomatosis, idiopathic
pulmonary hemosiderosis, gastrointestinal or liver diseases
(inflammatory bowel disease, primary biliary cirrhosis, chronic
active hepatitis), graft-versus-host disease (bone marrow
transplant), lymphocytic infiltrative diseases, and alveolar
microlithiasis

What is The association of rheumatoid arthritis and pulmonary nodules

Caplan's in patients with pneumoconiosis, particularly coal workers'
syndrome? pneumoconiosis

What BO is obstructive, and OP is restrictive.

pulmonary
function
abnormalities
occur with BO
and OP?

What are the >10% change in FVC or TLC; >15% change in DLco; >4% increase
ATS criteria in O 2 sat; >4 mm Hg change in PaO 2 during exercise
to determine
improvement?

What should Infection or pneumonitis, including with unusual organisms

you think of such as Pneumocystis jiroveci (PCP). HF, pulmonary embolism,
if your ARDS, and an acute exacerbation of ILD are other
patient's considerations.
illness
worsens
during
treatment
with
prednisone
and cytotoxic
agents?

P.473

Cystic Fibrosis
What laboratory tests are Chest radiograph
performed for CF? PFTs
Sweat chloride test
Search for genetic mutations

What are the typical findings Shows hyperinflation, bronchiectasis, and

seen on the CXR in patients reticular nodular fibrosis; rarely shows
with CF? atelectasis or pneumothorax
 What are the typical findings Early, shows obstructive lung disease; late,
seen on the PFTs in patients shows restrictive lung disease
with CF?

What are common organisms Staphylococcus aureus, Haemophilus

found in the sputum of influenzae, and Pseudomonas aeruginosa
patients with CF?

What antibiotic class should Quinolones rapidly induce resistance.

be avoided and why?

P.474

Pulmonary Thromboembolism and Deep Venous

Thrombosis
What are the Family history of thrombosis, recurrent thrombosis without
clinical indicators an obvious predisposing factor, thrombosis at an unusual
of a primary anatomic site (e.g., artery), thrombosis at a young age,
hypercoagulable multiple miscarriages, and resistance to conventional
state? antithrombotic therapy

How sensitive is No better than 50%

Homans' sign?

In what disease More likely to occur with HF, COPD, and mitral stenosis
states are
pulmonary
infarctions more
likely to occur?

How reliable is Because of its good sensitivity (negative predictive value),

the D-dimer? a value <500 indicates a low probability of DVT or PE.
Because of its poor specificity (positive predictive value),
a positive value is not helpful and requires further
evaluation.

What is the
likelihood of PE if
the [V with dot
above][Q with dot
above] scan is
one of the
following:

Low probability? <10% to 20%

Intermediate 40% to 50%

probability?
High probability? 90%

What is the A recent study demonstrated a sensitivity of 83% and a

sensitivity and negative predictive value of 95%; adding a CT venogram
negative increased the sensitivity for diagnosing PE/DVT to 90% and
predictive value the negative predictive value to 97%.
for CTPA?

What is the CT angiogram if the pretest probability and D-dimer

imaging test to indicate further workup is needed, particularly if the CXR
use if the D- is abnormal and renal function is OK (creatinine "1.4)
dimer is elevated
with or without a
normal CXR?

What other test A [V with dot above][Q with dot above] scan can also be
could be used to performed at this step, particularly if the chest radiograph
image the patient is normal and/or renal function significantly abnormal
if the chest film (creatinine >1.4). An MRPA may also be used in some
was normal? centers.

When should a PA Pulmonary angiogram if the pretest probability plus D-

gram be dimer plus the [V with dot above][Q with dot above] or CT
considered? angiogram indicate further workup is needed despite
negative IPG or Doppler ultrasound of the lower
extremities
When the suspicion for PE is very high, one should
continue evaluation until a positive result requiring
treatment is obtained or a PA gram is performed.

When should When iliac veins are involved

thrombolysis be
considered for
DVT?

What are the Thrombolysis (indications are not based on prospective

treatment options studies) when hemodynamically unstable patients are
for a unresponsive to maximal medical management
hemodynamically Surgical embolectomy for hemodynamically unstable
significant PE? patients (PE) who are unresponsive to thrombolysis or with
a contraindication to thrombolysis (as for thrombolysis,
there are no prospective studies)

When should an For patients who have failed anticoagulation (rare) or in

IVC filter be whom anticoagulation is contraindicated (i.e., patients
considered? with active gastrointestinal bleeding) or in patients with
PE who are at high risk of dying should another PE occur
(i.e., massive PE or chronic thromboembolic pulmonary
hypertension)
 P.475

Pulmonary Hypertension
What are the 5 World 1. Idiopathic PPH
Health Organization 2. Associated with left heart disease (e.g., left
(WHO) categories for ventricular failure, valvular heart disease, left
pulmonary HTN? atrial obstruction)
3. Associated with lung diseases and/or hypoxemia
(e.g., ILD, COPD, sleep-disordered breathing,
alveolar hypoventilation disorders, high altitude,
neuromuscular diseases, thoracic cage
abnormalities)
4. Due to chronic thrombotic or embolic disease
5. Miscellaneous (e.g., sarcoidosis, compression of
pulmonary vasculature by adenopathy, tumor,
fibrosing mediastinitis)

What other laboratory C-T disease serologic tests, LFTs, and HIV serologies
tests may be useful in
detecting pulmonary
HTN?

What other testing Sleep study for sleep-disordered breathing

should be considered? [V with dot above][Q with dot above] scanning to
rule out chronic PE

In addition to history, 6-minute walk test

what test can be
helpful in determining
the patients' functional
class?

What is the definition Defined as a decrease in mean PA pressure by at

of a significant least 10 mm Hg to a level "40 mm Hg and with a
response to stable or increased cardiac output
vasodilators on cardiac
catheterization?

What prostatcyclins Intravenous: epoprostinol, treprostinol

can be considered for Subcutaneous: treprostinol
treatment? Inhaled: iloprost

What other oral Endothelin receptor antagonist (bosentan, sitaxetan

medications can be in Europe); phosphodiesterase-5 inhibitor (sildenafil)
considered for
treatment?

P.476
P.477
Pulmonary Neoplasms (See Chapter 9, Oncology)

Sleep-Related Breathing Disorders

What is A pattern of central apnea, characterized by periodic,
Cheyne-Stokes regular waxing and waning of ventilation. During the waning
respiration? phase, there is frank apnea. Major causes include HF, CNS
lesions, renal failure, and high altitude.

What is the In obstructive apnea, there is no airflow with persistent

difference respiratory effort.
between In central apnea, there is no airflow with no associated
obstructive respiratory effort (presumably secondary to the absence of
and central the central drive to breathe).
apnea? Mixed apnea is a combination of the two.

What is a A CNS arousal terminating obstructed events that do not

RERA? meet the criteria for an apnea or hypopnea

What is the A clinical syndrome of excessive sleepiness resulting from

UARS? RERAs

What is the Much more common than previously thought: 24% of men and
incidence of 9% of women have sleep apnea; 4% of men and 2% of women
OSA? have sleep apnea syndrome.

What is the The AHI is the number of apneic plus hypopneic episodes per
AHI? hour of sleep. It is a measure of the severity of sleep-
disordered breathing.

What is the The number of apneas plus hypopneas plus RERAs per hour of
RDI? sleep.

What is the Sleep apnea (AHI >5) plus some physiologic consequence
sleep apnea (e.g., EDS)
syndrome?

What are some Polycythemia, pulmonary HTN, cor pulmonale, chronic

of the hypercapnia, morning and nighttime headache, HF, nocturnal
consequences arrhythmias, nocturnal angina, and systemic HTN
of hypoxia and
hypercapnia?

What is the Tracheotomy is only rarely required and should be considered

therapy for a last resort. Rapid-eye-movement (REM) sleep suppressant
patients who drugs (i.e., tricyclic antidepressants) should be used only in
fail to respond select cases. Respiratory stimulants (e.g., progesterone and
to weight loss, acetazolamide) should also be used only in select cases.
CPAP, or
 BiPAP?

What is the With CPAP, the inspiratory and expiratory positive airway
difference pressures are and must be the same; with BiPAP, the
between CPAP inspiratory positive airway pressure and the expiratory
and BiPAP? positive airway pressure can vary, allowing you to set the
inspiratory higher then the expiratory positive airway
pressure.

What is an BiPAP also allows you to set a backup respiratory rate;

additional use consequently you can ventilate a patient with BiPAP.
of BiPAP?

When would When a patient with OSA has difficulty tolerating CPAP or
you consider when the patient has CSA or is hypoventilating
using BiPAP
instead of
CPAP?

P.478
P.479
P.480
P.481
P.482

Bronchitis and Pneumonias 3

Bronchitis
How is the Because cough is a symptom associated with a variety of
diagnosis of pulmonary diseases, other causes must be ruled out before
acute bronchitis the diagnosis of acute bronchitis is made.
made?

Pneumonia 4
How is CAP CAP is defined as a pneumonia beginning outside the
defined? hospital or diagnosed within 48 hours after admission.

How is HAP HAP occurs more than 48 hours after admission to the
defined? hospital and excludes any infection that began before or
was present at the time of admission.

What are risk Hospitalization for #2 days in the preceding 90 days,

factors for health residence in a nursing home or extended care facility,
careassociated home infusion therapy (including antibiotics), chronic
pneumonia? dialysis within 30 days, home wound care, family member
with a multidrug-resistant pathogen
What is the These individuals are at risk for multidrug-resistant
clinical pathogens such as Pseudomonas and methicillin-resistant
importance of Staphylococcal aureus. Empiric therapy therefore must
health care cover these organisms.
associated
pneumonia?

What clinical Hoarseness and fever starting first, with respiratory tract
signs suggest symptoms not appearing for a few days
chlamydial
pneumonia?

What symptoms Ear pain, bullous myringitis, skin rashes, hemolytic anemia,
and signs can and persistent, nonproductive cough
suggest
mycoplasmal
pneumonia?

Is there a Advanced age carries an increasing risk of fatal pneumonia

difference in with an increased risk of infection with more virulent
prognosis for pathogens, including S. aureus and gram-negative bacilli.
elderly patients
with pneumonia?

What PE, HSP, ARDS, acute eosinophilic pneumonia, COP, drug-

noninfectious induced pneumonitis, systemic vasculitis, AIP, lung cancer,
diseases can and atelectasis
mimic CAP?

For the following

epidemiologic
circumstances,
list the typical
pathogen(s):

COPD? H. influenzae and parainfluenza, Moraxella catarrhalis,

and S. pneumoniae

Health care Gram-negative bacilli (many drug-resistant, including

associated? Pseudomonas), S. aureus, including methicillin resistant,
pneumococcus, C. pneumoniae

Rabbit exposure? Tularemia

Exposure to cats, Coxiella burnetii (Q fever)

cattle, sheep,
and goats?

Exposure to Chlamydia psittaci

turkeys,
chickens, and
psittacine birds?

Caves? Histoplasma

What are the risk Extremes of age (>65 years, <5 years), beta-lactam
factors for drug- antibiotic in the last 3 months, immunosuppressive illness
resistant or (alcoholism, nephrotic syndrome, HIV, sickle cell disease,
nonsusceptible S. corticosteroids >10 mg/day), day-care attendance or family
pneumoniae? member of day-care attendee, and multiple medical
comorbidities

What are the risk >10 mg/day of prednisone, renal failure, neutropenia,
factors for chemotherapy, malignancy, including hairy cell leukemia,
Legionella transplants, and exposure to contaminated water sources
pneumonia? such as cooling towers, air conditioning, or saunas.
Legionella should also be considered in the late summer.

Who is likely to Cigarette smokers, COPD patients, diabetics, patients with

be infected with malignancies, alcoholics, and patients taking
Moraxella? corticosteroids. Such infection is rare in normal adults.

What are the Approximately 10% of patients require admission to the ICU
complications for respiratory (and often, multisystemic) failure with or
associated with without hemodynamic shock.
severe
pneumonia?

What are the The most common pathogens are S. pneumoniae and
pathogens Legionella pneumophila, but it may also be caused by
associated with gram-negative bacilli or M. pneumoniae.
severe
pneumonia?

What are If untreated, necrosis, cavitation, and empyema

complications of
anaerobic
pneumonia?

What is the 5% to 25%

mortality rate of
CAP?

What do the
following findings
on CXR suggest:

Lobar Bacterial pneumonia

consolidation,
cavitation, and
effusion?

Diffuse bilateral PCP, Legionella infection, mycoplasma, or virus

involvement?

Superior segment Aspiration

of the lower lobe
or posterior
segment of the
upper lobe
involvement?

What is CURB-65 Like the PSI, it is a clinical prediction rule that has been
and how can it validated in nonimmunosuppressed adults and permits
assist in the quantitative assessment of an individual patient's risk of
management of dying during an episode of acute pneumonia.
patients with
CAP?

What are the C = confusion; U = urea >20 mg/dL, B = blood pressure

components of (systolic <90 or diastolic "60 mm Hg), age #65.
the CURB-65?

How do the
CURB-65 point
scores correlate
with mortality
and admission
recommendation:

0 to 1 points? 0.4% mortality: can treat as outpatient

2 points? 7.6% mortality: hospitalize or closely supervised outpatient

therapy

3 points? 14.0% mortality: hospitalize, consider intensive care unit.

4 to 5 points? 27.8% mortality: hospitalize, consider ICU.

What is the CRB- CRB-65 correlates well with CURB-65 and avoids the need
65? for laboratory studies.

How do the CRB-

65 point scores
correlate with
mortality and
admission
recommendation
-

0 points? 0.9% mortality: can treat as outpatient.

1 point? 5.2% mortality: consider hospitalization.

2 points? 12.0% mortality: consider hospitalization.

3 to 4 points? 31.2% mortality: high risk of death, hospitalize, consider

ICU.

What are the A patient has severe CAP if he or she has two of three
determinants of minor criteria (PaO 2 /FIO 2 <250, systolic blood pressure "90
severe CAP? mm Hg, multilobar involvement) or one of two major
criteria (need for mechanical ventilation, septic shock)

What is a general It is important to cover for both typical and atypical

rule for the organisms. In addition, as a very general rule, the older a
treatment of patient is, the more comorbid conditions he or she has,
CAP? the sicker he or she is, the more likely he or she has a
gram-negative bacillus, Legionella, or S. aureus as the
cause of pneumonia.

For a patient Include a macrolide (e.g., azithromycin, clarithromycin,

with CAP and a erythromycin), tetracycline (doxycycline), or a respiratory
PSI risk class of fluoroquinolone (levofloxacin, gatifloxacin, moxifloxacin).
I, II, and some Take into account risk factors for certain organisms. For
III, what would instance, in outpatients with risk factors for Gram-negative
be reasonable bacilli, add a beta-lactam antibiotic to a macrolide or
antibiotic doxycycline, or treat the person with a respiratory
choices? fluoroquinolone alone. With risk factors for anaerobes, add
amoxicillinclavulanate, clindamycin, or metronidazole.

For hospitalized Reasonable antibiotic choices for this group include a

patients with macrolide or doxycycline plus a third-generation
CAP (risk class cephalosporin (ceftriaxone, cefotaxime) or
IV, V, some III), ampicillin/sulbactam or piperacillin-tazobactam or high-
without severe dose amoxicillin or a respiratory fluoroquinolone alone.
CAP (outlined These patients can usually be treated on a general
above), what medicine ward.
would be
reasonable
antibiotic
coverage?

How should In general, they should be admitted to the ICU. A

patients with macrolide or a respiratory fluoroquinolone plus a third-
severe CAP and generation cephalosporin (ceftriaxone, cefotaxime) or
 no risk factors piperacillin-tazobactam or ampicillin/sulbactam is a
for P. aeruginosa reasonable regimen.
be treated?

How should In general they should be in the ICU. Recommended

patients with treatment includes a macrolide or respiratory
severe CAP and fluoroquinolone plus an antipseudomonal beta lactam
risk factors for [cefepime, ceftazidime, carbapenem (imipenem,
P. aeruginosa be meropenem), piperacillin, piperacillin-tazobactam, or
treated? ticarcillinclavulanate] plus an aminoglycoside; or
antipseudomonal beta lactam plus fluoroquinolone.

What percentage Approximately 40% of chemical aspirations become

of aspiration infected. Bacterial superinfection usually develops slowly
pneumonias over days and may evolve into necrotizing pneumonia,
become abscess, or empyema.
infected?

What are some Other consequences of aspiration include bronchospasm,

of the other late bronchiectasis, pulmonary fibrosis, and ARDS.
consequences of
aspiration?

P.483
P.484

Nosocomial (Hospital-Acquired) Pneumonia 5

What are the CXR evidence of an infiltrate that is alveolar, has an air
features used bronchogram sign, is new or progressive, plus two or more of
to make the the following: fever or hypothermia, purulent secretions, WBC
diagnosis of >12,000 or <4000 or >10% band forms, or decreased PaO 2
HAP?

Why is it Because of bacterial colonization of the upper airway and

more difficult oropharynx, the development of tracheobronchitis in many
to diagnose intubated patients, the numerous causes of chest radiographic
pneumonias infiltrates, and the many causes of fever in hospitalized
in intubated patients
patients?

What would
be a typical
regimen for:

Patient with Unlikely to have P. aeruginosa, Acinetobacter, or methicillin-

HAP and resistant
hospitalized S. aureus causing the pneumonia. Therefore a second-
for <5 days? generation cephalosporin (cefuroxime), nonpseudomonal third-
generation cephalosporin, or beta lactam/beta lactamase
 inhibitor would be recommended.

Same patient Could use a fluoroquinolone or clindamycin plus aztreonam

with a
penicillin
allergy?

Same patient Treat as #5 days in hospital

with risk
factors for
Pseudomonas?

Patient with Need to double cover P. aeruginosa in this group; at least

HAP, initially, it increases the likelihood that you are adequately
hospitalized covering the organism. Recommended regimens include an
"5 days? aminoglycoside or fluoroquinolone plus an antipseudomonal
beta lactam or aztreonam plus vancomycin.
The prevalence as well as the antibiotic sensitivity in the
individual hospital and in individual units must be taken into
consideration as well.

Same patient Add clindamycin, or treat with beta lactam/beta-lactamase

with risk inhibitor alone.
factors for
anaerobes?

Same patient Add vancomycin.

with risk
factors for
methicillin-
resistant S.
aureus?

Same patient Add erythromycin with or without rifampin; consider a

with risk quinolone.
factors for
Legionella?

P.485

Mycobacterium Tuberculosis 6
What group is at It is more common in the HIV population.
higher risk of
extrapulmonary TB?

What organ systems Extrapulmonary TB occurs in approximately one in six

are involved with cases and may involve the CNS, bone, genitourinary
extrapulmonary TB? system, lymph nodes, or gastrointestinal tract.
How is the tuberculin Induration is read at 48 to 72 hours.
skin test read?

What does the Remember that the tuberculin skin test identifies
tuberculin skin test people who have been infected with M. tuberculosis
identify? but does not distinguish between active and latent
infections.

What groups are

considered to have a
positive PPD test if
the induration is one
of the following:

"5 mm but <10 mm? Persons in the high-risk group above

"10 mm but <15 mm? Persons in the intermediate group above

"15 mm? Individuals not at increased risk of becoming infected

with or developing TB

What is MDR-TB? Multidrug-resistant TB, defined as resistant to both

INH and rifampin

Why is MDR-TB Different drug regimens are needed for a longer time.
important? Cure rates are much lower than for susceptible TB.

What is the association Active TB is more likely to develop in HIV-positive

between HIV and TB? patients once infected (50% first year versus 5% to
15% in general; 8% to 10% per year versus 0.3% per
year). TB can develop at any time in patients with
HIV.

What is different Associated with atypical disease; such patients are

about the TB less likely to have a positive PPD and more likely to
infections in HIV have extrapulmonary TB.
patients with lower
CD4 counts?

How should HIV-

positive patients be
treated if they have:

A positive PPD? INH preventive therapy given for 9 months;

alternative: rifampin for 4 months

A negative PPD? Preventive therapy if in recent contact with a patient

with active TB, history of prior untreated or
inadequately treated prior TB, unavoidable high-risk
 of TB exposure (e.g., residents of prisons or homeless
shelters)

Active disease? Treatment of disease is with the same four-drug

regimen given for 9 months.

P.486
P.487
P.488
P.489

Pleural Effusions
Why does Secondary to lung consolidation and/or atelectasis
egophony
occur above
the effusion?

Which way Away from the side of effusion

does the
mediastinum
shift with a
pleural
effusion?

Which way Toward the side of effusion

does the
mediastinum
shift with a
pneumothorax?

How do you Obtain a lateral decubitus film or do an ultrasound.

confirm the
presence of a
subpulmonic
effusion?

Which pleural Associated with HF; small, right-sided pleural effusion with
effusions do ascites; small, asymptomatic effusions in the following
not require circumstances: documented pneumococcal pneumonia, ARDS,
thoracentesis? the first few days after abdominal surgery

Which Presence of a fever, pleuritic chest pain, hemoptysis,

effusions in pulmonary infiltrate or mass, unexplained elevated WBC
the setting of count, or weight loss
HF require a
thoracentesis?

How much If pleural pressure is not monitored, up to 1500 mL of fluid

pleural fluid may be removed for symptomatic relief.
may be
removed at
one time?

What is the Removal of more than 1500 mL may lead to

danger of postthoracentesis pulmonary edema.
removing too
much pleural
fluid?

Is there a way With gravity drainage, one can remove as much of the pleural
to remove effusion as desired.
more fluid
without
causing
trouble?

Give some The most common cause of a transudative pleural effusion is

examples of HF. Other causes include nephrotic syndrome, cirrhosis,
transudative hypoalbuminemia, acute glomerulonephritis, urinothorax,
effusions. peritoneal dialysis, superior vena cava obstruction,
atelectasis, trapped lung, and constrictive pericarditis.

What are the Infections, malignancy, and PE are the most common causes.
three most
common
causes of
exudative
pleural
effusions?

What are some Other common examples are TB, trauma, collagen vascular
of the other disease, and abdominal disease.
common
causes of an
exudative
pleural
effusion?

What are some Unusual causes include esophageal rupture, drug-induced,

of the more asbestos, postcardiac injury syndrome, chylothorax, uremia,
unusual causes radiation therapy, sarcoid, yellow nail syndrome,
of an hypothyroidism, and Meig's syndrome.
exudative
pleural
effusion?

What are Malignancy, PE, sarcoidosis, hypothyroidism

examples of
classic
exudates that
can present as
transudates?

What is a Pleural fluid obtained after diuresing HF sometimes meets

classic exudative criteria. It is important to note that any effusion
transudate tends to become exudative the longer it stays in the pleural
that can space.
present as an
exudate?

What should A serum to pleural fluid albumin gradient >1.2 g/dL indicates
one measure that diuresed HF is the cause of the exudate.
to decide
whether the
effusion is a
true exudate
or an exudate
from diuresis?

How much A hematocrit of 1% to 2% is bloody appearing (and has no

blood does it clinical importance), as little as 1 mL of blood can turn a
take to make 500-mL pleural effusion bloody.
an effusion
look bloody?

What should be
suspected with
the following:

Eosinophils The most common cause is air, followed by blood in the

(>10%)? pleural space. Examples include pneumothorax, hemothorax,
PE or infarction, previous thoracentesis, pulmonary
contusions, parasitic disease such as echinococcus, drug-
induced such as nitrofurantoin, fungal disease such as
histoplasmosis, postcardiac injury syndrome, asbestos,
lymphoma (especially Hodgkin's disease) and carcinoma
(uncommon).

Brown fluid? Amebic liver abscess and long-standing bloody effusion

Black fluid? Aspergillus

Yellow-green Rheumatoid pleurisy

fluid?

Bloody fluid? A hematocrit should be performed on all bloody pleural

effusions.
If the pleural/serum hematocrit is >2% but <50%: pulmonary
 embolism leading to pulmonary infarction, pleural
carcinomatosis, trauma, benign asbestos pleural effusion, and
postcardiac injury syndrome

What is a An effusion associated with a pneumonia that is nonpurulent

complicated
parapneumonic
effusion?

What are the One or more of the following characteristics:

characteristics pH <7.20
of a Glucose <60 mg/dL
complicated Positive Gram's stain
parapneumonic Positive culture
effusion? Loculations

Are Recent evidence has indicated that thrombolytics are not

thrombolytics useful.
helpful in the
treatment of
these
effusions?

Which drugs Frequently: hydralazine, procainamide, isoniazid, phenytoin,

can cause and chlorpromazine
effusions? Infrequently: nitrofurantoin, bromocriptine, dantrolene, and
procarbazine

What is the The choice between a closed needle biopsy and a surgical
preferred pleural biopsy depends on clinical suspicion. If TB is likely,
method for a the less invasive closed needle biopsy is preferred. If
pleural biopsy? malignancy is suspected despite negative cytology, VATS is
more likely to yield a diagnosis.

When is If the patient has a parenchymal abnormality on chest film or

bronchoscopy CT scan or to rule out an obstruction if atelectasis is
indicated? associated with the effusion

What chronic Pleural fibrosis, resulting from organization of the pleural

complications effusion. Extensive fibrosis can pull the trachea to the
are associated affected side and cause trapped lung (late finding; see
with pleural below).
effusions?

What is the A trapped lung results from remote pleural inflammation. An

difference entrapped lung is secondary to active inflammation or
between malignancy.
trapped and
entrapped
 lung?

What is the Both result from decreased visceral pleural compliance

overall (increased stiffness).
physiologic
cause of both
of these?

What is the A trapped or entrapped lung should be considered when

clue to suspect a pleural effusion rapidly reaccumulates after thoracentesis.
one of these
has occurred?

What causes a It results from remote pleural inflammation; this creates a

trapped lung? negative intrapleural pressure.

Does a trapped A transudative pleural effusion

lung cause
transudate or
exudate?

What causes an An entrapped lung is secondary to active inflammation or

entrapped malignancy.
lung?

Does an The resultant effusion is usually an exudate.

entrapped lung
cause a
transudate or
exudate?

What is the Treatment is of the underlying cause and possibly

treatment for decortication.
trapped and
entrapped
lungs?

P.490

Immunosuppressed Patients

Lung Transplantation
What is the survival rate 75% at 1 year; 60% at 2 years
after lung transplantation?

Why is the standard A double lung involves a tracheal anastomosis

procedure for CF patients and the bilateral sequential is two separate
referred to as bilateral single-lung transplants.
sequential as opposed to
 double lung?

Why is a bilateral A bronchial anastomosis heals better and there

sequential operation the is less chance for phrenic injury.
preferred procedure?

What complications need to Bleeding, air leak, and bronchial anastomotic

be watched for in the dehiscence
immediate posttransplant
period?

How is acute rejection Diffuse pulmonary infiltrates in the transplanted

recognized? lungs, decreased PaO 2 , rales, cough, dyspnea,
and low-grade fever. After the first month or
so, the chest radiograph may be normal.

When does acute rejection It is most common during the first 3 weeks after
usually occur? transplantation, with the peak incidence in the
second week.

How is the diagnosis of The gold standard is the presence of

acute rejection made? perivascular infiltrate of lymphocytes on
transbronchial biopsy.

What else causes BO? Cytomegalovirus infection, ischemic reperfusion

injury, and gastroesophageal reflux

What is the classification of BO is classified as stage 0 to 3 depending on the

BO? severity of decline in FEF 2575 and FEV1
compared to baseline values after transplant.

What diseases recur in the Sarcoid, giant cell interstitial pneumonitis, and
transplanted lung? lymphangioleiomyomatosis

Stem Cell Transplants

What is the most common pulmonary problem in stem Interstitial
cell transplantation? pneumonitis

P.491

Other Immunosuppressed Patients

What are the
major organisms
responsible for
pulmonary
infections in each
of the following:
 Primary Gram-positive organisms, especially S. aureus,
neutrophil Streptococcus viridans, enterococci, and Corynebacterium
defects? jeikeium; Gram-negative organisms, especially
Enterobacteriaceae and P. aeruginosa; anaerobes; and
fungi, especially Candida and Aspergillus

Cell-mediated? Intracellular organisms such as mycobacteria (M.

tuberculosis and Mycobacterium avium complex) and
Nocardia; fungi such as Pneumocystis and Cryptococcus,
and endemic organisms like Histoplasma; viruses,
especially DNA viruses such as CMV; and parasites and
protozoa

Humoral? Encapsulated bacteria, including S. pneumoniae, H.

influenzae, Neisseria spp., and E. coli

Acquired Immunodeficiency Syndrome

What is the Patients with serum LDH levels of <220 U/L and an ESR <50
likelihood of mm/hr are unlikely to have PCP and may be clinically
PCP with a low followed.
LDH and low
ESR?

How does KS KS may present as infiltrates, interstitial disease, effusions,

present in the lymphadenopathy, or endobronchial involvement.
lung? Hemorrhage may occur. Gallium scans are negative, unlike
those for infections and lymphoma.

P.492
P.493
P.494
P.495
P.496

Critical Care
What are the 1. Compensated hypotension (blood flow to brain, heart,
phases of liver, and kidney is maintained)
shock? 2. Decompensated hypotension (end-organ malperfusion)
3. Irreversible shock (microcirculatory failure and cell death)

What are the Hypoventilation

six causes of Decreased inspired pressure of oxygen (PIO 2 ) (e.g., living at
hypoxemia? high altitude)
[V with dot above][Q with dot above] mismatch
Shunt
Decreased diffusion
Decreased mixed venous oxygen saturation
How do you Simplified method:
calculate an A- PaO 2 PaO 2
a gradient? PaO 2 = 7 $ FiO2
PaO 2 = PO2 (Paco2 $ 1.25)
Normal is <20.

What does a That hypoventilation or decreased PIO 2 is the cause

normal A-a
gradient
indicate?

What does Complete improvement indicates that the cause of the

complete hypoxemia is [V with dot above][Q with dot above] mismatch;
improvement incomplete improvement indicates that shunt is the
to 100% O 2 mechanism.
indicate?

What are the O 2 delivery = cardiac output $ arterial oxygen content (CaO2 )
determinants CaO 2 = (1.34 $ hemoglobin $ oxygen saturation) + (0.003 $
of oxygen
PaO 2 )
delivery?

In a hypoxic Because [V with dot above][Q with dot above] mismatch

patient, what responds well to increasing the concentration of oxygen, one
is a good clue typically requires no more than 2 to 4 L/min oxygen. If more
that shunting oxygen is required, a component of shunt exists. Thus, if a
is occurring? patient with a COPD exacerbation is requiring more than 4
L/min oxygen, you should look for causes of shunt such as
pneumonia, cardiac pulmonary edema, and atelectasis.

What are the Sepsis, multiple trauma with multiple transfusions, aspiration
four most of gastric contents, and diffuse pneumonia
common
causes of
ARDS?

What are Inability to protect airway (e.g., mental status changes)

general Copious secretions
indications for Hypoxemic respiratory failure (e.g., PaO 2 <50 mm Hg on 100%
intubation? nonrebreathing face mask)
Ventilatory failure (e.g., Paco 2 >45 mm Hg with a pH <7.2)
caused by excessive
work of breathing (e.g., asthma), neuromuscular weakness
(e.g., myasthenia gravis), or a combination
Hypoperfusion or shock states
Treatment of increased intracranial pressure

Why is tube Resistance, which affects the patient's work of breathing, is

size important directly related to tube length and inversely related to tube
for weaning? radius to the fourth power.

What is the With volume-limited ventilator modes, the peak pressure is

peak airway the maximum pressure generated at the completion of
pressure? inspiratione.g., after the entire tidal volume has been
delivered by the ventilator

What is the Provides information about the resistance and compliance of

significance of the respiratory system. It is important to keep in mind that
peak airway ventilatory pressures such as the peak airway pressure
pressure? provide information about the entire respiratory system
including the extrapulmonary structures and the ventilator
circuit.

Besides lung- An obstructed endotracheal tube and a taut abdomen will

related issues, cause elevated airway pressures.
what can raise
a peak airway
pressure?

What is the With volume-limited ventilator modes, the plateau or static

plateau or pressure is measured by initiating an inspiratory hold or pause
static maneuver.
pressure?

What is the The plateau or static pressure provides information about the
significance of compliance or stiffness of the respiratory system. The plateau
the plateau or pressure also provides an estimate of the average pressure to
static which most alveoli are exposed.
pressure?

What would be Minimizing alveolar pressure by keeping the plateau pressure

the goal "25 to 30 cm H2 O pressure has been shown to decrease
plateau morbidity (e.g., pneumothorax) and mortality in patients with
pressure to COPD and ARDS.
maintain
below?

For pressure- Set pressure + PEEP + auto-PEEP

limited modes
of ventilation,
what is a
reasonable
approximation
of plateau
pressure or
mean alveolar
pressure?
What is the In patients on volume-limited ventilation, this measure
clinical provides information about the resistance of the respiratory
significance of system. One can calculate resistance by dividing this
the peak difference by inspiratory flow. As a very general rule, for an
inspiratory endotracheal tube size #7.0 cm and normal inspiratory flows
pressure (60 L/min), a normal peak inspiratory pressure minus plateau
minus the pressure difference is "5 to 10 cm H2 O. Higher values
plateau indicate increased respiratory system resistance.
pressure?

How does one Set tidal volume/(plateau pressure PEEP auto-PEEP)

calculate the
compliance of
the respiratory
system in a
patient on a
volume mode
of ventilation?

How does one Although there is no true plateau pressure with pressure
estimate the modes of ventilation, one can estimate the respiratory system
compliance of compliance as exhaled tidal volume/set pressure.
the respiratory
system in a
patient on a
pressure mode
of ventilation?

What are Because most CXRs are anterior, one may not see classic
chest findings such as a pleural line. Look for a deep sulcus sign,
radiographic sharp heart border or diaphragm, absent lung markings,
signs of a pleural reflection, and mediastinal shift.
pneumothorax
in a
mechanically
ventilated
patient?

What are the Paco 2 [V with dot above] co /[MV (1 Vd/Vt)]

2
major
Where [V with dot above] co is CO 2 production
2
determinants
of Paco 2? MV is minute ventilation
Vd/Vt is the ratio of dead space to tidal volume
MV = tidal volume $ respiratory rate

What adverse Similar to those seen with positive-pressure ventilation. In

effects are addition, because the patient must overcome auto-PEEP
associated before triggering the ventilator or air entering the lungs,
with auto- auto-PEEP results in increased inspiratory work of breathing
PEEP? and, for those on a ventilator, patient-ventilator
 dyssynchrony.

What is the Possible methods include T-piece, CPAP, PS, and SIMV.
best mode for Multiple studies have not demonstrated a clear advantage of
liberating a any single technique. However, SIMV has been shown to be
patient from inferior.
the ventilator?

What are Patients with COPD and HF achieve the best outcomes,
appropriate although there are data supporting the use of noninvasive
situations for ventilation for all causes of respiratory failure.
using
noninvasive
ventilation for
acute
respiratory
failure?

What are Patients with frank apnea or respiratory arrest, inability to

inappropriate protect the airway, voluminous secretions, facial trauma or
situations for other factors preventing a tight mask seal, upper airway
using obstruction, inability or refusal to cooperate, respiratory
noninvasive failure so severe that the patient cannot tolerate even a
ventilation for brief disconnect, and hemodynamic instability.
acute
respiratory
failure?
Editors: Bergin, James D.
Title: Advanced Medicine Recall, 1st Edition
Copyright 2009 Lippincott Williams & Wilkins

> Table of Contents > Section II - The Specialties > Chapter 11 - Rheumatology

Chapter 11
Rheumatology

P.498

Abbreviations
ANA Antinuclear antibody

ANCA Antineutrophil cytoplasmic antibodies

APS Antiphospholipid antibody syndrome

AS Ankylosing spondylitis

AVN Avascular necrosis

BUN Blood urea nitrogen

CBC Complete blood count

CH50 Total complement

CK Creatine kinase

CNS Central nervous system

CPP Calcium pyrophosphate

CPPD Calcium pyrophosphate dihydrate deposition disease

CTD Connective tissue disease

dcSSc Diffuse cutaneous systemic sclerosis

DGI Disseminated gonococcal infection

DIL Drug-induced lupus

DIP Distal interphalangeal joint

DM Dermatomyositis

DMARD Disease-modifying antirheumatic drug

FMS Fibromyalgia syndrome

ESR Erythrocyte sedimentation rate

GC Gonococcal

HIV Human immunodeficiency virus

HTN Hypertension

IBD Inflammatory bowel disease

JRA Juvenile rheumatoid arthritis

lcSSc Limited cutaneous systemic sclerosis

LFT Liver function test

MCP Metacarpophalangeal

MCTD Mixed connective tissue disease

MSU Monosodium urate

NSAID Nonsteroidal anti-inflammatory drug

OA Osteoarthritis

PAN Polyarteritis nodosa

PCP Pneumocystic carinii

PIP Proximal interphalangeal joint

 PM Polymyositis

PMN Polymorphonuclear neutrophils

PMR Polymyalgia rheumatica

PsA Psoriatic arthritis

RA Rheumatoid arthritis

RF Rheumatoid factor

RNP Ribonucleoprotein

ROM Range of motion

SCLE Subacute cutaneous lupus erythematosus

SjS Sjgren's syndrome

SLE Systemic lupus erythematosus

SSc Systemic sclerosis

UA Urinalysis

VAS Vasculitis

P.499

History and Physical Examination

What are the common diseases that OA
present as monoarthritis? Crystal-induced arthritis (gout,
pseudogout, hydroxyapatite)
Infection
AVN
Tumor
Trauma
Hemarthrosis
Collagen vascular diseases

What are the common diseases that OA

present as oligoarthritis (<4 joints)? Collagen vascular diseases
Infections
 Postinfectious arthritis
Seronegative spondoarthropathy
(e.g., PsA, AS)
Hematologic disorders (leukemia,
hemophilia, sickle cell disease)

What are the common diseases that Viral infections (e.g., parvo,
present as polyarticular arthritis? rubella, hepatitis B & C)
RA
SLE
Sarcoidosis
Other collagen vascular diseases
Crystal-induced arthritis
(polyarticular gout)
Hypertrophic pulmonary
osteoarthropathy

What are the common diseases that AS

present with axial skeletal involvement? PsA
IBD-associated arthritis
Reactive arthritis
Degenerative arthritis

P.500

Laboratory and Other Diagnostic Studies

Why order a A CBC can establish the presence of anemia (anemia of chronic
CBC? disease, hemolytic anemia, drug side effect); leukopenia,
lymphopenia, thrombocytopenia (all may be induced by
autoimmunity or can be a drug side effect); thrombocytosis (can
be a marker of inflammation)

Why order LFTs can be abnormal in autoimmune liver disease, liver disease
liver associated with arthritis such as hemochromatosis or Wilson's
enzymes? disease. Preexisting liver disease can also impact the choice of
drug therapy.

Why order a A UA can demonstrate evidence of an inflammatory process

urinalysis? involving the glomeruli (dysmorphic RBCs, RBC casts, protein in
urine)

Why order a These studies can demonstrate evidence of renal involvement

serum with an inflammatory process or evidence of medication
creatinine toxicity. They can also estimate the current renal function,
and BUN? which can result in modification of therapy.
 Why order Genetic testing can be suggestive of a condition like AS (HLA
genetic B27 gene).
testing in
autoimmune
diseases?

What is the Genetic testing is not diagnostic of any particular condition (a

drawback of positive HLA B27 is found in up to 8% of the normal population)
genetic and a negative result does not necessarily rule out the
testing? possibility of a certain autoimmune disease.

P.501

Autoantibody and Disease Match

What diseases are
commonly seen with:

ANA Positive ANA can be found in SLE, lupus subsets,

SjS, RA (targetnuclear proteins)

What percentage of healthy Up to 14% of healthy subjects may have low-

people have a positive titer ANA.
ANA?

Anti-dsDNA SLE (targetDNA) Double-stranded DNA

antibodies are best examined by the Crithidia
assay.

Anti-ENA (extractable ENA is a test that examines the specificity of

nuclear antigens) the ANA. Some of the commonly tested
specificities are: anti-Smith, anti-SSA, anti-SSB,
and anti-RNP.

Anti-Sm (Smith) SLE (targetRNP proteins). This test should not

be confused with SM (smooth muscle antibody),
seen in autoimmune hepatitis.

Anti-RNP SLE, MCTD (targetother RNP proteins)

AntiSS-A (Ro) SjS, SCLE, neonatal SLE, SLE (targetproteins

associated with RNA)

AntiSS-B (La) SjS, SCLE, neonatal SLE, SLE (targetother RNA

proteins)
 Anticentromere Raynaud's phenomenon, lcSSc, primary biliary
cirrhosis (targetcentromere proteins)

AntiScl-70 dcSSc (targetantitopoisomerase I)

AntiJo-1 Seen in PM > DM, especially with lung

involvement (targetanti-histidyl-tRNA
synthetase)

c-ANCA Wegener's granulomatosis (targetproteinase 3)

p-ANCA PAN and other vasculitides. However, this

antibody can be found in a variety of
nonvasculitic conditions (IBD, autoimmune
hepatitis, RA, SLE, AS).

Anti-Mi2 DM and PM

Anti-Ku SSc/PM overlap >SLE>SSc> PM and DM

Anti-PM-Scl SSc/PM overlap > PM and DM

Anti-histone SLE, DIL

Are there other serologic There are many other serologic tests that can
markers that are useful in be useful, such as TTG in celiac sprue.
patients with rheumatic
complaints?

P.502

Imaging Studies in Rheumatology

What is the Periarticular osteopenia
earliest sign on
plain films of an
inflammatory
process?

What Erosive joint changes

radiographic sign
on plain films
are the hallmark
of an
 inflammatory
process?

What are Reactive bony changes seen in degenerative arthritis

osteophytes?

What are Osteophytes seen in the spondyloarthropathies

syndesmophytes?

What else should Fractures

be looked for on
plain films?

What if the plain In such cases an MRI (or ultrasound) may be useful in some
films are clinical settings.
negative in a
patient with a
suggestive
clinical history?

Why order a A bone scan measures abnormal metabolic processes

bone scan? involving the bone. This can occur in fractures, bone
metastases, metabolic bone disease, and degenerative
bone disease.

Why order an It is a critical tool to demonstrate early erosive changes

MRI? and pannus (synovitis). It is also useful to examine the
spine, the neuroforamina, and the CNS. It is most useful to
evaluate disc space infection, osteomyelitis, bone tumor,
and insufficiency fractures. MRI and MRA are useful in
evaluating patients with vasculitis.

Why order an This study is the gold standard in evaluating the presence
angiogram? of medium and large vessel vasculitis.

Why order an This technique has gained a significant place in the

ultrasound? evaluation of patients with inflammatory arthritis since it is
less expensive than MRI, yet it can demonstrate synovitis
and erosive changes early

P.503
P.504

Treatment of Rheumatic Diseases

What might a
What might a 1. Education
treatment plan for 2. Physical therapy/occupational therapy
a patient with 3. NSAIDs, which are used for their anti-inflammatory
inflammatory and analgesic effect
rheumatic disease 4. Corticosteroids, which are used when a strong anti-
include? inflammatory effect is needed
5. DMARDs, when an immunosuppressive drug is needed
6. Antibiotics such as doxycycline or minocycline and
drugs that have immunomodulatory effect, such as
sulfasalazine and hydroxychloroquine

What are biologic These drugs are DMARDs. They include anti-TNF-! drugs,
therapies? antiB cell agents, and a drug that inhibits the
costimulation of T cells.

What are the 1. Infliximab (Remicade) is a chimeric (hybrid)

current antiTNF-! murine/human monoclonal antibody directed to TNF-
drugs used in !.
rheumatology? 2. Etanercept (Enbrel) is a recombinant fusion protein
consisting of the ligand-binding domains of the TNF-
! receptor (the business end of the receptor) and
the Fc portion of immunoglobulin (IgG1).
3. Adalimumab (Humira) is a humanized monoclonal
antibody directed against TNF-!.

What is an antiB Rituximab is a monoclonal antibody against CD20, a

cell drug? surface antigen found on B cells.

What is Abatacept? Abatacept is a fusion protein that blocks the

costimulation of T cells.

Do some Yes, there is an association between certain collagen

rheumatologic vascular diseases and malignancy. In most cases an
illnesses pose a ageappropriate malignancy screening is adequate.
higher risk for However, in other cases (e.g., dermatomyositis and
malignancy? paraneoplastic syndromes), a more extensive evaluation
for malignancy is needed at the time of diagnosis and
periodically thereafter.

What should be Evidence of infectious disease process. Vaccines need to

screened for in be up to date (no live vaccine for patients who are
patients who will immunosuppressed).
require
immunosuppressive
therapy?
 Should any Gastroprotection for patients on high-dose
prophylaxis be corticosteroids and/or NSAIDs
considered for
patients on NSAIDs?

For patients on long PCP prophylaxis

term
immunosuppression,
should any
prophylaxis be
considered?

In patients who Corticosteroid replacement

have been on long-
term steroids, what
should be
considered if they
are to undergo
surgery or medical
stress?

P.505

Major Toxicity of Rheumatic Drugs

What is a major toxicity
of:

Hydroxychloroquine Macular degeneration

Methotrexate Myelosuppression, hepatic injury and cirrhosis, and

pulmonary fibrosis

Azathioprine Myelosuppression, hepatotoxicity,

immunosuppression, and lymphoproliferative
disorders

Leflunomide Myelosuppression, hepatotoxicity,

immunosuppression

Sulfasalazine Myelosuppression and hepatic toxicity

AntiTNF-! drugs Immunosuppression, increased risk of malignancy

 Cyclophosphamide Immunosuppression, myeloproliferative disorders,
malignancy, hemorrhagic cystitis, infertility

Rituximab Immunosuppression

What is the time to

onset of effectiveness
for:

Intramuscular gold? 4 to 5 months

Methotrexate (MTX)? 1 to 2 months

Sulfasalazine (SSZ)? Weeks to months

Hydroxychloroquine 3 to 4 months
(Plaquenil)?

Cyclophosphamide Weeks
(Cytoxan, CTX)?

Azathioprine (Imuran, Weeks to months

AZA)?

Etanercept? Weeks

Infliximab? Weeks

Anakinra? Weeks

Adalimumab? Weeks

Rituximab? Weeks

Abatacept? Weeks

P.506

Avascular Necrosis
How does AVN present? With pain

How is AVN diagnosed? Radiographs (late)

MRI (early) (classical surreptitious pattern)
 What is the treatment of Analgesics and orthopedic surgery
AVN? consultation

Back Pain
What are physical
examination features for disk
disease at the following
levels?

L45 Decreased ability to walk on toes

L5S1 Decreased ability to walk on heels

What are the major Education, physical therapy, optimizing

treatment options for back weight, analgesics, pain clinic referral,
pain? orthopedic or neurosurgical consultation

Osteoarthritis
What is the OA occurs in 30% of adults and is the most common form of
incidence arthritis.
of OA?

What is Crepitus, bony enlargement, decreased ROM, pain with ROM, and
found on mild inflammation. Distribution is bilateral and often
examination asymmetrical, involving hands, feet, knees, and hips and usually
in OA? sparing shoulders and elbows.

P.507

Rheumatoid Arthritis
What is the RA occurs in 1% to 2% of all adults. It is the most common
incidence of autoimmune disease.
RA?

What risk Female gender and family history. Several genetic

factors are susceptibility markers have been identified, and some of
associated these markers are associated with more aggressive disease
with RA? (heterozygote for DRB1 0401 and DRB1 0404).

What does Synovitis (inflammation of the synovium) localized to the

examination MCPs and PIPs (DIPs spared)
of the
rheumatoid
hand find
early in the
illness?

What does Ulnar drift caused by tendon laxity; subluxation of proximal

examination phalanges under MCP heads; and nodules on bony
of the prominences and extensor surfaces
rheumatoid
hand find late
in the illness?

What are Interstitial fibrosis; pleural, pericardial and cardiac

some involvement; episcleritis/scleritis; Felty's syndrome
extraarticular (splenomegaly and leukopenia)
manifestations
of RA?

What are the RF is present in 80% of cases. Anti-CCP antibody is found in

laboratory test 60% of RA patients.
findings in RA?

What other Subacute bacterial endocarditis, viral and other infections

conditions are (e.g., infectious mononucleosis, hepatitis C, tuberculosis,
associated Lyme disease), increasing age, SLE, SjS, and sarcoidosis
with RF?

What is anti- An antibody directed against cyclic citrullinated peptide,

CCP? more specific than RF for the diagnosis of RA

How is the Documentation of inflammatory synovitis by the following:

diagnosis of
1. Synovial fluid WBC count >2000/mm3
RA made?
2. Chronic synovitis on histologic study
3. Radiologic evidence of erosions
4. Symptoms present for longer than 6 weeks
5. Symmetric joint involvement

When are DMARD therapy should be initiated as soon as a definitive

DMARDs diagnosis is established. The goal is a clinical and laboratory
started? remission.

In addition to The overall treatment plan should also include physical and
DMARDs, what occupational therapy, joint injections with steroids, and
other surgery for joint stabilization. For progressive disease,
 therapies consider synovectomy (unresponsive to medical treatment) or
should be joint replacement (advanced disease).
considered in
RA?

When are oral Oral steroids should be used for bridge treatment (i.e.,
steroids used? while waiting for DMARDs to be effective).

When is In cases of severe flares, vasculitis, relative steroid

treatment of insufficiency, or joint or systemic infections
RA urgent?

When is When there is severe adrenal insufficiency (addisonian crisis)

treatment of or atlantoaxial (C1-C2) instability
RA emergent?

P.508
P.509

Connective Tissue Disease

Systemic Lupus Erythematosus

What tests CBC, ESR, C-reactive protein, UA, electrolytes, BUN,
should be creatinine, ANA (high sensitivity), anti-dsDNA (high
ordered for specificity), anti-Smith, anti-RNP, anticardiolipin antibodies,
suspected CH50, and possibly C3 and C4
SLE?

Once the CBC, anti-dsDNA, CH50, UA, BUN, and creatinine. It is

diagnosis of noteworthy that the usefulness of anti-dsDNA and CH50 as
SLE is indicators of disease activity is limited.
established,
what tests are
used to follow
up disease
activity?

What are Increase in constitutional symptoms and other symptoms

urgent indicative of a flare
indications for Infection
treatment in New signs of renal involvementdecreasing renal function,
SLE? increasing BUN and creatinine from baseline, increasing
proteinuria, and increasing urine RBCs, WBCs, and casts
Other laboratory evidence of a flare such as the development
of hemolytic anemia or thrombocytopenia
 What should
also be
considered in
the following
SLE
emergencies?

Mental status CNS infection and vasculitis

change and/or
headache?

Acute Pericardial effusion, tamponade, or pulmonary embolus

shortness of
breath and/or
chest pain?

Leg pain, Hypercoagulable state

shortness of
breath,
pulmonary
embolus,
and/or CNS
changes?

Ischemic Raynaud's phenomenon, APS, vasculitis, and necrosis

digits?

Pregnant Patients with preeclampsia also have proteinuria, CNS

patient with disease, and HTN, making it difficult to differentiate toxemia
flare? from an SLE flare; however, SLE has low complement levels,
while the complement levels are usually normal in toxemia.
Also, serum uric acid levels are usually elevated in
preeclampsia and normal in an SLE flare.

P.510

Lupus Disease Subcategories

What is APS? Antiphospholipid antibody syndrome. This is a hypercoagulable
state that occurs in association with SLE, certain cancers, and
infections, or it can occur as a primary disorder in itself.

What is The diagnosis requires a history of a thrombotic event and a

required for positive lab test (lupus anticoagulant, anticardiolipin, or B2-
the diagnosis glycoprotein I antibody).
 of APS?

What is the Long-term anticoagulation with warfarin

treatment
for APS?

What Tests include anticardiolipin antibodies, prothrombin time,

laboratory partial thromboplastin time, Venereal Disease Research
tests are Laboratory tests, and modified Russell's viper venom time, anti
ordered in beta-2 glycoprotein-I, or local test for lupus anticoagulant.
the workup
of APS?

What agents Chlorpromazine, methyldopa, hydralazine, TNF-! inhibitors,

have been procainamide, isoniazid, and interferon
implicated in
DIL?

Systemic Sclerosis
What is SSc? A disorder of connective tissue characterized by
overproduction of collagen (types I and III) and matrix
proteins

What is the treatment Calcium channel blockers, losartan, and sildenafil

for Raynaud's
syndrome?

What is the treatment Angiotensin-converting enzyme inhibitors, hydralazine

for renal crisis?

GERD? H2 blockers, omeprazole

Lung disease? Cyclophosphamide

Pulmonary Sildenafil, bosentan, and/or epoprostenol

hypertension?

P.511

Sjgren's Syndrome
What are ANA, antiSS-A (anti-Ro), antiSS-B (anti-La), RF, cryoglobulins,
the anemia, leukopenia, thrombocytopenia, increased ESR. SjS is
laboratory known for high levels of multiple antibodies in nonspecific
 findings in patterns.
SjS?

Vasculitis

Polyarteritis Nodosa
What are the Hepatitis B surface antigen or antibody is found in 15%
laboratory findings of cases, urine RBCs, RBC casts, and proteinuria
in PAN?

Wegener's Granulomatosis
What are the laboratory findings UAmicrohematuria, RBC casts,
in Wegener's granulomatosis? proteinuria, and increased BUN and
creatinine
c-ANCApresent in 80% of cases
CXRbilateral, nodular fixed infiltrates
that usually cavitate

ChurgStrauss Syndrome
What are the 1. Prodrome that can last for many years. Allergic
three phases of manifestations include rhinitis, polyposis, and asthma.
Churg-Strauss 2. Peripheral blood and tissue eosinophilia with infiltration
disease? of organs like the lungs and the GI tract
3. Systemic vasculitis (heralded by fever and weight loss)
chest radiograph abnormalities, skin lesions,
mononeuritis multiplex, congestive heart failure,
abdominal symptoms, and renal disease

What are the Peripheral blood eosinophilia in more than 10% of cases.
laboratory Biopsy of lung or skin shows eosinophilic necrotizing
findings in granulomas and necrotizing small vessel disease.
Churg-Strauss
syndrome?

P.512

Other Vasculitides
Name three to four
distinctive features of
each of the following
vasculitides:
Giant cell arteritis 1. Headache, scalp tenderness, jaw claudication,
constitutional symptoms, PMR, depression, dry
cough, and ischemic optic neuritis
2. Occurrence in persons approximately 50 years
of age and more commonly in women than in
men
3. High ESR (>50)

Behet's syndrome 1. Recurrent painful aphthous oral and genital

ulcers
2. Uveitis and retinal vasculitis
3. Erythema nodosum and papulopustular skin
lesions
4. Possible CNS involvement

Cryoglobulinemia 1. Immunoglobulins that precipitate at cold

temperatures, and are usually RF.
2. Raynaud's phenomenon, purpura, and ischemic
ulcers, which are a result of hyperviscosity and
plugging of small vessels. Vasculitis is
uncommon.
3. Mixed cryoglobulins are associated with CTDs,
hepatitis A/B/C, parasites, many infections,
and lymphoproliferative diseases.

Takayasu's arteritis 1. Chronic vasculitis of the aorta and its branches

2. Occurrence in young women and in persons of
Asian descent
3. Asymmetrically decreased peripheral pulses

Henoch-Schnlein 1. Occurrence usually in 5- to 15-year-old

purpura children with history of upper respiratory
infection
2. Palpable purpura on buttocks and legs (IgA
found on biopsy of the skin lesions)
3. Crampy umbilical pain and nephritis

Primary angitis of the 1. Small and medium vessel vasculitis in the CNS
CNS 2. Laboratory workup usually negative
3. Diagnosis based on MRI, angiogram, and/or
biopsy

Cholesterol emboli
 Cholesterol emboli 1. Fever, livedo, digital ischemia, gangrene
2. Mononeuritis multiplex
3. Renal insufficiency

P.513

Seronegative Spondyloarthropathies
Name the five seronegative 1. Ankylosing spondylitis
spondyloarthropathies. 2. Reactive arthritis
3. Reiter's syndrome
4. Psoriatic arthritis
5. Enteropathic arthritis

Ankylosing Spondylitis
What are the imaging The earliest changes may be erosions involving the
findings in ankylosing sacroiliac joints and squaring of the vertebral bodies,
spondylitis? especially at the thoracic-lumbar junction.
Radiographs show symmetric ankylosis of sacroiliac
joints and spine, absence of subluxation and cysts, and
generalized osteopenia after ankylosis.

How is the diagnosis Clinical presentation and radiographic findings.

of ankylosing In early cases, radiographs may be normal; MRI may be
spondylitis made? useful in establishing the diagnosis.

What are the Include NSAIDs (e.g., indomethacin), sulfasalazine (may

medications used for be effective as a DMARD), and antiTNF-! therapy
ankylosing
spondylitis?

What are emergent The ankylosed spine is susceptible to fracture, usually

considerations in transverse, at C5C6 or C6C7, with risk of spinal cord
ankylosing injury.
spondylitis?

P.514

Reactive Arthritis
What microbes are Yersinia, Salmonella, Shigella, and Campylobacter in
associated with the gastrointestinal tract; Chlamydia in the
reactive arthritis? genitourinary tract

What are the There are no diagnostic tests, but the clinician should
 laboratory findings in try to isolate pathogens and rule out septic arthritis
reactive arthritis? and GC arthritis.

Reiter's Syndrome
What is the classic triad of Reiter's Arthritis, urethritis (nongonococcal), and
syndrome? conjunctivitis

Psoriatic Arthritis
What are some Involvement of the DIP, inflammation involving a ray
of the clinical distribution (DIP, PIP, MCP, of the same digit). Usually skin
distinguishing involvement precedes arthritis; however, approximately 15%
features of of patients present first with joint inflammation.
PsA?

What are the 1. Oligoarticular (asymmetric), 50%

five disease 2. Spondyloarthropathy, 20%
patterns of 3. Polyarticular (RA-like), 20%
PsA? 4. DIP disease (classic), 8%
5. Mutilans (deforming), 2%

What is a Proliferative bone changes adjacent to the erosions

distinguishing
feature of
radiographic
findings?

Enteropathic Arthritis
How frequently does arthritis occur in In 20% of cases
Crohn's disease?

What is the distribution of the arthritis? Distribution is pauciarticular,

asymmetric, transient, and
migratory.

Which joints are affected? Affects large and small joints of

lower extremities

What are the classic hand and foot Sausage digits (dactylitis) and
changes? heel enthesopathies

How does the arthritis correspond with They do not strictly coincide.
 the activity of the bowel disease?

How frequently does arthritis occur in In <20% of cases

ulcerative colitis?

How do the arthritic features compare to They are the same.

those of Crohn's disease?

How does the timing of the bowel Has a more distinct temporal
activity and the arthritis compare to that relationship between flares of
of Crohn's disease? arthritis and colitis

P.515

Gout and Pseudogout

Gout
What are the four stages of gout? 1. Asymptomatic hyperuricemia
2. Acute gouty arthritis
3. Intercritical gout
4. Chronic tophaceous gout

Acute Gouty Arthritis

What are attack Alcohol, surgical stress, trauma, acute medical illness,
triggers for acute and drugs (diuretics, allopurinol, or probenecid
gouty arthritis? without colchicine)

What is intercritical Avoidance of alcohol, weight loss, and colchicine;

treatment of chronic probenecid (uricosuric); and allopurinol (xanthine
gout? oxidase inhibitor)

Chronic Tophaceous Gout

What are complications of chronic Renal stones, proteinuria, HTN, and
tophaceous gout? chronic renal insufficiency

What are some of the Kidney stones

contraindications for uricosuric Renal insufficiency
treatment? Tophaceous gout

P.516

Pseudogout
 What is the incidence of Approximately half as common as gout
pseudogout?

What are risk factors for Aging, OA, amyloid, hypothyroidism,

pseudogout? hyperparathyroidism, and hemochromatosis

What are the laboratory In synovial fluid, CPP crystals are short,
findings in pseudogout? cuboidal, and blue when parallel to axis.

What is the therapy for NSAIDs, colchicines, or steroids

acute pseudogout?

Infectious Arthritis
List the infectious arthritis GC, nongonococcal, Lyme, and viral
syndromes.

What pathogens are associated Neisseria gonorrhoeae is most common in

with infectious arthritis? sexually active adults. Staphylococcus aureus
is most common otherwise.

What are the microbiologic S. aureus (60%), streptococci (15%), gram-

findings in nongonococcal negative rods (15%), Pneumococcus (5%), and
bacterial arthritis? polymicrobial (5%)

What is the differential RA and crystalline joint disease

diagnosis of increased WBCs
and PMNs in synovial fluid?

Gonococcal Arthritis
What is the incidence Of the 1 million cases of gonorrhea in the United
of GC arthritis? States per year, 1% have bacteremia and arthritis.

What is the clue to Tenosynovitis and dermatitis are rare in nonneisserial

the diagnosis of DGI? bacterial arthritis.

P.517

Nongonococcal Bacterial Arthritis

What are risk factors for Trauma, surgery, and arthrocentesis
nongonococcal bacterial Chronic medical illness (e.g., RA, diabetes
arthritis? mellitus, SLE, and chronic liver disease)
Age extremes
 Immunosuppression
Prosthetic joints

How often is the knee Distribution of 50% in knee

affected?

How often is it 80% monoarticular (polyarticular cases are

monoarticular? usually associated with a risk factor)

Which microbes are usually S. aureus, 60%; beta-hemolytic streptococci,

associated with 15%; gram-negative rods, 15%; Pneumococcus,
nongonococcal arthritis? 15%; and polymicrobial, 5%

Lyme Arthritis
What are the three 1. Early, localizederythema migrans
stages of Lyme arthritis, 2. Early, disseminatedmigratory musculoskeletal
and how are they pain, in joints, bursae, tendons, muscle and
characterized? bone
3. Latein 6 months, onset of brief attacks of
oligoarthritis, usually involving large joints
(knee). Episodes become longer, with erosion of
cartilage and bone.

What laboratory tests Enzyme-linked immunosorbent assay with Western

are ordered for Lyme blot to confirm. Both acute and convalescent titers
arthritis? should be evaluated.

Viral Arthritis

Parvovirus B19
What are features of Severe, self-limited flu-like illness with
parvovirus B19 illness in arthralgias and arthritis and a rheumatoid-like
adults? distribution

Hepatitis C Virus
List four rheumatic manifestations 1. Arthralgias
of hepatitis C. 2. Arthritis, palpable purpura, and
cryoglobulinemia
3. Fibromyalgia
4. Membranoproliferative
glomerulonephritis
 P.518

Hepatitis B Virus
List five arthritis features 1. Clinical presentation is immune complex
of hepatitis infection. mediated, occurring early in course.
2. Onset of arthritis is sudden and severe.
3. Distribution is symmetric, migratory, and
additive.
4. Joints involved are hands and knees.
5. Urticaria is a feature.

Human Immunodeficiency Virus

List six rheumatic syndromes seen in HIV. 1. Sjgren-like syndrome
2. Lupus-like syndrome
3. Vasculitis
4. Fibromyalgia
5. Hypertrophic osteoarthropathy
6. AVN

Arthritis Secondary to Systemic Diseases

Diabetes Mellitus
What is the differential diagnosis of pain and Acute mononeuritis
weakness in the proximal thigh of a diabetic? (femoral nerve)
Meralgia paresthetica
(lateral cutaneous nerve)
Diabetic amyotrophy
(polyneuropathy)
Lumbar plexopathy
Herniated disk
Herpes zoster (before
eruption)
OA in hip joint
AVN of femoral head
Trochanteric bursitis

Thyroid Disease
Name five rheumatologic 1. Osteoporosis
features of 2. Onycholysis (separation of nail from bed)
hyperthyroidism. differential diagnosis: Reiter's syndrome,
 psoriasis, PsA
3. Painless proximal muscle weakness with
normal creatine phosphokinase differential
diagnosis: PM

1. Frozen shoulder
2. Thyroid acropachy (distal soft tissue swelling,
clubbing, and periostitis of MCP joints)

Name four rheumatologic 1. Carpal tunnel syndrome

features of 2. Polyarthritis
hypothyroidism. 3. AVN of hip
4. Myalgias (may have elevated CK)

P.519

Sarcoidosis
What is the incidence of arthritis in sarcoidosis? 10%

Amyloidosis
How are types of amyloidosis classified? By type of amyloid protein
deposited (e.g., AA, AL, Ab2M,
and Ab)

What is the mean age of onset of Mean age at diagnosis, 60 years

idiopathic and myeloma-associated (AL)
amyloidosis?

What organs are commonly affected? Heart and kidney

How common is arthropathy? <5%

What is the shoulder-pad sign? Amyloid infiltration of the

shoulder, a nearly
pathognomonic sign

What illnesses is reactive amyloid (AA) Seen with RA, JRA, and
seen with? ankylosing spondylitis

What rheumatologic illnesses is AA rarely Extremely rare in SLE and PM

seen with?
 What inflammatory bowel disease is AA Seen in Crohn's disease; rare in
seen with? ulcerative colitis

What general category of patients develop Seen in long-term dialysis

beta 2-microglobulin amyloid? patients

What peripheral neuropathy is seen? Carpal tunnel syndrome

What bony manifestations are seen? Arthropathy, cystic bone lesions,

and pathologic fractures

Where are the amyloid deposits of aging- Localized microdeposits in joints

associated amyloid seen?

What other arthritis syndromes may occur OA and CPPD

with aging associated amyloid?

P.520

Arthritis Associated with Malignancies

Name five ways in 1. Metastatic disease to bone
which musculoskeletal 2. Primary malignant disease (rare)
syndromes may be 3. Paraneoplastic syndromes [e.g., PM,
related to scleroderma, lupus-like syndrome, and Sweet's
malignancies. syndrome (fever; abrupt onset of painful plaques
on arms, neck and head; and neutrophilia)]
4. Increased incidence of malignancy in preexisting
CTDs (e.g., SjS)
5. Malignancy as a complication of treatment (e.g.,
with cyclophosphamide, methotrexate, biologics
or radiotherapy) or rheumatic disease

Arthritis Secondary to Sickle Cell Disease

What are the most common sites of arthritis in Knees and ankles
sickle cell disease?

What are the most serious complications of AVN (hip, 10%);

arthritis in sickle cell disease? osteomyelitis (Salmonella)

P.521

Arthritis Secondary to Hemophilia

What is the incidence of 85%. It is the most common major
hemarthrosis (bleeding into a hemorrhagic event in the disease.
joint) in hemophilia?

What are features of an acute Swollen, warm, exquisitely painful

hemarthrosis? Held in flexion from muscle spasm
Progressive loss of form and function

What are features of a chronic Bony enlargement with atrophic muscle

hemarthrosis? affecting knees, then elbows, ankles, and
shoulders
Flexion contracture
Asymmetric, sporadic distribution
Editors: Bergin, James D.
Title: Advanced Medicine Recall, 1st Edition

Copyright 2009 Lippincott Williams & Wilkins

> Table of Contents > Section III - Related Specialties > Chapter 12 - Dermatology

Chapter 12
Dermatology

P.524
P.525

Abbreviations
ANA Antinuclear antibody

EN Erythema nodosum

H&P History and physical examination

HHV Human herpesvirus

HIV Human immunodeficiency virus

HPV Human papillomavirus

HSV Herpes simplex virus

KOH Potassium hydroxide

MF Mycosis fungoides

MM Multiple myeloma

MMR Measles, mumps, rubella

NL Necrobiosis lipoidica

NSAID Nonsteroidal anti-inflammatory drug

PUVA Psoralen plus ultraviolet light of A wavelength

RMSF Rocky Mountain spotted fever

RPR Rapid plasma reagin

 SCC Squamous cell carcinoma

SLE Systemic lupus erythematosus

SPF Sun protection factor

SSSS Staphylococcal scalded skin syndrome

STD Sexually transmitted disease

TEN Toxic epidermal necrolysis

TPN Total parenteral nutrition

UV Ultraviolet

VZV Varicella zoster virus

VZVIg Varicella zoster immunoglobulin

Introduction
What are the general rules of If it is wetdry it.
dermatology? If it's drywet it.
When in doubtcut it out.
If they are not on steroidsadd
them.

P.526

Topical Therapy
What is a A powder in water
shake lotion?

What is a To cool and dry the skin (e.g., calamine lotion)

shake lotion
used for?

What is a A liquid mix of oil in water

milky lotion?

What is a To cool and dry the skin or lubricate it (more oil or

milky lotion lubrication)
used for?

What is a A mix of oil in water

cream?
 What is a Acts as an intermediate agent between a lotion and an
cream used ointment. The higher the oil content, the more lubricating the
for? cream.

What is an A mix of water in oil

ointment?

What is an To lubricate and occlude the skin

ointment used
for?

What is a gel? Oil in water and alcohol

What is a gel Often used on hairy areas or when drying is desired (e.g.,
used for? fungus between toes)

P.527

Primary Skin Lesions

What is a macule? A flat, discolored, nonpalpable skin lesion <1 cm in
diameter

What is a patch? A flat, discolored, nonpalpable skin lesion >1 cm in

diameter

What is a papule? An elevated, circumscribed, palpable lesion <0.5 cm in

diameter

What is a nodule? An elevated, circumscribed, palpable lesion >0.5 cm in

diameter

What is a plaque? A flat-topped elevated lesion >0.5 cm in diameter with

elevation

What is a pustule? A circumscribed elevated lesion or papule containing pus

What is a vesicle? A small blister <0.5 cm in diameter

What is a bulla? A large blister >0.5 cm in diameter

What is a wheal An edematous elevated skin lesion, usually migratory,

(hive)? lasting 24 to 48 hours

What is a cyst? A cavity with an epidermal lining containing fluid or

cheesy material

What is a A dilated superficial blood vessel, usually blanchable

telangiectasia?
Secondary Skin Lesions
What is a crust? A dried skin exudate

What is a scale? A superficial group of dead epidermal cells

What is an The focal loss of superficial epidermis

erosion?

What is an Loss of epidermis and some dermis

ulceration?

What is a fissure? A deep split through the epidermis into the dermis

What is atrophy? Skin thinning

What is a scar? Fibrous tissue laid down in response to skin injury

What is an A skin abrasion caused by scratching

excoriation?

What is Thickening of the skin in response to rubbing, with

lichenification? increased skin markings

What are Small, nonblanchable lesions caused by extravasated blood

petechiae?

What is purpura? Larger areas of extravasated blood

P.528

Configuration and Morphologic Terms

How are the following
lesions shaped?

Nummular Coin-shaped

Serpiginous Snake-like

Herpetiform Grouped vesicles resembling HSV (but may also

result from noninfectious etiology)

Annular Ring-shaped

Targetoid Concentric rings

Dermatomal Follows the distribution of a cutaneous sensory

nerve
 Verrucous Warty

Discoid Oval or round

Morbilliform Maculopapular, resembling the exanthem of measles

P.529

History and Physical Examination

What 15 key questions should be What are the age and gender of the
asked in a dermatologic history? patient?
When did the problem start?
Where on the body did the lesion start, and
where is it now?
How did the condition appear at first, and
how has it changed?
What are the symptoms?
Is anyone else at home affected?
Have there been any occupational or hobby
exposures?
Has this or something like it happened
before?
Does the patient have any chronic medical
problems?
Has the patient had any particular life
stresses?
What medication is the patient taking?
Does the patient have allergies?
Are there any diseases that run in the
family?
What treatments have been tried?
Did any treatment help?

What six rashes should be RMSF, secondary syphilis, StevensJohnson

considered when the rash syndrome, erythema multiforme, toxic
involves the palms and soles? shock syndrome, and SSSS

P.530

Common Dermatologic Diagnostic Tools

What Usually HSV and VZV infection
does a
Tzanck
prep
help
diagnose?

How is a The base of an intact vesicle is scraped with a scalpel blade onto a
 Tzanck slide. It is air-dried, fixed in methanol, stained with Giemsa or
test Wright's stain, and then examined under a microscope.
done?

When are When multinucleated giant cells are seen

results of
a Tzanck
test
positive?

What Dermatophyte and yeast infections

does a
KOH
prep
help
diagnose?

When When a lesion has pustules, vesicles, or scales (if it scales, scrape
should a it)
KOH test
be done?

How is a Skin scales on the edge of a lesion or on the roof of a vesicle or

KOH test pustule are scraped onto a slide with a no. 15 scalpel blade or
done? another slide, 1 to 2 drops of KOH are applied, the sample is
covered with a coverslip and gently heated over an alcohol lamp.
The sample is allowed to sit for a few minutes and is then
examined under a microscope.

When are When hyphae, pseudohyphae, or yeasts are seen

the
results of
a KOH
test
positive?

How is a A papule or burrow is scraped with a no. 15 blade moistened with

scabies a drop of oil. The scrapings are transferred to a slide, covered,
scraping and examined. A positive result shows mites, eggs, or feces.
done?

How is a As the lamp is held over a skin lesion, typical colors are seen.
Wood's Certain infections fluoresce, and hypopigmented lesions are
lamp accentuated.
used?

P.531

Topical Corticosteroids
 How are topical steroids rated? From class VII (weakest) to class I
(strongest)

What determines the strength of Chemical structure, vehicle, and

a topical corticosteroid? concentration

What are some commonly used

weak, medium, potent, and
superpotent topical steroids?

Weak Hydrocortisone

Medium Triamcinolone acetonide

Potent Fluocinonide

Superpotent Clobetasol propionate

How strong a steroid can be Typically, weak steroids in class VII;

used on the face? sometimes, medium- or high-potency
steroids for 2 weeks or less

What are the side effects of Striae, atrophy, acne, rosacea, perioral
topical steroids? dermatitis, pigmentation abnormalities,
glaucoma, and systemic absorption

What factors may promote Prolonged treatment, use of potent topical

systemic absorption of topical steroids, large treated areas, and inflamed
steroids? skin (disrupts barrier function)

Infectious Diseases

Viral Infection
What is an Acute generalized cutaneous eruption, often symmetric,
exanthem? associated most commonly with viral infection or drug reaction,
occasionally with bacterial infection

What are Rubella, roseola infantum, adenovirus, echovirus, measles,

some scarlet fever, coxsackievirus A and B, and mononucleosis
common
exanthems?

What is an Lesions on the oral mucosa (e.g., Koplik's spots in patients with
enanthem? measles)

P.532

Chickenpox and Herpes Zoster

What is chickenpox? Highly contagious, primary infection of VZV (herpes
family)

What is the route of Respiratory route

transmission for
chickenpox?

What is the incubation 10 to 21 days

period?

What are the Fever, malaise, and pruritic vesicular rash. The rate
symptoms of of morbidity increases in adults and
chickenpox? immunocompromised patients.

What is the Dewdrop on a rose petal. Crops of vesicles with

appearance of surrounding erythema that are often excoriated and
chickenpox? crusted. An important feature is presence of lesions
in all stages of evolution.

What is the Starts on the head, then rains down the body
distribution of
chickenpox?

How is the diagnosis of Usually clinically. Tzanck smear or culture can verify
chickenpox made? the diagnosis.

What is the duration New lesions erupt for approximately 5 days, and then
of chickenpox? crusting begins.

What is Reye's A sometimes fatal combination of encephalopathy

syndrome? and hepatitis, most often in children with VZV who
have received aspirin

How is chickenpox A live attenuated varicella vaccine is available in the

prevented? United States. Vaccination is recommended for
children aged 12 to 18 months and anyone over 13
years old with a VZV-negative titer.

What is herpes zoster Acute, usually painful reactivation of the VZV from a
(shingles)? dorsal root ganglion in a unilateral dermatomal
pattern

Where is the source Sensory nerve ganglia harbor latent infection.

for herpes zoster
(shingles)?

What is the Grouped vesicles along a dermatome progressing to

appearance of herpes crusted papules
zoster?
 What are the most Thoracic dermatomes and the ophthalmic branch of
common locations for the fifth cranial nerve (V1)
herpes zoster on the
body and on the face?

What is Hutchinson's Vesicles on the nasal tip indicate involvement of the

sign and why is it of nasociliary nerve and can herald eye involvement.
concern?

What is the most Postherpetic neuralgia, in which pain may last for
common complication weeks, months, or years after resolution of the rash
of herpes zoster?

What demographic The incidence of postherpetic neuralgia increases

group is most affected with advancing age.
by postherpetic
neuralgia?

What is the treatment Oral acyclovir, famciclovir, or valacyclovir or

for herpes zoster? intravenous acyclovir for severe cases. Sometimes
steroids may be used to decrease inflammation.

Is there a preventive A vaccine for shingles is available for patients aged

therapy? 60 and over.

P.533

Warts
What are Also known as verrucae vulgaris, warts are caused by infection
warts? of the epithelium by HPV, which causes epithelial hyperplasia.
Warts are common in children and immunosuppressed persons.

What is the Appearance varies with location. Often, warts appear as firm
appearance keratotic papules with typical black dots (thrombosed
of warts? capillaries) and an irregular surface.

What are Some types of HPV (e.g., 6, 11, 16, 18, 31, 33), especially
complications genital, predispose the patient to malignancy. If warts are
of warts? perianal, vulvar, or perimeatal, an internal examination is
necessary because there may be mucosal involvement.

What are the Treatments include cryotherapy, topical acids, imiquimod,

treatment podophyllin, cantharidin, and laser.
options for
warts?

P.534
Molluscum Contagiosum
What is molluscum Small papules usually with central umbilication
contagiosum? caused by a poxvirus infection. These are very
common.

What are the risk factors for Attendance at day-care centers, sexual
molluscum contagiosum? activity, and HIV infection

What are the symptoms of Usually none, but the lesions may itch and
molluscum contagiosum? become eczematized.

What is the distribution of Anywhere on the body, but the genital area
molluscum contagiosum? raises suspicion of sexual transmission.

What is the duration of Months to years. They usually regress

molluscum contagiosum? spontaneously.

How is the diagnosis of Usually clinically. Lesions may also be curetted

molluscum contagiosum and placed on a slide for identification of
made? molluscum bodies.

What is the treatment for Curettage and freezing with liquid nitrogen are
molluscum contagiosum? the most common treatments. Imiquimod and
cantharidin may be used in children (less
painful).

What diagnosis should be HIV infection, especially when lesions are on

considered in a patient with the face. Many mollusca may also be seen in
many mollusca in unusual patients with atopic dermatitis.
locations?

P.535

Measles (Rubeola)
What is Paramyxovirus infection that is rarely seen as a result of
measles? administration of the MMR vaccine

What is the 8 to 13 days

incubation
period for
measles?

What are the The three C's: cough, coryza, and conjunctivitis, plus high
symptoms of fever and rash
measles?

What is the Petechiae on the soft palate, then white Koplik's spots on the
appearance mucosa adjacent to the second molars, followed 1 to 2 days
 of measles? later by erythematous macules and papules

What is the The rash starts postauricularly, then moves down to the trunk
distribution as the upper rash fades in 24 to 48 hours.
of measles?

What is Because of the vaccine, German measles (rubella) has become

rubella, and a rare viral infection. It is milder than rubeola but significant
how does it because it can cause serious congenital defects if infection
differ from occurs during pregnancy.
rubeola?

When should In a patient with an exanthem plus posterior cervical

rubella be lymphadenopathy
suspected?

Roseola Infantum
What is A common infection in children aged 6 months to 2 years, which
roseola is caused by HHV-6 or occasionally HHV-7
infantum?

What is the Exanthem subitum

rash in
roseola
called?

How is the Clinical diagnosis is made by the rash that follows the fever.
diagnosis Fever lasts 3 to 5 days; then, 1 to 2 days after defervescence, an
of roseola exanthematous rash appears. Infants generally appear well.
made?

P.536

Erythema Infectiosum
What is An exanthem common during the winter in children 5 to 15
erythema years old. It is caused by parvovirus B19 infection and is also
infectiosum? called fifth disease.

What are the Children are often asymptomatic but may have fever, sore
symptoms of throat, and malaise, followed 1 to 4 days later by a rash.
erythema Adults have more severe constitutional symptoms and
infectiosum? transient arthralgias.

What is the Diagnosis is made by the classic slapped cheek appearance,

appearance of which evolves into reticulate erythema on the trunk, proximal
erythema arms, and legs.
infectiosum?
 What is the None is necessary; however, infected pregnant women need
treatment for to be followed for the possibility of fetal complications.
erythema
infectiosum?

Bacterial Infection

Folliculitis
What infectious agents Primarily Staphylococcus aureus, also gram-
are associated with negative organisms and Pityrosporum
folliculitis?

What are the risk factors Shaving, hot-tub use (gram-negative organisms),
for folliculitis? prior steroid use, and antibiotics (Pityrosporum)

What is the appearance Pruritic or painful scattered erythematous papules

of folliculitis? and pustules around hair follicles

What is the distribution Any hair-bearing area (e.g., scalp, extremities,

of folliculitis? beard area)

How is the diagnosis of Clinically or by culture

folliculitis made?

What is the treatment for S. aureusantistaphylococcal antibiotics

folliculitis? Gram-negativeusually clears spontaneously with
cessation of hot-tub use or correction of the tub
pH
Pityrosporumtopical antifungal preparations

P.537

Cellulitis
What infectious
agents are associated
with cellulitis in:

Patients who are Group A beta-hemolytic streptococci, followed by S.

immunocompetent? aureus

Immunocompromised Gram-negative rods, including Pseudomonas

patients?

Periorbital location in Haemophilus influenzae

children?

After dog or cat bite? Pasteurella multocida

After saltwater Vibrio vulnificus
trauma?

What are the risk Diabetes mellitus, intravenous drug use,

factors for cellulitis? immunocompromised state, trauma, venous stasis, and
lymphedema

What are the Fever, chills, mild pain, lymphadenopathy, nausea,

symptoms of vomiting, and confusion, especially in the elderly
cellulitis?

What is the An erythematous, warm, indurated plaque

appearance of
cellulitis?

What is the Extremities are most commonly involved.

distribution of
cellulitis?

What is St. Anthony's Erysipelasa rapidly spreading superficial cellulitis

fire? most often on the face with well-defined margins

What is the most Group A streptococci

common cause of St.
Anthony's fire?

What clues help Crepitus (a sign of gas from bacterial metabolism),

determine the need extreme pain, rapid extension, dusky cyanosis, and
for surgical superficial gangrene may be signs of necrotizing
consultation in cases fasciitis.
of cellulitis?

What is necrotizing Fournier's gangrene

fasciitis in the
genitalia called?

What diagnostic tests Blood cultures, Doppler ultrasound if a severe

are ordered for infection or clot is suspected. The yield from
cellulitis? aspiration culture of the leading edge is low.

How is the diagnosis Usually clinically

of cellulitis made?

What is the treatment In the uncomplicated patient, staphylococcal or

for cellulitis? streptococcal coverage is needed; broader coverage is
needed in patients with medical problems such as
diabetes to cover gram-negative rods.

P.538
Abscesses
What is the most common Staphylococcus aureus
bacterial cause of skin
abscesses?

What type of skin infection is Methicillin-resistant S. aureus (MRSA)

commonly misdiagnosed as a infection
spider bite?

What is the most common An abscess or furuncle

presentation of MRSA infection
of the skin?

What is the treatment for Drainage of the abscess and coverage with
community-acquired MRSA either trimethoprim/sulfamethoxazole or
abscess of the skin? minocycline

Erythrasma
What is A common chronic superficial bacterial infection of the
erythrasma? intertriginous areas caused by Corynebacterium
minutissimum

What is the Sharply demarcated pink to brown macules coalesced

appearance of into confluent patches with a fine scale
erythrasma?

How is the Wood's lamp shows coral-red fluorescence.

diagnosis of
erythrasma made?

P.539

Impetigo
What is impetigo? A contagious superficial bacterial skin infection common
in children in the summer

What infectious Staphylococci, group A beta-hemolytic streptococci

agents are
associated with
impetigo?

What are the risk Poor hygiene and trauma

factors for
impetigo?

What is the A honey-colored crusting of erosions. The presence of

appearance of bullae implies infection with S. aureus.
 impetigo?

What is the Face is most common but any site is possible.

distribution of
impetigo?

How is the Usually clinically. Occasionally cultures are obtained.

diagnosis of
impetigo made?

What is the Usually oral antibiotics for coverage of staphylococci and

treatment for streptococci. Topical mupirocin may be given if the
impetigo? lesions are localized.

What is the Lesions should clear in approximately 1 week with

duration of treatment.
impetigo?

What complication Poststreptococcal glomerulonephritis, which is caused by

can follow certain strains of Streptococcus pyogenes
impetigo?

What is scarlet Toxin produced by S. pyogenes, usually in the setting of

fever? streptococcal pharyngitis

What Sandpaper texture of the exanthem, strawberry

characteristics help tongue, linear petechiae in skinfolds (called Pastia's
in the diagnosis of lines), and desquamation, which usually follows the rash
scarlet fever?

P.540

Fungal Infection

CandidiasisMucocutaneous and Intertriginous

What are the risk factors Diabetes, immunosuppression, oral contraceptive
for candidiasis? use, obesity, pregnancy, and antibiotics

What are the symptoms of Pruritus and occasionally pain. Or the patient
candidiasis? may be asymptomatic.

What is the distribution of Any mucosal surface and intertriginous skin (e.g.,
candidiasis? groin and under breasts)

What is the appearance of

candidiasis in the:

Oral cavity? White patches on mucosal surfaces and tongue

that can be scraped off
 Vagina? White cheesy discharge with vaginal inflammation

Intertriginous areas? Erythematous plaques, papules, and pustules;

well-demarcated raw surface with satellite
lesions

What does involvement of Candida affects the scrotum; tinea cruris does
the scrotum imply in cases not.
of superficial fungal
infection?

How is the diagnosis of Clinically, by KOH prep, and sometimes by

candidiasis made? culture

What is the treatment for A wide variety of oral and topical antifungal
candidiasis? regimens. Griseofulvin is not effective against
yeast, and nystatin is not effective against
dermatophytes.

P.541

Tinea (Dermatophytosis)
What is A common superficial fungal infection of keratin-containing skin
tinea? structures

What three Microsporum, Epidermophyton, and Trichophyton

genera of
fungi
commonly
cause tinea?

What are Diabetes mellitus and immunosuppression

the risk
factors for
tinea?

What is the Scaly erythematous plaque with an active border and central
appearance clearing
of tinea?

What are KOH prep of scraping reveals hyphal elements. In resistant or

the questionable cases, fungus may be cultured. Some types of
laboratory microsporum fluoresce bright green under a Wood's lamp.
findings in
tinea?

What is the Many are caused by dermatophytes; other causes include

cause of inflammatory diseases (e.g., psoriasis) or trauma. Therefore,
 dystrophic before initiating systemic treatment for fungus of the nail,
nails? positive KOH or culture must be demonstrated.

What is the Topical or oral antifungals, depending on location and severity

treatment
for tinea?

What is Common pattern of tinea involvement usually caused by

two foot, Trichophyton rubrum. Both soles and one palm are scaly and
one hand erythematous.
syndrome?

What is a A boggy, inflamed mass, usually on the scalp, representing an

kerion? immunologic reaction to tinea infection. Treatment is with oral
antifungals and often prednisone.

What is an A hypersensitivity reaction to a dermatophyte or cutaneous

id bacterial infection that is most often manifest as vesicles or
reaction? pustules on the palms and soles

Tinea Versicolor
What is tinea A common superficial yeast infection caused by Malassezia
versicolor? furfur. The rash is asymptomatic or occasionally pruritic with
pigment alterations.

What is the Scattered sharp roundoval macules with a fine scale made
appearance more obvious by scraping. On sun-protected skin, lesions are
of tinea hyperpigmented; on sun-exposed skin, lesions are
versicolor? hypopigmented.

What is the Usually the upper trunk and back

distribution
of tinea
versicolor?

How is the KOH scraping demonstrates spaghetti and meatballs hyphae.

diagnosis of
tinea
versicolor
made?

What is the A 2.5% selenium sulfide shampoo to the affected area is cost-
treatment effective, although most antifungal agents are adequate.
for tinea Reinfection is common. Normal pigmentation may take months
versicolor? to return.

P.542

Sexually Transmitted Diseases

 What is the differential diagnosis Think: Always Show Caution Getting
of genital ulcers? Lunch From The Hospital:
Aphthous ulcers
Syphilis
Chancroid
Granuloma inguinale
Lymphogranuloma venereum
Fixed drug eruption
Trauma (zipper or factitial)
Herpes

Syphilis
What are the Painless chancreulcer with an indurated border
classic skin signs
of primary
syphilis?

What are the Condylomata latasoft, fleshy papules in the genital

classic skin signs region
of secondary Moth-eaten alopecia
syphilis? Copper penny macules or papules with erythema on the
palms, soles, and trunk

What are the Noduloulcerative syphilidesplaques and nodules with

classic skin signs scalloped edges, with or without ulcers and scale
of tertiary Gummatous syphilispunched-out ulcers on an
syphilis? erythematous base on the scalp, face, and lower
extremities
Both skin findings are extremely rare

What is the Intramuscular penicillin G for primary syphilis. RPR tests

treatment for should be repeated periodically to confirm a decreasing
syphilis? titer, which indicates successful treatment.

P.543

Gonorrhea
What are the In men, urethral discharge; in women, discharge, pain,
symptoms of fever, or no symptoms
gonorrhea?

What is the In men, periurethral edema and discharge; in women,

appearance of vaginal discharge, endometritis, and salpingitis
gonorrhea?

How is the diagnosis On clinical grounds plus demonstration of gram-

of gonorrhea made? negative intracellular diplococci on Gram's stain
Herpes Simplex
What are the Fever blisters are likely acquired in childhood from relatives.
risk factors for Genital infection is transmitted sexually.
herpes
simplex?

What are the Initial symptoms include fever, malaise, pain, or no

symptoms of symptoms. In recurrent cases, symptoms include pruritic or
herpes painful vesicular lesions (systemic symptoms are uncommon in
simplex? recurrent cases).

What is the Clusters of vesicles or erosions on an erythematous base. In

appearance of immunocompromised patients, atypical presentation and
herpes location may occur.
simplex?

What is the Mucous membranes, lips, and nose, but any location is
distribution of possible
herpes
simplex?

How is the Clinically or by Tzanck smear or culture

diagnosis of
herpes simplex
made?

What is the Acyclovir, valacyclovir, and famciclovir may shorten the

treatment for duration, but they may be ineffective if not started in the
herpes first 24 hours. Generalized infection or infection in an
simplex? immunocompromised host may require higher dosing or
intravenous therapy.

What is the A hypersensitivity reaction after herpes infection

most common
cause of
recurring
erythema
multiforme?

What is Herpetic whitlow, classically seen in dental hygienists who do

herpetic not wear protective gloves
infection of
the finger
called?

What is Widespread florid herpes infection, usually in patients with

eczema eczema (atopic dermatitis)
herpeticum?
 What is the Herpes can be detected in (and probably transmitted by)
significance of infected individuals even when they are asymptomatic.
viral shedding?

P.544

Condylomata Acuminata
What is HPV infection of the genital epithelium
condylomata
acuminata?

What is the It is the most common sexually transmitted disease.

incidence of
condylomata
acuminata?

What is the Soft, flesh-colored, verrucous papule or plaque that may be

appearance of pedunculated or cauliflower-shaped
condylomata
acuminata?

How is the Clinically, by application of acetic acid on suspicious lesions

diagnosis of or by biopsy
condylomata
acuminata
made?

What is the Freezing with liquid nitrogen or application of topical

treatment for podofilox, imiquimod, or podophyllin. Large lesions may
condylomata require surgical or laser removal. They often recur because
acuminata? the wart virus is in surrounding normal skin.

What else is Sexual partners require examination; many do not realize

essential after that they are infected. Women require gynecologic
making the examination, and perirectal involvement requires rectal
diagnosis of examination. Association with cancer risk should be
condyloma discussed with the patient.
acuminata?

What types of 6, 11, 16, and 18

HPV does the
papillomavirus
vaccine target?

P.545

Human Immunodeficiency Virus

What are Condylomata acuminata, seborrheic dermatitis, psoriasis,
some skin pruritus, molluscum contagiosum, verrucae, cryptococcosis
conditions (mimicking molluscum), and Kaposi's sarcoma
associated
with HIV
infection?

Is there a Yes, a morbilliform exanthem in one third of patients

rash
associated
with primary
HIV infection?

What is A tumor derived from proliferative endothelial cells. Recent

Kaposi's polymerase chain reaction studies have found HHV-8 particles
sarcoma? in all types of Kaposi's sarcoma.

What are the 1. Classicoccurs in elderly Mediterranean men

three 2. Immunosuppressedespecially occurs with cyclosporine use
subvariants of 3. African
Kaposi's
sarcoma seen
in patients
who are HIV-
negative?

What is the Vascular-appearing macules or nodules that may require

appearance of biopsy for confirmation
Kaposi's
sarcoma?

What is the Any location, especially the face in HIV-positive patients and
distribution of lower extremity in classic variants
Kaposi's
sarcoma?

What is the Because all the treatments have side effects and do not
treatment for provide a cure, treatment varies per patient. Treatments
Kaposi's range from observation (if disease is localized) and
sarcoma? antiretroviral therapy to radiation, surgical excision, laser,
bexarotene, cryotherapy, intralesional or systemic vincristine,
paclitaxel or docetaxel (if disease is extensive or debilitating).

What skin Skin lesions of bacillary angiomatosis

lesions may
be confused
with Kaposi's
sarcoma in
AIDS patients?
 What is Skin lesions resulting from the proliferation of small blood
bacillary vessels
angiomatosis?

What are the Bartonella henselae and Bartonella quintana

two most
common
causes of
bacillary
angiomatosis?

What is the Doxycycline

treatment for
bacillary
angiomatosis?

What is oral White, asymptomatic, verrucous thickening of the inferolateral

hairy surface of the tongue caused by Epstein-Barr virus. It is
leukoplakia? virtually pathognomonic for HIV infection.

How can oral Thrush can be scraped off; hairy leukoplakia cannot.
hairy
leukoplakia
be
differentiated
from thrush?

P.546

Infestations

Scabies
What is Common infestation of the skin with a burrowing mite, Sarcoptes
scabies? scabiei, transmitted by skin contact

What is Linear burrows, papules, and excoriations

seen on
physical
examination
in scabies?

What are Extreme pruritus, especially at night

the
symptoms
of scabies?

What is the The wrists and ankles and the webs of fingers and toes are the
distribution most classic locations, but scabies also occurs in the pubic area
of scabies? (scrotum in men), lower abdomen, trunk, and legs.
 What Scabies scraping
diagnostic
tests are
performed
for scabies?

What is the A variety of scabicides are available. Permethrin is first-line,

treatment lindane and crotamiton are less used due to concerns about
of scabies? toxicity. A single dose of oral ivermectin also appears to be
effective.

What is Whereas typical infestation involves approximately 20 mites, in

Norwegian Norwegian scabies, thousands of mites infest the patient. It is
scabies? seen in mentally impaired persons, immunosuppressed patients,
and patients with decreased sensation.

P.547

Pediculosis (Lice)
What is Lice infestations of the scalp, body, or pubic area
pediculosis?

How are Scalp lice can be epidemic in school children, or they may occur
lice in adults after close contact. Body lice are usually seen in
transmitted? patients with poor hygiene and reside in clothing seams or
sheets. Pubic lice are typically sexually transmitted.

What are Pruritus

symptoms of
pediculosis?

What is the
appearance
of
pediculosis
on the:

Scalp? A few lice and many nits are seen firmly attached to hairs. Nits
are glued to hair shafts close to the scalp. If they appear more
than 1 cm from the scalp, they are probably hatched eggs.

Body? Itchy papules may be seen anywhere on the body. The lice are
rarely seen because they are nocturnal.

What is the Pubic lice are seen clinging to individual pubic hairs. They may
distribution also be found on axillary hair, chest hair, and eyelashes.
of pubic
lice?
 How is the On clinical grounds, with visualization of a louse
diagnosis of
pediculosis
made?

What is the
treatment
for lice on
the:

Scalp? Permethrin cream is first line and is applied for 10 minutes,

then nits are
combed out after loosening with vinegar. Treatment is repeated
in 7 days. Close contacts should be examined and fomites
cleaned. Malathion, pyrethrins, lindane, and oral ivermectin are
alternatives.

Body? Clothing and bedding are washed in scalding water or discarded.

Pubic area? As for scalp lice. The eyelashes should be checked for nits, and
treated with petroleum jelly if present. As these represent an
STD, the patient should be checked and treated for other STDs.

P.548

Cutaneous Larva Migrans

What is cutaneous larva Lesion caused by migration of a nematode larva
migrans? (commonly Ancylostoma braziliense) under the
skin

What is the epidemiology of Common in southeastern U.S. coastal areas

cutaneous larva migrans?

What are the risk factors for Walking barefoot or sitting on infested sand or
cutaneous larva migrans? soil

What are the symptoms of Extreme pruritus

cutaneous larva migrans?

What is the appearance of A thin serpiginous, erythematous trail that

cutaneous larva migrans? advances

What is the distribution of Feet and buttocks

cutaneous larva migrans?

What is the duration of Larvae die in 4 to 6 weeks because humans are

infection in cutaneous larva not the natural host.
migrans?
 How is the diagnosis of Clinically
cutaneous larva migrans
made?

What is the treatment for Thiabendazole applied topically under an

cutaneous larva migrans? occlusive wrap or administered orally

P.549

Eczematous Dermatitis

Contact Dermatitis
What is Pruritic acute or chronic inflammation of the skin caused by
contact contact with either a primary irritant or an allergen
dermatitis?

What is the Allergens cause type IV hypersensitivity reactions and require

difference prior antigen exposure for reaction to develop. Irritants probably
between represent 80% of contact dermatitis and do not require prior
an allergen sensitization. Allergic reaction occurs 1 to 3 days after exposure,
and an whereas irritant responses tend to occur soon after exposure.
irritant?

What are Poison ivy, nickel, rubber, fragrances, and preservatives

common
causes of
allergic
contact
dermatitis?

What is the Erythematous, scaly skin. Allergic contact dermatitis may be

appearance more indurated and less vesicular. Poison ivy causes linear
of contact streaks; sometimes oxidized black sap is seen on the skin.
dermatitis?

What is the Location may give clues to the cause; for example, nickel
distribution (earrings) earlobes, perfumeneck, toothpasteperioral.
of contact
dermatitis?

What Patch testing. A prepackaged kit, the T.R.U.E. Test, contains the
diagnostic 24 most common allergens.
tests are
done for
contact
dermatitis?

What is the In acute cases, topical corticosteroids two to three times per day
treatment and cool compresses. The precipitant should be identified and
 for contact avoided. If the case is severe, a prednisone taper may be
dermatitis? indicated. The reaction of poison ivy generally lasts 3 weeks from
exposure.

P.550

Atopic Dermatitis
What is atopic A chronic, pruritic eczematous skin disease associated
dermatitis? with asthma, hay fever, and allergic rhinitis

What is the Commonly starts in infancy and usually (but not always)
natural history of improves with time
atopic dermatitis?

What is the major Family history of asthma, hay fever, or eczema

risk factor for
atopic dermatitis?

What are the Pruritus, which may be severe enough to disrupt normal
symptoms of life and may worsen in winter or with stress. Exposure to
atopic dermatitis? allergens (e.g., dust mites, food antigens, and pollens)
may exacerbate the condition.

What is the Erythematous scaly plaques and papules with excoriations

appearance of and lichenification of affected skin
atopic dermatitis?

What is the In infants, extensor surfaces and face; in children, flexural

typical areas (popliteal and antecubital fossae); in adults, hands
distribution of
atopic dermatitis?

What tests are Scratch test to specific antigens, serum IgE level, and
helpful in atopic bacterial cultures of infected excoriations
dermatitis?

How is the Clinically

diagnosis of
atopic dermatitis
made?

What is the Soak and grease: avoidance of soap, wool, and fragrance
typical treatment Tepid baths with bath oil and followed immediately by
for atopic effective lubricants (e.g., petroleum jelly)
dermatitis? Topical corticosteroids to relieve inflammation
Allergen avoidance in the home
Antibiotics for secondary infection

What Generalized HSV infection and S. aureus superinfection

 complications
may be seen in
patients with
atopic dermatitis?

P.551

Stasis Dermatitis
What is Edema resulting from venous insufficiency with eczematous skin
stasis changes of the lower legs
dermatitis?

What are Pain, pruritus, or no symptoms

symptoms
of stasis
dermatitis?

What is the Edema, mild scale, weeping, hyperpigmentation (hemosiderin

appearance deposits), and lichenification. Lesions may progress to ulceration,
of stasis particularly at the medial malleolus.
dermatitis?

What is the Leg elevation, oral antibiotics for superinfection, pressure

treatment stockings of 30 to 40 mm Hg (not on active ulcers), and Unna's
for stasis boot (zinc gelatin) to decrease edema and help healing of ulcers
dermatitis? (Silvadene cream or DuoDERM may be applied to ulcers under
Unna boot)

Lichen Simplex Chronicus

What is lichen Chronic inflammation and thickening of the skin from
simplex constant scratching
chronicus?

What is the It is a common condition, especially in those with atopic

incidence of dermatitis.
lichen simplex
chronicus?

What is the An itch-scratch-itch cycle is set up and the patient cannot

cause of lichen stop scratching. Stress exacerbates the condition.
simplex
chronicus?

What is the Solitary or multiple well-demarcated plaques of itchy,

appearance of thickened, often hyperpigmented dry skin
lichen simplex
chronicus?
 What is the Hairline, wrists, neck, anal area, and extensor forearms
distribution of and shins
lichen simplex
chronicus?

How is the Clinically

diagnosis of
lichen simplex
chronicus made?

What is the The patient should attempt to keep from scratching, so as

treatment for to break the cycle. Topical corticosteroids are helpful.
lichen simplex Topical doxepin and oral antihistamines may also be
chronicus? useful.

P.552

Nummular Eczema
What are the Localized pruritus
symptoms of
nummular
eczema?

What is the Coin-shaped pink plaques, dull red in color with dry scale;
appearance of may ooze and form a crust
nummular
eczema?

What is the Any skin surface, especially lower legs and arms
distribution of
nummular
eczema?

How is the On clinical grounds after fungus has been ruled out by a KOH
diagnosis of preparation
nummular
eczema made?

What is the Lubrication of the skin with or without topical hydrocortisone

treatment for to relieve inflammation and antibiotics for secondary
nummular infection. Despite treatment, the condition is likely to recur.
eczema?

P.553

Papulosquamous Diseases

Psoriasis
What is psoriasis? A skin disease of multifactorial causes, in which epithelial
 proliferation is increased

What is the Common, occurring in 2% of Caucasians in the United

incidence of States
psoriasis?

What are the risk Psoriasis is a disease of Western populations and may be
factors for hereditary. Severe psoriasis can occur in HIV-infected
psoriasis? patients.

What are the Possible pruritus, arthritis in 10% of cases, and dystrophic
symptoms of nails
psoriasis?

What is the Discrete erythematous plaques with silvery white scale.

appearance of When scale is removed, typical spots of bleeding occur
psoriasis? underneath. Pitting of nails and the appearance of oil
spots underneath may be seen, and there may be
generalized exfoliative erythroderma.

What is the name Auspitz sign

of the sign when
a scale of
psoriasis is
removed and
bleeding occurs?

What is the Elbows, knees, scalp, umbilicus, and buttocks are most
distribution of common.
psoriasis?

What is Kbner's Psoriatic lesions that may be induced by trauma (a

phenomenon? nonspecific sign, as it may occur in lichen planus)

How is the Clinically

diagnosis of
psoriasis made?

What are the Topicaltar, anthralin, steroids, calcipotriol, salicylic

treatments for acid, PUVA, and UVA and UVB light
mild to moderate
psoriasis?

What are the Oralmethotrexate, etretinate, and cyclosporine

treatments for Subcutaneous and intravenous injections; biologic
moderate to therapies include alefacept, efalizumab, etanercept,
severe psoriasis? infliximab

How do the Either by reducing the number or activation of T cells or

 biologic therapies inhibiting tumor necrosis factor alpha made by activated T
work? cells

What is guttate Explosive eruption of small psoriatic papules and plaques,

psoriasis? often after streptococcal pharyngitis

P.554

Pityriasis Rosea
What is A common erythematous, scaling eruption of unknown cause,
pityriasis usually occurring in young adults. It is generally
rosea? asymptomatic.

What is the Starts with an erythematous scaly herald patch several

appearance of centimeters in diameter, then erupts with pink, oval, scaly
pityriasis macules on the trunk in a Christmas tree pattern
rosea?

How is the Clinically

diagnosis of
pityriasis rosea
made?

What is the None. The condition generally resolves spontaneously in 3 to

treatment for 12 weeks.
pityriasis
rosea?

What infection Secondary syphilis (which lacks a herald patch) should always
can mimic be considered in the differential diagnosis. If there is doubt,
pityriasis an RPR should be ordered.
rosea?

Seborrheic Dermatitis
What is seborrheic A chronic inflamed scaling condition of unknown
dermatitis? cause. Pityrosporum ovale infection has been
implicated as a contributing factor.

What is the incidence Very common, beginning at puberty (common

of seborrheic dandruff); also common in the newborn (cradle cap
dermatitis? and diaper dermatitis)

What is the Erythematous, sometimes pruritic rash with greasy

appearance of scales
seborrheic
dermatitis?

What is the Scalp, eyebrows, nasolabial folds, ear canals, chest,

 distribution of and groin
seborrheic
dermatitis?

How is the diagnosis Clinically

of seborrheic
dermatitis made?

What is the treatment Ketoconazole, selenium sulfide, or other dandruff

for seborrheic shampoo three times per week can be applied to
dermatitis? scalp, eyebrows, and skin. Topical steroids are used to
control inflammation. The goal is control, not cure.

What diagnosis should HIV infection. In the elderly, it may be associated

be considered in with Parkinson's disease or other central nervous
adults with sudden, system disorders.
florid seborrheic
dermatitis?

P.555

Inflammatory Disease

Acne
What is Inflammation of the sebaceous glands of multifactorial cause,
acne? including Propionibacterium acnes infection and hormones,
commonly the first sign of puberty

What are Family history

the risk
factors for
acne?

What is the Open (whitehead) and closed (blackhead) comedones,

appearance erythematous papules, and pustules
of acne? Cystic acnedeep nodules and pus-filled cysts. Even though all
lesions can cause scarring, it is more common in cystic acne.

What is the Face, chest, back, and neck

distribution
of acne?

How is the Clinically

diagnosis
of acne
made?

What is the Topical tretinoin (Retin-A), adapalene, benzoyl peroxide,

treatment erythromycin, clindamycin, azelaic acid, sulfur, and salicylic acid
 for mild
cases of
acne?

What is the Topical agents as for mild cases plus oral antibiotics
treatment (tetracycline, erythromycin, doxycycline, or minocycline).
for Trimethoprim/sulfamethoxazole is effective for resistant acne but
moderate is associated with a higher incidence of severe allergic reactions
cases of (e.g., Stevens-Johnson syndrome).
acne?

What is the Isotretinoin

treatment
for severe
or cystic
cases of
acne?

P.556

Rosacea
What is Chronic inflammation of the central face, commonly involving
rosacea? flushing erythema and intermittent acneiform eruptions. There
is a wide spectrum of severity from flushing and telangiectasias
to disfiguring papules and pustules.

Whom does Especially fair-complexioned persons of Celtic origin

rosacea
affect?

What is the Erythema with papules, pustules, and telangiectasia but no

appearance comedones
of rosacea?

What is Rhinophyma is seen almost exclusively in older men. The nose

rhinophyma? has a bulbous W.C. Fields appearance, which is caused by
chronic hyperplasia of the sebaceous glands secondary to
rosacea.

What are Conditions that induce flushing consumption of alcohol (red

the wine more than beer, beer more than liquor), hot beverages,
aggravating and spicy foods
factors for
rosacea?

What is the Avoidance of aggravating factors, tetracycline, doxycycline, and

treatment minocycline. Topical metronidazole, sulfur plus sulfacetamide
for rosacea? lotion, and many alternative therapies that are similar to
acne treatments. Surgical or laser therapy can be used to treat
 rhinophyma. Vascular lesion lasers can be used to treat
telangiectasias.

P.557

Granuloma Annulare
What is granuloma Chronic granulomatous inflammation of the dermis
annulare?

Whom does granuloma Children

annulare most
commonly affect?

What are the symptoms None

of granuloma annulare?

What is the appearance Annular dermal papules spreading outward, varying

of granuloma annulare? from flesh-colored to pink or violaceous, with no
scale present

What is the distribution Most commonly, lesions occur on the hands, feet,
of granuloma annulare? wrists, and ankles, but they may occur in a
generalized form.

How is the diagnosis of On clinical grounds and by biopsy

granuloma annulare
made?

What is the treatment Lesions tend to be recalcitrant, although many

for granuloma annulare? treatments have been tried.

P.558

Lichen Planus
What is A common, usually pruritic inflammation of the skin and mucous
lichen membranes, with a characteristic clinical and histopathologic
planus? appearance

What is the It is usually idiopathic but may be associated with hepatitis C.

pathogenesis Lichen planus, especially when extensive, has been associated
of lichen with many drugs (e.g., thiazides).
planus?

What is the Think the 5 P's:

appearance Purple
of lichen Polygonal
planus? Pruritic
Papules
Plaques
 What is the Lesions heal with hyperpigmentation. In the mouth, lacy
appearance reticular white lesions are seen. Chronic, painful mucosal
of healing ulcerations occur in both the mouth and vagina. There may be
lesions? nail loss or pterygium formation.

What is the Symmetric, most common in flexor areas, wrist, oral cavity, and
distribution genitalia
of lichen
planus?

What are White, lacy lines on the surface of lichen planus lesions, best
Wickham's visible with a hand lens after applying oil to the surface of the
striae? lesion

How is the There is a distinctive clinical picture; occasionally biopsy is

diagnosis of done. Lesions demonstrate Kbner's phenomenon at sites of
lichen trauma.
planus
made?

What is the Topical steroids are used frequently and may help pruritus, but
treatment the condition is poorly responsive to treatment. Most cases
for lichen resolve spontaneously in <1 year; 50% of oral lesions recur.
planus?

P.559

Dermatologic Manifestations of Systemic Disease

Skin Metastases
Which cancers Breast (no. 1 in women), lung (no. 1 in men), colon, and
commonly lymphoma
metastasize to skin?

To what areas of
the skin do the
following cancers
metastasize?

Breast Local skin (peau d'orange, en curasse [superficial

spreading cancer nodules across the trunk]) and scalp

Lung Trunk along intercostals and scalp

What is Sister Mary A round, dark, periumbilical nodule representing a

Joseph's nodule? cutaneous metastasis, usually of gastric cancer

What is erythema A wood grain pattern of annular, migrating

 gyratum repens? erythematous bands on the trunk associated with
internal malignancy

What is necrolytic Erythema, pustules, and erosions typically of the groin

migratory that mark a glucagonproducing pancreatic tumor.
erythema? Necrolytic migratory erythema can mimic candidal
infection.

P.560

Cutaneous T-Cell Lymphomas

What is cutaneous Cutaneous lymphomas are predominantly T-cell
T-cell lymphoma? lymphomas. Mycosis fungoides (MF) is probably the most
common and well described; it is a malignancy of the
CD4+ helper T cells.

What is the Uncommon but not rare. Occurs in middle-aged people,

incidence of in men more than women, and in blacks more than
cutaneous T-cell whites.
lymphoma?

What are the risk Human T-lymphocyte virus has been detected in some
factors for patients.
cutaneous T-cell
lymphoma?

What is the initial Variable, often starting as nonspecific large,

appearance of erythematous, superficial patches with fine scale. It can
mycosis fungoides? be serpiginous or annular.

What can the The lesions may mimic eczema or tinea infection.
lesions of mycosis
fungoides mimic?

What is the late Later MF evolves into plaques and reddish purple
appearance of nodules with lymphadenopathy. There may also be
mycosis fungoides? hyperkeratosis of the palms and soles and alopecia.

What is the Often starts on buttocks, thighs, and abdomen and later
distribution of becomes generalized
mycosis fungoides?

What is the course Variable progression

of mycosis
fungoides?

What is Szary's A variation of MF including erythroderma,

syndrome? lymphadenopathy, and more than 10% atypical
lymphocytes in the buffy coat
 What is large plaque An eczematous condition involving erythematous patches
parapsoriasis? >5 cm with fine scale

What is the Progression to MF occurs in 10% of cases.

potential late
complication of
large plaque
parapsoriasis?

How is the diagnosis On clinical grounds and by biopsy. The diagnosis of MF

of cutaneous T-cell may require multiple samples over time; biopsy is
lymphoma made? required for cell typing.

What is the Topical nitrogen mustard, topical steroids, topical

treatment for retinoids and UVB therapy
indolent cases of
mycosis fungoides?

What is the Aggressive or widespread diseasePUVA, electron beam,

treatment for extracorporeal photophoresis, and chemotherapy
aggressive cases of
mycosis fungoides?

P.561

Acanthosis Nigricans
What is acanthosis A common hyperpigmented, velvety thickening of
nigricans? intertriginous skin, especially at the back of neck and
in the axillae

What conditions are Diabetes mellitus, Cushing's disease, oral

associated with contraceptive use, Addison's disease, obesity,
acanthosis nigricans? hypothyroidism, niacin therapy, and malignancies
(90% are abdominal)

What is the most Gastric adenocarcinoma

common cancer
associated with
acanthosis nigricans?

How is the diagnosis of Clinically

acanthosis nigricans
made?

What is the treatment Although no treatment is necessary, ammonium

for acanthosis lactate may be used; obese patients should be
nigricans? encouraged to lose weight.
Necrobiosis Lipoidica
What is Granulomatous disease of unknown cause
necrobiosis
lipoidica?

Whom does Usually occurs in young adults and in women more than
necrobiosis men
lipoidica affect?

What are the risk Diabetes mellitus and trauma. (Whereas <1% of diabetics
factors for have necrobiosis lipoidica, most patients with necrobiosis
necrobiosis lipoidica have diabetes.)
lipoidica?

What are the Usually none, but lesions are painful if ulcerated.
symptoms of
necrobiosis
lipoidica?

What is the Starts as an erythematous macule, then enlarges into a

appearance of yellow-brown plaque with a waxy atrophic center,
necrobiosis telangiectasia, and an elevated shiny border.
lipoidica?

What is the Most are pretibial.

distribution of
necrobiosis
lipoidica?

How is the Usually clinically, with biopsy undertaken if there is doubt

diagnosis of
necrobiosis
lipoidica made?

What is the Minimal success has been achieved with any treatment,
treatment for including glucose control.
necrobiosis
lipoidica?

P.562

Skin Manifestations of Diabetes Mellitus

What skin conditions are Think CENTURY:
associated with diabetes Cellulitis
mellitus? Eruptive xanthomas
Necrobiosis lipoidica diabeticorum
Tense bullae on lower legs (diabetic bullae)
Ulcers
 Rubeosischronic flushed appearance of face
caused by decreased vasoconstrictor tone and
pooling of blood
Yellow skinincreased levels of beta-carotene

Pruritus
What is the differential diagnosis of Think DOC HELP X THE DAMN
generalized pruritus? ITCHES:
Drugs (opiates)
Onchocerciasis
Crabs
Hookworms
Expecting (pregnancy)
Lymphoma (Hodgkin's disease,
MF)
Paraproteinemia
Xerosis
Thrombocytosis
Hepatic disease
Elusive infections
Diabetes mellitus
Allergies (food)
Multiple myeloma
Neuroses
Iron deficiency
Thyroid (hyper or hypo)
Chronic renal failure
Hyperparathyroidism
Erythrocytosis
Scabies

P.563

Rheumatic Fever
What is the classic rash of Erythema marginatum
rheumatic fever?

What is the appearance of Transient, asymptomatic, faint,

erythema marginatum? migratory serpiginous rash

Bacterial Endocarditis
What are Osler's nodes? Painful purple-red subcutaneous nodules on finger
and toe pads

What are Janeway Nonpainful petechial and nodular lesions on the

lesions? palms or soles
 Are Janeway lesions Acute
more common in acute
or subacute bacterial
endocarditis?

What is the most Trauma. However, bacterial endocarditis is also in

common cause of the differential diagnosis, especially when multiple
splinter hemorrhage of nails are involved and the splinters are near the
the nails? nail bed.

Sarcoidosis
How commonly is 25% of patients have skin involvement. It is possible to
the skin involved have cutaneous sarcoid without systemic involvement.
in patients who
have sarcoidosis?

What are the skin Sarcoidosis is considered a great imitator, with a wide
signs of spectrum of appearances. All lesions are apple jelly
sarcoidosis? color when blanched with a glass slide:
Erythema nodosummost common
Lupus pernio
Scarring alopecia, pruritus, ichthyosis, papules,
hypopigmented macules, and ulceration

What is lupus Cutaneous sarcoidosis manifested as small pink, tan, or

pernio? violaceous papules on the nose and acral areas that are
often associated with upper respiratory disease and
granulomas in the bones

Are any of the skin No. Even when sarcoid is clinically suspected, biopsy is
signs almost always done for confirmation.
pathognomonic of
sarcoidosis?

What does the skin Biopsy shows classic noncaseating granulomas.

biopsy of
sarcoidosis show?

What is Lfgren A combination of sarcoid, eosinophilia, erythema

syndrome? nodosum, bilateral hilar adenopathy, and fever. Prognosis
is good.

P.564

Erythema Nodosum
What is erythema The most common panniculitis, it is an acute
nodosum? inflammation of the subcutaneous fat.
 In what group is More common in young women
erythema nodosum
seen?

What are the common Streptococcal infection, sarcoidosis, oral

causes of erythema contraceptive use, ulcerative colitis, and idiopathic
nodosum?

What are the Pain, fever, and malaise

symptoms of erythema
nodosum?

What is the Diffuse, warm, erythematous nodules that are

appearance of indurated to touch, producing a very characteristic
erythema nodosum? clinical examination

What is the Pretibial more than arms, and usually symmetric

distribution of
erythema nodosum?

What is the duration Days to weeks

of erythema nodosum?

What diagnostic tests Culture for Streptococcus and chest film for sarcoid
are ordered for
erythema nodosum?

How is the diagnosis of Clinically, with confirmation by biopsy if necessary

erythema nodosum
made?

What is the treatment NSAIDs, rarely systemic steroids, potassium iodide,

for erythema treatment of the underlying disease, and bed rest.
nodosum? The condition often recurs.

P.565
P.566

Nutritional Deficiencies
What is the vitamin C Scurvy
deficiency syndrome?

What are the skin signs of Think RIPE-C:

scurvy? Red, bleeding gums
Impaired wound healing
Perifollicular petechiae
Ecchymoses on arms and legs
Corkscrew hairs
What is the zinc deficiency Acrodermatitis enteropathica, which is
syndrome? characterized by acral and perioral
eczematous lesions

What are the common causes Generally occurs in infants as an inability to

of zinc absorb zinc (can be fatal) or can be acquired
deficiency/acrodermatitis through malnutrition
enteropathica?

What is the disease of niacin Pellagra. Certain drugs such as INH (a niacin
deficiency? analog) can induce a similar state, as can
carcinoid (because of tryptophan
consumption).

What are the symptoms of The 3 D's:

pellagra? Diarrhea
Dementia
Dermatitis

What are the skin signs of Erythematous, hyperpigmented scaling

pellagra? eruption in a photodistribution

What is the rash around the Casal's necklace

neck called?

Can pellagra be a serious Yes. Patients can die if not treated.

problem?

A bright-red atrophic tongue Folic acid and B12 (among others)

indicates what deficiencies?

What causes vitamin B6 Alcoholism and INH use

deficiency?

What are the skin signs of Seborrheic dermatitis of the face, angular
vitamin B6 deficiency? cheilitis, and glossitis

Which essential fatty acid Linoleic acid, causing dry, scaly, easily
deficiency can result from bleeding lesions
prolonged use of total
parenteral nutrition?

How can this be treated? By rubbing the skin with sunflower oil

What is koilonychia? Spoon-shaped nails

What deficiency is koilonychia Iron deficiency, which may be seen in

associated with? Plummer-Vinson syndrome
 What are the cutaneous signs Flag signalternating bands of light and
of kwashiorkor (protein dark hair
malnutrition)? Enamel paint dermatosishard, scaly
erythema

What causes a yellow Excessive carrot eating. This is also often

discoloration to the skin in seen in otherwise healthy babies who are fed
anorexia? large amounts of cooked carrots and sweet
potatoes.

How is this skin discoloration There is no involvement of the sclera.

distinguished from jaundice?

P.567

Porphyria Cutanea Tarda

What is porphyria The most common of the porphyrias, it is a disease
cutanea tarda? of accumulation of porphyrin metabolites in the
skin.

What are the risk Alcoholism and other liver disease, iron overload,
factors for porphyria HIV infection, drugs (e.g., furosemide, tetracycline,
cutanea tarda? estrogens, and chloroquine), and genetic
predisposition

What is unique about It is the only porphyria that can be either acquired
porphyria cutanea or genetic.
tarda?

What is the deficiency Heterozygous uroporphyrinogen decarboxylase

in the genetic form of deficiency
porphyria cutanea
tarda?

What viral illness is the Strong association with hepatitis C

acquired form of
porphyria cutanea tarda
associated with?

What is the appearance Scarring blisters on the dorsal hands with milia
of porphyria cutanea formation, hypertrichosis of the temples, and
tarda? variable signs (sclerodermal-like plaques, alopecia,
and pigmentary changes)

What is the distribution Photodistributionblisters usually first appear on

of porphyria cutanea the dorsa of the hands.
tarda?

What do diagnostic tests Urine darkens on exposure to air. Samples fluoresce

 demonstrate in orange-red under Wood's lamp. Quantitative
porphyria cutanea porphyrin analysis shows uroporphyrins to
tarda? coporphyrins in a 3:1 ratio.

What is the treatment Avoidance of hepatotoxins (stop alcohol

for porphyria cutanea consumption)
tarda? Phlebotomy (1 unit per week) until a hemoglobin of
10 is reached; expect improvement in 3 to 6 months
Low-dose hydroxychloroquine

P.568

Lyme Disease (See Also Chapter 7, Infectious

Disease)
What is the Erythema chronicum migrans (or erythema migrans)
classic rash
of Lyme
disease?

What is the Expanding annular rash >5 cm with central clearing at the site
appearance of a tick bite. The rash of erythema chronicum migrans takes
and clinical several days to enlarge; if there is an immediate rash after
course of tick bite, this may be a hypersensitivity reaction to the bite.
Lyme
disease?

What Borrelia burgdorferi

bacterial
species is the
cause of
Lyme
disease?

What type of Ixodes scapulariseastern United States

tick bite Ixodes pacificuswestern United States
transmits this
bacterium to
humans?

How is the It is usually made clinically. A minority of patients notice the

diagnosis of tick bite.
Lyme disease
made?

What is the Doxycycline, 100 mg twice a day for 21 days

treatment for
Lyme
disease?
Thyroid Disease
What are the skin The 10 P's:
manifestations of Pretibial myxedema
hyperthyroidism? Palmar erythema
Periorbital swelling
Persistent facial flush
Poor hair growth
Pink papules, plaques, and nodules
Pigmentation increased
Proptosis (exophthalmos)
Palms are sweaty
Plummer's nails

What are Plummer's nails? Onycholysis (nails separating from nail bed)
and a scooplike upward curve on nails

What are the skin Think COLD MAN:

manifestations of Coarse hair and skin
hypothyroidism? Orange palms
Large tongue
Dry skin
Myxedema
Alopecia of the lateral one third of the
eyebrow
Nails brittle

P.569

Cushing's Disease
What are the skin manifestations of Cushing's Think STEROID BLAST:
disease? Striae
Telangiectasia
Ecchymoses
Round facies
Obesity, central
Increased hair growth
Dermatophyte
infections
Buffalo hump
Large clitoris
Acne
Skin atrophy
Tinea versicolor

Neurofibromatosis Type I (Von Recklinghausen's

Disease)
What are four skin signs of Caf au lait spotshyperpigmented macules
neurofibromatosis type I? on the trunk and legs
 Neurofibromassoft, fleshy nodules (up to
thousands)
Axillary frecklingCrowe's sign
Lisch noduleshamartomas of the iris (the
most common manifestation of
neurofibromatosis type I)

What is the buttonhole sign? Invagination of neurofibromas when pressed

Are caf au lait spots No. Diagnostic criteria require more than
pathognomonic for six lesions of >1.5 cm; 10% of normal
neurofibromatosis? individuals have one to three caf au lait
spots.

What anatomic location of Female areola and nipple

neurofibroma is almost always
pathognomonic for
neurofibromatosis type I?

What are the characteristics of Bilateral acoustic neuromas, schwannomas,

neurofibromatosis type II? and neurofibromas but no caf au lait spots
or axillary freckling

What diagnosis should be Albright's syndrome, which is manifest by

considered with extensive caf bone lesions and precocious puberty in
au lait macules with a coast of girls. The large macules respect the
Maine, or irregular, edge? midline and rarely involve the face.

P.570

Tuberous Sclerosis
What is tuberous A genodermatosis inherited in an autosomal dominant
sclerosis? pattern with mental retardation, seizures, and specific
skin changes

What are skin Ash leaf spotsoften the first sign, hypopigmented
manifestations of macules shaped like a thumbprint on thighs and legs
tuberous sclerosis? Adenoma sebaceum
Facial angiofibromas
Shagreen patches
Periungual fibromas on the nails

Miscellaneous Systemic Disease

What is the differential Think HYPERPIGMENTS:
diagnosis of diffuse Hemochromatosis
hyperpigmentation? mYxoma
Porphyria
Expecting (pregnancy)
 aRsenic
Pheochromocytoma
Iatrogenicdrugs, PUVA therapy
Gutmalabsorption, Peutz-Jeghers
Melanoma
Excess thyroid hormone
Neurofibromatosis
Tumorssecreting adrenocorticotropic hormone
and melanocyte-stimulating hormone
Scleroderma

What are Cullen's and Periumbilical and flank pooling of blood resulting
GreyTurner's signs? from hemorrhagic pancreatitis (or ruptured tubal
pregnancy)

P.571

Nail Signs and Systemic Disease

What are nail Terry's nailsopaque white proximal nail plate with normal-
signs of colored distal nails
cirrhosis? Muehrcke's nailstransverse white bands across nails seen
in hypoalbuminemia

What are Beau's Transverse nail ridges secondary to arrested nail growth
lines? during severe illness

What are half- Lindsey's nailsproximal half of nail bed is white and distal
and-half nails? half is brown, as seen in chronic renal failure

What are Mees' White, transverse nail plate lines secondary to arsenic
lines? poisoning or renal failure

Bullous Disease
What is the Bullous erythema multiforme, TEN, dermatitis herpetiformis,
differential porphyria, renal disease, diabetes, carbon monoxide toxicity,
diagnosis of barbiturate use, pemphigus vulgaris, bullous pemphigoid, and
bullae? epidermolysis bullosa

P.572

Pemphigus Vulgaris
What is The most dramatic and serious of the family of pemphigus
pemphigus diseases, pemphigus vulgaris is a chronic, life-threatening
vulgaris? autoimmune bullous disease of mucous membranes and skin,
with defective cellular adhesion of epidermal cells.

What is the Uncommon, occurs at any age

incidence
of
pemphigus
vulgaris?

What are Jewish or Mediterranean ethnicity

the risk
factors for
pemphigus
vulgaris?

What is the Flaccid blisters that break easily and become weeping erosions
appearance
of
pemphigus
vulgaris?

Where does On mucous membranes in more than 50% of casesa distinctive

pemphigus feature that helps in the diagnosis
vulgaris
start?

What is the It may remain localized to mucous membranes or spread to

distribution scalp, face, chest, axilla, and groin.
of
pemphigus
vulgaris?

What is The ability to extend a pemphigus vulgaris blister by pressing on

Asboe the lateral edge
Hansen's
sign?

What is Creation of a new pemphigus vulgaris blister by pressing on

Nikolsky's uninvolved skin
sign?

How is the Skin biopsy

diagnosis of
pemphigus
vulgaris
made?

What is Histologic examination reveals a suprabasilar blister;

seen on the immunofluorescence shows intracellular IgG.
biopsy?

What is the Systemic steroids, azathioprine, and cyclophosphamide

treatment
for
 pemphigus
vulgaris?

What is the Fatal if untreated and 10% mortality rate with treatment.
prognosis Exacerbations and remissions occur.
for
pemphigus
vulgaris?

P.573

Bullous Pemphigoid
What is bullous Seen in older patients, bullous pemphigoid is a chronic
pemphigoid? autoimmune blistering disease that is usually not life-
threatening.

What is the Much more common than pemphigus vulgaris

incidence of
bullous
pemphigoid?

What is the Large tense bullae on erythematous or normal skin. A

appearance of minority of patients have mucous membrane involvement.
bullous
pemphigoid?

What is the Common on lower extremities and flexural areas but can
distribution of be generalized
bullous
pemphigoid?

How is the Clinical suspicion is confirmed by biopsy.

diagnosis of
bullous
pemphigoid
made?

What is seen on Histologic examination reveals a subepidermal blister.

the biopsy? Immunofluorescence shows deposition of IgG and C3 in the
epidermis along the basement membrane.

What is the Tetracycline in mild cases; systemic steroids, azathioprine,

treatment for and methotrexate in more severe cases
bullous
pemphigoid?

What is the It is a self-limited disease that characteristically remits

prognosis for after years.
bullous
 pemphigoid?

P.574

Other Bullous Diseases

What is An intensely pruritic, vesicular eruption over extensor surfaces
dermatitis
herpetiformis?

What is A gluten-sensitive enteropathy. Lesions disappear when a

associated strictly gluten-free diet is followed.
with
dermatitis
herpetiformis?

What is the Dapsone

treatment of
choice for
dermatitis
herpetiformis?

What is SSSS? Staphylococcal scalded skin syndrome infection. It is caused

by S. aureus, which releases an epidermolytic toxin that can
act at distant sites, causing a generalized desquamative
disease in young children, whose kidneys cannot clear the
toxin.

How can SSSS At times it is difficult to distinguish between the two by

be clinical examination, but biopsy reveals a higher cleavage
differentiated plane in SSSS than in TEN.
from TEN?

From where Mucous membranes

should the
culture be
obtained in
SSSS?

Benign Skin Tumors

Keloid
What is a keloid? Overgrowth of scar tissue extending beyond the original
site of injury, more common in dark-skinned people

What is the Skin-colored, shiny, protuberant firm nodule

appearance of a
keloid?
 What is the Earlobe and areas of high skin tension (chest, shoulders,
distribution of and knees)
keloids?

How is the Clinically. Biopsy should be avoided unless necessary

diagnosis of because it may cause further overgrowth.
keloids made?

What is the Intralesional steroids or surgery plus intralesional

treatment for steroids. Pressure dressings using silicone may help.
keloids?

P.575

Dermatofibroma
What is a A firm dermal papule or nodule. It is skin-colored or
dermatofibroma? hyperpigmented, often occurring on the legs. It exhibits
dimpling when surrounding skin is pinched and may form
at sites of insect bites or trauma.

What is the Treatment is not required unless it is desired for cosmetic

treatment for reasons.
dermatofibromas?

Seborrheic Keratosis
What is a Benign epidermal proliferation with a greasy stuck on
seborrheic appearance, which may contain keratin horns. Keratoses can
keratosis? be tan, gray, or black and occur most commonly in elderly
white patients.

What is the None necessary; however, cryotherapy is effective if desired

treatment for for cosmetic purposes.
seborrheic
keratoses?

What is the Explosive growth of seborrheic keratoses associated with

sign of Leser gastrointestinal malignancy
Trlat?

Skin Tag (Acrochordon)

What is a skin A benign pedunculated skin growth associated with obesity
tag? and aging. Intertriginous sites and eyelids are the most
common sites.

What is the Removal by snipping or freezing, only for cosmesis

treatment for a
skin tag?
Sun Damage and Cancers
How do They block UVB (short-wavelength) and sometimes UVA
sunscreens work? (long-wavelength) light by either a chemical or physical
process.

Which range of UVB is the most important cause outdoors, but UVA is
UV light causes used in tanning salons; both contribute to aging and skin
sunburn? cancer.

What does SPF 15 Protection from sunburn 15 times longer with the
indicate? sunscreen than without

P.576

Actinic Keratosis
What is an actinic Precancer of epidermis caused by chronic sun exposure
keratosis? (actinic = sun)

What is the 1-mm to 1-cm rough, scaling pink patches and papules
appearance of with indistinct margins
actinic keratoses?

How is the Clinically. The lesion is often more easily felt by

diagnosis of palpation than it is seen. If there is induration, biopsy
actinic keratosis rules out SCC.
made?

What is the Reduction of sun exposure, freezing with liquid nitrogen,

treatment for or curetting. If there are many lesions, topical 5-
actinic keratosis? fluorouracil can be used.

What is the It is suspected that 1 in 1000 lesions progresses to SCC

prognosis for per year, but SCC develops eventually in 20% of patients
actinic keratosis? with actinic keratoses.

Basal Cell Carcinoma

What is basal cell Malignant neoplasm of epidermal basal cells
carcinoma?

What is the incidence of It is the most common form of cancer in the

basal cell carcinoma? world.

What are risk factors for Sun exposure and fair skin
basal cell carcinoma?

What are symptoms of Bleeding, itching, or no symptoms

 basal cell carcinoma?

What is the appearance of Most common of the group, with a pearly

nodular basal cell translucent papule with surface telangiectasias
carcinoma?

What is the appearance of Shiny blue-black nodule

pigmented basal cell
carcinoma?

What is the appearance of Red, scaly, eczematoid patch with or without

a superficial basal cell crust or ulcer
carcinoma?

What is the appearance of A sclerotic plaque

a morpheaform basal cell
carcinoma?

What is the distribution of Nose, then nasolabial fold, ear, face, back, and
basal cell carcinoma? chest, but may occur anywhere

How is the diagnosis of Clinical concern necessitates biopsy or excision.

basal cell carcinoma
made?

What is the treatment for Excision with margin if small.

basal cell carcinoma? Mohs' micrographic surgery if larger or in a
difficult area.
Radiation if surgery is not practical.
Curettage or imiquimod may be effective for
superficial basal cell carcinoma.

What is the prognosis for Good, as they spread by direct extension and
basal cell carcinomas? rarely metastasize

What is nevoid basal cell An autosomal dominant genodermatosis with a

carcinoma syndrome? susceptibility to forming many basal cell
carcinomas throughout life

P.577

Squamous Cell Carcinoma

What is SCC? Malignant neoplasm of epidermis

What is the incidence of 20% of all cutaneous malignancies

SCC?

What are the risk factors Sun exposure, family history, and
for SCC? immunosuppression after transplantation
What is the appearance of Erythematous, scaling, indurated plaque or hard
SCC? nodule with smooth, keratotic, or ulcerated
surface

What is the distribution of Sun-exposed skin and in burns and scars

SCC?

What is the term for SCC Marjolin's ulcer

arising in a wound or burn
scar?

What is the term for SCC Erythroplasia of Queyrat

in situ of the glans penis?

What is the term for SCC Bowen's disease, which may also occur in non
in situ of the skin? sun-exposed skin

How is the diagnosis of SCC Clinical suspicion necessitates biopsy.

made?

What is the treatment for Excision

SCC?

What is the prognosis for Metastasis is location-dependent. Most common

SCC? in high-risk areas such as the lip and ear.

P.578
P.579

Melanoma1
What is Malignant neoplasm of melanocytes
melanoma?

What is the In 1930, the lifetime risk of an American developing invasive

incidence of melanoma was 1 in 1500. The risk in the year 2000 was 1 in
melanoma? 74.

What are the Caucasian race, red and blonde hair, fair skin, exposure to
risk factors light (especially UVB), tendency to develop sunburn, frequent
for sunburn as a child or adolescent, dysplastic nevus syndrome,
melanoma? xeroderma pigmentosum, family history, and
immunosuppression

What other A new pigmented lesion (or skin-colored in the case of

factors should amelanotic melanoma); a change in color, size, shape, or
raise surface (ulcer, scaling, crusting, or bleeding) of an existing
suspicion of mole; and itching, burning, or pain of an existing mole
melanoma?
What Think ABCDE:
characteristics Asymmetry
of a mole Border (irregular, indistinct)
suggest Color (variegated or dark black)
melanoma? Diameter (>0.6 cm)
Elevated from skin surface

What are the 1. Superficial spreading (70%)

four clinical 2. Nodular (15% to 30%)
and histologic 3. Lentigo maligna (4% to 10%)
subtypes of 4. Acral lentiginous (2% to 8%)
melanoma?

What is a Lentigo malignaa large flat brown macule on an older

Hutchinson's patient.
freckle?

What is the In 10 years, MM develops in one third of these patients.

incidence of
malignant
melanoma
with lentigo
maligna?

What is Periungual pigmentation associated with subungual (under the

Hutchinson's nail plate) MM
sign?

What is the Anywhere on the body. Legs are the most common site in
distribution of women; the back is the most common site in men.
melanoma?

What is the Excisional biopsy. An incisional biopsy can be used if the

approach to lesion is of a size or in a location that would result in
biopsy a disfigurement if an excisional biopsy was performed.
suspicious
cutaneous
lesion?

How deep Biopsy should extend to subcutaneous tissue to allow depth

should the measurement, because tumor thickness is the most important
biopsy extend prognostic factor.
in suspected
MM?

What margins For melanoma in situ, 0.5 cm. For <2-mm-thick lesions, 1 cm;
are used in for 2-mm-thick lesions, 2 cm.
reexcision of
 melanoma?

What are poor Tumor thickness and depth of vertical invasion (Breslow's
prognostic thickness and Clark's level); location on scalp, feet, soles,
factors in head, neck, and trunk; male gender; nodular and acral
melanoma? lentiginous histologic subtypes; ulceration; increased mitotic
rate; larger tumor volume; microscopic satellites of tumor;
older age; and DNA aneuploidy

What are the Subcutaneous tissue, skin, lymph nodes, bone, liver, spleen,
common sites and central nervous system
of metastases
for
melanoma?

What is the Routine lab tests and imaging studies are not necessary for
workup of a melanomas <4 mm thick in asymptomatic patients. Sentinel
patient with node biopsy may be indicated for melanoma with a tumor
melanoma? thickness between 1 and 4 mm.

Is there any Yes. Interferon-alpha-2b has been approved for the adjuvant
adjuvant treatment of melanoma stages IIB and III. Studies show
treatment for increased disease-free survival but no increase in overall
melanoma? survival. Treatment is associated with significant toxicity.

What is the The disease is incurable at this time; therefore palliation of

treatment for symptoms is the goal. Surgical resection of symptomatic
metastatic metastases, if possible, is the best option. Melanoma is
melanoma? relatively radioresistant and chemoresistant; however, local
radiotherapy can offer some benefit. Melanoma vaccines are
being studied.

P.580

Immune and Autoimmune Disease (See Also Chapter

11, Rheumatology)

Sjgren's Syndrome
What is the appearance of Keratoconjunctivitis sicca (denuded
Sjgren's syndrome? epithelium of the conjunctiva)

What are the symptoms of Dry mouth and eyes, difficulty speaking,
Sjgren's syndrome? and dyspareunia

How is the diagnosis of On clinical grounds plus biopsy of salivary

Sjgren's syndrome made? gland

What is the treatment for Immunosuppressants and artificial

Sjgren's syndrome? lubricants
 P.581

Systemic Lupus Erythematosus

What is the Skin involvement in 75% of patients, with lesions being
appearance photosensitive; brightly erythematous, macular malar butterfly
of SLE? rash; erythematous papules; bullae; Raynaud's phenomenon;
palpable purpura (vasculitis); and periungual telangiectases

What is the Scarring plaques usually localized above the neck, with dilated
appearance follicles and horny plugs
of discoid
lupus?

What is the Polycyclic, annular, or psoriasiform lesions on sun-exposed

appearance surfaces and upper trunk
of
subacute
lupus?

What is the Face is most common, but symmetric lesions are seen on arms,
distribution legs, fingers, chest, and back.
of SLE?

Scleroderma
What are the
features of the
following
subtypes of
scleroderma:

Progressive Occurs in elderly women. More than 95% of patients have

systemic Raynaud's phenomenon. There is internal involvement,
sclerosis? especially of the heart, lung, and kidney. Sclerosis of the
skin is a major diagnostic feature.

CREST? Calcinosis cutis

Raynaud's phenomenon
Esophageal dysfunction
Sclerodactyly
Telangiectasias

Morphea Violaceous macules advance to hard, smooth, ivory-colored

(localized lesions most common on trunk, with possible motion-
scleroderma)? limiting joint involvement.

Linear? Lines of sclerosis on extremities or scalp (en coup de

sabre), with possible bone atrophy beneath
 P.582

Pyoderma Gangrenosum
What is pyoderma A chronic ulcerative condition of the skin
gangrenosum?

What are the risk Inflammatory bowel disease, hepatitis, Behet's disease,
factors for rheumatoid arthritis, SLE, and monoclonal gammopathy.
pyoderma One half of cases are idiopathic.
gangrenosum?

What is the Pustule progressing to a painful necrotic ulcer with

appearance of purple overhanging border
pyoderma
gangrenosum?

What is the Legs, buttocks, and abdomen most common

distribution of
pyoderma
gangrenosum?

How is the Clinically suspected but biopsy needed to rule out other
diagnosis of diseases
pyoderma
gangrenosum
made?

What is the Steroids, dapsone, minocycline, and cyclosporine

treatment for
pyoderma
gangrenosum?

Vitiligo
What is An autoimmune disorder resulting in destruction of melanocytes
vitiligo? and depigmentation

What is the Depigmented patches that are more disfiguring in dark-skinned

appearance patients
of vitiligo?

What Graves' disease and Addison's disease

diseases
are
associated
with
vitiligo?

What is the Starts distally on fingers, face, or genitalia and may spread
 distribution anywhere
of vitiligo?

How is the Clinicallythe lesions are more obvious under a Wood's lamp
diagnosis
of vitiligo
made?

What is the In light-skinned patients, no treatment may be necessary other

treatment than skin protection; in dark-skinned patients, topical steroids
for vitiligo? may be given for local disease. PUVA therapy may be effective in
restoring skin pigment; in severe cases, chemical depigmentation
of the remaining skin may be necessary.

P.583

Alopecia Areata
What is Autoimmune process characterized by localized loss of hair
alopecia
areata?

What is the Most common in young people

incidence
of alopecia
areata?

What is the Round area of hair loss without skin lesions and with no scarring.
appearance There may be diagnostic exclamation point hairs, which are
of alopecia thinner at the base than at the end. Alopecia areata can progress
areata? to complete body hair loss in alopecia universalis. There may
also be nail pitting.

How is the Usually clinically

diagnosis
of alopecia
areata
made?

What is the There is no cure, but intralesional steroid injections may

treatment stimulate hair growth at least temporarily. It takes
for approximately 1 month to see results, and new hairs may initially
alopecia be white. Sometimes oral steroids are used.
areata?

What is the In 75% of patients, hair regrows after treatment. In many

prognosis patients, regrowth is spontaneous. Younger age, more extensive
for loss, atopic diathesis, and ophiasis (hat-band loss) are poor
alopecia prognostic indicators.
areata?
Dermatomyositis
What is A systemic autoimmune disease with inflammation of skin
dermatomyositis? and muscles

What is the age Occurs from infancy to old age

of onset for
dermatomyositis?

What association In patients >60 years, there is a strong association with

is made with internal malignancy.
dermatomyositis?

What are the Fever, weight loss, arthralgias, and proximal muscle
symptoms of weakness
dermatomyositis?

What is the May have butterfly malar rash, photosensitivity, periorbital

appearance of heliotrope rash; periorbital edema; periungual
dermatomyositis? telangiectasias; Gottron's papules (flat-topped violaceous
papules); calcinosis cutis (more common in juvenile
diabetes mellitus); and Raynaud's phenomenon (one third of
patients)

How is the On clinical grounds, plus laboratory findings of elevated

diagnosis of creatine kinase and ANA. Skin biopsy may be helpful, but
dermatomyositis histologic findings are indistinguishable from cutaneous
made? lupus.

What is the Steroids plus immunosuppressants

treatment for
dermatomyositis?

P.584

Dermatologic Urgencies and Emergencies

What are some of the Bullous pemphigoid, pemphigus vulgaris (see Bullous
dermatologic Disease, above), SSSS, toxic shock syndrome,
urgencies and cutaneous vasculitis, RMSF, and meningococcemia
emergencies?

Erythema Multiforme
What are the HSV-1 infection is by far the most common cause; other
causes of factors include hepatitis A or B infection, pregnancy, drugs,
erythema streptococcal infection, other infections, poison ivy, or
multiforme? idiopathic.
 What is the Erythematous target lesions, papules, and plaques
appearance of
erythema
multiforme?

What is the Often localized to extremities, especially elbows, knees, the

distribution of dorsum of the hands, palms, and soles.
erythema
multiforme?

What is the Stop any potentially offending drug. Prophylactic acyclovir

treatment for should be considered in recurrent HSV-induced erythema
erythema multiforme.
multiforme?

What is the Episodes usually resolve in 2 to 3 weeks. The major concern

prognosis for is progression to Stevens-Johnson syndrome.
erythema
multiforme?

P.585

StevensJohnson Syndrome
What is Stevens Extensive cutaneous and mucosal involvement, often
Johnson syndrome? with atypical target lesions, vesicles, and erosions.
StevensJohnson is predominantly a drug reaction
and may be fatal.

Which medications are Phenobarbital, phenytoin, beta lactams,

the most common sulfonamides, and NSAIDs
culprits in Stevens
Johnson syndrome?

Toxic Epidermal Necrolysis

What is Severe, extensive, full-epidermalthickness necrosis associated
TEN? with a high mortality rate

What is the Bullae, exfoliation, mucosal involvement, and nail loss are
appearance common.
of TEN?

What is the Generally a drug reaction

cause of
TEN?

What is the Stop all medications, correct electrolyte imbalances, administer

treatment pain control, and give antibiotics as needed. Supportive and
for TEN? aggressive skin care in a burn unit is recommended. Use of
 systemic corticosteroids is controversial.

P.586

Exfoliative Erythroderma
What is A severe, generalized red inflammation and exfoliation of
exfoliative the skin
erythroderma?

What are the Think D-SCALPP:

common causes Drug eruptions
of exfoliative Seborrhea
erythroderma? Contact dermatitis
Atopic dermatitis
Lymphoma
Pityriasis rubra pilaris
Psoriasis

What are the Pruritus, chills, fevers, or no symptoms

symptoms of
exfoliative
erythroderma?

What is the Admit patient to hospital, stop all medications, give

treatment for topical or oral steroids, soak and grease, and monitor
exfoliative fluids and electrolytes. Skin biopsy may help confirm the
erythroderma? diagnosis.

What severe High-output cardiac failure from increased blood flow

consequence may through skin
follow
erythroderma?

Meningococcemia
What are the skin Petechiae and purpura on the lower extremities and
signs of trunk. Larger lesions with stellate, sharp, angulated
meningococcemia? borders with central necrosis are caused by septic emboli.

Rocky Mountain Spotted Fever

What is Petechiae and ecchymoses begin on the wrists and ankles and
the rash of spread to the palms and soles. They later generalize and become
RMSF? purpuric.

Drug Eruptions
What are the three most common drug 1. Morbilliform exanthem
eruptions? 2. Urticaria
 3. Fixed drug eruption

How common are drug eruptions? Occur in 3% of hospitalized

patients

P.587

Fixed Drug Eruption

What is a fixed drug Localized inflammation of the skin resulting
eruption? from ingested drug

What is the appearance of Well-circumscribed red to purple macule on

fixed drug eruption? the skin or mucous membranes

What is the distribution of Same location each time the drug is taken
fixed drug eruption?

How is the diagnosis of fixed Clinically

drug eruption made?

What is the treatment for Stop the offending drug

fixed drug eruption?

Palpable Purpura
What is palpable purpura? Vasculitic inflammation (vasculitis)

What is the differential diagnosis for Connective tissue disease

palpable purpura? Henoch-Schnlein purpura
Internal malignancy (lymphoma
and leukemia)
Polyarteritis nodosa
Wegener's granulomatosis
Infection
Cryoglobulinemia
Churg-Strauss disease
Drugs
Idiopathic
Editors: Bergin, James D.
Title: Advanced Medicine Recall, 1st Edition
Copyright 2009 Lippincott Williams & Wilkins

> Table of Contents > Section III - Related Specialties > Chapter 13 - Environmental Medicine:
Diseases Resulting from Environmental and Chemical Causes

Chapter 13
Environmental Medicine: Diseases Resulting
from Environmental and Chemical Causes

Abbreviations
ACLS Advanced cardiac life support

ADME Absorption, distribution, metabolism, or elimination

ALT Alanine aminotransferase

ARDS Adult respiratory distress syndrome

AST Aspartate aminotransferase

AV Atrioventricular

BUN Blood urea nitrogen

CNS Central nervous system

D5W Dextrose 5% in water

DT Delirium tremors

ECG Electrocardiogram

EtOH Ethyl Alcohol

INH Isoniazid

LFT Liver function test

 LSD Lysergic acid diethylamide

MCV Mean corpuscular volume

PCI Percutaneous intervention

PCP Phencyclidine

PT Prothrombin time

SR Sustained release

TCA Tricyclic antidepressant

THC Tetrahydrocannabinol

P.589

Poisoning

General Information
What is the incidence of According to the 2004 annual report of the
toxic exposures reported American Association of Poison Control Centers,
in the United States? approximately 2.5 million toxic exposures were
reported in humans and 141,000 toxic exposures
in animals.

What percentage of these Approximately 50% of these were reported in

exposures were in young children below 6 years of age with 40% being
children? children below age 3.

How often were the Roughly 10,000 of the exposures were severe,
exposures severe? and death occurred in more than 1200 cases.

What is the most common In 2004, ingestion accounted for approximately

route of exposure? 75% of exposures.

Of the common poisonings

that occur, approximately
what percentage are
caused by:

Medications? 50%
 Cosmetics, pesticides, 20%
petroleum products, and
turpentine?

Cleaning and polishing 15%

agents?

Other substances? 15%

What can be done to Education, proper marking of containers, and

reduce the incidence of removal of poisonous substances from areas with
toxic exposure? small children

What are some of the Local poison control center; hospital drug
sources of information information centers, pharmacists, and the
available to investigate following computer and text references:
diagnosis and treatment of Poisindex
toxic exposures? www.micromedex.com
Shannon MW, Stephen Barrm, Michael Burns.
Haddad and Winchester's Clinical Management of
Poisoning and Drug Overdose, 4th ed.
Philadelphia: Saunders, 2007.
Olson KR. Poisoning and Drug Overdose, 4th ed.
McGraw-Hill, 2004.
Flomenbaum NE, Goldfrank LF, Hoffman RS, et
al. Toxicologic Emergencies, 8th ed. McGraw-
Hill, 2006.

P.590
P.591
P.592
P.593
P.594
P.595

Basic Principles
What is the first First, stabilize the patient using the ABCs: Airway,
rule to remember Breathing, and Circulation. Provide continual monitoring
in toxic exposure? and support of vital signs throughout treatment.

After stabilizing the Information about the exposure should be obtained and
patient, what supportive care given. A physical examination should be
should be done performed and clinical assessment made. Laboratory
next? screening and analysis should be considered, as should
 gastric decontamination. Improving elimination from the
body and checking for antidotes should also be
considered.

What are important Time, type, and amount of exposure as well as past
features of the medical history. Allergies, previous admissions, and
history of access to medication and chemicals are important to
exposure? know. Ingestions of multiple substances are common in
suicide attempts and gestures, and alcohol is commonly
used to wash down pills.

In cases of suicide Psychiatric consultation should be obtained. Patients

attempt or gesture, thought to be at risk to themselves or others should be
what additional detained against their will if necessary (requires legal
steps are needed intervention).
once the patient is
medically stable?

What physical
examination
features suggest
exposure to the
following poisons:

Cyanide Cyanide odor

Carbon monoxide Cherry-red flush of the skin and mucous membranes

Lead Lead line and paralysis of extensor muscles

What are the

characteristic
physical
examination
findings in the
following common
toxic syndromes:

Anticholinergics Red as a beet, hot as a hare, dry as a bone, blind as a

(e.g., atropine, bat, mad as a hatter, crazy as a loon (i.e., dry, flushed
belladonna skin and mucous membranes, fever, dilated pupils, and
alkaloid, TCAs, delirium)
antipsychotics,
antiparkinsonian
medications, and
antihistamines)?

Cholinergics Think SLUDGE:

(e.g., Salivation
organophosphates)? Lacrimation
Urination
Defecation
Gastrointestinal upset
Emesis

Opiates (e.g., Triad of miosis, depressed mental status, and depressed

morphine, codeine, respiration
heroin, and
methadone)?

Barbiturates Depressed mental status and respiration, bradycardia,

(e.g., phenobarbital hypothermia, hypotension, pulmonary edema, and
and pentobarbital)? areflexia

Stimulants (e.g., Excitation and agitation, tachycardia and arrhythmias,

amphetamines, hypertension, mydriasis, and seizures
cocaine, and
aminophylline)?

Substance Agitation, confusion, mydriasis, tachycardia,

withdrawal? hypertension, abdominal pain, nausea and vomiting, and
seizures

What are the four 1. When no patient history is attainable

times when 2. When clinical signs and symptoms differ from patient
qualitative tests history
are useful in 3. When multiple toxins are suspected
patients with toxic 4. When medicolegal documentation is needed. Such
exposure? documents can be used in court only if the legal
chain of custody is observed.

What are the three 1. When the drugs have documented associations
times when between adverse effects and therapeutic
quantitative tests concentration
are useful in 2. When there is rapid analysis time
patients with toxic 3. When levels of drug present may direct medical
exposure? management

Do pharmacokinetic Yes. Drug pharmacokinetics may be unpredictable in

alterations change toxic exposures. In general, all variablesADMEmay be
laboratory variables prolonged over those of the normal dose. Volumes of
or clinical signs? distribution are altered, and metabolism may invoke
pathways that are not commonly used for normal doses
of substances.

Why consider To inhibit further adsorption from ingested toxins that

gastric may be present in the gastrointestinal tract. This
decontamination in prevents or decreases continued toxicity.
patients with toxic
exposure?

What determines (1) The substance ingested, (2) length of time for
the efficacy of exposure, (3) patient age, and (4) underlying medical
gastric problems
decontamination?

What are the Gastric lavage, activated charcoal, cathartics, and whole
different types of bowel irrigation
gastric
decontamination?

How is gastric Typically, with the airway protected, a large-bore tube

lavage performed? is used to remove the stomach contents. Serial aliquots
of warm lavage solution (saline or tap water) are
used. The procedure is repeated until the fluid removed
is clear.

In whom should Patients who are obtunded or intubated, those with life-
gastric lavage be threatening ingestions or patients with very recent
used? ingestions, or patients who have ingested a substance
that decreases gastric motility (e.g., anticholinergic
agents)

What are Gastric contents are larger than the lavage tube or hose,
contraindications to are alkalotic, or are sharp; or when the airway cannot
gastric lavage? be protected

What are Accidental tracheal intubation, perforation of the

complications of esophagus or gastric area, and adverse cardiorespiratory
gastric lavage? effects

What are In most toxic exposures, use as a single agent or after

indications for the gastric emptying
use of activated
charcoal?

What are the Should be used with caution in patients at risk for
contraindications to aspiration and those with decreased gastrointestinal
the use of motility
activated charcoal?

What are the Activated charcoal may complicate endoscopy.

complications with
the use of
activated charcoal?

What are the In cases of caustic ingestion, activated charcoal has

limitations to the questionable efficacy. Activated charcoal is incapable of
use of activated adsorbing cyanide, ferrous sulfate, lithium, boric acid,
charcoal? dichlorodiphenyl trichloroethane, and carbamate
insecticides.

How should 60 to 100 g

activated charcoal
be dosed in adults?

Approximately An approximate 10-to-1 ratio. This ratio may be

what ratio of unattainable in some ingestions.
activated charcoal
to toxin is needed
to absorb the
entire ingested
toxin?

What else is Administer with 70% sorbitol to reduce gastrointestinal

administered with transit time and prevent charcoal from remaining in gut
the activated (to decrease time for gut absorption of toxin).
charcoal and why?

Can multiple doses Yes. The premise is to disrupt enterohepatic circulation

of activated such that available free toxin may be absorbed from the
charcoal be used? bloodstream back into the gastrointestinal tract for
adsorption by charcoal.

What doses are 1.0 to 1.5 g/kg, then 0.5 to 1.0 g/kg every 2 to 6 hours.
used for multiple Sorbitol is given with the initial dose but not with every
dosing of activated dose.
charcoal?
What are Large ingestions, ingestion of extended-release products,
indications for and especially overdose of theophylline and digoxin
multiple dosing of
activated charcoal?

What are additional Use may increase the risk of perforation, cause diarrhea
cautions and (and consequently electrolyte disturbances), or cause
limitations of using constipation.
activated charcoal?

What is the To shorten gastrointestinal transit time and to reduce

rationale for whole the absorption of toxic substrate
bowel irrigation?

In what patients Patients in whom toxic substances are not adsorbed by

should whole bowel activated charcoal, patients who have ingested a large
irrigation be used? amount of extended-release drug products, and patients
who have packed body orifices with drug

What are Gastrointestinal ileus, obstruction, bleeding, and

contraindications of perforation
whole bowel
irrigation?

What is the dosing Oral or nasogastric polyethylene glycol electrolyte

for whole bowel solution (e.g., GoLYTELY or Colyte) is given until rectal
irrigation? fluid is clear. Use up to 0.5 L/hr for children and 2 L/hr
for adults.

What is the To shorten gastrointestinal transit time in order to

rationale for reduce absorption of toxic substances
cathartic use of
whole bowel
irrigation?

What types of Most commonsaline and osmotic agents (i.e., sorbitol)

cathartics are used Other agentssodium sulfate, magnesium sulfate,
in whole bowel magnesium citrate
irrigation?

What are The primary indication is for use of sorbitol with

indications for activated charcoal. Otherwise, they are seldom used
cathartics? because of adverse effects and questionable efficacy.

What are Fluid and electrolyte alterationssodium products may

complications of produce hypernatremia and should be avoided in heart
cathartics? failure; magnesium products may cause magnesium
toxicity in patients with renal failure and dehydration.

What methods may Extracorporeal removal by hemodialysis or

be used to promote hemoperfusion, alterations in urinary pH and forced
renal elimination of diuresis
toxins?

When are When toxins can be removed by hemodialysis or

extracorporeal hemoperfusion, when clinical status declines after
methods used for appropriate initial management, and in cases of life-
renal elimination of threatening hyperkalemia with or without renal
toxins? dysfunction

What types of Drugs with low molecular weight

drugs are removed Low plasma proteinbinding drugs
by hemodialysis? Drugs with volume of distribution <1.0 L/kg
Un-ionized, uncharged substances

How does Toxic substances are extracted from blood as it washes

hemoperfusion over a column of activated charcoal or carbon.
work?

What are Those related to placement of the large-bore line

complications of (depending on location; bleeding, hemo/pneumothorax,
hemoperfusion? infection, etc.), hypotension, thrombocytopenia,
hypocalcemia, and embolus (air or charcoal)

What is the premise To increase removal of toxin by reducing the time for
of forced diuresis? renal reabsorption. Forced diuresis can be done with any
crystalline fluid with or without altering urinary pH.

Why use alterations To increase urine output. Toxin is trapped as an ion in

in urinary pH with the urine, therefore inhibiting reabsorption (i.e., weak
forced diuresis? acids are inhibited by alkalotic urine, and weak bases
are inhibited by acidotic urine).

What agents are Sodium bicarbonate and ammonium chloride

used to promote
forced diuresis?

What are Fluid overload, electrolyte imbalance, altered urinary

complications of pH, and serum acidbase disturbances
forced diuresis?
 P.596
P.597
P.598

Common Pharmacologic Toxins

Acetaminophen
What are the
clinical stages of
acetaminophen
toxicitywhen
does each stage
occur, and what
are its
symptoms?

Stage 1 Ingestion to 24 hours after ingestion. Symptoms include

nausea, vomiting, gastrointestinal irritation, lethargy,
diaphoresis, and malaise.

Stage 2 24 to 48 hours after ingestion (a deceptive asymptomatic

phase). There may be slight elevation of hepatic enzymes
and right-upper-quadrant pain.

Stage 3 72 to 96 hours after ingestion. Symptoms include severe

nausea, vomiting, jaundice, CNS changes ranging from
lethargy to coma, elevated AST and ALT (may be >10,000
IU/L), coagulation dysfunction, and renal failure.

Stage 4 4 to 14 days after ingestion. Symptoms and laboratory

values resolve or hepatic dysfunction progresses.

What type of Gastric lavage may be useful if administered within 4 hours

gastric of exposure; sometimes activated charcoal may help.
decontamination
is used in
acetaminophen
toxicity?

What are the Activated charcoal effectively adsorbs acetaminophen. It

considerations may also reduce the systemic absorption of the antidote
for the use of acetylcysteine, but it can cause nausea and vomiting,
activated making it difficult to give the acetylcysteine. If
charcoal in administration of acetylcysteine is delayed by at least 1
acetaminophen hour for some reason, then activated charcoal is an
toxicity? appropriate option for decontamination.

What is the Acetylcysteine is administered to replace the sulfhydryl

mechanism for substance that detoxifies the N-acetylimidoquinone
acetylcysteine metabolite. Also, acetylcysteine may prevent liver damage
antidotal by replenishing the glutathione stores, thereby stopping the
therapy in accumulation of the toxic intermediary.
acetaminophen
overdose?

What are 1. Serum levels of acetaminophen in the possibly toxic

indications for range
acetylcysteine 2. Ingestion exceeding 140 mg/kg
antidotal 3. Unclear time of ingestion but a predicted half-life
therapy in exceeding 4 hours
acetaminophen
It is best to substantiate the predicated half-life and the
toxicity?
amount of ingestion with serum acetaminophen levels.
Delaying initiation of antidote for >10 hours escalates the
risk of toxicity. Acetylcysteine therapy may be ineffective if
begun more than 24 hours after ingestion.

What is the 140 mg/kg orally, then 70 mg/kg every 4 hours for 17
antidotal dose doses. The solution is manufactured as 10% and 20%. The
of 20%
acetylcysteine solution is mixed with soda or orange juice to a 5% solution
in before administering for oral use. The dose may be
acetaminophen increased by 30% if activated charcoal is used.
toxicity?

What are LFTs should be monitored every 24 hours for approximately

additional 3 to 4 days. Serum bilirubin should be measured in stages 1
monitoring and 2. AST and ALT levels typically peak 3 to 4 days after
concerns in ingestion; levels >1000 IU/L may signify liver cell damage.
acetaminophen Electrolytes and fluid status should be monitored for
toxicity? supportive care. BUN and creatinine should be measured
because kidney damage may also occur.

What are Nausea and vomiting (acetylcysteine has a rotten-egg odor)

adverse effects
of
acetylcysteine?

What is alcohol People with underlying liver disease, whether clinical or

acetaminophen subclinical and usually caused by alcohol use, are at high
 syndrome? risk for acetaminophen-induced hepatic necrosis. Less than
1 g of acetaminophen may be toxic. This is an often
underrecognized cause of acute hepatic failure.

What is the Serum transaminase levels may reach >10,000 and do not
prognosis for correlate with prognosis. Because the patient may be
acetaminophen acutely encephalopathic and significant hepatic necrosis
toxicity in portends a poor prognosis, transplant consideration should
alcohol be initiated early in the course of hospitalization.
acetaminophen
syndrome?

P.599

Beta Blockers
What are the Bradycardia, hypotension, and shock. Neurologic findings
symptoms and include delirium, coma, and seizure. Other effects include
signs of beta- bronchospasm and hypoglycemia.
blocker
overdose?

How is beta- Gastric decontamination. Fluids and atropine for

blocker toxicity hypotension and bradycardia. If those are ineffective then
treated? calcium, insulin plus glucose, vasopressor agents, and
inotropes. Glucagon may also be effective.

How does It activates the formation of cAMP independent of the beta-

glucagon work receptor mechanism, causing normal intracellular calcium
in beta-blocker exchange to occur.
toxicity?

What is the One (or two boluses if needed) of 5 mg over 1 minute each
glucagon dose (15-minute interval between doses), followed by an infusion
for beta- of 1 to 5 mg/hr.
blocker
toxicity?

What is a Vomiting
common side
effect of
glucagon used
in this way?

P.600
P.601
Cyclic Antidepressant Toxicity
What drugs are Traditional TCAs (e.g., amitriptyline, imipramine,
cyclic doxepin, nortriptyline, desipramine), monocyclics (e.g.,
antidepressants? bupropion), tetracyclics (e.g., maprotiline), and
amoxapine (a dibenzoxazepine)

What are the Inhibition of norepinephrine and serotonin reuptake,

mechanisms alpha-adrenergic blockade, cardiac membrane
behind cyclic stabilization (an anesthetic-like property), and
antidepressant anticholinergic effects. Toxicity is then exhibited through
induced toxicity? CNS, cardiac, and anticholinergic manifestations.

What are CNS Anticholinergic effects and central adrenergic effects,

effects of cyclic possibly beginning with agitation and progressing to
antidepressant delirium, hallucinations, lethargy, and coma.
toxicity? Hyperreflexia, myoclonus, and seizures may occur. When
seizures develop, they are typically brief, occurring
within the initial 6 to 8 hours.

What are Hypotension may result from peripheral alpha-adrenergic

cardiovascular blockade and from catechol depletion. Cardiac
manifestations of arrhythmias result from the membrane-stabilizing and
cyclic anesthetic property.
antidepressant
toxicity?

What are the most Sinus tachycardia, QRS prolongation, AV blocks (including
frequent signs of complete heart block), prolongation of the QT interval,
cardiac toxicity and bundle branch blocks
with cyclic
antidepressants?

What are the non- Gastrointestinal symptoms (decreased bowel sounds,

CNS reduced motility, and prolonged gastric emptying, making
anticholinergic absorption of overdose erratic and unpredictable), urinary
effects of cyclic retention, respiratory depression, mydriasis, blurred
antidepressant vision, tachycardia, dry skin, and flushing
toxicity?

Does the amount No. The dose ingested is a poor indicator of patient
of cyclic outcome.
antidepressant
ingested predict
severity of
toxicity?

What is the Supportive care (a major component), gastric

treatment for decontamination, and treatment of cardiac, CNS, and
cyclic respiratory manifestations
antidepressant
toxicity?

What types of Gastric lavage, single-dose activated charcoal, multiple-

gastric dose activated charcoal, and lavage followed by charcoal
decontamination
are used in cyclic
antidepressant
toxicity?

Is extracorporeal No. Cyclic antidepressants are highly protein-bound and

removal of toxins have large volumes of distribution, making extracorporeal
helpful in removal ineffective.
treatment of
cyclic
antidepressant
toxicity?

Is cardiac toxicity Cardiac toxicity is responsible for most of the deaths.

an important part
of cyclic
antidepressant
toxicity?

What is the Treatment is with intravenous sodium bicarbonate, 1 to 2

treatment for mEq/kg bolus, then continuous infusion (isotonic 150
cardiac toxicity mEq sodium bicarbonate/L D5W) titrated to systemic pH
with cyclic 7.45 to 7.5.
antidepressants?

How does sodium Sodium loading to reverse the inhibition of slow sodium
bicarbonate work channels in cardiac tissue. Alkalinization may help
in cyclic decrease binding of cyclics to cardiac tissue.
antidepressant
treatment?

What are Acidosis, resistant hypotension, abnormal cardiac

indications to conduction, ventricular arrhythmias, significant QT
treat cardiac prolongation, and cardiac arrest. Some sources
toxicity with recommend use with QRS duration !0.10 second, whereas
 sodium others recommend use with QRS !0.16 second.
bicarbonate in
cyclic
antidepressant
toxicity?

How should Hypoxia, hypotension, and acidosis should be treated;

cardiac then sodium bicarbonate therapy should begin.
arrhythmias be Lidocaine may be used for ventricular arrhythmias.
treated in cyclic Beta-adrenergic blockers have been used successfully to
antidepressant treat supraventricular and ventricular tachycardias, but
toxicity? adverse effects of hypotension, bradycardia, and cardiac
arrest may occur.
Isoproterenol or pacemakers may be needed for
bradyarrhythmias and heart block.

What cardiac Class IA (quinidine, procainamide, diisopyramide) and IC

antiarrhythmic (flecainide, propafenone, moricizine) should not be used
medications because they act similarly to the cyclic antidepressants.
should be Atropine also cannot be used to treat cyclic
avoided? antidepressant bradycardia.

Why is atropine Because these antidepressants inhibit muscarinic

ineffective? receptors

How is refractory Fluids and sodium bicarbonate if required, then

hypotension norepinephrine, phenylephrine, and dopamine may be
treated in cyclic used as pressor agents.
antidepressant
toxicity?

What is the Supportive care. Agitation and seizures respond to

treatment for CNS benzodiazepines. Second-line seizure treatment is
toxicity in cyclic phenobarbital.
antidepressant
toxicity?

P.602
P.603
P.604

IronAcute Intoxication
What dose of !20 mg/kg of elemental iron. Doses of 20 to 60 mg/kg
iron is typically produce mild to moderate toxicity; doses exceeding
considered 60 mg/kg produce severe toxicity.
toxic?

How does iron Locally, iron may cause injury to the gastrointestinal mucosa
cause ranging from irritation to ulceration, bleeding, loss of
gastrointestinal oxygenation, and perforation. Hepatic necrosis may occur as
toxicity? the portal circulation receives the initial toxic iron
concentration from the blood.

What are the Multiple systemic effects may occur, including venodilation
systemic (decreased systemic and central venous pressures), enhanced
toxicities of capillary membrane permeability (third spacing and
iron? hypotension), interference with serum proteases (may
increase PT), cellular destruction, and metabolic acidosis.

What are
symptoms and
signs of iron
toxicity for the
following
stages, and
how long do
the stages last?

Stage I Nausea, vomiting, diarrhea, and abdominal pain. Fluid losses

with or without bleeding may result in decreased perfusion,
hypotension, and acidosis. Symptoms occur rapidly after
ingestion and may be relieved after 6 to 12 hours.

Stage II Lethargy, metabolic acidosis, and possibly hypotension

occurring in the period between relief of gastrointestinal
symptoms and development of severe systemic effects. Onset
is 6 to 12 hours after ingestion; duration is 12 to 24 hours.

Stage III Multiple-organ dysfunction, including cerebral damage, coma,

cardiac depression, renal dysfunction, liver failure, and
ischemic bowel. Liver failure may result in coagulopathy or
decreased blood glucose.

Stage IV Gastrointestinal scarring resulting in gastric outlet and small

bowel obstruction

What is most Diagnosis is based on clinical presentation regardless of time

important to since ingestion or laboratory test results.
remember
when making
the diagnosis
of iron
toxicity?

What are the Normal serum iron is 50 to 150 "g/dL; levels >300 to 350
normal iron "g/dL typically result in toxicity; levels >500 "g/dL may
levels and cause severe toxicity.
what levels
cause toxicity?

When do peak Peak serum iron levels occur approximately 2 to 6 hours

serum iron after ingestion.
levels occur?

Is the serum No. The intracellular concentration of iron creates the

concentration toxicity.
of iron the
etiology of the
toxicity?

Do the iron Association between level and symptoms varies among

levels predict patients.
symptoms?

Is measuring Total iron-binding capacity is not a helpful measurement

TIBC helpful in because it may be inappropriately high when serum iron
cases of iron levels are high.
toxicity?

How are blood Blood glucose levels and white blood cell counts may become
glucose and elevated with serum iron >300 "g/dL and may give additional
white blood information about severity of toxicity.
cell counts
helpful in
monitoring
iron toxicity?

What is the 1. Stabilization of the patient.

treatment for 2. Gastric decontamination: gastric lavage may be used, but
iron toxicity? activated charcoal is ineffective.
3. Chelation therapy with deferoxamine.
4. Supportive care: fluid and electrolyte replacement,
management of acidbase abnormalities, and
coagulopathy.
 How does It acts as a chelating agent by converting ferric ions in the
deferoxamine blood to ferrioxamine, which is renally eliminated.
work?

What are 1. Serum iron >300 to 350 "g/dL in symptomatic patients or

indications for >400 "g/dL in asymptomatic patients
deferoxamine 2. Ingestion of >180 to 300 mg of elemental iron
therapy? 3. Moderate level clinical symptoms and signs (i.e., more
than one bout of emesis or more than one soft stool)

What is the Therapy is most effective if given as 15 mg/kg/hr via

most effective continuous IV infusion for adults or approximately 4
dose and route mg/kg/hr continuous IV infusion for children. Intravenous
of delivery of administration is preferred for all patients because total dose
deferoxamine given may be more accurately controlled.
for iron
toxicity?

What are These primarily occur with rapid intravenous injection and
adverse effects include flushing, erythema, urticaria, hypotension, shock,
of and seizures.
deferoxamine
therapy?

What is the Treatment is continued until serum iron levels are within
appropriate normal limits and the patient has resolution of clinical
duration for symptoms and signs. Treatment duration is typically 6 to 12
deferoxamine hours. Some patients produce vin-roscolored urine during
therapy? chelation with deferoxamine. When this color resolves,
therapy may be discontinued. The vin-roscolored urine is
not an absolute marker for presence of toxicity.

P.605
P.606

Salicylate Toxicity
What is the 1. The agent acts centrally to stimulate the respiratory
mechanism for center.
salicylate- 2. Skeletal muscle metabolism is increased, raising the
induced demand for oxygen and elevating production of carbon
toxicity? dioxide, resulting in hyperventilation and further
respiratory alkalosis.
3. The agent interferes with central and peripheral glucose
metabolism and utilization.
How is salicylate Acute or chronic
poisoning
classified?

What acute Acute intoxicationdoses of 150 to 300 mg/kg typically

levels of cause mild to moderate symptoms.
salicylate cause Doses >300 mg/kg produce severe toxicity, and doses >500
toxicity? mg/kg may be lethal.

What chronic Chronic intoxicationtypically >100 mg/kg per day for more
levels of than 2 to 3 days
salicylate cause
chronic toxicity?

What is the Dehydration, hearing loss, tinnitus, tachypnea, nausea,

clinical vomiting, elevated PT, alterations in platelet function,
presentation in electrolyte loss, and proteinuria
acute salicylate
toxicity?

What is the Older children and adults typically present with mixed acid
usual acidbase base states, as seen in respiratory alkalosis, elevated anion
abnormality in gap metabolic acidosis, and alkalemia.
salicylate
toxicity?

What is the Same as acute toxicity but may also include pulmonary
clinical edema, CNS manifestations (e.g., agitation, confusion,
presentation in blunted mental status, seizures, and coma), elevated LFTs,
chronic and kidney failure
salicylate
toxicity?

When should Levels should not be obtained sooner than 6 hours after
salicylate levels ingestion because they may be falsely low. Salicylate levels
be measured? may escalate for approximately 24 hours, depending on the
amount and type of product ingested. If SR products are
ingested, peak salicylate levels may be prolonged to 10 to
60 hours after ingestion. Repeated salicylate levels obtained
4 to 6 hours after the original level may be useful to
monitor or document the status of the blood concentration.

Is there a Yes, the Dome nomogram. First, though, the patient's

treatment clinical presentation should be used to determine the
nomogram for severity of toxicity and subsequent treatment.
salicylate
toxicity?

When is the 1. When the salicylate is taken over several hours or days
Dome nomogram 2. When the salicylate is enteric-coated or there is
not an ingestion of a SR product
appropriate 3. When the product has oil of wintergreen, which causes
tool? quick absorption
4. When patients have kidney dysfunction
5. When the time of ingestion is unclear
6. When there is acidemia

What is the Stabilization of the patient, then gastric decontamination,

treatment for fluid therapy, intravenous sodium bicarbonate, possible
salicylate extracorporeal elimination, treatment of seizure, and
toxicity? treatment of coagulopathy as needed

What type of A variety may be used, including gastric lavage alone or

gastric with activated charcoal, activated charcoal alone, or whole
decontamination bowel irrigation
is used in
salicylate
toxicity?

Why is sodium As the blood becomes more alkalinized, salicylate moves

bicarbonate into the ionized form and penetration into all tissues is
used in the reduced. Sodium bicarbonate also enhances salicylate
treatment of elimination through alkalinization of the urine to trap and
salicylate remove drug in ionized form.
toxicity?

How much 1 to 2 mEq/kg per liter of intravenous solution. D5W is

sodium recommended for solution to keep the intravenous fluid
bicarbonate is from being hypertonic. Serum pH of 7.55 should not be
used in the exceeded. If the clinician is attempting to create alkalotic
treatment of urine, then urine pH should be >7.5.
salicylate
toxicity?

What are Hypernatremia, increasing alkalosis in patients with

adverse effects respiratory alkalosis, hypokalemia, and fluid overload
of treatment
with sodium
bicarbonate?
 When should When salicylate levels reach 35 to 40 mg/dL and when the
bicarbonate patient's clinical status improves and signs and symptoms
therapy be resolve
stopped in
salicylate
toxicity?

When is When standard management is ineffective, there is evident

extracorporeal damage in vital organs, the patient is at an extreme of age,
elimination or the liver or kidney cannot clear the drug
appropriate in
salicylate
toxicity?

P.607

Miscellaneous
What is the primary Hemorrhagic gastroenteritis
symptom of arsenic
poisoning?

What are the Acute encephalopathy, seizure, coma, and death

primary symptoms
of acute lead
poisoning (high
level)?

What are the Gastroenteritis, nephritic syndrome and acute renal

primary symptoms failure, cardiovascular collapse and death
of mercury
ingestion?

What are the Pneumonitis, noncardiogenic pulmonary edema, CNS

symptoms of acute symptoms, and polyneuropathy
mercury inhalation?

What are antidotes

(adult dose) for the
following?

Opiates Naloxone, initial dose of 2 mg unless the patient has a

history of chronic narcotic use, in which case starting
dose is 0.4 mg, which is titrated accordingly. Larger
doses may precipitate severe withdrawal.
 Methanol or Ethanolloading dose, 10 mL/kg (10% solution), then
ethylene glycol continuous infusion of 0.15 mL/kg/hr

Anticholinergic Physostigmine, 1 to 2 mg intravenously over 5 minutes

agents

Organophosphates Atropine, 2 mg intravenously; may be repeated to

or carbamate dehydrate pulmonary secretions

INH and Pyridoxine gram/gram. Give an equivalent amount of

hydralazine pyridoxine to the estimated amount of hydralazine or
INH ingested. If unknown then administer 5 g pyridoxine
or repeat as needed to control seizure.

Alpha-adrenergic Phentolamine
blockers

Beta-adrenergic Glucagon 5 to 10 mg intravenously, then 2 to 10 mg/hr

blockers

TCAs Bicarbonate 1 to 2 mmol/kg

Digitalis Digibind (mg of digoxin ingested/0.6 = number of vials)

Benzodiazepines Flumazenil, 0.2 mg intravenously; if no effect after 30

seconds, then 0.3 mg is administered intravenously; if
no effect after 30 seconds, then 0.5 mg is administered
intravenously every minute to a total dose of 3 mg.
Seizures may occur during therapy.

Calcium channel Calcium chloride 1 g

blockers

P.608
P.609

Bites and Other Toxins

Should a totally Although it is shown in the movies, total occlusion should be
occlusive band avoided. This usually leads to further tissue necrosis of the
be applied limb and bite site in addition to the local tissue damage
following a caused by the bite itself.
reptile bite?
Should suction It looks good in the movies, but the amount of venom that is
be applied extracted by this method is minimal and likely of no
following a consequence.
reptile bite?

What is the <1%. The eastern and western diamondback rattlesnakes are
annual responsible for most of the deaths.
mortality rate
for snakebites
in the United
States?

What snakes Cobras (Asia and Africa), carpet- and saw-scaled vipers
are responsible (Middle East and Africa), Russell's viper (Middle East and
for large Asia), African vipers, and lancehead pit vipers (Central and
numbers of South America)
deaths?

Bites from Brown or fiddler spiders and widow spiders are the most
which spiders common. Others include the hobo spider (Pacific Northwest)
may be lethal? and sac spiders.

What is the Local tissue necrosis due to vascular thrombosis. Injury to

major injury of the local nerve and secondary infection may occur. Rarely,
the brown hemolytic anemia, hemoglobinuria, and death occur.
spider bites?

What are the Painful cramps at the bite site that spread to the body;
symptoms of salivation, diaphoresis, nausea, vomiting, headache,
widow spider paresthesias, rhabdomyolysis, renal failure, respiratory
bites? arrest, and death

What is the A sterile pustule preceded by a wheal-and-flare reaction.

usual sign of a Anaphylaxis occurs in 1% to 2% of people.
fire ant bite?

What is the 0.4% to 4.0%

incidence of
immediate-
type
hypersensitivity
to bee stings?

Are all No. There are 40 different scorpions in the United States but
scorpions in only the bark scorpion (Centruroides sculpturatus or C.
 the United exilicauda), found in the southwestern United States and
States northern Mexico, is lethal. The rest just cause localized
potentially reactions with pain.
lethal?

What common Vinegar, baking soda, rubbing alcohol, papain, fresh lemon
products may or lime juice, and ammonia. Topical steroids, antihistamines,
help treat and lidocaine preparations may also help. Fresh water and
stings of perfumes should be avoided.
marine
creature?

Eating which 75% of cases involve barracuda, snapper, jack, and grouper.
fish may cause
ciguatera
poisoning?

What are the GI: pain, nausea, vomiting, diarrhea; neurologic:

symptoms of paresthesias, tongue and throat numbness, dysesthesias,
ciguatera tremor, fasciculations, etc.
poisoning?

What are the Histamine-related: flushing, a sensation of warmth without

symptoms of fever, pruritus, conjunctival hyperemia, urticaria,
scromboid? angioneurotic edema, bronchospasm, and many others

P.610

Food-Borne Disease
How common is food- Common. There are estimated to be 75 million cases
borne disease? of diarrhea annually in the United States secondary to
foodborne disease. These lead to 325,000
hospitalizations and 5000 deaths.

What are the most Salmonella, Campylobacter, Shigella, and

common food-borne Cryptosporidium account for 94% of the pathogens.
pathogens?

If nausea and vomiting Bacterial are Staphylococcus aureus and Bacillus

are the presenting cereus. Viral are noroviruses.
symptoms, what
pathogens are
common?

What food-borne Clostridium botulinum, ciguatera toxin, scombroid,

 pathogens cause other shellfish, and mushrooms, Listeria
neurologic symptoms? monocytogenes, Vibrio vulnificus, Toxoplasma gondii,
and hepatitis A.

P.611

Electrical Injury
How common Approximately 1000 deaths per year are caused by electrical
are deaths current, and 200 deaths per year are caused by lightning
caused by strikes; also, 5% of admissions to burn units are from
electrical electrical injuries.
injury?

What factors Duration of contact, alternating current (tetanic contraction

determine the does not allow release of the contact), pathway through the
extent of body (what is in between), and resistance to the flow of
electrical electricity (lowered by moisture)
injury?

What renal 1. Direct injury to the kidney secondary to electrical injury

injuries occur 2. Hypotensive injury
after an 3. Renal tubular damage from myoglobin and hemoglobin
electrical secondary to muscle necrosis and hemolysis
injury? 4. Rapid volume loss into the destroyed or injured tissue

What other Swelling may result in compartment syndrome, metabolic

complications acidosis may result from lactate production, and infection
may occur in may result from inadequately dbrided tissue.
electrical
injury?

What are late Visual disturbances, peripheral neuropathy, incomplete

neurologic transection of the spinal cord, reflex sympathetic dystrophies,
sequelae of late convulsive disorders, and intractable headaches
electrical
injury?

What does 1. Removal of the victim from the contact without touching
acute the victim directly (unless power is definitely terminated)
management 2. ACLS (there is high risk for cardiac arrhythmias)
of electrical 3. Rapid fluid and electrolyte replacement (standard
injury entail? formulas estimating replacement based on surface burn
are inaccurate because of the extensive internal injury)
4. Wound management
 5. Administration of tetanus toxoid and antibiotics

P.612

Drowning
What is the In dry drowning, laryngospasm develops and the victim dies
mechanism of hypoxia caused by mechanical obstruction of airflow. In
of injury in wet drowning, water reaches the alveoli and directly
drowning? interferes with oxygen exchange or damages alveoli and causes
ARDS.

Does water Yes. Hypothermia induced by cold water slows metabolic rate
temperature and may induce a protective mechanism against hypoxia.
affect Patients should be rewarmed per hypothermia protocol in
prognosis in addition to receiving respiratory support. The presence of
drowning? hypothermia should lead to longer resuscitative efforts (i.e.,
the patient is not dead until he or she is warm and dead).

What is the Victims should be removed from the water as soon as possible
acute and given ACLS, with particular attention to airway and
management breathing. If any trauma is suspected, the patient's head and
of drowning? neck should be immediately stabilized. ACLS may be started in
the water if immediate removal is impossible. A low threshold
for endotracheal intubation is indicated. The patient should be
placed on a cardiac monitor as soon as possible.

Should Current ACLS recommendations are that abdominal thrust is not

abdominal indicated except to remove a foreign body from the airway or
thrust be to clear the airway if the patient does not ventilate with
administered standard basic cardiac life support procedures.
in the field?

What is a The thrust may lead to aspiration of gastric contents and

potential further alveolar damage.
downside to
the
abdominal
thrust?

What else Drowning often follows an inciting event such as head trauma,
should be cardiac arrhythmia, myocardial infarction, alcohol intoxication,
done acutely or drug use. These events should be treated accordingly during
in drowning resuscitative efforts.
cases?
 What Hypoxia dominates over hypercapnia. The victim is often
laboratory acidotic. Both hypoxia and acidosis may depress cardiac
abnormalities function. Blood chemistries are usually normal.
are common
in drowning
cases?

What are Prolonged submersion, severe metabolic acidosis (pH <7.1),

poor asystole, fixed and dilated pupils, and low Glasgow Coma Scale
prognostic score (<5)
indicators in
drowning
cases?

P.613
P.614
P.615

Alcohol
How much of The average American intake is two drinks per day, and two
a problem is thirds of Americans drink alcohol. Alcohol use, both acute and
alcohol chronic, is responsible for 10% of all deaths, and 50% of fatal
consumption accidents and trauma cases are alcohol-related.
in the United
States?

What are the 1. Prealcoholic syndrome

four phases 2. Prodrome (marked by guilt, sneaking drinks, and blackouts)
of 3. Addiction
alcoholism? 4. Chronic health decline

What There is growing evidence for a genetic cause of susceptibility

predisposes a to alcohol abuse, although environmental pressures also play a
person to role. A strong family history of alcohol abuse should lead to a
alcoholism? higher index of suspicion.

What are The patient becomes suspicious, notes periods of amnesia,

clues to the disruption of personal life, a downward career drift, gastritis,
diagnosis of diarrhea, myopathy, and tremor.
alcoholism?

How is the 1. EtOH level >150 mg/dL without intoxication is a positive

diagnosis of indicator.
alcoholism 2. The CAGE questions have an 80% sensitivity.
made?

What are the Have you ever tried to Cut down on drinking?
CAGE Have you ever felt Annoyed by criticism about your drinking?
questions? Have you ever had Guilty feelings about drinking?
Have you ever taken an Eye opener in the morning?

What are LFTs include elevated gammaglutamyltranspeptidase, AST/ALT

common ratio >2:1, or isolated elevated AST.
laboratory MCV may be elevated with normal or low hematocrit.
abnormalities PT may be prolonged.
in A decreased BUN may signify chronic malnutrition.
alcoholism?

What is A state of physical and psychological distress created by a

alcohol decline in the steady-state alcohol level that a person is
withdrawal? accustomed to. A chronic alcoholic may withdraw long
before the EtOH level reaches 0 mg/dL.

What The rate of metabolism is influenced by the chronicity of use,

influences amount consumed acutely, and presence of metabolic disorders
the rate of (e.g., liver disease) or other drugs (e.g., benzodiazepines).
alcohol
metabolism?

How long Acute abstinence usually leads to symptoms within 7 days

after (often 48 to 72 hours).
cessation of
drinking is
alcohol
withdrawal
seen?

What are Mild withdrawal presents with autonomic excitability (e.g.,

signs of tachycardia, hypertension, and low-grade fever) and
alcohol increasing agitation, often with tremor and confusion. In
withdrawal? patients with severe withdrawal, autonomic instability and
respiratory distress, agitation, and seizures may develop.

What is Delirium tremens signifies severe withdrawal and has both a

delirium physical component (tremors and seizures) and a hallucinatory
tremens component. This is a life-threatening condition.
(DTs)?

How is risk Any patient with a history of withdrawal or heavy drinking

 for alcohol should receive benzodiazepine prophylaxis and careful
withdrawal monitoring.
treated?

What is the If liver function is normal, the patient should receive

treatment chlordiazepoxide HCl (Librium), either by mouth or
for alcohol intravenously in a tapering fashion. A good starting dose is 50
withdrawal? mg every 4 hours the first day, then every 6 hours, then the
dose is halved and the interval is tapered. If liver disease is
present, 1 to 2 mg of lorazepam is used as a starting dose. The
patient must be monitored for excessive sedation and the dose
adjusted accordingly.

P.616
P.617
P.618
P.619
P.620

Drugs of Abuse
What are the signs of Development of psychiatric problems such as
chronic drug use? depression or paranoia may signal abuse problems. As
the addiction grows, antisocial behavior in the form of
lying, manipulation, and failure to meet personal and
business obligations becomes more prominent. Casual
users may hide their use indefinitely.

What are the effects Acutely, the effects mimic those of severe alcohol
of cannabinoids? intoxication with depression.
Intoxication with cannabinoids can precipitate a
severe depressive state. Physical examination may
show conjunctival erythema and tachycardia. Angina
may develop even hours after use. Chronic bronchitis
may develop as well. Gynecomastia and infertility
may result and the immune system may be depressed.

What are some of the Withdrawal is marked by tremor, nystagmus,

cannabinoid gastrointestinal distress, and sleep disturbance.
withdrawal
symptoms?

Are there any legal Cannabinoids are potent antiemetics and can be used
uses for for control of intractable nausea in cancer patients in
cannabinoids? some states. They may also be used to stimulate
appetite in some patients (in the form of
 tetrahydrocannabinol, or THC).

What are the effects Opiates cause CNS depression through several
of opiates? different receptors. Common findings include lethargy,
somnolence, miosis, and respiratory and cardiac
depression. Intravenous preparations may cause more
rapid and profound effects than oral use. Abuse may
develop from illegal street use or medical use of
prescribed drugs.

Do opiates cause Yes. Factors influencing severity include the drug half-
significant life, dose, and chronicity of use.
withdrawal?

What are signs of The opposite effects of intoxication, including nausea,

opiate withdrawal? diarrhea, lacrimation, rhinorrhea, myoclonus,
insomnia, and piloerection

How soon after Drugs with short half-lives, namely morphine and
discontinuation of heroin, may lead to withdrawal within 8 to 16 hours
opiate use is of last use.
withdrawal seen?

What is the treatment Treatment consists of observed, controlled

for opiate administration of long-acting agents such as
withdrawal? methadone. Clonidine (0.1 to 0.3 mg two to four
times daily) may counteract some of the physical
symptoms. A mild withdrawal syndrome consisting of
autonomic dysfunction and sleep disturbance may
persist for up to 6 months and interfere with long-
term abstinence.

What are the dangers The most obvious is transmission of infectious diseases
of intravenous drug including hepatitis B and C and HIV because of shared
use? needles.
Endocarditis of the tricuspid valve is seen almost
exclusively in this group, and causative agents include
normal skin flora (Staphylococcus) and unusual
organisms such as Pseudomonas. Osteomyelitis may
also develop, often in vertebral bodies. Intravenous
drug abuse should be suspected in patients with
sternoclavicular osteomyelitis, often a result of
injecting into the jugular or subclavian veins.
Injection of contaminated material may also lead to
painful local phlebitis.
Are barbiturates Yes. Both act as CNS depressants. Prescriptions for
similar in action to barbiturates, except to treat seizure disorders, have
opiates? declined. Because these are usually long-acting
agents, withdrawal signs take longer to appear and
are generally less severe.

What are the These cross-react with EtOH, which is why they are
symptoms of used to treat alcohol withdrawal. Abuse of anxiolytics
withdrawal of is not uncommon; they are often prescribed
anxiolytics such as inappropriately to treat anxiety and nerves.
benzodiazepines? Withdrawal symptoms are similar to those of alcohol
withdrawal but do not appear for many days because
anxiolytics are longer-acting agents.

What are the effects Hydrocarbon-based commercial products such as glue

of sniffing glue? and paint thinner can cause CNS depression and
feelings of euphoria. They are often used by younger
persons and may create long-term-memory and
cognitive deficits. Prolonged exposure may lead to
life-threatening CNS and respiratory depression.

Why is cocaine abuse Because it creates a high sympathetic discharge,

dangerous? cocaine use increases myocardial oxygen demands and
may induce myocardial ischemia. It also induces
coronary and peripheral vasospasm, which can cause a
myocardial infarction or stroke. This effect may occur
up to several days after cocaine use. Hyperpyrexia
and malignant hypertension may also occur.

What is the treatment Other than avoiding beta blockers, the key is to open
for cocaine-induced the blood vessel with PCI or thrombolysis.
myocardial infarction?

Why are beta The theoretical concern of blocking the beta receptor
blockers avoided in and leaving unopposed alpha activity, which can cause
cocaine-induced vasospasm.
myocardial infarction?

What other Intravenous diazepam at 0.5 mg/kg over 8 hours

medication should be
used for the
treatment of cocaine
overdose?
What is crack lung? ARDS-like damage, often unilateral, seen acutely after
smoking cocaine

What is crashing? Cocaine products produce a rapid, intense euphoric

state, which may occur as quickly as 8 to 10 seconds
after smoking crack. This is followed by an abrupt
drop in mood. Alcohol is often used to modulate this
reaction.

What class of street Potent metabolic stimulants. Milder forms are legally
drugs are available and are often used as weight control aids.
amphetamines part
of?

What are the Overdose causes tachycardia, anxiety, and agitation. A

symptoms of synthetic methamphetamine known as ice has
amphetamine gained popularity. Overdose may lead to
overdose? hyperpyrexia, dilated pupils, tachypnea,
rhabdomyolysis, hypertensive crisis, seizures, and
cardiac arrhythmias.

What is the treatment Treatment should be directed at the manifestations

of amphetamine and include control of seizures with benzodiazepines
overdose? and blood pressure control with labetalol or
nifedipine.

What is the street Ecstasy

name for MDMA (3,4-
methylenedioxy-N-
methylamphetamine)?

What class or classes It has properties of amphetamines and hallucinogenic

of street drugs does properties of mescaline.
MDMA fall into?

What are some of the As with other stimulants, there have been reports of
toxic effects of hyperpyrexia, rhabdomyolysis, intravascular
MDMA? coagulopathy and hepatic necrosis, arrhythmias, and
drug-related accidents or suicide.

What are the effects LSD, or acid, causes hyperpyrexia, tachycardia,

of acid? tremor, hypertension, pupillary dilatation, labile
moods, and visual hallucinations. There are no reports
of deaths directly attributable to the physiologic
effects of LSD.
What is a bad trip? LSD can provoke a prolonged panic episode lasting up
to 24 hours. Supportive care consisting of talking
down the patient and small doses of anxiolytic drugs
may help.

What is angel dust? Phencyclidine, or PCP

What are the effects PCP produces a state of intense agitation and
of PCP? analgesia. It has been described as causing acts of
superhuman strength
(e.g., ripping off handcuffs), but the effect is more
due to the analgesia than enhanced muscle strength.
It may cause horizontal or vertical nystagmus,
hyperacusis, and diaphoresis. Feelings of estrangement
and distorted images of self develop. Overdose may
lead to coma, which is treated with gastric lavage and
acidification of urine.

Can drug use be Yes. Cocaine may induce a state of paranoid

confused with delusions. Also, chronic cocaine use can unmask
psychiatric disorders? schizoform disorders. PCP use may appear to be an
acute schizophrenic break.
Editors: Bergin, James D.
Title: Advanced Medicine Recall, 1st Edition
Copyright 2009 Lippincott Williams & Wilkins

> Table of Contents > Section III - Related Specialties > Chapter 14 - Neurology

Chapter 14
Neurology

P.622

Abbreviations
ACA Anterior cerebral artery

AD Alzheimer's disease

ADC AIDS dementia complex

AIDS Acquired immunodeficiency syndrome

AMS Altered mental status

BPPV Benign paroxysmal positional vertigo

BUN Blood urea nitrogen

CBC Complete blood count

CIDP Chronic inflammatory demyelinating polyneuropathy

CJD Creutzfeldt-Jakob disease

CNS Central nervous system

c/s Cycles per second (Hz)

CSF Cerebrospinal fluid

CT Computed tomography

EEG Electroencephalogram

EMG Electromyogram

ESR Erythrocyte sedimentation rate

GBS Guillain-Barr syndrome

GCS Glasgow Coma Scale

GTC Generalized tonicclonic seizure

HIV Human immunodeficiency virus

HSV Herpes simplex virus

ICP Intracranial pressure

 JME Juvenile myoclonic epilepsy

LEMS LambertEaton myasthenic syndrome

LP Lumbar puncture

MCA Middle cerebral artery

MG Myasthenia gravis

MRA Magnetic resonance arteriography

MRI Magnetic resonance imaging

MS Multiple sclerosis

NPO Nil per os (nothing by mouth)

NSAID Nonsteroidal anti-inflammatory drug

PCA Posterior cerebral artery

PD Parkinson's disease

PICA Posterior inferior cerebellar artery

PML Progressive multifocal leukoencephalopathy

RAS Reticular activating system

SAH Subarachnoid hemorrhage

SDH Subdural hematoma

SE Status epilepticus

TB Tuberculosis

TEE Transesophageal echocardiogram

TIA Transient ischemic attack

TLE Temporal lobe epilepsy

t-PA Tissue plasminogen activator

TTE Transthoracic echocardiogram

WBC White blood cell

P.623

Altered Mental Status

What three things should be Oxygenation, perfusion (i.e., blood
evaluated immediately in a pressure and pulse), and glucose level
patient with AMS?

What treatment should be given Oxygen, naloxone (opiate antagonist), and

for an impaired level of glucose. If alcoholism is suspected,
consciousness of unknown thiamine should be given with the glucose.
 etiology?

What is the most common cause Drugs

of toxicmetabolic
encephalopathy in the hospital?

List three other general medical 1. Infection: CNS or systemic infections

conditions that may cause toxic- 2. Organ failure: hepatic or renal
metabolic encephalopathy. 3. Electrolyte imbalance: hypoglycemia,
hyperglycemia, hyponatremia,
hypercalcemia

P.624
P.625
P.626

Coma and Brain Death

What is coma? An unarousable state of unconsciousness

What therapy Glucose, thiamine, and naloxone.

should be
given in the
emergency
department,
before the
cause of coma
is established?

If the The primary consideration is that of a stroke syndrome

brainstem is (hemorrhage or ischemia) or pressure on the brainstem
not intact, (herniation).
what causes of
coma should
be
considered?

If the Stroke syndromes can still be considered, but it is more likely

brainstem is that the cause is toxicmetabolic encephalopathy, seizure,
intact, what trauma, or infection, all things that can diffusely scramble
causes of cortical activity bilaterally.
coma should
be
considered?

What lab tests Blood chemistry, toxicology screen (including alcohol, aspirin
should be and acetaminophen levels), ABG, CBC, and blood culture
considered?

What Head CT and lumbar puncture initially. MR should be

procedures considered.
should be
considered in
comatose
patients?

Coma suggests Either the midbrain RAS, which wakes up the cortex, or
dysfunction of both cerebral cortices
which brain
structures?

Which bedside Cranial nerve reflex actions, particularly those of the eye
tests help movements and the pupillary light response
establish
whether coma
results from
dysfunction of
the RAS or
from
bihemispheric
dysfunction?

With regard to These reflexes should be intact and symmetric.

examination
of the cranial
nerves, what
is seen with
bihemispheric
dysfunction?

With regard to The normal reflexes or symmetry of the reflexes is lost

examination because the neurologic pathways that mediate these reflexes
of the cranial are located very close to the RAS.
nerves, what
is seen with
midbrain
damage?

What are four 1. Pupillary light reflex

bedside tests 2. Corneal response
of cranial 3. Vestibulo-ocular reflex (caloric response)
nerve function 4. Doll's eyes (oculocephalic response)
that are
useful in a
comatose
patient?

What is the Instillation of ice-cold water against the tympanic membrane.

vestibulo-
ocular reflex
(or cold water
calorics test)?

How is the The patient's head should be 30 degrees above supine and
vestibulo- looking straight ahead. Approximately 100 mL of ice-cold
ocular reflex water should be instilled into the ear canal for 1 to 2 minutes
performed? (a butterfly tubing from which the needle has been removed
is helpful when placed on the end of a 30-mL syringe).

What is seen The normal tendency is for the eyes to conjugately deviate
with toward the side of the cold water instillation. The mnemonic
vestibulo- COWS (ColdOpposite, WarmSame) is a popular way of
ocular testing? remembering the direction of nystagmus, not the direction of
eye deviation.

What does the Is proof that the patient has an intact connection between
presence of the cortex and the brainstem
COWS
indicate?

How much Approximately 5 minutes should elapse before the test is

time should attempted in the other ear. In some circumstances, the
elapse before patient may display nystagmus with the fast component in the
the second direction opposite to the instilled ear.
ear is tested?
What are doll's A less confusing term for this is the oculocephalic reflex or
eyes? the cervico-ocular reflex.

How is this With the patient's eyes open, the patient's head is briskly
tested? nodded back and forth (e.g., from left to right and back).

How does this Movement activates the same pathways as cold water
test work? instillation does in the vestibulo-ocular reflex, partly through
causing movement of the endolymphatic fluid in the inner ear
(as with cold calorics) and partly through activating
proprioceptive receptors in the neck that feed position
information to the vestibular system.

What is looked The active part of the reflex is the turning of the eyes
for during this away from the direction of head turning, so that eye
testing? movement appears to lag behind head movement. The active
reflex should not be confused with the passive return of the
eyes to midgaze position after the head rotation is complete
and there is no more stimulation to the system. Eye
movements should be symmetric and conjugate, with equal
excursion distances in both eyes.

What does Posturing usually indicates that the cortex is disconnected

posturing from the brainstem.
indicate?

What does In decorticate posturing, the brainstem is probably mostly

decorticate intact.
posturing
indicate?

What does Decerebrate posturing implies a worse injury and prognosis

decerebrate and indicates not only hemispheric dysfunction but also
posturing dysfunction of the rostral brainstem.
indicate?

What is the Decorticate posturing indicates dysfunction above the

physiologic midbrain's red nucleus.
basis of
decorticate
posturing?

What is the Decerebrate posturing indicates a lesion of the brainstem

physiologic between the red nucleus and the vestibular nuclei at the
basis of pontomedullary junction.
decerebrate
posturing?

What From rostral to caudal (i.e., top to bottom):

breathing Cheyne-Stokes, central neurogenic hyperventilation, apneustic
patterns are breathing, and ataxic breathing.
characteristic
in a comatose
patient and
may assist in
localization of
the lesion?

What does May indicate a metabolic abnormality or disconnection of the

Cheyne-Stokes cerebral cortex from the diencephalon or brainstem
breathing
indicate?
 Where is the Irritation to the midbrain
lesion if
central
neurogenic
breathing is
seen?

Where is the A lesion at the level of the pons

lesion if
apneustic
breathing is
noted?

Where is the Ataxic breathing originates from the medulla, suggesting that
lesion if ataxic all higher portions of the CNS above the medulla are
breathing is dysfunctional.
noted?

What factors Barbiturates, drug overdose or sedation, neuromuscular

may confound blocking agents, anticholinergics (e.g., atropine), and
the brain- hypothermia (body temperature <32.2C)
death
evaluation?

What findings No posturing or withdrawal to torso, head, or appendicular

must be noxious stimulation, absent pupillary light response, absent
documented corneal response, absent oculocephalic and vestibulo-ocular
on the brain- reflexes, and absent gag or cough. Absence of spontaneous
death respiration must also be demonstrated.
examination?

What is an To rule out the presence of spontaneous respirations, the

apnea test, patient is initially ventilated to a state of hyperoxia (PO 2
and how is it >200 mm Hg) and Pco 2 <40 mm Hg. The ventilator rate is
performed?
lowered to 1 breath per minute (or continuous positive airway
pressure of 10 mm Hg). Arterial blood gases are checked
every 5 minutes until the Pco 2 is >60 mm Hg or Pco 2 rises >20
mm Hg. Spontaneous ventilation during this time is evidence
that the brain is not dead.

P.627

Brain Trauma
What are the 3 components of the 1. Eye responsiveness
Glasgow Coma Scale? 2. Verbal responsiveness
3. Motor responsiveness

How is the GCS scored? Scores range from 3 (no responses)

to 15 (normal). See Table 14-1.

What are the three signs of Cushing's Hypertension, bradycardia,

triad of increased ICP? respiratory irregularity

What are the typical symptoms seen in Headache, dizziness, psychologic

postconcussive syndrome? disorders, cognitive impairment

Which vessel is most often implicated Middle meningeal artery

in traumatic epidural hematoma?

What is the classic CT finding of an Convex (lens-shaped) hyperdensity

epidural hematoma? that respects suture lines

P.628

Table 14-1. Glasgow Coma Scale Scoring

Category Points for a Given Response

Eye 4 Spontaneously opens eyes

opening 3 Opens eyes to speech
2 Opens eyes to painful stimuli
1 No eye opening

Verbal 5 Fully oriented

response 4 Not fully oriented
3 Verbalizes, but not normally conversant
2 Vocalized unintelligible sounds
1 No vocalization

Motor 6 Obeys verbal command to move

response 5 Localizes to painful stimuli
4 Withdraws arm from stimulus
3 Stimulus causes flexion posturing
2 Stimulus causes extension posturing
1 No response

Which Bridging veins between inner and outer meningeal

vessels are membranes
often
implicated
in SDH?

What is the Concave (crescent-shaped) hyperdensity that does

classic CT not respect suture lines
finding of
a SDH?

What is Disruption of cerebral or brainstem white matter tracts

diffuse secondary to acceleration/deceleration injury, often
axonal from motor vehicle accidents
injury?

How is MRI is much more sensitive than CT

diffuse
axonal
injury
diagnosed?

What is The intracranial compartment is divided into two parts

cerebral by the tentorium, an invagination of dura mater that
herniation? is fairly rigid and has a circular opening, or notch, in
its center, through which the brainstem passes. When
pressure increases in the supratentorial compartment,
in which the cerebral hemispheres lie, the brain may
be displaced or herniated through the tentorial notch,
which causes pressure on the brainstem.
 How can If pressure increases enough in the supratentorial
pupillary compartment, the brainstem may be forced further
size down into the infratentorial space, which can stretch
changes the ipsilateral oculomotor nerve and cause the pupil
indicate to dilate. Additionally, as the uncus (the most medial
cerebral part of the temporal lobe) swells into the tentorial
herniation opening, it may compress the third nerve on that side,
is blowing that pupil. On rare occasions, though,
occurring? pupillary dilation may occur contralateral to the side
of the pressure-inducing lesion.

Name five 1. Elevate the patient's head of bed above 30

ways to degrees.
manage 2. Hyperventilate to keep Pco 2 25 to 30 mm Hg.
elevated
3. Administer 25% Mannitol (0.5 mg/kg) for osmotic
ICP.
diuresis.
4. Remove CSF by ventriculostomy.
5. Barbiturate/other general anesthetic-induced
coma.

P.629
P.630

Dementia
What is the The neurodegenerative diseases are the most common cause of
most dementia. AD accounts for approximately 50% to 60% of all
common dementia. The incidence of AD increases with age and is
cause of present in 30% to 50% of persons above 85 years of age.
dementia?

What are PD, Huntington's disease, Pick's disease, progressive

some of the supranuclear palsy, and dementia with Lewy bodies (DLB)
other causes
of dementia?

How often Rarely (<5%)

are
dementias
reversible?

What are the Reversible dementias include dementia secondary to an

reversible infection of the CNS (such as neurosyphilis), metabolic and
dementias? nutritional dementias (vitamin B12 deficiency), inflammatory
dementias (vasculitis involving cerebral blood vessels), dementia
caused by a structural defect impinging on the brain (a subdural
hematoma or tumor), normal-pressure hydrocephalus, and
endocrine-related dementia (hypothyroidism).

When should When onset of dementia is fairly rapid (over months) and when
an EEG be the patient complains of, or is noticed to have, multifocal
obtained in myoclonic jerks. These symptoms may be a result of the prion
the disease Creutzfeldt-Jakob disease. The classic EEG findings
evaluation of include periodic epileptiform discharges.
the
demented
patient?
 What should Large ventricles (that are enlarged out of proportion to
the clinician whatever cortical atrophy might be present), which could
look for suggest the presence of normal-pressure hydrocephalus;
when evidence of previous strokes, which could yield a diagnosis of a
reviewing vascular dementia; and evidence to rule out existing reversible
the traumatic sequelae, such as a subdural hematoma, or a
neuroimaging surgically remedial lesion, such as a neoplasm
of a
demented
patient?

When should When chronic meningitis or an inflammatory disease affecting

an LP be the brain is suspected to be the cause (e.g., in the
considered immunosuppressed patient). Also, in the patient with suspected
in the normal pressure hydrocephalus, a high-volume LP (in which at
evaluation of least 30 mL of CSF is removed) may cause the patient to
dementia? improve acutely, thus helping to establish the diagnosis.

P.631

Alzheimer's Disease
Name a gene Three different variants of the apolipoprotein E gene exist on
polymorphism chromosome 19 (E2, E3, and E4). E4 is associated with an
that is increased risk of dementia. However, many people with apo E4
associated never develop dementia, whereas many people without apo E4
with AD. do.

Should apo E Screening relatives of patients with AD with apo E should

be used for probably be discouraged. Its role as a diagnostic tool is
screening or unclear and is less important than the dementia workup
diagnosis? above.

How is AD There is no cure for AD, although anticholinesterase drugs

managed? (tacrine, donepezil, rivastigmine, galantamine) and one NMDA
receptor antagonist (memantine) are approved for use in the
disease (see Table 14-2). By increasing cholinergic activity in
some patients with AD, some improvement in memory function
may be elicited. Antipsychotic medications may help control
some of the behavioral problems (e.g., agitation) that may
develop in patients with AD.

Table 14-2. Cognition-Enhancing Medications

Common Side
Medication Class Dose Effects

Donepezil Cholinesterase 510 mg qd Nausea,

inhibitor vomiting,
fatigue,
dizziness

Rivastigmine Cholinesterase 36 mg bid Same as

inhibitor above

Galantamine Cholinesterase 812 mg bid or Same as

inhibitor 1624 mg qd above
(extended
release)
 Memantine NMDA 10 mg bid Dizziness,
receptor confusion,
antagonist agitation,
headache

P.632

Vascular Dementia
How They are the second most common type of dementia after the
common degenerative dementias and often occur concomitantly with
are degenerative dementias. Pure vascular dementias, however, are
vascular relatively rare in patients without a known history of clinical
dementias? stroke.

Other Dementias
What is the clinical triad Gait apraxia (a specific form of ataxia), urinary
of normal-pressure incontinence, and dementia
hydrocephalus?

How is the diagnosis of Marked improvement in gait after highvolume

NPH established? lumbar puncture (>30 mL of CSF)

What is the main Subdural hematoma

serious risk of a large-
volume LP?

What features Mental status fluctuations, parkinsonian features,

distinguish dementia and frequent visual hallucinations often are seen in
with Lewy bodies from dementia with Lewy bodies.
AD?

P.633

Endocrine Abnormalities and Vitamin Deficiencies

What vitamin deficiency, which is Thiamine (vitamin B1)
often found in alcoholics, can
result in an acute neurologic
syndrome when glucose is
administered to deficient patients?

What vitamin deficiency causes Vitamin B12 (cyanocobalamin)

subacute combined degeneration?

What are the neurologic sequelae Both excess and deficiency of vitamin
of pyridoxine (vitamin B6) B6 can cause neuropathy. The deficient
deficiency? state tends to cause a mixed
sensorimotor neuropathy. In neonates,
deficiency may cause seizures.

What is the purpose of folate Because of the increased risk of

supplementation? neonatal neural tube defects

What is the purpose of vitamin K Phenytoin, carbamazepine,

supplementation? phenobarbital, and primidone can cause
a deficiency of vitamin Kdependent
clotting factors in the neonate.
 When should vitamin K be given? Women on these drugs should take 20
mg/day of vitamin K1 (phytonadione)
during the last few weeks of pregnancy.
Neonates should be given vitamin K1 at
birth.

What are the neurologic Decreased cerebellar coordination,

manifestations of vitamin E peripheral neuropathy, night blindness,
deficiency? and eye movement abnormalities

Calcifications seen on head CT in Hypoparathyroidism. Other neurologic

the basal ganglia, dentate nuclei of effects of hypoparathyroidism result
the cerebellum, and the cerebellar from hypocalcemia and include tetany,
cortex suggest what potential cramps, seizures, and paresthesias.
endocrine abnormality?

Which is associated with seizures Both

and coma, hypoglycemia or
hyperglycemia?

Too rapid correction of Osmotic myelinolysis or central pontine

hyponatremia can cause what myelinolysis
neurologic condition?

Headache and Facial Pain

What are four important causes of an CNS infection, elevated ICP, SAH,
organic headache syndrome? and CNS tumor

Which is more common, functional or Functional headache occurs in 95%

organic headache? of headache patients.

P.634

Organic Headache
Who are susceptible to Primarily young obese women
pseudotumor cerebri?

How is the diagnosis of Elevated opening CSF pressure (>20 cm H2 O) but

pseudotumor cerebri made? no mass lesion seen on imaging studies

Vascular Headache
What is common migraine? Migraine headache with neither aura nor
transient neurologic deficit

What are three types of Triptans, mixed analgesics (such as Fiorinal),

prescription drugs used to and ergotamine derivatives (see Table 14-3)
abort the headache of a
migraine attack?

Why is the amount of To avoid the risk of ergotism with higher

ergotamine that a patient may doses
take limited to 10 mg per
week?

What is ergotism? Excessive vascular contraction, resulting in

symptomatic peripheral vascular ischemia or
symptomatic coronary artery constriction

What are three Symptomatic coronary artery disease,

 contraindications to peripheral vascular disease, or complicated
ergotamine use? migraine

How are triptans administered? All may be administered orally, and other
preparations include nasal spray,
subcutaneous injection, or orally
disintegrating tablet.

What five prophylactic drug 1. Beta-adrenergic blockers such as

therapies prevent or reduce propranolol
the frequency of migraine? 2. Calcium-channel blockers such as
verapamil
3. Tricyclic antidepressants such as
amitriptyline
4. Valproic acid
5. Topiramate

What is a cluster headache? Clustered attacks of severe, unilateral,

orbital headache with nasal congestion and
lacrimation

Which gender is most affected Men

by cluster headache?

Distinguish the behavior of a The patient with cluster headache paces.

patient with cluster headache.

Table 14-3. Triptans

Generic Name Formulation and Dosage

Sumatriptan Subcutaneous injection (6 mg), nasal spray (5, 20 mg),

oral tablet (25, 50, 100 mg)

Rizatriptan Oral tablets and rapidly dissolving tablet (5, 10 mg)

Zolmitriptan Oral tablet (2.5, 5 mg), oral disintegrating tablet (2.5,

5 mg), nasal spray (5 mg)

Naratriptan Oral tablet (1, 2.5 mg)

Almotriptan Oral tablet (6.2, 12.5 mg)

Frovatriptan Oral tablet (2.5 mg)

Eletriptan Oral tablet (20, 40 mg)

P.635

Tension-Type Headache
What two types of drugs are useful for 1. Tricyclic antidepressants,
treating tension headache? such as amitriptyline
 2. Analgesics, especially NSAIDs

Facial Pain
What is an important laboratory Elevated ESR
finding frequently seen in
patients with temporal arteritis?

Why is temporal arteritis a If not treated, it may result in blindness.

relative emergency?

What is the treatment for Anticonvulsants such as carbamazepine,

trigeminal neuralgia? gabapentin, or phenytoin or tricyclic
antidepressants

What surgical procedures are Microvascular decompression, stereotactic

used in patients with trigeminal gamma knife surgery, and chemical
neuralgia who fail medical ablation of the trigeminal sensory
management? ganglion

Where does temporomandibular In front of the ear

joint pain occur?

P.636

Other Head Pains

How is post-LP By using a small-bore needle. Keeping the patient supine
headache may also help.
prevented?

What is A blood patch. Sterile blood is removed from the patient

definitive and injected into the LP site (but not into the dural space),
therapy for where it presumably patches the leak in the dura.
post-LP
headache?

Back Pain
What findings Weakness and sensory loss related to a specific nerve root
on neurologic associated with an absent deep tendon reflex. For example,
examination weakness of plantarflexion with sensory loss in the S1
support back dermatome associated with an absent ankle jerk would be
pain of consistent with an S1 radiculopathy.
neurologic
origin?

What two Leg weakness and urinary or bowel incontinence.

complaints
should be
urgently
evaluated in a
patient with
back pain?

Table 14-4. Common Radiculopathies

Spinal Cord
Level Pain Weakness Sensory Deficit Hyporeflexia
1 Lateral Biceps/infraspinatus Deltoid Biceps
forearm/index
finger

2 C6 Biceps Shoulder to Biceps and

thumb brachioradialis

3 C7 Scapula/axilla Lateral hand Triceps

4 L5 Buttocks/thigh Great toe None

dorsiflexion

5 S1 Buttocks/posterior Ankle plantar Posterolateral

leg flexion calf and foot

What do leg These

weakness suggest that
and spinal cord
incontinence compression
suggest? may be
present.

In Table 14-
4 on the
prior page,
fill in the
open cells of
the table.

Row 1 C5

Row 2 Trapezius to
thumb

Row 3 Triceps

Row 4 Skin and

dorsum of
foot

Row 5 Ankle

What is Precipitation
neurogenic of symptoms
claudication? of lumbar
stenosis
during
ambulation,
presumably
because of
ischemia of
lumbosacral
roots
 P.637

Vertigo and Dizziness

What symptoms Presyncope may have transient autonomic symptoms (e.g.,
help distinguish tachycardia, diaphoresis, nausea).
light-
headedness
attributable to
presyncope from
disequilibrium?

Where is the Vestibular apparatus and vestibular nerve

anatomic defect
that causes
peripheral
vertigo?

Where is the Vestibular nucleus and pathways in the brainstem

anatomic defect
that causes
central vertigo?

What are the 1. BPPV

three most 2. Labyrinthitis (also called vestibular neuronitis)
common 3. Mnire's disease
peripheral
causes of
vertigo?

How is the Dix The sitting patient quickly lies supine and drops his or her
Halpike head 30 degrees down and over the end of the exam table.
maneuver Lateral rotation of the head stimulates the posterior
performed? semicircular canal of the ear that is toward the floor. After
a short latency, horizontal or rotatory nystagmus and/or
vertigo may be produced.

What are three 1. Unilateral tinnitus

classic 2. Unilateral deafness
symptoms of 3. Paroxysmal vertigo
Mnire's
syndrome?

List the two 1. Vertebrobasilar TIA or stroke

most common 2. Brainstem tumor
causes of
central vertigo.

P.638

Peripheral Neuropathy, Numbness, and Tingling

What is the most common cause Systemic vasculitis (e.g., polyarteritis
of mononeuritis multiplex? nodosa)

What is the most common CharcotMarieTooth disease (hereditary

inherited neuropathy? sensorimotor neuropathy type 1)

What is the initial treatment for If the case is mild, treatment is usually
carpal tunnel syndrome? with NSAIDs and a wrist splint.

What is the indication for surgery If initial treatment fails or there is

 for carpal tunnel syndrome? associated denervation seen on the EMG

What are examples of common CharcotMarieTooth disease and uremia

demyelinating neuropathies?

What are examples of axonal Alcohol and chemotherapeutic agents

neuropathies? (e.g., vincristine)

What is an example of a common Diabetes

cause of a mixed neuropathy?

P.639

Guillain-Barr Syndrome and Other Neuromuscular

Diseases
What is the Miller Ophthalmoplegia, ataxia, areflexia
Fisher variant of
GBS?

What laboratory CSF shows protein >55 mg/dL without a significant

evidence supports pleocytosis (i.e., albuminocytologic dissociation). EMG is
the diagnosis of normal initially but eventually shows findings of
GBS? demyelination.

What is CIDP? Chronic inflammatory demyelinating polyneuropathy, a

recurrent form of GBS

How does CIDP CIDP is characterized by frequent relapses, whereas GBS

differ from GBS? is usually monophasic.

How is CIDP High dose prednisone or other immunosuppressants more

treated? often than plasma exchange or intravenous
immunoglobulin

What is myasthenia A disease characterized by neuromuscular transmission

gravis? defect, producing weakness

What causes the Autoantibodies against postsynaptic skeletal muscle

defect in nicotinic acetylcholine receptors
neuromuscular
transmission?

What clinical Fatigable weakness of skeletal muscles

features are classic
of MG?

Which muscles are Eyelid and extraocular muscles, causing ptosis and
most frequently fluctuating diplopia
involved?

What tests are 1. EMG/NCS

useful in diagnosing 2. ACh receptor antibody titer
MG? 3. Edrophonium (Tensilon) test

What radiograph is Chest CT looking for a thymoma

important to obtain
in a patient with
MG?

What are three 1. Anticholinesterase [e.g., pyridostigmine (Mestinon)]

types of therapy? 2. Immunosuppressants [e.g., prednisone, azathioprine
 (Imuran), mycophenolate mofetil (CellCept)]
3. Immunomodulation with plasma exchange or
intravenous immunoglobulin

List 10 medications Azithromycin, aminoglycosides, clindamycin

that should be Procainamide, beta blockers, lidocaine, IV magnesium
avoided in patients Chloroquine
with MG. Phenytoin, lithium

P.640

Parkinson's Disease
What is the PD is an idiopathic disorder that is responsive to L-dopa.
difference Parkinsonism has similar features to PD but is secondary to
between PD another cause and is often not responsive to L-dopa.
and
parkinsonism?

Why is Carbidopa prevents the peripheral catabolism of L-dopa to

carbidopa dopamine. L-dopa can penetrate the bloodbrain barrier, but
included with dopamine cannot. Once in the brain, L-dopa is used to
the L-dopa? synthesize dopamine, which alleviates the symptoms of PD.

For the
following
medications,
list their mode
of action:

Benztropine, Muscarinic anticholinergic

trihexyphenidyl

Amantadine Stimulates release of dopamine; glutamate antagonist

Levodopa Precursor to dopamine

Carbidopa Dopa decarboxylase inhibitor

Pramipexole, Dopamine agonist

ropinirole

Selegiline, Monoamine oxidase-B inhibitor

rasagiline

Entacapone, Catechol-O-methyl transferase inhibitor

tolcapone

Name five Typical antipsychotics, metoclopramide, prochlorperazine,

medications to reserpine, MAOIs
avoid in PD.

P.641
P.642

Stroke and Subarachnoid Hemorrhage

What risk factors Hypertension, diabetes, smoking, and advancing age.
are associated Hypercholesterolemia has not been shown definitively to
with a first be a stroke risk factor, although treatment for
stroke? hypercholesterolemia has been shown to reduce risk of
stroke recurrence.
What can be done Having had one stroke increases the risk of having
for secondary another. Aspirin and other antiplatelet agents decrease
stroke prevention? the annual risk of repeat stroke by approximately 25% to
30%. For patients with carotid stenosis of >70% who are
symptomatic (e.g., with TIAs or a history of stroke), and
certain asymptomatic patients with tight carotid stenoses,
consider carotid endarterectomy.

How is stroke In appropriate patients (consider risk of falling),

prevented in the anticoagulation with warfarin is the most effective
patient with atrial treatment and may lessen the risk of cardioembolic stroke
fibrillation or in such patients by 60% to 80%.
another
cardioembolic
source of stroke?

What is the role of The use of heparin in acute stroke is controversial, but it
heparin in stroke? may be useful for strokes that appear to be actively
progressing (stroke in progress), particularly if progressive
thrombosis of the basilar artery is suspected. Heparin may
also lower the risk of an imminent repeat cardioembolic
event after a primary cardioembolic event has occurred,
and it may be helpful in patients with crescendo TIAs
or in selected arterial dissections.

What is a potential Conversion of an uncomplicated ischemic stroke into a

complication of devastating hemorrhagic stroke
heparin therapy in
an acute stroke?

What are the Ischemic stroke (no hemorrhage on CT). No history of

major criteria for hemorrhagic illness, current warfarin, heparin, or
administering IV t- enoxaparin, or recent history of stroke, head trauma,
PA? lumbar puncture, or surgery. No uncontrollable
hypertension and adequate platelet count. Onset time <3
hours.

When a patient is CT of the brain should be performed to distinguish the

thought to cause of the perceived stroke as being either ischemic or
clinically have had hemorrhagic. Ischemic stroke may take more than 24
a stroke, what hours to manifest on CT, so CT is expected to be normal
initial ancillary initially.
test should be
performed
immediately?

What is the initial Administration of aspirin, 325 mg

management of Permissive hypertension
the patient with Avoidance of hypoglycemia, hyperglycemia,
ischemic stroke overhydration, and dehydration
who is not a Electrocardiographic monitoring to check for arrhythmias,
candidate for t- left ventricular and atrial hypertrophy or enlargement,
PA? and old or new myocardial infarction

Why is permissive Because hypotension may increase the area of infarction.

hypertension
acceptable?

What other Swallow evaluation, physical therapy, and occupational

therapies are therapy consultations
important prior to
discharging the
stroke patient?

When is the risk 2 to 5 days after the stroke, when the edema around the
of herniation after infarcted area is maximal
a stroke the
greatest?

What are the MRI has better resolution than CT and may show a small
advantages of MRI stroke that is not evident on CT. It is superior for imaging
over CT for acute the posterior fossa and allows performance of MRA to
stroke? evaluate cerebral blood vessels noninvasively.

What are the MRI is inferior to CT in detecting acute bleeding and

disadvantages of requires an extended period of time (approximately 30
MRI compared minutes to 1 hour), during which the patient cannot be
with CT in the observed closely.
setting of an
acute stroke?

What techniques Carotid ultrasound and Doppler can image the carotid
are used to arteries in the neck.
evaluate the MRA and CT angiography can image either intracranial
status of the blood vessels or extracranial arteries.
blood vessels to Conventional angiography is the gold standard, but it is
the brain? invasive and carries risks.

In addition to an TTE and TEE can help determine whether a

electrocardiogram, cardioembolism was likely to have been the source of
what other cardiac stroke. TEE is more sensitive for detecting left atrial
workup should be thrombi and cardiac vegetations, but it is costly and
considered in the invasive.
patient with a
new stroke?

For Table 14-5

above, fill in the
open cells with
regard to the
neurologic exam
features:

Row 1 Impaired

Row 2 Preserved

Row 3 Preserved

Row 4 Impaired

Row 5 Preserved

After the diagnosis Angiography, to look for a ruptured aneurysm (the most
of SAH is made, common source of SAH)
what additional
study is essential?

If an aneurysm is Surgical clipping or endovascular coiling of the aneurysm

found, what can
be done to
prevent
rebleeding?
 P.643

Table 14-5. Aphasia

Syndrome Fluency Comprehension Repetition

1 Broca's (+) (+)

2 Wernicke's () ()

3 Conduction (+) ()

4 Transcortical motor (+) (+)

5 Transcortical (+) ()
sensory

() = impaired (+) = preserved

P.644
P.645

Table 14-6. ILAE Seizure Classification

Seizures

Definitions
What is A continuing tendency toward spontaneous recurrent seizures
epilepsy? as a result of some persistent pathologic process affecting the
brain. The latter criterion excludes patients with provoked
seizures, who have an otherwise normal brain. The
International League Against Epilepsy has classified epilepsy
syndromes according to the predominant type of seizure, EEG
findings, age of onset, interictal abnormalities, and natural
history.
 What is the Approximately 10% of the population may experience a
prevalence of seizure at some time of life, but only 3% of people develop
seizures and epilepsy.
epilepsy?

What is the Childhood absence epilepsy is an idiopathic generalized

most common epilepsy syndrome in which absence seizures begin in early
generalized childhood and usually abate by late adolescence. (The
epilepsy syndrome is caused by an inherited abnormality of
syndrome neurotransmission involving the thalamus and cortex.
arising in The EEG characteristically shows generalized 3 c/s spike-and-
childhood? wave activity in between and during seizures. MRI is normal.)

What is the Juvenile myoclonic epilepsy is an idiopathic generalized

most common epilepsy syndrome in which brief generalized myoclonic jerks
generalized and convulsions begin in late adolescence and persist
epilepsy throughout life. (It is inherited as an autosomal dominant
syndrome trait, but the pathologic abnormality is not known. The
arising in interictal EEG shows characteristic generalized multiple
adolescence or spike-and-wave activity in between seizures and occasionally
early with myoclonic jerks. MRI is normal.)
adulthood?

What is the TLE is a symptomatic partial epilepsy syndrome in which

most common complex partial seizures begin in late adolescence or early
epilepsy adulthood and more or less persist throughout life. It is
syndrome of usually associated with mesial temporal sclerosis, but the
adults? etiology is not known. (The interictal EEG demonstrates
spikes originating from the temporal lobe. MRI may show
atrophy and sclerosis of mesial temporal structures.)

What EEG A normal EEG

findings
suggest
pseudoseizure?

Diagnostic Tests
What is the most sensitive and Simultaneous video and EEG monitoring
specific method for during a spell. However, during simple
determining that a spell is a partial seizures, the EEG is usually normal.
seizure?

What is the most sensitive MRI defines brain anatomy with greater
neuroimaging study in the detail and often identifies subtle
evaluation of epilepsy? abnormalities that are not seen on CT.

P.646

Table 14-7. Antiepileptic Medications

Traditional AEDs Newer AEDs

Carbamazepine Felbamate

Clonazepam Gabapentin

Clorazepate Lamotrigine
 Diazepam Levetiracetam

Ethosuximide Oxcarbazepine

Phenobarbital Pregabalin

Phenytoin Tiagabine

Primidone Topiramate

Valproic Acid Zonisamide

Table 14-8. Important Side Effects of Selected AEDs

Medication Adverse Effect

1 Carbamazepine

2 Ethosuximide Nausea, headache, blood dyscrasias

3 Felbamate Aplastic anemia, hepatitis

4 Lamotrigine Rash (Stevens-Johnson), especially with

valproic acid

5 Phenobarbital

6 Phenytoin

7 Topiramate Cognitive impairment, nephrolithiasis,

glaucoma, weight loss

8 Valproic acid

Treatment
Which drugs have the broadest Valproic acid, lamotrigine, and
spectrum of antiseizure activity? topiramate

In Table 14-8, fill in the open cells

with regard to medication side
effects.

Row 1 Leukopenia, hyponatremia from SIADH,

rare aplastic anemia or hepatitis
 Row 5 Sedation, depression

Row 6 Gingival hyperplasia, hirsutism, coarse

features, cerebellar ataxia,
osteoporosis

Row 8 Weight gain, alopecia, neural tube

defects, thrombocytopenia, tremor

P.647

Table 14-9. Monitoring AED Blood Levels

Medication Therapeutic Range (!g/mL)

Phenytoin 1020

Valproic acid 50100

Carbamazepine 412

Phenobarbital 1540

What is the risk of seizure Risk of seizure recurrence remains 20%

recurrence in patients to 70%, even for patients who are
withdrawn from good candidates for drug withdrawal.
medications?

Table 14-9 shows the

common therapeutic
levels.

Status Epilepticus
What is status 30 minutes of continuous seizure activity or
epilepticus? intermittent seizures without return to baseline level
of consciousness

How long should a About 5 minutes. If seizure activity continues for

seizure continue more than 5 or 10 minutes, it is unlikely to stop
before intervention is spontaneously.
started?

When does brain After about 30 minutes of seizure activity; but keep
injury become an issue in mind it takes time for emergency medical help to
with a seizure? arrive and begin medication, so intervention must
start early.

What is the most Anticonvulsant noncompliance

common etiology of
status epilepticus?

How is nonconvulsive By EEG

 status epilepticus
diagnosed?

What are some Lorazepam, diazepam, phenytoin, fosphenytoin,

commonly used drugs phenobarbital, midazolam, and propofol
in the treatment of
status epilepticus?

P.648

Paraneoplastic Syndromes
What are four Encephalomyelitis, peripheral neuropathy, cerebellar
neurologic degeneration, and LEMS
autoimmune-related
paraneoplastic
syndromes?

What are the most Lung cancer (small cell), ovarian cancer, and breast
common cancers that cancer
result in a
paraneoplastic
syndrome?

How is LEMS By EMG. The response to repetitive nerve stimulation

distinguished from in patients with myasthenia gravis usually becomes
myasthenia gravis? progressively weaker, whereas in LEMS patients it
grows stronger.

P.649

CNS Infections1

Meningitis
What is the >3 cases per 100,000 population. Neisseria meningitidis
incidence of and Streptococcus pneumoniae are the most common
bacterial offending pathogens.
meningitis?

What is the Overall mortality rate is >10%.

mortality rate for
bacterial
meningitis?

What is the Exact incidence is unknown because it is underreported

incidence of viral and difficult to make an exact diagnosis. One study
meningitis? reported >10 cases per 100,000 person-years.

What are normal

measurements for
CSF for the
following:

Opening 50 to 195 mm H2 O (equivalent to <18 cm of CSF)

pressure?

WBCs/PMNs? WBCs <5/PMNs <1

CSF 0.6
glucose:blood?

CSF protein? 15 to 40 mg/dL

 What is the If bacterial meningitis is suspected, the patient should
treatment for be treated with antibiotics immediately.
bacterial
meningitis?

Tuberculous Meningitis
What organism Mycobacterium tuberculosis and, rarely, Mycobacterium
usually causes bovis
tuberculous
meningitis?

How long does Up to 1 month. As much CSF as possible must be submitted

it take to to the laboratory because there are usually very few
culture tubercle bacilli.
Mycobacterium?

What is the Even with appropriate treatment, 10% to 30% of patients

prognosis of die. Coma at the time of presentation is the most significant
tuberculous predictor of a poor outcome.
meningitis?

What are the Exudate in the subarachnoid space, especially at the base of
pathologic the brain involving adjacent brain (causing basal
findings seen in meningoencephalitis), cranial nerves (causing cranial
tuberculous neuropathies), arteries (causing stroke), or obstruction of
meningitis? basal cisterns (causing hydrocephalus)

What is the Confusion progressing to stupor and coma, with cranial

natural history nerve palsies, elevated intracerebral pressure, decerebrate
of untreated posturing, and death in 1 to 2 months
tuberculous
meningitis?

P.650

Encephalitis
What is the HSV (HSV-1 in adults and HSV-2 in neonates)
most common
cause of
identifiable
encephalitis?

Are there No
seasons or
geographic
areas of
increased risk
for herpes
encephalitis?

What can be Serum antibodies may be helpful for some pathogens, but
checked in the both acute and convalescent (taken 13 weeks later)
serum to specimens are required. Checking IgM in serum or CSF may
evaluate for be helpful in some cases but is not definitive.
viral
encephalitis?

Are any Available for HSV and VZV encephalitis

polymerase
chain reaction
tests available
 for viral
encephalitis?

What do the
following
diagnostic
tests show in
encephalitis?

CT scan (of Often shows enhancement in the region of the brain involved.
the head with In HSV encephalitis, the temporal lobes are most commonly
contrast) involved. Listeria monocytogenes causes a rhombencephalitis
(involvement of the brainstem), and focal enhancement in the
region of the brainstem may be seen on CT.

EEG May demonstrate focal abnormalities in the temporal lobe

region (periodic lateralized epileptiform discharges or PLEDS)

MRI of the More sensitive than CT and more likely to reveal

head abnormalities early in the disease process. MRI is also more
sensitive for Listeria rhombencephalitis due to improved
visualization of the brainstem. The combination of CT, EEG,
and MRI reveals 99% of cases of HSV encephalitis.

What are the Hemorrhagic necrosis of frontal and temporal lobes

common gross
pathologic
changes seen
in
encephalitis?

What Necrosis and inflammation with eosinophilic intranuclear

microscopic inclusion bodies (Cowdry type A)
pathologic
changes are
seen in HSV
encephalitis?

What is the High-dose intravenous acyclovir for 14 to 21 days (relapses

treatment for occur with shorter courses)
HSV
encephalitis?

P.651

Brain Abscess
What is the incidence of <1 in 10,000 hospital admissions
brain abscess?

What are the demographics It is more common in men, with a median age
of brain abscesses? of incidence of 30 to 45 years.

What is cerebritis? Area of low density seen on CT or altered signal

on MRI with an area of ring enhancement that
does not decay on delayed scans. This is the
early stage of a brain abscess before it
develops into a capsule.

What pathogens cause brain Streptococci, bacteroides and Prevotella,

abscess in Enterobacteriaceae, Staphylococcus aureus,
immunocompetent persons? fungi, S. pneumoniae, and Haemophilus
influenzae
 What pathogens cause brain Toxoplasma gondii, Nocardia, Listeria, and M.
abscess in tuberculosis in addition to those listed for
immunocompromised persons who are immunocompetent
persons (i.e., persons with
defects in cell-mediated
immunity)?

What is the most common T. gondii. Empiric therapy for toxoplasmosis is

cause of a focal CNS lesion given if the IgG is positive and CT and MRI
in patients with AIDS? findings are compatible.

When should a brain biopsy For patients who fail to respond to empiric
be considered? therapy or have unusual features

What is the most common There is no single predominant cause of a focal

cause of a focal CNS lesion CNS lesion, and an early brain biopsy is
in immunocompromised required.
patients other than AIDS
patients?

When is medical therapy Cerebritis (hemorrhage may result with biopsy)

alone appropriate for brain Underlying condition that greatly increases
abscess? surgical risk
Abscess that is deep or in a dominant location
Multiple abscesses, especially if remote from
each other
Abscess <2.5 cm
Early abscess improvement (in many cases
cerebritis)
Concomitant meningitis or ependymitis

What factors indicate a poor Delayed diagnosis

prognosis in brain abscess? Poor localization
Multiple, deep, or loculated abscesses
Ventricular rupture
Coma
Fungal abscess
Inappropriate antibiotics

P.652

Prion Disease
What is a prion? Small, infectious proteinaceous
particle

What laboratory test can aid in the Elevated 14-3-3 protein levels in
diagnosis of CJD? the CSF

What is the prognosis for CJD? Invariably fatal

HIV and the Nervous System

What are three CNS diseases caused HIV meningitis, vacuolar
specifically by HIV? myelopathy, ADC

P.653

HIV Meningitis
What are the clinical characteristics of Indistinguishable from any other
primary HIV meningitis? aseptic meningitis
AIDS Dementia Complex
What are typical CSF Mild CSF lymphocytosis, increased protein, and
findings in ADC? sometimes oligoclonal bands

What do imaging Cerebral atrophy, ventricular dilation, and subcortical

studies in ADC white matter disease (suggesting demyelination)
demonstrate?

HIV Vacuolar Myelopathy

What is the prevalence of HIV It is found at autopsy in approximately 25%
vacuolar myelopathy? of AIDS patients.

What other HIV neurologic ADC

disease is comorbid with
vacuolar myelopathy?

What is the major differential Cervical stenosis and vitamin B12

diagnosis of vacuolar myelopathy, which also affect
myelopathy? corticospinal and posterior columns

Is the course of vitamin B12 Vacuolar myelopathy usually has earlier

myelopathy different from incontinence and fewer sensory
vacuolar myelopathy? abnormalities.

Peripheral Nervous System Complications of HIV

How common is peripheral nerve Approximately 50% of patients have
disease in patients with AIDS? disease of peripheral nerves at autopsy.

Solitary Brain Lesions and HIV

What is the differential diagnosis for a Toxoplasmosis, primary CNS
solitary brain lesion seen on MRI in AIDS? lymphoma, and brain abscess

P.654

Multiple Sclerosis
What are the demographics of Approximately 65% of those with MS are
MS? white women, who typically present
between the ages of 20 and 40 years.

What is seen in the CSF

examination of patients with MS
with regard to:

Electrophoresis? In approximately 90% of cases, the CSF

contains oligoclonal bands unique to the
CSF (i.e., they are not found in blood).

White blood cells? There may occasionally be a slightly

elevated leukocyte count (<25), which
tends to be lymphocytic.

Protein? Mildly elevated protein occurs in

approximately 25% of cases.

What in the CSF can be used as Myelin basic protein can be a good
an indicator of an acute indicator of an acute exacerbation, but it
exacerbation? is present for only approximately 2 to 3
 days after an exacerbation occurs.

How often does the MRI show In approximately 90% of patients with MS.
demyelination in patients with
MS?

What is Lhermitte's sign? Trunk and limb paresthesias induced by

neck flexion

What is Uthoff's phenomenon? Worsening neurologic deficits precipitated

by elevated temperatures

What treatment may provide High-dose methylprednisolone at the time

symptomatic relief for patients of the acute attack. A common dose and
with an acute exacerbation of schedule is to give 1000 mg daily for 3 to
MS? 5 days, followed by a 2- to 3-week
prednisone taper.

What outpatient regimen is often Oral prednisone tapers

used for MS patients having an
acute attack, even though there
is only anecdotal evidence of its
efficacy?

After 10 years, how many MS At 10 years, approximately two thirds are

patients are ambulatory rather ambulatory.
than wheelchair bound?
Editors: Bergin, James D.
Title: Advanced Medicine Recall, 1st Edition
Copyright 2009 Lippincott Williams & Wilkins

> Table of Contents > Section III - Related Specialties > Chapter 15 - Pharmacology

Chapter 15
Pharmacology

Abbreviations
ACE Angiotensin-converting enzyme

ACTH Adrenocorticotropic hormone

ARB Angiotensin II receptor blocker

cGMP Cyclic guanine monophosphate

CNS Central nervous system

COPD Chronic obstructive pulmonary disease

CR Controlled-release

CYP 3 4A Cytochrome P-450 enzyme 3 4A

DMARD Disease-modifying antirheumatic agent

EPS Extrapyramidal side effects

H2RA Histamine-2 receptor antagonist

HIT Heparin induced thrombocytopenia

HMG-CoA Hydroxymethyl glutaryl coenzyme A

INR International normalized ratio

IVP Intravenous push

 LDL Low-density lipoprotein

LFT Liver function test

MDI Metered dose inhaler

MIC Minimum inhibitory concentration

MSSA Methicillin-susceptible Staphylococcus aureus

NHL Non-Hodgkin's lymphomas

NSAID Nonsteroidal anti-inflammatory drug

PE Pulmonary embolism

PEA Pulseless electrical activity

PPV Polyvalent pneumococcal vaccine

SSRI Selective serotonin reuptake inhibitor

TFTs Thyroid function tests

TZDs Thiazolidinediones

VT/VF Ventricular tachycardia/ventricular fibrillation

VTE Venous thromboembolism

P.656
P.657

Allergy and Immunology

An anaphylactic Within as little as 30 minutes and almost always within 2
reaction is most hours.
likely to be
observed over
what time period
following drug
administration?

After a patient Yes, following recovery, the reaction can recur 6 to 8

recovers from hours following exposure.
anaphylaxis, is
there a value in
observing them for
a longer period of
time?

Should patients If the patient experienced only mild cutaneous eruptions,

with a penicillin the incidence of a serious reaction to cephalosporins is
allergy be advised relatively low and these agents may be used.
to also avoid the
use of
cephalosporins?

What medications Sulfonamides, cephalosporins (especially cefaclor),

have been minocycline, hydantoins, and penicillins.
associated with
the development
of serum sickness
reactions?

Does the No, this is a pseudoallergic reaction and it is most likely

development of due to fast rate of infusion of the drug. Usually slowing
red-man the infusion rate is all that is needed.
syndrome
following
vancomycin
administration
require
discontinuation of
the drug?

What causes red- Release of histamine as well as other mediators from

man syndrome? cutaneous mast cells

Is it necessary to Although routinely done in clinical practice, pretreatment

pretreat patients of these patients is not necessary.
with a shellfish
allergy with
steroids prior to
receiving contrast
media?

What causes the Iodine allergies reflect primarily the hyperosmolarity of

contrast reaction? the contrast agent with resultant non-IgE mediated mast
 cell degranulation.

What are shellfish Although shellfish may be rich in iodine, the reaction to
allergies usually shellfish is usually caused by IgE antibodies to the
due to? proteins in the fish and not the iodine.

Which class of Most allergic reactions occur from sulfa-containing

medications that antimicrobial agents.
contain a sulfa
moiety is often
associated with an
allergic reaction?

Can a person with Yes. While both contain sulfa moieties, the configuration
a known reaction of the sulfa component on the benzene ring is very
to different and the likelihood of a reaction is more
sulfamethoxazole theoretical than factual.
be administered
furosemide?

What other sulfa- This also holds true for medications such as celecoxib,
containing oral sulfonylureas, and sumatriptan.
medications are
also unlikely to
cause reactions?

What is the These agents inhibit T-cell proliferation by inhibiting the

mechanism of production of IL-2 and other cytokines by T cells.
action of
calcineurin
inhibitors
(cyclosporine,
tacrolimus)?

When is the most The blood levels for these agents should be ordered at a
appropriate time trough. Levels should be drawn ! hour prior to the next
to draw blood dose.
levels for the
calcineurin
inhibitors?

What are the most Hypertension, nephrotoxicity, hyperkalemia,

common adverse hypomagnesemia, and neurotoxicity
effects associated
with the
 calcineurin
inhibitors?

What is the Mycophenolate mofetil works through noncompetitive

mechanism of binding to inosine monophosphate dehydrogenase (IM-
action of PDH). The inhibition of this enzyme reduces lymphocyte
mycophenolate proliferation.
mofetil?

What are the risks Azathioprine is an inactive compound that is converted to

of administering 6-mercaptopurine (6-MP). The 6-MP is metabolized
azathioprine in primarily by xanthine oxidase. Since allopurinol inhibits
combination with xanthine oxidase, the bioavailability of 6-MP and
allopurinol? azathioprine can be increased by as much as fourfold,
increasing the risk of bone marrow suppression and
pancytopenia.

P.658
P.659

Cardiology
What is the dose of 300 mg IVP
amiodarone for a patient
with pulseless VT/VF?

What is the appropriate 40 units administered IVP

dose of vasopressin in
pulseless VT/VF, PEA, and
asystole?

What medications should Those medications with negative inotropic

be avoided in patients activity. Some of these are verapamil, diltiazem,
receiving a continuous procainamide, and beta-adrenergic blocking
infusion of dobutamine? agents.

What is the risk of using May worsen ischemic injury through vasodilatation
nitroprusside in patients of nondiseased vessels diverting blood from
with acute myocardial regions supplied by stenotic vessels (coronary
infarction? steal syndrome) and reflex tachycardia.

Which vasopressor may Phenylephrine, owing to its effect of reflex

be preferentially used in bradycardia. Vasopressin also has a relatively
septic patients with neutral impact on arrhythmias.
arrhythmic disturbances?
Should HMG-CoA Not necessarily. It depends on the dose of the
reductase inhibitors statin and whether or not other LFT abnormalities
(statins) be discontinued coexist, such as elevated total bilirubin. In the
when the hepatic majority of cases (70%), transaminase elevations
transaminases increase to will resolve spontaneously without intervention.
above three times the
upper limit of normal?

Do patients taking HMG- Yes and no. Inhibition of CYP3A4 results in

CoA reductase inhibitors increased level of medications that are
(statins) metabolized metabolized through this pathway, possibly
through the CYP 3A4 increasing the risk of adverse effects. However, to
enzyme system be clinically significant, patients would have to
(atorvastatin, simvastatin, consume >1 quart of grapefruit juice daily.
lovastatin) have to avoid Therefore a daily glass of grapefruit juice along
the consumption of with these agents is unlikely to cause any harm.
grapefruit juice?

What is the most Angiotensin receptor blocker (ARB). Although both

appropriate alternative classes of agents can cause this reaction, the
agent to prescribe in a mechanism between the two is different and ARBs
patient who developed can be utilized.
angioedema with ACE
inhibitors?

What side effects of Reflex tachycardia, increased renin activity, and

hydralazine therapy fluid retention can result from the stimulation of
contribute to ineffective sympathetic outflow secondary to hydralazine's
and unpredictable blood potent vasodilation.
pressure control in
patients?

What hypoglycemic Sweating

symptom is not masked
by beta blockers?

When is the onset of the 2 to 3 days in which overlapping with oral

antihypertensive effect clonidine is required when transitioning from oral
of a clonidine patch? to transdermal clonidine to prevent rebound
hypertension.

What additional effect of Furosemide causes direct vasodilation, resulting in

furosemide that occurs a rapid decrease in blood pressure.
prior to diuretic effects
may provide relief to
 patients with pulmonary
edema?

When should serum Levels are most reliable if drawn just before the
digoxin concentrations be next dose and no sooner than 6 to 8 hours after
drawn to avoid the last dose because of slow digoxin distribution
misinterpretation of between the blood and tissues.
falsely elevated levels?

How should warfarin The warfarin dose should be decreased by half

dosing be empirically when amiodarone is started, with close monitoring
adjusted when of the INR owing to amiodarone's inhibition of
amiodarone therapy is warfarin metabolism.
started?

Above what cumulative 450 to 550 mg/m 2

dose of doxorubicin is
there a higher risk of
irreversible myocardial
toxicity and heart
failure?

P.660

Dermatology
What amount and No more than 50 g/week for up to 2 weeks of use
duration of use should
high-potency topical
steroids be limited to?

What kind of Blue-gray discoloration occurs in 1% to 3% of

hyperpigmentation may patients on chronic amiodarone therapy. It may
result from chronic take up to a year or more after discontinuation to
amiodarone therapy? resolve. Sunlight can exacerbate this.

For which fungal skin Tinea capitis treatment with topical antifungals
infection should topical should also include an oral antifungal agent owing
antifungal treatment not to reduced absorption of topical formulations. In
be used alone? particular, ketoconazole shampoo should not be
used because it is ineffective against scalp
ringworm.

What topical preparations Pyrethrin (Rid, A-200) and permethrin (Elimite,

for the treatment of lice Nix)
and scabies should not be
 used in patients with
ragweed or
chrysanthemum allergies?

How soon after varicella It should be administered within 3 days of

zoster exposure is the exposure to varicella zoster.
varicella vaccine effective
for postexposure
prophylaxis?

What topical antibiotic Neomycin causes hypersensitivity reactions in 4%

causes more frequent to 6% of patients.
allergic contact dermatitis
than others?

When does phenytoin- This usually occurs 7 to 21 days after initiation

induced skin eruption and almost always within the first 2 months of
usually occur during therapy.
treatment?

If a phenytoin-induced Yes, these reactions may proceed to fatal

skin eruptions occur, reactions, like toxic epidermal necrolysis.
should the drug be
stopped?

How can warfarin-induced Discontinuation of warfarin with vitamin K

tissue necrosis be reversal and the use of heparin
managed?

What drug can be used to Phentolamine

minimize tissue injury
from extravasation of
sympathomimetic agents?

P.661

Endocrinology
What sulfonylureas are Chlorpropamide and glyburide
associated with the longest
duration of hypoglycemia?

Which insulin should not be Insulin glargine (Lantus)

mixed with any other kind of
insulin due to its acidic pH?
 When should patients on When a meal is skipped, doses of
repaglinide or nateglinide be meglitinide should be skipped too.
told to skip a dose?

How much time should pass Up to 3 to 4 months may be needed for

after initiating or changing the the full effect TZDs.
dose of TZDs before assessing
the full effect?

How much weight gain may be Mild weight gain of 1.2 to 3.5 kg may be
seen with the TZDs? seen with rosiglitazone, and mild to
moderate weight gain of 2 to 8 kg may be
seen with pioglitazone

What drugs may be used in Chlorpropamide and carbamazepine

central diabetes insipidus
secondary to their antidiuretic
effects?

What corticosteroid may be Dexamethasone

administered prior to an ACTH
stimulation test due to lack of
interference with the cortisol
assay?

When should TFTs be monitored 6 to 8 weeks after dose adjustments until a

after adjusting thyroid maintenance dose is achieved
replacement medications?

What effects on thyroid function Both hypothyroidism and hyperthyroidism

does interferon alpha-2B for may be observed, and in most patients
hepatitis C infection have? these abnormalities are transient, requiring
treatment if symptomatic.

What treatment for Iodides such as Lugol's solution should not

hyperthyroidism should not be be used because they cause decreased
given before radioactive iodine uptake of RAI by the thyroid gland.
(RAI) treatment? Thioamides should be stopped 3 days prior
to RAI.

P.662

Gastroenterology
What are five risk factors Age over 60 years, previous upper GI bleeding,
for NSAID-induced ulcers? concomitant corticosteroid therapy, concomitant
 anticoagulant therapy, high-dose and multiple
NSAID use

What is the most common Thrombocytopenia. It is reversible once the drug

hematologic effect of the is discontinued.
H2RAs?

What specific medications Include chlorpromazine, prochlorperazine,

fall in the class of promethazine, and thiethylperazine
phenothiazines?

What are the concerns QT prolongation and torsades de pointes (black-

that limit the use of box warning). The drug should be reserved for use
droperidol? after failure of other treatment options.

What is the appropriate The initial dose is 4 mg, followed by 2 mg after

dose of loperamide for each loose stool up to a maximum of 16 mg/day.
the management of acute
diarrhea?

In what clinical situations In the setting of Clostridium difficile and

should the use of bacterial enteritis caused by Escherichia coli,
antidiarrheals be avoided? Shigella, or Salmonella.

P.663

Hematology
What is the appropriate 100 "g IM daily for 1 week, weekly for 1 month,
dose of vitamin B12 for then monthly thereafter for maintenance
the treatment of B12
deficiency?

What are the vitamin K They are factors II, VII, IX, X, and their half-lives
dependent clotting factors are approximately 60, 6, 24, and 25 to 60 hours
and their respective half- respectively.
lives?

What is the most Tissue factor

prothrombotic substance
in the body?

What is the mechanism of Selectively inhibits antithrombin III that

action of fondaparinux? potentiates the neutralization of factor Xa, thus
inhibiting thrombin and subsequent thrombus
 formation

What is the dosing of 5 mg for patients <50 kg, 7.5 mg for patients 50
fondaparinux for the to 100 kg, and 10 mg for patients >100 kg
treatment of PE?

What is the appropriate A trial of desmopressin that works to stimulate

first-line therapy in endothelial cell release of von Willebrand factor
patients with von and factor VIII
Willebrand disease type I?

What is the likelihood of Approximately 97%; these drugs should not be

cross-reactivity with a used in the setting of HIT.
low-molecular-weight
heparin in a patient with
documented HIT?

Name six drugs that have Abciximab, ticlopidine, linezolid, heparin,

been associated with isotretinoin, H2Ras, and trimethoprim
thrombocytopenia.

What is the most Hold the warfarin and allow the INR to fall on its
appropriate course of own. Reversing with vitamin K can lead to delays
action in a patient with in reanticoagulation.
an INR of 5 who is not
actively bleeding or in
need of an emergent
procedure?

Can the anticoagulant Yes, partially. Protamine can be administered at

effect of enoxaparin be a dose of 1 mg for every 1 mg of enoxaparin, and
reversed? 60% to 75% reversibility may be achieved.

What patients are at Patients taking protamine-containing insulin,

highest risk for the vasectomized or infertile males, and those with
development of a serious sensitivity to fish. These patients have a higher
adverse effect with risk of developing antiprotamine antibodies and
protamine? subsequently there is an adverse effect upon
protamine administration.

P.664

Immunizations
What is the dosing schedule for The dosing is 0.5 mL administered IM at 2,
the hepatitis B vaccine? 4, and 6 months of age.
 How many pneumococcal 23
bacteria does the pneumococcal
polysaccharide vaccine (PPV)
protect against?

What are six indications for the Patients over the age of 65, patients with
administration of the PPV heart disease, lung disease, sick cell
vaccine? disease, diabetes, or kidney failure

How is the pneumococcal 0.5 mL given either IM or SQ

vaccine administered?

What is the appropriate dose of This vaccine is given intranasally and is

live attenuated influenza administered by spraying the vaccine into
vaccine in adults? each nostril.

What are the most common Injection-site tenderness and low-grade

adverse effects associated with fever that can begin as early as 6 to 12
the influenza vaccine hours following the vaccine and may last
administered IM? for 1 to 2 days

What is a rare adverse effect of Cases of Guillain-Barr syndrome have been

the influenza vaccine? reported.

What vaccine should be made The meningococcal vaccine

readily available for college
freshmen?

P.665
P.666

Infectious Diseases
What is one laboratory Calculate the patient's creatinine clearance prior to
calculation that should prescribing any antibiotic.
be performed before
prescribing the vast
majority of antimicrobial
agents?

Do vancomycin levels No. Oral vancomycin exhibits a local effect in the

need to be monitored GI tract and is not absorbed.
when the drug is
administered orally for
the treatment of
Clostridium difficile?

What antifungal drug and Anidulafungin and moxifloxacin are not effective
fluoroquinolone should agents for urinary tract infections.
not be used for urinary
tract infections due to
lack of urinary
penetration?

What is the most Aztreonam

appropriate antibiotic to
prescribe for gram
negative coverage in a
patient who is
anaphylactic to
penicillin?

What are two common Linezolid is not a bactericidal agent; it is a static

problems associated with drug. Additionally, the drug requires monitoring of
the use of linezolid? platelet counts due to the risk of
thrombocytopenia.

When should Patients with CrCl < 30 mL/min due to decreased

nitrofurantoin use be ability to concentrate in the urine. Should also be
avoided for the avoided in elderly patients due to the risk of
treatment of urinary developing pulmonary fibrosis.
tract infections caused
by E. coli?

What are the most They include streptococci, staphylococci, and

common causative enterococci.
organisms for infective
endocarditis?

What is the Nafcillin 2 g every 4 hours for a treatment period

recommended antibiotic of 4 to 6 weeks
and treatment duration
for left-sided
endocarditis due to
MSSA?

What is the appropriate 1 mg/kg every 8 hours provided the patient has
dose of gentamicin for normal renal function
synergy in the treatment
 of endocarditis?

What are the difficulties No single agent is bactericidal against this

in treating a patient with organism. Usually penicillin has high MICs and
enterococcal intrinsic resistance occurs with all cephalosporins.
endocarditis? Therefore, combination therapy with a cell wall
active agent along with an aminoglycoside is
necessary.

P.667

Nephrology
In patients with With or directly before meals (calcium
hyperphosphatemia, when should carbonate is more soluble at a lower
calcium carbonate be taken to gastric pH)
enhance its dissolution in the
stomach?

What calcium-containing product Calcium citrate should not be used

should not be used as a phosphate because it increases the risk of aluminum
binder in patients with renal toxicity by increasing gastric absorption
failure? of aluminum.

How frequently should No more than every 6 weeks

darbepoetin dosages be adjusted
in the treatment of anemia of
chronic kidney disease?

Which intravenous iron products Iron sucrose and sodium ferric gluconate
do not require a test dose before
treatment?

What antihypertensive drugdrug Diltiazem is often used because it

interaction is often used in inhibits the hepatic elimination of
transplant patients to achieve cyclosporine and allows lower doses of
desired cyclosporine levels with cyclosporine to be used.
lower cyclosporine doses?

What side effects may result from Neurotoxic side effects such as tremors,
accumulation of the active myoclonus, and seizures are particular
metabolite of meperidine, risks associated with use of meperidine in
normeperidine, in patients with patients with compromised renal
renal impairment? function.

When does acute tubular necrosis Usually after 7 to 10 days of therapy

 from aminoglycoside therapy
typically occur?

What is the advantage of They have similar efficacy but

extended-release and transdermal transdermal and oral extended-release
forms of oxybutynin over products have fewer anticholinergic side
immediate-release forms? effects, such as dry mouth and
constipation, but with added costs.

P.668

Neurology
When should serum concentrations of In general, samples should be drawn
antiepileptic drugs be obtained? before the morning dose and after
four or five half-lives after initiation
or dosage change.

What second-generation Lamotrigine, especially with rapid

anticonvulsant is known to cause a dose escalation. Phenytoin,
skin rash for which the patient should carbamazepine, and phenobarbital
seek immediate medical attention? are all first-generation
anticonvulsants that also may cause
a rash.

What cardiovascular effects may occur Hypotension, bradycardia, and

with rapid intravenous administration cardiac dysrhythmias, including
of phenytoin? ventricular fibrillation, are effects
most likely due to the propylene
glycol diluent of the IV formulation.

What anticonvulsants are also FDA- Divalproex or valproic acid and

approved for migraine prophylaxis? topiramate

How long after dosing initiation of Autoinduction of carbamazepine's

carbamazepine might a patient be at metabolism begins 3 to 5 days after
risk for loss of seizure control dosing and is complete in about 1
secondary to carbamazepine's month.
induction of its own metabolism?

At what total phenytoin serum Total phenytoin levels >20 "g/mL.

concentration do many patients have Ataxia and diplopia frequently occur
nystagmus? with levels >30 "g/mL and seizures
and coma at concentrations >40
"g/mL.
 What are two ways to overcome the Supplement morning sustained-
slow onset of sustained-release release carbidopa-levodopa with an
carbidopa-levodopa (Sinemet CR) to immediate-release product
improve morning immobility in Give sustained-release carbidopa-
patients with Parkinson's disease? levodopa to be taken 1 hour before
arising

What medication used to control Ropinirole

motor fluctuations in Parkinson's
disease is also beneficial in the
treatment of restless legs syndrome?

What CNS side effects may occur with Peripheral neuropathy and seizures
metronidazole at high doses (>1.5 g)? are potential side effects.

P.669

Oncology
What is the most Nephrotoxicity. Cisplatin is directly toxic to the renal
concerning adverse tubules.
effect associated with
the use of cisplatin?

What should be done Hydration. Patients should be administered 1 to 2 L of

to minimize the 0.9% normal saline pre- and postadministration; lower
adverse event with doses of the drug should be used in patients with renal
cisplatin? insufficiency.

In what types of Aldesleukin (interleukin-2, IL-2) is indicated for renal

cancers does cell cancer and melanoma.
aldesleukin have a
role?

How does aldesleukin The drug stimulates the growth, differentiation, and
work? proliferation of activated T cells. IL-2 also generates
lymphokine-activated killer-cell activity and
stimulates the immune system against tumor cells.

What Mucositis is most commonly associated with 5-FU,

chemotherapeutic methotrexate, and doxorubicin.
agents are most
commonly implicated
in the development
of mucositis?
 What medications are The available agents include aminoglutethimide,
available that fall anastrazole, exemestane, fulvestrant, letrozole,
into the antiestrogen megestrol acetate, tamoxifen, and toremifene.
class for the
treatment of breast
cancer?

What is the 5 "g/kg/day with the exception of peripheral blood

appropriate dose of stem cell mobilization, where the recommended dose
filgrastim (G-CSF) in is 10 "g/kg/day.
patients with
neutropenia
secondary to
chemotherapy?

At what point should When platelet counts drop below 20,000/mm 3 , there
platelet transfusions is increased risk for intracranial hemorrhage. Platelet
be considered in a transfusions are usually indicated when the platelet
patient with
count drops to <10,000/mm 3 , or possibly sooner if the
chemotherapy-
patient experiences signs or symptoms of hemorrhage.
induced
thrombocytopenia?

P.670
P.671

Pregnancy
What are the Those that have low molecular weight (usually
pharmacokinetic <1000 Da) and are highly lipophilic, un-ionized
properties that make a drugs
drug more likely to cross
the placenta and cause
potential harm to the
fetus?

What are pharmacokinetic Drugs that have low lipid solubility, high
properties that make a molecular weight, and are ionized or highly
drug less likely to cross protein-binding are less likely to cross into
into breast milk? breast milk.

What does each FDA drug

class mean during
pregnancy?

Class A No documented fetal risk

 Class B Animal studies suggest risk, but this has not been
confirmed in human studies.

Class C No controlled human studies, but animal studies

demonstrate adverse fetal effects. Use only if
the benefit outweighs the risk.

Class D There is evidence in humans of adverse fetal

effects. Use only in life-threatening cases.

Class X Documented adverse fetal effects in humans.

These drugs are contraindicated.

Are loop diuretics They are class C agents. Other methods to

acceptable to use in control volume in patients should be tried first.
pregnant women?

Are loop diuretics Yes. However, these agents will often reduce
acceptable to use in milk production.
breast-feeding women?

Can ACE inhibitors be No. They fall into a class C group for the first
prescribed for women who trimester and class D for the second and third
are pregnant? trimesters.

Can ACE inhibitors be ACE inhibitors are regarded by the American

prescribed for women who Academy of Pediatrics to be compatible with
are breast-feeding? breast-feeding. Enalapril and captopril are
secreted in lesser amounts in breast milk
compared to others, but all are considered
acceptable.

In which pregnancy Statins are listed in pregnancy category X and

category are the statin should not be used.
agents listed?

What about statin use It is unknown but possibly unsafe to use.

during breast-feeding?

Can warfarin be used for Warfarin should be avoided due to the potential
treatment of VTE or PE in for fetal bleeding, stippled epiphyses,
pregnancy? malformations of the nose, or CNS abnormalities
(class X).
 What antithrombotic Low-molecular-weight heparins are the preferred
agents can be used for agent, but unfractionated heparin may also be
prophylaxis or treatment used in these conditions.
of VTE or PE in pregnancy?

What medications may be Acetaminophen is the preferred agent.

recommended for the Nonsteroidal anti-inflammatory agents may be
management of migraine acceptable early in pregnancy but are
or tension headaches contraindicated after 37 weeks of gestation.
during pregnancy?

What antimicrobials are Ampicillin, amoxicillin, cephalexin, and

considered safe to use for nitrofurantoin are considered safe.
the treatment of urinary
tract infections in
pregnancy?

What types of vaccinations Any vaccine that is a live virus should be avoided
should be avoided during during the course of the pregnancy.
pregnancy?

Should hypothyroidism be Absolutely. Untreated hypothyroidism can result

treated during pregnancy? in significant cognitive and other neurologic
deficits in the fetus. There is also an increased
risk of preeclampsia, low birth weight, and
premature birth.

What medication can be Metoclopramide 10 mg three times a day for 7 to

prescribed to increase 14 days
milk supply in a patient
with declining serum
prolactin concentrations?

P.672
P.673

Pulmonology
What class of medications Inhaled short acting beta-2 receptor agonist by
should be administered nebulizer or MDI every 20 minutes
first to treat an acute
asthma exacerbation?

How do anticholinergic The anticholinergic agents produce

agents work in the setting bronchodilation by competitively inhibiting
of COPD? cholinergic receptors in the bronchial smooth
muscle.

What is the appropriate Ipratropium: 2 puffs four times daily; tiotropium:

dose of anticholinergic 1 capsule inhaled once daily
agents for the
management of COPD?

What are the most likely Haemophilus influenzae, Moraxella catarrhalis,

pathogens in Streptococcus pneumoniae, and Haemophilus
uncomplicated acute parainfluenzae
exacerbations of COPD?

What is the description Nonproductive, persistent, and paroxysmal. The

and when is the most cough may be observed as early as 3 days
likely time course for a following initiation of therapy or may not occur
patient to experience an for up to 1 year.
ACE inhibitorinduced
cough?

If the patient has an ACE It will usually dissipate within 4 days but may
inhibitorinduced cough, take up to 4 weeks.
how long does it take to
resolve?

What is the proposed Inhibition in the breakdown of bradykinin and

mechanism ACE inhibitor substance P. These substances then facilitate
induced cough? inflammation and stimulate lung irritation.

What are four medications Some of the agents are bleomycin, amiodarone,
that can induce carmustine, and busulfan.
pneumonitis and/or
fibrosis?

What is the mechanism of It acts on both the ET-A and ET-B receptors in
action of bosentan? the endothelium and vascular smooth muscle.
Levels of endothelin 1 are elevated in pulmonary
hypertension and can promote fibrosis, cell
proliferation, and tissue remodeling.

What is the appropriate 62.5 mg twice daily for 4 weeks, then increase to
dose of bosentan for 125 mg twice daily
treatment of pulmonary
hypertension?
 What is the mechanism of Sildenafil citrate is an inhibitor of cGMP-specific
action of sildenafil for the phosphodiesterase type-5 (PDE5) in smooth
treatment of pulmonary muscle, resulting in relaxation and vasodilation.
hypertension? In pulmonary hypertension, this leads to
vasodilation of the pulmonary vascular bed.

P.674

Psychiatry
What SSRI does Fluoxetine may be stopped abruptly because it has a long
not require half-life of 60 hours and will clear the body after 2 weeks
tapering? without major risk of withdrawal side effects.

What drug- Concomitant use of linezolid and SSRIs may increase the risk
drug of serotonin syndrome. The literature supports
interaction discontinuation of the serotonergic agent 2 weeks before
occurs starting linezolid.
between the
antimicrobial
linezolid and
SSRIs?

At what dose The risk is dose-dependent, with increased risk at daily doses
of bupropion >450 mg. Bupropion is contraindicated in patients
do patients with a history of seizures, bulimia or anorexia secondary to
have an increased seizure risk.
increased
seizure risk?

What For the first weeks of treatment, SSRIs may need to be

considerations overlapped with benzodiazepines due to a lag time of 2 to 4
should be weeks for effectiveness and the occurrence of initial
taken when increased agitation and anxiety within a week of SSRI
using initiation.
antidepressants
to treat
anxiety
disorders?

Which Two conventional antipsychotics available are haloperidol

antipsychotic given every 28 days and fluphenazine given as fluphenazine
drugs are decanoate every 2 to 4 weeks or fluphenazine enanthate
available as every 1 to 2 weeks. Risperidone is the only second-
long-acting generation antipsychotic available as a long-acting injection
depot given every 2 weeks, but it has a 3-week lag time to full
 preparations effect, requiring 3 weeks of concurrent oral antipsychotics.
that can assist
with patient
compliance?

What atypical Olanzapine and clozapine have the highest incidence of

antipsychotics weight gain followed by quetiapine. This is usually most
are associated significant during the first 12 weeks of treatment, with a 3-
with weight to 15-lb weight gain.
gain?

Which atypical Ziprasidone and aripiprazole have a low tendency to promote

antipsychotics weight gain.
cause the least
weight gain?

What drugs NSAIDs, ACE inhibitors, and diuretics (thiazide-like diuretics

may cause an having the greatest impact)
increase in
lithium levels?

P.675

Rheumatology
How often should intra- Injections should be given no more than once
articular depot every 3 months in the same joint.
corticosteroids be given
for rheumatoid arthritis
joint pain?

Why are intra-articular Because too many injections may accelerate joint
injections limited? destruction

When are liver biopsies For patients with suspected or known liver
indicated during disease, a history of hepatitis, or jaundice, and
methotrexate (MTX) for patients with persistent LFT abnormalities
therapy? during or after MTX therapy

What FDA class, with Class X. It is also unsafe during lactation.

regard to pregnancy, is
leflunomide?

What medication is Cholestyramine given 8 g three times a day for 11

recommended for days is recommended for all childbearing women
childbearing women to stopping leflunomide, since up to 2 years may be
enhance the elimination required to reach undetectable levels of the
of leflunomide? active metabolite.

What medication must be Methotrexate to minimize the formation of

used in combination with antibodies to infliximab
infliximab for rheumatoid
arthritis and why?

What warning regarding Patients are at risk for tuberculosis (TB) infection,
infection risk do the and use is cautioned in patients with a history of
DMARDs adalimumab, TB or who are predisposed to infection.
etanercept, and
infliximab have?

What dose of hydralazine Daily dosages of >200 mg or a cumulative dose of

is associated with drug 1g
induced lupus?

When is colchicine most Use within the first 12 to 24 hours of an attack is

effective during an acute most effective because effectiveness decreases as
gout attack? duration of inflammation increases.

What class of ACE inhibitors

antihypertensive drugs
increases the risk of
Stevens-Johnson
syndrome when given
with allopurinol?
Editors: Bergin, James D.
Title: Advanced Medicine Recall, 1st Edition
Copyright 2009 Lippincott Williams & Wilkins

> Table of Contents > Section III - Related Specialties > Chapter 16 - Psychiatry

Chapter 16
Psychiatry

P.677

Abbreviations
ADHD Attention-deficit/hyperactivity disorder

ANC Absolute neutrophil count

APAP Acetaminophen

ASA Aspirin

AVH Auditory and/or visual hallucinations

B-52 Benadryl 50 mg, haloperidol 5 mg, lorazepam 2 mg

BAL Blood alcohol level

BPAD Bipolar affective disorder

BPD Borderline personality disorder

CBC Complete blood count

CBT Cognitive behavioral therapy

CBZ Carbamazepine

CHF Congestive heart failure

CNS Central nervous system

CK Creatine phosphokinase
CSF Cerebrospinal fluid

CT Computed tomography

CVA Cerebrovascular accident

DBT Dialectical behavioral therapy

DTs Delirium tremens

ECT Electroconvulsive therapy

EEG Electroencephalogram

EPS Extrapyramidal symptoms

GAD Generalized anxiety disorder

GMC General medical condition

HCG Human chorionic gonadotropin

HI Homicidal ideation

HIV Human immunodeficiency virus

LFT Liver function test

LOC Loss of consciousness

MAOI Monoamine oxidase inhibitor

MDD Major depressive disorder

MDE Major depressive episode

MMPI Minnesota Multiphasic Personality Inventory

MMSE Mini-Mental State Exam

MRI Magnetic resonance imaging

 NMS Neuroleptic malignant syndrome

NPH Normal-pressure hydrocephalus

OCD Obsessive compulsive disorder

PTSD Posttraumatic stress disorder

RPR Rapid plasmin reagin

SA Suicide attempt

SI Suicidal ideation

SNRI Serotonin-norepinephrine reuptake inhibitor

SSRI Selective serotonin reuptake inhibitor

TCA Tricyclic antidepressant

TD Tardive dyskinesia

TFT Thyroid function test

TLE Temporal lobe epilepsy

UA Urinalysis

UDS Urine Drug Screen

VPA Valproic acid

5-2-1 Haloperidol 5 mg, lorazepam 2 mg, benztropine 1 mg

P.678
P.679
P.680

Psychiatric Assessment
What should Information regarding onset, duration, temporal features,
be included in intensity, progression, and alleviating and exacerbating
a psychiatric conditions of psychiatric symptoms. A thorough history must
history? include a general medical history and review of systems, past
psychiatric and medical histories, developmental and family
 history, social history including substance abuse, neurological
history, current medications, and allergies. Owing to the
nature of psychiatric illness, outside informants should be
used whenever possible.

What is a A detailed description of appearance, behavior and

mental status psychomotor activity, speech and language, mood (the
examination? patient's expression of his internal emotional state, usually a
quote), affect (the examiner's description of the patient's
emotional state), thought process, thought content,
perceptual disturbances (i.e., hallucinations, delusions),
insight, judgment, estimated intelligence (usually based on
the history, vocabulary, and use of language), and
neuropsychiatric and cognitive function (MMSE)

In performing
the Mini-
Mental State
Exam (MMSE): 1

What The date, day, month, season, year, floor, hospital, town,
questions can county, and state (10 points)
be asked to
test
orientation?

What is a Serial 7ssubtract 7 from 100 serially; stop after 5 answers.

common way (5 points)
to test the Alternatively, have the patient spell world backwards.
patient's
attention and
ability to
calculate?

How can Give the patient the names of three unrelated objects and
short-term make sure they register (3 points); 5 minutes later ask the
memory be patient to recall them. (3 points)
tested?

In what Ask the patient to name a pen and a watch by sight. (2

ways can points)
language and Ask the patient to repeat, No ifs, ands, or buts. (1 point)
language Give written (Close your eyes) (1 point) and verbal (three-
comprehension stage) commands for the patient to follow. (3 points)
be tested? Ask the patient to write a sentence. (1 point)
 How is Ask the patient to copy two intersecting pentagons. (1 point)
spatial ability
tested?

How is the The scores from the patient's correct answers are summed
overall test and compared to the total possible points. (30)
scored?

When can Poor effort, pseudodementia (i.e., dementia of depression)

false-positive
results occur
on a mental
state exam?

When can Highly educated or intelligent individuals with early dementia

false-negative and patients with right hemisphere lesions
results occur
on a mental
state exam?

What is the Without exception, a thorough physical and neurologic

role of the examination is required for a complete psychiatric
physical assessment. The brain is the substrate of behavior and can be
examination in affected by a myriad of medical illnesses.
evaluating
patients with
psychiatric
disorders?

What medical
illnesses in the
following
categories can
present with
psychiatric
problems?

Neurologic CVA, head trauma, epilepsy (especially complex partial),

narcolepsy, NPH, Parkinson's disease, multiple sclerosis,
Huntington's disease, and dementia [Alzheimer's type,
vascular, Lewy body, Pick's disease (frontotemporal)]

Endocrine Hypo- or hyperthyroidism, adrenal and parathyroid conditions,

hypo- or hyperglycemia, hypopituitarism, pheochromocytoma,
 and gonadotrophic hormone

Metabolic Fluid and electrolyte imbalance, hepatic encephalopathy,

uremia, porphyria, Wilson's disease, hypoxia, hypotension, and
hypertensive encephalopathy

Toxic Intoxication or withdrawal from alcohol or drugs of abuse,

side effects of prescription or over-the-counter drugs, herbals
or natural health supplements, and exposure to
environmental toxins

Nutritional Deficiencies of vitamin B12, thiamine, nicotinic acid, or trace

metals; malnutrition and dehydration

Infectious AIDS, neurosyphilis, encephalitis, meningitis, brain abscess,

viral hepatitis, infectious mononucleosis, tuberculosis, Lyme
disease, and systemic bacterial or viral infections

Autoimmune CNS vasculitis due to systemic lupus erythematosus or other

autoimmune/rheumatologic diseases

Neoplastic CNS primary or metastatic tumors, endocrine tumors, and

pancreatic carcinoma

What common CBC, basic chemistries, LFTs, TFTs, HCG, RPR, B12, folate,
laboratory UA, toxicology screens (APAP, ASA, UDS, BAL, etc.),
tests are therapeutic drug concentrations, occasionally CSF studies,
ordered for head CT or MRI, EEG, and electrocardiogram
psychiatric
problems?

How many 5 Axis I to axis V

axes are there
in the
multiaxial
categories?

For each
category,
describe the
multiaxial
category:

Axis I Clinical psychiatric disorders

 Axis II Personality disorders and specific developmental disorders

Axis III Existing medical, surgical, or neurologic conditions

Axis IV Psychosocial and environmental stressors

Axis V Global assessment of functioning, reflecting the current or

most recent highest level of functioning (social, occupational,
psychological) on a scale from 1 (grossly impaired: danger of
hurting self or others) to 100 (superior function)

1
From Folstein MF, Folstein SE, McHugh PR. Mini-mental state. A practical
method for grading the cognitive state of patients for the clinician. J Psychiatr
Res 1975;12(3):189198.

P.681

Mood Disorders
What illnesses are comprised Major depression, dysthymic disorder, bipolar
by the mood disorders? disorder, and cyclothymic disorder

P.682
P.683
P.684

Major Depression
What is major A significant disturbance of mood and neurovegetative
depression? function (i.e., appetite, sleep, energy, libido, and
concentration), which is persistent for a minimum of 2
weeks and not caused by the direct physiologic effects of
a general medical condition or substance abuse

What is the Lifetime, 15%; 10% to 25% for women and 5% to 10% for
prevalence of men. The incidence of major depression is 10% in primary
major care patients, 15% in medical inpatients, and even higher
depression? for elderly patients.

What is the risk 50%

for relapse after
one episode of
major
depression?

What is the risk 80%

for relapse after
three episodes of
major
depression?

What are risk Female gender (up to twofold greater prevalence),

factors for major environmental stress (e.g., loss of a spouse,
depression? unemployment), and genetics. First-degree relatives have
a 1.5 to 3 times greater chance of development of major
depression than the general population.

What are Persistent presence of depressed mood, diminished

symptoms and interest (anhedonia), significant weight loss or weight gain
signs of major reflecting appetite disturbance, insomnia or hypersomnia,
depression? psychomotor agitation or retardation, decreased energy,
excessive guilt, feelings of worthlessness, inability to
concentrate, impaired memory, and suicidal ideation.
Anxiety, somatic complaints, or psychotic symptoms may
be associated.

For each of the

potential aspects
of major
depression below,
list the features
of each:

Psychotic Delusions and hallucinations are present along with

symptoms of major depression.

Catatonic Immobility or excessive, purposeless motor activity,

features mutism, posturing, echolalia or echopraxia

Melancholic Loss of pleasure, lack of reactivity to usually pleasurable

stimuli, mood worse in the morning, early-morning
awakening, marked psychomotor retardation, anorexia,
and excessive guilt

Atypical Mood reactivity, hypersomnia, leaden paralysis, weight

gain, rejection sensitivity

Postpartum Depression within 4 weeks of delivery

Seasonal Depression generally in the fall or winter

pattern
What laboratory About 10% of hospitalized depressed patients have a
findings are diagnosis of hypothyroidism.
associated with
major
depression?

What is the Mood disorder resulting from a general medical condition,

differential substance-induced mood disorder, dysthymic disorder,
diagnosis of dementia, ADHD, bipolar depressed, adjustment disorder
major with depressed mood, and schizoaffective disorder
depression?

What percentage 5% to 10%

of individuals
with a single
episode of major
depression will
eventually
develop bipolar
disorder?

What are the Suicidality, psychotic depression, or inability to care for

reasons to self (e.g., malnutrition)
hospitalize
someone with
major
depression?

What is the Antidepressant medications (e.g., SSRIs, SNRIs, TCAs,

treatment for MAOIs) or benzodiazepines for short-term treatment of
major anxiety symptoms; augmentation with lithium, thyroid
depression? hormone, or buspirone; individual psychotherapy; ECT

How well do More than 50% of patients with major depression will
antidepressants recover fully when an adequate dose of an antidepressant
work? is used for an adequate duration of time (at least 6
weeks).

Why are SSRIs Efficacy and tolerability

first-line
treatments for
depressive
disorder
illnesses?
What are some of Most troubling side effects include gastrointestinal and
the side effects sexual dysfunction
of SSRIs?

Why are TCAs TCAs have multiple side effects (anticholinergic,

infrequently used antihistaminergic, cardiac) and a low threshold for
to treat toxicity; an overdose on a 1-week supply can be deadly.
depression when
they are as
effective as
SSRIs?

Why are MAOIs One must follow strict dietary restrictions and avoid
infrequently tyramine-containing foods as well as serotonergic and
used? sympathomimetic medications. Additionally, MAOIs can
cause severe orthostasis.

What can happen An adrenergic crisis (hypertension, fever, tachycardia,

if MAOIs are used arrhythmia) may occur.
in combination
with tyramine-
containing foods
or with
serotonergic or
sympathomimetic
medications?

What advantage At the lowest dosage, no dietary modification is required.

does the MAOI
transdermal patch
selegiline offer?

What medications Venlafaxine and duloxetine

are SNRIs?

How does Buspirone is a 5-HT1A partial agonist.

buspirone work? It increases dopamine and norepinephrine in the CNS.

How does It rarely induces sexual dysfunction and may be used as an

bupropion differ adjunct in SSRI-induced sexual dysfunction.
from SSRIs?

What side effect Seizures (especially in patients with anorexia); but this risk
is most is comparable to that of SSRIs when administered in a
worrisome with sustained-release preparation.
bupropion
immediate
release?

How does It is an alpha-1 adrenergic antagonist (which increases

mirtazapine serotonin and norepinephrine at the synapse), potent
work? histaminergic H1 receptor antagonist (somnolence and
weight gain), and a 5-HT2 and 5-HT3 receptor antagonist.

How does It inhibits serotonin reuptake, antagonizes alpha-1

trazodone work? adrenergic receptors, and has antihistaminergic activity. It
is usually used as a treatment for insomnia in lower than
therapeutic doses (i.e., 100 mg vs. 400 mg).

What side effect Priapism (especially in older men with vascular disease)
of trazodone is
rare, but requires
immediate
medical
attention?

What are the Failure of several antidepressant trials, severe depression

primary with psychotic features, high risk of suicide, and previous
indications for good response to ECT
ECT?

What are the Increased intracranial pressure is the only absolute

contraindications contraindication; however, other high risk medical
to ECT? conditions (i.e., recent myocardial infarction or CVA) must
be thoroughly reviewed.

What is the 70% to 90%, thus making it the most effective treatment
response rate for for major depression
ECT?

What are the Memory loss and delirium

primary side
effects of ECT?

What is the Up to 15% of patients die by suicide; 50% of patients will

prognosis for have a second episode.
major
depression?
 P.685

Dysthymic Disorder
What is dysthymic A chronic illness characterized by depressed mood more
disorder? days than not for at least 2 years.

How does Two or more neurovegetative symptoms including poor

dysthymic disorder appetite or overeating, sleep disturbance, decreased
present? sexual interest, decreased energy, low self-esteem, and
poor concentration. It may present with irritability in
adolescents. No major depressive episode is present
during the first 2 years.

What is the Lifetime, 6%

prevalence of
dysthymic
disorder?

What are risk Adolescence and family history of mood disorders; there
factors for are no gender differences for incidence rates.
dysthymic
disorder?

What is the Major depression, minor depressive disorder, mood

differential disorder caused by a general medical condition,
diagnosis for substance-induced mood disorder, and personality
dysthymic disorder
disorder?

What is the Antidepressants, cognitive therapy, and insight-oriented

treatment for (psychoanalytic) psychotherapy
dysthymic
disorder?

How common is 40% of patients with MDD also meet criteria for dysthymic
double depression, disorder (double depression).
and what is it?

What percentage 50%; 20% of patients with dysthymic disorder progress to

of patients with MDD, 15% to bipolar II, and <5% to bipolar I.
dysthymic disorder
experience onset
of symptoms
before age 25
 years?

P.686
P.687
P.688
P.689

Bipolar Disorder (Manic-Depressive Illness)

What is bipolar A chronic, remitting mood disorder characterized by
disorder? periods of mania, depression, or mixed mood episodes. It
may be associated with psychotic symptoms.

What is a manic A distinct period of persistently and abnormally

episode? elevated, irritable, or expansive mood lasting at least 1
week; the episode causes marked impairment.

What is a A distinct period of persistently elevated, irritable, or

hypomanic expansive mood lasting at least 4 days; it is not severe
episode? enough to cause marked impairment, and there is no
psychosis.

What are some of Inflated self-esteem or grandiosity, decreased sleep

the features of a (rested after 3 hours), pressured speech, racing thoughts,
manic or distractibility, psychomotor agitation, and enhanced
hypomanic libido or unrestrained buying sprees
episode?

What drugs are Amphetamines, baclofen, bromide, bromocriptine,

associated with caffeine, captopril, cimetidine, cocaine, corticosteroids,
manic-like cyclosporine, disulfiram, hallucinogens, hydralazine,
episodes? isoniazid, levodopa, methylphenidate, metrizamide,
opiates and opioids, procarbazine, and procyclidine

What is a mixed Features of both major depression and mania are present
mood episode? for at least 1 week. Also known as dysphoric mania, a
mixed mood episode is thought to be a rapid alteration
of mania and depression and places one at a higher risk
of suicide.

What is the Lifetime, 1% to 2%

prevalence of Type I has a 0.4% to 1.6% lifetime prevalence
bipolar disorder? Type II has a 0.5% lifetime prevalence

What is the Patients with bipolar type I have at least had one manic
difference between or mixed episode; a depressive episode is not necessary.
bipolar type I and Patients with bipolar type II have had at least one
type II? depressive and one hypomanic episode without having a
manic or mixed episode.

What gender The incidence is equivalent among males and females;

differences exist in however, some studies suggest that a rapid-cycling
bipolar disorder? bipolar course is more common in women.

What does it mean At least four episodes of a mood disturbance (depressive,

for one to be mixed, manic, or hypomanic) in the past year
bipolar with rapid
cycling?

What is the 19 years; new-onset bipolar disorder is uncommon after

average age of the fifth decade of life.
onset for bipolar
disorder?

What are risk First-degree relatives of bipolar patients have increased

factors for bipolar rates of mood disorders. Twin and adoption studies
disorder? support a strong genetic influence. Varied stressors often
serve as environmental triggers for mood episodes.

What is the Mood disorder caused by a general medical condition,

differential substance-induced mood disorder, cyclothymia,
diagnosis for personality disorders (especially borderline),
bipolar disorder? schizophrenia, and schizoaffective disorder

What is the Consider hospitalization for acute mania, severe

treatment for depression, and associated psychosis; mood stabilizers
bipolar disorder? (e.g., lithium, lamotrigine, and VPA), benzodiazepines,
and antipsychotic medications for acute mania and
psychosis; ECT for severe, intractable mania; and
psychotherapy.

Which mediations Antidepressants are avoided because they commonly

should be avoided precipitate mania.
and why?

Which medications Lithium, valproic acid, and atypical antipsychotics

are indicated for
acute mania?

What are the side Lithium is generally nontoxic below 1.2 mEq/L; however,
effects and sedation, poor memory and concentration, fine hand
toxicities tremor, nausea, diarrhea, polyuria, polydipsia, psoriasis,
associated with and weight gain may all be signs of minor toxicity. For
lithium? severe toxicity (i.e., delirium, arrhythmia, acute renal
failure, etc.) dialysis is needed.

What is lithium's Randomized studies have shown a powerful preventive

effect on suicide? effect on suicide.

What is the Ebstein's anomaly, a malformation of the tricuspid valve,

teratogenicity is associated with lithium use in the first trimester.
associated with
lithium?

Which Valproic acid

anticonvulsant is
likely to be more
effective than
lithium in treating
mixed and rapid-
cycling bipolar
states?

What are the toxic Mild and transient elevations of AST and ALT and
effects of valproic possible fatal hepatotoxicity, hemorrhagic pancreatitis,
acid? thrombocytopenia, aplastic anemia; thus, monitor LFTs
and CBC.

What are the Neural tube defects and neonatal liver disease
teratogenic effects
associated with
valproic acid?

What is the most A rash, which may lead to Stevens-Johnson syndrome

serious side effect
of lamotrigine?

What other Carbamazepine, oxcarbazepine, topiramate, and

medications can be gabapentin
used for bipolar
disorder?

Does the frequency Each episode makes an additional future episode more
of mood likely (kindling theory); the subsequent episodes may be
disturbances longer in duration and less likely to respond to
change with age, medication.
 and how does this
affect treatment?

What is the Rule of thirds:

prognosis for One third develop a chronic, unremitting course.
bipolar disorder? One third continue to have intermittent episodes.
One third have remission with treatment.
Up to 15% of patients die by suicide.

What comorbid Substance abuse: 60% lifetime prevalence

conditions exist in Anxiety disorders: 50% lifetime prevalence
conjunction with Attention deficit hyperactivity disorder
bipolar disorder? Cluster B personality disorders (especially borderline)
Eating disorders

P.690

Cyclothymic Disorder
What is A chronic mood disturbance lasting at least 2 years and
cyclothymic characterized by fluctuating periods of depressive symptoms
disorder? (which do not meet criteria for major depression) and
hypomanic symptoms

What is the Lifetime, 1%

prevalence of
cyclothymic
disorder?

What are risk First-degree relatives have an increased incidence of mood

factors for disorders, especially bipolar I. There is an increased family
cyclothymic history of substance abuse.
disorder?

What are Chronic, persistent presence of mood disturbance with

symptoms and features of hypomania and depression. Substance abuse is
signs of common; 5% to 10% have substance dependence.
cyclothymic
disorder?

What is the Teens or early twenties; 33% develop a major mood disorder,
average age of primarily bipolar II.
onset for
cyclothymic
disorder?
 What is the Mood disorder caused by a general medical condition,
differential substance-induced mood disorder, rapid-cycling bipolar
diagnosis for disorder, borderline personality disorder, and ADHD.
cyclothymic
disorder?

What is the Mood stabilizers (e.g., lithium, lamotrigine, VPA, and CBZ)
treatment for and antimanic drugs; not antidepressants because they may
cyclothymic induce manic or hypomanic episodes in 40% to 50% of
disorder? cyclothymic patients; and psychotherapy

P.691

Cognitive Disorders

Delirium
What is delirium? A potentially reversible cognitive disturbance caused by a
general medical condition that typically develops acutely
and fluctuates over time

What percent of 10% to 30%; the percentage is higher in surgical and

medically ill cardiac intensive care units.
hospitalized
patients exhibit
delirium?

For each system,

name the major
causes of
delirium:

Cardiovascular? Heart failure, arrhythmias, hypotension

Endocrine? Dysfunction of the pituitary, thyroid, parathyroid,

adrenal, or pancreas

Gastrointestinal? Hepatic encephalopathy, impaction in the elderly

Infectious? Sepsis, urinary tract infection

Neurologic? Epilepsy, postictal states, concussions, meningitis or

encephalitis, brain tumor, etc.

Pulmonary? Carbon dioxide narcosis, hypoxia

 Renal? Uremic encephalopathy

For each of the

following, name
what can be
associated with
delirium:

Metabolic? Electrolyte imbalance

Nutritional Thiamine, B12, folic acid

deficiency?

Drugs? Anticholinergic agents, opiates, sedatives, steroids, etc.

Poisons? Heavy metals, carbon monoxide

Surgical? Postoperative states

What are the risk Elderly, history of brain damage, having cardiac surgery,
factors for the burn injury, and sleep deprivation
development of
delirium?

What is the The primary goal is to treat the underlying cause.

treatment for
delirium?

How can the Minimize medications if possible. However, haloperidol is

psychosis often used to treat the agitated, delirious patient; off-
associated with label use of atypical antipsychotics is also done. Of note,
delirium be antipsychotics are associated with prolongation of the
treated? QTc, leading to arrhythmias.

P.692

Dementia
What is Chronic and continuing cognitive decline involving deficits in
dementia? memory and one additional impairment (aphasia, apraxia,
agnosia, or executive dysfunction)

What is 1.5%
the
prevalence
of
dementia
in those
over 65
years of
age?

What is 16% to 25%

the
prevalence
of
dementia
in those
over 85
years of
age?

What Alzheimer's disease, Parkinson's disease, Huntington's disease,

disorders Pick's disease, Lewy body disease, vascular disease [e.g., multi-
may cause infarct dementia or small vessel (Binswanger's) dementia], drugs
dementia? (e.g., chronic alcoholic dementia/thiamine deficiency), head
trauma, normalpressure hydrocephalus, intracranial masses,
thyroid disease, neurosyphilis, B12 deficiency, AIDS, chronic sleep
apnea, lupus, and severe depression (dementia of depression)

What is For reversible causes (although they are evident in less than 15%
the of cases): psychosocial interventions (e.g., patient safety, legal
treatment issues, finances); behavioral interventions (e.g., wandering,
for psychosis, agitation); medications (e.g., cognitive enhancers)
dementia?

What are Cholinesterase inhibitorsdonepezil, rivastigmine, and

the galantamine
cognitive N-methyl-D-aspartate receptor antagonistmemantine
enhancers?

What are Alzheimer's disease, vascular dementia

the FDA
indications
for
cognitive
enhancers?

How do None of these medications stop the progression of cognitive

the decline; rather, they may slow the rate of decline by up to a
 cognitive year.
enhancers
work?

P.693

Psychotic Disorders
What are Delusions, hallucinations, disorganized speech (e.g.,
psychotic incoherence, marked loosening of associations, neologisms),
symptoms? and grossly disorganized or catatonic behavior. Symptoms may
be described as impairment in reality testing.

What Delirium, dementia, mood disorders, substance use disorders,

psychiatric schizophrenia, and the schizophrenia-like disorders [e.g.,
diseases can schizophreniform disorder, brief psychotic disorder,
present with schizoaffective disorder, delusional disorder, and shared
psychotic psychotic disorder (folie deux)]
symptoms?

P.694
P.695
P.696

Schizophrenia
What is A chronic, relapsing-remitting psychotic illness of at least
schizophrenia? 6 months' duration that includes at least 1 month of two
or more active phase symptoms. Impairment in social and
occupational functioning is a key feature.

What are the Positive symptoms (e.g., delusions, hallucinations),

active-phase disorganized speech, grossly disorganized or catatonic
symptoms of behavior, and negative symptoms (e.g., affective
schizophrenia? flattening, paucity of thought and speech, and lack of
motivation)

What are the Paranoid, disorganized, catatonic, undifferentiated, and

subtypes of residual
schizophrenia?

What is the 0.5 to 5.0 per 10,000; prevalence, 1 in 100

annual incidence
of schizophrenia?

What gender Although the prevalence is equal in men and women, men
differences exist tend to be afflicted earlier than women; the peak age of
in schizophrenia? onset for men is between 10 and 25 years of age,
whereas for women it is between 25 and 35 years. Men
also are more likely to be impaired by negative
symptoms.

What are risk Genetic predispositiontwin studies show 45% to 50%

factors for monozygotic concordance compared with 10% to 15%
schizophrenia? dizygotic concordance. First-degree relatives have a 5- to
10-fold increased risk. Birth during early winter months
and spring, obstetric complications, lower socioeconomic
status, and immigration have all been associated.

What features Late or acute onset, an obvious precipitant, good

have a good premorbid functioning, married, strong support system,
prognosis? positive symptoms, mood disorder component, family
history of mood disorders

What features Young or insidious onset, no precipitant, poor premorbid

have a poor functioning, unmarried, poor support, negative symptoms,
prognosis? withdrawn behavior, many relapses

What is the Psychotic disorder due to a general medical condition

differential (e.g., AIDS, B12 deficiency, CNS tumor, CVA, herpes
diagnosis of encephalitis, lupus, neurosyphilis, porphyria, Wilson's
schizophrenia disease); substance-induced psychotic disorder; epilepsy
with regard to (especially TLE); delirium; dementia
medical
conditions?

What is the Mood disorder with psychotic features, schizoaffective

differential disorder, schizophreniform disorder, brief psychotic
diagnosis of disorder, delusional disorder, and cluster A personality
schizophrenia disorder
with regard to
psychiatric
conditions?

What is the Antipsychotic medications (e.g., typical or atypical

treatment for neuroleptics) and behavioral and group therapies; consider
schizophrenia? hospitalization.

How do typical These agents antagonize dopamine D 2 receptors.

antipsychotics
work?
What side effects Dystonia, akathisia, and parkinsonian symptoms (e.g.,
are seen with haloperidol, fluphenazine)
typical high-
potency
antipsychotics?

What side effects Sedation, hypotension, weight gain, and anticholinergic

are seen with symptoms (e.g., chlorpromazine)
typical low-
potency
antipsychotics?

Are the side TD and NMS are unrelated to the neuroleptic's potency.
effects of TD and
NMS related to
drug potency?

How do atypical These agents antagonize dopamine D 2 as well as serotonin

antipsychotics 5-HT2 receptors.
work?

What advantages Reduced EPS and better effectiveness in treating negative

do atypical symptoms
antipsychotics
have over typical
antipsychotics?

What They are more costly and linked to hyperglycemia and

disadvantages diabetes; certain atypicals are also linked to weight gain
exist? and hyperlipidemia. The FDA warns of an increased
mortality risk in elderly dementia patients on atypical
antipsychotics.

What are the Clozapine, olanzapine, quetiapine, risperidone,

atypical agents? paliperidone, ziprasidone, and aripiprazole

Which atypical is Clozapineprevents relapse, improves negative symptoms,

most effective for reduces aggression, and it may decrease the risk of
treatmentresistant suicide in patients with schizophrenia
psychotic
patients?

Why is clozapine Side effects, including agranulocytosis (granulocytes

used <500/mm 3 ) in 1% of patients; weekly monitoring of the
infrequently? ANC is required.
 Which atypical Risperidone (as Risperdal Consta)
can be given
every 2 weeks in
depot
formulation?

How is It is a partial agonist at D 2 and 5-HT1A receptors and a

aripiprazole potent antagonist at 5-HT2A receptors.
unique?

What adjuvant Dual antipsychotic therapy, lithium, ECT, antidepressants,

therapies can be buspirone, anticonvulsants (CBZ, VPA), benzodiazepines,
considered for and beta blockers
treatment
resistant
schizophrenia?

What percentage 25% to 50%; in fact, only about 20% have a good outcome.
of schizophrenics
will have disabling
residual symptoms
and impaired
social functioning?

What other Suicide; over 50% of schizophrenics attempt suicide and

problems are 10% to 15% succeed.
associated with At least 75% of schizophrenics smoke cigarettes, 30% to
schizophrenia? 50% are alcoholics, 15% to 25% are cannabis users, and
<10% are cocaine users.
Schizophrenics have an increased rate of violence,
especially in those who experience paranoia.
Around 50% of the homeless probably have schizophrenia.

P.697

Schizophreniform Disorder
What is Essential features (risk factors, signs/symptoms,
schizophreniform differential, and treatment) are the same as those of
disorder? schizophrenia except (1) total duration of the illness is at
least 1 month but less than 6 months and (2) impaired
social and occupational functioning is not required for
diagnosis. When the diagnosis is made without waiting for
recovery, it should be qualified as provisional.
 What is the Lifetime, 1 in 500
prevalence of
schizophreniform
disorder?

What is the Prognosis is better with short duration of illness. 60% to

prognosis for 80% will progress to schizophrenia or schizoaffective
schizophreniform disorder. There is a high suicide risk.
disorder?

Brief Psychotic Disorder

What is a Sudden onset of one or more of the following psychotic
brief symptoms: delusions, hallucinations, disorganized speech, or
psychotic disorganized or catatonic behavior. Duration is at least 1 day but
disorder? less than 1 month with ultimate return to premorbid functioning.

What is the Unknown, but it is considered rare.

prevalence
of brief
psychotic
disorder?

What are Catastrophic stressors, young adulthood, and associated

risk factors premorbid personality disorders
for brief
psychotic
disorder?

What is the Factitious disorder, malingering, psychotic disorder resulting

differential from a general medical condition, substanceinduced psychosis,
diagnosis delirium, epilepsy, dissociative identity disorder, borderline
for brief personality disorder, and schizotypal personality disorder
psychotic
disorder?

What is the Hospitalization, antipsychotic medications, benzodiazepines (for

treatment 2 to 3 weeks), and psychotherapy
for brief
psychotic
disorder?

What is the 50% of patients who are first classified as having brief psychotic
prognosis disorder are later diagnosed with schizophrenia or other chronic
for brief psychiatric syndromes. However, European studies have reported
 psychotic a good prognosis, with 50% to 80% of patients having no further
disorder? major psychiatric ailments.

P.698

Schizoaffective Disorder
What is An illness with features of both schizophrenia and mood
schizoaffective disorders characterized by an uninterrupted period of illness
disorder? during which, at some point, there is a major depressive,
manic, or mixed episode concurrent with psychotic symptoms
consistent with schizophrenia. In addition, there is a period of
at least 2 weeks that consists of delusions or hallucinations in
the absence of mood symptoms.

What are the Bipolar and depressive

subtypes of
schizoaffective
disorder?

What is the Lifetime, 0.5% to 0.8%

prevalence of
schizoaffective
disorder?

What gender There is a lower prevalence in men than in women. As in

differences schizophrenia, the age of onset for women is later than for
exist in men.
schizoaffective
disorder?

What are risk Genetics and female gender. There is increased risk for
factors for schizophrenia among the relatives of probands with
schizoaffective schizoaffective disorder.
disorder?

What are The presence of symptoms consistent with mania, major

symptoms and depression, or a mixed mood state concurrent with psychotic
signs of symptoms consistent with schizophrenia. Furthermore, one
schizoaffective must have additional psychotic symptoms without the mood
disorder? syndrome.

What is the Psychotic disorder resulting from a general medical condition,

differential delirium, dementia, substance-induced psychotic disorder,
diagnosis of delusional disorder, and mood disorder with psychotic
schizoaffective features
 disorder?

What is the Hospitalization, antipsychotic medications, mood stabilizers,

treatment for antidepressants, and group psychotherapy; ECT can be
schizoaffective considered.
disorder?

What is the In general, prognosis ranges between that of patients with

prognosis for schizophrenia and those with mood disorders. Those with
schizoaffective predominantly affective symptoms have a better prognosis
disorder? than those with predominantly schizophrenic symptoms.

P.699

Delusional Disorder
What is An illness characterized by the presence of one or more
delusional nonbizarre delusions for at least 1 month. Delusions may be
disorder? erotomanic, grandiose, jealous, persecutory, somatic, mixed, or
unspecified.

What is 0.025% to 0.03%

the
prevalence
of
delusional
disorder?

What There are slightly more female patients than male. Men are more
gender likely to have paranoid delusions or delusions of infidelity,
differences whereas women are more likely to have erotomanic delusions.
exist in
delusional
disorder?

What are Midlife, recent immigration, low socioeconomic status, family

risk factors history, personality features (e.g., atypical interpersonal
for sensitivity), sensory impairment, and social isolation
delusional
disorder?

What are One or more nonbizarre delusions for at least 1 month. Tactile
signs and and olfactory hallucinations may be present, but there are no
symptoms other symptoms of schizophrenia.
of
delusional
 disorder?

What is Delirium, dementia, malingering, factitious disorder, psychotic

the disorder caused by a general medical condition, substance-
differential induced psychotic disorder, schizophrenia, mood disorders with
diagnosis psychotic features, shared psychotic disorder, OCD, somatoform
of disorders, paranoid personality disorder
delusional
disorder?

What is Generally difficult to treat owing to the patient's poor insight and
the compliance with treatment. Hospitalization if the patient is
treatment agitated, antipsychotic medications, psychotherapy, and family
for therapy
delusional
disorder?

P.700

Shared Psychotic Disorder (Folie Deux)

What is a A delusion that develops in one person (the secondary case) who
shared is involved in a close relationship with another person (the
psychotic primary case) who has a preexisting delusion. Usually, the
disorder? primary case is dominant in the relationship and chronically ill
(e.g., schizophrenia). The secondary case is typically more
gullible and passive. The relationship may involve more than two
people and has been reported in families (folie famille).

What is Rare. It may be more common in women.

the
incidence
of shared
psychotic
disorder?

What are Affected individuals often have a family history of schizophrenia.

risk factors A genetic predisposition has also been suggested. Old age, low
for shared intelligence, cerebrovascular disease, and alcohol abuse are often
psychotic involved factors.
disorder?

What is Malingering, factitious disorder, psychotic disorder caused by a

the general medical condition, substance-induced psychotic disorder,
differential schizophrenia, mood disorders with psychotic features, delusional
diagnosis disorder, OCD, somatoform disorders, paranoid personality
 of shared disorder, delirium, and dementia
psychotic
disorder?

What is Separation from the primary case may be all that is necessary for
the the secondary case to give up the delusional belief. Family
treatment therapy with nondelusional members of the family and
for shared antipsychotic medications may be necessary. Treatment of the
psychotic psychiatric disorder afflicting the primary case is necessary.
disorder?

P.701

Anxiety Disorders
What illnesses Panic disorder with and without agoraphobia, specific
are comprised by phobia, social phobia, obsessive-compulsive disorder,
the anxiety posttraumatic stress disorder, acute stress disorder, and
disorders? generalized anxiety disorder

What is the 25%, thus making anxiety disorders the most prevalent
lifetime psychiatric disorders in the population
prevalence of
pathologic
anxiety?

What medical Endocrine: diabetes, thyroid or parathyroid disease,

conditions are pheochromocytoma
commonly Drug-related: caffeine, steroids, sympathomimetics,
associated with thyroid hormone, or withdrawal from alcohol, sedatives,
anxiety? or narcotics
Metabolic: electrolyte abnormalities, acidosis
Neurologic: seizures (e.g., TLE), vestibular dysfunction
Respiratory: causes of hypoxia (e.g., COPD, CHF)

P.702

Panic Disorder
What is panic Recurrent, unexpected panic attacks with or without
disorder? agoraphobia; one panic attack must be followed by at least
1 month of fear about having further attacks, worry about
the consequences of an attack, or change in behavior
related to the attack.

What is a panic The sudden development of a discrete period of intense fear

attack? or discomfort
What are some Tachycardia, palpitations, sweating, trembling, shortness of
of the signs and breath, choking sensation, chest pain or tightness,
symptoms of a abdominal discomfort, dizziness, derealization or
panic attack? depersonalization, fear of losing control or dying,
paresthesias, or chills or hot flushes

What is Anxiety of being in places where escape is difficult or

agoraphobia? impossible (e.g., public, crowded places). The fear is
usually associated with having a panic attack in an
unprotected place.

What is the Lifetime, 1.5% to 3.5%

prevalence of
panic disorder?

What is the Attacks usually begin with a 10-minute period of escalating

usual duration symptoms and last 20 to 30 minutes.
and course of
symptoms of
panic disorder?

What is the Anxiety disorder caused by a general medical condition and

differential substance-induced anxiety disorder
diagnosis for
panic disorder?

What is the Antidepressants, benzodiazepines (e.g., alprazolam,

treatment for clonazepam, and lorazepam), and cognitive therapies
panic disorder?

What advantage Benzodiazepines have the most rapid onset of action,

do usually within the first week. They can also be used
benzodiazepines effectively on an as-needed basis.
have in treating
panic disorder?

What Potential for abuse, dependence, withdrawal effects, and

disadvantage do cognitive impairment (especially in the elderly); patients
benzodiazepines should not drive or operate dangerous equipment while
have in treating taking benzodiazepines.
panic disorder?

P.703
Specific Phobia (Simple Phobia)
What is specific A persistent, unreasonable fear brought about by the
phobia? presence or anticipation of a specific object or situation
(e.g., animals, blood, heights, enclosed spaces, etc.)

What is the 10%

lifetime
prevalence of
specific phobia?

What is the Exposure-based interventions (utilizing CBT) are the

treatment for mainstay of treatment. Benzodiazepines used on an as-
specific phobia? needed basis can limit anxiety and facilitate exposure.

Social Phobia (Social Anxiety Disorder)

What is social A persistent, unreasonable fear of social or performance
phobia? situations where the individual is exposed to possible
scrutiny and is afraid of acting in a way that is embarrassing

What is the 3% to 15%

lifetime
prevalence of
social phobia?

What is the SSRIs, MAOIs, beta blockers, benzodiazepines, and CBT,

treatment for including exposure interventions and role playing
social phobia?

P.704

Obsessive-Compulsive Disorder
What is An illness characterized by recurrent obsessions or compulsions
OCD? that cause significant distress or impairment in functioning

What are Persistent and recurrent images, impulses, or thoughts that are
obsessions? not merely excessive worries about real-life problems but
rather intrusive and inappropriate

What are Repetitive behaviors (e.g., hand washing, checking) or mental

compulsions? acts (e.g., praying, counting) that a person feels compelled to
perform in order to reduce anxiety or prevent an imagined
dreaded event or situation
 What is the Lifetime, 2% to 3%
prevalence
of OCD?

What are Studies show a higher rate of concordance for monozygotic than
risk factors dizygotic twins; 35% of first-degree relatives of patients are
for OCD? also afflicted with the disorder.

What are Generally, gradual onset of obsessions or compulsions, usually

symptoms in late teens or early twenties. The patient generally has
and signs of insight into the irrationality of the illness. Skin problems may
OCD? be present owing to excessive washing.

What is the Anxiety disorder caused by a general medical condition,

differential substance-induced anxiety disorder, body dysmorphic disorder,
diagnosis of major depressive episode, hypochondriasis, specific phobia, and
OCD? tic disorders

What is the High-dose SSRIs; clomipramine; MAOIs; augmentation with

treatment lithium, VPA, or CBZ; buspirone; benzodiazepines; and cognitive
for OCD? behavioral therapy

P.705

Posttraumatic Stress Disorder

What is Characteristic symptoms that develop after a person is exposed
PTSD? to a traumatic event involving actual or threatened death or
serious injury to self or others and the person's response involved
horror, helplessness, or intense fear

What is Lifetime, 8%; for those injured in combat, the prevalence is 20%
the
prevalence
of PTSD?

What are Exposure to considerable conflict or unrest; suffering a life-

risk factors threatening accident or assault
for PTSD?

What are Greater than 1 month of persistent reexperiencing of the

symptoms traumatic event through recurrent and intrusive images, thoughts,
and signs or perceptions; recurrent distressing dreams of the event;
of PTSD? flashbacks; avoidance of stimuli associated with the trauma; and
hyperarousal and hypervigilance, including difficulty sleeping,
 irritability, difficulty concentrating, hypervigilance, and
exaggerated startle response

What is Head injury from sustained trauma, substance-related disorders,

the adjustment disorder, acute stress disorder, OCD, malingering,
differential factitious disorder, dissociative disorders, and borderline
diagnosis personality disorder
of PTSD?

How does For acute stress disorder, symptoms occur within 4 weeks of the
acute traumatic event and last no more than 4 weeks.
stress
disorder
differ from
PTSD?

What is Mainstays of treatment are SSRIs, TCAs, MAOIs, and buspirone.

the Other treatments include lithium, VPA, CBZ, clonidine,
treatment propranolol, benzodiazepines, antipsychotics, and psychotherapy
for PTSD? (e.g., individual, CBT, or group).

P.706

Generalized Anxiety Disorder

What is Excessive worry and anxiety over a number of activities or
generalized situations occurring for a period of at least 6 months
anxiety
disorder?

What are Anxiety associated with restlessness, easy fatigability,

symptoms and difficulty concentrating, irritability, muscle tension, or
signs of disturbed sleep
generalized
anxiety
disorder?

What is the Lifetime, 5%; women are twice as likely to be affected.

prevalence of
GAD?

What is the Anxiety disorder resulting from a general medical condition,

differential substance-induced anxiety disorder, mood disorder with
diagnosis for anxious features, adjustment disorder, ADHD,
generalized hypochondriasis, somatization disorder, and personality
anxiety disorders
 disorder?

What is the SSRIs, SNRIs, TCAs, MAOIs, buspirone, beta blockers,

treatment for benzodiazepines, CBT, and anxiety management skills (e.g.,
generalized relaxation techniques)
anxiety
disorder?

Adjustment Disorders
What is an Development of clinically significant behavioral or emotional
adjustment symptoms in excess of what would normally be expected
disorder? within 3 months of an identifiable stressor.

What is the The condition resolves within 6 months of the stressor being
natural history terminated.
of the illness?

What are the Adjustment disorder with depressed mood, anxiety, mixed
different types anxiety and depressed mood, disturbance of conduct, mixed
of adjustment disturbance of emotions and conduct, and unspecified
disorders?

What is the 2% to 10%; women are diagnosed twice as often as men;

prevalence of nearly 50% of patients with specific medical problems or
adjustment stressors have been diagnosed with an adjustment disorder.
disorder?

What is the Personality disorders, mood disorders, anxiety disorders

differential (e.g., PTSD, acute stress disorder), substance-related
diagnosis of disorders, bereavement, and nonpathologic response to
adjustment stress
disorder?

What is the Psychotherapy primarily; may augment with SSRIs for

treatment for traumatic grief, low-dose antipsychotic medications if there
adjustment are signs of decompensation, and short-term use of
disorder? benzodiazepines for anxiety

P.707

Substance-Related Disorders
What is A pathologic pattern of substance use manifest by the
substance development of tolerance, withdrawal, and inability to
dependence? decrease the amount of usage despite repeated attempts. A
 large amount of time is spent obtaining the substance, or an
individual gives up social, occupational, or recreational
activities to obtain or use the substance.

What is A pathologic pattern of substance use characterized by

substance recurrent substance-related legal problems, recurrent
abuse? substance use in situations that are physically hazardous, and
failure to fulfill personal, occupational, and educational
responsibility as a result of substance use.

What is the 10% in women, 20% in men

lifetime
prevalence for
alcohol
dependence
(alcoholism)?

What is the 5% in women, 10% in men

lifetime
prevalence for
alcohol abuse?

What is the C: Have you felt you should cut down on drinking?
CAGE A: Are you annoyed by people criticizing drinking?
questionnaire? G: Have you felt guilty about drinking?
E: Have you ever had an eye-opener in the morning?
Each letter is scored either 0 or 1; a score of 2 or more is
clinically significant.

What are the Precontemplation, contemplation, preparation, action,

stages of maintenance, relapse
behavioral
change?

What is the Failure to adequately diagnosis and treat comorbid psychiatric

most common disorders in these dual-diagnosis patients
cause for
failure of
alcoholism
treatment?

What Disulfiram, naltrexone, and acamprosate

pharmacologic
treatments
are there for
 alcoholism?

P.708

Eating Disorders
What is A condition resulting in refusal to eat normally and fear of
anorexia gaining weight such that body weight is less than 85% of that
nervosa? expected for a given age and height. Furthermore, there is a
disturbance in how one's weight or shape is experienced.

What are the Restricting type and binge-eating/purging type

subtypes of
anorexia
nervosa?

What is the 0.3% of young adult females are affected

prevalence of
anorexia
nervosa?

What Depression, social phobia, and OCD

psychiatric
disorders are
often comorbid
with anorexia
nervosa?

What is the Hospitalization if needed to restore the patient's nutritional

treatment for state; inpatient eating disorder programs using behavioral
anorexia management and psychotherapy; CBT; family therapy;
nervosa? medications (e.g., fluoxetine, cyproheptadine)

What is bulimia A condition marked by recurrent episodes of binge eating as

nervosa? well as recurrent inappropriate compensatory behavior (e.g.,
self-induced vomiting, diuretics, laxatives, etc.) in order to
prevent weight gain

What are the Purging type and nonpurging type

subtypes of
bulimia
nervosa?

What is the 1% to 3% of young adult females

prevalence of
bulimia
 nervosa?

What is the First-line treatment is CBT; use antidepressants to treat

treatment for associated depression and anxiety.
bulimia
nervosa?

P.709

Somatoform Disorders
What are the Somatization disorder, conversion disorder, pain disorder,
somatoform hypochondriasis, and body dysmorphic disorder
disorders?

What is A chronic disorder marked by multiple physical complaints

somatization that occur over several years and result in impairment
disorder? and/or frequent use of medical services

What is There are symptoms or deficits affecting voluntary motor

conversion or sensory function suggesting a neurologic or general
disorder? medical condition, but it is better explained by
psychological factors.

What is pain Pain at one or more sites is the primary focus; the pain
disorder? causes clinically significant impairment, and psychological
factors play an important role.

What is Preoccupation with fears of having, or the belief that one

hypochondriasis? has, a serious medical illness

What is body Preoccupation with an imagined defect in the way one looks
dysmorphic or exaggerated concern about a minor physical anomaly
disorder?

P.710

Factitious Disorders
What is factitious disorder? A condition marked by the intentional
production of physical or psychological
symptoms where the motivation for such
behavior is to assume the sick role

What eponym refers to Mnchhausen syndrome

factitious disorder with
 predominantly physical
signs and symptoms?

What is Mnchhausen Someone (usually a parent) intentionally

syndrome by proxy? produces physical signs or symptoms in another
person (usually a child) who is under his or her
care.

How does malingering Malingerers have secondary gain (e.g., financial

differ from factitious gain, evading criminal prosecution, avoiding
disorder? work) for feigning physical or psychological
symptoms.

How do somatization The production of symptoms in somatization

disorder and conversion disorder and conversion disorder is not under
disorder differ from voluntary control but rather the result of an
factitious disorders? unconscious conflict.

P.711

Attention-Deficit/Hyperactivity Disorder
What are the Inattention the individual pays poor attention to detail, has
symptoms of difficulty sustaining attention, fails to listen when spoken to,
ADHD? loses things easily, and is distractible and forgetful
Hyperactivity the individual fidgets, is unable to sit still,
feels on the go, has difficulty playing quietly, talks
excessively
Impulsivityblurts out answers, unable to wait his or her turn,
interrupts others

What is the 3% to 5% in school-age children; unknown in adults, although

prevalence of the disorder is thought to persist into adolescence and
ADHD? adulthood in half of those affected

What gender The male-to-female ratio is between 4:1 and 9:1

differences
exist in
ADHD?

What are the Evidence supports genetic factors; developmental factors and
risk factors psychosocial factors may contribute.
for ADHD?

What is the Anxiety disorders, mood disorders, learning disorders

differential
 diagnosis of
ADHD?

What is the CNS stimulants: methylphenidate, d-enantiomer of

treatment for methylphenidate, amphetamine salt and dextroamphetamine
ADHD? combinations
Norepinephrine reuptake inhibitor: atomoxetine
Psychosocial interventions: behavioral interventions, social
skills groups

P.712

Personality Disorders
What is a An enduring pattern of behavior and inner experience that
personality deviates significantly from the expectations of an individual's
disorder? culture. This pattern may be manifest in the individual's way
of perceiving and interpreting self or others; range, intensity,
lability, or appropriateness of affect; impulse control; or
interpersonal functioning.

What percent 35%; of note, in the general population the prevalence of

of patients personality disorders is 10% to 20%.
with an axis I
diagnosis have
comorbid
personality
disorders?

When is the In adolescence; the patterns are of long standing.

onset for
personality
disorders?

What are the Cluster A (weird)

major Cluster B (wild)
categories of Cluster C (wimpy)
personality
disorders?

Give examples Cluster A (weird): odd or eccentric; includes paranoid,

of cluster A schizoid, and schizotypal personality disorders
behaviors and
the
personality
disorders in
 the group.

Give examples Cluster B (wild): dramatic, emotional, or erratic; includes

of cluster B antisocial, borderline, histrionic, and narcissistic personality
behaviors and disorders
the
personality
disorders in
the group.

Give examples Cluster C (wimpy): excessive fearfulness or anxiety;

of cluster C includes avoidant, dependent, and obsessive-compulsive
behaviors and personality disorders
the
personality
disorders in
the group.

P.713

Urgencies and Emergencies

Acute Psychosis
What is The acute or subacute onset of psychotic symptoms
acute
psychosis?

What are Delusions, hallucinations, disorganized speech (e.g., incoherence,

symptoms loosening of associations, thought blocking), grossly disorganized
and signs behavior, and catatonic excitement or stupor
of acute
psychosis?

What Tests to rule out organic causes including CBC, basic chemistries,
diagnostic LFTs, TFTs, RPR, B12, folate, UA, toxicology screens (APAP, ASA,
tests are UDS, BAL, heavy metals, etc.), urine porphyrins, HIV, antinuclear
ordered antibody (ANA), ceruloplasmin, head CT or MRI, EEG, and
for the occasionally CSF studies
workup of
acute
psychosis?

What is Psychotic disorder due to a general medical condition [e.g., AIDS,

the B12 deficiency, CNS tumor, CVA, herpes
differential encephalitis, endocrine disorders, iatrogenic (e.g., steroids),
 diagnosis lupus, metabolic disarray, neurosyphilis, porphyria, toxic causes,
for acute Wilson's disease]; substance-induced psychotic disorder; epilepsy
psychosis? (especially TLE); delirium; dementia; primary psychotic disorder;
primary mood disorder with psychotic features; and cluster A
personality disorders

What is Hospitalization, treatment of underlying cause (whether organic

the or psychiatric), antipsychotic medications, and benzodiazepines
treatment for acute agitation
for acute
psychosis?

P.714

Neuroleptic Malignant Syndrome

What is NMS? A life-threatening complication of antipsychotic medications
that can occur at any time in treatment

What is the 0.02% to 2.5% of patients exposed to dopamine receptor

prevalence of antagonists (e.g., antipsychotics)
NMS?

What are risk Use of high-potency antipsychotic medications (e.g.,

factors for haloperidol and fluphenazine) in high doses, particularly when
NMS? the dosage is increased rapidly; higher number of
intramuscular injections; and concurrent use of lithium

What are Hyperthermia, severe muscular rigidity, autonomic instability

symptoms and including tachycardia, hypertension, tachypnea, and
signs of NMS? diaphoresis, as well as changes in level of consciousness

What CK (elevated in 50% of cases), aldolase, white blood cell count

laboratory (leukocytosis), electrolytes, creatinine, LFTs, and urine
tests are myoglobin
ordered for
NMS?

What is the Discontinue antipsychotic medications; transfer to the

treatment for intensive care unit for supportive measures (e.g., hydration,
NMS? cooling, hemodynamic monitoring); electrolyte balance;
dialysis may be necessary given renal function;
pharmacotherapy.

What Dantrolene 2.5 mg/kg initial dose, then 2 mg/kg intravenously

pharmacologic every 6 to 12 hours; avoid if LFTs are very abnormal
 interventions Bromocriptine: 2.5 mg orally every 6 hours, titrated to a
exist for maximum dose of 40 mg/day (divided qid)
NMS? Amantadine: 100 mg orally, titrated to 200 mg every 12 hours
Other treatments: clonazepam, carbamazepine, ECT

What is the 10% to 20% mortality rate

prognosis for
NMS?

Acute Dystonic Reaction

What is an An extrapyramidal symptom consisting of intermittent and
acute sustained muscle spasms of the head, neck, and trunk leading
dystonic to involuntary movements. It is a direct result of treatment
reaction? with antipsychotic medications and is now much less likely with
atypical neuroleptics.

What are Male gender, age younger than 30 years, and high dosages of
risk factors potent typical antipsychotic medications
for an acute
dystonic
reaction?

What are Opisthotonos, retrocollis, torticollis, oculogyric crisis, tongue

symptoms protrusion, dysarthria, dysphonia, and dysphagia
and signs of
an acute
dystonic
reaction?

What is the Tetanus and seizures

differential
diagnosis of
an acute
dystonic
reaction?

What is the Intramuscular benztropine 2 mg or diphenhydramine 50 mg;

treatment repeat in 15 minutes if not effective
for an acute
dystonic
reaction?

P.715
Alcohol Withdrawal and Delirium Tremens
What is alcohol A physiologic syndrome resulting from the cessation of
withdrawal? prolonged and heavy alcohol use. The syndrome progresses
soon after the cessation of alcohol use and may include
grand mal seizures or DTs (alcohol withdrawal delirium).

What are the Tremulousness

symptoms and
signs of alcohol
withdrawal in
the first 6 to 8
hours?

What are the Seizures

symptoms and
signs of alcohol
withdrawal at
12 hours?

What are the DTs (vivid visual or tactile hallucinations, profound

symptoms and disorientation, increased autonomic activity, fluctuating
signs of alcohol psychomotor activity)
withdrawal at
72 hours to 1
week?

What are the Elevated delta-glutamyl transferase (GGT), mean corpuscular

laboratory volume (MCV), triglycerides, high-density lipoprotein (HDL),
findings in aspartate aminotransferase (AST) and alanine
alcohol aminotransferase (ALT) (2:1 AST:ALT ratio)
dependence?

What is the Sedative or hypnotic withdrawal (including benzodiazepines)

differential
diagnosis for
alcohol
withdrawal?

What is the Thiamine, folate, magnesium (banana bag or rally pack);

treatment for detoxification with benzodiazepine taper given orally
alcohol (preferred) or parenterally, depending on severity;
withdrawal? benzodiazepines as needed for autonomic hyperactivity or
agitation associated with delirium; and antipsychotic
medications for delirium (but keep in mind that they lower
 the seizure threshold)

Which A long-acting benzodiazepine such as chlordiazepoxide;

benzodiazepine however, chlordiazepoxide has erratic absorption
is preferred in intramuscularly so give it orally only.
the setting of
normal liver
function and
alcohol
withdrawal?

Which A benzodiazepine with no active metabolites such as

benzodiazepine lorazepam
is preferred in
the setting of
abnormal liver
function and
alcohol
withdrawal?

P.716
P.717

Suicide
What is the In the year 2000, suicide represented 1.2% of all
epidemiologic makeup deaths, thus averaging 80 suicides per day in the
of suicide? United States.

What is the In the year 2004, 11 per 100,000 in the United States
prevalence of (1 person every 16.2 minutes with 1 attempt every 39
suicide? seconds)

What major factors in

the following
categories affect
suicide risk?

Personal and social Male gender

Age older than 45 years; !85 is the highest-risk group
Widowed, divorced, or separated marital status
White or Native American
Immigrant status
Lone dweller or socially isolated
Unemployed, retired, or having financial difficulties
 Previous history Family history of affective disorder, suicide, or
alcoholism
Previous history of an affective disorder, suicide
attempt, or alcoholism
Beginning psychiatric treatment or 6 months after
discharge from treatment
Impulsivity

Life stresses Bereavement and separation

Loss of job or house
Incapacitating or terminal illness

Psychiatric illnesses Depression

Antisocial personality
Alcohol or drug addiction
Dementia, delirium, and organic brain syndromes

What symptoms are Insomnia, weight loss, slowed speech, agitation,

worrisome with severe anxiety, listlessness, social withdrawal, loss of
regard to suicide risk? interest, hopelessness, feelings of worthlessness, and
suicidal thoughts

What signs are When the patient takes precautions against discovery,
worrisome with takes preparatory action (e.g., procures means of
regard to suicide suicide, makes warning statements, writes suicide
attempts? notes, and gets personal affairs in order), and uses
violent methods or lethal drugs

What is the Greater than 90%

prevalence of
psychiatric illness
among patients who
commit suicide?

What psychiatric Major depression, substance abuse, anxiety disorders,

illnesses are personality disorders (borderline, antisocial), and
predominant in schizophrenia
suicidal patients?

What is the treatment Hospitalization and treatment of underlying disorder

for suicidality?

What medications Lithium maintenance for bipolar patients; clozapine

have been shown to for schizophrenic patients
decrease the risk of
suicide?

What percent of 50%

suicides occur in
people who have
tried suicide before?

Of those who attempt 15% to 35%

suicide
unsuccessfully, how
many will make
another attempt in
the next 2 years?
Editors: Bergin, James D.
Title: Advanced Medicine Recall, 1st Edition
Copyright 2009 Lippincott Williams & Wilkins

> Table of Contents > Section IV - The Consultant > Chapter 17 - The Consultant

Chapter 17
The Consultant

P.720

Abbreviations
BUN Blood urea nitrogen

CABG Coronary artery bypass grafting

CAD Coronary artery disease

CBC Complete blood count

COPD Chronic obstructive pulmonary disease

CRI Cardiac risk index

CVD Carotid vascular disease

DVT Deep venous thrombosis

ECG Electrocardiogram

FEV 1 Forced expiratory volume during the first second

FVC Forced vital capacity

GI Gastrointestinal

GU Genitourinary

HF or CHF Heart failure or congestive heart failure

 HgbAlC Glycosylated hemoglobin

H/O History of

JVD Jugular venous distension

MET Metabolic equivalent

MI Myocardial infarction

MRSA Methicillin-resistant Staphylococcus aureus

NPO Nil per os (nothing by mouth)

PFT Pulmonary function test

PVD or PAD Peripheral vascular disease or peripheral arterial disease

PVC Premature ventricular contraction

VT Ventricular tachycardia

P.721
P.722

Role of the Medical Consultant

What is the role of To provide expertise in medical areas of patient care,
the medical often when the patient's primary care team specializes in
consultant? an area other than internal medicine

When should the Consults may be emergent, urgent, or elective. It is

consult be carried important to determine the nature of the consult and to
out? respond appropriately. In general, a courteous and rapid
response to any consult is appreciated by the primary
team.

How broad are the The recommendations are usually relatively narrow in
recommendations scope and limited to those needed to answer the clinical
generated by the question posed to the consultant. The consult
consultant? recommendations are considered to be goal-directed. It
is usually not helpful to point out obvious/standard
medical issues (e.g., avoid hypotension).

Are any peripheral Yes. Under some circumstances, it is appropriate to

 recommendations provide contingency plans. In a patient whose condition
appropriate? is changing or who may fail an initial therapeutic
recommendation, it may be helpful to include a backup
plan.

Should there be Sometimes it is appropriate to provide recent, concise

any other articles from a journal that the primary team is unlikely
information to have been exposed to. This is never a substitute for
included in the direct communication with the primary team.
consult?

How are the The recommendations are recorded in writing in the

consultant's patient's chart on the consult note. If the note is
recommendations dictated the key points should still be written in the
reported? chart.

Whose The patient's primary care team. If the consultant feels

responsibility is it that patient care is significantly compromised by failure
to ultimately to carry out the recommendations, it would be
decide how and appropriate for the consultant to discuss them in person
whether or not to with the primary team. It is not appropriate to engage in
carry out a chart wars.
consultant's
recommendations?

How long should Each case varies, but generally the patient is followed
the consulting team up until the clinical questions at hand are resolved or
follow up the until the consult team is no longer providing useful
patient? input. After signing off the case, the consultant should
indicate willingness to become involved again if the
patient's status changes.

P.723
P.724
P.725
P.726
P.727
P.728
P.729

Preoperative Clearance of the Surgical Patient

Why is it important To assess the patient's risk for cardiac and other
to perform adverse events, trying to ensure the best medical and
preoperative surgical outcome with the lowest adverse event rate
evaluations on
patients undergoing
surgery?

What are the Any existing medical problems can be treated before
benefits of a surgery to maximize the patient's chances of having an
preoperative uneventful procedure and recovery. This is especially
evaluation? important before elective surgery because clearance is
a process of weighing the need for surgery against the
risk of surgery. A higher level of risk is tolerated when
a patient needs emergency surgery than when the
patient is undergoing an elective procedure.

What is the cardiac >5% risk of a cardiac event

risk for patients
undergoing high-risk
procedures?

What are examples Emergency operations (major surgery)

of high-risk Aortic or major suprapubic vascular surgeries
operations? Prolonged surgical procedures with significant fluid
shifts

What is the cardiac Risk of a cardiac event between 1 and 5%

risk for patients
undergoing
intermediate-risk
procedures?

What are examples Carotid or distal peripheral vascular surgeries

of intermediate-risk Head and neck
procedures? Intraperitoneal or intrathoracic surgeries
Orthopedic and prostate surgeries

What is the cardiac <1% risk of a cardiac event

risk for patients
undergoing low-risk
procedures?

What are examples Endoscopic procedures

of low-risk Superficial procedures
procedures? Cataract surgery
Breast surgery

If a patient does About two to four times that over an MI not occurring
suffer a in the perioperative period.
perioperative MI,
what is the relative
increased risk of
death?

When in the surgical During induction of anesthesia, 10%

course is death most During surgery, 35%
likely to occur? Within 48 hours of surgery, 55%

Other than specific Yes. Age is a contributor to surgical risk. Patients

medical illness, are below 65 years of age have a 1% mortality rate,
there any general whereas those above 65 years of age have a 5%
risk factors for mortality rate.
patients undergoing
surgery?

What important Previous MI, chest pain, dyspnea, syncope,

elements of a dysrhythmias, history of rheumatic fever, and history of
patient's history diabetes
should be discussed
with cardiac patients
about to undergo
surgery?

What elements of Vital signs are important, as are JVD, bruits, slow
the physical carotid upstroke, a displaced point of maximal impulse
examination are (PMI), murmurs, S3 gallop, and rubs.
especially important
for cardiac patients
about to undergo
surgery?

What is the Goldman Developed in 1977, the Goldman scale quantifies

scale? operative risk for MI based on several variables assessed
by history, physical examination, and simple laboratory
data.

What nine variables Table 17-1. Goldman Scale

are associated with
Point
an increased risk of
Variable Value
perioperative MI or
death in Goldman's
work, and what Third heart sound or JVD 11
were their point
values? MI within 6 months 10
 Nonsinus rhythm 7

>5 PVCs per minute 7

Age >70 years 5

Emergency procedure 4

Hemodynamically significant aortic 3

stenosis

Aortic, intra-abdominal, or 3
intrathoracic surgery

Poor general health 3

How do the point Table 17-2. Preoperative Risk

values help
Points MI, Pulmonary Edema, VT Death
determine
preoperative risk?
05 0.7% 0.2%

612 5.0% 2.0%

1325 11.0% 2.0%

>26 22.0% 56.0%

What other In addition to Goldman, Detsky (Arch Int Med 146:2131

preoperative 2134:1986), L'Italien (JACC 1996;27:779), and Eagle (J
evaluation indices Am Coll Cardiol 1996;27:77986) have excellent risk
are there? indices.

What is the Cardiac History of:

Risk Index? 1 Ischemic heart disease
Cerebrovascular disease: any H/O TIA or CVA.
Diabetes mellitus: use of insulin
Renal insufficiency: creatinine >2.0 mg/dL
High-risk surgery: intrathoracic, intraabdominal, or
suprapubic vascular

How is this index One point is assigned for each positive; scores >2 are
useful? higher-risk and warrant use of beta blockade.
What is Indicators of significance (in the absence of
hemodynamically echocardiography) are poor exercise tolerance, a
significant aortic history of syncope, HF, or angina, a late-peaking
stenosis? systolic murmur, delayed pulses, and absence of the
aortic component of the second heart sound (A 2 ).

Dysrhythmia is more Dysrhythmias are a marker for ischemic heart disease.

likely to result in
complications of
what nature?

How much is risk Two times for male diabetics and four times for female
increased for diabetics
cardiovascular
events for diabetic
patients compared
with their
nondiabetic
counterparts?

Is hypertension a By itself, no, although diastolic pressure greater than

marker for an 110 mm Hg is sometimes considered a relative
increased risk of contraindication to elective surgery. When hypertension
cardiac is a manifestation of other serious illness such as renal
complications? artery stenosis, hyperaldosteronism, or
pheochromocytoma, the illness should be treated
before the patient undergoes elective surgery.

What is the most The history and physical examination is the most
important tool for important element of the evaluation.
assessing risk
associated with
surgery for
cardiovascular
patients?

Do patients with Yes. One third of patients with PVD/CVD have no

vascular disease significant CAD (<50% stenosis). One third have
(peripheral or moderate CAD (>50% stenosis). One third have severe
cerebrovascular) CAD (>70% stenosis), with 5% to 10% being inoperable.
have a higher rate
of CAD?

Can patients who Patients who have undergone CABG have an

have undergone approximately 1% incidence of a cardiac event while
CABG and are undergoing surgery.
symptom-free then
undergo other
surgery?

When is a 1. A history of cardiac disease, or with history and

preoperative ECG physical examination findings that suggest cardiac
indicated? disease (e.g., diabetes mellitus, atherosclerosis,
hypertension, dysrhythmias, certain malignancies,
collagen vascular diseases, and infectious diseases)
2. Undergoing intrathoracic, intra-abdominal, aortic,
or emergency surgery
3. At risk for electrolyte abnormality
4. Any patient taking a potentially cardiotoxic
medication
5. Any man above 45 years of age or any woman above
age 50

When should 1. A history of cardiovascular disease (e.g., valvular

preoperative chest disease, CHF, and coronary or cerebrovascular
films be obtained? disease)
2. A history of pulmonary disease (e.g., asthma, COPD,
occupational lung disease, and tobacco use)
3. A history of a malignancy
4. Age greater than 60 years
5. Symptoms and signs of an infection

What are the two Presence of heart failure and recent MI

most important risk
factors for
significant
postoperative
cardiac events?

What is a significant Sudden death, MI, unstable angina, pulmonary edema,

cardiac event? or serious dysrhythmia (e.g., such as VT or ventricular
fibrillation)

What is the risk of a Approximately 0.5% (10 times less than in a patient
cardiac event with cardiac history)
occurring in a
surgery patient
without a cardiac
history?

How does the It has never been studied, but it seems logical that
presence of unstable patients with unstable angina should not undergo
angina affect elective surgery (except CABG). These patients should
operative risk? have the extent of their disease defined and should
then receive appropriate medical therapy.

What is the risk that The risk depends on how recently the patient
a patient who experienced the cardiac event and how large a stress
undergoes surgery the surgery causes (e.g., thoracic aneurysm more
and has had a prior stressful than a cataract operation). In general, the risk
MI will have another of subsequent MI is approximately 5%. In the first 4 to 6
such cardiac event? weeks after an MI, however, the risk is higher.

What is the 6% if MI was less than 3 months before surgery, 2% if MI

mortality rate of was 3 to 6 months before surgery, and 1.5% if MI was
surgical patients >6 months before surgery
who have had a
recent MI?

Is there anything Yes. Some evaluation for residual ischemia (and

that can be done to treating it if found) is helpful. Beta-blocker therapy
lower the has been shown to be helpful and should be considered
perioperative risk in in all high-risk patients.
patients who have
had a recent MI and
need surgery?

Do high-risk patients Some high-risk patients may benefit, but there is also
benefit from the use the risk of the line placement to be considered.
of a pulmonary
artery catheter?

Do low-risk patients No. Using the CRI scale, patients with <2 points have a
also benefit from higher likelihood of harm with preoperative beta
perioperative beta- blockers.
blocker use?

What noninvasive 1. An exercise stress radionucleotide test (test of

cardiac tests are choice if patient can ambulate) has a negative
thought to be most predictive value (the test is negative and no cardiac
predictive of complication occurs) of 93%.
ischemic 2. The negative predictive value of a dipyridamole
complications in the radionucleotide test (for those who cannot attain
perioperative high workload on a treadmill) is >95%.
period, and what 3. The negative predictive value of a dobutamine
are their echocardiogram is 93% to 100%.
approximate
predictive values?

Can a stress test Patients can be divided into functional class based on
help predict risk in the maximal metabolic stress level they can achieve
other ways? before stopping a treadmill test. The higher the
functional class, the lower the perioperative risk.

How many METs Patients who achieve only 1 to 3 METs are in the low-
achieved is a low functional category.
functional class
(i.e., higher risk)?

How many METs Patients who achieve only 4 to 7 METs fall into the
achieved is a moderate category.
moderate functional
class (i.e., moderate
risk)?

How many METs Patients who exercise to >7 METs are in the high-
achieved is a high functioning category.
functional class
(i.e., low risk)?

What types of >10 METs, equivalent to participation in strenuous

routine activities sports like swimming, singles tennis, football,
are consistent with basketball, skiing
a high functional
class?

What types of 4 to 10 METs (in increasing order): the ability to do

routine activities light housework (dusting, dishes); climb a flight of
are consistent with stairs or a hill; walk at 4 mph; run a short distance; do
a moderate heavy housework (lifting, moving furniture); participate
functional class? in bowling, dancing, and doubles tennis

What types of 1 to 4 METs: the ability for self-care (eating, dressing,

routine activities using the toilet); walking indoors and around the house;
are consistent with walking a block or two on level ground at 2 to 3 mph
a low functional
class?
 Do all patients with If the patient had surgical revascularization within 5
a history of cardiac years, percutaneous revascularization within the
disease require previous 2 years, or cardiac testing within 2 years and
preoperative stress has had no clinical deterioration or significant cardiac
testing? symptoms, more testing is not required.

Should patients who Yes, unless otherwise instructed. By not taking such
are NPO take blood previously prescribed treatment, the patient is
pressure medication predisposed to perioperative blood pressure variability
on the morning of and postoperative cardiac complications. The major
surgery? risks of anesthesia are related to hypotension and
rebound hypertension.

Does regional Except in patients with HF, the type of anesthesia

anesthesia reduce selected does not alter outcome with regard to cardiac
the rate of status. However, regional anesthesia is often used in
postoperative sicker patients undergoing surgery. The ultimate choice
cardiac of anesthetic is appropriately left to the
complications anesthesiologist.
compared with that
of general
anesthesia?

1
Lee TH. Circulation 1999;100:1043; Lindenauer PK. NEJM 2005;353:349.

P.730
P.731

Preoperative Evaluation of Lung Function

What is the Patient history and physical examination
most
important
element of
evaluation of
pulmonary
function?

List factors Obesity, smoking, COPD, chronic bronchitis, type of surgery or

that incision, asthma, occupational lung disease, sleep apnea,
predispose the neuromuscular disease, coma, nutritional depletion, acidosis,
patient to endotracheal intubation, hypotension, hypoxemia, and
pulmonary azotemia are all potential contributors to postoperative
complications. pulmonary complications.

Does a patient Yes.

benefit from
quitting
smoking
before
surgery?

How much Patients who quit smoking 8 weeks before surgery have a
time before statistically significant decrease in the number of pulmonary
surgery is complications compared with those who do not, independent
needed to of functional status as assessed by PFTs.
decrease
pulmonary
complications?

How soon Improvement in lung function and mucociliary clearance is

does detectable in <1 month after quitting.
mucociliary
function
improve after
smoking
cessation?

What other Carboxyhemoglobin levels decrease quickly, thus improving

benefit occurs oxygen delivery.
with smoking
cessation?

Which This is a judgment call. Functional limitation such as difficulty

patients with with walking steps or distances should prompt further
predisposing evaluation. Any patient with an abnormal lung examination
characteristics (e.g., wheezing or rhonchi) may benefit from PFTs.
for pulmonary
complications
should
undergo PFTs?

What other When indicated by the history and physical examination, chest
studies are radiographs, ECG, and arterial blood gases
useful for
evaluation of
pulmonary
risk?

What finding None. FVC, FEV1 , maximum breathing capacity, maximum

on PFTs is midexpiratory flow, and arterial blood gas findings have all
 truly failed to reliably predict pulmonary complications.
predictive of
perioperative
pulmonary
complications?

What PFT No degree of abnormality on PFT is considered prohibitive for

abnormality is non-lung surgery down to an FEV1 of 450 mL (or generally an
prohibitive for FEV1 of 1000 mL for chest cases).
surgery?

What are Patients with clusters of abnormalities on the PFT studies are
abnormal PFTs more likely to suffer complications than those without
predictive of, underlying pulmonary conditions.
or how are
they helpful?

Are certain Advanced age coupled with FEV1 <2 L, maximum voluntary
PFT findings ventilation <50% predicted, or an abnormal ECG has been
prohibitive for found to portend postoperative difficulties. In general, a
patients patient should have a predicted postoperative FEV1 of at least
undergoing
800 mL. As is the case with non-lung surgery, the correlation
lung
between the degree of abnormality on PFTs and postoperative
resection?
complications is poor (at least when predicted postoperative
FEV1 is >800 mL).

Does use of Yes and no. If the anesthesia is strictly local, as in a nerve
anesthesia block, the answer is yes. But with spinal anesthesia the
(other than answer is no.
general
anesthesia)
decrease
respiratory
complications?

Why is that? Anesthesia itself is only a small contributor to pulmonary

complications. Other factors such as the type of surgery (e.g.,
upper abdominal or thoracic), loss of hyperinflation by
sighing, pain, and sedation all contribute to the development
of pulmonary complications. These factors are present
regardless of the type of anesthesia used.

P.732

Preoperative Use of the Laboratory

 Should every No. The indications for these are provided by the history and
surgery physical examination or by the type of surgery planned.
patient have
preoperative
laboratory
tests?

Is a chemistry This study is appropriate for most individuals, such as those

profile a above 60 years of age with hypertension, diabetes, or renal
routine study disease. Also, patients who take diuretics, bowel preparations,
before or nephrotoxic drugs should undergo a preoperative chemistry
surgery? study.

Is a complete The CBC can be reserved for patients undergoing procedures

blood count in which large blood losses are expected or who have
profile a indication on history and physical examination of anemia.
routine study Others who require a CBC include patients above 60 years of
before age.
surgery?

In whom Any patient actively bleeding or with a known or suspected

should bleeding disorder (including causes such as warfarin or aspirin
coagulation therapy); also patients with liver disease or malabsorption.
studies be
obtained?

P.733

Antibiotic Prophylaxis Before Surgery

Are prophylactic No. Antibiotics are indicated when infection would be
antibiotics particularly serious, when prosthetic or artificial material
always indicated is to be implanted, or when the planned procedure is likely
before surgery? to give rise to infection.

All surgical Use of antibiotics is not without some risk, specifically the
procedures risks of toxicity, allergic reaction, superinfection, and the
involve some risk development of resistance.
of infection, so
why not always
use antibiotic
prophylaxis?

Should the The coverage should be focusedthat is, directed at the

coverage most likely pathogens of potential infectious complication.
 provided by
prophylactic
antibiotics be
broad or narrow?

When would 1. When likely pathogens would not be well covered by

prophylactic cefazolin, as in colorectal surgery or appendectomy.
antibiotics other Under these circumstances, providing
than cefazolin be
indicated?
1. better protection against anaerobic organisms, including
Bacteroides fragilis, would be necessary.
2. When the patient is allergic to beta-lactam antibiotics.
3. In cases of MRSA, which is susceptible to vancomycin.
4. When the patient has prosthetic material in place.

In preoperative The antibiotic should be given just before the procedure to

cases, when ensure that there are adequate drug levels throughout the
should the surgery. In cases of major blood loss or prolonged
antibiotic be operation, a second dose might be indicated.
given?

Should Not usually. An exception is when infectious complications

antibiotics be are likely, as when there is accidental spillage of stool
continued during an abdominal procedure. In such a case, antibiotics
postoperatively? are no longer considered prophylaxis but rather therapeutic
and necessary.

Are prophylactic The need for prophylaxis is determined by the type of

antibiotics procedure performed, not the method of surgery. The use
indicated for of prophylactic antibiotics in laparoscopic surgery is less
laparoscopic well studied than the use of prophylactic antibiotics in
surgery? traditional surgical incisions, but currently
recommendations are the same for both.

Indications and Regimen for Subacute Bacterial

Endocarditis Prophylaxis (Refer to Chapter 3,
Cardiology)
In general terms, for Procedures that are likely to produce bacteremia.
which procedures Sterile procedures do not require specific prophylaxis.
should prophylaxis be Each procedure should be evaluated individually.
given?

P.734
P.735
Deep Venous Thrombosis Prophylaxis
What are the Age older than 40 years, surgery lasting more than 1 hour,
risk factors previous DVT or pulmonary embolus, extensive tumor, hip or
for DVT? knee surgery, major trauma or fractures, and stroke. Other
risk factors include MI, HF, obesity, immobility, postpartum
state, and hypercoagulable state.

Do all surgical Yes, but not necessarily pharmacologic prophylaxis. Patients at

patients low risk of DVT can wear graduated compression stockings and
benefit from undertake early ambulation as prophylactic measures.
DVT
prophylaxis?

Who are the Patients below 40 years of age who are undergoing procedures
patients at lasting <1 hour or patients who are pregnant
low risk for
DVT?

Which Patients include those above 40 years of age who are

patients are undergoing a procedure lasting >1 hour or who have medical
at moderate conditions such as MI or HF. Postpartum patients have
DVT risk? moderate risk of DVT.

What DVT Patients with a moderate risk of DVT often are given
prophylaxis is pharmacologic prophylaxis. Prophylaxis involves the methods
recommended used for low-risk patients plus one of the following:
for patients subcutaneous low-molecular-weight heparin, heparin (5000 U)
at moderate twice per day, intravenous dextran, or external pneumatic
DVT risk? compression devices.

Which Patients above 40 years of age who are undergoing long

patients are procedures, often orthopedic, and might have a history of
at high risk of DVT, pulmonary embolism, stroke, or recent trauma
DVT?

What DVT The best outcomes may occur when a heparin-based therapy
prophylaxis is or oral warfarin is combined with a nonpharmacologic
appropriate intervention such as a pneumatic compression device. May also
for high-risk consider subcutaneous heparin three times daily. Other
patients? therapies used for these patients include warfarin or vena
caval interruption (filter).

Why not use Warfarin is associated with a higher risk of bleeding

 warfarin only complications (approximately 6%) than heparin (approximately
in patients at 2%).
high risk for
DVT?

Is aspirin ever Aspirin is not as effective as the other methods discussed;

used as therefore it is not recommended.
prophylaxis
against DVT?

Why are Dextrans have been associated with anaphylactic reactions,

dextrans they are expensive, and they require intravenous
rarely used as administration.
prophylaxis
for DVT?

What other Fondaparinux has been shown to be beneficial in patients at

methods of moderate DVT risk. Hirudin is promising based on results of
DVT early trials. Murine monoclonal antibodies that bind the
prophylaxis fibrinogen receptor on platelets are in development.
are in
development?

P.736
P.737

Perioperative Management of the Diabetic Patient

Why is the type Type 1 diabetic patients are prone to ketoacidosis, whereas
of diabetes type 2 diabetic patients generally are not. Both are subject
(i.e., type 1 or to variations in glucose control perioperatively, given NPO
type 2) status (hypoglycemia) and the stress of illness and surgery
important to (hyperglycemia).
distinguish
during the
perioperative
period?

In general, how While NPO, the patient is given intravenous glucose and
is the type 1 insulin drips at 1 to 3 U/hr with titration (sliding scale)
diabetic patient based on serum glucose levels.
managed
perioperatively?

How is the Type 2 insulin-requiring diabetic patients are generally given

insulin- half their usual dose of long-acting insulin on the morning of
requiring type the surgery. Their blood glucose is then monitored
2 diabetic frequently via finger sticks. Infusions or subcutaneous
patient injections of insulin and glucose are adjusted accordingly.
managed
perioperatively?

In general, how Patients should have their oral agent discontinued 1 day
should the before surgery; those on metformin 1 to 2 days before; and
patient whose those on chlorpropamide 2 to 3 days before. Patients often
diabetes is require no exogenous glucose or insulin, but these may be
controlled on used if necessary. Serum glucose should be monitored in
oral anticipation of such a possibility.
hypoglycemics
be managed for
surgery?

How is the Diet-controlled diabetic patients can often undergo surgery

patient with without any glucose or insulin. Intravenous fluids should lack
diet-controlled dextrose, and the patient's blood glucose level should be
diabetes monitored throughout the procedure. Insulin and glucose
managed for should be administered if needed.
surgery?

What is a Generally, <140 mg/dL is considered an acceptable range.

reasonable
target range for
blood sugars in
diabetic
patients
undergoing
surgery?

In patients It is better to have blood sugars run somewhat high than to

whose blood risk insulin shock. However, it should also be kept in mind
sugar is difficult that higher blood sugars predispose to worse outcomes
to maintain, is owing to infections and wound healing.
it better to be
on the high side
or the low side
of the
acceptable
range?

Why is the Small-vessel disease results in tissue ischemia. Also,

diabetic patient hyperglycemia impairs phagocytosis, and gastroparesis
at increased increases the risk of aspiration pneumonia.
risk of
infection?

Does the No. The pathology in diabetic circulation is microvascular in

presence of nature.
palpable
peripheral
pulses rule out
the presence of
tissue ischemia
in diabetic
patients?

What are the Important elements in the history include duration of

factors that disease, current medications, current diet, typical blood
play a role in sugar levels, and preexisting complications such as
determining retinopathy, nephropathy, and neuropathy. Also, a history of
postoperative angina, previous MI, claudication, activity limitation, and
complications in other major cardiac risk factors (e.g., family history,
diabetic smoking, hypertension, and hyperlipidemia). The type of
patients? surgery planned and type of anesthesia are also factors.

What should be Vital signs, heart and lung examination findings, and
observed on condition of extremities. Degree of hygiene, any ulcers,
physical evidence of poor perfusion (e.g., decreased hair growth and
examination of decreased pulses), and neurologic findings should be noted.
a diabetic
patient?

Why is Patients with peripheral neuropathy are much more prone to

peripheral extremity complications, with their attendant morbidity and
neuropathy an mortality.
important
perioperative
finding?

What laboratory Blood glucose level, HbA1C, electrolytes (especially sodium

evaluations are and potassium), BUN, creatinine, and urinalysis. Thyroid
needed for studies may be indicated if history and physical examination
diabetic suggest any abnormality.
patients
preoperatively?

Is chronic renal No, but it indicates a need for meticulous attention to

 insufficiency a volume and electrolyte status perioperatively.
contraindication
to surgery?

Why might a Diabetic gastroparesis predisposes the patient to aspiration

diabetic patient during surgery.
be instructed to
fast for a full
12 hours before
surgery?

P.738

Postoperative Fever
What are the The 5 W's of postoperative fever are as follows:
common Wind (atelectasis)
causes of Water (urinary tract infection)
postoperative Wound (wound infection)
fever? Walking (DVT)
Wonder drugs (drug reaction)

Which of the Atelectasis.

five W's is
the most
common
cause of
fever?

What is the Treatment involves incentive spirometry, chest physical

treatment of therapy, and ambulation.
atelectasis?

Should Antibiotics should be avoided until a source of infection is

antibiotics be diagnosed by repeated careful, comprehensive history and
given to physical examinations. Surgical wounds should be carefully
patients with evaluated for evidence of infection. Urinalysis and culture as
postoperative well as culture of blood and all invasive catheters should be
fever? carried out.

Miscellaneous Mnemonics
What is the mnemonic for altered mental TIPS AEIOU:
status? Trauma and Temperature
Infection
Psychiatric disorder or
 Poison
Sepsis, Stroke, Seizure, or
Space-occupying lesion
Alcohol intoxication or
withdrawal
Electrolyte imbalance
Insulin (hyperglycemia or
hypoglycemia)
Overdose or O 2 deficit
Uremia

What is the mnemonic for acidosis without HEART CCU:

anion gap? Hyperaldosteronism
Expansion (volume)
Acid loading
Renal tubular acidosis
Turds (diarrhea,
pancreatitis)
Chronic pyelonephritis
Carbonic anhydrase
inhibitors
Ureterojejunostomy

How do the glucocorticoids compare in Don't Stop Prednisone

potency with respect to hydrocortisone? Hastily:
Dexamethasone (25 times
more potent)
Solumedrol (5 times more
potent)
Prednisone (4 times more
potent)
Hydrocortisone

P.739

Alternative Medications and Surgery

How often do Approximately 30% to 50% of patients use
patients use neutraceuticals.
alternative
(neutraceutical)
medications?

What percent of Approximately 10%

patients admit to
using
 neutraceuticals?

Why should the

following herbal
medications be
discontinued before
surgery?

Echinacea Associated with liver dysfunction in patients with

preexisting liver disease

Ephedra Associated with hyperpyrexia, hypertension, and coma

(when used with monoamine oxidase inhibitors); MI,
cerebrovascular accident, cardiovascular collapse (the
latter caused by catechol depletion)

Garlic Associated with bleeding as a result of inhibition of

platelet function

Gingko Potential to increase bleeding

Ginseng Associated with bleeding as a result of inhibition of

platelet function

Kava May produce prolonged sedation (interaction with

anesthetics)

St. John's wort May increase metabolism of several medications like

warfarin, cyclosporine, calcium channel blockers,
selective serotonin reuptake inhibitors, midazolam, and
nonsteroidal anti-inflammatory drugs

Valerian Benzodiazepine-like withdrawal after abrupt

discontinuation

P.740

Trials
Goldman L, Caldera DL, Nussbaum SR. Multifactorial index of cardiac risk in
noncardiac surgical procedures. N Engl J Med 1977;297:845580.

A classic perioperative screening tool.

L'Italien GJ, Paul SD, Hendel RC, et al. Development and validation of a
Bayesian model for perioperative cardiac risk assessment in a cohort of 1081
vascular surgical candidates. J Am Coll Cardiol 1996;27:779786.
A perioperative screening tool.

Lee TH, Marcantonio ER, Mangione CM, et al. Derivation and prospective
validation of a simple index for prediction of cardiac risk of major noncardiac
surgery. Circulation 1999;100:10431049.

The Cardiac Risk Index scale.

Lindenauer PK, Pekow P, Wang K, et al. Perioperative beta-blocker therapy

and mortality after major noncardiac surgery. N Engl J Med 2005;353:349361.

An adaptation of the Lee Cardiac Risk Index.

Hertzer NR, Beven EG, Young JR, et al. Coronary artery disease in peripheral
vascular patients. A classification of 1000 coronary angiograms and results of
surgical management. Ann Surg 1984;199:223233.

An observational study looking at the incidence of CAD in patients undergoing

vascular surgery at the Cleveland Clinic.

Eagle KA, Berger PB, Calkins H, et al. ACC/AHA guideline update for
perioperative cardiovascular evaluation for noncardiac surgeryexecutive
summary: a report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines

P.741
(Committee to Update the 1996 Guidelines on Perioperative Cardiovascular
Evaluation for Noncardiac Surgery). J Am Coll Cardiol 2002;39:542553.

The statement of the American College of Cardiology and the American Heart
Association on preoperative care.

Landesberg G, Shatz V, Akopnik I, et al. Association of cardiac troponin, CK-

MB, and postoperative myocardial ischemia with long-term survival after major
vascular surgery. J Am Coll Cardiol 2003;42:15471554.

At 5 years patients who suffered a perioperative MI and had a troponin I >3.1

(troponin T >0.2) had a survival rate of only 35% compared with patients with a
troponin I of <0.06 (troponin T of <0.03) with a survival of >80%.

McFalls EO, Ward HB, Moritz TE, et al. Coronary-artery revascularization before
elective major vascular surgery. N Engl J Med 2004;351:27952804.

Survival in 510 patients randomized to revascularization or not. A total of 5859

patients screened at 18 VAs for an expanding AAA, or PAD of the legs. Patients
were excluded for emergency surgery, severe comorbids, or prior
revascularization without evidence of recurrent ischemia, or LMCA >50%, EF <20%
and severe AS. Patients had cath and eligible if >70% stenosis and suitable for
revascularization; 240 had revasc: CABG 41% (99) and PTCI 141 (59%) but only
225 had the planned vascular procedure (10 died after CABG or PTCI). This study
was underpowered and applicability is limited.
Harvey S, Harrison DA, Singer M, et al. Assessment of the clinical effectiveness
of pulmonary artery catheters in management of patients in intensive care (PAC-
Man): a randomised controlled trial. Lancet 2005;366:472477.

The routine use of a PA catheter in medical and surgical patients does not lower
the risk of events.