General pathology

Dr Noura H:Abdirahman
 Course out line
 Chapter 1:introduction of pathology
 Chapter 2: Cell injury ,adaptation and cell death .
 Chapter 3 : Inflammation
 Chapter 4 : Repear and healing
 Chapter 5 : Hemodynamic disorder
 Chapter 6 : Neplasia
 Chapter 7 :Infectious disease
 Chapter 8 : Genetic disesase
 Chapter 9 : Immunopathology
 Chapter 10 ; Enviromental and nutritional pathology
 Chapter 11 : Disease of infancy and childhood
Marks
 5% Quiz
 5% Assignment
 10% Presentation/class
discussion
 30% Mid term
 50 % Final exam
 Total 100
Reference books
 Text book of pathology Harsh mohan
 Robbins Basic pathology
General pathology
INTRODUCTION
INTRODUCTION TO PATHOLOGY

 Learning Objectives
1. Define pathology
2. Discuss the core aspects of disease in
pathology
3. Know the diagnostic techniques used in
pathology
4. Know the various categories of the causes
of diseases
5. Know the course, outcome, consequences
of diseases
6. clinical and biological death
The core aspects of diseases in
pathology
Pathology is the study of disease by
scientific methods. The word
pathology came from the Latin words
“patho” & “logy”. ‘Patho’ means
disease and ‘logy’ means study,
therefore pathology is a scientific
study of disease.
 Diseases may, in turn, be defined as
an abnormal variation in structure or
function of any part of the body.
Pathology gives explanations of a
disease by studying the following
four aspects of the disease.
1. Etiology.
2. Pathogenesis
3. Morphologic changes .
4. Functional derangements and
clinical significance.
 1. Etiology

 Etiology of a disease means the cause of the disease.
 If the cause of a disease is known it is called primary
etiology.
 If the cause of the disease is unknown it is called
idiopathic.
 Knowledge or discovery of the primary cause
remains the backbone on which a diagnosis can be
made, a disease understood, & a treatment developed.
There are two major classes of etiologic factors:
genetic and acquired (infectious, nutritional, chemical,
physical, etc).
 The etiology is followed by pathogenesis.
 2. Pathogenesis

Pathogenesis means the mechanism
through which the cause operates to
produce the pathological and clinical
manifestations.
The pathogenetic mechanisms could
take place in the latent or incubation
period.
Pathogenesis leads to morphologic
changes.
 3. Morphologic changes
The morphologic changes refer to the
structural alterations in cells or tissues that
occur following the pathogenetic
mechanisms.
The structural changes in the organ can be
seen with the naked eye or they may only be
seen under the microscope.
Those changes that can be seen with the
naked eye are called gross morphologic
changes & those that are seen under the
microscope are called microscopic changes.
Both the gross & the microscopic
morphologic changes may only be seen in
that disease, i.e. they may be specific to
that disease.
Therefore, such morphologic changes can
be used by the pathologist to identify (i.e. to
diagnose) the disease.
In addition, the morphologic changes will
lead to functional alteration & to the clinical
signs & symptoms of the disease.
 4. Functional derangements and
clinical significance
The morphologic changes in the organ
influence the normal function of the organ.
By doing so, they determine the clinical
features (symptoms and signs), course,
and prognosis of the disease.
In summary, pathology studies:-
Etiology
Pathogenesis
Morphologic changes
Clinical features & Prognosis of all
Understanding of the above core aspects
of disease (i.e. understanding pathology)
will help one to understand how the
clinical features of different diseases
occur & how their treatments work.
In addition, the pathologist can use the
morphologic changes seen in diseases to
diagnose different diseases.
There are different diagnostic modalities
used in pathology.
Most of these diagnostic techniques are
based on morphologic changes.
 III. Diagnostic techniques used in
pathology

The pathologist uses the following techniques

to the diagnose diseases:
a. Histopathology
b. Cytopathology
c. Hematopathology
d. Immunohistochemistry
e. Microbiological examination
f. Biochemical examination
g. Cytogenetics
h. Molecular techniques
 A. Histopathological techniques

Histopathological examination studies

tissues under the microscope. During this
study, the pathologist looks for abnormal
structures in the tissue.
Tissues for histopathological examination
are obtained by biopsy. Biopsy is a tissue
sample from a living person to identify the
disease.
 Biopsy can be either incisional or
excisional.
Once the tissue is removed from the patient,
The purpose of fixation is:
1. To prevent autolysis and bacterial
decomposition
2. To coagulate the tissue to prevent
loss of easily diffusible substances
3 To leave the tissues in a
condition which facilitates
differential staining with dyes and
other reagents.
Once the tissue arrives at the pathology
department, the pathologist will exam it
macroscopically (i.e. naked-eye examination of
tissues).
Then the tissue is processed to make it ready
for microscopic examination. The whole
purpose of the tissue processing is to prepare a
very thin tissue (i.e. five to seven μm or one cell
thick tissue) which can be clearly seen under
the microscope.
The tissue is processed by putting it into
different chemicals. It is then impregnated
(embedded) in paraffin, sectioned (cut) into thin
 B. Cytopathologic techniques

 Cytopathology is the study of cells from various body
sites to determine the cause or nature of disease.
Applications of cytopathology:
The main applications of cytology include the following:
1. Screening for the early detection of asymptomatic
cancer For example, the examination of scrapings from
cervix for early detection and prevention of cervical
cancer.
2. Diagnosis of symptomatic cancer Cytopathology may
be used alone or in conjunction with other modalities
to diagnose tumors revealed by physical or radiological
examinations.
 It can be used in the diagnosis of cysts, inflammatory
conditions and infections of various organs.
3. Surveillance of patients treated for
cancer For some types of cancers,
cytology is the most of easible method
of surveillance to detect recurrence. The
best example is periodic urine cytology
to monitor the recurrence of cancer of
the urinary tract.
Advantages of cytologic examination

Compared to histopathologic technique

a. It is cheap,
b. Takes less time
c. Needs no anesthesia to take
specimens.
 Cytopathologic methods

 There are different cytopathologic methods including:
1. Fine-needle aspiration cytology (FNAC)
 In FNAC, cells are obtained by aspirating the
diseased organ using a very thin needle under
negative pressure. Virtually any organ or tissue
can be sampled by fine-needle aspiration.
 The aspirated cells are then stained & are studied
under the microscope. Superficial organs (e.g.
thyroid, breast, lymph nodes, skin and soft tissues)
can be easily aspirated.
 Deep organs, such as the lung, mediastinum, liver,
pancreas, kidney, adrenal gland, and
retroperitoneum are aspirated with guidance by
fluoroscopy, ultrasound or CT scan. FNAC is
cheap, fast, & accurate in diagnosing many
diseases.
2. Exfoliative cytology

Refers to the examination of cells that

are shed spontaneously into body fluids
or secretions.
Examples include sputum, cerebrospinal
fluid, urine, effusions in body cavities
(pleura, pericardium, peritoneum).
 3. Abrasive cytology

Refers to methods by which cells are

dislodged by various tools from body
surfaces (skin, mucous membranes, and
serous membranes).
 E.g. preparation of cervical smears with a
spatula or a small brush to detect cancer
of the uterine cervix at early stages.
Such cervical smears, also called Pap
smears, can significantly reduce the
mortality from cervical cancer..
 C. Hematological examination

This is a method by which abnormalities

of the cells of the blood and their
precursors in the bone marrow are
investigated to diagnose the different
kinds of anemia & leukemia.

D. Immunohistochemistry
This is a method is used to detect a
specific antigen in the tissue in order to
identify the type of disease.
 E. Microbiological examination

 This is a method by which body fluids,

excised tissue, etc. are examined by
microscopical, cultural and serological
techniques to identify micro-organisms
responsible for many diseases.

F. Biochemical examination
 This is a method by which the metabolic
disturbances of disease are investigated by
assay of various normal and abnormal
compounds in the blood, urine, etc.
 G. Clinical genetics (cytogenetics),

This is a method in which inherited
chromosomal abnormalities in the germ
cells or acquired chromosomal
abnormalities in somatic cells are
investigated using the techniques of
molecular biology.

H. Molecular techniques
Different molecular techniques such as
fluorescent in situ hybridization, Southern
blot, etc.
can be used to detect genetic diseases.
 I. Autopsy

 Autopsy is examination of the dead body to
identify the cause of death. This can be for
clinical purposes.
 The relative importance of each of the above
disciplines to our understanding of disease varies
for different types of diseases.
 For example, in diabetes mellitus, biochemical
investigation provides the best means of
diagnosis and is of greatest value in the control of
the disease.
 Whereas in the diagnosis of tumors, FNAC &
histopathology contribute much.
 However, for most diseases, diagnosis is based
 IV. The causes of disease

 Diseases can be caused by either
environmental factors, genetic factors or a
combination of the two.
A. Environmental factors
Environmental causes of disease are many and
are classified into:
1. Physical agents
2. Chemicals
3. Nutritional deficiencies & excesses
4. Infections
5. Immunological factors
6. Psychogenic factors
 1. Physical agents

 These include trauma, radiation, extremes of temperature,
and electric power. These agents apply excess physical
energy in any form to the body.
2. Chemicals
 With the use of an ever-increasing number of chemical
agents such as drugs, in industrial processes, and at home,
chemically induced injury has become very common. Their
effects vary:
 Some act in a general manner, for example cyanide is toxic
to all cells.
 Others act locally at the site of application, for example
strong acids and caustics.
 Another group exhibit a predilection for certain organs, for
example – the effect of paracetamol and alcohol on liver.
Many toxic chemicals are metabolized in liver and
excreted in kidney, as a result, these organs are susceptible
to chemical injury.
 3. Nutritional deficiencies and excesses

 Nutritional deficiencies may arise as a result of poor

supply, interference with absorption, inefficient
transport within the body, or defective utilization.
 It may take the form of deficiency either of major
classes of food, usually protein and energy, or
vitamins or elements essential for specific
metabolic processes, e.g. iron for haemoglobin
production.
 Often, the deficiencies are multiple and complex.
 Obesity has become increasingly common, with
its attendant dangers of type 2 diabetes, high
blood pressure and heart disease.
 4. Infections
 Viruses, bacteria, fungi, protozoa, and metazoa
all cause diseases.
 They may do so by causing cell destruction
directly as in virus infections (for example
poliomyelitis) or protozoal infections (for
example malaria).
 However, in others the damage is done by toxins
elaborated by the infecting agent as in diphtheria
and tetanus.
 Like chemicals, they may have a general effect
or they may show a predilection for certain
tissues.
 5. Immunological factors

 The immune process is essential for protection
against micro-organisms and parasites.
 However, the immune system can be abnormal
which can lead to diseases.
 The abnormalities of the immune system include:

A. Hypersensitivity reaction
 This is exaggerated immune response to an antigen.
 For example, bronchial asthma can occur due to
exaggerated immune response to the harmless
pollen.
B. Immunodeficiency
 This is due to deficiency of a component of the
immune system which leads to increased
susceptibility to different diseases. An example is
AIDS.

C. Autoimmunity
 This is an abnormal immune reaction against the
self antigens of the host.
 Therefore, autoimmunity is a hypersensitivity
reaction against the self antigens.
 For example, type 1 diabetes mellitus is caused by
autoimmune destruction of the beta cells of the
islets of Langerhans of the pancreas.
 6. Psychogenic factors

 The mental stresses imposed by conditions of life,

particularly in technologically advanced
communities, are probably contributory factors in
some groups of diseases.
B. Genetic Factors

 These are hereditary factors that are inherited

genetically from parents.
V. Course of disease

 The course of disease is shown with a simplified

diagram as follows.
a. Exposure (causative)
b. latency period
C. biological onset
d. Clinical onset
e. Permanent damage
f. Death
 The course of a disease in the absence of any
intervention is called the natural history of the disease.
 The different stages in the natural history of disease
include:
a. Exposure to various risk factors (causative agents)
b. Latency, period between exposure and biological
onset of disease
c. Biological onset of disease; this marks the initiation
of the disease process, however, without any sign or
symptom. Following biological onset of disease, it
may remain asymptomatic or subclinical (i.e. without
any clinical manifestations), or may lead to overt
clinical disease.
d. Incubation (induction) period refers to variable period
of time without any obvious signs or symptoms from
the time of exposure.
e) The clinical onset of the disease, when the signs
and symptoms of the disease become apparent.
The expression of the disease may be variable in
severity or in terms of range of manifestations.
f)The onset of permanent damage.
g) Death
 VI. Outcome and consequences of
disease

 Following clinical onset, disease may follow any

of the following trends:
a. Resolution can occur leaving no sequelae,
b. The disease can settle down, but sequelae are
left.
c. It may result in death.
 VII. Clinical & biologic death

Clinical death
Clinical death is the reversible
transmission between life and biologic
death.
 Clinical death is defined as the period of
respiratory, circulatory and brain arrest
during which initiation of resuscitation
can lead to recovery.
 Clinical death begins with either the last agonal
inhalation or the last cardiac contraction.
 Signs indicating clinical death are
The patient is without pulse or blood pressure
and is completely unresponsive to the most
painful stimulus.
The pupils are widely dilated
Some reflex reactions to external stimulation are
preserved. For example, during intubations,
respiration may be restored in response to
stimulation of the receptors of the superior
laryngeal nerve, the nucleus of which is located
in the medulla oblongata near the respiratory
center.
Recovery can occur with resuscitation.
 Biological Death

Biological death (sure sign of death),

which sets in after clinical death, is an
irreversible state of cellular destruction.
It manifests with irreversible cessation of
circulatory and respiratory functions, or
irreversible cessation of all functions of
the entire brain, including brain stem.
CELL INJURY ,CELL DEATH AND
CELL ADAPTATIONS

OVERVIEW OF CELLULAR
RESPONSES

TO STRESS AND NOXIOUS STIMULI.
 Cells are active participants in their environment,
constantly adjusting their structure and function
to accommodate changing demands and
extracellular stresses.
 Cells normally maintain a steady state called
homeostasis in which the intracellular milieu is
kept within a fairly narrow range of physiologic
parameters.
 As cells encounter physiologic stresses or
pathologic stimuli, they can undergo adaptation,
achieving a new steady state and preserving
viability and function.
 The principal adaptive responses are hypertrophy,
hyperplasia, atrophy, and metaplasia.
 If the adaptive capability is exceeded or if the
external stress is inherently harmful, cell injury
develops .
 Within certain limits, injury is reversible, and cells
return to a stable baseline; however, if the stress
is severe, persistent and rapid in onset, it results
in irreversible injury and death of the affected
cells.
Cellular adaptation
 Adaptations are reversible changes in the number,
size, phenotype, metabolic activity, or functions of
cells in response to changes in their environment.
 Physiologic adaptations usually represent
responses of cells to normal stimulation by
hormones or endogenous chemical mediators
(e.g., the hormone-induced enlargement of the
breast and uterus during pregnancy).
 Pathologic adaptations are responses to stress
that allow cells to modulate their structure and
function and thus escape injury Such adaptations
can take several distinct forms.
Types of cellular adaptation

 The types of cellular adaptation include

1 Hypertrophy.
2 Hyperplasia.
3 Atrophy.
4 Metaplasia .
5 Displasia
 Hypertrophy
Definition :hypertrophy is an increase in
the size of cells resulting in increase in
the size of the organ.
Hypertrophy can be physiologic or
pathologic and is caused either by
increased functional demand or by growth
factor or hormonal stimulation.
Examples: the enlargement of the left
ventricle in hypertensive heart disease &
the increase in skeletal muscle during
sternous exercise
 Hyperplasia
Definition :hyperplasia is an increase in the number
of cell in a tissue or organ .
 Hyperplasia can be physiologic or pathologic. In
both situations, cellular proliferation is
stimulated by growth factors that are produced
by a variety of cell types.
 The two types of physiologic hyperplasia are
(1) hormonal hyperplasia, exemplified by the
proliferation of the glandular epithelium of the
female breast at puberty and during pregnancy.
(2) Compensatory hyperplasia, that is, hyperplasia
that occurs when a portion of the tissue is
removed or diseased.
Cont…
 Most forms of pathologic hyperplasia are
caused by excessive hormonal or growth
factor stimulation.
 Atrophy

 Definition :Shrinkage in the size of the cell by the loss

of cell substance is known as atrophy.
Causes
 Decreased workload .
 Loss of innervations.
 Diminished blood supply.
 Inadequate nutrition .
 Loss of endocrine stimulation .
 Aging (senile atrophy).
 metaplasia
Metaplasia is the replacement of one differentiated
tissue by another differentiated tissue. There are
different types of metaplasia include:
1. Squamous metaplasia
This is replacement of another type of epithelium
by squamous epithelium. For example, the
columnar epithelium of the bronchus can be
replaced by squamous epithelium in cigarette
smokers
2. Osseous metaplasia
This replacement of a connective tissue by bone,
for example at sites of injury
Dysplasia
Definition : dysplasia is an abnormal
proliferation of cells that is
characterized by changes in cell size ,
shape and loss of cellular organization.
Dysplasia is not cancer but may
progress to cancer .
Example cervical dysplasia.