Memorix

Clinical
Medicine
Conrad Droste and
Martin von Planta

CHAPMAN & HALL MEDICAL

 /

Memorix Clinical Medicine

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Memorix
The Memorix series consists of easy to use pocket books in a number of
different medical and surgical specialities. They contain a vast amount of
practical information in very concise form through the extensive use of tables
and charts, lists and hundreds of clear line diagrams, often in two colours.

Memorix will give students, junior doctors and some of their senior colleagues a
handy and comprehensive reference in their pockets.

Titles in the series include:

Obstetrics
Thomas Rabe

Gynecology
Thomas Rabe

Neurology
Peter Berlit

Emergency Medicine
Sonke Miiller

Surgery
Jiirgen Hussmann and Robert Russell

Clinical Medicine
Conrad Droste and Martin von Planta

Pediatrics
Dieter Harms and Jochem Scharf

Physiology
Robert Schmidt, W.D. Willis and L. Reuss
Memorix
Clinical Medicine

Conrad Droste and

Martin von Planta
Translated and adapted by
Dennis Guttmann ma, bm BCh, bsc, frcp

CHAPMAN & HALL MEDICAL

London •
Weinheim •
New York
Tokyo •
Madras
Published by Chapman & Hall, 2-6 Boundary Row, London SE1 8HN, UK
Chapman & Hall, 2-6 Boundary Row, London SE1 8HN, UK
Chapman & Hall GmbH, Pappelallee 3, 69469 Weinheim, Germany
Chapman & Hall USA, 115 Fifth Avenue, New York, NY 10003, USA
Chapman & Hall Japan, ITP-Japan, Kyowa Building, 3F, 2-2-1 Hirakawacho, Chiyodaku,
Tokyo 102, Japan
Chapman & Hall India, R. Seshadri, 32 Second Main Road, CIT East, Madras 600 035, India

English language edition 1997

© 1997 Chapman & Hall

Original German language edition - Memorix Konstanten der Klinischen Medizin. Third edition
© 1993, VCH Verlagsgesellschaft mbH, D-6940 Weinheim, Germany
Typeset in Times by Best-set Typesetter Ltd, Hong Kong
Printed and bound in Hong Kong
ISBN 412 56050 X
Apart from any fair dealing for the purposes of research or private study, or criticism or review,
as permitted under the UK Copyright Designs and Patents Act, 1988, this publication may not be
reproduced, stored, or transmitted, in any form or by any means, without the prior permission in
writing of the publishers, or in the case of reprographic reproduction only in accordance with the
terms of the licences issued by the Copyright Licensing Agency in the UK, or in accordance with
the terms of licences issued by the appropriate Reproduction Rights Organization outside the
UK. Enquiries concerning reproduction outside the terms stated here should be sent to the
publishers at the London address printed on this page.
The publisher makes no representation, express or implied, with regard to the accuracy of the
information contained in this book and cannot accept any legal responsibility or liability for any
errors or omissions that may be made.

A catalogue record for this book is available from the British Library

Library of Congress Catalog Card Number: 96-83979

 CONTENTS
List of contributors xv
Preface xvii

Preface to the first and second editions xviii

Translator's note xix

List of symbols xx
Short contents xxi

General principles 1

Nomogram for determination of body surface area 1

Determination of expected date of delivery 2
Skin alterations 3
Clinical classification of skin lesions 3
Eye test chart 4
Hearing tests 5
Adult dentition 5
Catheter and needle sizes 6
Calculation of the drip rate of infusions 7
Patient population 8
Epidemiological and demographic parameters 8
SI units 9
Normal chemical values 10
Normal enzyme values 11
Plasma alcohol (blood alcohol) determination 11
Alcohol intoxication 11
Antabuse reaction 11
Conversion scales 1 12
Conversion scales 2 13
Conversion scales 3 14
Conversion scales 4 15
US & UK/metric system conversion scales: length and weight 16
US/metric system conversion scales: volume and temperature 17
UK/metric system conversion scales: volume 18

Radiology 19
Radiological unit conversion scales 19
Patient positions for X-rays 20
Checklist for assessing a chest X-ray 21
Chest X-rays: diagnostic procedure 21
CONTENTS
Common sources of diagnostic errors 21
Systematic analysis of morphological structures in chest X-rays 22
Identifiable mediastinal lines 22
Differentiation between interstitial and alveolar shadowing 23
Lung alterations 23
Diagnosis of lymph node enlargement 24
Bronchopulmonary segments - CT 25
Radiological appearance of consolidation of individual
bronchopulmonary segments 26
Cardiac outlines 27
Cardiothoracic ratio 28
Enlargement of individual heart chambers 28
Pulmonary venous congestion 30
Radiological signs of pulmonary hypertension 31
Summary of skeletal radiology 32
Osteoarthritis/inflammatory arthritis 33
Radiological signs of non-inflammatory changes of the spine 34
Radiology of the vertebra 34
Bone metastases 35
Typical distribution of bone metastases 35
Lateral skull 36
Skull AP 37
Sinuses 38
CT cross-sectional topography 39
CT retroperitoneal spaces and pelvis 43
Retroperitoneal fascial spaces 43
CT anatomy of (left) acetabulum - axial section 43
CT skull 44
Magnetic resonance imaging - indications 45
Magnetic resonance imaging - head 46
MRI appearances of brain structures 47
Image planes 47
Female pelvis - normal anatomy 47
Retroperitoneal space 47
Knee joint - sagittal 47

Cardiology and angiology 49

NYHA criteria 49
Assessment of cardiovascular risk before non-cardiac operation 49
Central venous pressure 50
Hepatojugular reflux 50
Auscultation areas 51
 CONTENTS
Heart sounds and extra sounds 51
Sound intensity 51
ECG - electrode positions 52
Long-term ECG 52
ECG - normal values 53
ECG - ruler 54
ECG axes/QT duration 55
Points system for left ventricular hypertrophy 56
Points system for right ventricular hypertrophy 57
Stress testing 58
Coronary arteries - nomenclature 59
Myocardial scintigram 60
X-ray ventriculogram 61
Echocardiography 61
Nuclear medicine 61
Echocardiography TM - normal values 62
Echocardiography TM - ventricle 63
ECG changes in infarct 64
Time course of typical changes after acute myocardial infarct 65
Heart valve abnormalities 66
Heart valve prostheses 70
Systolic and diastolic flow rates of the normal and diseased heart 72
Endocarditis prophylaxis 73
Cardiac cycle 74
Cardiovascular normal values 75
Swan-Ganz balloon catheter 76
Cardiomyopathies 77
Cardiac transplantation 78
Conducting system of the heart 79
Heart block 80
Lown classification of VES 81
WHO classification of calcium antagonists 81
Classification of anti-arrhythmic agents 82
Beta-adrenergic blocking agents 84
Pacemakers 85
Pacemaker (PM) testing 85
De Bakey's classification of aortic dissections 86
Allen test 86
Fontaine's classification of peripheral vascular disease 87
Ratschow's positioning test 87
Abdominal arteries 88
Pelvic arteries 89
Arteries of the leg 90

vii
CONTENTS
Radiological anatomy of the great veins of the leg 91
Common anatomical variants 91
Varicose veins 92
Orthostatic hypotension 93
Classification of hypertension 94
Step scheme for treatment of arterial hypertension 95
Recommendations for combination therapy 95
Investigation of hypertension 96
Assessment and treatment of 'mild hypertension' 98
Differential therapy in hypertension 98
Unwanted effects of hypertension therapy 99
Hyperlipidaemias 100
Lipid-lowering drugs 101
Hyperlipidaemia therapy 102

Chest medicine 105

Estimation of daily cigarette consumption 105
Differential diagnosis of pleural effusion 106
Lung function tests 107
Bronchial asthma 108
Management of chronic asthma in adults 109
Recommendations for diagnosis, staging and surgical
treatment of carcinoma of bronchus 110
TNM categories 111
Carcinoma of bronchus - histology 112
Carcinoma of bronchus - surgery 113
Scheme for preoperative function tests 113
Treatment of tuberculosis 114
Dosage for standard unsupervised (daily) 6-month regimen 114
Dosage for fully supervised intermittent 6-month regimen 114
Tuberculin testing 115
International classification of pneumoconiosis 116

Emergencies, acid-base balance and disturbances,

electrolytes 117
Cardiopulmonary resuscitation 117
Cardiac arrest 118
Antidotes in poisoning 119
Activated charcoal administration in poisoning 120
Vesicle formation in poisoning 120
Poisons information centres 121
Estimation of suicide risk 122
 CONTENTS
Activity profiles of antidepressants 122
Side effects of tri- and tetracyclics 122
Review of psychotropic drugs 123
Activity profile of neuroleptic drugs 123
Short test of cerebral function 124
Substance abuse 125
acid-base disturbances 126
acid-base nomogram 127
Blood gas analysis (normal values) 128
Estimation of acid-base disturbances 128
Sodium and potassium 129
Potassium replacement and pH 129
Calcium and phosphorus 130
Magnesium 131
Syndrome of inappropriate ADH secretion (SIADH) 131

Gastroenterology 133
Anatomy of the digestive organs 133
Abdominal ultrasound - anatomy and technique 134
Ultrasound of the liver 135
Ultrasound of gall bladder, pancreas and kidney 136
Ultrasound of adrenals and spleen 137
Acute abdomen 138
Ileus 140
Gastrointestinal bleeding 141
Diagnostic sequence of upper GI bleeding 141
Crohn's disease/ulcerative colitis 142
Classification of degree of severity 143
Pancreas and pancreatitis 144
Oesophageal varices haemorrhage 145
Diagnosis of ascites 147
Treatment of portal ascites 147
Portal hypertension 148
Jaundice 149
Gallstones 150
Types of hepatitis 152
Hepatitis immunization 152
Serological course of hepatitis 153
Hepatitis B markers 154
Hepatitis A markers 154
Interpretation of serological markers in acute and chronic
viral hepatitis 154
CONTENTS
Chronic active hepatitis 155
Liver transplantation 156
Endoscopic staging of abdominal disorders 157
Gastrointestinal tumours 158
Function tests 159
Ulcer therapy 159
Chronic gastritis 159

Nephrology 161
Renal anatomy 161
Nephrological formulae 162
Urine normal values 163
Erythropoietin 163
Summary of renal syndromes 164
Differential diagnosis of acute renal failure 165
Urine findings in acute renal failure 165
Subjective symptoms dependent on renal failure 165
Management of renal failure 166
Uraemia 167
Nephrolithiasis 168
Proteinuria 168
Haematuria 168
Red urine 169
Erythrocytes 169
Urinary tract infection 170
Diuretics 171
Dialysis 172
Organ donation 173
Renal transplantation 174

Infections 175
Pyrexia 175
Types of fever 175
Pyrexia of undetermined origin 176
Bacteriological stains - direct preparations 177
The commonest pathogens in Gram stain preparations 177
Interpretation of aspirates 178
Common viral infections 179
Methods of laboratory diagnosis in viral illnesses 180
Collection and despatch of material for investigation 181
Antiviral agents 182
 CONTENTS
The immunocompromised patient 183
AIDS: definition and classification 184
Investigation of AIDS 186
Therapy of the most important pathogens in HIV infection 187
Empirical therapy of infections 189
Sepsis with unknown primary site 189
Endocarditis 190
Pneumonia 190
Intra-abdominal infection 192
Urinary sepsis 192
Infections of the central nervous system 193
Pyrexia with neutropenia 195
Antituberculous drugs 196
Syphilis 197
Immunization recommendations for childen and adults 198
Childhood immunization schedule 199
Adult immunizations important for individual and public health 200

Haematology 201
Sedimentation rate 201
Protein electrophoresis 201
Peripheral blood and bone marrow cells 202
Haematological normal values 204
Blood count 204
Iron metabolism 204
Important laboratory parameters for iron metabolism 204
Stages of blood cell formation 205
Red cell morphology 206
Investigation of anaemia 207
Diagnostic criteria of polycythemia vera 207
Coombs' test 208
Differential diagnosis of enlarged lymph nodes 209
Differential diagnosis of splenomegaly 209
Neutrophilia 210
Leukaemia 211
Myelodysplastic syndrome 211
Hodgkin's lymphoma 212
Staging of CLL 212
Kiel classification of non-Hodgkin's lymphoma 213
Clinical staging of plasmacytoma 213
Types of allergic reactions 214
Assessment of immune system illnesses 214
CONTENTS
Anaphylaxis 215
Haemorrhagic diatheses 216
Coagulation cascade 217
Coagulation tests 218
Coagulation factors 219
Drugs affecting coagulation and their antidotes in the
coagulation system 219
Thromboembolism 220
Thrombolytics 220
Standardization of thromboplastins; INR/Quick's test 221
Oral anticoagulants - interfering factors 222
Blood replacement 224
Exclusion criteria for own blood donation 224

Oncology 225
Basic tumour therapy 225
Definitions of response of solid tumours to therapy 225
Prognoses 226
Early warning symptoms of tumours 227
Tumour markers 227
Tumour staging 228
Occult primary tumour with metastases 229
Metastases and possible primary tumour 229
Scales for asessment of the physical condition of tumour patients 230
Mode of action of cytostatic drugs 231
Side effects of cytostatic drugs 232
Dose reduction of cytostatic drugs 233
Antiemetics 234

Endocrinology 235
Endocrine system - summary 235
Endocrine normal values 237
Endocrine tests 238
Thyrotoxicosis and hypothyroidism 239
Adrenal cortex 240
Cushing's syndrome 241
Replacement therapy 242
Endocrine crises 243
Corticosteroids 244
Classification of renal osteodystrophy 244
Types of multiple endocrine neoplasia 244
 CONTENTS
Diabetology 245
Classification of diabetes mellitus 245
Diabetic therapy 246
Oral hypoglycaemics 246
Insulin therapy 247
Intermediate- and long-acting insulins 247
Biphasic insulins 248
Diabetic coma 250

Rheumatology and the locomotor system 253

Check-up of the rheumatological patient 253
Rheumatological status 254
Examination of the range of joint mobility (neutral-null
method) 255
Classification of inflammatory illnesses 257
Classification of degenerative illnesses 258
Classification of extra-articular illnesses 258
Classification of illnesses of bone 258
Laboratory investigations 259
Joint aspirates 260
Revised ARA criteria for the classification of rheumatoid
arthritis 261
ARA criteria for systemic lupus erythematosus (SLE) 261
Revised Jones criteria for diagnosis of rheumatic fever 261
ARC criteria for fibromyalgia 262
Diagnostic criteria for the spondylarthropathies 263
Principal symptoms of syndromes of vertebral origin 263
Osteoporosis 264
The radiologist's 'osteoporosis tree' 264
Non-steroidal anti-inflammatory drugs 265

Neurology 267
blood-CSF barrier disturbances and
Differentiation of
autochthonous IgG production in CNS 267
Common CNS findings 267
Visual pathway lesions and visual field defects 268
Trigeminal nerve distribution 268
Eliciting the corneal reflex 268
Neurological examination 269
Cranial nerves 270
Symptoms of autonomic involvement in polyneuropathies 272
Sensory dermatomes 273
xiii
CONTENTS
Cervical root compression syndromes 274
Lumbosacral root compression syndromes 275
Muscle function testing 276
Glasgow coma scale 278
Scale for assessment of pupil size 278
Staging of subarachnoid haemorrhage 278
Disturbances of consciousness 279
Anatomy of the cerebral arteries 280
Classification of cerebral ischaemia 281
Risk factors, accompanying illnesses and findings that
increase the risk of cerebral infarction 281
Doppler ultrasonography of the extracranial cerebral arteries 282
Possibilities of ultrasound investigation of supra-aortic vessels 282
Doppler ultrasonographic criteria for quantification of carotid
stenoses 283
International classification of epileptic seizures 284
Anticonvulsants 285
Syncope 286
Therapy for parkinsonism 287
Differential diagnosis of headache 288
Differential diagnosis of vertigo 289
Neurological syndromes of malignancy 289

Clinical pharmacology 291

Pharmacokinetic formulae 291
Nomogram for calculation of loading dose 292
Nomogram for estimation of half life 293
Removal of drugs by dialysis 295
Drug interactions 296
Pharmacokinetic and toxicological data 298
Drugs in pregnancy 328
Drugs and breast feeding 328
Drug metabolism 329
Side effects of drugs: central nervous system 331
Side effects of drugs: gastrointestinal tract 332
Side effects of drugs: cardiac 333
Side effects of drugs: genitourinary system 334

References 335
Index 341

xiv
 CONTRIBUTORS

PD Dr Andre Aeschlimann Dr Beat Huser

Chefarzt Dialysestation
Rheumaklinik Kantonsspital
CH-8437 Zurzach CH-6000 Luzern 16
(Rheumatology and the locomotor (Nephrology)
system)
Dr Rolf Kroidl
Prof. Dr Peter Berlit
Lungenarzt, Allergologe
Internist,
Neurologische Klinik
HokerstraBe 37
Alfried-Krupp-Krankenhaus
D-2160 Stade
Alfried-Krupp-StraBe 21
(Chest medicine)
D-4300 Esssen 1
(Neurology)
PD Dr Thomas Schurmeyer
Prof. Dr Klaus Bross Medizinische Hochschule
Abteilung Innere Medizin I Hannover
Medizinische Klinik I Krankenhaus Oststadt
der Universitat PodbielskistraBe 380
Franz-Josef-StrauB-Allee D-3000 Hannover 51
D-8400 Regensburg (Endocrinology)
(Haematology and oncology)
PD Dr Brigitte Volk
Dr Michael Droste Abteilung Innere Medizin II
Internist und Endokrinologe Medizinische Universitatsklinik
ElisenstraBe 12 Hugstetter StraBe 55
D-2900 Oldenburg D-7800 Freiburg
(Diabetology)
( Gastroenterology)

PD Dr Walter Haefeli
Klin. Pharmakologie Dr Christian Wussler
Kantonsspital Arzt fur Radiologic
Petersgraben 4 Basler StraBe 78a
CH-4031 Basel D-7850 Lorrach
(Clinical pharmacology) (Radiology)

Dr Michael Henke Prof. Dr Werner Zimmerli

Medizinische Universitatsklinik Infektiologie
Freiburg Kantonsspital
Hugstetter StraBe 55 Petersgraben 4
D-7800 Freiburg CH-4031 Basel
(Haematology and oncology) (Infections)
 PREFACE
Preface

This third edition of Memorix - Clinical Medicine offers a compact pocket reference
manual of constants of clinical medicine which will be of value to the busy practitioner in
hospital and doctors in general practice.

The authors decided on a complete revision of Memorix in view of the profusion of

similar publications that have appeared recently. Thus, over half of the information
included in this edition is completely new. Representatives of sub-specialities of internal
medicine were enrolled as co-authors in order to improve the topicality and clinical
relevance of the volume.

As a result of close collaboration between the publishers, authors and users of Memorix,
many critical suggestions have been considered. We were stimulated by this feedback
from students, graduates in pre-registration year, practising doctors and many others to
refine the choice of important and often essential anatomical and radiological diagrams,
international classifications, treatment strategies and tables of differential diagnoses. It
thus became possible to bring Memorix up to date without increasing the size of the
volume. into the coat pocket, so that it is readily available at the bedside, in the
It still fits
office and in the interpretation of results. The format of the volume, its tabular
style and the keyword presentation of the data, however, have inevitably led to some
deficiencies.

Conrad Droste
Martin von Planta
PREFACE
Preface to the first and second editions
Most doctors carry a small notebook in their coat pocket in which they have recorded
important data for quick reference as necessary.

We have looked at many of these books and have found that in the main they contain the
same information: established and expanded tables, schedules and plans which one
knows in outline but which are so complex that one cannot commit them to memory in
detail.

The purpose of Memorix is to compile a systematic aide memoire for the coat pocket.

This book offers the reader important and often essential anatomical and radiological
schedules, international classifications, medication summaries, treatment plans and tables
of differential diagnoses for everyday use in the clinic and in practice.

The book has been kept deliberately small enough to fit into the coat pocket. It is
designed to permit a rapid orientation at the bedside, when composing medical reports
and when evaluating findings, and to act as a prompt and as a check to ensure that nothing
has been forgotten.

Our book cannot, of course, replace personal observations and notes, but, where appro-
priate, it should complement personal interpretation, preferred preparations and local
normal values.
The authors are aware that the limitation of the scope, the tabular format and the
keyword presentation of the material may not make the volume fully comprehensive.
We were delighted with the concept of a book of this kind and we hope that our readers
will share our enthusiasm.

This book was developed during our joint clinical activity in the Canton Hospital in Basle.
We would like to thank our Chief, Dr W. Stauffacher, Director of the Department of
Internal Medicine, for the generous support of our work. The realization of Memorix
would not have been possible without the support and generous production of the
publishers, VCH. We would like to express our sincere thanks to all those involved, the
publisher's management, Mrs Sylvia Osteen and Mrs Myriam Nothacker. We are particu-
larly grateful to Mr Jorg Kuhn, Heidelberg, for his splendid illustrations, and to Mrs Doris
Engel, Biengen, for the frequently tedious secretarial work on the manuscripts.

Conrad Droste
Martin von Planta

xviii
 TRANSLATOR'S NOTE
Translator's note

In order to preserve the intention of providing a convenient and comprehensive pocket

reference book, I have kept to the format of the Swiss original as far as possible. Some
alterations have been required to conform to British clinical practice. These include the
diagnosis of brain death, the treatment of tuberculosis, immunization schedules and
vaccination for travellers. Drugs not available in the UK
have been omitted, and dosage
recommendations have been modified where they differed from those in the British
National Formulary, which should in any case be consulted as a revised edition appears
every six months.

In a volume that attempts to cover all clinical disciplines, there will inevitably be some
omissions, and the reader working in a specialty may find it helpful to consult one of the
specialized companion volumes.

My thanks are due to Drs B.F. Millet, N.E. Williams, J.M. Roland and D.B. Rowlands for
helpful suggestions with the radiology, rheumatology, endocrinology and cardiology

Dennis Guttmann
Peterborough
October, 1996

xix
SYMBOLS
Symbols used in this volume

- Not available/not known

n normal (unchanged)

= unchanged (equivalent)

+ ++ +++ present (positive)

absent (negative)

TTTTTT increased

+ >W- 4«W' reduced

< less than (below)

> greater than (above)

diameter

Symbols for recording a family history

Example: Symbols:
Stroke, varicose
veins, migraine Patient

Hypertension &
*1
— A
<?8
jU-
'
54
*iA
1
Mv,
in infancy

Myocardial infarct
male, deceased/affected
female, deceased/affected
male, living/not affected
female, living/not affected
abortion

Migraine 6 1 D male carrier

female carrier
=o consangumous marriage
 SHORT CONTENTS
Short contents

General principles 1

Radiology 19

Cardiology and angiology 49

Chest medicine 105

Emergencies, acid-base balance and disturbances, electrolytes 117

Gastroenterolgy 133

Nephrology 161

Infections 175

Haematology 201

Oncology 225

Endocrinology 235

Diabetology 245

Rheumatology and the locomotor system 253

Neurology 267

Clinical pharmacology 291

References 335

Index 341
 GENERAL PRINCIPLES
Nomogram for determination of body surface area of adults
from height and weight8
(From Lentner (1977))

Height (cm) Body surface (m 2 ) Weight (kg)

200-

195 -E
140-=
190 -^ 135-

130 -3:
'85 -E 125 -=

180- 120 -|

•2.30 115-=

110-|
;120
105-

Example
Connect height and weight and
read body surface area from the
middle scale.
(180 cm, 100 kg = 2.19 m 2 )

Alternative calculation
Body surface area in m 2 :

height (cm) X weight (kg)

V 3600

Valid for children and adults. (After

Mosteller (1987).) 0.90

0.86

• After the formula ofDu Bois and Du Bois (1916) O = A/0425 x L 0725 X 71.84
orlogO = logM x 0.425 + logL x 0.725 + 1.8564.
(O = body surface area (in cm ), M = weight (in kg), L = height (in cm))
2
MEMORIX CLINICAL MEDICINE

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 GENERAL PRINCIPLES
Skin alterations
Primary eruptions

Vesicle

Secondary eruptions

Ulcer Fissure '

Scar Atrophy

Clinical classification of skin lesions

Stratum Within the skin plane Above the skin plane Below the skin plane

Epidermis Hypomelanotic and

Melanocytes hypermelanotic
(brown) macule

Keratinocytes Macule Papule, vesicle, bulla, pustule, Atrophy

plaque, hyperkeratosis Fissure
excematous dermatitis,
exudative (impetiginous) lesion

Dermis Atrophy Papule, nodule, oedema Ulcer, sclerosis

Connective tissue Sclerosis atrophy, excoriation

Vessels Telangiectasia Urticaria,erythema multiforme,

Purpura morbilliform, scarlatiniform

Adipose layer Nodule, erythema nodosum Atrophy

MEMORIX CLINICAL MEDICINE

Eye test chart

Equivalent
distance

0.025

0.05
C 00

SS43 26 16 0.1

638 LU XOO 14 10 0.2

8 7 4 5 miu 0X0 10 7 0.29

6 3 9 2 5 m E 3 X O X 8 5 0.4

4 2 8 3 6 5 uiEm 0X0 6 3 0.5

3 7 4 2 5 8 5 2 0.67

• a 7 • 2 6 4 1 0.8

3 1+ 1.0

View at a distance of 35 cm under good illumination. Test with and without spectacles,
ensuring that long-sighted patients look through the close-vision segment of the lens.
Short-sighted patients are tested only with spectacles. (After Rosenbaum, J.G., Graham-
Field Surgical, New Hyde Park, NY11040)
 GENERAL PRINCIPLES
Hearing tests
Conductive (usually middle ear) or perceptive (usually inner ear) deafness?
1. Weber test: Place a tuning fork on the vertex of the
skull.The patient indicates whether the
tone is heard centrally or is lateralized

to one ear.

Conductive (middle ear) deafness:

lateralization into the affected
(deafer) ear

Perceptive (inner ear) deafness:

lateralization into the healthy (better)
ear
Tuning fork is placed on mastoid

process (bone conduction). If no sound

is heard, hold the tuning fork in front of
2. Rhine's test: the ear
Evaluation:
Rinne's test normal (= positive): Air
conduction is heard about twice as
long as bone conduction (30 s longer)
Rinne's test abnormal (= negative): Air
conduction is briefer than bone
conduction
Conductive (middle ear) deafness:
Rinne abnormal (negative)
Perceptive (inner ear) deafness: Rinne
1 (positive)
Conductive deafness Perceptive deafness
right left

Lesion of Weber Rinne

Middle ear Lateralization to abnormal ear Abnormal (= negative)

Inner ear Lateralization to healthy ear Normal (= positive)

Adult dentition
View from in front of the patient

Two-digit dental scheme (after the

Federation Dentaire Internationale,
London, 1970); now universally
accepted.
Each quadrant of the permanent
dentition receives a reference
number (1 to 4), clockwise: right
upper - left upper - left lower -
right lower

Reference Number 1 Reference Number 2

18 17 16 15 i4 13 i2 ll 21 22 23 24 25 26 27 28
Right Left
48 47 46 45 44 43 42 4l 31 32 33 34 35 36 37 38
Reference Number 4 Reference Number 3
MEMORIX CLINICAL MEDICINE
Gauge External diameter
Catheter and needle sizes (gg.) mm inch

35 0.13 0.005
^fl^^ French mm French mm
34 0.18 0.007
M H-3
^^ 34
• 3
33

32
0.20
0.23
0.008
0.009

^^^ • 31 0.25 0.010

1 1 32 10.7 #5 1.67
30 0.30 0.012
^^^ • 6 29
.

0.33 0.013

^^k 30 10.0
• 7 28
27
0.36 0.014
. 0.41 0.016
^^^ • 8 26 0.46 0.018

^^ 28 9.3
# 9
25 0.51 0.020

^^F # io 24
23
. 0.56

0.64
0.022
0.025

4fe 26 • " 22
21 •
0.71

0.81
0.028
0.032

X
MM •
^
12 4 '°
20 0.89 0.035

^^ 24 8.0
^ 13 19 1.07 0.042

^^
^A 22 ^ 18

17
• 1.27

1.50
0.050
0.059
14
16 1.65 0.065

^fc 20 ^ 15
15 1.83 0.072

A
^^ 16
14

13 •
2.11

2.41
0.083
0.095

A 18 £ 7
12

11
2.77

3.05
0.109
0.120

10 9 3.40 0.134
For an oval-shaped instrument: lay a strip of paper 9 3.76 0.148
around the circumference of the instrument and read the 8 4.19 0.165
value from
5 10 15 20 25 30 35 40 the scale 7 4.57 0.180

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 i 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 ll
6 ^fc 0.203
 GENERAL PRINCIPLES
Calculation of the drip rate of infusions

Calculation of number of drops Infusion duration (hours)

per minute (drip rate) 1

/2 1 2 3 A
160 f

/ rz /
Given: 150 I
/ /
Required infusion volume in litres (1)
Desired infusion duration in hours (h)
140 / / 7 / /
130 / / Z_ / /
Explanation of the use of the graph:
(Example: 1.51 to be infused in 6h)
120 1 / / /
/
/ /

1. Find 1.5 on the lower horizontal

110 / / / 7_
n f

/ /,, f /
2.
scale (infusion volume).

Draw a vertical line

point to the intersection with the
from this d
100

90
'

1 , z
7y '//-
r /
//
80 1
//
/ A V^
j ,
diagonal line 'Infusion duration
6h' (scale above and on I 70 //
Draw a horizontal line from this
right).
n
$ 60
'

/
/ /

[// i/
/ //
z
Z
i
3. I

1
intersection to the scale on the 5
/ //>
left,where the answer, '65 drops
per minute', can be read.
50

40
/ //,
L' / ti '/ % ^
= 30
'/
nW
Valid for 1 ml liquid 16 drops
20
7/
mV
fay m
10 p 3

0.25 0.75 1.5 2.0 2.5 3.0 3.5 4.0

Infusion volume (I)

Calculation: Number of drops per minute (drip rate)

Given: Desired infusion volume in millilitres (ml)
Desired infusion volume in hours (h)

Milli- Hours
litres 0.5 1 2 3 4 5 6 7 8 9 10 11 12 14 16 18 20 24 48

100 66 33 16 11 8 6 5 4 3
200 133 66 33 22 16 13 11 10 9 7
250 166 83 42 24 17 16 14 13 11 10 9
300 200 100 50 33 25 20 17 15 13 12 11
400 266 133 66 44 33 27 22 19 17 14 13 12 11
500 333 166 83 55 41 33 28 24 21 19 17 15 14 12 10 9 8 7 -
1000 666 333 166 111 83 66 56 48 42 37 33 30 28 24 21 19 16 14 7

2000 - 667 333 222 167 133 111 95 83 74 67 61 56 48 42 37 33 28 14

3000 - - 500 333 250 200 167 142 125 111 100 91 83 71 63 56 50 42 21

4000 - - 666 444 333 267 222 190 167 148 133 121 111 95 83 74 67 56 28
5000 - - 833 555 417 333 278 238 208 185 167 152 139 119 104 9? 83 69 35

Table valid for: 1 ml liquid - 20 drops

Infusion volume in millilitres

Drops per minute K for 16 drops/ml: 3.75
Infusion duration in hours x K K for 20 drops/ml: 3
MEMORIX CLINICAL MEDICINE

Patient population
111 Healthy

Positive Correct-positive (CP) False-positive (FP)

T
Sensitivity
E
S
Negative False-negative (FN) Correct-negative (CN)
T Specificity

The character of a test is defined as follows:

CN CP
Sensitivity
FP + CN CP + CN
CP CN
Per Neg. prediction
CP + FP FN + CN

50 pen :entile
Normal distribution
<

16 percentile, ,84 percentile

'
f/ \s '

2 percentile . / 5
\. .98 percentile

-r^2S% 14% 34% 34% 14% 2.5%^-p

-3SD -2SD -1 SD -1 SD + 2SD +3SD
I
68% _l
I
95% |p<0.05
L 99% jp<0.01

M ± 2 standard deviations (SD) = 95% of the values in a 'normal' population

sum of x SD
Mean (A/) SEM

Null hypothesis (H ) Is correct Is false

Is disproved Error of the first kind No error

Probability of error a (a-error) Probability 1 - a

Is confirmed No error Error of the second kind

Probability 1 - p** Probability of error P (P-error)

Epidemiological and demographic parameters

Number of deaths Number of new cases
Mortality = Incidence =
Average total population Average total population

Number of deaths Number of cases**

Lethality = Prevalence =
Number of completed cases Average total population

'Power' ** Number at a particular point in time

 GENERAL PRINCIPLES
SI units
Measurement Unit Symbol Equivalents

Length metre m
Area square metre m 2

Volume cubic metre m 3 = 1000dm 3 = 10001

litre 1

Mass kilogram kg
Amount of substance mole mol
Concentration (molarity) mole per cubic metre mol/m 3 = 103 X mol/1
Catalytic activity catal cat = mol/s

Force newton N = 0.102 kgf

Power watt W = J/s
Energy, work, amount of heat joule J = 0.239 cal lh
kilojoule kJ = 0.239 kcal th
Thermodynamic temperature kelvin K 1 K=1°C
celsius °C 0°C = 273.15 K
Pressure pascal Pa = 0.0075mmHg
kilopascal kPa = 7.5 mmHg
bar bar = 100 kPa
standard physical
atmosphere atm = 101.3 kPa

Velocity metres per second m/s

Acceleration metres per second 2 m/s2

Frequency hertz Hz
Electric current ampere A
Electric charge coulomb C
Electric potential difference volt V
Electric capacity farad F
Electric resistance ohm Q
Electric conductivity siemen S

Luminous intensity candela cd

Illuminance lux lx
Wavelength angstrSm A = 0.1 nm = 10-'°m

Radioactivity becquerel Bq = 0.27x 10- ,0 Ci

cune Ci = 3.7 X 10 l0 Bq
Absorbed dose gray Gy = 100 rd
rad rd = 0.01 Gy
Exposure roentgen R = 2.58 x 10- 4 C/kg
Dose equivalent sievert Sv = 100 rem
rem rem = 0.01 Sv

Prefixes for SI units

Factor Prefix Symbol Factor Prefix Symbol Factor Prefix Symbol

10 18 exa E IO6 mega M 10" 9 nano n
10 15 peta P IO3 kilo k io- 12 pico p
10 12 tera T io- 3 milli m io- ,s femto f
IO9 giga G lO" 6 micro IO" 18 atto a
MEMORIX CLINICAL MEDICINE
Normal chemical values
Determination Normal Values

Conventional SI units In-house

Albumin (p. 201) 3.5-5.0 g/dl 35-50 g/1

Ammonia 80-110ug/dl 47-65 umol/1
Anion gap (p. 126) 8-12meq/l 8-12mmol/l
Bilirubin: total (p. 149) 0.3-1.0 mg/dl 5-17 umol/1
indirect 0.2-0.7 mg/dl 3.4-12 umol/1
direct 0.1-0.3 mg/dl 1.7-5.0 umol/1
Blood coagulation (p. 218)
Blood count (p. 208)
Blood gases (p. 128)
Calcium: total 8.5-10.6 mg/dl 2.12-2.65 mmol/1
ionized 4.0-5.0 mg/dl 1.0-1 .25 mmol/1
Cerebrospinal fluid (p. 178)
Chloride 95-105 meq/1 95-105 mmol/1
Cholesterol (p. 100) 140-250 mg/dl 3.6-6.4 mmol/1
Cholesterol HDL
(p. 100) 30-75 mg/dl 0.78-1.94 mmol/1
Complement CH50 150-250 U/ml 1.5-2.5 g/1
C3 55-120 mg/dl 0.55-1 .2 g/1
C4 20-50 mg/dl 0.2-0.5 g/1
C-reactive protein <10mg/l
Creatinine (p. 162) 0.6-1 .5 mg/dl 60-130 umol/1
Drug assay (pp. 298-326)
Ferritin 15-200 ng/ml 1 5-200 (ig/1
Folic acid 6-15ng/ml 14-34 nmol/1
Glucose 70-1 10 mg/dl 4.0-6.0 mmol/1
Glucose load (p. 245)
Hormones (p. 235)
Iron 70-140 ug/dl 13-25 umol/1
Ketones/acetoacetate 0.3-2.0 mg/dl < 0.3 mmol/1
Lactate 0.6-1 .8 meq/1 0.6-1. 8 mmol/1
Lipid electrophoresis (p. 100)
Magnesium 1.5-2.1 meq/1 0.75-1 .05 mmol/1
Osmolarity 285-295 mosm/1 285-298 mosm/1
Phosphate (inorganic) 3.0-4.5 meq/1 1.0-1.5 mmol/1
Potassium 3.5-5.0 meq/1 3.5-5.0 mmol/1
Protein (total) (p. 201) 6-8.5 g/dl 60-80 g/1
Sodium 135-145 meq/1 135-145 mmol/1
Triglycerides 50-250 mg/dl 0.6-3.0 mmol/1
Tumour markers (p. 227)
Urea 15-40 mg/dl 2.5-6.7 mmol/1
Uric acid 3.0-7.0 mg/dl 180- 420 umol/1
Urine (p. 163)
Vitamin B 12
40-150 mg/dl 0.45-1.5 mmol/1

Note: Commonly used laboratory results are with average normal values. The interpretation of
listed
normal values must include consideration of the following parameters: method of sample
collection, analytical technique, transport time, and age and sex of the patient.

10
 GENERAL PRINCIPLES
Normal enzyme values
Due to the large number of analytical methods, it is not possible to give normal values.

Abbreviation Determination Conversion

Aldolase Ukat U nkat U

a-Amylase _£ 1000 r 100
_: 700 1600 i
Cholinesterase ,
-90
CK Creatine phosphokinase ! *1 1400 -i

CK-MB Cardiac isoenzyme of CK 4 i

3 -
- 200
r80
Y-GT y-Glutamyl transferase 2 - 1200 i -70
HBDH Hydroxybutyrate dehydrogenase :
70
-60
LAP Leucine aminopeptidase 7 l'l S 1000 -j

LDH Lactate dehydrogenase 0.5 -

0.4
' :
-
35 -50
20
Lipase 0.3 :
- 40
5 '-Nucleotidase 2 _, 10
600^
AP Phosphatase: alkaline
oSl fc '» -30
: 4 400-3
acid 05 -E
- 3
- - 20
004
prostate specific 003 - - 2
200-
SGOT/ASAT Aspartate aminotransferase 0.02 - - 10

SGPT/ALAT Alanine aminotransferase 01 -E 7 o- L

"«— x 016 67 <«— x16.67

x60 0—*• x 0060—

Plasma alcohol (blood alcohol) determination

Conversion of g/l to nunol/l: Conversion of mmol/1 to g/l:

Factor = 21.71 Factor = 0.04607

(0.8 g/l x 21.71 = 17.37 mmol/1) (17.37 mmol/1 X 0.04607 = 0.8 g/l)

Alcohol intoxication
Degree of intoxication mg/dl mmol/1 g/l

Mild 80-200 17-43 0.8-2.0

Moderate 200-400 43-87 2.0-4.0
Severe >400 >87 >4.0

Antabuse reaction
Disulfiram-like reactions have been described with the following drugs:
cefamandol, cefmenoxim, cefoperazon, chloral hydrate, chloramphenicol, chlorpro-
pamide, disulfiram, moxalactam, metronidazole, nitrofurantoin, tinidazole, tolbutamide.
Estimation of the alcohol concentration:

0.8 x ml alcohol
Men: alcohol (in %) =
0.68 x weight (kg)

0.8 x ml alcohol
Women: alcohol (in %) =
x weight
0.55 (kg)
Conversion factor 1 mg/1 = 0.1% by weight
Breakdown per hour: 0.015-0.02%/h
MEMORIX CLINICAL MEDICINE

Conversion scales 1 (From Deom (1992))

o
oo o OO O O
O O OO O
O O
OO00 CD

Il-
ls
kcal ID ^t CO
I

O
o
I
"
i I

!'
'
Im
o
oo
o
CN

o oo
o o
o o_
/
mmV i W 1

!
1 1

!
1 '
! '
Wmm' i'I'
1

kJ
o
o Oo00 CD
o
^ o
00

g/100ml cn cn r- f~ r~ t~ r- oo cd <*
| ' i

'i
i

M | il i | | , i ,l , i li l ,l ,

r
|, i

"i H
OOCNr-OOOOP^COLO^OO
, < i
JQ i i i i
l
i
>
i i
'
i
' l
i
'

I mmol/l
...
<- «- *- *- it

rtrtl OLDOLDOlDOLDO
g/1 OOmlLD^^OOOOCNCNT-T-
o I
I I I I
I
I I I
1

I
I
I I I
l'l I l' l I
I
'l I I 1

5 mmol/l oo
LD
CN CN
LO
II

I
o
pg >^^0O0OCNCN<-<- 1
tiX
1

'
I / I I I I I I I I I I I I I I 'l I I I

ii
I I I I I I

fmol X T

c
mg/l t-8
Mi Ml i
I
i
I
i
I
i '
l
'l l
'l I
1

|jmol/l
o
O o
CD
o
oo
o o
CD
o
ID r^

12
 GENERAL PRINCIPLES
Conversion Scales 2 (From Deom (1992))

o
O o o
O o
LD
o
o o A co
cmH 2 CO
LD
CN CM t- t- LD O 5X
t
1

I I ll I I II I I 1 1 I I I I I I ll I
I
ill '
1
co 1

o
I I

0) mm Hg o" O co LD- gO LD $
2
X \T
3 CN *- r- *"*-
(0
CO
2>
D.
O
O O O
O O CO
mm
i

Hg LD LD o
i i 1
CN
1 i i i i
<—
1 i i 1 i
t—
1 1 i i 1 1 i 1
tioX
1

|
1 ll 1 | 1 1 1 1
| 1 1 1 1 | 1 it l
|
I 1 I I
| 1 i 1 1
1

O LD O LD O LD o 8 i
kPa CO CN CN wr r-

(0
9 00 CD CO CN
g/i ID ""nT 00 CN t-OO OO
-sf

O d
Q) 1.1,1.1 i lilihli 1 1 1 i 1 1 i i I i i

o |l i
|
i
|
i
|
i
n|l|f|>l'l I
1
'
1
' 1 '
1

>%
o>
*C
mmol/l ld ^t co cn <-b
00 CO
dodo rt CO CN
d
S5
oX
i
f

ID LD LD ID ID
mg/100ml LD^^COoOCvJcN^T— d
A
t
1
CJ>
^
C\J
x
1
1
h*
I
1
1
\ 1
1
1
1
1 1
1
1
1
.
1
1
1
1
1
.
1
1

1 ' 00 1

mmol/l
CN O 00 CO <nT CM
sX 1
o
9
(A
CD
o
.c
o mg/100 ml
ooooooooo
OLDOLDOLDOLDO
LD^^-COCOCMCMt-t-
O
LD
.

ti
LO

1
1 1 1

1 | \ |
I
| 1 | 1 | 'l | I | 1 '| i | . | 1
1 '

o
I

cn oo co ^r CM
mmol/l

^
g/i
LD "sT 00 CM <—
Mill
00
O O
CO
do CO CM
d
A

1
lO

LO
X
.1

OO
1 1 i 1 . 1 i 1 i 1 i 1 i 1 1

1
|

' 1 '
II 1 1 1 1 1 1 1
II
|

1
1
1
o
O
1

00 CO "tf 00 CN

tt
mmol/l CO CN r-
1*
X
o
o
3
o mg/100 ml
ooo
OOO o
O ooo oo
^fCO 00 (D
o
CM
1
LO
LO
LO

LD "^f CO CM r-
hhhl ti
Ml
OO
1 i I i 1

*
i. J

O
I I

00
.

1 1

CO
1 1

-*t
1
ill

00
1
l.i !

CN
M
i 1

>
,

' '
1

mmol/l CO CM r- X "
MEMORIX CLINICAL MEDICINE
Conversion scales 3 (From Deom (1992))

m m m
m
00
meq/l
in
ih LO
in
CO CO CM CM
in
>-<— do A
1
^
ox
5.
T
i

1
1

1 1
|
l l l l
|
i

i i i
1

i
|
1

1 i i
1

i
|
i
i

i i i
1

|
i i
i

i i
1

CO
mmol/l m m m 11
o CO c\j CM t-' i- d o
.c
o.
o
c
CO
2>
o o
o CD
o
oo
o
r^
OOOOOO
CD LO <vt CO CM «— O A
CO
CO

1 mg/l
L 1 1
|
1

1 1
l
J
i

i
'

i ii
I I

1 |
1

1 1
i

1
1

1 |
i

1 M
1 i

1 |
1

1
i

1 II
1

|
I

1
1

1 1
I

1
1

|
o
1
ox

mmol/l
m m m 51
CO CM cm -- t- d o

E o o
o o
o o o
o o oo
oo o O
o CN
O OOOOOO
O Nn ifl'sf IN
O
r-
N Ifl'J
o o o
3
CO
mg/l 1 en cm
Ui.,,.1..., ,,.,1.1,
r~
r- o«fr co

.1 ll
If)

1 1 I....I .„l„„i,,,.l,i,i,i
r-

1 1 1 i L.I....L. .1., ..l.i.i, ill il 1

tjX
IT! r|T( Vj ll
T"| ii
M iiii|i,i|i r i,,|
1
p»n|.m,MM|,|, ,.,>!,! 1

pm.|....|i.i.|
CO || | , |
CO
CO h*. to^rco
|

cm t- m 1

B mmol/l o o o oo c
in <* en
or^m-d-oocN "~ O OOO d O C\J
f
OL
r»» c\
dX

E meq/l CD LO ^T CO t 1
B
O
CM X
3 1
,

1
1

1
,

1
1

| 1
'

1
'

1
i

l
1

1 1
i

1
1

1
i

1
1

| 1
i

1
1

1
i

1
1

1 1
i

1
i

1C mmol/l
m m m
CO CO CM CM -r^

O)

£
E
3
O CO CM t- O CD 00 1^ CD LD

o
CO mg/100 ml
T 7 fgox
1

T. iiT ,-
' i i i i i i i . i i i

i i i i i i i i i i i i i
1
i I I

mmol/l
m m m x T
CO CO CM CM <-

O o O 00 CD ^T CO CM r- m
^
23 mg/100 ml CO CM d 1

i i all 1 1 1 i I 1 1 1 1 1 1 1
X
m
1 1 1 i 1 1 1 1 1
1
. .1 ,

' i | i |ij!| i| I
j
l
j
i i
[ i | I

OO
' |
I I

o o o o o
1 1

O
1

o
o o
o O OOO CD CO CM r-
CO 1

s Mmol/l
LO CO CM
"tf

1
 GENERAL PRINCIPLES
Conversion SCaleS 4 (From Deom (1992))

o
o o
o o
o o
o o
o
mg/l
o oo CD
ill
or
I I , I

o I
I

o
I

o
1

/
vo \

|jmol/l o
o o
o o
o o
o o
o oX
CD 00
o
"5
CO
u
5 mg/100ml CN O
, '

o
|
'*
V Wo ') '

' V W'"l'
o
I
I

'l
"
I I

i
I
I

<JU I

Mmol/l o
00
o
CD
o

o
CO
o CvJ
LO ID
O
CvJ

O
g/i

'l ''l
'i
''"I'iW'I'I'm'i •
I ''"WM'Wl I
I

o o
I

mmol/l
o
o CM
o r- ^ CM

CO CM
*>

3
o o
o o o
o o o
cd ^r
mg/100ml CO CM to
MM
o o
i
"
I

O00
Ll Vi^M
CD ^T
'
1

! ' i
1

o
mmol/l CO CN CD
X

mg/l
ooooooooo
LOOLDOLDOLDOLD-
^-^cococmcmt— t— c

I
I I I I
I
I I I I
I
I I I I
I
I I I I
I
I I I I
I
I I I I
I
ll M I
I I I I
I

pmol/l
= 1

o LD
CO

CD ^T CO CM
^r co cn r-
mg/100 ml
' ' 1 1 1 1 1 1

ll'l' 'l
'l H i'l'llll . ! !

I' i
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15
 MEMORIX CLINICAL MEDICINE

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 : 3

GENERAL PRINCIPLES

Volume Temperature
us us US cubic
cubic centf- deci- op o
fluid liquid liquid c
Unit ounce pint quart inch metre litre litre

1 US fl oz = 1 0.0625 0.03125 1.8047 29.524 0.2957 0.0296

320° — 160°

= 4.7316 0.4732
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1

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290° — ^—140°
centimetre = cm 3 cm 3 cm 3 cm 3 cm 3 cm 3
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decilitrre = 3.3815 0.2113 0.1057 6.1025 100 1 0.1 °
1

1 litre = 33.815 2.1134 1.0567 61.025 1000 10 1

260°—^
r~ 130

Quarts Pints US
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inches
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17
MEMORIX CLINICAL MEDICINE

UK/metric system conversion scales: volume

Volume
UK Cubic
fluid liquid liquid Cubic centi- Deci-
Unit ounce pint quart inch metre litre Litre

1UKfloz= 1 0.0625 0.01732 1.7339 28.413 0.2841 0.0284

1 UK liq pt = 20 1 0.5 34.677 568.26 5.683 0.5682
1 UK liq qt = 40 2 1 69.355 1136.5 113.65 1 1365
1 cubic inch = 0.5767 0.02883 0.01442 16.39 0.1639 0.0164
1 cubic

centimetre = cm 3 cm 3 cm 3 cm 3 cm 3 cm 3
1 millilitre = 0.0352 0.00176 0.00088 0.06102 0.001
1 decilitre = 3.5195 0.17596 0.08799 6.1024 100 0.1
1 litre = 35 195 1.7596 0.87987 61.024 1000

18
 1

RADIOLOGY

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19
MEMORIX CLINICAL MEDICINE

Patient positions for X-rays supine recumbent, face up

prone recumbent, face down
erect sitting or standing

Projection determined by the direction which the X-rays take through the patient
(from X-ray tube to cassette)

AP Anteroposterior PA Posteroanterior
The back of the patient The front of the patient
is next to the film is next to the film

Lat. Lateral
One side of the body
faces the film

Oblique Any position between AP or PA and lateral (for special purposes, e.g. coronary
arteriography, the angle is commonly specified)

RAO Right anterior oblique

(1st oblique position)
right shoulder forwards

LAO Left anterior oblique

(2nd oblique position)
left shoulder forwards

i«3!j
Left lateral oblique Right lateral oblique
 RADIOLOGY
Checklist for assessing a chest X-ray

Method Technical evaluation

Routine diagnostic chest X-rays should be taken • Centring (symmetrical sternoclavicular joints,
with at least 120 kV. The thorax should central spinous processes)
preferably be examined in two planes (i.e. also a • Exposure (4th intervetrebal space just visible
lateral view). Advantages afforded by lateral behind cardiac shadow)
views: atelectases often only visible in one plane; • The lungs should be demonstrated to the pe-
retrocardiac and retrosternal lesions and hilar riphery (subpleural)
changes often only seen on lateral films. • Degree of inspiration (with adequate inspira-
tion the diaphragms should lie between the 10th
and 11th ribs dorsally)
• The whole lung is demonstrated (pleural apices
and costophrenic angles)
• Sharp outlines (no respiratory movement)
• Patient: age, sex, position, PA/AP, lateral

Chest X-rays: diagnostic procedure

Systematic analysis of the X-ray according to Chest X-ray sectors in which diagnosis may be
morphological structures easy or difficult
Attempt to follow the course of all important
lines and structures and to interpret them
A viewing distance of 2 metres is
advantageous
Free analysis, diagnosis by general
impression
Negative findings should be checked after
an interval
1 few diagnostic errors
4 common diagnostic
errors

Common sources of diagnostic errors

1 Cervical rib

2 Sternomastoid outline
3 1st and 2nd rib shadow
4 Azygos lobe
5 Bony articulation between 1st and 2nd ribs
anteriorly
6 Bone bridge between 5th and 6th ribs
posteriorly
7 Bifid 3rd rib
8 Horizontal fissure between upper and
middle lobes
9 Low-lying accessory fissure of apical
segment of lower lobe
10 Cardiac lobe
11 Nipple
12 Breast shadow
13 Subclavian artery
14 Calcified costal cartilage
15 Costal groove
16 Fissure of accessory left middle lobe
17 Pectoralisshadow
(From Freye and Lammers (1985)) 18 Edge of scapula

21
MEMORIX CLINICAL MEDICINE
Systematic analysis of morphological structures in chest
X-rays
Bony thorax: harmonious, coniform, symmetrically sloping ribs; emphysematous subjects: barrel
shaped; ribs widely spread, running horizontally, vertebral, sternal, rib deformity; cervical rib:
fractures

Soft tissues neck/thorax: subcutaneous emphysema, foreign bodies, calcification

Pleura: pneumothorax, effusion, thickening, tumours, interlobar fissures, sinus

Diaphragm: dome (right higher than left in 90% of subjects); smooth surfaces, flattening, adhe-

Mediastinum: widening, displacement, emphysema

Trachea: position, lumen, stenosis (natural narrowing

in laryngeal region, slight deviation to right in
region of aortic arch), angle of bifurcation
(normal 56°, range 41-71°)

Thoracic aorta: size, dilated, elongated?

Normally reaches to 1 finger's breadth below
clavicle in adequate inspiration; calcification;
ectasia; stenoses

Heart: size, outline (p. 27), valves (see below),

coronary calcification, pacing electrode, prosthetic
valve

Differential diagnosis: calcification of aortic or

mitral valve:
line between heart apex and hilum on lateral
view —» aortic above, mitral below
Hila: (p. 24): size, shape
• Pulmonary arteries, main and branches (normal r. pulmonary artery < 15 mm)
• Pulmonary veins (open below arteries in 1st atrium; arteries and veins parallel in upper
lobes; veins lateral to arteries)
• Left hilum higher than right in 97% (range 0.75-2.25 cm)
• Lymph node enlargement
• Calcified lymph nodes
Pulmonary vessels (p. 30)
Distribution alteration - especially well seen in lateral view;
alteration of calibre
//'Trachea Posterior pleural
Identifiable mediastinal lines reflexion

Anterior pleural
reflexion

Aorta

(From Burgener and Kormano (1985))

22
 RADIOLOGY
Lungs: parenchyma and interstitial tissues
Air bronchogram, outlines, calcification, interstitial/alveolar infiltrates (see below),
Kerley lines (pp. 30, 31), double track phenomenon in bronchitis

Differentiation between interstitial and alveolar shadowing

Shadow pattern of interstitial disorders:
1. Ground glass appearance, uniform opalescence

2. Increased reticular lung markings

(see ILO classification: symbols 's\ 't\ 'u'; p. 116)
3. Macular opacities, micronodular, nodular
(see ILO classification: symbols
'p', 'q\ 'r'; p. 116)
4. Hila usually not enlarged, often blurred
5. Elevation of diaphragm
6. Cysts (honeycombing)
7. Cardiac shadow may be deformed (right ventricular strain)

Alveolar shadowing:
1. Blurred contours

2. Tendency to confluence
3. Segmental/lobar distribution
4. Symmetrical left and right parahilar butterfly pattern
5. Air bronchogram
6. Peribronchial acinar rounded consolidations
7. Rapid evolution

General remarks:
Round opacities are recognizable early and are often overdiagnosed.
Linear opacities are recognized late and therefore often underdiagnosed.
In the normal chest X-ray one does not find rounded opacities, but numerous linear
opacities may be seen.

Lung alterations
Topography
Position, shape, boundaries, one or more lobes, single segments (pp. 25, 26)

Character

Opacification (relative reduction of air content)

• Zonal (esp. parenchyma: infiltrates, neoplasms, atelectases)
homogeneous - mottled sharp - blurred borders
(round-/wedge-shaped opacity)

• Linear/streaky reticular: (esp. changes of the lung framework, blood/lymph vessels,

bronchi)

• Patchy: (parenchyma or interstitium)

Translucencies (relative increase of air content)

Hyperplasia, malformation, reduced perfusion, expanded bronchial tree, bronchiectasis,
Cysts, reduced lung parenchyma (emphysema)
Condensation of lung tissues

23
MEMORIX CLINICAL MEDICINE

Diagnosis of lymph node enlargement

Lymph nodes in aortopulmonary window

Fold between descending aorta and right
Aortopulmonary window pulmonary artery
• is concave (1): normal
fa
'Sign of the rising sun' • is straight (2): suspicion of lymph node
enlargement
• is convex (3): definite lymph node
enlargement ('sign of the rising sun')

Topography of the hila Trachea

(lateral chest X-ray)
Scapula
The first branches Brachiocephalic
of the pulmonary trunk
vessels can be Right UL bronchus
identified on a
technically Left UL bronchus
satisfactory film.
Division of left
If this is not pulmonary artery
possible, a
pathological
condition can be
assumed,
Right hyparterial
e.g. neoplasm,
bronchus
lymphadenopathy,
vascular
enlargement
Left
hemidiphragm

Differential diagnosis: prominent azygos vein or lymph gland?

Problem: On PA film a
spherical opacity in the
position of the azygos vein
-» Lymphadenopathy or
prominent (engorged)
vein?

Solution:
Attempt to identify the
opacity on the lateral film
lymph node lies in front
of the trachea.
A lymph node can be
identified in both planes,
but a vessel cannot be.

24
 RADIOLOGY
Bronchopulmonary segments - CT
Horizontal fissure Greater (oblique) fissure Bronchopulmonary segments
Right Trachea Left

r apical Wk Wk apical

posterior ;

25
MEMORIX CLINICAL MEDICINE
Upper lobe (UL) Lower lobe(LL)

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26
 RADIOLOGY
Cardiac outlines in the four standard radiological positions

Posterioanterior Left lateral

\^) Aortic valve position

Ao Aorta
PA Pulmonary artery
\m J Mitral valve position LA Left atrium
LV Left ventricle

\_J Pulmonary valve position RA Right atrium

RV Right ventricle
SVC Superior vena cava
\^J Tricuspid valve position IVC Inferior vena cava

27
MEMORIX CLINICAL MEDICINE

Cardiothoracic ratio

—— <0.5
A + Bn _ (Mean 0.45)
(Q.39-0.50)
ML midline

A maximal deviation of right heart

border from ML
i B maximal deviation of left heart
border from ML
greatest inner diameter of thorax,
internal to ribs

Measurements are valid only with good positioning and maximal

inspiration.
Cardiothoracic ratio has no absolute validity as it is dependent on body
build and concurrent illnesses (emphysema).
Very suitable for comparison in the same individual.

Enlargement of individual heart chambers: criteria

(From Burgener and Kormano (1985))
Left ventricle
- heart apex bulges to left and
downwards - cardiothoracic ratio
>0.5 - Hoffmann-
Rigler sign
positive
(approximate
indication only):

HI posterior border
of left ventricle
bulges in a dorsal
direction more
than 1.8 cm
<2cm past the
posterior edge
of the inferior
vena cava, 2 cm
above their
intersection
and/or

[0 posterior border of left ventricle crosses posterior border of inferior

vena cava less than 2cm above the dome of the left diaphragm
28
 RADIOLOGY
Left atrium

Displacement of oesophagus
posteriorly (barium swallow) -
prominent left auricle - heavy
shadow (superimposed
projection of right and left atria)
- double contour on right (r./l.
atria) - elevated left main
bronchus - carina angle
widened, normal 56° (41-71°) ->
collapse of left lower lobe with extreme enlargement, due to obstruction
of left lower lobe bronchus

Right ventricle
Cardiac enlargement to left with
elevated, often rounded, cardiac
apex (due to displacement of
left ventricle) - filling of

retrosternal space (> 1/3) - right

atrium can be displaced to right
- left ventricle can be displaced
posteriorly - seldom an isolated
finding. Exception: pulmonary stenosis, Fallot's tetralogy, etc.

Right atrium
Cardiac shadow occupies more
than a third of right hemithorax -
rounded right cardiac contour -
retrosternal space can be filled
- seldom an isolated finding

29
MEMORIX CLINICAL MEDICINE

Pulmonary venous congestion

Normal
• Vessels at lung bases wider
Arteries than at apices (greater
volume due to hydrostatic
Veins pressure)
• Progressive reduction of cali-
PVP (pulmonary venous
pressure) < lOmmHg bre to periphery
• Vessels no longer recogniz-
Entry of pulmonary veins (into
atria) lower than pulmonary able as individual structures
arteries. Arteries and veins run in peripheral third of lung

parallel to each other in upper field

lobes, veins lateral to arteries

Early Diversion
division
Basal
Dilatation of pulmonary
upper lobe veins narrowed
veins -> vessels with distinctly
inupper and dilated upper
lower lung lobe veins (vein
equally filled diameter
> 3 mm in first
intercostal
PVP 10- space)
15 mmHg
PVP 15-
20 mmHg

Kerley A Diversion and interstitial oedema

lines
• Perivascular oedema, near hilum and/
or peripherally
• Blurred vascular shadows
• Cuff formation around bronchi and
vessels (peribronchial oedema)
• Ground glass-like shadowing
• Possibly pleural effusion (costo-
PVP 20-25 mmHg phrenic, interlobular)
• Development of Kerley A and B lines
Kerley B lines

(Modified from Burgener and Kormano (1985))

 RADIOLOGY
Kerley lines: Kerley B lines:

oedematous interlobar septa, peripheral, near pleura (mostly basal,

denser than vascular structures, posterior), horizontal distinct lines,
no branching perpendicular to pleura, up to 1 cm in
length

Kerley A lines:
radiating from hila, possibly curved, up to
4 cm in length

Intra-alveolar oedema:
• Homogeneous, confluent macular shad-
ows
• Positive bronchogram in region of shad-
PVP owing becomes visible due to fluid
(air
filling of adjacent alveoli)
25-35 mmHg

Additional, non-pathognomonic indica-

tions: pleural effusion, haemosiderosis
(nodular), fibrosis, aneurysmal pulmonary
veins, right heart hypertrophy

Radiological signs of pulmonary hypertension

(Pulmonary arterial hypertension, e.g. primary, after pulmonary embolus, response to
pulmonary venous hypertension)
persistent

Pulmonary arterial hpertension

• Dilatation of pulmonary artery main

PAP stem and main branches (normal right
(pulmonary pulmonary artery < 15 mm)
arterial pressure)
• Transition in calibre centrally to periph-
> 50 mmHg
eral pulmonary vessels (ratio usually
more than 7:1): pruning of vessels, in-
(PVP<
creased translucency of peripheral lung
10 mmHg)
fields

PVP pulmonary venous pressure

PAP pulmonary arterial pressure

31
 ) )

MEMORIX CLINICAL MEDICINE

Summary of skeletal radiology

(Modified from Voegeli (1981))
rr~~ Quantitative reduction of bone tissue, increased X-ray transradiency (however, beware
|
eopenia
: I

j ^ use Qf ^qqt tecnm q Ue or overexposure)

|
Osteoporosis |
Osteomalacia |
Hyperparathyroktia
• Increased transradiency of • Radiological signs mainly • Subperiosteal bone resorption
bone ('brilliance') similar to those of (early: radial side of middle
• Reduced number of osteoporosis phalanx of 2nd and 3rd
trabeculae of spongiosa Differences: digits)
(coarse-stranded spongiosa) • Distal osteolysis (tuft
• Looser zones
outside the lines of stress (pseudofractures, incomplete erosions)
(spongiolysis)
fatigue fractures, often
• Osteoporosis (see above, esp.
• Splintering of the cortex from in primary
symmetrical in pelvis, e.g.
within
pubis, ischium, neck of femur,
hyperparathyroidism
• Enhanced prominence of ribs, running perpendicular to
• Brown tumours (esp. in
cortex ('frame' appearance of cortex. If numerous and secondary
vertebrae)
symmetrical: Milkman's hyperparathyroidism
• Reduced load-bearing • Calcification in arteries, soft
syndrome)
capacity of bone -» tissues and articular cartilage
• Bone deformity (bell-shaped
incomplete fractures (spine: rib cage, 'ace of hearts'
(chondrocalcinosis
wedging, collapse of pelvis, kyphoscoliosis,
• Band
sclerosis of vertebrae
vertebrae) • 'Pepper pot' mottling of
biconcave vertebrae ('cod-fish
skull
spine'))
• Hazy, indistinct outlines of
trabeculae

j
Osteolysis Destruction of bone (neoplastic: primary, metastatic; inflammatory)
|

• Spongy bone destroyed more quickly than compact bone

• Bone destruction visible on X-ray after about 10 days

Types of osteolysis
• Geographical (sharp boundary to surrounding bone)
• Moth-eaten (indistinct boundary)
• Infiltrating (boundary between affected and healthy bone difficult to determine)

|
Osteosclerosis
|
New bone formation, increased bone density, reduced transradiency
1 Reactive new bone formation by pre-existing bone-forming elements (osteoblasts) as reaction to
diverse irritants (inflammation, tumour, trauma) is a non-specific sign
• Condensation of pre-existing bone elements (spongiosa, compacta) follows original organization
of the bone
la Endosteal reactive new bone formation
(e.g. geographic lysis with sclerotic borders)

lb Periosteal reactive new bone formation

Solid
Interrupted
• Lamellar
• Radial (ray-like, sunburst)
• Amorphous
New bone formation by tumour cells
(chondrogenic, osteogenic tumours)
Calcification of tumour matrix
• Disorganized nests of new bone formation independent of the original organization of the bone

Bone death
I Osteonecrosis I

I I (Ischaemic, e.g. trauma, embolism, compression of blood vessels)

• Alteration of bone density -4 increased transradiency
• In surrounding osteoporosis or repair (sequestrum)
• Patchy picture of osteolysis and osteosclerosis

32
 RADIOLOGY
Osteoarthritis/inflammatory arthritis

Osteoarthritis of knee Early Inflammatory arthritis of knee

1 Joint space reduction 5 Soft-tissue swelling
2 Subchondral sclerosis (distension of the joint
3a Osteophytes capsule by effusion or
3b Inner margin pad synovial swelling)
4a Subchondral/periarticular 6 Periarticular osteoporosis
cystic erosions 7 Erosions, destruction
4b Marginal erosions 8 Joint space reduction

t
Late
NB: Radiological signs of arthritis may only be visible after days or weeks.
Scintigraphy (bone scan) is more sensitive and enables earlier diagnosis.

Osteoarthritis of hip
(After Freye and Lammers (1982))

9 Wavy outline of joint line

10 Reduplication of joint line

11 Calcification of joint capsule

12 Cystic defects

13 Reactive new bone or cartilage

formation
14 Incongruence of joint surfaces

15 Deformation of femoral head

Joint space reduction
MEMORIK CLINICAL MEDICINE

Radiological signs of non-inflammatory changes of the spine

(After Miiller and Schillung (1982))

1 Juvenile developmental defect

(Scheuermann's disease) with wedged
vertebra, irregularities of the end plates
and Schmorl's nodes*
2 Fish vertebra in osteoporosis

3 Osteochondrosis with spondylosis

4 Hyperostotic spondylosis

5 Spondylarthrosis

6 Spondylolysis with 7 Spondylolisthesis

8 Baastrup's syndrome ('kissing

osteophytes')

Radiology of the vertebra

( After Schinz et al. (1979))

1 Body
2 Spinous process
3 Transverse process
4 Superior articular process
5 Inferior articular process
6 Vertebral foramen

Q 3^3 4 .4

a Projection of the vertebral body

b Projection of the region of the arch
c Pedicles which connect a with b
d Superimposed view of a-c

34
 RADIOLOGY
Bone metastases
• Sclerotic (osteoblastic) metastases (common in carcinoma of prostate, breast, stomach, pancreas, etc.)
• Osteolytic (osteoclastic) metastases (common in carcinoma of bronchus, thyroid, breast, ovary, colon,
gall bladder; renal cell carcinoma, primary carcinoma of liver)
• Mixed osteolytic-osteoblastic metastases

Primary tumour in: Bone metastases (% of cases)

Breast 61
Prostate 50
Lung (carcinoma of bronchus) 33
Kidney 25
Thyroid 20
Liver 17
Pancreas 14
Bladder 12
Stomach 12
Body and cervix of uterus 11

Preferred sites
• Spine 70% (lumbar > thoracic > cervical)
• Femur 50%
• Humerus 17%
• Ribs 10%
• Cranial vault 9%
• Pelvis 9%
• Shoulder girdle 6%
• Tibia 1%
Solitary bone metastases —25%

Typical distribution of bone

metastases
Individual regions of the skeleton are affected by
bone metastases with different frequencies.
In patients with carcinoma of the breast, bone
metastases involve pelvis, spine, femur, ribs and skull
in decreasing order of frequency. Patients with
carcinoma of the prostate show skeletal metastases
(in decreasing order of frequency) in the lumbar
spine, sacrum, pelvis, upper half of femur and
humerus, ribs, scapula and skull.

Very frequent
Frequent
:
Typical distribution of bone metastases

MR:
pelvis, spine,

ribs, skull
femur

Infrequent ML extremities
35
MEMORIX CLINICAL MEDICINE

Lateral skull

1 Sagittal suture 13 Impressions of cerebral gyri 24 Calcification at insertion

2 Coronal suture (partly calcified) 14 Calcification of falx* of tentorium*
3 Squamous suture 15 Frontal emissary* 25 Anterior clinoid process
4 Lambdoid suture 16 Arachnoid granulations* 26 Sphenoidal plane
5 Nasofrontal suture 17 Sphenoparietal sulcus 27 Clivus
6 Spheno-occipital 18 Groove for middle 28 Greater and lesser wings
cartilaginous joint* meningeal artery of sphenoid
7 Frontozygomatic suture 19 Occipital protuberance* 29 Crista galli
8 Sutural bone* 20 Anterior wall of middle 30 Sphenoidal sinus
9 Diploetic canals cranial fossa 31 Frontal sinus
10 Calcified pineal* 21 Roof of orbit 32 Ethmoidal air cells

11 Calcification in choroid 22 Floor of posterior 33 Wall of maxillary sinus

plexus* cranial fossa * Inconstant or variable
12 External ear 23 Dorsum sellae

(After Gerlach J., Viehweger G. and Pupp J.S. With permission of Boehringer, Ingelheim)

36
 RADIOLOGY
Skull AP

34 Nasal bone 40 Margin of orbit 47 Petrous part of temporal bone

35 Nasal septum 41 Innominate line 48 Mastoid process
36 Inferior turbinate 42 Hard palate 49 Mastoid air cells
37 Zygomatic bone 43 Anterior nasal spine 50 External auditory meatus
38 Frontosphenoidal 44 Superior orbital fissure 51 Styloid process
process of zygoma 45 Optic foramen 52 Arcuate eminence
39 Zygomatic process of 46 Lesser wing of sphenoid * Inconstant or variable

frontal bone
(After Gerlach J., Viehweger G. and Pupp J.S. With permission of Boehringer, Ingelheim)

37
MEMORIX CLINICAL MEDICINE

Sinuses

53 Internal auditory meatus 64 Foramen magnum 73 Foramen lacerum

and foramen 65 Anterior arch of atlas 76 Infraorbital foramen
54 Cochlea 66 Transverse process of atlas 77 Hyoid bone with
55 Vestibulum 67 Atlanto-occipital joint greater cornua
56 Upper and lateral 68 Atlantoaxial joint 78 Tongue
semicircular canals 69 Odontoid process of axis 79 Uvula
57 Trigeminal notch 70 Split vertebral spine 80 Ear lobe
58 Head of mandible 71 Pterygoid process 81 Pharyngeal cavity
59 Muscular process of 72 Foramen rotundum 82 Trachea
mandible 73 Foramen ovale * Inconstant or variable
60 Mandibular canal 74 Foramen spinosum
61 Temporomandibular joint

(After Gerlach J., Viehweger G. and Pupp J.S. With permission of Boehringer, Ingclheim)

38
 RADIOLOGY
CT cross-sectional topography
(From Wegener, O.H. Ganzkorper-Computertomographie. With permission of the au-
thor and Schering AG, Berlin)

22 4
1
13 J^
fi
1

l / ^/^ g

33 23 30 29 27 30 23 33

32 1] 4 11 5 6 32 23

23 24 27 29 33

n 1 31 8/15 ?4 97

3 7/14

23 29 16 i

Hounsfield units (HU)

Water OHU Blood, clotted 50-100 HU
Cerebrospinal fluid 10 HU Bone >500HU
Brain 30-40 HU Fat -50 to -100 HU
Blood, liquid 40-50 HU

39
MEMORIX CLINICAL MEDICINE
Arteries
1 Aorta
2 Pulmonary trunk
3 Pulmonary artery
4 Innominate artery
5 Common carotid artery
6 Subclavian artery
7 Axillary artery
8 Internal mammary artery

Veins
9 Superior vena cava
10 Pulmonary vein
11 Innominate vein
12 Internal jugular vein
13 Subclavian vein
14 Axillary vein
15 Internal mammary vein
16 Azygos vein

Organs
17 Heart, left ventricle
18 Heart, right ventricle
19 Heart, left atrium
20 Heart, right atrium
21 Interventricular septum
22 Pericardium
23 Lung
24 Trachea
25 Main bronchus
26 Lobar bronchus
27 Oesophagus
28 Thyroid gland

Skeleton
29 Spinal column
30 Rib(s)
31 Sternum
32 Clavicle
33 Scapula

27 1 26 3

40
 RADIOLOGY

Arteries
1 Abdominal aorta
2 Superior mesenteric artery
3 Lumbar artery
4 Internal iliac artery
5 External iliac artery
6 Femoral artery
7 Pudendal artery
8 Dorsalis penis artery

41
MEMORIX CLINICAL MEDICINE
13 25 32 5 25 Veins
5/17
9 Inferior vena cava
10 Azygos vein
11 Splenic vein
12 Portal vein
13 Superior mesenteric vein
14 Lumbar vein
15 Vertebral vein
16 Internal iliac vein
17 External iliac vein
18 Femoral vein
19 Pudendal vein

Organs
20 Liver
21 Gall bladder
22 Pancreas
23 Spleen
24 Kidney
25 Ureter
26 Urinary bladder
27 Urethra
28 Prostate
29 Spermatic cord
30 Duodenum
31 Jejunum
32 Ileum
33 Colon
34 Rectum
35 Adrenal gland

Skeleton, etc.

36 Spinal column
37 Rib(s)
38 Hip bone
39 Ilium
40 Ischial tuberosity
41 Symphysis pubis
42 Femur
7/19
48 3 4 4v^27 28
,

43 Sacrum
44 Sacroiliac joint
45 Coccyx
46 Sciatic nerve
47 Lumbosacral plexus
48 Ischiorectal fossa
49 Lymph nodes
50 Spinal nerve root

42
 RADIOLOGY
CT retroperitoneal spaces and pelvis
Pancreas Spinal column

IVC Liver Adrenal I Diaphragm Spleen

Superior mesenteric a. and v

Colon
/
Aorta
Duodenum
m
'

Colon

Left kidney Psoas

Right kidney Renal fascia
I Renal fascia muscle
Renal fascia
Common iliac artery
Aorta Renal cortex

Retroperitoneal fascial spaces

Rectus abdominis
muscle
Kid-
ney Endometrium
Paranephric
space
Perinephric Myometrium
space
Rectum
Ascending colon-
Vagina

Ala of ilium Bladder

Symphysis

Caecum

CT anatomy of (left) acetabulum - axial section

43
MEMORIX CLINICAL MEDICINE

CT skull

I. and r. lateral
ventricles
Sylvian fissure

Internal capsule

Basal ganglia
Calvaria"

v
/ ventricle Occipital lobe
Pons Cerebellum i ventricle
4th ventricle

Body of lateral
ventricle Calcar avis
Corpus callosui

Insula

Falx cerebri

Falx cerebri Thalamus Pre-central gyrus

Lesions
More dense Less dense Equal density

Fresh haemorrhages Infarcts (from 3rd day) Cerebral infarct

Calcification Tumours (first 3 days, 2nd week with
Bones Inflammatory foci contrast, dependent on the
Metastases Foci of demyelinization collateral supply over weeks)
Meningiomata Fat
Air Subacute haematoma
Old haemorrhages
Cerebral oedema Astrocytoma
Consequences of trauma
 RADIOLOGY
Magnetic resonance imaging - indications
Brain
Demyelinating lesions Primary imaging procedure in cases of uncertain clinical diagnosis
Second examination with unremarkable first examination and
persisting symptoms
In first episode (patient aged < 40 years)

Tumours After unremarkable or non-diagnostic CT examination (with contrast)

Primary indication in brain stem region with therapeutic possibility
Temporal lobe epilepsy After unremarkable or non-diagnostic CT examination (with contrast)
Primary indication if treatment resistance
Vascular lesions After unremarkable or non-diagnostic CT examination (with contrast)
Primary indication in region of brain stem

Mediastinal tumours
Primary and secondary tumours After unremarkable or non -diagnostic CT examination
Before CT if vascular infiltration demonstrated
Inflammatory lesions Possibly primary for determination of operability

Abdomen
Upper abdomen
Liver Haemangioma, adenoma, focal nodular hyperplasia
Retroperitoneal organs Tumours for preoperative clarification after CT (selection of free planes)
Vascular diagnosis in case of intolerance of contrast media
Tumour staging (after CT)

Spinal column
Intramedullary conditions Primary imaging procedure
Extramedullar conditions With intraspinal masses primary imaging procedure
(before CT and myelography)
With smaller lesions possibly Gd-DTPA
In clinically unequivocal segmental association primary CT
In discrepancy between symptomatology and CT —» MR
clinical
With unclear segmental association MR possible as diagnostic procedure

Vessels
Aneurysms Alternative to CT with contrast
Dissections Primary indication
Large- and medium-calibre vessels
Thrombi Alternative to CT with contrast
Coarctation of the aorta Primary indication

Musculoskeletal system
Cartilage MR best non-invasive Temporomandibular arthropathy
imaging procedure MR if therapeutically relevant

Articular cartilage and menisci of other joints

MR only after conventional investigation and if

therapeutically relevant
o Ligaments Non-invasive demonstration Knee
of the ligaments MR if therapeutically relevant and in cases not
clarifiable with other non-invasive procedures

Necroses MR most sensitive MR for early recognition if therapeutically relevant,

imaging procedure in cases inexplicable by other procedures and
clinicalexamination
Tumours MR highly sensitive, MR if therapeutic relevance, if not explicable by other

„ but not specific (noDD procedures (after conventional radiography including

between malignant and benign) tomography, but before CT)
(§ Metastases Demonstration of bone marrow MR with negative conventional radiography and
nuclear scintigraphy with positive clinical findings
and therapeutic relevance

Muscle Demonstration of neuromuscular disorders, MR for planning of biopsy

(Modified from Lissner and Seiderer (1990))

45
MEMORIX CLINICAL MEDICINE

Magnetic resonance imaging - head

Dorsum sellae Frontal pole Longitudinal cerebral fissure

Anterior arch of atlas

Epiglottis
Head of caudate
nucleus

Thalamus
Insular sulcus

Vein of Gaier

Longitudinal cerebral fissure

Cervical spine (T, image) Axial skull (proton density image)

Interventricular foramen Subependymal layer Superior sagittal sinus

Septum pellucidum Body of corpus callosum nucleus

Thalamus Globus pallidus
Anterior commisure Internal capsule
Skull bone
Hypothalamus Putamen
Optic chiasma^ Diploe
Splenium of corpus
^callosum |
nsu ar
Pituitary |

cistern

Genu of Mamillary \'*'

corpus
callosum

Aqueduct
i ventricle

Cerebellum

Medulla oblongata

Internal carotid
artery
Optic chiasma
Pituitary Pharynx

Sphenoidal sinus Amygdaloid body

Saggital skull (spin-echo image) Coronal skull (T, image)

46
 RADIOLOGY
MRI appearances of Image planes
Sagittal section (Z-section)
brain structures
Transverse section
T, image Proton T 2
image (axial, Y-section)

density

Coronal section
Fluid space Dark Grey Light
(frontal, X-section)
Vessel Dark Dark Dark
Grey Grey Light Light
matter grey grey

White Light Grey Grey

matter grey

Fat White Light Light

Bone/air Dark Dark Dark

Female pelvis - normal anatomy

Intervertebral disc

Bladder Rectum Uterus Fat

I
%^ Jwal
^mm>^a^:Wmm
^Egg&m£p\
Symphysis Bladder Uterus
la: T, 1b: proton density 1c: T2

Retroperitoneal space, Knee joint - sagittal (T,)

gradient echo

Kidney
Wt
Posterior cruciate
ligament
Tibia

47
 CARDIOLOGY/ANGIOLOGY
NYHA criteria

NYHA grade Criteria

Grade I Exercise tolerance is uncompromised

(exceptionally strenuous physical effort can produce symptoms)

Grade II Exercise tolerance is slightly compromised

Symptoms with increased but not unusual effort (e.g. walking uphill).
Mild effort without symptoms

Grade ID Exercise tolerance is moderately compromised

Symptoms with mild effort (e.g. walking on the level), no symptoms
at rest

Grade IV Exercise tolerance is severely compromised

Symptoms at rest: none of the effort above possible

Assessment of cardiovascular risk before non-cardiac

operation
(After Goldman et al. (1977))

Points

History a) Age > 70 years 5

b) Myocardial infarct < 6 months previously 10

Clinical a) Grade 3 hypertension, distended neck veins 11

examination b) Significant aortic stenosis 3

ECG a) Not in sinus rhythm, or supraventricular ES in last 7

preoperative ECG
b) More than 5 VES/min at any time preoperatively 7

Poor general p0 2 < 8kPa or pC0 2 > 6.7 kPa 3

condition K < 3.0 or HC0 < 20mmol/l
3

Urea > 8.3mmol/l or creatinine > 300umol/l

SGOT T, signs of chronic liver disease or patient
bedridden for non-cardiac reasons

Nature of intended a) Intraperitoneal, intrathoracic or on aorta 3

operation b) Emergency surgery 4

Greatest possible point count 53

Severe complications to be expected*

Grade Point Risk e.g. perioperative infarct, Cardiac

count pulmonary oedema, non-fatal death
ventricular tachycardia

I 0-5 Small 0.5-0.7% 0.2%

II 6-12 Small to moderate 2-5% 1-2%
III 13-25 Moderate to high 11-12% 2-4%
IV >25 Very high to 22% 26-56%
* Approximate data from various references.

49
MEMORIX CLINICAL MEDICINE

Central venous pressure

Jugular veins cm
filled above this H2
level at 45°
pathological:
indication of
right
heart (volume)
overload
1 mmHg =
1.36 cm H2
Normal: 1 cm H 2 =
Jugular veins 0.73mmHg
not filled,

since column of
blood
with normal
pressure
in right atrium
(5-6mmHg =
8 cm H 2 0)
only reaches to
clavicle
Measurement:
With patient at 45°,
estimate
the neck vein filling

Raised central venous pressure (jugular veins filled at 45°). Causes: raised right atrial
pressure == manifest right heart failure; Differential diagnosis: constrictive pericarditis,
superior vena cava obstruction, etc. The pressure can be estimated by increasing or
decreasing the angle and determining the distance from the baseline to the height of the
jugular vein filling.

Determination of baseline (level of right atrium):

4th intercostal space, perpendicular through the thorax, level at border between 2nd and
3rd fifths of diameter of thorax.

Hepatojugular reflux
Examination: Patient positioned with upper body at 45°, apply pressure with palm of
hand (about 30-60 s) to right upper quadrant of abdomen or epigastrium; patient should
be informed and should continue to breathe quietly.
Interpretation:
Volume loading by pressure on splanchnic region
Normal: Correction within a few heart beats, neck veins no longer visible or collapsed
on inspiration (negative intrathoracic pressure -» improved venous return)
Positive: (pathological): Neck veins continuously visible, remain engorged even in in-
spiration
Causes: Latent right heart failure
Differential diagnosis: constrictive pericarditis, superior caval obstruction

50
 CARDIOLOGY/ANGIOLOGY
Auscultation areas
(After Shah, Slodki and Luisada (1964))

PA Pulmonary area
5= AO Aortic area Pulmonary point
P Pulmonary valve
BE Aortic point

A Aortic valve

Left ventricular
area

Mitral point

M Mitral valve

Heart sounds and extra sounds Sound intensity

Degree
Systole
1/6: only just heard with
L Left ventricle
concentration
J-I Right ventricle
2/6: heard immediately at
beginning of ausculta-
tion, not through hand
laid on chest
3/6: heard distinctly (also
\\ \\ *" Ventricular filling sound (3rd HS) through hand)
X X\ Tricuspid opening sound TOS 4/6: loud, accompanied by
>>\^" Mitral opening sound MOS faint thrill, conducted to
\ s_ Pulmonary v closing
\ sound P ? 1 2nd HS wrist
Aortic v closing sound A ?
N 5/6: very loud with strong
Midsystolic click
s Pulmonary (e)ection) click thrill, only heard with

\\ Aortic (ejection) click stethoscope applied to

\\ Tricuspid closure (T,) } 1st HS chest wall
\' Mitral closure (M,) 6/6: very loud, still heard
1
Atrial sound 4th HS when stethoscope is a
few centimetres from
chest wall

51
MEMORIX CLINICAL MEDICINE
ECG - electrode positions
Vg V8

+90° +75<

Chest leads
(unipolar)
V -
1
4th r. ICS parasternal
V2 - 4th ICS parasternal
I.
Special
-
V3 between V 2 and V 4 chest leads
V 4 - 5th ICS in I.
V7 - posterior axillary line at height of V4
midclavicular line V8 - I. middle scapular line at height of V4
(normally heart apex) V9 - I. paravertebral line at height of V 4
V5 - I. anterior axillary line at
height of V4 Right precordial leads:
V6 - I. midaxillary line at V3 r, V 5R l at positions corresponding to
height of V4 V 4R V 6R
, J those of the left-sided leads

Extremity leads: Bipolar extremity leads

right arm: red (or 1 ring) afterEinthoven
left arm: yellow (or 2 rings) lead I left arm -» right arm
left leg: green (or 3 rings) lead II left leg -> right arm
(right leg: black [earth]) lead III left leg -> left arm

d Yeiiow Unipolar leads after Golberger

(a: augmented)
aVR - right arm potential
aVL - left arm potential
<hd Green
aVF - left foot potential

Frequently used leads in

Long-term ECG
(positive [+] and negative [- bipolar electrode positions
'usually designated C])
Manubrium sterni (or close by to right or left)
Left, infraclavicular
Infrascapular on back
r. 5th ICS, anterior axillary line

Standard leads (see above)

Left costal margin, anterior axillary line
In xiphoid region

Recording of ischemia Anterior Inferior

CM-V S CS - aVF,
CM-V, CM - aVF
CC-V, CS-V,
CB-V $
CM-V,
52
 I '

CARDIOLOGY/ANGIOLOGY
ECG - normal
25 mm Is
values
50mm/s
1 mm = 0.04 s 1 mm = 0.02 s

1.5 -
"* 50 ni!

Estimation of frequency

* ;o. mi i
- at 25mm/s

f5/jnin -
u> -f~
f
> " ;,
'

0/rnin
E t

L
"Trtf
6C
rw
> at50mm4
| 0.5 -?- *
$w
—
^~ 20 D/n
n50/min

i I U )/rr in
I I

- 1 0s —
^..-l .J
PQ QRS U-
P-wave ST segment T-wave
segment complex wave

0.05 -0.10s

«0.25mV iso-elec 0.06-0.10S iso-elec 1/6-2/3 of R inconst.

R
"> o
! !

tr / I

o / I

5* / I

V / I

0.04 0.6-2.6mV
0.06mV

=£

Q
<
/ ^ M

' P >
J-pomt / T \^ <^-^
S
1 \ I

^-|
PQir iterval
12- 0.20s
QT in terval (frequer cy dependent)

M I I I I I I I I I I I I | I I I I I I I I I I I I I I I I I I I I I ill I I I I I I II
idol 8bl
q [— RQRS I

IE: 160 130 110 90 70 50

I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I.I I I, I I I I I I

tJ I

I 60
I'
50

53
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g £ T3
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g E g 0.3
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CD
n
<D
0- _o 0.2
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(A
o
*>
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o
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0)
0.1
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3 E E
i
CC CC o cc cc iO
(J
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LU
XX
CC
cc
CO
cc
c\>
cc
<-
x
cc
CO
X
cc
x
csi
CM

54
 CARDIOLOGY/ANGIOLOGY
ECG axes/QT duration

V ^-»-^^^_ i
+90°
ii in
AAa
-30° to +90° = normal axis -y A 7 Y
+90° to ±180° = right axis deviation
±180° to -90° = extreme right or left axis deviation
-30° to —90° = left axis deviation

Deviation of QT duration from normal value

Method:
1. Read off normal value of QT duration
(QT norm ) for relevant pulse rate (p. 53).

2. Align the isoelectric line with the horizontal

line relating to thedetermined QT norm value,
so that the end of the T-wave lies under the
numbered oblique line. The origin of Q
then indicates the desired percentage value.
(Example in illustration: QTnorm = 0.4 s,
relative QT difference = +10%). 40 30 20 10 10 20 30 40

55
MEMORIX CLINICAL MEDICINE

Points system for left ventricular hypertrophy

after Romhilt and Estes
(After Csapo and Kalusche (1989))

1. Amplitude criteria 3 points

a) greatest R or S wave in the extremity leads ^2mV
(20 mm; typically an increase of R in I and/or aVL)
b) greatest S wave in V„ V2 orV 3
2*2.5mV (25 mm)
c) greatest R wave in V4 , V 5 or V 6 s*2.5mV (25 mm)

The presence of one or more criteria fulfills the three points.

2. ST-T criteria
In patients not on digitalis 3 points
In patients on digitalis 1 point
ST segment and T-wave shift in opposite direction to QRS complex
(typically: ST
depressed in I, aVL or aVF; V^
[ST elevation in V 2_3 also ,

T flat, biphasic or negative in I, aVL, W^] possibly aVF; QT interval

prolonged)

3. Axis criteria

Left axis deviation greater than -15° 2 points

4. QRS criteria
a) left bundle delay: intrinsicoid
deflection (ID) begins at
> 0.04 sin 6V 1 point

> 0.04 s

b) QRS duration >0.9s 1 point

Maximum points: 10 points

Left ventricular hypertrophy 5^5 points

Suspicion of left ventricular hypertrophy 4 points

In patients in sinus rhythm, a leftward shift of P-wave axis (P mitrale) provides 3

additional points (provided that mitral stenosis has been excluded).

Conventional indices for left ventricular hypertrophy (all amplitudes are counted as
positive)

Sokolow-Lyon index:
S in V, or V 2 (whichever is greater) + R in V 5 or V >3.5mV
6
Lewis index:
RinI + SinHI>2.5mV
56
 CARDIOLOGY/ANGIOLOGY
Points system for right ventricular hypertrophy
1. Amplitude criteria 3 points
a) V,: R high (>0.7mV), S small (<0.2mV);
with incomplete right bundle-branch block V,: R > l.OmV;
with complete right bundle-branch block V,: R > 1.5 mV
b) V5^: R small, S deep (>0.7mV)
2. ST-T criteria 3 points
ST-T in opposite direction to QRS in V,_3 : ST segment depressed,
T-wave negative or biphasic
3. Axis criteria 2 points
Right axis: QRS > 120° (if > 150°, II predominantly negative)
4. QRS criteria
a) Right bundle delay: ID begins at > 0.03 s in V, 1 point
b) QRS duration between 0.09 and 0.11s 1 point

Maximum points 10 points

Right ventricular hypertrophy >5 points

Suspicion of right ventricular hypertrophy 4 points

Sokolow-Lyon index: for right ventricular hypertrophy: R in V 2 or V 3

+ S in V 5
or V6
(whichever is greater) >1.05mV
Atrial Alteration of the P-wave
strain configuration Representative lead Lead V.
(where esp. obvious)
Left Widened, notched I, II, aVL, V*. Negative 2nd part
(P mitrale
sinistroatrial P)
= (>0.11s)
^1
Macruz quotient
(measured in II) =
Duration of P (ms)
Duration of PR (ms)
>1.6
(normal 1.0-1.6)
Right Pointed, high II, III, aVF Positive
(P pulmonale = ,
(>3mm)
dextroatrial P)
A-

Both atria Widened I, II, III, aVL, Biphasic

(P cardiale and/or pointed, aVF, V^ (pointed and
biatrial P) high
A? widened)

57
MEMORIX CLINICAL MEDICINE

Stress testing
Nomogram for determination of target performance (75% of maximal
performance) for women and men in relation to age and weight (WHO nomogram)
(especially for progressive stress test in recumbent patient)

Alternatively: Calculation
(maximal target performance
in watts) (100%):

(Men): 3 W/kg body weight for

age 20-30, subtract 10% per
decade of life.
(Women): 2.5 W/kg body
weight, subtract 10%
per decade of life.

Alternatively: Nomogram for determination of target value of work capacity. The iden-
tified values indicate the maximal target performance (100%)

Age (years)

20-29 30-39 40-49 50-59 60-69

Maximal
heart
c? rate 190
Years
Submax.
85% 162 155
(Ellestad et al. (1979))

Rule of thumb for blood pressure:

At 100 W the arterial blood pressure
should not exceed 200/100 lying and 210/
105 sitting in patients aged 30-50. Above
<50Y 170/min 50 years of age the pressure should not
>50Y 160/min exceed 215/105 (sitting)
(After Lollgen and Ulmer (1985))

58
 CARDIOLOGY /ANGIOLOGY
Coronary arteries - nomenclature
(International Nomenclature Commission, Leningrad, 1970; after Kaltenbach and
Roskamm (1980))
Abbreviations
|
RCA Right coronary artery |

Bca Branch to conus arteriosus

San Sinoatrial node branch
Ra Right atrial branch
Rv Right ventricular branch
Km Right marginal branches
Pd Posterior descending branch
Ps Posterior septal branch
Avn Atrioventricular node branch
Rpl Right posterolateral branch
Rav Right atrioventricular branch

|lca Left coronary artery

|

CXA Circumflex artery

La Left atrial branch
Lav Left atrioventricular branch
Lpl Left posterolateral branch
Piv Posterior interventricular branch
Lm Left marginal branch
Ps Posterior septal branch
LI Left lateral branch
Avn Atrioventricular node branch

LAD Left anterior descending artery

Db Diagonal branch
Balanced supply As Anterior septal

Left-sided supply Right-sided supply

59
MEMORIX CLINICAL MEDICINE

Myocardial scintigram

60
 CARDIOLOGY/ANGIOLOGY
X-ray ventriculogram

Posterolateral

Parasternal Parasternal
coronal section longitudinal section*

Level of mitral valve

Nuclear medlcine\?Poste^
\ \medial i

61
MEMORIX CLINICAL MEDICINE

Echocardiography TM - normal values

Chest wall

Aortic root 50 it t t
50: 111
(mm) :

~rr~
40 40 IT"
30

20
P p 30

20

60
Left
"tfr -tUi m. RA
"Iff
70-1
-111
atrium (LA)
(mm)
L
50 j.
50 J

:
M_
TT~ atrium
(mm)
< ) \T"
;^- 70
j

40 |H 40 i^^^ 60 p- 60 ^^^_
3o|iiMi 30 9 50 B 50 fl|
20j| 2oJj 4o|
40J|

Outflow tract;
Right t t t
90 Sum of pre-aortic (RV,) and
ventricle
pre-septal (RV 2 ) diameters
(RV)
80 (mm)

70

60

50
i
'Leading edge method': measurement from leading edge to leading edge of the respective
echo structures.

62
 —
CARDIOLOGY/ANGIOLOGY
Echocardiography TM - ventricle

Left ventricular (LV) diameter

ED end-diastolic (measured at beginning of QRS)
ES end-systolic

LV
rf ED

80 ^j

70
LV
ES
® 60
Posterior wall ES ^picard.um

-Xx_j(
Pericardium

'Ju^L—
5U

40
50

40
P 40
50

tT

LV ED -LV ES
P
(Segmental) shortening fraction
LV ED

Myocardial thickness (ED): septum and posterior wall (mm)

J 9

Systolic increase in thickness (%)

fe
Normal range

Limits of normal range

(make allowance for height, weight
surface area, degree of training, etc.)

Modified after Bubenheimer (1982)

Posterior wall

63
 MEMORIX CLINICAL MEDICINE
ECG changes in infarct
posterior*

Infarct Coronary findings ECG changes in:

localization to be expected
(p. 59) i ii in aVR aVL aVF v, V, v, v4 v, vjv.
_^_
Large anterior Proximal occlusion
wall infarct of LAD
Anteroseptal Occlusion of
infarct peripheral parts of
LAD and As
Apical anterior Occlusion of
wall infarct peripheral
parts of LAD
Anterolateral Occlusion of peripheral
infarct parts of LAD and
inclusion of Db
Inferolateral Occlusion of Lm
infarct

Occlusion of
1 I

Inferior (diaphrag-
matic) posterior peripheral parts of
wall infarct

Posterior (basal)
RCA or CXA
Occlusion of peripheral
1
posterior wall parts and branches of
*
(*) (•)
infarct CXA, especially of Lav
1
always involved, unequivocal criteria (Q)

I often additionally involved, criteria not unequivocal (T wave inversion)

* posterior infarct -» indirect signs: especially high R waves in (V,) V 2
(V,)
(relation of R to S > 1 ) together with tall pointed positive T-waves

64
 CARDIOLOGY/ANGIOLOGY
Time course of typical changes after acute myocardial
infarct

7x •
CPK Creatine phosphokinase
6x r/ \

MB-CPK Isoenzyme of CPK (cardiac type)

GOT^
5x (Indication of infarct:
CK
4x MB-CPK > 6% of total CPK)
3x •
LDH GOT Glutamic oxaloacetic transaminase
2x
.^BSR (aspartate aminotransferase (AsT))
/LC
line ^V^ "-- LDH Lactate dehydrogenase

2 3 4 5
LC Leucocytes
Days ESR Erythrocyte sedimentation rate

Beginning of significant Greatest value of Average greatest multiple Average time to

change in activity (h) change in activity of normal value normalization

CPK 4-8 16-36 7 (2-25) 3rd to 6th day

MB-CPK 4-8 16-32 7 (-30) 2nd to 3rd day

GOT 4-8 16-48 7 (2-25) 3rd to 6th day

LDH 6-12 24-60 3.3 (2-8) 7th to 15th day

HBDH 6-12 30-72 3.5 (2-8) 10th to 20th day

Indication of 1st to 3rd hour 4th to 6th hour 7th to 9th hour 10th to 12th hour
infarct on ECG -40% -50% -90% up to 100%

Killip classification of cardiac insufficiency in acute infarct (after Killip and Kimball (1967))
I: No signs of cardiac insufficiency (no moist Rs (rales), no 3rd HS (heart sound))
II: Mild to moderate cardiac insufficiency: Rs over up to 50% of both lung fields or 3rd HS
III: Severe cardiac insufficiency, often pulmonary oedema: Rs over 50% of both lung fields, 3rd HS
IV: Cardiogenic shock

j
Intermediate ] Chronic stage
,
stage

-T"v-
 ' : ;

MEMORIX CLINICAL MEDICINE

Heart valve abnormalities

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66
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CARDIOLOGY/ANGIOLOGY

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70
 CARDIOLOGY/ANGIOLOGY

&. Pi
p o
at
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of

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71
MEMORIX CLINICAL MEDICINE

Systolic and diastolic flow rates of the normal and diseased

heart
(Modified after Bubenheimer and Kneissl (1990))

72
 CARDIOLOGY/ANGIOLOGY
Endocarditis prophylaxis
Prevention of endocarditis in patients with heart valve lesions, septal defect, patent ductus or prosthetic
valve:

Dental procedures that require antibiotic prophylaxis are:

Extractions
Scaling
Surgery involving gingival tissues

Antibiotic prophylaxis for dental procedures may be supplemented with chlorhexidine gluconate gel 1 %
or chlorhexidine gluconate mouthwash 0.2%, used 5 minutes before procedure.

Note. Oral clindamycin now replaces oral erythromycin (which caused nausea and vomit-
clindamycin is used, periodontal or other multistage procedures should not be
ing); if
repeated at intervals of less than 2 weeks.

Dental procedures under local or no anaesthesia.

1. Patients who have not received a penicillin more than once in the previous month, including

those with a prosthetic valve (but not those who have had endocarditis): oral amoxycillin 3g 1

hour before procedure; CHILD under 5 years, quarter adult dose; 5-10 years, half adult dose.
2. Patients who are penicillin-allergic or have received a penicillin more than once in the preceding
month: oral clindamycin 600 mg 1 hour before procedure; CHILD under 5 years, quarter adult
dose; 5-10 years, half adult dose.

3. Patients who have had endocarditis, amoxycillin + gentamicin, as under general anaesthesia.

Dental procedures under general anaesthesia.

1. No special risk (including patients who have not received a penicillin more than once in the

previous month):
either i.m. or i.v. amoxycillin lg at induction, then oral amoxycillin 500 mg 6 hours later; CHILD
under 5 years, quarter adult dose; 5-10 years, half adult dose
or oral amoxycillin 3g 4 hours before induction then oral amoxycillin 3g as soon as possible after
procedure; CHILD under 5 years quarter adult dose; 5-10 years, half adult dose
or oral amoxycillin 3g + oral probenecid lg 4 hours before procedure.
2. Special risk (patients with a prosthetic valve of who have had endocarditis): i.m. or i.v.
amoxycillin lg + i.m. or i.v. gentamicin 120 mg at induction, then oral amoxycillin 500 mg 6 hours
later; CHILD under 5 years, amoxycillin quarter adult dose, gentamicin 2mg/kg; 5-10 years,
amoxycillin half adult dose, gentamicin 2mg/kg.
3. Patients who are penicillin-allergic or who have received a penicillin more than once in the

preceding month:
either i.v. vancomycin lg over at least 100 minutes then i/v gentamicin 120mg at induction or 15
minutes before procedure; CHILD under 10 years, vancomycin 20mg/kg, gentamicin 2mg/kg
or i.v. teicoplanin 400mg + gentamicin 120 mg at induction or 15 minutes before procedure; CHILD
under 14 years, teicoplanin 6mg/kg, gentamicin 2mg/kg
or i.v. clindamycin 300 mg over at least 10 minutes at induction or 15 minutes before procedure then
oral or i.v. clindamycin 150 mg 6h later; CHILD under 5 years, quarter adult dose; 5-10 years,
half adult dose.

Upper respiratory-tract procedures

as for dental procedures; postoperative dose may be given parenterally if swallowing is painful.

Genito-urinary procedures
as for special risk patients undergoing dental procedures under general anaesthesia except that
clindamycin is not given, see above; if urine infected, prophylaxis should also cover infective
organism.

Obstetric, gynaecological and gastrointestinal procedures

(prophylaxis required for patients with prosthetic valves or those who have had endocarditis only),
as for genito-urinary procedures.

(After BNF)

73
 —
MEMORIX CLINICAL MEDICINE
Cardiac cycle
Calculations:
(cardiac output) =
SV x HR (stroke volume
x heart rate)
00
*
ti
5a DO ?! O-C T3 C 2 CI (cardiac index) =
< i2Q.CC = CO cardiac output

—
CC<B i2 ff CC CC^r / \

-1 1

- BSA ^body surface area'

120
S "*\ Aortic valve closure
3 SV (stroke volume) =
100
Aortic
valve
f \ >
/
tortic pressure"
EDV LV - ESV LV (end-diastolic
opennc /
\ / volume minus end-systolic volume of
1
\
- left ventricle)
380
1 4 SVI (stroke volume index) =
E
Left cha nber pressij e- SV / stroke volume \

f 60
1

5 Y \
BSA ^body surface area'
-
1
Q-
4° 5 EF (ejection fraction) =
_ Mitral

-
valve
closure Mitral valve - EDV 1V -ESV LV SV
20 \
~-
/ op< ning
sy^f --"-
T x^«_ __—— ^^
' EDV LV EDV LV
0L1 V.—-
Left atrial pressure
6 AP (mean arterial pressure) =
3 20
fl5 /
%!t Pi Imonary artery^
pr essure
syst. pressure + 2 x diast. pressure

/ 3
g 10 f
Righ t cham Der
pres sure
Right atrial pressu 9* (diast. pressure + 1/3 pulse pressure)
<^N / ,. , syst. -
— diast. \
diast. pressure +
«s cr r "
1

5
"
/ \ -
7 RCWI = CI x PAP m x 0.0136
1
r
4
3 /
\\ -

-
8 LCWI = CI x MAP x 0.0136
1 2
CI x PAP m x 13.6
/
/ \ \
1 1 / 9 RVSWI
< „
0^ -
/ HF
\r CI X MAP x 13.6
' - 10 LVSWI
38 r' HF
-
I
"
11 SVR (systemic vascular resistance):
'
32
i AP - CVP (or RAP) on

1 26 _ -
CO
mean arterial pressure -
20 L central venous pressure
_T3 1
2 (or mean pressure r. atrium)

iJ 1
i" I i,U
f
^ JJUL.
n heart minute volume
x 80
a C V
12 PVR (pulmonary vascular resistance)
PA - PCP
£l 1 x \

CO
R mean pulmonary artery pressure -
(pulmonary capillary pressure \

.1 OJ ^ Cha nber
T 3
heart minute volume /

<
5 systole

1. 'ill' ,
1 1

0.1 02 0.3 0.4 0.5 0.6 0.7 0.8

Time (s)

(After Berne and Levy (1977))

74
 CARDIOLOGY/ANGIOLOGY
Cardiovascular normal values
Parameter Units Normal
Abbreviation values

Cardiac volumes
CO Cardiac output (1) 1/min 5-6
CI Cardiac index (2) 1/min /m 2 2.6-4.2
SV Stroke volume (3) ml /beat 60-70
SVI (SI) Stroke volume index (4) ml /beat /m 2 30-65
(stroke index)
EDV End-diastolic volume ml
EDVI End-diastolic volume index ml/m 2 50-90
ESV End-systolic volume ml
ESVI End-systolic volume index ml/m 2 9-32
EF Ejection fraction (5) % 60-75

Cardiac pressures
CVP Central venous pressure cmH 2
5-12
RA (RAPm ) Right atrial pressure, mean mmHg 2-8
a-wave mmHg 2-10
v-wave mmHg 2-10
RVPs Right ventricular pressure, systolic mmHg 15-30
RVEDP Right ventricular end-diastolic mmHg 2-8
pressure
PA (PAPm ) Pulmonary artery pressure
mean mmHg 9-18
PAPs systolic mmHg 15-30
PAP ED end-diastolic mmHg 4-12
PCP (PCWP) Pulmonary capillary (wedge)
pressure mmHg 5-12
LA (LAP m ) Left atrial pressure, mean mmHg 2-12
a-wave mmHg 3-15
v-wave mmHg 3-15
LVPs Left ventricular pressure, systolic mmHg 100-140
LVEDP Left ventricular end-diastolic mmHg 3-12
pressure
AP (SA) Mean (systemic) arterial
(SAP) (MAP) pressure (6) mmHg 70-105
SAP, Systemic arterial pressure, systolic mmHg 100-140
SAPd Systemic arterial pressure, diastolic mmHg 60-90

Cardiac work indices

RCWI Right cardiac work index (7) kg m/min/m 2 BSA 0.6
LCWI Left cardiac work index (8) kg m/min/m 2 BSA 3.8
RVSWI Right ventricular stroke g m/m BSA
2
8-12
work index (9)
LVSWI Left ventricular stroke g m/m BSA
2
51-61
work index (10)

Resistances
SVR Systemic vascular resistance (11) dynes sec cm 5 700-1600
PVR Pulmonary vascular resistance (12) dynes sec cm -5 100-230*
also reported
in Wood units
(1 Wood unit =
80 dynes sec cm s
)

(After Grossman (1980))

75
MEMORIX CLINICAL MEDICINE

Swan-Ganz balloon
catheter

[mmHg]
40-

30

20

10
^JiJ\/\J\J\J\I^AN^K^
Work (W) 25 50 75 100 125 150
**. '', ,r -

18 '
.*' ,r- -
(# l* ,*'
16
I 14
y* > ,'
.' ,'
J -

ei2
,
- V i, -
'' -'
> -

' '
.'' .
% ,f*
.
'

-
-

8
,'
'*,
^ ;
-
.,
--

1 / '*'?
*' '
-
*'
8 6
'!'
---"'
»/;
<a 4
!

-J
PCP mr
T3
«
O
2 [rapJ
]

0.2 0.6

[
1.0

l/min ] —1.4 5
HMV
10
[ l/min ]
15
-*-
20

Cardiac output (CO) or oxygen Mean pulmonary capillary pressure

consumption (Vo 2 ) in relation to work (in (PCP m ) and mean pressure right atrium
watts); cycle ergometer recumbent (RAP m ) in relation to heart minute
(Values modified after Ekelund and Holmgren volume (HMV); at rest and on exercise
(1976), quoted in Gornandt (1989)) (cycle ergometer recumbent)

Upper limit of normal range of PVP m

I Upper limit of normal range of R AP m

76
 CARDIOLOGY/ANGIOLOGY
Cardiomyopathies
Categories1 Congestive Hypertrophic Restrictive
(dilated) (COCM) obstructive (HOCM)

V° X^^X \\
A°
x/T^^ \Ao^==^

a\X mtt- V~vl

Hypertrophy

Systolic pump
insufficiency
xJ Hz
Eccentric

+++
Concentric, mostly

-
asymmetric
+
V
Concentric, mostly
symmetric

Ejection fraction (EF) III n-T n - I

Diastolic congestive + ++ ++
insufficiency

Filling pressure (PCP) T TT TT

Echo criteria
LV ED (p. 63) TTT (n)-l
VF U(i) n-T l(i)
Wall thickness
septum n - I TTT T(T)
posterior wall n - I n-T T(T)

Echo abbreviations Asymmetric

and normal values, (eccentric) * 90%
see pp. 62, 63 mostly basal septum
TT; posterior septal
wall quotient > 1.5 b
with /without
obstruction
Symmetric - =5%
LA n (rel. MI,
mitral incompetence) T TT TT
RV T (advanced stage) n n
Mitral valve Septum-E-point distance SAM (systolic EF slope steep
TT anterior movement)
Often rel. MI due to - sign of obstruction
stretching of mitral EF slope flattened
valve ring
Aortic valve Reduced, delayed opening Mid-systolic notch
Muscular stenosis
with obstruction

a
Classification after WHO/ISFC (1980, 1981)
h
Also idiopathic hypertrophic subaortic stenosis (IHSS).
c
Hypertrophic obstructive cardiomyopathy (HOCM).

77
MEMORIX CLINICAL MEDICINE

Cardiac transplantation
Indication End-stage heart disorders (mostly, at present, cardiomyopathies —40%,
coronary heart disease ~40%, valve abnormalities, myocarditis, etc.).

End stage indicated by: despite maximal therapy, frequent and progressive clinical
events such as cardiac arrest (resuscitation), recurrent heart failure, considerable effort
intolerance, chronic hypotension, incipient reduction of renal or hepatic function,
increasing cachexia, low heart output, supraventricular or ventricular arrhythmias,
heart size TT, signs of congestion, etc.

Contraindications
(After Copeland J.G. et al (1987))

• Age
> 55-65 years, indication increasingly widened
(also young patients), dependent on 'physiological' age

• Severe pulmonary hypertension

(PA, > 65-70mmHg, PCP > 40mmHg),
pulmonary vascular resistance (PVR) > 6 (trend to > 8) Wood units
(~500dynessec cm 5 ); important whether PVR reversible

• Irreversible renal or hepatic damage

• Active systemic infection

• Systemic disease
(trend: less strong)

• History of behavioural disturbances, psychiatric illnesses

(trend: less strong, compliance!)

• Pulmonary infarcts, lung disorders of undetermind origin

(mostly only temporary contraindication)

• Insulin-dependent diabetes
(no longer a contraindication)

• Peripheral arterial occlusive vascular disease, cerebrovascular disease

Relative contraindication (e.g. surgically correctable?)

• Gastric or duodenal ulcer

(only temporary contraindication)

• Inadequate psychosocial support

(trend: less strong, compliance!)

78
 CARDIOLOGY/ANGIOLOGY
Conducting system of the heart

-Superior vena cava

3undle of Bachmann
Right bundle branch

Left bundle branch

HBE His bundle

electrocardiogram
(normal values)
PA time, which
corresponds
to the excitation in the
atrial regions near the AV
HBE node (25-50 ms)
AH conduction time in AV node
(60-1 00 ms)
HV conduction time in intranodal conducting
system up to myocardium (30-50 ms)
ECG V conduction time in the chambers

79
MEMORIX CLINICAL MEDICINE

Heart block
Type of block in ECG Diagnostic criteria

AV block = atrioventricular block

First degree PR interval > 0.02 s

Second degree
Type 1 (Mobitz I, Wenckebach) PR interval increases progressively to
maximal value, then failure of AV
conduction

Type II (Mobitz II) Single/multiple failure of AV conduction

(e.g. 2:1, 3:1, etc.)

With conduction the PR interval remains

constant

Third degree (complete AV block) AV conduction completely interrupted

RBBB: right bundle-branch block Delay of largest negative deflection
(>0.03s)inV, (V 2 )
Broad positive QRS complexes in III, aVF,
aVR,V„V (R<R' 2
in V,)
QRS 5* 0.12 s
compl ete-
QRS < 0.12 s
incompl ete-

"3
LAH: left anterior hemiblock Left axis deviation (-30° to -90°)
(very common) qR in I, aVL
rS in aVF, V 6
II, III,

QRS normal or slightly prolonged

5
LPH: left posterior hemiblock qR in II, III, aVF
rS in I, aVL
(rare, poor prognosis) Right axis deviation, > +110°
QRS < 0.12s
(exclude right ventricular hypertrophy)

LBBB: left bundle-branch block Broad, positive QRS complexes in I, aVL,

v ,v 5 6

Largest negative deflection in V 5,

V6 > 0.055 s
compl ete- QRS ^ 0.12 s
'0
incompl ete- QRS < 0.12 s
LAH + RBBB RBBB picture in V,, V broad, positive 2:

p (relatively common) QRS complexes + left axis deviation

qR in I, aVL, rS in II, III, aVF
LPH + RBBB Right axis, > +90°, rS in I, aVR
(very rare, poor prognosis) qR in II, III, aVF
(exclude right ventricular hypertrophy)

80
 CARDIOLOGY /ANGIOLOGY
Lown classification of VES
Lown class Definition

No ventricular extrasystoles (VES)

la Occasional VES (<l/min, <30/h)

lb Occasional VES (>l/min, <30/h)

2 Frequent VES (>30/h)

3 Multifocal VES
(some authors classify bigeminus as 3b)

4 Repetitive VES
4a Coupled VES
4b Salvoes of VES (3 or more consecutive VES)
(also ventricular tachycardia or fibrillation, in original Lown
classification, not retained)

5 Early VES (R-on-T phenomenon, normal ventricular complexes)

WHO classification of calcium antagonists

(After Vanhoutte (1987))

Class Typ c Substances

I Verapamil Verapamil

II Dihydropyridine Nifedipine, amlodipine,

Selective blockade
felodipine, isradipine,
A of slow calcium
lacidipine, nicardipine,
channels
nimodipine

III Diltiazem Diltiazem

IV Diphenylpiperazine Cinnarizine
No selective

B
blockade of V Prenylamine (not in use in UK)
slow calcium derivatives
channels
VI Others Perhexiline

81
 > > >

MEMORIX CLINICAL MEDICINE

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83
MEMORIX CLINICAL MEDICINE

Beta-adrenergic blocking agents

Substance ISA Cardioselecivity MSA H: hydrophiuc Half life

Product name ft L: lipophilic (h)*

Acebutolol + + + (L) 3-4

7-13

Atenolol - + - H 6-9
Betaxolol - + (+) L 16-22

Bisoprolol - + - L/H 10-12

Celiprolol + + - 4-5

Esmolol b - + - H 9

Labetalol 3 - - + (L) 3-4

Metoprolol - + - (L) 3-4

Nadolol - - - H 14-25

Oxprenolol ++ - (+) (L) 2-3

Penbutolol + (+) L 4-5

1-3
20

Pindolol + +(+) - (") (L) 3-4

Practolol ++ + - H 6-8

Propranolol - - +( + ) L 3-6

Sotalolc - - - H 10-15
5-12

Timolol -/(+> - - (L) 3-4

ISA intrinsic sympathomimetic activity.

MSA membrane-stabilizing activity.
* Differing data in the literature.
a
Simultaneous a, blockade.
b
Only i.v.
c
Additional anti-arrhythmic effect.

84
 CARDIOLOGY/ANGIOLOGY
Pacemakers
Always specified Possible additional data

1 2 3 4 5

Chamber(s) Chamber(s) Mode of Programmable Special

paced sensed pacemaker functions tachyarrhythmia
response functions

V Ventricle V Ventricle T Triggered Programmable B Bursts

(rate and/or Salvoes
output only)
A Atrium A Atrium I Inhibited M Multi- N Normal rate
programmable competition
(More than 3
functions)

D Dual D Dual D Atrium C Communicating S Scanning

(r. atrium + (r. atrium triggered, - possibility
ventricle) + ventricle) ventricle of non-invasive
inhibited interruption

O None O None None E External

These These These functions control
functions not functions not not present
present present

chamber chamber Pacing reacts Identification

to tachy- rather
than brady- code
arrhythmia
i

(Intersociety Commission for Heart Disease, after Parsonnet et al. (1981))

Pacemaker (PM) testing

ECG
Spontaneous rhythm, PM rhythm, PM impulse partially/completely effective (stimulation
loss), PM period duration constant (if not, — sensing defect), rate reduction, rate variation
>

(battery exhaustion), parasystole, extrasystole (-» spontaneous frequency too high with fixed-
frequency pacemaker, ?need for adjustment of medication)
(note hysteresis: fixed prolongation of basic interval after spontaneous heart beat).
• Possibly X-ray if suspicion of dysfunction: battery position, electrode course, continuity,
fracture, kink, displacement, disconnection of adaptor, myocardial or septal^perforation
• If spontaneous frequency greater than PM frequency:
- trial of carotid sinus massage, beta-blocker (beware side effects)
- Magnet ECG: switching from demand to fixed-frequency operation
(beware: occasional ventricular fibrillation -> defibrillator)
- Function analyses (specialized monitoring equipment)
a) Impulse interval (= stimulation interval, = period duration) = time interval
between 2 PM impulses in ms (increase = frequency reduction -* battery
exhaustion)
b) Constancy of impulse interval (inconstancy -» battery exhaustion)
c) Impulse duration (= impulse width, usually 0.3-1.5 ms, prolongation -> battery
exhaustion)
• Specialized investigations: stimulation threshold, sensing threshold, impulse amplitude,
impulse shape (oscillogram), antegrade, retrograde conduction, atrioventricular,
ventriculoatrial 'crosstalk', interference signal response
• Possibly stress test
• Possibly long-term ECG
MEMORIX CLINICAL MEDICINE

De Bakey's classification
of aortic dissections
Type I: The dissection involves the
ascending aorta, the aortic arch and
extends distally to varying degrees.
Type II: The dissection is confined to
the ascending aorta.
Type III: The dissection originates in

the region of the left subclavian artery

or distal to it, and extends distally to a
variable degree.

The arrows point to the site of the

intimal tear, with frequency in percent.

Radial artery Ulnar artery

86
 CARDIOLOGY/ANGIOLOGY
Fontaine's classification of peripheral vascular disease
Subgroups by Subgroups according to
Stage Classification criteria
|
|
|
|
walking distance Ratschow's positioning
test (see below)

I Objectively evident la Ratschow negative

perfusion defect without
subjective symptoms lb Ratschow positive
(Division into a and b in
stage I not universally
employed)

II Intermittent Ha Pain-free Ha Ratschow negative

claudication walking distance
greater than 200 m a

lib Pain-free lib Ratschow positive

walking distance
less than 200 a
m
III Rest pain

IV Ischaemic lesion
(gangrene)
a
100m and 300 m also used for subdivision.

Ratschow's positioning test

Interpretation Perfusion defect

Not present Mild Medium Severe

Patient lying Pallor of sole No pallor >60 <60 Immediate on

supine for 2 min: and toes elevation of
Alternate How rapidly? (s) legs
flexion and
extension
of ankle

Sit patient up Reddening of 5-10 10-30 30-60 >60

dorsum of foot
and toes
How rapidly? (s)
Uniform?
Bilaterally
symmetrical?
Filling of veins
of forefoot up to 15 20-30 30-60 >60
How rapidly? (s)
Bilaterally
symmetrical?
Persistent
reddening

87
MEMORIX CLINICAL MEDICINE

Abdominal arteries

1. Intercostal a. 14. Right gastric a. 27. Right colic a.

2. Subcostal a. 15. Hepatic a. 28. Branch to appendix
3. Lumbar aa. 16. Gastroduodenal a. 29. Inferior mesenteric a.
4. Coeliaca. 17. Superior pancreaticoduodenal 30. Left colic a.
5. Splenic a. a. 31. Sigmoid a.
6. Dorsal pancreatic a. 18. Right gastroepiploic a. 32. Renal a.
7. Artena pancreatica magna 19. Right branch of hepatic a. 33. Accessory renal a.

8. Terminal branches of splenic a. 20. Left branch of hepatic a. 34. Inferior phrenic a.
9. Short gastric aa. 21. Cystic a. 35. Superior suprarenal a.
10. Left gastroepiploic a. 22. Superior mesenteric a. 36. Middle suprarenal a.
11. Left gastric a. 23. Inferior pancreaticoduodenal a. 37. Inferior suprarenal a.
12. Branches to oesophagus from 24. Middle colic a. 38. Testicular a. (internal spermatic
11 25. Jejunal aa. a.) or ovarian a.

13. Common hepatic a. 26. Ileocaecal a. 39. Superior rectal a.

(From Muller, M.M., Rogoff, S.M. and deWeese, J.A. Arteries of the abdomen, pelvis and lower
R.F., Figley,
extremity. Kodak Publication No. M4-2. © Eastman Kodak Company. Reprinted courtesy of Eastman Kodak
Company)
 .

CARDIOLOGY/ANGIOLOGY
Pelvic arteries

40. Middle sacral a. 50. Internal pudendal a. 59. Femoral a.

41 Common iliac a. 51. Middle rectal a. 60. Perforating aa.
42. External iliac a. 52. Obturator a. 61. Superficial ilial circumflex a.
43. Inferior epigastric a. 53. Uterine a. 62. Medial circumflex femoral a.
44. Deep
circumflex ilial a. 54. Inferior vesical a. 63. Lateral circumflex femoral a.
45. Internal iliac (hypogastric) a. 55. Superficial epigastric a. 64. Ascending branch of lateral
46. Iliolumbar a. 56. Femoral a. circumflex femoral a.
47. Lateral sacral a. 57. External pudendal a. 65. Descending branch of lateral
48. Superior gluteal a. 58. Profunda femoris a. circumflex femoral a.
49. Inferior gluteal a.

(From Muller, R.F., Figley, M.M., Rogoff, S.M. and deWeese, J. A. Arteries of the abdomen, pelvis
and lower extremity. Kodak Publication No. M4-2. © Eastman Kodak Company. Reprinted courtesy
of Eastman Kodak Company)
MEMORIX CLINICAL MEDICINE

Arteries of the leg

External iliac a.
Inferior epigastric a.

ON Deep circumflex ilial a.

Internal iliac (hypogastric) a.
Iliolumbar a.
Lateral sacral a.
Superior gluteal a.
Inferior gluteal a.
Internal pudendal a.
Middle rectal a.
Obturator a.
Uterine a.

k Inferior vesical
Superficial epigastric a.
Common femoral
a.

a.

External pudendal a.
Profunda femoris a.
Femoral a.
v..
Perforating aa.
Superficial ilial circumflex a.
Medial circumflex femoral a.
Lateral circumflex femoral a.
Ascending branch of lateral circumflex femoral a.
Descending branch of lateral circumflex femoral a.
Transverse branch of lateral circumflex femoral a.
Muscular branches of femoral and profunda femoris aa.
Descending genicular a.
Popliteal a.

Articular branch of descending genicular a.

Saphenous branch of descending genicular a.
Lateral superior genicular a.
Medial superior genicular a.
Lateral inferior genicular a.
Medial inferior genicular a.
Sural a.
Anterior tibial a.
Posterior tibial a.

Peroneal a.

Anterior tibial recurrent a.

Dorsalis pedis a.
Perforating branch of peroneal a.
Medial tarsal a.
Lateral plantar a.
Lateral tarsal a.
Medial plantar a.
Arcuate a.
Deepest branch of dorsalis pedis a.
Dorsal and plantar metatarsal aa., dorsal and plantar
digital aa.
Anterior medial malleolar a.
Anterior lateral malleolar a.

(From Muller, R.F., Figley, M.M., Rogoff, S.M. and

deWeese, J.A. Arteries of the abdomen, pelvis and lower
extremity. Kodak Publication No. M4-2. © Eastman Kodak
Company. Reprinted courtesy of Eastman Kodak Company)

90
 CARDIOLOGY/ANGIOLOGY
Radiological anatomy of the great veins of the leg
(deWeese, J. A., Rogoff, S.M. and Tobin, C.E. Radiographic anatomy of major veins of the lower limb. Kodak
Publication M4-5. © Eastman Kodak Company. Reprinted courtesy of Eastman Kodak Company)

Femoral v. Femoral v.

Medial circumflex
femoral v.
'
Lateral accessory
saphenous v.

Profunda femoris v.

Femoral v.

Popliteal v. Popliteal v.

Sural vv.

Short saphenous v.

Anterior tibial vv.

Long saphenous v.

Peroneal vv.

Accessory Posterior tibial vv.

saphenous v.

Dorsal venous arch

Plantar venous arch -

|
Normal course of the veins j

Common anatomical
variants

91
MEMORIX CLINICAL MEDICINE

Varicose veins
Trendelenburg's test
Examination of the competence of the venous valves

Patient stands
Find and mark the opening of the long
saphenous vein into the femoral vein
Patient recumbent
a) Lift the leg until the varicosities empty, empty
fully by stroking
Compress the opening of the long saphenous with
venous tourniquet
Patient stands up
b) Observe varicosities for 10-1 5 s with compression
of opening
c) Then release compression

During compression (b) After release of compression (c)

Absent or only slow tilling from distally: No additional filling from the groin
valves of short saphenous and Valve at mouth of long saphenous competent
communicating veins competent Trendelenburg negative
Rapid filling from proximal to distal:
valve of short saphenous or Rapid or additional filling from the groin:
communicating veins incompetent valve at mouth of long saphenous incompetent
Trendelenburg positive

Perthes' test
Examination of the patency of the deep veins
Apply venous tourniquet and make patient walk about
a) Pathological:
Failure of emptying of varicosities with incompetent
deep veins
b) Normal:
Disappearance of the varicosities during walking
through drainage via intact communicating veins and
deep veins

Classification of chronic venous insufficiency of the leg

Chronic venous Symptoms
insufficiency (unilateral or bilateral)
Degree of severity
Oedema of ankle or calf; feeling of heaviness and tension of the
legs;dragging pain (possibly increased during menstruation or
pregnancy)
Paraplantar varicose corona
II Symptoms of grade I

also
Dystrophic skin changes:
Siderosclerosis, purpura jaune d'ocre,
atrophie blanche, pachydermia, acroangiodermatitis, hypodermitis

m Symptoms of Grade I and II

also
Florid or healed varicose ulcer

92
 "

CARDIOLOGY/ANGIOLOGY

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93
MEMORIX CLINICAL MEDICINE

Classification of hypertension
Joint National Committee
(by diastolic blood pressure only)

Diastolic Frequency Start therapy

WHO classification* (mmHg)
(by systolic and diastolic blood pressure)
> 115 'Severe' Normally at once
Systolic Diastolic hypertension
(mmHg) (mmHg)*** 20-30%
105-114 'Moderate' Control and individual,
Hypertension ^160 ^95 hypertension start within a few days

Mild'
90-104 } 70-80% See scheme, p. 98
Borderline 141-159 91-94 hypertension

Normal *£140 «90 <90 Normal

Isolated systolic hyperti systol. > 140 (>65 years > 160), diastol. < 90 mmHg

Classification by degree of damage to target organs (WHO*)

Grade I No organ changes
Grade II At least one of the following findings:
• Left heart hypertrophy on chest X-ray, ECG or echocardiogram
• Hypertensive retinopathy with generalized or regional narrowing of retinal
arteries (grade I—II)
• Proteinuria
Grade III Hypertension-mediated target organ damage:
• Hypertensive heart disease, left heart failure, cerebral haemorrhage,
hypertensive encephalopathy, malignant hypertensive retinopathy with
haemorrhages, exudates or papilledema (grade III-IV)
• Organ complications due to hypertension and other factors:
Coronary artery disease (angina pectoris, cardiac infarct), cerebral thrombosis,
transient ischaemic attacks, dissecting aortic aneurysm, peripheral vascular
disease, renal failure
Retinopathy***
Stage Arteries Relation Retina Optic disc
artery/vein

Normal Fine yellow reflex 3/4

Blood column visible

I Mild tortuosity 1/2

Broad yellow reflex
Blood column visible
II Arteriovenous nipping 1/3 Isolated

(yellow reflex)
Blood column visible
Early wall irregularities

III Silver wiring of arteries 1/4 Multiple margin

Indistinct
(white reflex) haemorrhages (prominence)
Blood column visible Cotton wool exudates
Marked wall irregularities

IV Fibrosed cords Multiple Papilloedema

Blood column invisible haemorrhages Engorged disc
Cotton wool exudates
* WHO (1978)
** Joint National Committee (1988)
•• After Keith, Wagener and Barker (1939)

94
 CARDIOLOGY/ANGIOLOGY
Step scheme for treatment of arterial hypertension 3

Further evaluation and/or referral to specialist or combination

with 3rd or 4th drug

Combination with 3rd drug from another class* or

substitution of the 2nd drug

Combination with 2nd drug from another class or

increased dose of 1st drug or substitution by another product

Diuretic or beta-blocker or calcium channel blocker or ACE inhibitor

Salt restriction Weight control

Non-drag treatment measures
Alcohol restriction Investigation of other cardiovascular risk factors

* Antihypertensives such as diuretics, beta-blockers, calcium channel blockers, ACE inhibitors,

alpha-blockers, centrally acting a-agonist, and vasodilators

Recommendations for combination therapy 6

Dual drag combination (recommended when blood pressure not below 140/90 mmHg
with monotherapy)

Diuretic
plus
Beta- or Calcium or ACE or ct,-

blocker antagonist inhibitor blocker

Calcium antagonist (t When combined,

choose Ca antagonist of
t plus dihydropyridine type
Beta- ACE (nifedipine, etc.))
blocker inhibitor

Tripl e drag combination

Alternative:
I
Diuretic plus beta-blocker plus vasodilator
a-agonist plus
{ Diuretic plus ACE inhibitor plus Ca antagonist
_J diuretic

[Diuretic plus a-agonist plus vasodilator

(Vasodilators: calcium antagonists, ACE inhibitors, postsynaptic

a, -blockers, hydralazine)

'Joint National Committee (1988)

b
Deutsche Liga (1990)

95
MEMORIX CLINICAL MEDICINE

Investigation of hypertension
Initial investigation*

History
Family: hypertension/ stroke/heart
attack?

Renal disease in family? in patient?

Pregnancy complications?
>-
Heart disease?

Drugs/oral contraceptives?

Hypertensive crises?

Tobacco habits?*'
Phaeochromocytoma
Physical
Multiple blood pressure measurements
examination
Obesity, general appearance? —-fr| Cushing's syndrome

Heart: auscultation

Pulse wrist/groin/foot
^ * | Coarctation of aorta?

Vascular bruit in abdomen?

Renal position: bimanual palpation

Sediment or dip stick test

Glucose*

Cholesterol**, triglycerides**, uric acid

Additional
Electrocardiogram
investigations

Renal ultrasound

When diastolic
Chest X-ray
pressure
repeatedly
>105mmHg Renal arteriography, especially
• with indirect indication of renal artery
stenosis,
• with hypertension that is difficult to
control medically
• in young patient

Fundoscopy —! Accelerated hypertension

96
 CARDIOLOGY/ANGIOLOGY

Suggestion of secondary hypertension/Investigation

Suggestion of phaeochromocytoma:
• Hypertensive crises (50% persistent hypertension)
• Paroxysmal somatic symptoms (headache, palpitation,
pallor, sweating attacks, tremor, nausea, tachycardia)
• Grade III or IV hypertensive retinopathy
• Loss of weight, glucose intolerance
• Extreme blood pressure rise during anaesthesia or
operation

—^Investigation
• Vanillylmandelic acid/catecholamines in 24-hour urine
• Possibly estimate in plasma, stimulation or suppression tests
• CT abdomen

Suggestion of renoparenchymatous or
renovascular hypertension:
• Urine protein t, serum creatinine T
• Renal history (oedema, nephritis, urinary infection, renal
trauma, polycystic kidney, etc.)
calculi, renal
• Age <30, > 55 years
• Diastolic > 120mmHg
• Lack of response to sufficiently high and combined
therapy
• Grade III or IV retinopathy
• Systolic/diastolic bruit over kidneys

-^Investigation:
• Excretion urography/early urography (difference between
sides)
• Isotope renography/divided renal clearance
• Digital subtraction angiography
• Intravenous angiotomography
• Renal arteriography

Suggestion of hypertension due to mineralocorticoid

excess (aldosteronism):
• Hypokalaemia (<3.5mmol/l)
• Exclusion of diuretic or laxative effect

Investigation:
• Repeated potassium estimations after withdrawal of
diuretics/laxatives (several weeks), high sodium diet
• Estimation of renin (low) and aldosterone (high) in plasma

* Deutsche Liga (1990) (Reprinted with permission).

** Not absolutely recommended
essential for investigation of hypertension, but for assessment of addi-
tional cardiovascular risk factors.

97
MEMORIX CLINICAL MEDICINE

Assessment and treatment of 'mild hypertension'*

Definition: diastolic blood pressure 90-104 mmHg (cf. p. 94)
Aim: diagnostic: accurate classification of the patient
therapeutic: reduction of diastolic blood pressure below 90 mmHg (and systolic,
if elevated)
Blood pressure recording at
least 3 times on 2 separate
occasions (days): if diast. BP
90-104 mmHg

Repetition of recording on
at least 2 further days within
4 weeks

After
Diast. BP < 90 mmHg Diast. BP 90-104 mmHg
4 weeks
Further recordings every Non-drug treatment
3 months for 1 year methods and supervision

Diast. BP 90-94 mmHg Diast. BP 95-99 mmHg Diast. BP > 100 mmHg
After total
ndt f Other risk factors
of 3 months
—> Supervision ndt + medical treatment ndt + medical treatment

After Diast.BP 90-94 mmHg Diast. BP 90-94 mmHg Diast. BP > 100 mmHg
further and no other risk factors and other risk factors with or without other
3 months Continuation of ndt and risk factors

supervision Medical treatment —» Medical treatment

* WHO/ISH (1989)
f
ndt = non-drug treatment

Differential therapy in hypertension

Differential therapy Recomendation

Older patient (>65y) Preferably Ca antagonists and diuretics

Coronary heart disease Preferabaly beta-blocker and Ca antagonists

Cardiac insufficiency Preferably diuretics and ACE inhibitors

Diabetes mellitus Non-selective beta-blockers and diuretics not recommended

Gout Avoid diuretics
Renal failure Serum creatinine over 180 umol/1: use loop diuretics
Potassium-sparing diuretics can lead to hyperkaiaemia
Delayed excretion of several antihypertensives (e.g. atenolol, nadolol, sotalol. captopnl.
enalapril, lisinopril, perindopril) should be noted

Pregnancy Methyldopa has been shown to be safe in pregnancy. Beta-blockers are safe in the third
trimester but may cause intrauterine growth retardation if used earlier

Hyperlipidaemia No long-term studies available which can justify specific therapeutic recommendations
 CARDIOLOGY/ANGIOLOGY
Unwanted effects of hypertension therapy

•
•

•
•
•
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uo o
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• •
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• •
• • •

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a
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z 1 c
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1 I 5 1 ft X i a 1 < z 5

Deutsche Liga zur Bekampfung des hohen Blutdrucks (1990) e.V., Heidelberg.
Reprinted with permission.

99
 1

MEMORIX CLINICAL MEDICINE

e and
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diet
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100
 > »
> » »

CARDIOLOGY/ANGIOLOGY

pain,

CPK, fibrates

of
prolonged

nausea,
of nausea,
nausea,

transaminases
Very drug
or eosinophilia

risk
epigastric
reduction Drug with

of about
nausea,
over
reduced
ECG. of
anticoagulants

increased
failure
of tolerance

transaminases possible.
in disturbances:

elevation
in disturbances: disturbances:

combination
Moderate
elevation
known
pruritus,
dosage
phosphatase;
renal
result elevation
interval

and
disturbances:
of glucose is
rhabdomyolisis)

8
of I
high in
ji
Possibly
phosphatase
QT
may
activity
dose of myositis.
Possible
Little

Avoid a
1 with gastrointestinal
impotence

elevation
treatment,
Possible gastrointestinal

of
gastrointestinal
03
q=
1 alkaline
drugs
of
TJ
i life CPK. C
interaction Reduce Reduction
(risk CO
of present.

gastrointestinal
vitamins
half CO
constipation.

and other alkaline

enhanced

discomfort.
and u
3 mild
myalgia, Possible
onset
diarrhoea.

mild
diarrhoea,
Prolongation

acid
3
at
of type. R
Drug
of acid.
at infrequent

•o biological
"w
c
a transaminases
fat-soluble

uric
transaminases
nicotinic
o
i Frequent
absorption Infrequent
diarrhoea;
gallstones.
reduction
interactions:

coumarin
Infrequent
possible.
abdominal
interactions

CO
g
flatulence, periods.
Flushing
vomiting,
flatulence,

u
e Very Q
9 of and long or
o
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1 vP
O
U <>
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2 2 2
SB <— <— <— — <—

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IS O o m
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£i
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u
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m
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"o
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CO
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Bezafibrate Fenofibrate

Nicotinic Acipimox
3
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101
MEMORIX CLINICAL MEDICINE

102
 CARPIOLOGY/ANGIOLOGY
^8
"O
CO
o
8 | « §
d
CO ^: £ 6 Q.
D)
t
D
CD life,
TOO
o Z «V J?

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t
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103
 CHEST MEDICINE
Estimation of daily cigarette consumption

55n 11 HbCO Cig./day

(%)
(approximately)

50- 10-

o
-45'
CD
c
2 40-
a. 0)
x E
<D
c35 2> 7

|30- 6-

|
3 25 ^ 5
i O
E o
c20-- £ A-
Calculation from HbCO (%)
15 Cig./day =
HbCO- 3.4
0.123

10
20 40 60
Cigarettes/day

Cigarette equivalent

1 cigarillo = 2 cigarettes
1 pipe = 2.5 cigarettes
1 cigar = 4 cigarettes

Estimation of cigarette consumption over the last 24-36 hours.

(Nodified after Vanuxem et al. (1980); see also Jarvis et al. (1986))

105
 c ' »
>

MEMORIX CLINICAL MEDICINE

duct t/3

ylothorax

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oracic
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106
 CHEST MEDICINE
Lung function tests
Abbreviations: Normal
5 ° IRV IC VC
values
:
IRV Inspiratory reserve 2.5 1
40
volume fl l\
/v/\/\i_ TV
TV Tidal volume
ERV Expiratory reserve 1.81
volume
RV Residual volume 1.21
20 ERV FRC TLC
IC Inspiratory capacity 3.01
FRC Functional residual 3.0 1 i.o

capacity
VC Vital capacity 4.81
RV RV
TLC Total lung capacity 6.0 1 Litre

Normal values after EGK (Europaische Gemeinschaft fur Kohle und Stahl) (Quanjer,
1983)

Tiffeneau test
Forced expiratory volume in the first second (FEV,)
Distinction: obstructive and restrictive ventilatory disturbances

Normal Obstruction, Restriction,

asthma, emphysema pulmonary fibrosis

, Is

FEV, =4.01 FEV, = 1.21 FEV, = 2.7 1

VC = 5.01 VC = 3.0 1 VC = 3.0 1

% = 80 ± 5 % =40 % =90
Present customary representation of spirometry as flow -volume curve ( V/V)
Expiratory flow (i/s) PEF Peak expiratory flow (= PEFR)
pef fef75 FEF75 Forced (maximal) expiratory flow at
75% residual VC (= MEF75 )
FEF50 Forced (maximal) expiratory flow at
50% residual VC (= MEF^)
FEF^ Forced (maximal) expiratory flow at
25% residual VC (= MEF^)
Volume (l) FEV] Forced expiratory volume in the first
second (= one-second capacity = Tiffeneau
test)
FIFjo Forced inspiratory flow at 50% VC
FVC- PIF Peak inspiratory flow
Inspiratory flow (1/s)
FVC Forced vital capacity

107
MEMORIX CLINICAL MEDICINE

Bronchial asthma
Type Extrinsic Intrinsic
Exogenous allergic Endogenous non-allergic

Patho- Release of bronchoconstrictor Induction of vagal reflexes

physiology substances from mast cells via 'sensitized' receptors
in mucosa

History Onset in childhood and young Onset in infancy and

adult life. adult life.

Allergy common in family history; Family history of allergy

often cradle cap, neurodermatitis, unusual; seldom cradle
rhinitis. cap, neurodermatitis,
Salicylate sensitivity common rhinitis.
Salicylate sensitivity
uncommon
Clinical Paroxysmal (seasonal) asthma; Chronic asthma;
course infrequent status asthmaticus. frequent status
Infrequent sinus infections or nasal asthmaticus.
polyps. Favourable course Sinus infections and nasal
polyps common.
Unfavourable course
Pathology IgE elevated, skin tests positive, IgE normal, skin tests
inhalation tests positive negative, inhalation tests
negative

Principal Desensitization effective, mast cell Desensitization ineffective,

therapeutic inhibitors (cromoglycate, ketotifen) mast cell inhibitors little
possibilities useful effect

Determine aetiology, stop smoking, avoid exposure, theophylline

preparations (serum assay), corticosteroids, p 2 -adrenergic agents,
oxygen (blood gas measurements!), adequate hydration,
mucolytics, anticholinergics, sedatives (cautiously!), antibiotics (if
signs of infection), inhalation therapy, physiotherapy; intubation
and ventilation (seldom necessary, after consultation with chest
physician and/or anaesthetist)

Classification by clinical severity

(After Schulze-Werninghaus and Debelic (1988))

I Incipient asthma:
Characterized by occasional dyspnoea or cough, also described as allergic
bronchitis or allergic tracheobronchitis.
II Mild asthma:
Occasional paroxysmal dyspnoea with irregular need for bronchodilators.
III Moderate asthma:
Variable paroxysmal dyspnoea with regular need for anti-asthmatic medication,
including occasional use of corticosteroids.

IV Severe asthma:
Frequent or continuous dyspnoea to severest asthmatic attack and continuous
requirement for corticosteroids.

108
 CHEST MEDICINE
Management of chronic asthma in adults*
Steps Notes

Stepl Note: Move to step 2 if needed more

Inhaled short-acting p -stimulant as required than once daily (or for night-time
(up to once daily). symptoms).

Step 2 Note: Higher dose of inhaled

Inhaled short-acting pVstimulant as required corticosteroid may be required to gain
plus initial control; some adults benefit from
Regular standard dose inhaled corticosteroid doubling for short period to cover
or try respiratory infection.
Regular cromoglycate or nedocromil (but change to
inhaled corticosteroid if control not achieved).

Step 3 Note: If problems with high-dose inhaled

Inhaled short-acting pVstimulant as required corticosteroids, continue with standard
plus dose and add regular inhaled long-
Regular high-dose inhaled corticosteroid (large-volume acting pVstimulant or regular modified-
spacer). release oral theophylline or may try
regular cromoglycate or nedocromil.
With proportionately prominent night-
time symptoms (despite otherwise good
control with standard or high-dose
corticosteroid inhalations) a modified-
release oral theophylline or a long-acting
inhaled pVstimulant may be considered
for administration at night.

Step 4 Note: High doses of inhaled

Inhaled short-acting pVstimulant as required bronchodilators should only be
with considered if the patient does not respond
Regular high-dose inhaled corticosteroid (large-volume to standard doses; pVstimulants and
spacer) ipratropium (or oxitropium) can be given
plus sequential therapeutic trial of one or more of using a nebulizer (or by multiple
Inhaled long-acting pVstimulant actuations of a metered dose inhaler
Modified-release oral theophylline with large-volume spacer).
Inhaled ipratropium or oxitropium
Modified release oral pVstimulant
High-dose inhaled bronchodilators
Cromoglycate or nedocromil

Step 5 Note: In addition to regular prednisolone

Inhaled short acting pVstimulant as required tablets, continue high-dose inhaled
with corticosteroids (in exceptional cases doses
Regular high-dose inhaled corticosteroids (large-volume exceeding 2 mg may be used).
spacer) and with one or more long-acting
bronchodilators (see step 4)
plus
Regular prednisolone tablets (as single daily dose).

Stepping down
Review treatment every 3-6 months; if control is achieved, stepwise reduction may be possible; in
patients whose treatment was started recently at step 4 or 5 (or contained corticosteroid tablets),
reduction may take place after a short interval; in chronic asthma a 3-6-month period of stability
should be shown before slow stepwise reduction is undertaken.
These recommendations are based on tables in: British Thoracic Society and others (1993) Guidelines on the
management of asthma. Thorax, 48, Supp, SI. Alternative recommendations are given for children. Reproduced
by permission of BMJ Specialist Journals.

109
MEMORIX CLINICAL MEDICINE

Recommendations for diagnosis, staging and surgical

treatment of carcinoma of bronchus
(Deutsche Gesellschaft fur Thorax-, Herz- und Gefasschirurgie, Deutsche Gesellschaft
Pneumologie und Tuberkulose (1988))
fiir

Basic diagnosis:
History, clinical examination, laboratory tests, radiology of thorax, lung function
tests, sputum cytology, bronchoscopy with cytology/biopsy.

Staging investigations:
Computerized tomography, upper abdominal ultrasound, skeletal scintigraphy, CT.

Staging of carcinoma of bronchus

T - Primary tumour
TX Primary tumour cannot be assessed, or demonstration of malignant cells in
sputum or bronchial washings but tumour not visible radiologically or at
bronchoscopy.
TO No evidence of primary tumour.
Tis Carcinoma in situ.
Tl Tumour 3 cm or less in widest diameter, surrounded by lung parenchyma or
no bronchoscopic evidence of infiltration proximal to a lobar
visceral pleura,
bronchus (main bronchus free).
T2 Tumour with one of the following characteristics regarding size or extent:
• Tumour greater than 3 cm in largest diameter,
• Tumour with involvement of main bronchus, 2 cm or more distal to carina,
• Tumour infiltrates visceral pleura,
• Associated atelectasis or obstructive inflammation up to hilum but not of
the entire lung.
T3 Tumour of any size with direct infiltration of one of the following structures:
Chest wall (including tumours of the superior fissure), diaphragm, mediastinal
pleura, pericardium; or tumour in main bronchus less than 2 cm distal to
carina but carina itself not involved; or tumour with atelectasis or obstructive
inflammation of the entire lung.
T4 Tumour of any size with infiltration of one of the following structures:
mediastinum, heart, great vessels, trachea, oesophagus, vertebral body,
carina; or tumour with malignant effusion.

N - Regional lymph nodes

NX Regional lymph nodes cannot be assessed.
NO No metastases in regional lymph nodes.
Nl Metastases in ipsilateral peribronchial lymph nodes and/or in ipsilateral hilar
lymph nodes (including direct extension of the primary tumour).
N2 Metastases in ipsilateral mediastinal and/or subcarinal lymph nodes.
N3 Metastases in contralateral mediastinal, contralateral hilar, ipsi- or
contralateral scalene or supraclavicular lymph nodes.

M - Distant metastases
MX The presence of distant metastases cannot be assessed.
MO No distant metastases.

110
 5

CHEST MEDICINE
TNM categories

Preoperative CTNM Final for

examination —>- (clinical —> inoperable
programme examination level) patient

>f

STNM Final for

9 Thoracotomy —^ (surgical —^ patient undergoing
examination level) exploratory
thoracotomy
> f

Histopathological examin-
pTNM Final for
3.
ation of the material —> (gross pathology —> patient after curative
resected with the intention
examination level) resection
of surgical cure

>
f

aTNM
4. Autopsy —> (staging on the basis —> Proof of staging
of autopsy findings)

10 •»»! 10

•mm* § 7
5|iil
•s •

Lymph node
distribution
1a Bronchopulmonary
1 b Lobar fissure
2 Hilum (main bronchus)
Carinal
Tracheobronchial
Paratracheal
Subaortic
Anterior mediastinum
Paraesophageal
Pulmonary ligament
Cervical

111
MEMORIX CLINICAL MEDICINE
Carcinoma of bronchus - histology
Histology

I
NSCLC J (non-small cell lung cancer): SCLC (small cell lung cancer):

Squamous cell carcinoma Small cell bronchial carcinoma

Adenocarcinoma
Large cell, undifferentiated carcinoma
Other, rare tumours
Classification |
SCLC; |

'Limited disease' (LD):

Tumour confined to one hemithorax, no major atelectases, no pleural effusion, no
venous inflow obstruction, no recurrent laryngeal paresis
'Extensive disease' (ED):
Tumour extension to contralateral hemithorax, major atelectases, pleural effusion,
venous obstruction, recurrent laryngeal paresis, involvement of supraclavicular
nodes, distant metastases

Histology

NSCLC SCLC
1

Supplementary investigations Possibly iliac crest biopsy

Mediastinoscopy
Pleural biopsy
Thoracoscopy
'Limited i 'Extensive disease*
Extended function tests
I

Localized tumour Extensive Chemotherapy

(T1N0M0), patient operable tumour (more
I

|
common) Possibly
Operation radiotherapy
I
Chemotherapy
Chemotherapy I

I
Consolidating
Radiotherapy radiotherapy
(mediastinum,
prophylactic
skull irradiation)

Operable Inoperable Primarily

metastasized
I I

Operation Primary
(lobectomy, radiotherapy
pneumonectomy) yv
Curative Palliative Symptom palliation
Ifappippriate,
(radiotherapy,
supplementary palliation chemotherapy)
radiotherapy
112
 1

CHEST MEDICINE
Carcinoma of bronchus - surgery
Exceptional case:
Peripheral round lesion, histology not obtainable by bronchoscopy,
no evidence of mediastinal or distant metastases

n_
Operable I
Inoperable
~f
Operation Percutaneous biopsy
I (guided by image
Histology intensifier or CT)
pTNM

NSCLC
L
— T
Further
'
ISCLCl
Chemotherapy
t Chemotherapy
investigation If appropriate, Follow-up; I

Reinforcing primary therapy only Reinforcing

radiotherapy radiotherapy when radiotherapy
symptomatic

Scheme for preoperative function tests

(for patients with carcinoma of bronchus) (Deutsche Gesellschaft fiir Thorax-, Herz-
und Gafasschirurgie, Deutsche Gesellschaft fiir Pneumologie und Tuberkulose (1988))

Definitive measurement: FEV, (preoperative), if appropriate supplemented by

regional analysis by means of

quantitative isotope perfusion scanning

1st stage I
FEV i 1

of function testing: plannd operation:

1 r If.

7*
> 2.50 ^-Pneumonectomy -> ^2.501 then: Calculated
Operable > 1.75 ^-Lobectomy -> ^ 1 .75 1 Isotope — >• postoperative

> 1.501 ^"Segmental resection "^ « 1.501 perfusion scan FEV,*

2nd stage of function testing: Calculated postoperative FEV,*

Operable High risk Inoperable
Pneumonectomy > 1.51 1.0-1.51 < 1.01
Lobectomy >1.51 0.8-1.21 <0.81
Segmental resection >1.21 0.8-1.21 <0.8l

Further investigations necessary (e.g. microcatheter)

* Calculation of postoperative FEV,: Example: Patient has tumour in right upper lobe and preop. FEV,
of 1.4 I. Perfusion in projection of right upper lobe is completely
100 - A- 0.37B
abolished. Residual perfusion of right lung amounts to 40%.
FE*i<po«op) FEV 1(preop) -
100
Calculation for resection of right upper lobe:
A Perfusion of resection - - (40 x 0.37)
100
B Perfusion of the side to be operated
0.37 Constant for the early postoperative
phase
Hence: postop. FEV, 1.19 1:
high risk for lobectomy

113
 MEMORIX CLINICAL MEDICINE

Treatment of tuberculosis
Standard therapy - duration 6 months
1
Initial phase (2 months) Continuation phase (4 months)

Triple therapy regimen

Isoniazid + rifampicin + pyrazinamide Isonazid + rifampicin

OR
Quadruple therapy regimen Ethambutol is added if resistance is

(if drug resistance is thought likely) thought likely

OR
Isoniazid + rifampicin + pyrazinamide Streptomycin is added if resistance to
+ ethambutol (or streptomycin*) isonazidis thought likely

* Now used only rarely

1
Longer treatment may be necessary for bone and joint infections; for meningitis or for resistant
organism

Dosage for standard unsupervised (daily) 6-month regimen

Antituberculous drug Children Adults
Daily dose (mg/kg Body weight Daily dose
body weight)

Isoniazid 10 All weights 300 mg

(max 300 mg)
Rifampicin 10 <50kg 450 mg
>50kg 600 mg
Pyrazinamide
(for first 2 months only) 35 <50kg 1-5 g
>50kg 2.0 g
Ethambutol**
first 2 months 15 or 25 All weights 15 or 25 mg/kg body weight
after 2 months 15 All weights 15 mg/kg body weight

** Not for children under 6 years of age

Dosage for fully supervised intermittent 6-month regimen

Antituberculous drug Regimen Children Adults
(mg/kg body
weight)

Isoniazid 3 times a week 15 15 mg/kg body weight

Rifampicin 3 times a week 15 600-900 mg
Pyrazinamide 3 times a week 50 2g (if body weight < 50 kg)
(for first 2 months only) 2.5 g (if body weight > 50 kg)
OR
Twice a week 75 3g body weight < 50 kg)
(if
3.5 gbody weight > 50 kg)
(if

Ethambutol** 3 times a week 30 30 mg/kg body weight

OR
Twice a week 45 45 mg/kg body weight

* Not for children under 6 years of age

114
 CHEST MEDICINE
Tuberculin testing
Only purified tuberculin (Tuberculin PPD) is available for skin testing.

Available as 100 000 units/ml (for Heaf test (multiple puncture)), and diluted 1 in 100
(1000 units/ml), 1 in 1000 (100 units/ml) and 1 in 10000 (10 units/ml).

1. Heaf test (multiple puncture test)

The reaction produced is equivalent to that produced by 5 international units of
intradermal PPD.

2. Mantoux test (intradermal test)

The initial diagnostic dose in patients in whom tuberculosis is suspected (or who are
known to be hypersensitive to tuberculin) is 1 unit of tuberculin PPD in 0.1 ml by
intradermal injection and in subsequent tests 10 and finally 100 units in 0.1 ml may
be given. For routine pre-BCG skin testing the 10-unit dose of tuberculin PPD is
used.

The tests are read after at least 72 hours and not later than 1 week.

The reaction is positive if there is palpable induration of 6 mm or more in diameter.

A negative result when testing with 100 international units makes the presence of
tuberculosis most unlikely.

115
MEMORIX CLINICAL MEDICINE
International classification of pneumoconiosis (ilo 1980)
(After Thurauf J., Erlangen. Reprinted with permission of Boehringer Ingelheim)
This classification is used for the evaluation of silicosis or asbestosis. Other interstitial lung diseases
and pleural disorders can be similarly assessed and classified by analogy.

image quality pn= good l±j= acceptable pi = inadequate [uj= useless

Opacities Profusion 0/- 1/0 2/1 3/2

12-step scale WO 1/1 2/2 3/3
(cf. standard film) 0/1 1/2 2/3 3/+
The first figure indicates the initial' classification choice, the second the possible
alternative.
Transitional forms are indicated, e.g. 1/2 or 2/1.

Definition of profusion
Category 0: Round or irregular opacities are absent, or less profuse than in
category 1

Category 1: Round or irregular opacities are clearly present, but in small numbers
Category 2: Numerous round or irregular opacities; normal lung markings still
visible
Category 3: Very numerous round or irregular opacities; normal lung markings
partly or totally obscured

Distribution (Lung fields) right upper RU LU :

left upper
right middle RM LM :
left middle
right lower RL LL :
left lower

Size small
Shape: round
(diameter)
[p]=il.5mm =
^ 1.5-3 mm [7]
= ^B 2

irregular
(width)
[s]=^6l.5mm Q] = ^d£ 1.5-3 mm [u] = 4^ :

mixed [p/s] [q/t]

(e-g.)
large [Aj = 1-5 cm (+0) [¥] = 5crn- |ru] [c1=>^U1
Type |wd[ = 9 well-defined [kT]= -^1' ill-defined

Pleural Diffuse Spread R)l = absent; <1 \T] = < 1/4 of lateral chest wall

thickening \2\ = 1/4-1/2 of lateral chest wall => 1/2 of lateral chest wall

Thickness [a] = < 5 mm [b] = 5-10 mm [c] = > 10 mm

Localization [r] = right sided [L]= left sided

Plaques Spread [0] = absent; < 1 [T] = < 2 cm max. length

121 2-10 cm max. length [3] = > 10 cm max. length

Thickness [a] = <5 mm [b] = 5-10 mm [c] = > 10 mm

Localization (chest wall, diaphragm) [r]= right sided [T] left sided

Costophrenic angle Obliteration QT] = right sided = left sided

Pleural Spread [0] = absent; < 1 |TJ = < 2 cm (+0) [2] = 2-10 cm Q]=>lOcm0
Localization (chest wall, diaphragm, elsewhere) right sided ] = left sided

Abbreviations
ax confluent small opacities em emphysema me mesothelioma of pleura
bu bullous emphysema es egg-shell hilus (calcification) od other disorders/phenomena (specify)
ca cancer of lung fr fracture of rib pi pleural thickening
en calcification in small opacities hi hilar/mediastinal lymph node englargement (interlobar/mediastinal)
co heart, size/alteration in shape ho honeycomb lung px pneumothorax
cp cor pulmonale idd indistinct diaphragm rp rheumatoid pneumoconiosis
cv cavity (>l/3 of hemidiaphragm) (Caplan's syndrome)
di distortion idh indistinct heart outline (>l/3 heart edge) tba active tuberculosis
ef pleural effusion kl Kerley lines (basal, perihilar) tbu inactive tuberculosis

116
 EMERGENCIES/ACID-BASE/ELECTROL YTES
Cardiopulmonary resuscitation (Marsden, 1989)

No response • Shout Establish Airway • Extend neck Summon help

• Shake • Chin upwards
and forwards
Clear oral
cavity

Including:
• Defibrillator
• Intubation equipment
• Oxygen
• Resuscitation trolley

No respiration Breathing • Mouth to nose Consider

• 2 initial breaths • Heimlich manoeuvre if

• 10-12/min airway obstruction

• Mouth to mouth
ventilation

No pulse Compression 2 assistants

Carotid artery • On hard surface
• 2 fingers above
xiphistemum
• Straight arms
• 4-5 cm
• 80-
100/min

Consider Defibrillation Electrode position

Precordial thump cardiac
if If flat ECG: Initially 200J
standstill, under monitor check switch, NB: do not
control leads and defibrillate
controls over
transdermal
glyceryl
trinitrate
patches
MEMORIX CLINICAL MEDICINE
Cardiac arrest
(Chamberlain, 1989)

w S> to

. Q. O >
0J O O CO
D co
ra
2

-o < O * ~
| §
no;?™
S-3

P CD 03 O

s ii
"O CO
c >—
CO o
cm oo c to
c\j o) co E O CD

£ ^ £ E .c Q
> '5 "5 *- 5 a
** I* c
52 S S c

2 c ® ra

- - £ c

</>"
8 o £ 5
S ' | .1 s
C > TJ O)
O CD o T3
E I

Io • ff KI
9z c "O
a>
o - «* jO

?£ > t (0 o— 0) 03 E O)
o OSo >CQ. o (0 3 c _ c
c O -£= Q. O Q) c CO ?
|

2? o o >
Q. OQ 2= Q. *- O O

118
 EMERGENCIES/ACID-BASE/ELECTROL YTES
Antidotes in poisoning
Conducting the telephone call

Caller Name, address, telephone number

Patient Who Age, weight, sex, location

What Description of poison (package label), consumption (route)

How much Most exact amount possible (if necessary, estimate)
When Time of consumption, confirmed or only suspected
Condition First symptoms, measures already taken, respiration,
circulation, state of consciousness

Advice Emergency measures before arrival of ambulance

Suspected poison Antidote

Amphetamine Ammonium chloride

Arsenic, organic and Dimercaprol (BAL) (chlorpromazine, ± beta-

inorganic mercury salts blockers)
Atropine, antihistamines Pyridostigmine, neostigmine

Barium Sodium sulphate

Benzodiazepines Flumazenil
Carbon monoxide Oxygen (hyperbaric if possible)

Cyanide Amylnitrite, dicobalt edetate, sodium nitrite, sodium

thiosulphate, hydroxocobalamin (vitamin B 12 )

Digoxin Digoxin-specific antibody (Digibind)

Extrapyramidal symptoms Biperiden

Iron Desferoxamine
Herbicides, paraquat Bentonite (Fuller's earth, activated charcoal)
Hyperthermia, malignant Dantroline
Isoniazid Pyridoxine (vitamin B6 )
Methaemoglobinaemia Methylene blue
(nitrites)

Methanol, glycol Ethyl alcohol

Opioids Naloxone
Organophosphorus Atropine (pralidoxime mesylate (P2S))
insecticides
(acetylcholinesterase
inhibitors)

Paracetamol Acetylcysteine, methionine

Phosgene Hexamine
Radioisotopes, heavy Sodium calcium edetate, dimercaprol (BAL),
metals penicillamine
Warfarin Vitamin K

119
MEMORIX CLINICAL MEDICINE

Activated charcoal administration in poisoning

Simultaneous administration of activated charcoal can delay the absorption of most
chemicals. Some substances are only insignificantly bound (see table). With several
drugs the administration of activated charcoal is appropriate even after absorption or
after parenteral administration (substances with small distribution volumes, weak
plasma protein binding and/or known enterohepatic circulation and/or known
secretion into the gastrointestinal tract) (see table).

Elimination accelerated even after Insignificant absorption by activated

absorption or parenteral administration charcoal

Antidepressants Acetylcysteine
Carbamazepine Alkali
Dapsone Boric acid
Digitoxin Caustic alkalis (sodium/potassium hydroxide)
Digoxin Cyanide
Glutethimide DDT
Meprobamate Ethanol
Methotrexate Malathion
Nadolol Mercury
Phenobarbitone Methanol
Phenylbutazone Mineral acids
Phenytoin Salts (lithium salts, iron salts)
Salicylate
Theophylline

Vesicle formation in poisoning

Amitriptyline, barbiturates, bites (snake, spider), CO, diphenoxylate, glutethimide,
meprobamate, methadone, methaqualone, nitrazepam, tricyclic antidepressants.

Fetor in poisoning Radio-opaque drugs

Drug Fetor Regularly radio-opaque

Amylnitrite Fruity Acetazolamide
Arsenic Garlic-like Acetylcarbromal
Chloral hydrate Pungent Barium
Chloroform Acetone-like, fruity Busulphan
Cyanide Bitter almonds Carbromal
Ethanol Alcohol-like Chloral hydrate
Ethchlorvynol Pungent Iodine-containing substances
Isopropanol Acetone-like, fruity Iron-containing substances
Malathion Garlic-like Potassium-containing substances
Mercaptan Rotten eggs
Methanol Alcohol-like Inconstantly radio-opaque
Organophosphate Garlic-like Antihistamines
Paraldehyde Pungent Phenothiazines
Parathion Garlic-like Tricyclic antidepressants
Phophorus Garlic-like
Salicylate Acetone-like
Hydrogen sulphide Rotten eggs
Tellurium Garlic-like
Thallium Garlic-like

120
 EMERGENCIES/ACID-BASE/ELECTROL YTES
Poisons information centres
(Consult day and night)

Belfast 01232 240503

Birmingham 0121 507 5588
or 0121 507 5589
Cardiff 01222 709901
Dublin Dublin 837 9964
or Dublin 837 9966
Edinburgh 0131 229 2477
Leeds 0113 243 0715
or 0113 292 3547
London 0171 635 9191
or 0171 955 5095
Newcastle 0191 232 5131

Note: Some of these centres also advise on laboratory analytical services which may be
of help in the diagnosis and management of a small number of cases.

121
MEMORIX CLINICAL MEDICINE

Estimation of suicide risk

(Kielholz, 1971)
1. Suicide indices

• Previous suicide attempts, direct or indirect suicide threats

• Expression of explicit ideas concerning the preparation and performance of a suicidal act, or 'unnatural
tranquillity'
• Dreamsof self-destruction, falls or disasters
• History of suicide in family or close contact (suggestion)
2. Morbid signs
• Onset or waning of depressive phases, confusional states
• Agitated anxiety, inhibition of affect or aggression
• Severe feelings of guilt or inadequacy
• Periods of biological upheaval (puberty, pregnancy, puerperium, menopause)
• Chronic sleep disturbances
• Incurable illness or delusion of illness
• Alcoholism and toxic confusional states
3. Enviromental factors
• Disrupted family relations in childhood (broken home)
• Loss or primary lack of human contacts (blighted love, loneliness, rejection)
• Loss of employment, lack of job satisfaction, financial worries
• Lack of religious affiliation

Activity profiles of antidepressants

(After Kielholz (1966))

S Psychomotor (thymeretics)
activating

Depression lifting (thymoleptics)

I Mood elevating

"™1 Sedating

Side effects of tri- and tetracyclics

Postural hypotension Anticholinergic Quinine-like Adrenergic

Amitriptyline ++++ + + ++++ + +

Doxepin +++ +++ ±
Imipramine ++++ ++++ + +++
Nortriptyline ++ ++ + +++
Desipramine ++ ++ + +++++
Maprotiline + + + +++++
Trazodone + + -
Trimipramine + ++ +
Amoxapine + + +++
Protriptyline + +++ +++

122
 EMERGENCIES/ACID-BASE/ELECTROLYTES
Review of psychotropic drugs
Classification Main action Principal agent

Minor tranquillizer Non-hypnotic sedative Benzodiazepine

without antipsychotic effect Meprobamate

Major tranquillizer Non-hypnotic sedative Phenothiazine

(neuroleptics) with antipsychotic effect Butyrophenone
Thioxanthene

Thymoleptics Mood-lightening Tricyclic

antidepressants antidepressants

Thymeretics Disinhibiting MAO inhibitors

antidepressants

Lithium Stabilization of cyclic Various salts

depression

Stimulants Motivation enhancing Amphetamine

Activity profile of neuroleptic drugs

Promazine

Methotrimeprazine

Thioridazine

Chlorpromazine

Haloperidol

Trifluoperazine

Perphenazine
Fluphenazine
^Thiopropazate
Flupenthixol

.Benperidol

123
MEMORIX CLINICAL MEDICINE

Short test of cerebral function

Questions Points

Orientation

1. What is today's date?

Day of week? Month? Year? Season? 5

2. Where are you now?

Hospital? Ward? Town? Country? 5

Memory
3. Memorize: lemon, key, ball*
(Dictate ca. every 1 s, have patient repeat until he or she can
remember the words) 3

Attention

4. Subtract 7s from 100 (93, 86, 79, 65)

or spell nature backwards (erutan) 5

Short-term memory
5. Repeat the words memorized at (3) above 3

Speech
6. Name: pencil (ballpoint), show patient a watch 2

7. Repeat: none and, when or but 1

8. Three-step command: take the paper in the left hand, fold it in

half, lay it on the floor 3

9. Write a sentence (must contain subject and object and make

sense; spelling mistakes do not count) 1

10. Draw the following figure with JL ^^^^

closed eyes:
.^r^^^^^^^^% 1

* Choose other words when repeating test

Total

0-23: Suspicion of organic lesion

124
 EMERGENCIES/ACID-BASE/ELECTROLYTES
Substance abuse
Opintes Hypnotics Tranquillizers Alcohol Stimulants Hallucinogens Cannabis

Examples Heroin Barbiturate Benzodiazepine Ethanol Amphetamine LSD* 8-9-

Cocaine Glutethimide Meprobamate C H,OH2 Sympathico- PCP* tetrahydro-

Morphine mimetics Mescalin cannabinol
Opium Appetite Psilocybin (THC)
Methadone suppressants

Respiration 1 1 Alcoholic 1 1
Hypoxia Hypoxia, possibly respiratory fetor Dry mouth
Toxic pulmonary acidosis Aspiration
oedema pneumonia

ConsOOUSDesS | to coma Possibly Possibly

delirium delirium,
coma

ftp* Contraction Contraction Dilatation Dilatation Dilatation Dilatation

Note: Nystagmus Nystagmus Conjunctival
Pethidine-* irritation

Dilatation

Circulation 1 1 1 ii f t t
Cocaine-* Hypothermia Facial Fever Palpitation
Cardiovascular flushing
complications

Psychological Euphoria Hallucination Slurred Right of Hallucinations Hallucinations

symptoms speech ideas
Hallucinations Agitation Incoordination Anxiety Anxiety Euphoria
Paranoia Confusion
Delusions
Violence
(PCP)

Therapy of
Airway, circulatory support, oxygen, gastric lavage, ia lysis, haemoperf usion.
hypothermia protection, rhabdomyolysis

Naloxone 1 Rumazenil Thiamine

Withdrawal Mydriasis
symptoms Myalgia Autonomic hyperactivity Autonomic Restlessness Agitation Anxiety
Abdominal Nausea, vomiting, anxiety hyperactivity Exhaustion "Bad trip" Tremor
cramps Sleep disturbances, tremor Sweating Psychomotor Nystagmus
Nausea Grand mal seizures Vomiting agitation (and others.
Vomiting Epilepsy cf. opiates)
Yawning Liver failure
Sweating Hallucinations
Tears Restlessness
Insomnia

Therapy Autonomic hyperactivity is an important pathophysi ological mechanisn i in the acute wi hdrawal phase: h ence
administration of alpha- and/or beta-blockers must r « considered

Clonidine Chlormcthiazoie Diazepam

Baclofen Anticonvulsants Talk down'
Methotri- Anxiolytics
meprazine PCP:
Haloperidol

Wanatag In emergency treatment of patients with substance a buse note danger c »f infection with HIV and hepatiti 5 viruses

* LSD, lysergic acid diethylamide; PCP, Phenycyclid rte

Lher-m, American Psychiatric Association (1987)

125
MEMORIX CLINICAL MEDICINE

Acid-base disturbances
Respiratory alkalosis (hyperventilation)

1. Central Stimulation of respiratory centre (anxiety, fever,

hypoxaemia, salicylate, exertion)

2. Thoracic Reflex stimulation of respiratory centre (pulmonary

embolus, pneumonia, atelectasis, pulmonary oedema,
asthma)

3. Various Sepsis, overbreathing, pregnancy, hepatic cirrhosis

Respiratory acidosis (Hypoventilation)

1. Central Disturbed function of respiratory centre (trauma, drugs/

poisoning)

2. Thoracic Disturbed mechanics of breathing (poliomyelitis,

myasthenia gravis, trauma)

Disturbed lung structure (emphysema)

Metabolic alkalosis

1. T Acid loss Loss of gastric juice, diuretic therapy, severe potassium

depletion, Cushing's syndrome, Conn's syndrome
2. T HC0 3 supply Iatrogenic HC0 3
~ administration, milk-alkali syndrome,
overventilation of chronically hypocapnic patients,
~
metabolism of ketone bodies and lactate to HC0 3

Metabolic acidosis (Kussmaul respiration)

1. t Acid supply Ketoacidosis (Diabetes, starvation, alcohol)

(T anion gap, Lactic acidosis (Shock, biguanide poisoning, CO
normochloraemia) poisoning, terminal hepatic cirrhosis,
leukaemia)
Drugs/poisoning (Methyl alcohol, ethylene glycol,
salicylate, isoniazid, cyanide,
nitroprusside)

2. t HCO,- loss HC0 3

~ loss (Diarrhoea, intestinal fistulae,

(normal anion gap, pancreatic fistulae, ileostomy, carbonic

hyperchloraemia) anhydrase inhibitor administration,
ureterosigmoidostomy)
Chloride retention (Renal tubular acidosis, administration
of arginine, lysine, NH C1)
4

3. i Acid excretion Renal failure, hypoaldosteronism, congenital enzyme

Anion gap:
Normal value: 8-12mmol/l Anion gap = Na + - (CI" + HCO,)
126
 EMERGENCIES/ACID-BASE/ELECTROL YTES
Acid-base nomogram
(After Siggaard-Andersen (1963))

HC0 3 in plasma
(mmol/l)
Total CO ?
60 -q -a

Acid-basa status in blood at 37°C

To use:
1. Connect pC0 and pH, read off on left HCCV or total C0
2
2
.

2. Measure Hb concentration, read off base excess on appropriate Hb line.

127
 r

MEMORIX CLINICAL MEDICINE

Blood gas analysis (normal values) Pressure PH

pQ 2 and pCQ 2
nmol/1
Estimation Units Arterial Venous Capillary [kPa] [mmHg]
30 —

PH 7.38-7.42 7.36-7.40 7.38-7.42

PO; mmHg 90-100 35-45 >80

kPa 12-13.3 4.6-6.0 >10.6

pCO :
mmHg 35-45 40-50 38-45
kPa 4.6-6.0 5.3-6.6 5.1-60

Oxygen
saturation % 95-97 55-70 95-97
(S0 2 )

Standard 10 -
bicarbonate mmol/1 21-29 24-30 21-29
(HOV)
Base
excess mmol/1 -2 to +2 -2 to +2 -2 to +2
(BE)

Estimation of acid-base disturbances

Required: pH, pCO and HC0 3 z

I>efi nit ions of acid-base

Acidosis: pH below 7.36 Alkalosis: pH above 7.44

Respiratory acidosis: p,C0 2 above 45 mmHg Metabolic acidosis: Bicarbonate
(=6kPa) below 21 mmol/1
Respiratory alkalosis: p,C0 2 below 35 mmHg Metabolic alkalosis: Bicarbonate
(=4.5 kPa) above 29 mmol/1
^^ «^~ HCO,
pCO, ^^^^ Under 21 mmol 21-29 mmol/1 Above 29 mmol/1

Above 6k Pa Combined metabolic Respiratory Metabolic alkalosis and

45 H
mmHg and respiratory acidosis acidosis respiratory acidosis

4.5-6.0kPa Metabolic Normal Metabolic

35-45 mmHg acidosis alkalosis

Below 4-5 kPa Metabolic acidosis Respiratory Combined metabolic

35 mmHg and respiratory alkalosis alkalosis and respiratory alkalosis

Calculation of the bicarbonate required to correct pH

I Bicarbonate required = negative base excess (base deficit) x 0.3 x body weight in kg

The formula permits the direct calculation of the required amount of sodium bicarbonate in
millilitres, if 8.4% sodium bicarbonate is used (1ml = 1 mmol)
Approximate relationship between pH and H* ion concentration
.»«pc°>
,„.,
HCO,
**«.=£
pCO,
nmol/1

128
 EMERGENCIES/ACID-BASE/ELECTROL YTES
Sodium and potassium
Hypernatremia Hyponatremia

1. T Intake 1 I Intake
Salt consumption Polydipsia
Sodium bicarbonate 2. T Gastrointestinal losses
Sodium penicillin Vomiting, diarrhoea
2. 4 Renal excretion Aspiration of gastric juice
Diabetes insipidus Fistulae
(renal, posterior pituitary) 3. T Renal losses
Osmotic Polyuric phase of acute renal failure
3 Endocrine Salt-losing nephritis
Cushing's syndrome Diuretics
Primary hyperaldosteronism Osmotic
Hyperosmolar diabetic coma 4. Endocrine
4. Others Addison's disease
Laboratory error Inappropriate ADH
secretion (see p. 130)
Ketoacidotic diabetic coma
5. With water balance disturbances
Sodium deficit in mmol/l (cf table p. 130)
6. Others
(142 - measured Na*) x body weight Laboratory error
Dilutional
s
False, in hyperlipidaemia, hyperproteinaemia

Hyperkalemia Hypokalemia

1 T Intake 1. 4. Intake
Potassium infusion Malnutrition
Stored blood transfusion 2. T Gastrointestinal losses
2. i Renal excretion Vomiting, diarrhoea, fistulae
Acute renal failure Laxative abuse
Chronic renal failure 3. T Renal losses
Addison's disease Osmotic diuresis
Hypoaldosteronism Diuretics (saliuretics, carbonic anhydrase inhibitors)
Potassium-sparing diuretics Cushing's syndrome
ACE inhibitors Hyperaldosteronism (primary and secondary)
3. Displacement from cells Renal tubular acidosis
Acidosis Metabolic alkalosis
Crush syndrome 4. Displacement into cells
Haemolysis, rhabdomyolysis Alkalosis
Burns Insulin therapy
Digitalis intoxication Hypokalemic periodic paralysis
Succinyl choline 5. Others
Hyperkalaemic periodic paralysis Magnesium deficiency
4 Others Laboratory error
Poor phlebotomy technique Diabetic ketoacidosis
haemolysis
in vitro
Laboratory error
Thrombocytosis, leucocytosis

Potassium replacement
and pH
Calculation:

1. Determine body potassium

mmol/kg Male Female

Normal 45 40

Moderate weight loss 38 33

Severe weight loss 30 26

2. Read off arterial pH and K+ from nomogram

and assess body weight condition.
3. Calculate K + requirement/excess by
multiplying body potassium by weight and
"20 -10 +10 +20
read off on the nomogram the percentage
adjustment. Body potassium (% deficiency or excess)

129
MEMORIX CLINICAL MEDICINE
Calcium and phosphorus
Hypercalcaemia Hypocalcemia
T Intake i Intake
Hypervitaminosis A/D Malabsorption
Milk-alkali syndrome
Endocrine
Endocrine Hypoparathyroidism
Primary hyperparathyroidism Secondary hyperparathyroidism
Tertiary hyperparathyroidism Vitamin D deficiency (rickets, osteomalacia)
Hyperthyroidism Electrolyte disturbances
Acromegaly Hypomagnesaemia
Adrenal cortical insufficiency
Hyperphosphataemia
Ectopic ADH production
Drugs
Drugs
Anticonvulsants
Thiazide diuretics
Lithium Others
Hypoalbuminaemia
Others
Pancreatitis
Bone metastases Distal renal tubular acidosis
Tnerapy of tumours with metastases
Laboratory error
Multiple myeloma
Immobilization
Sarcoidosis
Recovery phase of acute renal failure
Laboratory error

Correction for serum albumin

Add 0.02mmol/l Ca for each g/1 of serum albumin below 40g/l, subtract 0.02mmo!/l Ca
for each g/1 of serum albumin above 40 g/1.

Hyperphosphataemia Hypophosphataemia

T Intake 1 Intake
Malnutrition
Endocrine
Malabsorption
Hypoparathyroidism
Secondary and tertiary hyperparathyroidism
Parenteral nutrition without P supplement
Diabetic coma
Hyperthyroidism T Renal losses
Acromegaly Renal tubular acidosis
Fanconi syndrome
Drugs
Diphosphonate Endocrine
Cytostatic agents Primary hyperparathyroidism
Vitamin D-resistant rickets
Others
Acidosis Electrolyte disturbances
Renal failure Hypercalcaemia
Burns Hypomagnesaemia
Laboratory error
Drugs
Diuretics
Phosphate binders
Antacids, salicylate poisoning

Others
Alkalosis
Gram-negative septicaemia
Laboratory error

130
 EMERGENCIES/ACID-BASE/ELECTOROLYTES
Magnesium
Hypermagnesaemia Hypomagnesaemia
T Intake 1 Intake
Mg 2+ -containing antacids and laxatives Malnutrition
Mg 2+ infusions Malabsorption
Chronic alcoholism
Parenteral nutrition without Mg2+ -supplements
i Renal excretion T Renal losses
Renal failure Diuretics (apart from potassium sparers)
Diabetic ketoacidosis
Renal tubular defects
T Gastrointestinal losses
Vomiting, diarrhoea
Aspiration of gastric juice
Small intestine bypass

Endocrine
Hyperaldosteronism
Hyperthyroidism
Vitamin D therapy
Others Others
Rhabdomyolysis Pancreatitis
Burns With hypercalcaemia
Laboratory error After aminoglycoside antibiotics
After cisplatin treatment
Laboratory error

Syndrome of inappropriate ADH secretion (siadh)

Criteria: • Hyponatraemia and low serum osmolality
• No dehydration
• Urine osmolality higher than serum osmolality
• Increase of sodium and serum osmolality with water restriction
• Normal function of kidneys, pituitary, thyroid and adrenals

Causes
CNS disorders Encephalitis, meningitis, brain abscess, cerebral tumour, skull/cerebral
trauma, subarachnoid haemorrhage, subdural haematoma, venous sinus
thrombosis, Guillain-Barrd syndrome, cerebral lupus erythematosus

Lung disorders Pneumonia (bacterial and viral), tuberculosis, lung abscess, empyema,
chronic obstructive airways disease, PEEP ventilation

Ectopic ADH production Small cell carcinoma of bronchus, carcinoma of pancreas, carcinoma of
(paraneoplastic) duodenum, leukaemia, Hodgkin's lymphoma, thymoma
Drug induced Carbamazepine, chlorpropamide, clofibrate, cyclophosphamide,
lithium, narcotics, nicotine, oxytocin, thiazides, tricyclics, vasopressin,
vinblastine, vincristine

Hypothyroidism, Addison's disease, hypopituitarism, emotional stress

(142 - measured Na + ) x body weight

Water excess in litres
700

131
 GASTROENTEROLOGY
Anatomy of the digestive organs
Oesophagus Small bowel (2 5-4.5 m) 14 Jejunum
1 Mouth of oesophagus 15 Ileum
(Zenker's diverticulum Duodenum (25-30 cm) (Meckel's diverticulum)
2 Aortic impression 9a Duodenal bulb 30-100cm
(traction diverticulum) 10 First (superior) part prox. of 15a
2a Aorta 11 Second (descending) part
3 Diaphragmatic impression 11a Third (horizontal, inferior) part Large bowel (~ 1 5 m)
12 Fourth (ascending) part 15a lleocaecal valve
Stomach 13 Duodenojejunal flexure 16 Appendix
3a Cardia 17 Caecum
4 Fundus (with air bubble) 18 Ascending colon
5 Lesser curvature 19 Hepatic (right) flexure
5a Angular notch (incisure 20 Transverse colon
angularis) 21 Splenic (left) flexure
6 Greater curvature 22 Descending colon
7
8
Body
Antrum
3 t Wf 23
24
Sigmoid colon
Rectum
9 Pylorus o
15 cm i cB 25 Rectal ampulla
3

CD
3 25 cm
1
2 ib 2a

Typical
radiological wall
appearances

Liver
26 Falciform ligament
26 Ligamentum teres
(umbilical vein)
Haustrations
27 Right lobe
Semicircular folds
28 Left lobe

133
 .

MEMORIX CLINICAL MEDICINE

Abdominal ultrasound - anatomy and technique
Longitudinal section - anatomy

Sector scan

Transverse section - anatomy

Ventral
Transducer
Linear scan Sector scan
Superior mesenteric artery

• Stomach

Aorta
vena cava

Schematic examination Systematic method of ultrasound

sequence (l-VII) of liver nomenclature:
and gall bladder with the 1. Description of the echoes: strength

required planes of cut in (strong/weak), size (fine/coarse), interval

ultrasound between echoes (dense/isolated).
re
rti
i* 2.Assessment of the echo pattern:
distribution of the echoes
(homogeneous/patchy )
mC 3. Assessment of the sound distribution:
sound reduction (shadow), 'relative
sound enhancement' (behind fluids).
4. Circumscribed changes (weak echo).

Glossary of ultrasound morphology:

Echo-free with distal 'sound Homogeneous/regular
enhancement'
Patchy/irregular
Echo-poor/poor reflection Bright reflections/with distal sound ijjji
f

Echo-dense/echogenic/ shadow
reflective/rich reflections

134
 GASTROENTEROLOGY
Ultrasound of the liver
Characteristics of diffuse and circumscribed changes of hepatic parenchyma

Hepatic Normal liver Acute hepatitis, Fatty liver Cirrhosis

parenchym- acute congestion
atous diseases
Size (cm) 12cm (±2) >12cm >12cm >12cm
midclavicular or < 12cm
line

Contour ventral Flat Convex Convex Convex

dorsal Concave Convex Convex Convex

Caudal liver Acute-angled Rounded Blunt-angled Swollen

edge

Inner structure Fine Fine Coarse Coarse

Regular Regular Dense Dense
Regular Irregular

Sound Normal Mildly Moderately Moderately

conduction reducing reducing reducing

Margin Shape Size Echo Distal Localization

pattern reflections

Echogenic Metastases Smooth Irregular Variable Irregular, often Reduced Multiple/

(echo-dense) ca.30% lessechogenic overlapping
circumscribed rim - 'bull's eye'
liver lesions
Liver cell Irregular Irregular Variable Irregular Reduced Solitary/
neoplasms overlapping

Cholangio- Smooth Irregular Variable Irregular Reduced Solitary/

carcinoma portal

Haemangioma Smooth Regular Variable Regular Slightly Solitary/

enhanced multiple

Organized Anatom. Variable Variable Regular Reduced Solitary

haematoma determined

Localized fatty Irregular Determined Variable Regular Reduced Solitary/

infiltration multiple

Weaker echo- Metastases Irregular Round, Variable Irregular Enhanced/ Multiple/

genic circum- ca.60% oval reduced overlapping
scribed
Adenoma Regular Round, Variable Regular Reduced Often
liver lesions
oval solitary

Focal nodular Irregular Round, Variable Regular Reduced Often

hyperplasia oval solitary

Fresh abscess Irregular Round, Variable Irregular Reduced Mostly

oval solitary

Liver cell Irregular Round, Variable Irregular Reduced Mostly

neoplasm oval solitary/
overlapping

Lymphoma Regular Round, Variable Regular Reduced/ Multiple

oval enhanced

Non-echo- Congenital cyst Regular Round Variable Free Increased Ubiquitous

genic
Post-traumatic Regular Irregular Variable Free Increased Mostly
circum-
cyst solitary
scribed
liver lesions Hydatid Regular Round Variable Daughter cysts Increased Solitary/
multiple

Fresh Anatom. Irregular Variable Possibly Increased Solitary

haematoma determined

Chronic abscess Irregular Irregular Variable Possibly Increased Solitary/

multiple

Metastases Irregular Irregular Variable In region of rim Increased Often

multiple

135
MEMORIX CLINICAL MEDICINE
Ultrasound of gall bladder, pancreas and kidney

Normal findings Sonographic criteria in pathological findings

Gallstone Cholesterol- Acute Adeno-

normal polyps cholecystitis myomatosis
• Echogenic • Wall
Length 8-1 lcm reflections, • Wall- • Wall thickness • Irregular thickening
Thickness 3-4 cm often bowed associated >3mm, moderate '
Irregular
Capacity 30-55 ml • Distal sound echogenic several wall borders,
Wall «3mm shadow structures layers thickening often
(>3mm) • Immobile • Tenderness up to filling beyond
Intrahepatic • Mobile on • No sound on palpation of lumen gall

change of shadow • Pericholecystitis bladder

normal |4-6n posture » Usually
J

evidence
pathological >7mm
of stones
(After cholecystectomy
9-1 lmm normal)

Pancreas |
normal |A = 3ci Acute pancreatitis Chronic pancreatitis
B - 2cm • Pancreas enlarged • Pancreas reduced 1
Circumscribed
3 cm
=
• Poorly demarcated • Sometimes circumscribed enlargement
from surroundings enlargement, 'pseudo- •
Non-homogeneous
Pancreatic duct « 3-4 mm
• Homogeneous/non- tumorous pancreatitis' '
Pancreatic duct
homogeneous, faint • Pseudocysts widened
echo • Calcification •
Vascular
• Pancreatic duct dilated displacement

Pancreatic duct *s 3-4 mm

Confluent part
of superior
mesenteric
and portal
veins

Aorta Splenic vein

Kidney normal Atrophic kidney Obstructed kidney

6-12cm • Kidney small • Dilatation of renal •

Circumscribed
Cortical width • Poorly demarcated pelvicalyceal system organ border,
> 1.5 cm, • Ill-defined overlapping echos
age dependent
Difference between
sides > 1.5 cm,
pathological

136
 GASTROENTEROLOGY
Ultrasound of adrenals and spleen

[
Normal findings Sonographic criteria in pathological findings

normal Residual urine normal 10-30 ml after

| |
[ [

spontaneous voiding

right

Residual volume by ultrasound (ml) =

breadth (B) x height (H) x length (L) x 0.52 (in cm)

Transverse cut Longitudinal cut

Spleen Splenomegaly Splenic infarct

|
normal |
Splenic thickness Wedge-shaped anechoic
(1) Length (depth) cm] >4.5-5cm internal structure
(2) Breadth Rule of 4711'
(3) Length (from *s|
SI" From 5 cm moderately
pole to pole) enlarged
(4) Thickness « 4 cm
(From 5-6 cm just
(Normal spleen should not override left
palpable)
kidney by more than one-third)

Spleen thickness:
left lateral flank cut

Inferior vena cava

Diameter < 2.5 cm Size
normal
(age dependent) • Inspiration T
• Expiration 1
> 4 cm aneurysm (requiring control, perhaps
indication for surgery) Double pulsation abolished with right heart
(dividing line usually >5cm) inflow obstruction

137
MEMORIX CLINICAL MEDICINE
Acute abdomen
Definition: Undiagnosed abdominal pains which demand rapid diagnosis and surgical
or medical treatment.

Causes Intra-abdominal
Inflammation Acute appendicitis (—54%), acute cholecystitis (—14%), acute
pancreatitis(~ 5%), peritonitis of unknown origin (—1%),
subphrenic abscess, salpingitis,
diverticulitis, ileitis, colitis,
pyelonephritis
Infectious diseases: malaria, tuberculosis, typhoid fever, viral
hepatitis

Perforation/ Gastric/duodenal perforation (—7%) (ulcer, carcinoma), gall

haemorrhage bladder perforation, ectopic pregnancy, rupture of spleen or
liver, aortic dissection

Occlusion of Ileus (~ 11%), acute mesenteric artery occlusion (~3%), biliary

organ/vessel colic, hernia, renal calculi, torsion, volvulus (ovarian tumour/
cyst), acute hepatic vein occlusion (Budd-Chiari syndrome)

Extra-abdominal

Poisoning Foodstuffs, lead, alcohol, arsenic, thallium, vegetable poisons,

mushrooms, mercury, carbon tetrachloride

Metabolic Diabetic precoma, familial hyperlipidaemia, acute intermittent

porphyria, Addison's disease, periodic peritonitis
(familial Mediterranean fever), hypercalaemia, hyponatraemia

Cardiovascular Myocardial infarct (esp. posterior wall), acute right heart failure
(hepatic congestion), pulmonary embolus, thrombosis of
mesenteric artery/vein, periarteritis nodosa, lupus erythematosus

Haematological Haemolytic anaemia, acute/chronic leucosis, polycythaemia

Neurological Tabes dorsalis, herpes zoster, intervertebral disc prolapse,

vertebral fracture

Others Psychoses, acute urinary retention, basal pneumonia,

pneumothorax; acute glaucoma; haematoma of rectus abdominis,
Bornholm disease (Coxsackie)

In pregnancy, arising from reproductive organs:

(Note: also consider the above listed differential diagnoses)

Extrauterine pregnancy, premature separation of the placenta, rupture/perforation/
torsion of uterus, inversion of uterus, fibroid complications, hydramnios, postpartum
pneumoperitoneum, torsion of stalk or rupture of adnexal tumour

138
 GASTROENTEROLOGY
Principal symptoms

General condition: Shock, restlessness, shallow respiration, air hunger

Pain: Localization, time course and manner of onset, pain-
relieving/accentuating factors
Peritonitis Diffuse or local; rebound tenderness (visceral peritoneum),
guarding (visceral and parietal peritoneum); nausea,
vomiting, retention of faeces and flatus, urinary retention,
fever

Examination

Inspection: Operation scars, visible peristalsis; lips/buccal mucosa:

abnormal pigmentation (Addison's disease, Peutz-Jeghers
syndrome); gums: lead line; skin: pigmentation, petechial
haemorrhages, collagenoses
Palpation: Rebound tenderness, guarding, liver/spleen, tumour, rectal,
femoral pulses, hernial orifices, supraclavicular lymph nodes
(carcinoma of stomach), genitalia
Auscultation: Bowel sounds (normal/increased/absent); heart (persistent
arrhythmia, cardiac abnormality); lungs (pneumonia,
effusion, pneumothorax)
Percussion: Dullness in flanks
Others: Pupil reactions (tabes dorsalis), ocular pressure (glaucoma),
meningism

[X-ray |

Plain erect abdominal film

• Free air under diaphragm (Note: exclude previous laparotomy/laparoscopy,
tubal isufflation) -> perforation gastrointestinal tract; differential diagnosis:
subphrenic abscess, loop of colon between liver or spleen and diaphragm, rarely
gas-forming peritonitis; perhaps repeat film in left lateral position (air more
readily demonstrable), perhaps repeat after 1 hour
• Free air subhepatic, pericaecal, retroperitoneal
• Free air in bile ducts (— > perforation)
• Gas and fluid level in stomach, small bowel, large bowel (indicative of ileus)
• Calculi/calcification: pancreas, gall bladder, kidney, urinary tract, vessels,
hydatid cyst
• Size of kidneys, liver, spleen; psoas shadow

Chest X-ray: (Air under diaphragm, pleural effusion, infiltration, cardiac

outline)
Abdominal ultrasound
[Laboratory |
(Also preliminary for possible operation)
Red/white cells, platelets, prothrombin time, electrolytes,
creatinine, glucose, SGOT, SGPT, CPK, amylase (blood
gases)
|ecg!

139
MEMORIX CLINICAL MEDICINE

Ileus
Fluid level
Localization of Localization
of the suspected development
(above the obstruction) stenosis/obstruction

Fluid level in:

distended stomach Pyloric stenosis

stomach and duodenum No fluid Duodenum

levels in
standing loops of bowel in middle and left large bowel High small bowel ileus
upper abdomen

middle and right lower abdomen Low small bowel ileus

Colon and possibly small bowel considerably Fluid levels Large bowel ileus
distended (typical parietally placed gas- in large
filled loops of bowel), with fluid levels bowel

I
Ileus
|
Collective term for disturbances of intestinal transport

Mixed forms

I
Mechanical |
-90% Paralytic -10%
-24% / \ -65%
|
Strangulation | |
Obstruction |

Lumen blockage and Lumen blockage/ Hiccup, nausea, vomiting, stoppage of

disturbance of circulation compression stooland flatus, absent bowel sounds,
(usually history of 'deathly silence', succussion splash,
operation, scar!), acute Gradual onset, pains, meteorism, pains usually absent
dramatic onset, colicky increasing retention of
Causes:
pains, typically metallic, stool and flatus, • Peritoneal irritation
tinkling, gurgling bowel hyperperistalsis,
Peritonitis, pancreatitis,
sounds, later silence, increased bowel sounds
perforation, haemorrhage,
retention of faeces and
trauma, carcinomatosis
flatus, vomiting, shock
• Reflex
Causes: Adhesions, Causes: Adhesions, Renal colic, after laparotomy,
wedging of bowel in stenoses, strictures,
cholelithiasis, mesenteric
mesenteric lacunae, tumours, atresia, vascular thromboses
incarcerated hernia, reduplications, Crohn's • Toxic
intussusception, disease, megacolon, Sepsis, pneumonia, uraemia,
volvulus, malrotation peritoneal diabetic coma
carcinomatosis, • Neurogenic
irradiation damage,
Cerebral (stroke, tumour), vagal
foreign bodies
excitation, spinal cord affections
(gallstones, bezoars,
(injury, tumour, infections),
constipation), ascarides
disturbances of neuromuscular
transmission (hypokalemia,
anticholinergics)

140
 GASTROENTEROLOGY
Gastrointestinal bleeding

Upper gastroin
lastrointestinal 6% Mallory Weiss
(U6l) bleeding 23% Gastric ulcer
15% Erosions Haematemesis,
25% Duodenal ulcer melaena
8% Oesophagitis
1 5% Varices
3% Gastric carcinoma
Ligament of Treitz
Border between
UGI and LGI Intussusception
Polyps Melaena,
Diverticula rectal bleeding
Angiodysplasia
Colitis/Crohn's disease
(ascending colon)
Carcinoma
Lower gastrointestinal
(LGI) bleeding

Melaena: Grade I! -> with cardiovascular stability: primary

Arises when blood remains in the gut for at least exclusion of UGI by gastroduodenoscopy.
8h (Check: Tarry stool on finger stall?). Cause
Diagnosis of UGI:
70-80% UGI; <60ml blood: solitary tarry stool,
90% of all GI bleeds are UGI! -> nasogastric
>60ml blood: ca. 3 day tarry stool. intubation (altered blood: 'coffee grounds'?), ->
Rectal bleeding: examination (tarry stool on finger
digital rectal
Rectal blood loss (light- or dark-coloured blood) -» oesophagogastroduodenoscopy, later
stall?)
-» LGI, but be aware of profuse UGI with rapid proctosigmoidoscopy, colonoscopy.
intestinal passage, e.g. bleeding duodenal ulcer

(P- 157).

Diagnostic sequence of upper Gl bleeding

Haematmesis Melaena Rectal bleeding

Laboratory tests, cardiovascular control, nasogastric tube, digital examination per rectum

No blood in nasogastric aspirate | I Blood in nasogastric aspirate

Interim cardiovascular stability

J.
Oesophagogastroduodenoscopy |
< |
Cardiovascular stability \*—\ Cardiovascular instablity]

No stabilization

I
Cardiovascular Immediate surgery
Emergency gastroduodenoscopy
instability
I
— I

' Possibly intraoperative

.^angiography
Requirements for emergency endoscopy:
Cardiovascular stability (blood replacement available),
Bleeding point Source of bleeding
venous access, preferably central.
secured not determined
Pulse rate
Shock index - >1 = danger of shock!
Syst. BP
Arteriography
Aims of endoscopy: Scintigraphy
Therapy
Establish source and intensity of bleeding, possibly
LGI?
sclerotherapy, possibly indication for surgery.

Classification of intensity of bleeding:

p. 157 Proctosigmoidoscopy
Indication for angiographic demonstration of source of bleeding:
Colonoscopy
Blood loss 5 ml/min.
Indication for scintigraphic demonstration of source of bleeding:
Blood loss 0.1 ml/min. Localization of blood loss less specific!

141
MEMORIX CLINICAL MEDICINE
Crohn's disease/ulcerative colitis
I Regional enteritis I Ulcerative colitis
(Crohn's Disease)
Localization:
Oesophagus LI/
. .

\ Only small bowel

Stomach —\r^ \ 25-30%
1

Duodenum X" J/ Total colitis 15-20%

3-5%
W fl \ )

Small and large

bowel 45%
atvo^5
1 J c -J/v S>i-^^fr IB Partial colitis

><0*r{y H 30-50%
r -i I $^-

Terminal ileum
80%
^^B ^ Backwash ileitis

\w\ Anorect ii
s
Rectu ,11-20%
\J?™%
•"
ulae,
anal fiss ures,
perianal Proctitis 30-50%
abscess es)
30-40%

Onset Gradual Gradual, sometimes acute

Symptoms Diarrhoea, rarely rectal Rectal bleeding, blood and

bleeding mucus in stool

Pain Tenesmus rarely, cramping Tenesmus, cramping pains,

colicky pains right lower abdomen frequently left lower abdomen

Age of onset 20-40 years 20-40 years

(5% > 50 years) (10% > 50 years)

Complications Abscess, absorption of B, 2 and Anal bleeding, toxic megacolon

folic acid i, stenoses, perforation, (2-13%)
peritonitis

Risk of carcinoma ? Substantially increased

Perianal lesions 15-50% fistulae, fissures, abscesses Rarely

Associated Iritis, arthritis, cholecystitis, Iritis, arthritis, primary sclerosing

conditions gallstones, pyoderma gangrenosum, cholangitis, erythema nodosum,
erythema nodosum ankylosing spondylitis, pyoderma
gangrenosum
X-ray findings Fissures, strictures, especially Superficial ulcers, distal,
right-sided, distance phenomenon, continuous segmental, collar stud
wall thickening, cobblestoning, ulcers, pseudopolyps, loss
skip lesions; demonstration by of haustrations, hose-pipe
small bowel enema appearance

142
 GASTROENTEROLOGY
Regional ileitis (Crohn's Ulcerative colitis
disease)

Endoscopy Aphthoid lesions, confluent Initially only discrete mucosal

ulcers changes, often rectal involve-
ment, superficial and deep
ulcers, pseudopolyps, mucosal
bridging; end stage: shortening
of the bowel and stenoses
Histology Granulomata, transmural Crypt abscesses
inflammation
Therapy Vitamin and mineral
supplements
Mild/moderately Prednisolone Left-sided colitis
severe inflammation 1st week 60mg/day orally* Rectal: mesalazine l-4g/day,
2nd week 40mg/day orally possibly steroid enemas
3rd week 40mg/day orally • Left-sided involvement:
4th week 30mg/day orally topical 1 g mesalazine + oral
5th week 20mg/day orally sulphasalazine 2-4g/day or
6th week 20mg/day orally mesalazine 3^tg/day
Possibly longer
Maintenance dose: lOmg/day
Severe inflammation Prednisolone 60-100mg/day Prednisolone
weekly reduction by
orally; 60-100mg/day orally*
5-10mg
Refractory to therapy Bacterial superinfection? Bacterial superinfection?
Azathioprine 50 mg b.d. Colectomy, ileoanal pouch
(2mg/kg body weight daily)
Fistulae Metronidazole 400 mg t.d.s.

(lOmg/kg body weight)

(8-10 weeks) or azathioprine
50 mg b.d. (at least 3-4
months, as no effect earlier!)
* In 2 divided doses.

Classification of degree of severity

Mild attack: ^5 stools/day, little blood, temp. <37°C, little malaise
Moderately severe attack: 5-8 stools/day, mucus and blood, temp. >38°C, definite
malaise
Severe attack: >8 stools/day, bloody, temp. >38°C, pulse rate > 100/min,
anaemia, severe malaise
Differential diagnosis: Infective inflammations (Yersinia enterocolitica, Shigellae,
Salmonellae, Chlamidiae), drug-induced,
pseudomembranous colitis (Clostridium difficile),
ischaemic, post-irradiation colitis, collagenoses
Estimation of severity of the inflammatory changes, examination, laboratory
parameters after the classification of
• |
Best index] (Gastroenterology, 70, 439-444 (1976))
or
• van Heesindex[ (Gut, 21, 269-286 (1980))
|

143
MEMORIX CLINICAL MEDICINE

Pancreas and pancreatitis

Portal vein
Hepatic duct Inferior
Common hepatic artery
Cystic duct \ vena cava
Aorta
Liver

Coeliac trunk

Splenic artery and vein

Left epigastric artery

and vein
Tail of pancreas
Pancreatic duct
Mesenteric vein
Duodenojejunal flexure
Superior mesenteric artery and vein

Gall bladder Head of pancreas (uncinate process)

Duodenum
Common bile duct Ampulla of Vater (hepatopancreatic ampulla)

Clinical: Acute spontaneous pain in upper abdomen or back.

Morphology: Oedematous: 85%, mortality < 1%; interstitial oedema; mild
Acute
forms recovering spontaneously 5-7 days in 85-90% of cases pancreatitis
in
Necrotizing: 15%, mortality up to 100%. Severe forms with fat
and parenchymal necrosis, haemorrhages, shock, renal failure, encephalopathy,
cardiovascular and pulmonary disturbances; skin signs: Cullen's sign: periumbilical
dusky skin discoloration; Turner's sign: blue-red to brownish discoloration of the skin
in the flanks. Both signs are an expression of a severe necrotizing pancreatitis.
Clinical and morphological severity do not always correlate.
Basic diagnosis: 1. Laboratory: Amylase T in serum and urine, lipase T, leucocytes T, LDH T,
electrolytes (calcium i, arterial blood gases, pH I, pO z <8kPa), blood glucose T,
albumin i, serum urea, creatinine. 2. Chest X-ray: left-sided atelectasis, pleural
effusion? 3. Plain X-ray abdomen: Pancreatic calcification? 4. Ultrasound: Pancreatic
oedema, calcification, pseudocysts, retrocolic or intra-abdominal fluid, ascites,
gallstones. 5. CT with i.v. contrast: necrotizing pancreatitis demonstrable in 100%! 6.
ERCP: Outflow obstruction in common bile or pancreatic ducts?
Therapy: Nil by mouth, nasogastric tube, i.v. fluids (3-41/day), electrolyte replacement,
morphine derivatives contraindicated (spasm of papilla!), H 2 -blockers, if necessary
antibiotics (against aerobes and anaerobes), if necessary early PEEP ventilation (p0 2
< 9.5 kPa), insulin supplements.
Clinical: Recurrent persistent non-colicky girdle pains, in later stages
usually painless, weight loss, indigestion, diabetes.
Chronic
Diagnosis: Pancreatic calcification (confirming): CT/abdominal film/ pancreatitis
ultrasound/ERCP. Pancreatic pseudocysts, steatorrhoea,
diabetes mellitus.
Morphology: p. 157
Exocrine Only if > 70% of pancreatic tissue is destroyed -> abnormal pancreozymin-secretin
disturbances: test, faecal chymotrypsin <3U/g, abnormal B 12 absorption in 40%, faecal fat >9.5%.
Therapy: In acute attack treat as for acute pancreatitis. Alcohol restriction, enzyme
supplements, at least 60 000 FIP units lipase, enzymes at meal times, low-fat diet, if

necessary insulin.

144
 GASTROENTEROLOGY
Oesophageal varices haemorrhage
Classification of hepatic cirrhosis
(After Child and Turcotte (1964))

A B C
Serum bilirubin <40(<2) 40-50 (2-3) >50(>3)
umol/1 (mg/dl)

Serum albumin >35(>3.5) 30-35 (3-3.5) <30(<3)

g/1 (mg/dl)

Ascites None present Easily controllable Barely controllable

with drug therapy with drug therapy

Nutritional state Very good Good Poor, cachexia

Neurological symptoms None Minimal Advanced coma

Staging of oesophageal varices: see endoscopic staging, p. 157.

Treatment of haemorrhagic shock in hepatic cirrhosis

a) General measures
• Central venous access, or at least two peripheral lines of large calibre.

• Fresh blood, not older than 48 hours, ammonia T, transfused under pressure, fresh
plasma. Note: calcium supplements with citrated blood, ca. 10 ml 10% calcium
gluconate/1 1 blood.

• Empty stomach, rinse with water at normal temperature, exact balance.

• Vasopressin, 2mg bolus initially (slowly over 2min, 1 mg 4-6 times/day i.v.).

Attention: cardiovascular side effects!

• Somatostatin 500ug/hour, effectiveness 0-100%!

• Control: blood count, acid-base status, electrolytes, urea, creatinine (target: Hb 9g/
dl, potassium 4mmol/l, pH 7.4)

• Emergency endoscopy: aim sclerotherapy, localization of bleeding source

• Emergency endoscopy not possible -> see p. 146.

145
MEMORIX CLINICAL MEDICINE
b) Balloon tamponade with Sengstaken-Blakemore tube
Use the SB tube judiciously as many complications may occur. The
procedure is very unpleasant for the patient.

Do not use if patient:

• has severe encephalopathy with no pharyngeal reflex;
• has had recent oesophageal surgery;
• has known oesophageal stricture.
1. Check tube and balloons for patency. Cool in refrigerator.
(Makes insertion easier)
2. Turn patient on side, with head tilted slightly down.
3. Insert gag in patient's jaws to keep mouth open throughout
procedure.
4. Lubricate cooled tube and insert via mouth or nose. (Nasal
ulceration and trauma more common with nasal route.)
5. Insert to at least 60cm, and check tube is not coiled in pharynx.
(Suction on gastric aspiration port should produce large volumes
of blood.)
6. Inflate gastric balloon with about 300 ml air. Use e.g. bladder
irrigation syringe. Secure with clamp.
7. Withdraw tube until firm resistance is felt (at the
oesophagogastric junction).
8. Inflate oesophageal balloon with sphygmomanometer cuff to a
pressure of 40mmHg. Secure with clamp.
9. Secure tube with adhesive plaster to prevent displacement.
10. Check tube and balloon positions with chest X-ray.
11. Monitor pressure in oesophageal balloon hourly. Use low-
pressure suction on oesophageal aspiration port to prevent
blocking.

Keep tube in situ and balloons inflated for maximum 24 h, preferable 12 h. (To avoid oesophageal
ulceration.) When bleeding controlled: deflate (first oesophageal balloon, then gastric balloon); keep
deflated tube in situ without fixation at nose for 6-12 h; if bleeding remains controlled, check if
balloons are really empty, and then withdraw.

Note: Bleeding may not be arrested in up to 10% of patients.

Complications include oesophageal rupture, aspiration pneumonia (occurs in 10% of patients),
oesophageal ulceration, migration of oesophageal balloon with upper airway obstruction.

Continuous supervision of patient is essential

(After McCormick, Burroughs and Mclntyre (1990))

c) Prophylaxis of hepatic coma

Clearance of blood from intestinal tract, alteration of bacterial flora, correct acid-base balance and
electrolytes.
• High enema with 750ml water and 250 ml lactulose
• 20ml lactulose via gastric tube, at first 2-hourly, up to 150ml/day, stool pH <5
• Parenteral nutrition, high-calorie glucose solution, potassium supplements, special amino acid
infusion, no protein intake. Beware: sedatives and diuretics!

Prophylaxis of recurrent bleeding and indication for surgical intervention

Precondition: endoscopically confirmed variceal haemorrhage.

Therapy
1. Sclerotherapy: Obliteration of the varices or regression to Stages I-II.
Discontinuation of therapy: if no reduction in size of the varices, sclerotherapy ulcers, appearance
of fundal varices, mediastinitis.
2. Portosystemic shunt (always after medical/surgical consultation), emergency shunt obsolete.
• Portocaval shunt: patient <62 years, Child-Turotte class A/B (end-to-side)
• Distal-splenorenal shunt (Warren)
• Mesocaval shunt (H-shunt (Drapanas))

3. Perhaps transjugular intrahepatic stent (TIPS), Child-Turotte class C

4. Perhaps liver transplant

146
 g

GASTROENTEROLOGY
Disgnosis of ascites
Standard programme Portal ascites Malignant/ inflammatory

Colour of ascitic fluid Clear Clear/haemorrhagic/chylous

Protein concentration <3.0g/dl >3.0g/dl

Leucocytes <200/mm 3
> 500/mm 3
(or > 200
neutrophil granulocytes/mm 3 )

pH 5=7.45 <7.35
Cholesterol s=48mg% >48mg%
Cytology Negative Positive (carcinoembryonic
antigen, alpha-fetoprotein)

Blood cultures (aerobic/anaerobic) Negative Negative/positive

Optional
• Supicion of spontaneous bacterial peritonitis (SBP): > 200 neutrophil granulocytes/

mm 3
direct slide preparation, centrifuge 250 ml ascitic fluid, sediment in aerobic/
,

anaerobic blood cultures

• Suspicion of TB: glucose quotient serum/ascites > 1, Ziehl-Neelsen stain
• Suspicion of pancreatogenic ascites: amylase quotient serum/ascites > 1

Treatment of portal ascites

Target: weight reduction of ca. 0.5-1.5 kg/day

Basic therapy
Salt restriction, max. 3g daily, normalization of albumin concentration, if necessary
supplementation with 25% (salt-free!) human albumin; serum sodium <130mmol/l,
additional fluid restriction (e.g. max. 800-1000 ml/day); spontaneous diuresis sodium
< 10mmol/l, diuretics (spironolactone lOOmg/day). If no satisfactory weight reduction
after 4 days (< 1.5 kg), -» gradual increase of diuretic dose (spironolactone) by lOOmg
daily over 3-4 days to max. 400 mg/day, additionally small amounts of a loop diuretic
to max. 80 mg/day!

Causes of treatment failure

Sodium intake too high (through drugs dissolved in NaCl, e.g. antibiotics), cause of
ascites undetermined, SBP, worsening of liver function, impairment of renal function
(e.g. nephrotoxic substances, antibiotics, anti-inflammatory agents).

Paracentesis
Indication, e.g. excessive feeling of distension, dyspnoea. Substitution required: 6-8
albumin/1 1 ascites.

Ascites refractory to treatment

Only <5% unresponsive to conservative therapy. Palliative measure: peritoneal-
venous shunt (Denver/LeVeen shunt).

Treatment of malignant ascites

Paracentesis, Denver shunt as palliative measure. At present still experimental: trial of
tumour necrosis factor (TNFa): first paracentesis as complete as possible slowly over
24 h, then instillation of 50 ng TNFa dissolved in 500 ml NaCl into the ascites once a
week, repeated up to 3 times, side effect: temp. 38°C.
MEMORIX CLINICAL MEDICINE
Portal hypertension
Diaphragm Azygos vein
^ Vena cava
Central vein draining^
Coronary vein
to vena cava
Short gastric veins
Sinusoid-

Gastroepiploic vein

Paraum- Suprarenal vein

bilical vein Renal vein

Vein of Retzius
Inferior mesenteric vein
Superior mesenteric vein
Spermatic vein

Subcutaneous
abdominal veins Superior rectal vein

s Inferior
rectal vein
Internal

|
iliac vein
External iliac vein Anus

Localization of the Frequent Rarely Oesophageal Ascites Splenomegaly

obstruction to flow varices

A Prehepatic Portal vein Arteriovenous Marked Rarely Marked

thrombosis fistulae

B Intrahepatic

B, Presinusoidal Primary biliary cirrhosis Schistosomiasis* Marked Marked Rarely

Sarcoidosis Marked Rarely Marked
Haemochromatosis Marked Rarely Marked
Lymphatic system Marked Marked Marked
disease

Sinusoidal Cirrhosis of liver Nodular hyperplasia Marked Marked Marked

Alcoholic cirrhosis
B, Postsinusoidal Alcoholic cirrhosis Veno-occlusive Marked Marked Marked
syndrome
Budd-Chiari syndrome Marked Very marked Marked
C Posthepatic Right heart failure Budd-Chiari syndrome Marked Very marked Verv marked
Constrictive pericarditis Thrombosis of inferior Marked Marked Marked
vena cava
* Commonest cause of portal hypertension worldwide.

148
 GASTROENTEROLOGY
Jaundice
Differential Prehepatic jaundice, Intrahepatic jaundice Extrahepatic jaundice
diagnosis haemolysis, bilirubin (parenchymatous) (obstructive)
transport defect

Serum
Bilirubin
• indirect T -(t)
(unconjugated)
• direct (conjugated, T(T) T(T)
glucuronidated)

SGOT (t) TTT T/TT

SGPT - TTT T/TT

AP - (T)/TT TTT
LAP - (T)/TT T/TTT

Gamma-GT - T/TT TT/TTT

LDH TT/TTT T/TT T

Urine
Bilirubin _ T T

Urobilinogen T T/l 4/-

Urine colour Light Dark Dark

Stool colour Normal Normal/pale Pale (putty coloured)

Pruritus - ( +) +
Clinical Spleen T Liver values T Colic
Signs of anaemia Cirrhosis, skin signs Tumour, lymphoma
Weight 4

Special serological tests Reticulocytes T Hepatitis serology, Carcinoembryonic

Haptoglobin 1 CMV, EBV, malaria antigen
Triglycerides T leptospirosis, bacterial CA 19-9 tumour
(Zieve's syndrome) causes, antinuclear marker
Blood film antibodies,
antimitochondrial
antibodies, caeruloplasmin

Ultrasound/CT Bile passages normal Bile passages normal Bile passages dilated
Proximal obstruction/PTC
Distal obstruction/ERCP

Without haemolysis Haemoglobinopathy,

spherocytosis,
thalassaemia, sickle
cell anaemia,
Gilbert's syndrome*

* Gilbert's syndrome: 5-7% men four times more frequently, young persons, autosomal dominant.
of population,
Diagnosis: intermittent jaundice, indirect bilirubin up to 80umol/l Starvation test: 400cal/day -» doubling of
bilirubin; nicotinic acid:
50 mg i.v. -» bilirubin T; phenobarbitone 60 mg t.d.s. -» fall in bilirubin; treatment: none,
prognosis excellent. PTC, percutaneous transhepatic cholangiography; ERCP, endoscopic retrograde
cholangiopancreatography.

Drug induced jaundice

(Biouv era/. (1987))

Displacement of bilirubin from albumin binding Directly hepatotoxic

Sulphonamides, ampicillin, salicylate, indomethacin, Diclofenac, indomethacin, ketoconazole,

phenylbutazone, heparin (releases bilirubin by the methotrexate, mexilitine, oestrogens,
release of long-chain fatty acids), etc. phenytoin, tolbutamide, etc.

149
MEMORIX CLINICAL MEDICINE

Gallstones
Cause of 80-90% of all colicky abdominal pains, ca. 12% of the population
carry gallstones; maleifemale ratio 1:3; prevalence 30^0% at 70 years of
age.

Groups at risk:
Overweight, hyperlipoproteinaemia, infections and inflammations,
vagotomy/gastrectomy, disorders of the terminal ileum (resection, Crohn's
disease), diabetes mellitus, hepatic cirrhosis, chronic hepatitis, haemolytic
anaemia, immunodeficiency syndrome, hyperparathyroidism, pancreatitis,
oestrogen /progestogen therapy, clofibrate, cholestyramine.

. .
t
Cholesterol
Pathophysiology: hthogenic index
Bile salts + phospholipids

Symptoms: colicky pains, right upper to mid-abdomen, right shoulder,

vomiting.

Stone composition:
25% cholesterol stones (>70% cholesterol), 67% cholesterol-pigment-
calcium stones, 8% pigment stones.

Diagnosis:
Ultrasound sensitivity above 95%.

Complications of cholelithiasis:
Acute cholecystitis (Charcot's triad: colic, jaundice, intermittent fever);
Murphy's sign: pain on palpation of gall bladder region. Chronic
cholecystitis, choledocholithiasis, strangulation of gall bladder, cholangitis,
biliary pancreatitis, hydrocele, empyema, gangrene, perforation, gallstone
syndrome: obstructive jaundice, stone in neck of
ileus. Mirizzi gall bladder
with compression of hepatic duct, painful gall bladder region.

Incidence of carcinoma:
Increased; 70-100% of malignant gall bladders contain stones, but only 7%
of all carcinomas of the gastrointestinal tract are gall bladder carcinomas.
(Courvoisier' sign: painless enlarged gall bladder - strongly suggestive of
carcinoma.)

Treatment:
Asymptomatic (no colic): no interference!
Symptomatic (colic 1-2 times per week): -> op. Acute cholelithiasis, biliary
pancreatitis -> op.; operative mortality for elective surgery ca. 1.6%, over
50 years 2.8%.
150
 .

GASTROENTEROLOGY
Requirements for oral litholysis and MTBE treatment:
Gall bladder disease without complications, cholesterol stone up to 1.5 cm
(X-ray translucent stone), gall bladder motility preserved, cystic duct
patent (ultrasound: gall bladder contraction after test meal or positive
cholecystogram)

Litholysis:
Ursodesoxycholic acid (UDCA) 7-10mg/kg body weight, side effects: 10%
stone calcification. Chenodeoxycholic acid (CDCA), side effects: diarrhoea,
SGOT T, SGPT T. Therapy for several months; relapse T after stopping
treatment. Success rate ca. 90% stone dissolution after 2 years.

Local lysis with MTBE (methyl-tert-butyl ether): long-term catheter in gall

bladder, irrigation 1-3 days, > 90% success rate. Side effect: biliary
peritonitis.

ESWL (extracorporeal shock wave lithotripsy): requirements as for oral

stone size up to 2.5 cm, if more than five stones success doubtful,
litholysis,
after-treatment with bile acids required, recurrence after 5 years over 50%.

Choledocholithiasis:
Incidence ca. 1.3%; in 20% simultaneous stones in gall bladder and hepatic
duct; this coincidence increases with age.

Diagnosis:
Ultrasound: cystic duct > 0.7-0.9 cm normal, after cholecystectomy > 1.0-
1.2 cm; ERCPmost reliable method of demonstration. In patient with
gastrectomy or duodenal diverticulum -» i.v. cholangiography or
percutaneous transhepatic cholangiography (PTC).

Treatment:
Endoscopic stone extraction, combined with ESWL, mechanical lithotripsy,
local lysis (nasobiliary tube), endoscopic papillotomy (EPT), patient > 40
years mortality 1.1%; complications of EPT: haemorrhage, cholangitis,
pancreatitis. Complication rate 7.5%.

Complications:
Purulent cholangitis, sepsis, biliary pancreatitis.

Complication rate: 90-95%.

151
MEMORIX CLINICAL MEDICINE

Types of hepatitis
Hepatitis type A B C D E
Synonym Infectious 'Long 'Non-A-non-B' Delta' •Enteral NAND'
'short incubation (NANB) post- hepatitis, only
incubation hepatitis' transfusion associated
hepatitis
1
hepatitis with HBV
Abbreviation HAV HBV HCV HDV HEV
Incubation 15-45 days 90-180 days 6-12 weeks 3-15 weeks ~6 weeks
time

Virus RNA virus, Hepadna RNA virus, Defective E virus, RNA

picornavirus virus, C virus RNA virus. virus
DNA virus Delta virus

Mode of Faecal-oral Parenteral, Parenteral Parenteral, Faecal-oral

transmission sexual, sexual,
perinatal perinatal

Serology anti-HAV- HBs-Ag/AB Anti-HCV Anti-HDV- Anti-HDV in

IgM HBc-Ag/AB HCV-RNA IgM development
anti-HAV- HBe-Ag/AB HBs-Ag/AB
IgG HBV-DNA HD-Ag
HBV-DNA- HDV-RNA
polymerase

Course Recovery HBV carrier HCV carrier

Fulminant 0.1-0.2% 1-3% 2% HBV + HDV In pregnancy T
>2%
Chronic state No Yes, -6% Yes, -50% Yes No

Hepatitis immunization
Hepatitis A: passive immunization with 5 ml gammaglobulin i.m., up to 14 days after
presumed exposure; ca. 80% protection for 3 months.
Hepatitis B: passive immunization (anti-B hyperimmune serum) abandoned!
Active-passive (simultaneous) immunization: needle prick injury with HBV positive
blood.

'Needle prick hepatitis': confirmed needle prick with HBs-Ag-containing blood -» ^ 6

hours after exposure anti-B hyperimmune serum 5 ml gluteal and simultaneously one
dose active vaccine into upper arm.

Active immunization: (i.m. upper arm)

(Engerix-B, H-B-Vax) immunization at intervals of 4 weeks (2nd dose) and 6 months
(3rd dose), anti-HBs assay 1 month after last immunization dose.

Indicaton: Dialysis patients, frequent contact with blood, neonates of HBs-Ag-

positive mothers, spouse/contacts of HBs-Ag homosexuals,
carriers,
prostitutes, drug addicts, prisoners, carers of mentally handicapped.

Booster dose: Dependent on anti-HBs titre: *s 10mU/l immediate reimmunization;

over lOOOOmU/ml check titre after 3-6 years.

HBV immunization also protects against simultaneous or superinfection with HDV

virus.

152
 GASTROENTEROLOGY
Serological course of hepatitis
HAV

HDV
/ Incubation \
S. 3-15 weeks /

|
HDV-RNA
HBsAg ^^* '

HBeAg 1

HBV-DNA
1 ^ ^^^.^^Anti-HDV-IgG

Anti-HDV-IgM/^ ^^ \ ^-^^Anti-HBe
HDV
I
Months
1 l< 1 / 1

153 6
MEMORIX CLINICAL MEDICINE

Hepatitis B markers
HBV Hepatitis B virus Demonstrable in blood and serum (rarely necessary)

HBs-Ag Hepatitis B surface Already demonstrable ca. 14 days before clinical symptoms:
antigen (formerly: generally no longer present 6 weeks after onset of illness; if
'Australia antigen' longer than 6 months: chronic hepatitis, carrier often
asymptomatic
Anti-HBs Antibodies against Indicate of reactive immunity; appear relatively late (4-5
hepatitis B surface months after onset of illness) in convalescent patients
antigen

HBc-Ag Hepatitis B core Bound to the liver cell (liver biopsy); not demonstrable in
antigen blood
Anti-HBc Antibodies against Very sensitive marker for recovered or active hepatitis B;
B core
hepatitis carriers of anti-HBc without anti-HBs are potentially
antigen infectious; anti-HBc without HBs-Ag and anti-HBs can
indicate fresh hepatitis B
HBe-Ag Hepatitis B e-antigen Indicates presence of Dane particles in blood; best indicator
e: virus core for infectiousness; if persistent, sign of chronic active
hepatitis

Anti-HBe Antibodies against When present, patient probabaly no longer infectious

hepatitis B e-antigen

Hepatitis A markers
HAV Hepatitis A virus Already in stool before onset of illness
HAV-Ag Hepatitis A virus antigen (Determination rarely necessary)

Anti-HAV Antibodies against HAV

IgM Anti-HAV-IgM Already present at time of first clinical symptoms
(jaundice). Sign of acute phase

Interpretation of serological markers in acute and chronic

viral hepatitis
HBs-Ag HBe-Ag HBV- Anti-HBc Anti- Anti- Anti-HAV Anti- Interpretation
DNA IgM/IgG HBs HBe IgM/IgG HD-Ag
Early phase of acute hepatitis B
Acute hepatitis B, chronic
hepatitis B, HBV carrier
Chronic hepatitis B, HBV
carrier
Recent hepatitis B
Primary immune response
without HBV infection.
Immune response to HBV
vaccination
Acute HBV/HDV co-infection
Chronic HBV infection with
HDV superinfection
Acute/recently recovered
hepatitis A
Recovered hepatitis A

154
 GASTROENTEROLOGY
Chronic active hepatitis
Drugs 3%
Wilson's disease

« 25% alcohol
Haemochromatosis
- 20% viral 13%
(Hepatitis B, C, D) > Porphyria
23% immunological
'autoimmune'

PBC/PSC
Definition:
persistent transaminases over 6 months; histology: 'piecemeal' necroses.

Specific diagnosis Treatment

Alcoholic hepatitis Alcohol restriction

SGOT/SGPT > 2, gamma-GT T, histology
'wire mesh fibrosis'

Zieve syndrome: haemolysis, cholesterol T,

jaundice

Immunological-autoimmune hepatitis Initially: 60mg prednisolone daily (1st week)

40 mg prednisolone/day (2nd week)
90% women; ANA
type (ANA/SMA positive)
30 mg prednisolone/day (3rd and 4th weeks)
(anti-nuclear antibody (Ab), smooth muscle
25 mg prednisolone/day (5th and 6th weeks)
Ab)
LKM type (Ab against liver and kidney Maintenance dose: 20 mg prednisolone/day
microsomes) Alternative: combination with 50 mg
azathioprine/day; initially 30 mg prednisolone/
SLA type (Ab against liver soluble cytoplasmic
day (2 weeks); maintenance dose lOmg
antigens)
prednisolone/day, lOmg azathioprine

Primary biliary cirrhosis (PBC) Symptomatic:

90% women, peak > 50 years, jaundice, Cholestyramine 4-16g/day
pruritus, anti-M 2 >95% positive Mid-chain fatty acid diet, vitamins i.m. (A, D,
(antimitochondrial Ab, subtype M 2 ), E, K) once a month. Minimally life-prolonging:
IgMt azathioprine 50 mg b.d.; ursodeoxycholic acid
Primary sclerosing cholangitis (PSC) 13-15mg/kg body weight/day; effect on
Endoscopic retrograde cholangiography; prognosis still unclear; possibly liver transplant
typical diagnostic appearance, staging

Haemochromatosis idiopathic (IHC)

Serum Fe > 180ng%, transferrin saturation Venesection, 500 ml 1-2 times a week; 500 ml
>60%, serum ferritin >300mg/dl, liver blood 200 jig, -» therapy at least 2-3 years,
tissue Fe 80-1 000 ug/lOOmg dry weight (note: then venesection less frequently, but lifelong
false high serum ferritin in acute inflammation,
HLA-A3, B7, B14 no diagnostic significance)
Wilson's f Penicillamine 20-30 mg/kg/day in three doses,
Serum copper <70ug%, ceruloplasmin i hour before food, lifelong therapy. Also
< 10mg%, urine copper above 400ng/24 hours, during pregnancy. If intolerance, restart, slow
over 250 ug copper/g dry weight
liver tissue introduction of penicillamine, if necessary
Kayser-Fleischer corneal ring prednisolone 20mg/day for 2 weeks in addition

155
MFMnMX CLINICAL MEDICINE

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156
 GASTROENTEROLOGY
Endoscopic staging of abdominal disorders
Reflux oesophagitis Oesophageal varices
la Mucosal erythema, solitary, multiple Straight, pink-blue veins within level of
'red patches' the mucosa, < 2 mm
lb Mucosal lesions with fibrin deposits
More tortuous blue venous dilatations,
nodular calibre variations, projecting into
Ha Longitudinal or confluent streaky the lumen, =s 2-3 mm
lesions
Knotted convoluted blue varices, lumen
lib Longitudinal or confluent streaky constricted to one-half, *£ 3-4 mm
lesions with fibrin deposits IV Grape-like livid vascular convolutions
reaching to the centre of the oesophagus,
III Entire oesophageal circumference
with circumscribed blue-red fine
involved,no ulceration
telangiectases on their surface, 'varices
IV Ulceration, scarred stenoses, bleeding on varices'

(After Spech et al. (1982))

Gastric bleeding activity Carcinoma of stomach

la Arterial, 'spurting' bleeding 'Early cancer' Infiltrating mucosa and
submucosa only
lb Oozing
II Bleeding ceased, haematin or clot on 'Advanced cancer' Submucosa penetrated,
lesion, visible vessel stump polypoid, no ulceration

III Lesion without above criteria Linitis plastica Diffuse infiltrating

(After Forrest (1974))

Chronic pancreatitis

I
m» Normal

Calibre variations of side arms of

pancreatic duct

II Additionally, calibre variations of

main duct

III Marked calibre variations of

mm* pancreatic duct, cystic dilatations

of side arms, duct calculi,
calcification of parenchyma,
pseudocysts

(After Anacker and Loffler (1989))

157
MEMORIX CLINICAL MEDICINE

Gastrointestinal tumours
Early gastric carcinoma
(confined to mucosa and
submucosa)
Classification according to the Advanced gastric carcinoma
Japanese Society for
Macroscopic classification after Borrmann (1926)
Gastroenterological Endoscopy
(1962)

VHMHMIIIHHmHHNNni... .

-\ v.v.v.v
:
: : : : : ::^ : : : : : : :: - : : : : : - :
: : : ^^ :-: - :::: ^^^:' I Circumscribed solitary,
polyploid carcinoma'

I Bulging form without significant ulceration

II Superficial forms

*&!&& II Ulcerated carcinoma

**^~<^^~*m>»™"<^'**. with rampart-like edges
I la Elevated and sharp borders

1
III Ulcerated carcinoma,
• which in contrast to type II
'
isonly partly or not at all
*
sharply demarcated from
its surroundings. The tumour is spreading by diffuse
infiltration

IV Diffusely infiltrating
carcinoma, which often
lie Depressed progresses without mucosal lesions

Colorectal Carcinoma Staging after Dukes (1935)

Tumour confined
(movable)
to bowel wall Tumour penetrates
bowel wall, (not
Lymph nodes
involved
¥
Metastases,
liver, lung, bones
movable), lymph
Tumour-free lymph nodes nodes clear

w Metastases in lymph nodes 158

 GASTROENTEROLOGY
Function tests
Function test Disorder

D-xylose absorption test: Malabsorption in proximal jejunum

25 g xylose orally, excretion of <3g in
5h abnormal
Lactose tolerance test: Lactase deficiency
50 g lactose orally, rise in blood glucose
<20mg% (< llmmol/l)after 30min
abnormal
H -exhalation test:
2
Lactase deficiency, intestinal hurry, altered
50 g lactose orally, after 2h H 2 exhalation small bowel bacterial flora, e.g. in Billroth-II
(>20ppm) gastrectomy
Schilling test: Disturbed B, 2 absorption in terminal ileum
57
1 ug cyanocobalamin ( Co) orally,
excretion of < 7% in 24-hour urine. Note:
intrinsic factor deficiency in megaloblastic
anaemia
Iodine- 125-polyvinylpyrollidine: Exudative enteropathy
Iodine-125-PVP i.v., 4-day stool collection,
radioactivity above 1.8% of the total
activity pathological

a,-antitrypsin clearance: Exudative enteropathy

< 3 mg/g stool

Chymotrypsin: Exocrine pancreatic insufficiency after

Screening test in stool, pancreas Billroth-II operation and diarrhoea
enzymes 5 days or discontinue
Secretin test: Exocrine pancreatic insufficiency
Fractionated duodenal juice analysis
after secretin stimulation

Ulcer Therapy
a) Conservative Treatment
Avoidance of provocative factors (NSAIDs, glucocorticoids, salicylates, smoking, etc.).
H2 -receptor antagonists: cimetidine, ranitidine, famotidine, nizatidine; administration at
night. H /K -ATPase blocker: omeprazole. Antacids. Mucosa protection: sucralfate;
+ +

prostaglandins - misoprostol as prophylaxis during NSAID administration.

b) Surgical Treatment
Gastric ulcer: Two-thirds gastrectomy - Billroth-I (gastroduodenostomy).
Duodenal ulcer Selective proximal vagotomy (SPV). Combined gastric and duodenal
SPV with pyloroplasty, possibly two-thirds gastrectomy.
ulcers:
Indication for surgery: ulcer refractory to medical treatment, arterial bleeding, perforation,
pyloric stenosis.

Chronic gastritis
Type A: 'Body gastritis', autoimmune, autoantibodies in 90% against parietal cells, 50%
against intrinsic factor. Achlorhydria, B, 2 deficiency, pernicious anaemia.
Type B: 'Antrum gastritis', bacterial, associated with Helicobacter pylori (Gram-negative
bacterium).
Type C: 'Fundus gastritis', chemical, drug induced.

159
 NEPHROLOGY
Renal anatomy

Interlobular a.
Arcuate a. \ Glomerulus
Vasa recta
Interlobar a

Renal a

Medulla:
Calyx
Papilla
Int. medulla
Ext. medulla Cortex, renal column
Ureter

161
 :

MEMORIX CLINICAL MEDICINE

Nephrological formulae
Inulin (and PAH) clearance/body surface area (ml/min/m 2 )
'gold standard' of renal function tests, but is too inconvenient for practical
purposes, therefore:
Endogenous creatinine clearance
gives higher values than inulin clearance, since creatinine is also excreted by the
tubules; in practice relatively uncomplicated. Beware of collection error!
Check for correct collection (i.e. collection time):

Measurement of total creatinine excretion in urine collection.

Dependent on muscle mass.
Standard values: Male: 150-200 umol/kg/day
Female: 100-150 umol/kg/day
Measured value/calculated value = 1: correct collection
< 1 collection too short
:

>1: collection too long

For practical purposes and with constant renal function:
Creatinine clearance
Normal value: 90-125 ml/min
(150 - age) x body weight (kg) Men: 10%
Calculation:
plasma creatinine (umol/1) Women: •10% -

Urine volume (ml) x Urine creatinine (umol/1)

Plasma creatinine (umol/1) x time (min)

Times: 24h = 1440min, 12h = 720min, 8h = 480min, 6h = 360min,
4h = 240min

Creatinine
clearance
(ml/min)
Serum
150. Weight
creatinine
(kg)
120 -, Axis of umol/l mg/100ml
rotation
1000
:io

80-

60-

50- 50-

40 - 40-

x0.0113->
<- x88 4

Application: 1 . Connect age and weight.

2. Rotate ruler around crossing point on axis of rotation to lie on serum creatinine value
3. Read off the creatinine clearance on left scale.

162
 NEPHROLOGY
Urine normal values
Dip stick chemical test and examination of sediment - preferably to be performed immediately (max. 1 h)
after sample is voided. HPF = high-power field
Determination Normal values Determination Normal values

Dip stick test Quantitative

(semiquantitative) estimations
PH 4.5-8 (in 24 h)
Albumen - Volume Variable (according to
Glucose - fluid and NaCl intake)
Ketones - (positive if fasting) Specific gravity 1003-1030
Urobilinogen - Osmolality 350- 1400 mosmol/1
Bilirubin - Residual urine A few ml (if more than
Blood - 100-1 50 ml needs
Hb from erythrocytes - urological investigation)
Sodium 1 00-250 mmol
Sediment examination
Potassium 25-100 mmol
Casts: hyaline Normal (not significant)
Chloride 135 mmol
granular
Calcium Less than 3.8 mmol

red cell _ Phosphate 30 mmol

white cell _ Creatinine 9-15mmol
_ Creatinine clearance 90-125 ml/min
epithelial
Leucocytes Men 0-2/HPF; women 0-5/HPF Amylase 25-75 U/ml

Erythrocytes 0-5/HPF (glomerular forms) Albumen Less than 0.15 g/24h

Epithelial cells Usually present in women Glucose 0.3-1.7 mmol/24h

Fat droplets -
Bacteria As contaminants

Erythropoietin
Polypeptide (normal blood level 10-20 mU/ml). Barely measurable in dialysis patients. Production
probably in peritubular adventitial cells (90%); 10% extrarenal (lung).

Definition of renal anaemia:

Normocytic, normochromic anaemia with normal maturation and morphology of erythrocytes, but
reduction of the erythrocyte survival time by 50%.
Reticulocyte count normal to low. Platelet count normal to low.
White cell count normal. Normal bone marrow morphology with normal iron content.
The cause of the anaemia is multifactorial, but erythropoietin is significantly involved, since
erythropoietin therapy corrects the anaemia.

Use of erythropoietin:
i.v. or s.c. (practically identical action), intraperitoneal possible, but expensive.
Individual dosage very variable (mean value: 75U/kg (25-500) per week), divided into three doses,
building up initially. Maintenance dose with haematocrit about 30%.

Positive aspects of erythropoietin therapy, primarily subjective:

Intensified feeling of wellbeing, increased effort tolerance, improved appetite with weight gain
(observe for hyperkalaemia), less depression, improved sexual function, less dyspnoea and better
sleep.

Negative aspects as a result of improved haemoglobin:

Increased heparin consumption in dialysis, more frequent shunt thromboses, repeated use of dialysers
restricted, hyperkalaemia/hyperphosphataemia.

Disadvantages:
Arterial hypertension (20-30% of treated patients), hypertensive crises (infrequent), arthralgia, bone
pain, local urticaria, pruritus.

163
MEMORIX CLINICAL MEDICINE

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164
 NEPHROLOGY
Differential diagnosis of acute renal failure

(Cause prior to the kidney) Hypoperfusion in (still) intact kidney

Blood loss, gastrointestinal losses, renal losses (diuretics, osmotic diuresis in
diabetes), sequestration (burns, decompensated cirrhosis of liver), antihypertensive
therapy (reduction of filtration pressure), heart failure (arrhythmia or heart muscle
failure), vascular pooling (anaphylaxis)

2. Renal (Causes in the kidney)

Tubular necrosis (all prerenal causes which are not corrected immediately), drug
induced (cephalosporins, aminoglycosides, amphotericin B), contrast media, heavy
metals and organic solvents, poisoning (paraquat), tetanus, haemolysis and
rhabdomyolysis.

Acute interstitial nephritis (penicillin and derivatives, cephalosporins, rifampicin,

cotrimoxazole, tetracyclins, diuretics rarely, salicylates, NSAIDs and others), with
infections
Acute glomerulonephritis
Acute renal failure in collagenoses
Malignant nephrosclerosis
Bilateral diffuse pyelonephritis
Hypercalcaemia
Hepatorenal syndrome in literal sense (but mostly prerenal)
Pregnancy (abortion, toxaemia, premature separation of placenta, and placenta
praevia, haemolytic-uraemic syndrome after pregnancy)
Multiple myeloma
Vascular obstruction

3. Postrenal (Causes in disturbed drainage)

Prostatic hypertrophy, carcinoma of prostate or bladder, retroperitoneal and pelvic
floor lesions, urethral stricture/stenosis, unilalateral renal lesions with nonfunctioning
or absent contralateral kidney: ureteric calculus, papillary necrosis

Urine findings in acute renal failure

Ratios

Urine volume Urine Urine sodium Urine/ Urine/ Urea/

osmolality plasma plasma creatinine
creatinine urea in plasma

Normal values 750-1500 ml/d 350mosmol/l 15-40mmol/l -80 20 10

Prerenal Oliguria >500 <20 >40 >8 >10

Renal Oliguria <400 >40 <20 <2 -10
Postrenal Oliguria/anuria <400 >40 <8 -10

Subjective symptoms dependent on renal failure

Urine quantity Symptoms
1 30-50 ml/min None
50-20 ml/min Headache (hypertension)
Reduction of effort tolerance and rapid fatigue (anaemia)
20-10 ml/min Nausea, vomiting, depression, pruritus
10-0 ml/min Dyspnoea (pulmonary oedema and acidosis)
Haemorrhage (nasopharynx, gastrointestinal tract, skin)
Neurological symptoms (neuropathy, disturbance of consciousness to coma)

165
MEMORIX CLINICAL MEDICINE

Management of renal failure

Independent of the cause:

Assessment of the potentially lethal complications of acute renal failure,
i.e. hypervolaemia, disturbance of consciousness, hyperkalemia,

metabolic acidosis, pericarditis.

On this basis decision as to acute dialysis.

Initial measures 1. Rapid exclusion of pre- and postrenal causes (ultrasound)

2. Therapy: frusemide i.v., mannitol i.v.

3. Further search for aetiology

Clinical Daily weighing, fluid balance, assessment of state of hydration,

assessment of state of consciousness, investigation for pericarditis
and pulmonary oedema, examination of ocular fundus, care of
forearm veins, assessment of neuropathy and osteodystrophy 3 ,

psychological and family assessment as well as assessment of place

of work, possibly coronary artery assessment

Laboratory Plasma: Electrolytes, renal parameters, osmolality,

albumin, blood gases,
amylase 3 lipid status 3
,

Urine: Urine status, urinary bacteriology, osmolality, 24-

hour urine for: creatinine clearance, electrolyte/
protein/uric acid excretion
Haematology: White and red cells, platelets, coagulation state,
bleeding time
X-ray: Abdominal ultrasound, chest X-ray
Others: ECG, hepatitis and HIV serology 3 CT scan,
,

isotope renogram

Nutrition Salt and fluid restriction (general rule: daily excretion +500 ml,
except with polyuria), protein: untreated renal failure (0.7-1 .Og/kg/
day)
<haemodialysis <CAPD

Principles of Adjust dose of drugs to current renal function (cf. pp. 294-326),
therapy correction of hyperkalemia, treatment of hypertension, correction
of acidosis, loop diuretics, phosphate binders, ulcer prophylaxis,
control of anaemia 3 treatment of osteodystrophy 3 hepatitis
, ,

vaccination 3

Renal support Absolute indications: cf. above

measures Insert shunt 3 peritoneal catheter3 tissue typing for possible
, ,

transplantation 3

J
Additional investigations in chronic, terminal renal failure.

166
 ,

NEPHROLOGY
Uraemia
Main causes: Chronic glomerulonephritis
Chronic interstitial nephritis (analgesics)
Polycystic kidneys
Diabetic nephropathy
Chronic pyelonephritis
Hypertensive nephropathy

1. Cardiovascular 7. Neurological
Circulatory instability, Central
arterial hypertension, Sleep disturbance,
heart failure, headache,
cardiomyopathy, memory disturbance,
pericarditis, lethargy,
accelerated arteriosclerosis, flapping tremor,
uraemic pulmonary oedema hypertensive encephalopathy,
subdural haematoma,
2. Gastrointestinal epileptiform convulsions,
Anorexia, nausea, vomiting, dysequilibrium syndrome,
gastroenteritis, dialysis dementia,
ulcersand bleeding, uraemic coma
uraemic fetor, Peripheral
hepatitis Neuropathy (peripheral and
autonomic),
3. Electrolyte and water balance restless legs
Metabolic acidosis,
variability of sodium, potassium, 8. Psychological
phosphate, calcium, Depression,
magnesium concentrations, anxiety,
volume instability denial,
psychotic reactions
4. Locomotor system
Renal osteodystrophy, 9. Haematological
secondary hyperparathyroidism, Normochromic normocytic
growth disturbance, anaemia,
myoclonus, T ferritin, 1 erythropoietin,
motor weakness, haemolysis,
muscular irritability haemorrhagic diathesis,
splenomegaly, hypersplenism,
5. Metabolic T tendency to infection,
Carbohydrate intolerance, >l complement factors,

protein deficiency, T fibrinogen

hyperlipidaemia,
10. Dermatological
hyperuricaemia
Pallor,
hyperpigmentation
6. Endocrine pruritus,
Infertility,
ecchymoses
sexual dysfunction,
amenorrhoea, 11. Ophthalmic
thyroid dysfunction, Retinopathy,
hypothermia keratopathy,
'red eye' syndrome

167
MEMORIX CLINICAL MEDICINE

Nephrolithiasis
Diagnosis by means of ultrasound or IVU during acute attack (of little value after colic).

Primary treatment with spasmolytics and NSAIDs.

Early relief of obstruction because of recurrent colic and threatening infection with persistent obstruction.

Possibilities: Spontaneous passage after conservative treatment with volume loading and spasmolytics
Removal with ureteric snare at cystoscopy
Percutaneous lumbar lithopexy
Extracorporeal shock wave lithotripsy (ESWL)
Open operation

Chemical analysis of the calculus recommended in every case (with view to recurrence).
Frequency: 30% of the population will have a calculus once during their lifetime.
With recurrence appropriate laboratory investigations according to stone analysis.
Prophylaxis: High fluid intake; possibly long-term treatment with thiazide diuretics for hypercalciuria
and recurrent stone formation.
Frequency of urinary stone composition:
Calcium oxalate 75-^85%
Uric acid 5-10%
Non-metabolic (infective) 10%
Cystine stone: rarity

Proteinuria
Renal parenchymatous
Glomerulonephritis 3 , interstitial nephritis 3 , tubular disorders, polycystic kidneys,
glomerulosclerosis (diabetic, hypertensive)

Renovascular
Renal vein thrombosis 3

Extrarenal
Orthostatic, pronounced lumbar lordosis, infective

Systemic illnesses
Systemic lupus erythematosus 3 multiple myeloma, Waldenstrom's macroglobulinaemia, amyloidosis,
,

benign monoclonal gammopathy

a
With haematuria.

Haematuria
Renal parenchymatous
Glomerulonephritis", pyelonephritis", tuberculosis, renal cell carcinoma, carcinoma of renal pelvis,
polycystic kidneys,trauma (including heavy physical exertion)

Renovascular
Renal vein thrombosis", renal infarct, renal cortical necrosis

Urinary outflow tract and prostate

Urogenital tuberculosis, cystitis (bilharzia), urethritis, carcinoma of bladder and prostate, trauma
(including instrumentations), calculi

Systemic illnesses
Systemic lupus erythematosus", vasculitis, thrombo- and coagulopathies, polycythaemia

Others
Anticoagulant bleeding, benign familial haematuria

" With proteinuria.

168
 NEPHROLOGY
Red urine
(Modified after Sandoz (1988))

Red urine

Strip test

Positive = haem present Negative = no blood

(drugs, foodstuffs)

contrast microscopy
Search for erythrocytes

Non-glomerular forms Glomerular forms None

= glomerulopathy • Haemoglobinuria
• Myoglobinuria

Search for systemic

Recheck, perhaps
illnesses with:
single catheterization Golmerular erythrocytes
• Proteinuria
(exclude artefacts (From Thiele/fl/. (1986))
• Bacteriology
from gastrointestinal
• Immunology
or genital tract)

i
Renal biopsy
Further investigation
wj Simple ring form

• Coagulation status
• Bacteriology, TB Erythrocytes Wavy ring form
• Ultrasound
• IVU Normal erythrocytes

^g^ Fresh erythrocyte without \J Wavy ring form slit

^P/ double contour

• Cystoscopy Ring form with
t
• CTscan ©Fresh erythrocyte with external cone
• Retrograde urogram double contour
Ring form with
$Qf Crenated erythrocyte internal cone

O Ghost erythrocyte
without rim o Deformed erythrocyte

O Ghost erythrocyte with rim

remains ± spikes
With wavy double
contour

O Deformed ghost
erythrocyte Slit

Deformed erythrocyte with

wavy double contour ^J Dwarf form

169
MEMORIX CLINICAL MEDICINE

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 »
>

NEPHROLOGY

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171
MEMORIX CLINICAL MEDICINE

Dialysis
Drug therapy for dialysis patients (haemodialysis and peritoneal dialysis)

Use of substances which are mainly (50-100%) eliminated by the liver, and control of dose by
blood level determinations.
Dose of substances mainly (50-100%) eliminated through the kidneys: normal initial dose.
Haemodialysis: half the daily dose immediately after dialysis.
Peritoneal dialysis: half the usual daily dose.

Haemodialysis-associated problems
Acute: Exclusively iatrogenic.
Cardiovascular disturbances: volume depletion following inaccurate estimation of the ideal
weight.
Too rapid volume reduction in extracellular space expansion. Bleeding due to anticoagulants.
Incorrect or displaced position of the dialysis catheter. Drug-induced lowering of blood pressure
during dialysis. Haemodynamically relevant rhythm disturbances with volume reduction or rapid
changes of potassium.
Chronic Aluminium-induced neuropathy and microcytic hypochromic anaemia, pVmicroglobulin-
induced amyloidosis. Silicone deposition in practically all organs due to roller pump when using
silicone-containing equipment.

Emergency measures with severe complications:

Discontinue dialysis and examination of blood and dialysate.

Peritoneal dialysis-associated problems

Acute: Peritonitis (turbid dialysate first and often only sign).

Chronic Reduction of dialysing ability due to recurrent infective, chemical or allergic peritonitis.

Emergency measures:
Estimation of dialysate cell count at above 1000 (normal <100/ml) :

Bacteriological examination including fungi. Contact the attending centre.

Treatment suggestions for peritonitis: rapid irrigation with 3 times 2 1 (1.26% glucose). Inoculate
4th bag with cephalosporin (e.g. cephazolin lg) and aminoglycoside (e.g. tobramycin 80 mg).
Continue the dialysis. Subsequent bags inoculated with cephazolin 200 mg and tobramycin 16 mg
until bacteriological resistance is found (mostly staphylococci). Continue with cephalosporin or
aminoglycoside in the same dose according to resistance until cell count < 100/ml; after this only
inoculate night bag. Treatment duration 10-14 days. With fungal infections removal of the
catheter is usually required: temporary change to haemodialysis or trial of amphotericin B or
ketoconazole, but never with flucytosine alone because of rapid development of resistance.
Inadequate outflow of the dialysate with good inflow and rapid weight gain:
Valve mechanism at the catheter tip
Measures: try a position change (standing or prone); enema (often satisfactory dialysis outflow
after bowel emptying); removal of a possible
fibrin clot with urokinase, 10 000 units in 5 ml Dialyser

and 1000 units heparin to fill the catheter Arteriosclerotic

stenosis or
overnight. If unsuccessful: plain abdominal X-
occlusion
ray, check of catheter position (normal: tip
should lie at pelvic inlet). If there is «

displacement, attempt replacement with guide '

by an experienced operator. If unsuccessful:

surgical change of catheter (temporary
haemodialysis).
Perforation: persistent peritonitis with usually a
mixture of organisms, without severe symptoms.
Ileus with adhesions, bowel volvulus (clinical Causes of a Cimino shunt dysfunction.
picture of acute abdomen). (After Schinz)

172
 NEPHROLOGY
Organ donation
A code of practice concerning cadaveric organs for transplantation, including the diagnosis of brain
death, has been drawn up by a working party on behalf of the Health Departments of Great Britain
and Northern Ireland (Health Departments of Great Britain and Northern Ireland (1983)). This
publication, from which the recommendations below have been taken, should be consulted.

Conditions under which the diagnosis of brain death should be considered:

1. The patient is deeply comatose.

(a) There should be no suspicion that this state is due to depressant drugs.
(b) Primary hypothermia as a cause of coma should have been excluded.
(c) Metabolic and endocrine disturbances which can be responsible or can contribute to coma
should have been excluded.
2. The patient is being maintained on a ventilator because spontaneous respiration had previously

become inadequate or had ceased altogether.

(a) Relaxants (neuromuscular blocking agents) and other drugs should have been excluded as a
cause of respiratory inadequacy or failure.
3. There should be no doubt that the patients condition is due to irremediable structural brain
damage. The diagnosis of a disorder which can lead to brain death should have been fully
established.

Diagnostic tests for the confirmation of brain death

All brainstem reflexes are absent:

(i) The pupils are fixed in diameter and do not respond to sharp changes in the intensity of incident
light,
(ii) There is no corneal reflex,
(hi) The vestibulo-ocular reflexes are absent,
(iv) No motor responses within the cranial nerve distribution can be elicited by adequate stimulation
of any somatic area,
(v) There is no gag reflex or reflex response to bronchial stimulation by a suction catheter passed
down the trachea,
(vi) No respiratory movements occur when the patient is disconnected from the mechanical ventilator
for long enough to ensure that the arterial carbon dioxide tension rises above the threshold for
stimulation of respiration.

The diagnosis of brain death is to be made on the above criteria by two independent doctors, one a
consultant, preferably the one in charge of the case, and the other a consultant or senior registrar
clinicallyindependent of the first. Diagnosis should not normally be considered until at least 6 hours
after the onset of coma, or, if cardiac arrest was the cause of coma, until 24 hours after the circulation
has been restored. The tests should be repeated after an interval adequate for reassurance of all
directly concerned.

Once the diagnosis of brain death has been made, certain further criteria must be established to
determine whether the patient is suitable as an organ donor.
Criteria General
• Complete history (including HIV risk)
• State of health before acute cerebral event
• Laboratory: blood group, blood count, prothrombin time, plasma creatinine, liver
function tests, blood sugar
• Blood gas analysis, serology (HIV, hepatitis, CMV, tissue typing)
Special
• ECG, echocardiogram, size and weight, no resuscitation
Heart:
• Liver:prothrombin time, routine liver function tests, size and weight
• Kidneys: proteinuria (strip test)
• Pancreas: no special features
• Lungs: chest X-ray, normal blood gases, no resuscitation

Exclusion criteria for organ removal

Absolute: • Wasting diseases (malignancy, except primary brain tumour - arguable)
• Insulin-dependent diabetes mellitus
• Positive HIV test or hepatitis B antigen
Relative: • Arterial hypertension
• Bacterial infection
• Age

173
MEMORIX CLINICAL MEDICINE
Renal transplantation
Renal transplantation is the treatment of choice for terminal renal failure. It requires
the collaboration of all medical disciplines.

The measure of success of renal transplantation is the percentage of living patients

(optimum: 95%) and still functioning organs (optimum: 80-90%) after 1 year.

Immunosuppression

Postoperative immunosuppression with combinations of cyclosporin, azathioprine,

steroidsand antilymphocyte products with the aim of a basic immunosuppression low
in steroids.
Treatment of rejection primarily with methylprednisolone (0.5-1 g/day for 3 days by
short-term infusion).

Acute problems in renal transplantation

Most are general medical problems which are to be recognized and treated as such,
with consideration of the interaction with immunosuppressants. Consultation with the
attending transplant centre.

Acute deterioration of transplant function

Treat as rejection until proof to the contrary. Consider the differential diagnosis of
acute renal failure including cyclosporin nephrotoxicity.

Acute abdominal pain (especially in the early stage after transplantation)

Rejection, thrombosis of the renal artery or vein, primary or secondary in the course
of rejection, obstruction, urinary leak, rupture of kidney, acute abdomen of general
surgical nature.

Haematuria

From native urinary tract: cyst bleeding in polycystic kidneys, papillary necrosis
(analgesic or diabetic nephropathy), calculi in chronic pyelonephritis, infection of the
native urinary tract.

From the transplant: vascular catastrophe (rupture, infarct, arterial and venous
thrombosis); stones (rarely), infection.

174
 INFECTIONS
Pyrexia
Investigation plan
Establish: height, duration, type of fever (continuous, remittent, intermittent, periodic, undulant)
Clues to confirmation and localization of infection:
• History

Cough, headache, abdominal pain, diarrhoea, dysuria, backache, joint pains, muscular pains,
operations, i.m. injections, drugs, sexual behaviour, travel, animal contacts, profession, old TB.
• Findings
Rash, inflamed mucous membranes, lungs (pneumonia?), heart (valve defect?), locomotor
system, lymph nodes, focal neurological signs, meningism, peritonitis.
• Laboratory

C-reactive protein, ESR, differential white cell count, liver function tests, chest X-ray. Bacte-
riological cultures and/or serology, according to case history details or physical findings (urine,
sputum, blood, CSF).

Types of fever
MEMORIX CLINICAL MEDICINE
Pyrexia of undetermined origin
Definition: Fever 5=38°C lasting ^3 weeks, for which no cause is found with the
above-mentioned investigations after s= 1 week.

Causes

1. Infections (35%)
As a rule, infections with few local signs of inflammation.
Abscesses: intra-abdominal (liver, subphrenic, pancreas, spleen, also after
abdominal surgery, diverticulitis, Crohn's disease, intrauterine pessary, curettage,
dental abscess, brain abscess, muscle abscess after i.m. injection).
Biliary infections: cholecystitis, cholangitis, pancreatitis.
Osteomyelitis.
Urinary tract infections: rarely, as usually rapidly diagnosed, except in perinephric
abscess or ureteric obstruction.
Subacute bacterial endocarditis.
Tuberculosis: note also miliary tuberculosis in the elderly patient.
Others: gonococcal sepsis, chronic meningococcal sepsis, Q
fever, chlamydial
infections, leptospirosis, brucellosis (history of travel and animal contact important).
Viral infections: HIV, cytomegalovirus, infectious mononucleosis, hepatitis.
Parasitic infections: toxoplasmosis, malaria, according to travel history.

2. Tumours (20%)
Hodgkin's and non-Hodgkin's lymphoma, leukaemias, solid tumours (renal cell
carcinoma, hepatoma, cerebral tumour, atrial myxoma).

3. Collagen/vascular illnesses (15%)

Giant cell arteritis, Still's disease, polyarteritis nodosa, systemic lupus
erythematosus.

4. Miscellaneous (15%)
Drug fever, sarcoidosis, granulomatous hepatitis, Whipple's disease, factitious fever,
thyroiditis.

5. No diagnosis (15%)

Synopsis of nine studies from 1958-1980 (Good reviews include: Esposito et al. (1979)
and Larson et al. (1982))

176
 INFECTIONS
Bacteriological stains - direct preparations

Gram stain Ziehl-Neelsen stain

• Dry specimen in air • Heat with concentrated carbol-fuchsin
• Fix (draw through flame 3 times) solution until steaming
• Crystal violet 1 min • Rinse with water. Decolorize with HC1
• Rinse and stain with Lugol's iodine (3% alcohol)
solution: 2 min • Counterstain with methylene blue:
• Decolorize with acetone/alcohol until 1-5 min
no colour is discharged • Rinse with tap water
• Counterstain with safranin or diluted
carbol-fuchsin solution: \ -1 min Result
• Rinse with tap water Mycobacteria: red

Result
Gram-positive bacteria: dark blue
Gram-negative bacteria: red

The commonest pathogens in Gram stain preparations

Material* Gram-positive Gram •negative
Cocci Rods Cocci Rods

CSF Strep, pneumoniae Listeria N. meningitidis Haemophilus influenzae

Sputum Strep, pneumoniae Moraxella catarrhalis Haemophilus influenzae

Klebsiella pneumoniae

Pleural effusion Strep, pneumoniae Haemophilus influenzae

Staph, aureus Enterobacteriacae
Anaerobic streptococci

Ascites Strep, pneumoniae E. coli

Liver abscess Streptococci E. coli

Klebsiella pneumoniae
Bacteroides

Intra-abdominal Anaerobic streptococci Enterobacteriacae

abscess Enterococci Bacteroides

* Note: Any organisms demonstrable in specimens which are physiologically sterile (e.g. CSF) are pathological.
In sputum, however, demonstration of organisms by Gram stain is only relevant when numerous organisms and
leucocytes are found. If TB is suspected, a Ziehl-Neelsen stain is essential.

177
MEMORIX CLINICAL MEDICINE

Interpretation of aspirates
I. Cerebrospinal fluid (p. 267)

Normal Viral meningitis Bacterial meningitis Tuberculous meningitis

Appearance Water-clear Clear Turbid Clear-turbid

Pressure (cm H 2 0) 5-12 Normal or raised >20 Normal or raised

Cells (per litre) 1-4 x 10* < 109 (lymphocytes > 1.2 x 10' <1 X 109 (monocytes and
raised) Polymorphs raised lymphocytes raised)

Glucose (% of serum 50-80% 50-80% <40% <40%

concentration)

Protein (g/1) 0.1-0.45 Normal or raised Mostly > 1.0 Mostly 0.5-5.0

Lactate (mmol/1) <1.6 <1.6 >1.6 >1.6

Direct stain Negative Negative 80% positive 35% positive

Note: The findings mentioned are typical, but their absence does not exclude the corresponding aetiol-
ogy. For example, while a cell count > 1.2 x 109 1 points to a bacterial meningitis, a count of less than this
value does not by any means exclude it.

II. Pleural effusion

Findings in favour of an infective effusion:
• Protein > 30 g/1
• Rel. protein (% of serum value) >50%
• Rel. LDH (% of serum value) >60%
• pH <7.0
• Leucocytes >1 x 109/1 (>50% polymorphonuclear)
• Gram stain see p. 177

III. Ascites
Findings in favour of a bacterial peritonitis:
• Protein > 25 g/1 (>30g/l never cardiac or cirrhotic)
• Lactate > 3.7 mmol/1, or, more reliably 3 :

Lactate (ascites) - lactate (blood) < 2.2 mmol/1: sterile

> 2.2 mmol/1: infected
• Leucocytes:
<300 X lO /!, infection excluded, but sterile ascites possible up to 2
6
x 109
<25% granulocytes: infection excluded, but >25% granulocytes in ca. 50% of
cases with sterile ascites
Gram stain: see p. 177

IV. Joint aspirate (p. 260)

a
Permits the evaluation of ascitic lactate even with raised serum lactate.

178
 INFECTIONS
Common viral infections

Syndrome/illness Commonest pathogen Mode of transmission

Common cold Rhinoviruses Droplet

RS virus (respiratory syncytial) Hands
Pharyngitis Influenza virus Fomites
Laryngitis Parainfluenza virus
Croup Adenovirus

Hepatitis Hepatitis A (HAV) Faecal

Hepatitis B (HBV) Blood, sexual
Hepatitis C (HCV) Blood, sexual
Cytomegalovirus (CMV) Blood, sputum, sexual
Epstein-Barr virus (EBV) Sputum, blood
Herpes simplex (HSV) Lesion
Varicella-zoster (VZV) Lesion

CNS infection Herpes simplex (HSV) Mostly reactivation

Varicella-zoster (VZV) Droplet/lesion
Measles virus Droplet
Mumps virus Droplet
Tick-borne encephalitis Ticks (zoonosis)
HIV Blood, sexual

Lymphadenopathy Epstein-Barr virus (EBV) Sputum, blood

Cytomegalovirus (CMV) Blood, sputum, sexual
Rubella virus Droplet
HIV Blood, sexual

179
MEMORIX CLINICAL MEDICINE

Methods of laboratory diagnosis in viral illnesses

(Bundesamt fur Gesundheitswesen (1985))

Clinical picture Virus isolation Direct virus detection Serology

Vesicle-forming Yes, vesicle fluid or Yes, in herpes and No. Except: vari-
eruption smear from lesion, smallpox. Not in cella-zoster:
crusts not useful coxsackie Rising titre or
Time: 1-10 days Time: 2-24 h demonstration
of IgM

Diarrhoeal No Yes, essentially only No

illnesses rotavirus.
Time: 4-72 h

Central nervous Yes, only mumps Yes, only herpes and Yes: mumps,
system and enteroviruses. possibly measles measles, polio
Pharyngeal material, Biopsy material Rising titre

stool, possibly CSF No: all other

Time: 3-15 days viruses

Tick-borne No No Yes: IgM

encephalitis demonstration
or rising titre

Respiratory tract Yes, nasal, pharyn- Yes, rhinopharyngeal Yes: rising titre

geal, bronchial aspiration

secretions Time: 4-24 h
Time: 3-15 days

Eye conditions Yes, only herpes No No

(and possibly (Chlamydia yes)
chlamydia). Smear
Time 3-20 days

Hepatitis No No Yes: Hep. A:

IgM demonstra-
tion; Hep. B:
HBs-Ag, Anti-
HBc, Anti-HBc-
IgM
Supplement: anti-
HBs, Anti-HBe
Hep C: total Ig

Prenatal Yes. Pharyngeal No Yes for rubella

infections material, urine and CMV: IgM
Time: up to 6 weeks and IgG in
mother and
child simultane-
ously

180
 INFECTIONS
Collection and dispatch of material for investigation

Material Collection Dispatch for Dispatch for direct

virus isolation demonstration

Nasal smear With swab under 0°C, in VTM a -

turbinate

Nasopharyngeal Aspiration 0°C, no additive As for isolation

secretion

Throat swab With swab from tonsils 0°C, in VTM a -

and pharynx
Pharyngeal Gargle with pharyngeal 0°C, fluid -
washings rinsing fluid 3 without additive

Bronchial Use as little fluid as 0°C, fluid As for isolation

secretion possible without additive

Eyes (conjunctiva) With swab from upper 0°C, in VTM a

,
(Chlamydia: smear
and lower lid for Chlamydia in on microscope
special transport slide)
medium
Vesicle fluid Isolation: with swab or 0°C, in VTM a
Without additive,
needle. Direct direct in needle or
demonstration: glass pipette
puncture with needle
(not disposable needle
with silicone coating!)
or glass pipette

Mucosal erosions With swab, after 0°C, in VTM a

removal of necrotic
material, from edge
and floor of lesion
Urine Terminal stream 0°C, use of Without additive
VTM a
only after
discussion with
laboratory

Stool - Without additive Without additive

CSF Puncture 0°C, in VTM a -

Tissue (biopsy, - Only after -

autopsy) discussion with
laboratory
Blood: virus Puncture -70°C, -
isolation anticoagulant,
special transport!

Blood: serology Puncture without Room -

additive temperature

* VTM (virus transport medium) or rinsing fluid should be requested from the laboratory that
performs the examination.

181
MEMORIX CLINICAL MEDICINE

Antiviral agents

Drug Spectrum, indication Daily dose* Most important side

effects

Acyclovir!" HSVI and II, also VZV: Nephrotoxicity

HSV primary infection 5 times 200 mg (5 Neurotoxicity
(mucocutaneous) days) oral Adjust according
Suppression in 2 times 400 mg oral to renal function
recurrent HSV OR 4 times
infection 200 mg oral
VZV disseminated or 5 times 800 mg (7
ophthalmic zoster days) oral OR
HSV encephalitis 30mg/kg(10days)
HSV in immunoin- i.v. in 3 doses
competence

Ganciclovir! CMV (HSV, VZV, EBV) Neutropenia

Retinitis lOmg/kg (14-21 Thrombocytopenia
Colitis days) i.v. in Neurotoxixity
Pneumonia 2 doses Adjust according to
Maintenance therapy for 6mg/kg on 5
i.v. renal function
retinitis days/week OR
5 mg/kg i.v. daily

Zidovudine§ HIV IV A Anaemia

HIV IV B Neutropenia
HIV IV CI 500-600 mg Nausea
HIV II + CD4<200/ul in 2-5 divided Note: cumulative
or 2 of the following doses toxicity with high
criteria: OR 6-1 2 mg/kg doses of sulphona-
CD4-Ly 200-500/u.l (2 weeks) namides,
CD4-Ly 200-500/uI + i.v. in 6 doses trimethoprim,
30% fall pyrimethamine,
^-microglobulin ganciclovir
>5 mg/1 In general, avoid
Positive HIV-p24 combined therapy
antigen

Abbreviations:
HSV, herpes simplex virus; VZV, varicella-zoster virus; CMV, cytomegalovirus; EBV, Epstein-Barr
HIV, human immunodeficiency virus; CD4-Ly, T helper
virus; cells.

* For adults; refer to detailed prescibing information for children's doses.

t Alternative treatments for HSV or VZV include famciclovir, recommended for herpes zoster and
genital herpes, and valaciclovir for herpes zoster only. Idoxuridine may be used for topical treatment
of herpes simplex.
t Foscarnet is also active against cytomegalovirus, but indicated only for retinitis in AIDS patients for
whom ganciclovir is inappropriate.
§ Didanosine is indicated for treatment of HIV in adults intolerant of zidovudine; zalcitabine has
similar indications.

Tribavirin is used to treat bronchiolitis caused by respiratory syncytial virus in infants.

182
 INFECTIONS
The immunocompromised patient
Malignant tumours and their therapy lead to an increased risk of infection. This risk to
is related to the nature of the underlying disease and the type of immunologi-
the patient
cal defect.

Immunological defect Illness/therapy Commonest pathogens

Neutropenia Leukaemias (blast cell crisis) Staph, aureus

(< 1000/ul) Advanced lymphomas, myelomas Staph, epidermis
Solid tumour chemotherapy Gram-negative bacteria
causing aplasia Candida albicans
Bone marrow transplantation Aspergillus

Disturbed Chronic granulomatous illness Staph, aureus

granulocyte function Job syndrome (recurrent cold Staph, epidermis
staphylococcal abscesses) Gram-negative bacteria
Bone marrow transplantation Candida albicans
(graft-versus-host disease) Aspergillus
Antithymocyte globulin
Adriamycin and others
Disturbed barriers Cytotoxic drugs Staph, aureus
Catheter Staph, epidermis
Surgery Pseudomonas
Burns and others aeruginosa
Candida albicans
Disturbed cell- Hodgkin's and non-Hodgkin's Cytomegalovirus
mediated immunity lymphoma Herpes simplex
AIDS Herpes zoster
Status after transplantation Pneumocystis carinii
(cyclosporin, steroids, Toxoplasma gondii
azathioprine, etc. Listeria
Nocardia
Cryptococcus
neoformans
M. tuberculosis
Atypical mycobacteria
Hypogamma- Chronic lymphatic leukaemia Strep,pneumoniae
globulinaemia, myeloma
Multiple Haemophilus
dysgamma- Bone marrow transplantation influenzae
globulinaemia N. meningitidis
Splenectomy Hodgkin's lymphoma and others pneumoniae
Strep,
Haemophilus
influenzae

Note: In the febrile immunocompromised patient the investigation and empirical therapy must be
directed against the commonest pathogens, i.e. a patient with disturbed cell-mediated immunity
requires different investigation and therapy from a neutropenic patient.

Literature: Hughes et at. (1990) (Neutropenia)

Colonna et al. (1988) (Liver transplantation)
Oh et al. (1988) (Renal transplantation)
Zimmerli et al. (1991) (Bone marrow transplantation)

183
MEMORIX CLINICAL MEDICINE

AIDS: definition and classification

Human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS)

Definition
HIV demonstration in tissue or body fluid
HIV antibody demonstration (cf. illustration)
AIDS: acquired immune deficiency syndrome without other cause
(neoplasia, immunosuppressive therapy) and demonstration of an opportunistic infection or tumour
(see CDC classification)

(Modified after Schupbach (1991))

Generalized
AIDS clinical
symptoms

PGL
Infection Laboratory signs of
weakened immunity
CD
O 1
c
O 1

Acute
1!

Asymptomatic
in
Persistent
IV
Other
phase phase gener- illnesses:
opportunistic
CDC alized
lymphade- infections,
class nopathy tumours,
neurological
illnesses

Days 1-3
Time to
weeks
8-10 years Months to years
weeks

"""I I
HIV anti-
I

gen I
Useful
prognostically
(P24)
Q
1 Igm
i 1

Unsuitable for
I
1
antibody

igG
h CO c
I
1

.
diagnosis

Best for diagnosis

antibody:
HIV test SI .
due to persistence

Classification
1. CDC classification

Group I Acute infection: mononucleosis-like picture, meningoencephalitis, seroconversion

Group II Asymptomatic infection:

A Laboratory tests normal
B Laboratory tests abnormal (lymphopenia, thrombocytopenia, reduced CD4 lymphocytes)
Group III Persistent generalized lymphadenopathy:
Lymph nodes above 1 cm in at least 2 places apart from inguinal region lasting more than 3
months without other explanation
Group IV
A Constitutional clinical picture:
• Weight loss > 10% and/or
• Unexplained pyrexia over 1 month (continuous or intermittent) and/or
• Diarrhoea over 1 month

184
 INFECTIONS
B Neurological clinical picture:
• Dementia
• Myelopathy without other cause
• Peripheral neuropathy

C Secondary illness: opportunistic infections

CI • Pneumocystis carinii pneumonia
• Toxoplasmosis of CNS
• Cryptosporidiosis with diarrhoea > 1 month
• Isosporiasis with diarrhoea > 1 month
• Extraintestinal strongyloides infection
• Candidiasis (oesophagus, bronchi, lungs)
• Cryptococcosis, extrapulmonary
• Histoplasmosis, extrapulmonary
• Extrapulmonary tuberculosis
• Atypical mycobacterial infections (disseminated)
• Recurrent Salmonella bacteraemia (except S. typhi)
• Cytomegalovirus infections (not liver, spleen or lymph nodes)
• Chronic mucocutaneous or disseminated herpes simplex infection
• Progressive multifocal leucoencephalopathy
C2 • Oral leucoplakia
• Herpes zoster
• Nocardiosis
• Pulmonary tuberculosis
• Candida stomatitis
D Secondary illnesses: neoplasia
• Kaposi's sarcoma
• Non-Hodgkin's lymphoma
• Primary CNS lymphoma

E Other HIV-associated illnesses, e.g.

• Chronic lymphoid pneumonia
• Recurrent bacterial pneumonia

2. Walter Reed classification

The Walter Reed classification, introduced in 1985, divides the HIV infection into
clinical-immunological functional disturbances (Redfield et ai, 1986).
The stages WR3-WR6 indicate the progression towards AIDS.

Stage HIV antibodies Chronic CD4 Skin test Stomatitis Opportunistic

and/or virus lymph- lymphocytes infections
demonstration adenopathy

WRO - - >400 Normal _ _

WR1 + - >400 Normal - -
WR2 + + >400 Normal -
WR3 + ± <400 Normal :
WR4 + ± <400 P - -
WR5 + ± <400 A and/or P ± -
WR6 + ± <400 P/A ± +
P, partial anergy in Meneux Multitest.
A, complete anergy in Merieux Multitest.
The parameters that are important for the classification are shown in red.

185
 .

MEMORIX CLINICAL MEDICINE

Investigation of AIDS
Laboratory parameters for immune state

CD4 lymphocytes, CD8 lymphocytes, lymphocyte transformation test,

immunoglobulins, p24 antigen, ^-microglobulin, leucocytes, haemoglobin, platelets,
Merieux Multitest

Investigations of infections according to clinical problems

1 Respiratory syndrome
• If CD4 lymphocytes > 200/ul: sputum bacteriology -> probably bacterial
pneumonia, including Strep, pneumoniae, H. influenzae, Staph, aureus, Legionella,
M. tuberculosis
• If CD4 lymphocytes < 200/ul: provoked sputum or bronchial lavage for
bacteriology (including M. tuberculosis); also: Pneumocystis carinii,
cytomegalovirus, Candida, Aspergillus, cryptococci, histoplasma, cytology
(inclusion bodies), if indicated transbronchial biopsy (Kaposi's sarcoma)

2. CNS syndrome
• If meningitic syndrome: lumbar puncture for general bacteriology, cryptococcus
neoformans, virology (CMV, HSV, HZV), p24 antigen, CSF/serum antibodies
(CMV, HSV, HZV, HIV), protein, glucose, lactate, cells
• If encephalitic syndrome: CT without/with contrast. If CT lesion with nodular or
ring enhancement: serology (toxoplasma, HSV, HZV, CMV) — empirical
»

toxoplasma therapy (p. 187)

3. Retinitis
• Fundoscopy
• CMV serology, CMV demonstration in urine, sputum, heparinized blood
(leucocytes)

4. Oesophagitis, gastroenteritis, colitis

• In case of dysphagia and Candida stomatitis: empirical therapy against Candida
oesophagitis. If no repsonse: endoscopy with biopsy (histology, cytology, CMV,
HSV demonstration, Candida)
• In case of diarrhoea: stool bacteriology, including Ziehl-Neelsen stain, stool
parasites (Cryptosporidia, Isopora belli, amoebae, Giardia lamblia, Blastocystis
hominis, etc.), stool virology (adenoviruses)

5. Hepatitis
• Serology: HAV, HBV, HCV, CMV, EBV, HSV, HZV
• Heparinized blood for mycobacteria and CMV
• Possibly liver biopsy for histology, mycobacterial culture, CMV, HSV
demonstration

6. Generalized symptoms
• Blood cultures
• CMV demonstration in urine, sputum and heparinized blood
• Mycobacterial demonstration (heparinized blood, stool, lymph node biopsy)
• Serology (CMV, HSV, HZV, Toxoplasma gondii, Leishmania, Strongyloides)

186
 INFECTIONS
Therapy of the most important pathogens in HIV infection
Site of infection Pathogen Initial therapy Dose Duration Suppressive
therapy

Respiratory M. Triple therapy, 4-5 tab./day 2 months

tract tuberculosis e-g- oral
Rifater*
followed by
rifampicin lOmg/kg/day If necessary,
+ 4-7 months isoniazid
isoniazid 300mg/day

Pneumocystis Trimethoprim 20mg/kg/day Pentamidine

carinii + oral/i.v. 3 inhalation
sulfame- lOOmg/kg/day weeks (300 mg every
thoxazole 3 weeks)
or or
dapsone lOOmg/day trimethoprim

trimethoprim 20mg/day oral sulphame-

thoxazole (1
or forte tab. b.d. 3
times per week)
pentamidine 4mg/kg/day i.v. 3 weeks

Cytomegalo- Ganciclovir 7.5-15 mg/kg/ 2-3 weeks If necessary,

virus day i.v. ganciclovir
(5mg/kg/day)

Legionella sp. Erythromycin 3g/day oral/i.v. 3 weeks None

CNS
Brain abscess Toxoplasma Pyrimethamine lOOmg/day
gondii oral1 week,

followed by Pyrimethamine
50-75 mg/day (25 mg/day)
oral
+ +
sulphadiazine 4(-6)g/day oral 1
2-4 months sulphadiazine
+ (3g/day)
calcium folinate 5-15 mg/day
oral
+
sodium urine>pH7 ,

bicarbonate
or
pyrimethamine as above Lifelong

clindamycin > 2400 mg/day

oral or i.v.

Meningitis Cryptococcus Amphotericin B 0.5mg/kg/day ca. Fluconazole

neoformans i.v. 6-8 weeks (100-200mg/day
oral)

Retinitis Cytomegalo- Ganciclovir lOmg/kg/day i.v. 2-3 weeks Ganciclovir

virus or foscarnet 180mg/kg/day (5 mg/kg/day or
i.v. higher) 90-
120 mg/kg/day
i.v.

Encephalitis Herpes Acyclovir 3X 10 mg/kg i.v. 10 days

" Combined antitubcr as to US treatment

h
Dannemann ei al. (1992)
c
ACTG (1992)

187
MEMORIX CLINICAL MEDICINE

Site of infection Pathogen Initial therapy Dose Duration Suppressive

therapy

Oesophago- Candida spp. Fluconazole 400mg/day Single dose None

gastro- Herper Acyclovir 400mg q.i.d.

intestinal simplex oral

or 10 days ?

Oesophagitis 15mg/kg/day i.v.

Cytomegalo- Ganciclovir lOmg/kg/day i.v. 14 days ?

virus

Colitis lsospora belli Trimethoprim lOmg/kg/day 14 days

+ or 7
sulphame- 50mg/kg/day longer
thoxazole

Skin/mucous Herpes Acyclovir 200-400 mg 7-10 days Individually

membranes simplex 5 times per day
oral

Herpes zoster Acyclovir 800 mg 5 times 7-10 days None

per day oral

Candida spp. Fluconazole 150mg/day Single dose

or None
amphotericin B 4-5/day 2-3 weeks
lozenges

Systemic HIV Zidovudine 500-(1000)mg/ Lifelong

day

Cytomegalo- Ganciclovir lOmg/kg/day i.v. 2-3 weeks Ganciclovir at

virus least 5 mg/kg/

day i.v.

M. avium Clofazymine lOOmg/kg/day Stop

complex* oral Amikacin
+ after
rifampicin 600mg/day oral 4-6 weeks
+
ciprofloxacin 1500mg/day oral Lifelong
+
amikacin lOmg/kg/day i.v.

or
ethambutol 15mg/kg/day
oral

»Horsburgh(1991)

188
 INFECTIONS
Empirical therapy of infections
I Checklist before therapy
The following questions should be answered before any antibiotic therapy is

prescribed:
• Is antibiotic indicated on clinical grounds?
• Have microbiological samples been taken?
• Is immediate chemotherapy essential, or can the microbiologicalresults be
awaited?
• Best antibiotic for empirical therapy? (Spectrum, pharmacokinetics, toxicity,
price)
• combination necessary?
Is synergistic
• Additional problems (immunosuppression)?
• Drug allergies?
• Method of administration?
• Dose?
• Duration?

II Indication for empirical therapy

Antibiotic therapy should, as a rule, be directed against the causative organism(s).
In certain bacterial infections the prognosis is, however, dependent on the start of
adequate therapy. These therapies are summarized below. For infections where the
start of therapy can be delayed until the culture results are available, consult the
relevant textbooks. Empirical therapy is especially appropriate in the following
infections:
Sepsis with unknown primary site; endocarditis; pneumonia; intra-abdominal
infection; urinary tract infection; CNS infections; fever with neutropenia.

III Empirical therapy according to clinical diagnosis

Note: only one of the several alternatives is given for the empirical therapy.

Sepsis with unknown primary site

History: Short hospital stay? Intravenous drug abuse? Alcohol abuse? Additional
symptoms? Travel, animals? Epidemiological situation? Underlying
diseases?
Findings: Catheter? Puncture sites? Abnormal organ findings? Septic emboli?

Commonest organisms (O) and therapy (T), if no additional symptoms and no

abnormal organ findings:

a) No pointers: O: mostly Staphylococcus aureus

T: Flucloxacillin and aminoglycoside

b) Drug abuse O: Staphylococcus aureus or Gram-negative aerobes

T: Cephazolin and aminoglycoside
c) Alcohol abuse O: Streptococcus pneumoniae, Escherichia coli, Klebsiella
pneumoniae
T: Ceftriaxone or co-amoxiclav and aminoglycoside
d) Intravascular O: Coagulase-negative staphylococci, Staphylococcus aureus
catheter T: Cephamandole
MEMORIX CLINICAL MEDICINE

Endocarditis
Before therapy: • With acute endocarditis:
3 blood cultures over approx. 30min
• With subacute endocarditis:
3-6 blood cultures over approx. 24 h
• After previous antibiotic therapy:
5-10 blood cultures over several days, if clinical condition stable

Commonest organisms (O) and therapy (T):

a) Acute endocarditis
O: Staphylococcus aureus, group A or B staphylococci (less often),
Gram-negative rods (less often)
T: Flucloxacillin (2g 6 times daily i.v.)+ aminoglycoside

b) Acute endocarditis with prosthetic heart valve

O: Staphylococcus aureus, coagulase-negative staphylococci, other
organisms
T: Vancomycin (0.5 g q.i.d. as short infusion) + netilmycin

c) Subacute endocarditis
O: Streptococcus viridans, enterococci, Haemophilus spp.
T: Penicillin G (20 megaunits/day) + gentamicin or ceftriaxone (2g/
day)

Literature
Scheld and Sande (1990)

Pneumonia
Before therapy: • Empirical therapy necessary (neutropenia, sepsis)?
• Exclude other causes (pulmonary embolus, cardiac
decompensation)
• Bacterial pathogen (purulent sputum)?
• Non-bacterial pathogen (unproductive cough)?
• Underlying illnesses (alcoholism, condition after TB)?
• Necessary cultures taken (blood cultures, sputum)?

190
 INFECTIONS
Commonest organisms (O) and therapy (T):
(a) No underlying good general condition
illness,
O: Streptococcus pneumoniae
Mycoplasma pneumoniae (in younger patients)
T: Penicillin G i.v. or
amoxicillin orally or
erythromycin (in younger patients)

(b) Respiratory insufficiency

O: additionally Gram-negative organisms
T: Penicillin G, i.v.-t- aminoglycoside
or ceftriaxone

(c) Additional symptoms (diarrhoea, CNS symptoms, hyponatraemia)

O: Legionella species
T: In addition to ceftriaxone,
erythromycin (3-4g/day)

(d) With underlying illness

• Alcohol abuse
O: Klebsiella pneumoniae
T: Cephalosporin (2nd or 3rd generation)
• Chronic obstructive airways disease
O: Haemophilus influenzae
Streptococcus pneumoniae
T: Co-amoxiclav
• With history of influenza
O: Haemophilus influenzae
Staphylococcus aureus
T: Co-amoxiclav or
ceftriaxone
• HIV infection with purulent sputum
O: Haemophilus influenzae
Streptococcus pneumoniae
T: Co-amoxiclav or
ceftriaxone
• HIV infection without purulent sputum
(when CD4 lymphocytes < 200-400/1™^)
O: Pneumocystis carinii
(— > bronchoalveolar lavage!)
T: Cotrimoxazole (20/100mg/kg/day)
• Cystic fibrosis
O: Staphylococcus aureus
Pseudomonas aeruginosa
T: Quinolone (e.g. ciprofloxacin, ofloxacin)

Note: In hospital-acquired pneumonia the therapy must be individually chosen. In the

ventilated patient surveillance cultures are useful as a basis for decision-making.

Literature
Sanford(1991)

191
MEMORIX CLINICAL MEDICINE

Intra-abdominal infection
Before therapy: Clarification: cholecystitis (stone?), pancreatitis, perforated ulcer,
diverticulitis, appendicitis, ulcerative colitis, Crohn's disease,
infectious enterocolitis

Commonest organisms (O) and therapy (T):

a) Proximal to jejunum
O: Streptococci, enterococci, Gram-negative rods
T: • Surgery, when indicated
• Co-amoxiclav + aminoglycoside

b) Distal
O: Escherichia coli, Gram-negative anaerobes, etc.
T: • Surgery, when indicated
• Piperacillin + tobramycin + perhaps metronidazole
or
• Cefoxitin -I- tobramycin
or
• Imipenem (perhaps + aminoglycoside)
(Still unclear whether aminoglycoside necessary)

Urinary sepsis
Before therapy: Symptoms of urinary tract infection (dysuria, frequency, loin pain,
pyuria)?
Symptoms of sepsis (high pyrexia, rigors, hypotension, tachycardia)?

Commonest organisms (O) and therapy (T):

O: Escherichia coli, Enterococcus, Klebsiella pneumoniae,
Proteus mirabilis, Pseudomonas aeruginosa (esp. after
instrumentation or with calculi)
T: • Younger patients with normal renal function:
amoxicillin+ tobramycin
• Older patients and/or disturbed renal function:
newer quinolone
ciprofloxacin, ofloxacin or other

Note: This choice of antibiotics is valid for urinary sepsis, not for simple urinary tract
infection. With rapu esponse, therapy can be changed from intravenous to oral after
3-5 days.

Literature
Stamm et al. (1989)
Zimmerli (1990)

192
 INFECTIONS
Infections of the central nervous system
Before therapy: decide if meningitic or encephalitic syndrome

• Meningitic syndrome: meningism, pyrexia, photophobia, headache

• Encephalitic syndrome: clouding of consciousness, delirium,
confusion, convulsions, focal neurological signs, pyrexia

— If meningitis:lumbar puncture (interpretation, see p. 178),

blood cultures, differential white cell count, lactate, venous blood
gas analyses, search for primary focus (sinusitis, otitis, mastoiditis,
etc.)

— > If brain abscess or encephalitis:

CT scan without/with contrast (lumbar puncture contraindicated)
• brain abscess: search for primary focus (sinusitis, otitis, after
If
skull trauma, endocarditis, bronchiectasis, AIDS)
• If encephalitis: serology (mumps, measles, poliomyelitis,
coxsackie, echoviruses, rabies, tick-borne encephalitis, HSV,
CMV, HIV)

Commonest organisms (O) and therapy (T):

(a) Meningitis
O: • Newborn: Streptococci, group B, E. coli, Listeria monocytogenes
• Child: H. influenzae, Strep, pneumoniae, Neisseria meningitidis
• Adult: Strep, pneumoniae, Neisseria meningitidis
T: • Infant: amoxicillin, lOOmg/kg/day
+
ceftriaxone, lOOmg/kg/day
• Young child: ceftriaxone, lOOmg/kg/day
• Adult without
underlying illness: penicillin G, 24 megaunits/day
• Underlying ENT illness: ceftriaxone, 2g b.d.
• After organ amoxicillin, 2g 6 times/day
transplantation: +
gentamicin 5-7.5 mg/kg/day
• Neurosurgical shunt: rifampicin 450-600 mg b.d.
+
ceftriaxone 2g b.d.

Note: If a conclusive result on Gram preparation or if culture positive, treatment

should be targeted appropriately.

Literature
Schaad (1986)
Talan et al. (1988)

193
MEMORIX CLINICAL MEDICINE
(b) Brain abscess
O: Streptococcus sp. (anaerobic, aerobic),
H. influenzae, Strep, pneumoniae, Bacteroides sp.,
Staph, aureus, Nocardia, Toxoplasma gondii
T: • Unknown or ENT focus:
ceftriaxone 2g b.d. i.v.

+
metronidazole 0.5 g t.d.s. i.v.
• After skull or brain injury or neurosurgical operation:
flucloxacillin 2g 6 times/day i.v.

rifampicin 450-600mg b.d. i.v.

ceftriaxone 2g b.d. i.v.

• HIV infection
Empirical toxoplasma therapy

Literature
Chun etal. (1986)

(c) Encephalitis
treatable: Herpes simplex, varicella-zoster, cytomegalovirus,
Mycoplasma, Brucella, Borrelia burgdorferi,
Treponema pallidum, M. tuberculosis, Cryptococcus,
Toxoplasma gondii, Plasmodium falciparum
T: • Herpes simplex and varicella-zoster
acyclovir, 30mg/kg/day i.v. in 3 doses
• Cytomegalovirus
ganciclovir lOmg/kg/day in 2 doses
For remaining therapies see textbook.

Literature
Whitley (1990)

194
 INFECTIONS
Pyrexia with neutropenia
Before therapy: • Document pyrexia
• Actual number of neutrophil granulocytes?

Definition: Pyrexia: single measurement above 38°C

Persistent pyrexia: temperature > 38° C for >1 h
Neutropenia: < 1000 neutrophil granulocytes/ul
Note: The danger of infection increases greatly if < 500/ul, and very
greatly if < 100/ul. Rapid fall in neutrophil count and long duration
of the neutropenia are risk factors.

Clinical examination:
Gums, pharynx, perianal region, cannula puncture sites, fingernails,
chest auscultation, abdominal palpation.

Laboratory: Two aerobic/anaerobic blood cultures, Gram stain and culture of

skin lesions, culture of nasal smear, oropharynx, urine, stool,
possibly sputum.

Commonest organisms (O) and therapy (T):

O: Staph, aureus, coagulase-negative staphylococci, Gram-negative
bacilli (Ps. aeruginosa, E. coli, Klebsiella), Candida albicans,
Aspergillus.

T: Anti-pseudomonas betalactam antibiotic (e.g. ceftazidime or

+
piperacillin) aminoglycoside (e.g. amikacin), possibly
+ vancomycin if methicillin-resistant Staph, aureus in control
culture or if indication of cannula infection.

Procedure after initial empirical therapy:

Reassessment after 72 h:
If good response: continue empirical therapy.
change of empirical therapy on day 4:
If deterioration:
+ Vancomycin, if not used previously,
+ Amphotericin B if Candida or Aspergillus in control cultures.
For further procedures (antiviral therapy, duration of therapy, etc.)
see Hughes et al. (1990).

195
MEMORIX CLINICAL MEDICINE

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196
 INFECTIONS
Interpretation of Spontaneous course
Serology
syphilis test results of untreated spyhiiis

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197
MEMORIX CLINICAL MEDICINE
Immunization recommendations for children and adults
Note: Advice on vaccination and immunization varies from country to country.

In most countries there is an advisory schedule of immunizations for children (from birth
to around school-leaving age).

Further immunizations are performed in adults when it is important to reinforce child-

hood immunizations or to make up for any omitted for which natural immunity has not
been acquired (e.g. diphtheria, tetanus, rubella, measles). Other immunizations may be
considered in special epidemiological circumstances or risks in children and adults. Some
immunizations are required for travel in certain areas by international health regulations
or are desirable for individual protection. The decision concerning the nature and ex-
tent of the immunizations requires the physician to weigh the indications and
contraindications in each individual case. This also applies to passive and active immuni-
zation against hepatitis A.

There are no maximum intervals for killed vaccine immunizations. After a completed
basic immunization there is no need for a repeated basic programme.

198
 INFECTIONS
Childhood immunization schedule
Age (years) Vaccine Notes

0-1 Diphtheria, tetanus and pertussis First doses to be

and given at 2 months
Haemophilus influenzae b
and
Poliomyelitis (oral)

1-2 Measles/mumps/rubella At 12-15 months

(MMR) (live)
Haemophilus influenzae b At 13 months to 4
years if not previously
given

Entry to nursery school Diphtheria and tetanus Preferably allow

or school and interval of at least 3
(3-5 years) Poliomyelitis (oral) years after basic
course
Measles/mumps/rubella Unless history of
(MMR) (live) measle/mumps/rubella
immunization
or
contraindication
or
immunity

10-14 BCG For tuberculin-

negative children
10-14 allow at least 3 weeks
(females) Rubella (live) between BCG and
rubella immunization

On leaving school Poliomyelitis (oral)

or before employment and
or higher education Diphtheria and tetanus

199
MEMORIX CLINICAL MEDICINE

Adult immunizations important for individual and public

health

Vaccine Notes

Poliomyelitis (oral) if previously No adult should remain unimmunized

unimmunized

Rubella (live) Women of child-bearing age, if

sero-negative
(pregnancy should be excluded)

Tetanus if previously Reinforcing dose 10 years after primary

unimmunized course, then 10 years later

Hepatitis Aand B For all individuals in high-risk groups

Influenza Pneumococcal

Other vaccines and anti-sera available in special epidemiological circumstances and

required or recommended for travel to certain areas

Vaccine Notes

Anthrax Available to those subject to high exposure, e.g. infected

hides and carcasses, imported bone-meal, fishmeal
and feedstuffs

Botulism antitoxin Post-exposure prophylaxis

Cholera No longer required for travel to any country. Efficacy limited

Meningococcal Indicated for travel in parts of Africa and the

polysaccharide Indian subcontinent

Rabies Use prophylactically for those at high risk of exposure

Smallpox No longer required for travel

For laboratory workers subject to potential exposure

Typhoid

Yellow fever Certificate of vaccination required

travel to much of Africa and South America

In the UK, information and advice on immunization required for international travel is
issued by the Department of Health.
(The guidelines above reflect those of the UK
Joint Committee on Vaccination and
Immunization, modified from the British National Formulary.)

200
 HAEMATOLOGY
Sedimentation rate
Reaction Tumour Infection Connective tissue disorder/others

TTT
Raised (above Plasmacytoma Rheumatic fever Polymalgia rheumatica
100 mm after Waldenstrom's Sepsis Vasculitis ESR
In) macroglobulinaemia Peritonitis Polyarthritis Normal values:

Hodgkin's disease Nephrotic syndrome Mencf

after 1 h 3-8 mm
tt after 2 h 5-18 mm
Raised (above Metastasizing Bacterial Tissue necroses Women 9
SO mm tumours infections Myocardial infarct after 1 h 6-1 1 mm
after 1 h) Chronic liver diseases after 2 h 6-20 mm
T
Raised (up to Leukaemia Tuberculosis Postoperative, anaemia, hyperlipidaemia,
SO mm pregnancy (after 8th week), menstruation,
after 1 h) oral contraceptives, incorrect measurement
technique

i
Lowered Polycythemia vera Polycythemia, heart failure,
cryoglobulinemia, dehydration, anabolic
agents, plasma expanders, incorrect
measurement technique

Protein
(fluid blood component):
Serum + fibrinogen + coagulation factors
electro-
Serum: phoresis
Albumin + globulin
(McMorran and Paraskevas, 1981)

Alb. «i a2 3 Y

Total protein Albumin Globulins

60-84 g/1
a, a. P Y
Concentration g/1 35-40 0.6-1.5 0.4-3.4 2.1^*9 2.5-7.1

Proportion % 52-68 2.4^.4

J
6.1-10.1 8.5-14.5 10-21

Proteins Carrier protein for o^/a^-lipoprotein ^-lipoproteins Immunoglobulins

bilirubin, hormones, a, -antitrypsin Transferrin
fatty acids, drugs Oj-macroglobulin
Maintainance of Haptoglobulin
colloidal osmotic Caeruloplasmin
presssure Thyroxine-binding
globulin

Significance of 1 Synthesis Chronic liver Chronic hepatic Antibody deficiency,

low values T Losses disorders, disorders tumour of lymphatic
(renal, enteral) deficiency system, corticosteroids,
Tumour, inflammation dysproteinaemia imm unosuppressi ve
agents, nephrotic
syndrome, exudative
enteropathy

Significance of Dehydration, Acute inflammation, Paraproteinaemia, Rheumatic disorders,

high values hypoglobulinaemia nephrotic syndrome hyperlipidaemia. collagenoses, chronic
nephrotic infections, chronic
syndrome liver disorders,
paraproteinaemia

Acute inflammation Albumin reduced, alpha globulins increased

Chronic inflammation Albumin reduced, alpha and gammaglobulins icreased i

201
 )

MEMORIX CLINICAL MEDICINE

Peripheral blood and bone marrow i

1 Erythrocyte (basophil)

w
2 Neutrophil myelocyte
3 Normoblast with

1 2 3 4
• 5
karyorrhexia
4 Segmented neutrophil
(with vacuoles)
5 Middle normoblast
6 Basophil
7 Reticulocyte
8 Lymphocyte (spindle

•
form)
9 Lipophage (unripe)
10 Promegakaryocyte
• (granular cytoplasm)
11 Eosinophil
metamyelocyte
^.-ta&r 12 Monocyte (segmented
6 7 8 9 10
nucleus)
13 Platelets
14 LE cell

i
15 Myeloblast

i
16 Atypical lymphocyte

11
•9 12
**
13
^^^ 14 15
(clumped chromatin)
17 Erythrocyte (with
Cabot ring)
18 Basophil myelocyte
19 Erythrocyte (with
Howell-Jolly bodies)
20 Monocyte
21 Stippled erythrocyte
(basophil)

3 ^"^ 16 17 18
»

19 20
22 Eosinophil stab cell
23 Old normoblast (with
extruding nucleus)
24 Neutrophil (peroxidase
positive)
25 Fat-loaded histiocyte
26 Large lymphocyte (with

w
unusual plasma' outline
27 Hypochromic
3f« erythrocyte
28 Monocyte (evenly
distributed granules)
21 22 23 24 25 29 Eosinophil with
segmented nucleus
30 Monocyte (with
granules)

w § i
Half-moon body
31
due to smear
(artefact
being too thin)
32 Hypersegmentcd
macrocytic neutrophil
26 27 28 29 30 33 Tissue plasma cell
34 Lymphoblast
35 Large lymphocyte
36 Plasma cell (with

5§
***
vacuoles)
37 Basophil
metamyelocyte

31 32 33
^3 34 35
38 Monocyte (with
phagocytosed cell)
39 Lymphocyte (middle
aged)
40 Monocyte (with
phagocytosed pyknotic
nucleus)
41 Large lymphocyte
(azurophil granules)
42 Spherocyte
(erythrocyte)
36 37 38 39 40 43 Monocyte (with
pseudopodia)

#
44 Poikilocyte

i • H V* ;
45 Promyelocyte

41 42 43 44 45

(Reprinted with permission of Firma Ortho Diagnostic Systems GmbH, D-6903 Neckargemilnd)

202
 HAEMATOLOGY
46 Large lymphocyte (with
multiple vacuoles)

• 46 47
^mmm 48 ^^H^49 50
47 Erythrocyte (crcnated)
48 Hypersegmented large
neutrophil
49 Plasma cell (light red
cytoplasm)
50 Large lymphocyte (with
cytoplasmic
protrusions)
Monocyte (with

•
51

m 52
53
54
55
granules)
Megakaryocyte nucleus
Neutrophil ((stab cell)
Erythrocyte
Myeloblast (nucleoli,
no granules)
51 52 53 54 55
56 Young plasma cell
57 Lymphocyte (with
indented nucleus)

#
58 Neutrophil (peroxidase
positive)
59 Monocyte (multilobcd
nucleus, unusual form)
60 Proerythroblast
56 57 ^ 58 59 60
61 Prolymphocyte (double
nucleus)
62 Old normoblast
63 Atypical monocyte
64 Ripe neutrophil
myelocyte
65 Segmented basophil

61 62
ft 64 65
66 Eosinophil myelocyte
67 Plasma cell
68 Plasma cell (with
Russell bodies,
eosinophil granules)

# ••
69 Large lymphocyte (with
azure blue granules)
70 Sickle cell
71 Ripe neutrophil
(nucleus with clumped
chromatin)
66 67 68 69 70 72 Monocyte (fine
granules, vacuoles)
73 Macrocyte (increased
haemoglobin content)
74 'Old' neutrophil

iL..,„jr
'4 (pyknotic nucleus and
nuclear fragment)
75 Lymphocyte (with
nuclear fragment)
71 72 73 74 75 76 Small lymphocyte
77 Old normoblast (with
nuclear fragments)
78 Basophil stab cell
79 Histiocyte

• 76
•
77 78 79 80
80 Monocyte (with lobed
nucleus)
81 Reticulocyte
82 Segmented neutrophil
83 Megakaryoblast
84 Diffuse basophil
erythrocyte
85 Plasma cell (with
vacuoles)
86 Atypical young
-
megakaryocyte
(dark chromatin,
vacuolated
81 82 83 84 85 pseudopodia)
87 Erythrocyte (with
malaria ring)

o
88 Basophil erythroblast
89 Eosinophil cell
90 Lymphocyte (with
spiky cytoplasmic
protrusions)

86 87 88 89 90

(Reprinted with permission of Firma Ortho Diagnostic Systems GmbH, D-6903 NeckargemUnd)

203
MEMORIX CLINICAL MEDICINE

Haematological normal values

Hbg/dl 0" 14-18 $ 12-16 Blood count
Hct% 41-51 37^7 MCV, mean
Erythrocytes (RBC) (XlO6 ) 4.5-6.0 4.0-5.5
corpuscular volume;
HctXl ° MCH, mean
MCVfl 87±7
RBC corpuscular
*.****% Hb x 10 i». haemoglobin;
MCH pg
,
(= Hb \
c)
29 ±2
RBC MCHC, mean
MCHCg/dl
HbXl °° 34±2
corpuscular
Hct haemoglobin
concentration
Reticulocytes 7-15 %o 35 000-75 000/ul

Platelets 150 000-400 000/ul

Leucocytes 4 000-10 000/ul

Differential white cell count Percentage Absolute

Neutrophils Segmented 40-70 2000-7 000

stab cells 5-15 200-300
Eosinophils 2-10 100-600
Basophils 0-1 0-100
Lymphocytes 20^0 1500-5000
Monocytes 2-10 100-800

Iron metabolism
Transported from duodenum/jejunum to erythropoietic sites by transferrin (transport
protein).
Superfluous iron is stored by binding to iron storage protein (ferritin).
Daily iron loss = 1 mg/day; 2 ml blood — 1 mg Fe
Minimal daily iron = 12 mg/day (normal absorption 10-20%, absorption during
requirement for adults pregnancy ca. 40%)
Loss during menstruation ~ 15-45 mg; in pregnancy ~ 300-400 mg
(1 unit stored red cells = 200 mg iron)

Important laboratory parameters for iron metabolism

Ferritin (Normal 15-200 ng/ml) correlated with total body iron
i Iron deficiency anaemia

Normal T Anaemia of chronic illness

(tumour, infection, renal, chronic polyarthritis)

T Liver disorders, pernicious anaemia, leukaemia

TTT Haemochromatosis, liver necrosis, iron infusion

Transferrin: behaves in reciprocal fashion to ferritin (raised in iron deficiency)

Oral iron replacement is treatment of choice
Only ferrous iron (Fe 2+ ). Sulphate salts are well absorbed (absorption about 20% of
the administered amount, preferably taken fasting): because of side effects 100 mg
once, later 100 mg twice daily orally (after ca. 10 days reticulocytes T, Hb rise daily ca.
0.1-0.2 g%). After correction of blood count continue 50-100 mg daily for a further 2
months to replenish iron stores. Parenteral iron therapy very rarely.

204
 HAEMATOLOGY
Stem
Peripheral blood
lines

V,

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1
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I ft cm
* I /- Q.

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0)
MEMORIX CLINICAL MEDICINE

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206
 HAEMATOLOGY
Investigation of anaemia
Reticulocytes Smear Bone marrow Other tests Diagnosis

Normal Hypochromic No iron I Fe; i ferritin Iron deficiency

t HBA 2 T HBF , p-thalassaemia
Ring !hba 2 Sideroblastic
sideroblasts anaemia

Macrocytic Megaloblastic JB, 2 B, 2 deficiency

iB, 2 achlorhydria
; Pernicious anaemia
I Fe; T ferritin Chronic
inflammation
T Creatinine Uraemia
Disturbed liver Liver disease
function
Hypothyroidism
Aplastic Panmyelopathy

Normoblasts Infiltration Disseminated

malignancy
Fibrosis T Leucine Myelofibrosis
aminopeptidase

Increased Spherocytes Erythroid +ve Coombs' test Autoimmune

hyperplasia haemolytic anaemia
T Osmotic fragility Hereditary
spherocytosis
Internal/urogenital Anaemia of bleeding
bleeding
Heinz bodies Altered Hb Heinz body anaemia
electrophoresis
Heinz bodies G-6-PDH Enzyme deficiency
Polychromasia +ve Sucrose test Paroxysmal nocturnal
haemoglobinuria
Sickle cells +ve Sickling test Sickle cell anaemia
Target cells Altered Hb HbC, D and others
electrophoresis
Schistocytes Traumatic haemolysis
Acanthocytes Disturbed liver Abetalipopro-
function teinaemia,
liver disease

(Modified after Franklin Bunn (1983))

Diagnostic criteria of polycythaemia vera

(After the guidelines of the Polycythemia Vera Study Group)

Ali Red cell mass T Bl. Thrombocytosis

(d > 36 ml/kg) (> 400000/ul)
($ > 32 ml/kg)
A2. 2 saturation > 92% B2. Leucocytosis
(> 12000/ul)
A3. Splenomegaly B3. LAP* T or vitamin B 12 T
Diagnosis confirmed when Al + \2 + A3 or Ai + A2 + 2B criteria are fulfilled
MEMORIX CLINICAL MEDICINE

Coombs' test

Direct Diagnostic test (when positive, perform indirect Coombs' test).

Coombs' test Indication of incomplete antibodies bound to patient's red cells.

Red cell with bound + Coombs' serum = Agglutination

antibodies (washed) (bivalent antibodies
against human globulin)

%
Indirect Indication of antibodies circulating in patient
Coombs' test

Serum with incomplete + Red cells with Binding of antibodies

antibodies to be tested known antigen to test red cells

Second step - addition

Occurs in:
ofCoombs' serum

Acquired haemolytic anaemias, after transfusion

reactions, in leukaemia, lymphoma, systemic lupus N
erythematosus, primary chronic polyarthritis, CMV
infection, infectious mononucleosis, viral pneumonia,
therapy with penicillin, methyldopa; haemolytic disease N
of the newborn (infant: direct Coombs' test positive;
mother: indirect Coombs' test positive).

i
Agglutination

208
 HAEMATOLOGY
Differential diagnosis of enlarged lymph nodes

Infection
Streptococcal, staphylococcal and Salmonella infection, tuberculosis, brucellosis,
mononucleosis, cytomegalovirus infection, hepatitis, rubella, malaria,
syphilis,
toxoplasmosis, histoplasmosis, coccidioidomycosis

Systemic illnesses
Rheumatoid arthritis, SLE, dermatomyositis, sarcoidosis

Neoplasia
Lymphomas, chronic lymphatic leukaemia, myeloproliferative syndrome, acute
leukaemia, histiocytosis; metastases from breast, bronchus, ENT and urogenital
tumours

Endocrine
Hyperthyroidism, Addison's disease

Others
Serum sickness, hydantoin reaction, lymph node hyperplasia, histiocytosis,
dermatopathic lymphadenitis, Gaucher's disease, Niemann-Pick disease

Differential diagnosis of splenomegaly

Infection
Endocarditis, TB, brucellosis, mononucleosis, cytomegalovirus infection, syphilis,
malaria, histoplasmosis, schistosomiasis, kala-azar

Systemic illnesses
Rheumatoid arthritis, Felty's syndrome, SLE

Neoplasia
Lymphomas, CLL, myeloproliferative syndrome, acute leukaemia, histiocytosis

Haematological
autoimmune haemolytic anaemia, haemoglobinopathies,
Spherocytosis,
angioimmunoblastic lymphadenopathy with dysproteinaemia (AILD)

Congestion
Hepatic cirrhosis, portal vein/splenic vein thrombosis, extramedullary erythropoiesis,
vinyl chloride

Metabolic
Amyloidosis, Gaucher's disease, Niemann-Pick disease

Others
Abscess, cysts, haemangiomas, aneurysms

209
MEMORIX CLINICAL MEDICINE
 HAEMATOLOGY
Leukaemia
Leukaemia Acute
type
Lymphoblastic
leukaemia (ALL) ia !AML) leukaemia (CI 1
)
ia (CML)
Age Children 85% Adults 82% Over 50 years 25-45 years
Adults 15% Children 10%
Incidence per 2-3 2-3 Below 50 years 5 Over 60 years 3
100000 Over 60 years 20

Blood count
Leucocytes Lymphoblasts Myeloblasts TT Lymphocytes TT All maturation stages
Leukaemic hiatus Leukaemic hiatus
Platelets u u ni nT
Erythrocytes Anaemia Anaemia Anaemia Anaemia
Others Auer rods Gumprecht's nuclear il Leucocyte
shadow alkaline phosphatase
Philadelphia chromosome

Therapy Emergency admission to treatment centre Treat according to 1. Leucocytes should be

Urgent cytoreductive therapy stage (see below) <20000 (e.g.
chlorambucil)
2. Introduction to a
treatment cantre

FAB classification of acute leukaemias (French -American-British Cooperative Group (1976))

Acute lymphoblastic leukaemia

L-l Acute lymphoblastic leukaemia in children, homogeneous cell population
1-2 Acute lymphoblastic leukaemia in adults, heterogeneous cell population
1.3 Leukaemia resembling Burkitt's lymphoma, large cells, homogeneous cell population

Acute myeloblastic leukaemia

Ml Little granulocytic differentiation, no maturation
M-2 Granulocytic differentiation with promyelocytes
Granulocytic differentiation with hypergfanular promyelocytes
(often disseminated intravascular coagulation (DIC))
M-4 Myelomonocytic differentiation
M-5 Monocytic cells of differing degrees of differentiation
M-6 Predominantly erythroblasts with severe dyserythropoiesis
M-7 Acute megakaryocyte leukaemia (acute myelofibrosis)

Myelodysplastic syndrome
Definition: Maturation defect of myelopoiesis with, usually, normo- to hypercellular marrow and
ineffective haemopoiesis (thrombopenia and/or leucopenia)
Classification Abbreviation Peripheral blood count Marrow
Refractory anaemia Anaemia, reticulocytopenia, Normo- or hypercellularity,
dyserythropoiesis, predominant dyserythropoiesis,
dysgranulopoiesis, blasts < 1% blasts < 5%
Refractory anaemia with AsRA As RA and: > 15% sideroblasts
ringed sideroblasts in marrow

Refractory anaemia with R « fi B At least bilinear cytopenia, Hypercellularity. Blasts 5-20%

excess of blasts blasts <5%
Refractory anaemia with RAEB-1 RAEB criteria and Either 20-30% blasts
excess of blasts >5% blasts or Auer rods
in transformation

Chronic Monocytes > 1000/ul As in RA or RAEB:

myelomonocytic Blasts < 5% blasts up to 20%. Increase
leukaemia in monocyte precursors

Therapy: supportive (erythrocyte and/or platelet transfusions).

211
MEMORIX CLINICAL MEDICINE

Hodgkin's lymphoma
Clinical staging (Ann Arbor classification)

I: Involvement of a single lymph node region or of a single extralymphatic organ or

site

II: Two or more lymph node regions, or lymph node regions and one extralymphatic
organ on the same side of the diaphragm

III: Lymph node regions on both sides of the diaphragm, involvement of one
extralymphatic organ or splenic involvement possible

IV: Diffuse extralymphatic organ involvement

E: Extranodal involvement

S: Splenic involvement

A: No general symptoms
B: General symptoms:
Fever above 38°C (Pel-Ebstein), night sweats, loss of weight (more than 10% of
body weight in 6 months)

Histological classification

Lymphocyte predominant, giant cell deficient, nodular sclerosing, mixed cellularity,

lymphocyte depleted, giant cell rich.

Staging Of CLL after Rai (1975)

Stage Definition

Lymphocytosis >15000/mm 3
Bone marrow infiltration >40%
I Lymphocytosis and adenopathy

II Lymphocytosis and hepatomegaly and/or splenomegaly

(with or without adenopathy)

III Lymphocytosis and anaemia (Hb < 110g/l)

(with or without adenopathy and/or organomegaly)

IV Lymphocytosis and thrombocytopenia (< 100000/mnv ) 1

(with or without anaemia, adenopathy, organomegaly)

Therapy: from stage III and/or with symptomatic lymphomas

212
 HAEMATOLOGY
Kiel classification of non-Hodgkin's lymphoma
Low malignancy grade
Lymphocytic
• Bcell
• Tcell
• Hairy cell leukaemia
• Mycosis fungoides/Sezary syndrome
• T zone lymphoma
Lymphoplasmocytic/cytoid (LP-immunocytoma)
Plasmocytic
Centrocytic
Centroblastic/centrocytic
Unclassified (low malignancy)

High malignancy grade

Centroblastic
Lymphoblastic
• B lymphoblastic, Burkitt type and others
• T lymphoblastic, convoluted cell type and others
• Unclassified
Immunoblastic
• with plasmoblastic/plasmocytic differentiation(B-immunoblastic)
• without plasmoblastic/plasmocytic differentiation (B- or T-immunoblastic)
Unclassified (high malignancy)

Clinical staging of plasmacytoma

(After Durie and Salmon)

Stage Criteria Tumour cell

mass/m2 body
surface

I All of the following:

1. Hb>100g/1 <0.6 x 10 12
2. Serum Ca normal (s£l0.5mmol/l)
3. Radiologically normal bony skeleton; or only
a single solitary plasmacytoma localized in bone
4. Low concentration of paraprotein
a) IgG <50g/l
b) IgA <30g/l
c) Light chains in urine <4g/24h

II Not fitting into either stage I or stage HI 0.6-1.2 x 10' 2

III One or more of the following:

1. Hb<85g/1 >1.2 X 10 12
2. Serum Ca >8.5mmol/l
3. Advanced osteolytic bone changes
4. High concentration of paraprotein
a) IgG >70g/l
b) IgA >50g/l
c) Light chains in urine > 12g/24h
Subclassification: A Relatively normal renal function:
serum creatinine < 180umol/l
B Impaired renal function:
serum creatinine 2sl80umol/l
Therapy: from stage II and/or for local problems (e.g. danger of fracture)

213
 h

MEMORIX CLINICAL MEDICINE

Types Of allergic reactions (After Coombs and Gell)

Type Time Agent Illnesses

I Immediate Minutes IgE Anaphylaxis (shock), bronchial

anaphylaxis asthma, allergic rhinitis, urticaria,
angioneurotic oedema
II Cytotoxic 4-8h IgG Transfusion reaction autoimmune ,

(IgM) haemolytic anaemia, Goodpasture's

syndrome

HI Immune 4-8h IgG Serum sickness allergic alveolitis,

,

complex (IgA, IgM) vasculitis, systemic lupus

erythematosus, glomerulonephritis

IV Late type, 24-72 T cells Tuberculin reaction contact ,

cell eczema, transplant rejection,

mediated chronic hepatitis

Assessment of immune system illnesses

(After Lawton and Cooper (1983))
I cell system B cell system

History Fatigue, deterioration of general condition, fever, infections, loss

of weight

Reaction against nettles, atypical Reaction against

infections, chronic diarrhoea vaccinations

Laboratory ESR, red and white cell counts, chest X-ray,

(simple) immunoelectrophoresis, complement C3, C4, CH50
Skin test (multitest: diphtheria, tetanus, Antibodies against
streptococcal, tuberculin, Candida, rubella, influenza,
Trichophyton, Proteus, glycerine) tetanus, diphtheria

Laboratory T lymphocyte count, surface markers, B lymphocyte count,

(specialized) lymph node biopsy membrane markers
(for v-globulins, C3,
Epstein-Barr virus)
Immunofluorescence
bone
investigation of
marrow, lymph node
biopsy

214
 HAEMATOLOGY
Anaphylaxis
Classification of anaphylactic/anaphylactoid reactions by degree of severity
(After Ring and Messmer (1977))

Grade Skin Abdomen Respiratory Heart

tract circulation

II Nausea Rhinorrhoea Tachycardia

Itching Cramps Hoarseness (A> 20/min)
Flush Dyspnoea Hypotension
Urticaria (A>20mmHg
Angioneurotic systolic)
oedema Arrhythmia
III (not Laryngeal oedema Shock
obligatory) Vomiting Bronchospasm
Defecation Cyanosis
IV Respiratory arrest Cardiac arrest

Emergency measures in anaphylactic/anaphylactoid reaction of different degrees of

severity

Symptoms Therapy

Cardiorespiratory arrest

Shock
Cyanosis

BPi
Lung
Gastrointestinal

Skin

Stop antigen (precipitant) intake! i.v. access

Degree of
severity

215
MEMORIX CLINICAL MEDICINE

I)
+
(E I)
(I)
+ I) (I)
4-
(E
deficiency
(E rinsic

disease (I) h.
intravascular

(I) c *
(DIC)
bleeding

factor
A/B deficiency

therapy

-
Willebrand's
W
_ Afibrinogenaemia
diseases
K coagulopathy _CJ
: Haemophilia Anticoagulant
Disseminated
Coagulation

c
+ + +
Fibrinolytic

+
-

Vitamin

: Von
Liver + + + ^r+ + + + * "co ^
1 + + + z*+ + + + + c UJ c a. c c c

s
acid,

(Werihof

thrombocytopenic

disease

(Acetylsalicylic phenylbutazone

sulphinpyrazone

>- thrombopathies

(ITP)
dipyridamole

heparin)

-
- Thrombocytopenia

_: purpura
Glanzmann's

E disease)

:
Idiopathic
Uraemia
+ + + + + jr
— Giant Drugs + + + + + + + + ±j
c c e<— c

treatment)

syndrome

(Henoch- purpura)

haemangioma

disease, deficiency,

meningococcal)

— C
- Osler-Rendu-Weber
infections

toxicity
-. corticosteroid

Schonlein's
(Cushing's
z syndrome
Ehlers-Danlos

Autoimmune

Metabolic vitamin
Cavernous

(e.g.
<—
-
Drug
With
+ +t-+7i 4 J
> + + + + + ;l 1 1 1 1 ^ c c c ~e* c

test

bleeding

bleeding
bleeding

haematomata haemorrhage

tourniquet

time
time
test

•0
2 Haematomata
Gastrointestinal

Menorrhagia
Haematuria
Haemarthroses

Post-traumatic
Postoperative

'•B
8 9 Petechiae
Epistaxis

Visceral
Cerebral
Positive
Platelets Quick's
Bleeding Clotting

u PTT
<
sassaiqi] suio)duiA*s Xjo|RJoqir|

216
 ,

HAEMATOLOGY
Coagulation cascade

Injury

« o> Exposure of

o re collagen Vasoconstriction
S o. Endothelial Tissue
> cells Slowed injury

I
blood flow
# % _l_
2 8
Platelets Adhesion ^ Aggregation
Platelet
thrombus

/
io
c
1 Plasminogen —* Plasmin
—
degradation
?§ 1
Fibrin

E Sf, products
1

Coagulation tests: Bleeding time, @ PTT, Prothrombin time (Quick), Thrombin time
(TT), Euglobulin lysis time

217
 ss

MEMORIX CLINICAL MEDICINE

Coagulation tests

Test Test function Causes of abnormal test result

(normal values)

Platelets Thrombocytosis
150 000-400 000 Thrombocytopenia

Quick's test Global test of extrinsic Deficiency or inhibition of I,

(Thromboplastin time, system, control of II, V, VII, X.

prothrombin time) coumarin therapy Vitamin K deficiency.

70-100% Anticoagulation with
coumarins, liver diseases

PTT Global test of intrinsic Deficiency or inhibition of I,

Partial thromboplastin system II,V, VIII, IX, X, XI, XII.

time Vitamin K deficiency,
Standard: 68-82 s anticoagulation with
Activated: 11— 15s coumarins
(method dependent)

Thrombin time Control of heparin Afibrinogenaemia, thrombin

13-17 therapy inhibitors, heparin therapy

Bleeding time Global test of platelet Thrombocytopenia, von

1-9 min
Ivy: function Willebrand's disease,
Duke: 1-4 min thrombasthenia, aspirin

Clotting time Global test of extrinsic Factor deficiency (less than

Lee-White: 8-18min and common coagulation 3%): I, II, V, VIII, IX, X, XI,

systems XII

Coagulation factors Hereditary deficiency, liver

50-200% of normal diseases, DIC
Fibrinogen Afibrinogenaemia, DIC,
15O-450mg% infections
1.5-4.5 g/1

Fibrinogen degradation Semiquantitative latex DIC, fibrinolytic therapy,

products (FDP) demonstration of FDP liver diseases
Over 8mg/ml (X, Y, D, E)

Ethanol test Demonstration of fibrin DIC, fibrinolytic therapy

monomer
Euglohulin lysis time Global test of fibrinolytic DIC, fibrinolytic therapy,
Over 2 hours activity liver diseases

Reptilase time Heparin independent: Prolonged with fibrin-

18-22 demonstration of DIC in fibrinogen degradation
heparinized patient products: DIC

DIC, disseminated intravascular coagulation.

218
 HAEMATOLOGY
Coagulation factors (cf. p. 217)

Factor Synonyms Site of action in Illnesses

coagulation system

Fibrinogen Common Afibrinogenaemia

11 Prothrombin Common Vitamin K

deficiency, liver disease

in Tissue thromboplastin Extrinsic

IV Calcium ions Universal

V Labile factor, proaccelerin Common Hereditary deficiency

Vli Proconvertin Extrinsic Vitamin K deficiency,

liver disease, hereditary

VIII Antihaemophilic factor Intrinsic Haemophilia A

IX Christmas factor Intrinsic Haemophilia B
(antihaemophilic factor B) (Christmas disease),
vitamin K deficiency,
liver diseases

X Stuart Prower factor Common Vitamin K deficiency,

liver disease, hereditary

XI Plasma thromboplastin Intrinsic Hereditary

antecedent (PTA)

XII Hagemann factor Intrinsic Hereditary

XIII Fibrin stabilizing factor Common Hereditary

Drugs affecting coagulation and their antidotes in the

coagulation system
Drug Antidote

Heparin Protamine
Main action: antithrombin. Inactivates: Ila, IX, X;
inhibits the conversion of prothrombin to thrombin.
Develops its activity in the presence of heparin
cofactor (antithrombin III). Short half life

Couinarins Vitamin K,
Main action: vitamin K antagonist. Is used in liver for synthesis of
Inactivates: II, VII, IX, X. Long half life factors II, VII, IX, X
Fibrinolytics Antifibrinolytics
Streptokinase, Urokinase, t-PA, APSAC Tranexamic axid (AMCA)
Main action: promote the conversion of Main action: inhibits the
plasminogen to plasmin activation of plasminogen
MEMORIX CLINICAL MEDICINE
Thromboembolism
Clinical risk factors for venous Congenital, in part also acquired
thromboembolism disturbances of the haemostatic and
fibrinolytic systems which can cause
increased tendency to thrombosis
Age (> 40 years)

Antithrombin III deficiency (type I defect)

Surgery (dependent on nature and or abnormal AT III molecule (type II
duration of operation, esp. hip surgery!) defect)

Trauma, burns Protein C deficiency

Protein S deficiency
Immobilization (confinement to bed; e.g. Dysfibrinogenaemia
also immobilization of limb in plaster, or Factor XII deficiency
long car/air journeys) Plasminogen deficiency/abnormal
plasminogen
Malignancy
Diminished fibrinolytic capacity due to
Previous venous thrombosis a) reduced liberation of tissue
plasminogen activator (t-PA) from the
Varicose veins vessel wall or
b) increased plasma activity of the

Obesity plasminogen activator inhibitors (PAI)

Appearance of a lupus anticoagulant'

Pareses and paralyses of legs
1
The designation anticoagulant is misleading and
Oral contraceptives (oestrogen content) refers to the in vitro inhibitory activity of this
immunoglobulin on clotting. Patients more
commonly develop a tendency to thrombosis than
Pregnancy, puerperium to bleeding.

(After Kienast and van de Loo (1991))

Thrombolytics
Streptokinase (SK) (half life 25min)

Urokinase (UK) (half life lOmin)

Plasminogen activator Tissue-type plasminogen activator (t-PA) (half life 2-7 min)

Acylated plasminogen streptokinase activator complex

(APS AC) (half life 80-90 min)

- Plasminogen activator inhibitor-1 (PAI-1)

Plasminogen -* Plasmin

- ovAntiplasmin

Fibrin ^ — Fibrin degradation products

Scheme of the fibrinolytic systems

220
 HAEMATOLOGY
Standardization of thromboplastins; INR/Quick's test

Calculation of the International Normalized Ratio for therapy control under

stable anticoagulation with vitamin K antagonists
(After Kienast and van de Loo (1991))

INI = R' SI

INR International Normalized Ratio

R Quotient from thromboplastin time (prothrombin time) of the
patient's plasma divided by thromboplastin time of a normal plasma
pool (usually commercial calibration or standard human plasma)
ISI International Sensitivity Index
This index is determined by the manufacturer for the respective
thromboplastin batch by calibration against an international reference
thromboplastin

If a thromboplastin with a sensitivity factor of 1.1 (e.g. Thromborel S) is

used, the INR range of 2.0-3.0 is equivalent to a Quick's test value of

24-48%

Thromboplastins

70 CRB (Roche)
• FS Dade (Baxter)
+ Hepatoquick
60 O Thrombotest
x Diaplastm B (Diamed)
n Thromborel S (Behring)
T 50"
a Thrombokinase (Geigy)

• Thrombocalcique
<d 40"
k.
;?
e
1 30 2 a
O
20- n
8 2
10
o oo
Moderate intensity High intensity

1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0

INR

221
MEMORIX CLINICAL MEDICINE
Oral anticoagulants - interfering factors

Enhancement of activity Reduction of activity (Quicks test rises,

(Quick's test falls, danger of bleeding) inadequate protection against thrombosis)

Drugs: Drugs:

Allopurinol Activated charcoal

Amiodarone Acetylcholine

Anabolic steroids ACTH

Antibiotics (oral) Adrenaline

Aperients, especially those containing Antithyroid drugs

paraffin Atropine

Aspirin 1 Barbiturates 3

Azapropazone 3 Biguanides

Bezafibrate Carbamazepine
Carbamazepine Cholestyramine

Chloral hydrate b Contraceptives (oral)

Chloramphenicol (Digitalis)

Chlorpropamide (Diuretics)

Cimetidine Ganglion blockers

Clofibrate Glutethimide

Dextran preparations Griseofulvin

Disulfiram Haloperidol b

Ergot alkaloids Laxatives

Ethacrynic acid Meprobamate
Flufenamic acid 3 Mercaptopurine
Glucagon Metformin
Indomethacin 3 Metronidazole

Local anaesthetics Multivitamin preparations

Mefenamic acid 3 Neuroleptics 6
Methyldopa Penicillins

Metronidazole Phenytoin (with prolonged treatment)

Monoamine oxidase inhibitors Propylthiouracil

Nalidixic acid Purine derivatives

Rifampicin

Steroids 8

Strophanthin (ouabain)

222
 )

HAEMATOLOGY
Enhancement of activity Reduction of activity (Quick's te^t ris'es,
(Quick's test falls, danger of bleeding) inadequate protection against thrombosis)

Naproxen
Neomycin
Nicotinic acid derivatives

Nortriptyline Vitamin K (preparations)

Oxyphenbutazone*
Phenothiazine preparations Foodstuffs containing large amounts of
vitamin K*

Phenylbutazone 3 (>0.1 mg vitamin K/lOOg):

Phenytoin (at start of therapy) Spinach (3-4.6)

Piroxicam Cabbage, sauerkraut
Probenecid Tomatoes (0.4-0.8)

Propafenone (Pig's) liver (0.4-0.8) offal

Quinine, quinidine Soya beans, also bean sprouts (0.2)

Ranitidine Bean (0.3), peas (ca. 0.3)

Salicylates 3 Pork and other meats (ca. 0.2)

Sulphinpyrazone Sunflower seed oil (ca. 0.5)

Sulphonamides
Sulphonylureas * alsodependent on fat consumption;
Thyroid hormones (thyroxine, avoid excessively fatty foods
triiodothyronine
Tolbutamide
Tricyclic antidepressants

Others: Others:
Alcoholism Obesity
Hepatic illness of other types Hypothyroidism, myxoedema
Gall bladder disease
Fever
Heart failure with hepatic congestion

Hyperthyroidism
Old age
Malabsorption
Radiotherapy

Alternative drugs:
* Analgesics: paracetamol, centrally acting analgesics;
Antirheumatic agents: diclofenac, sulindac, ketoprofen, tolmetin.
h
Hypnotics: diazepam, flurazepam, nitrazepam.

223
MEMORIX CLINICAL MEDICINE

Blood r eplacement

Fresh blood Plasma-depleted Concentrated Platelet FFP

blood red cells concentrate

Definition Whole blood Whole blood Concentrated Platelet concentrate Fresh frozen
(minus 100ml red cells (minus pooled from 4-6 plasma
plasma) 200ml plasma) donors

Indication Not used in Major haemorrhage RBC replacement Bleeding with Bleeding with
practice: single (little circulatory thrombocytopenia deficiency of
preparations load) clotting factors,
preferred Hct rise/ anticoagulants
concentrate: 2-3% or DIC

Hct 40 ± 7% 47 ± 3% 70 ± 10%

Volume 500 ml 400 ml 300 ml 250 ± 50ml 250 ± 50 ml

Procedure in case of transfusion reaction Complications of blood transfusion

• Repeated typing of donor and recipient blood • Cooling, air embolism, hypervolaemia
• Detection of free Hb, haemoglobinuria, haptoglobin • Citrate intoxication, hyperkalaemia, acidosis
fall • Contamination with bacteria, viruses, parasites
• Hyperbilirubinaemia, search for intravascular
coagulation

Exclusion criteria for own blood donation

1. Hb below 120g/l

2. Poor general condition, signs of hypovolaemia

3. Acute infection

4. Less than 48 h before surgery

5. 24 h after contrast medium administration

6. Further invasive measures on day of own blood donation

7. Tendency to convulsion: epilepsy

8. Haematological illnesses: e.g. leukaemia, autoimmune haemolytic anaemia

9. Manifest cardiac failure

10. Myocardial infarct within last 3 months (time interval dependent on general
condition and cardiac catheterization findings)

11. Aortic stenosis (moderate to severe)

12. Unstable angina pectoris

13. Severe arrhythmias: bradycardia

(Johannesson et al. 1990)

224
 ONCOLOGY
Basic tumour therapy
Preconditions for all tumour therapy
• Confirmation of diagnosis
Histology? Stage? Prognosis?
• Assessment of progress
Measurable parameters (X-ray, ultrasound, markers)? Side effects?
• Treatment strategy
Curative? Aggressive to total remission; 2 consolidation treatments; but:
change of therapy if failure of response!

Palliative? Low side effects, aimed at symptoms

Modality? Local (surgery, radiotherapy)? Systemic?
• No contraindication

Clinical trial of cytostatic agents

Phase I Determination of maximum tolerable dose
Phase II Determination of toxicity and effectiveness of a drug for one tumour
type
Phase III Comparison with established therapy
Quality of life

100

1. Cure
2. Palliative therapy
3. No therapy
Death | \ ^ , 4. Inadequate therapy
Time

Definitions of response of solid tumours to therapy

Definition Measurable disease Non-measurable disease Bony metastases

Complete Disappearance of all known Disappearance of all known Complete disappearance of all
response manifestations of disease manifestations of disease lesions on X-ray or bone
(CR) for at least 4 weeks for at least 4 weeks scintigram for at least 4 weeks

Partial Reduction of measurable Estimated reduction of Partial size reduction of lytic

response tumour mass by at least tumour mass. by at least lesions, recalcification of lytic
(PR) 50% for at least 4 weeks. 50% in 4 weeks lesions, density reduction of
No new lesions or progression sclerotic lesion for at least
of a solitary lesion 4 weeks

No PR and PD criteria not PR and PD criteria not An assessment is only

change (NC) fulfilled fulfilled possible after 8 weeks

Progressive Enlargement by at least 25% Estimated enlargement by Enlargement of existing

disease (PD) or appearance of new lesions at least 25% or appearance lesions, appearance of new
of new lesions lesions

(After Miller, Hoogstraten, Staquet and Winkler (1981))

225
MEMORIX CLINICAL MEDICINE

Prognoses
Curable tumours (10-20% of all neoplasms)

Tumour Complete % Survival

remissions (%) after ^ 5 years
Chorioncarcinoma (women) 80-90 80-90
Testicular carcinoma 90-90 75-90
Acute lymphatic leukaemia (<20 years) 90-90 50-90
Hodgkin's disease III-IV 80-90 50-80
Burkitt's lymphoma III-IV 80-90 50-70
Non-Hodgkin's lymphoma II-IV 70-90 30-40
Acute myeloid leukaemia 70-90 10-20
Small cell carcinoma of bronchus 60-90 s*10

Palliative therapy with prolongation of life (ca. 40% of all neoplasms)

Tumour Response Mean survival time

rate (%) with remission (years)

Chronic leukaemias (CML, CLL) 90-100 3-5

Carcinoma of prostate 70-80 2-3
Multiple myeloma 60-70 2-3
Carcinoma of breast 60-70 2
Carcinoma of ovary, FIGO III-IV 60-70 1-2
Carcinoma of endometrium 50 1-2
Sarcoma of supporting tissue 40 l(-2)
Squamous carcinoma of ENT region 50 1-2

Palliative chemotherapy without increased survival, but improvement in quality of life

(ca. 30% of all tumours)

Tumour Remission Mean survival time

rate (%) with remission (months)

Adenocarcinoma of stomach 40(-50) 10-12

Urothelial carcinoma 40(-50) 8-10
Non-small cell carcinoma of bronchus 30(-40) 8-12
Carcinoma of adrenal cortex 30-40 8-12
Other carcinomas of gastrointestinal tract 20(-30) 6-8
Malignant melanoma 20-40 6-8
Squamous carcinoma in gynaecological region ( 10-)20 5-6

Tumours hardly responsive to chemotherapy

Tumour Partial remission rate

(inoperable, metastasizing)

Carcinoma of kidney 10-25%

Primary CNS tumours (except medulloblastoma) 10-20%
Carcinoma of liver 10-20%
Slow-growing sarcomata (e.g. chondrosarcoma) 10%
Anaplastic carcinoma of thyroid 10-20%
(After Handschuh and Diehl (1986))

226
 ONCOLOGY
Early warning symptoms of tumours
• Loss of weight (> 10%)
• Frequent attacks of fever
• Alteration of bowel or bladder habit; frequent digestive disturbances
• Persistent hoarseness, intractable (bloody) cough
• Persistent dysphagia
• Changes in warts or naevi
• Bleeding or discharge from body orifices (extramenstrual bleeding)
• Development of lumps or hardening (breast, testicular swelling, etc.)
• Non-healing wounds; persistent swellings

Tumour markers
Employment Aftercare
Diagnostic: • Within follow-up programme (e.g. quarterly)
• In symptomatic patients • Postoperative after curative resection
• Supervision of risk groups • Prior to extensive therapeutic measures
• Not in asymptomatic partients • Before change of therapy
• In case of unclear changes in clinical picture
• With renewed staging

ENT: SCC
Thyroid:
hCT, NSE, Tg

9 Breast:
CEA + CA 15-3

Stomach:
CEA + CA 19-9

Bladder: TPA
9 Ovary:
Cf Prostate: CA 125, HCG, AFP
PAP/PSA
9 Cervix: SCC
Cf Testis:
AFP, HCG Tumour markers and
organ attribution

SCC, squamous cell carcinoma antigen; CEA, carcinoembryonic antigen; NSE,

neuron-specific enolase; TPA, tissue polypeptide antigen; hCT, human calcitonin; Tg,
thyroglobulin; AFP, alpha-fetoprotein; HCG, human chorionic gonadotrophin; PAP,
prostatic acid phosphatase; PSA, prostate-specific antigen; ENT, tumours in ENT
region

(After Lamerz (1986))

227
MEMORIX CLINICAL MEDICINE

Tumour staging
Tumour Tissue identification (non-operative)/laboratory X-ray/ultrasound
(Tumour markers see p. 227) (MRI indications cf. pp. 45-7)

Lung Sputum cytology, bronchoscopy with biopsy, trans- CT thorax

thoracic biopsy, mediastinoscopy, pleural biopsy, CT skull
tapping of pleural effusion, lung function tests, blood Bone scintigram
gas analysis, cf. p. 128 Sonogram
Breast Biopsy/hormone receptors, lymph node biopsy Mammography, chest X-ray,
sonogram, bone scintigram
Prostate Transrectal biopsy, cystoscopy, prostate-specific IVU, X-ray pelvis, bone
acid phosphatase scintigram, transrectal
sonography
Oesophagus Endoscopy + biopsy, mediastinoscopy CT thorax, barium swallow

Stomach Endoscopy + biopsy (laparotomy), stool occult blood Ultrasound, chest X-ray, CT
abdomen
Colon Endoscopy + biopsy (laparotomy), stool occult blood Ultrasound, CT abdomen
Pancreas Needle biopsy Barium enema ultrasound,
CT abdomen, ERCP (i.v.

cholangiogram)
Liver Laparoscopy + biopsy, hepatitis serology Ultrasound, CT abdomen
Lymph Lymph node biopsy, biopsy with contrast medium, CT thorax, CT abdomen,
nodes liver biopsy, laparotomy, possibly splenectomy, lymphography, skeletal
lymphocyte typing scintigraphy

Ovary, Laparoscopy + biopsy, cervical smear, cytology of Ultrasound, CT abdomen

uterus washings, curettage, proctoscopy, possibly (IVU)
oophoropexy, hormone receptors
Testes (Testicular biopsy) CT pelvis, CT thorax.
CT skull, lymphography
Kidney, Urine cytology, cystoscopy, proctoscopy, Ultrasound, IVU, chest
bladder erythropoietin X-ray, CT abdomen,
cavogram, arteriography
CNS CSF cytology CT skull,cerebral
arteriography
Thyroid Needle biopsy Chest X-ray, radioiodine
uptake, ultrasound

Aim: Staging: histological diagnosis and recording of tumour extent

TNM Syste
T Primary tumour size
Tis Non-invasive carcinoma (carcinoma in situ)
T1.T2.T3,T4 Increasing size and extent of the primary tumour (all sizes in 2 dimensions)
TX Minimal requirements for assessment of primary tumour not fulfilled
N Regional lymph nodes
NO No evidence of regional lymph node involvement
Nl, N2, N3 Regional lymph node involvement
N4 Involvement of juxtaregional lymph nodes
NX Minimal requirements for assessment of regional lymph nodes not fulfilled

M Metastases
MO No distant metastases
Ml Distant metastases
MX Minimal requirements for assessment of distant metastases not fulfilled

G Histopathological grading
Gl-3 Increasingly undifferentiated tumour
GX Grading not ascertainable
(Modified after UICC (1982))

228
 ONCOLOGY
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229
MEMORIX CLINICAL MEDICINE

Scales for assessment of the physical condition of tumour

patients
ECOG - Eastern Cooperative Oncology Group; AJC - American Joint
Commission for Cancer Staging and End Results Reporting

Description of condition Karnofsky Zubrod Description of

scale (%) scale (ECOG) condition
(ECOG, AJC)

No complaints, no 100 Normal activity

evidence of the illness

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minor symptoms of illness patient ambulant,
is

and can master the

activities of everyday
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in bed; self-caring

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but can still look after own
personal bodily functions

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and frequent medical attention 50% of time;
requires assistance
Handicapped, requires 40
specialized nursing and support

Severely disabled, admission to 30 4 Bedridden, requires

hospital indicated, not in admission to hospital
immediate danger of death

Very ill, requires admission to 20

hospital, requires active and
supportive therapy

Moribund 10

Dead

230
 ONCOLOGY
Mode of action of cytostatic drugs
Precursor

[PCZ
Mefhylation Fixation of amino acids |^ /
Mitotic
spindle
ACD, actinomycin D; ADM, doxorubicin; Alkyl., alkylating substances; ASP, asparaginase;
BCNU, carmustine; BLM, bleomycin; CAR, cytarabine; CCNU; lomustine; DHF, dihydrofolic acid;
DIC, dacarbazine; DRB, daunorubicin; EPE, etoposide; EPT, teniposide; FU, fluorouracil;
FUdR, 5-fluorodesoxyuridine; HUR, hydroxyurea; MeCCNU, methyl-CCNU; MGGH, methyl-GAG;
MP, mercaptopurine; MTC, mitomycin C; MTM, plicamycin; PCZ, procarbazine; PRM, puromycin;
QNC, quinacrin; STN, streptonigrin; TG, thioguanine; THF, tetrahydrofolic acid; VCR, vincristine;
VLB, vinblastine

(After Pfreundschuh and Diehl (1986))

231
MEMORIX CLINICAL MEDICINE

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ONCOLOGY
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MEMORIX CLINICAL MEDICINE

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234
 ENDOCRINOLOGY
Endocrine system - summary
Hypothalamus
Hormone GHRH TRH CRH Gn-RH
Inhibited by Somatostatin Thyroxine Cortisol Oestradiol
Hypofunction Retarded growth Tertiary Tertiary adrenal Kallmann's syndrome,
hypothyroidism insufficiency hypothalamic
amenorrhoea, idiopathic
delayed puberty
Stimulation Insulin test, None known Insulin test Clomiphene test
test physical stress, (metopirone test)
arginine test

Anterior pituits»«T

Hormone STH (GH) TSH ACTH LH, FSH

Stimulated by GHRH TRH CRH Gn-RH
Inhibited by Somatostatin Thyroxine Cortisol Oestradiol, testosterone,
inhibin
Stimulation test GHRH test TRH test CRH test Gn-RH test
Hypofunction In children: Secondary Secondary adrenal Secondary hypogonadism:
retarded growth hypothyroidism insufficiency subfertility, oligo-/
amenorrhoea, impotence,
delayed puberty
Excessive STH-secreting TSH-secreting ACTH-secreting Gonadotrophin-secreting
function anterior pituitary anterior pituitary anterior pituitary anterior pituitary
adenoma; adenoma: adenoma: adenoma: oligo-/
in children: secondary Cushing's disease amenorrhoea, impotence
gigantism; hyperthyroidism
in adults:
acromegaly

Effector gland Liver Thyroid Adrenals Ovaries, testes

Hormone Somatomedin C Thyroxine Cortisol Oestradiol, testosterone

Triiodothyronine Adrenal androgens
Stimulated by STH (GH) TSH ACTH LH; Steroid secretion
FSH: Follicle ripening,
spermatogenesis
Excessive - Primary Cortisol-secreting Testotoxicosis (rare)
function hyperthyroidism adrenal adenoma Polycystic ovary syndrome
Hypofunction Laron dwarfism Primary Primary adrenal Primary hypogonadism.
hypothyroidism cortical menopause, Turner's
insufficiency: syndrome (9:X0),
Addison's disease Klinefelter's syndrome
(Cf:XXY)

Principal Bone growth Energy Immune Oestrogens: feminization

action metabolism modulation Androgens: virilization
Stress response Gonadotrophins: fertility
End-organ Dwarfism Partial effects Very rare Testicular feminization
resistance only anterior (Reifenstein's syndrome:
(rare) pituitary or 5ct-reductase deficiency)
complete (rare)

Abbreviations:
GHRH Growth hormone releasing hormone; STH (GH) Growth hormone (somatotrophin);
TRH Thyrotrophin releasing hormone; TSH Thyrotrophs hormone (thyrotrophin);
CRH Corticotrophin releasing hormone; ACTH Adrenocorticotrophic hormone (corticotrophin);
Gn-RH Gonadotrophin releasing hormone LH Luteinizing hormone (luteotrophin);
FSH Follicle stimulating hormone

235
MEMORIX CLINICAL MEDICINE

Gland Anterior pituitary Posterior pituitary Parathyroid Thyroid C-cells

Hormone Prolactin AVP (ADH) Parathormone Calcitonin

(PTH)
Stimulated by TRH Osmolarity t Calcium 1 Calcium T
Hypovolaemia Gastrin

Inhibited by Dopamine Osmolarity X Calcium T Calcium X

Effect Lactation Renal water Calcium liberation Calcium retention

retention from bone by bone

Stimulation TRH test Water deprivation - Pentagastrin test

test if urine osmolarity test
< 350 mosmol/kg

Hypofunction Disturbed lactation Diabetes insipidus Hypocalcaemia, "

tetany

Hyperfunction Prolactinoma: SIADH: usually Hypercalcaemia C-cell carcinoma of

9: Sterility paraneoplastic (nephrolithiasis. thyroid, e.g. with
Oligomenorrhoea Syndrome of pancreatitis. multiple endocrine
Galactorrhoea inappropriate psychiatric neoplasia
Cf: Impotence ADH secretion disturbances) (diarrhoea)
Hypogonadism (oedema,
hyponatraemia)

Abbreviations:

AVP Arginine vasopressin; TRH Thyrotrophin releasing hormone; ADH Antidiuretic hormone

Gland Kidney (juxtaglome- Adrenal cortex Adrenal cortex Adrenal medulla

rular apparatus) Sympath. ganglia

Hormone Renin liberates Aldosterone DHEAS, DHEA, Adrenaline (esp. in

angiotensin by 17a-OH- adr. medulla),

proteolysis progesterone, dopamine,
testosterone noradrenaline

Stimulated by Renal perfusion X Angiotensin ACTH Neuronal control

Hyponatraemia (ACTH)
Inhibited by Hypernatraemia - - Neuronal control
Hypokalemia
Effect Arteriolar Renal potassium Slight androgenic Cardiovascular
constriction loss, sodium action
Aldosterone t retention

Stimulation Frusemide test (ACTH test) ACTH test All stimulation tests
test Captopril test are obsolete

Hyperfunction Secondary Primary Adrenogenital Phaeochromocytoma.

hyperaldosteronism hyperaldosteronism syndrome paraganglioma
(Conn's syndrome) (complete or
incomplete)

Hypofunction Very rare Often in primary Shy-Drager syndrome

adrenal cortical (very rare)
insufficiency
(Addison's disease)

Abbreviations:

ACTH Adrenocorticotrophic hormone (corticotrophin) DHEA Dehydroepiandrosterone

DHEAS Dehydroepiandrosterone sulphate

236
 ENDOCRINOLOGY
3
Endocrine normal values

Comments, normal values in SI units

Gland and measurement Unit Normal value and conversion factors (CF)

Thyroid
Total thyroxine ug/dl 4.5-12.0 nmol/1 60-160 (CF: X 12.9)
Total triiodothyronine ng/ml 0.45-2.0 pmol/1 0.6-3.0 (CF: X 1.54)
TBG ug/ml 12.0-30.0 T in pregnancy, with oral contraceptives, etc.
T4/TBG ratio ug/dl 0.2-0.5 nmol/1 200-500
Free thyroxine ng/dl 0.8-2.4 pmol/1 10-31 (CF: x 12.9)
Free triiodothyronine pg/dl 230-660 pmol/1 3.5-10.2 (CF: x 0.0154)
TSH (basal) U/l 0.3-4.0
Thyroglobulin antibodies (TAb) U/ml <500
Microsomal antibodies (MAb) U/ml <500
TRAb (TSH receptor Ab) U/l <5.0
Thyroglobulin ng/ml <50 After thyroid ablation <5

Parathyroid
Parathormone peptide 44-68 pg/ml <300 Interpretation in relation to
Intact PTH pg/ml <50 plasma calcium concentration
Osteocalcin ng/ml 3.0-16.0 Age dependent! nmol/1 0.6-3.0
25-hydroxy vitamin D 3 ng/ml 15-120 nmol/1 40-300 (CF: x 2.5)
l,25ndihydroxy vitamin D, pg/ml 25-45 pmol/1 60-110 (CF: x 2.4)

Adrenal
Cortisol Ug/dl 5.0-25.0 nmol/1 140-700 (CF: x 27.6)
ACTH pg/ml <100 nmol/1 < 25 (CF: x 0.23)
Cortisone-binding globulin Ug/ml 30-50 T in pregnancy
(CBG) (transcortin)
Dehydroepiandrosterone ng/ml <10 nmol/1 < 35 (CF: x 3.47)
DHEA sulphate ng/ml <5000 umol/1 < 13 (CF: x 0.0026)
1 7-a-hydroxyprogesterone ng/dl <150 nmol/I < 4.5 (CF: x 0.03)
11-desoxycortisol ng/ml <10 nmol/1 < 30 (CF: x 2.9)
Aldosterone pg/ml < 120 pmol/1 < 330 (CF: x 2.77)
Plasma renin activity ng/ml/h 0.2-2.0 Resting value (recumbent), increased
by standing, diuretics, low-salt diet
Noradrenaline ng/1 <500 pmol/1 < 3000 (CF: x 5.91)
Adrenaline ng/1 <120 pmol/1 < 700 (CF: x 5.46)
Dopamine ng/1 < 120 gmol/1 < 800 (CF: x 6.53)
IT by stress and standing

Gonads Men Women Men Women

Testosterone ng/ml >3.0 <1.0 nmol/1 > 10 <3 (CF: x 3.47)
Sex hormone binding globulin Ug/ml 6-16 12-23 Increased in pregnancy
(SHBG)
Oestradiol (E2) pg/ml <60 >40 pmol/1 < 200 > 150 | In 2nd phase of cycle
Oestrone (El) pg/ml < 80 > 40 pmol/1 < 300 > 150
J
increased to approx.
Total oestrogens pg/ml < 120 > 80 nmol/1 <8 > 5 J double value
Progesterone ng/ml 6-20 nmol/1 20-100 In 2nd phase of cycle.
LH 071 <15 <15 Around ovulation briefly strongly T
FSH U/l <10 <10
Prolactin ng/ml < 20 < 25 TT through stress (e.g. phlebotomy)!

Metabolism
Growth hormone (STH) ng/ml <5.0 T through stress and physical exercise
Insulin U/l 10.0-30.0 Fasting value
C-peptide ng/ml 1.5-5.0 pmol/1 0.6-1.3 Fasting value
Glucagon pg/ml <100 Fasting value
Gastrin pg/ml <100 Zollinger-Ellison syndrome > 300 pg/ml

Urine determinations (urine assay s are superior to plasma determina ions for screening!)
Cortisol excretion ug/24 h <75.0 Important if suspicion of Cushing's syndrome
Aldosterone excretion ug/24 h <14.0 Important if suspicion of Conn's syndrome
C-peptide nmol/24h < Important if suspicion of insulinoma
Vallinylmandelic acid (VMA) mg/24h <7.0 Liable to interference, better:
Noradrenaline ug/24 h <40.0 Unequivocally abnormal > 100.0 ug/24 h
Adrenaline ug/24 h <16.0 Unequivocally abnormal > 50.0 ug/24 h
Dopamine ug/24 h < 430.0 Unequivocally abnormal > 500.0 ug/24 h

• Beware local laboratory differences.

237
MEMORIX CLINICAL MEDICINE
Endocrine tests
Indication, method, assay requirement and normal ranges

TRH test Insulin hypoglycaemia test

I: Suspicion of borderline hyperthyroidism I: 1. Suspicion of secondary adrenal insufficiency

Suspicion of borderline hypothyroidism 2. Suspicion of growth hormone deficiency
M: 1 amp. TRH (200ug) i.v. 3. Suspicion of pseudo-Cushing's syndrome
A: Omin TSH >0.2 < 4.0 U/l M: 0.15IU insulin/kg i.v.
30min TSH >2.0 <25.0 U/l A: min BS ACTH Cortisol / STH (for 2.)

15
Gn-RH test 30 <2.0 >100
45
I: Suspicion and DD of
hypogonadotrophic hypogonadism 60
90
M: lamp. Gn-RH (lOOug) i.v .

120 mmol/1 pg/ml ug/dl / ng/ml

A: Omin LH .... FSH
30min (*2) LH .... FSH
Combined anterior pituitary test
(without insulin hypoglycaemia)
CRH test
Test of anterior pituitary functions
1 DD of Cushing's syndrome and I: all

M: Simultaneous i.v. 1 amp, each of Gn-RH, TRH and CRH

secondary adrenal insufficiency
M lamp. CRH (lOOug) i.v. A: min LH TSH PRL ACTH Cort. poss. STH
A: Omin ACTH Cortisol
15min .... ACTH Cortisol
30min >25 ACTH >15 Cortisol
(*2) >2.0 TT >25 >15 >5
45min .... ACTH Cortisol
U/l pg/ml pg/dl ng/ml
60min pg/ml ACTH ug/dl Cortisol

Combined anterior pituitary test

GHRH test (with insulin hypoglycaemia)
1: DD of growth retardation Test of all anterior pituitary functions and in part of
M: GHRH (lug/kg) i.v.
I:

hypothalamic regulation
A: Omin STH M: Simultaneous i.v. 1 amp, each of Gn-RH and TRH
15min STH and 0.15IU insulin/kg
30min >5ng/ml STH
45min STH A: min LH THS PRL BS ACTH Cort. STH
60min STH 15 - .... .... ....
30 (*2) >2.0 TT <2.0 >100 >20 >5
45 - - .... .... ....
Dexamethasone suppression test
60 -
I: 1.Suspicion of Cushing's syndrome 90 - - - mmol/1
2. Suspicion of androgen-secreting - -
120 U/l
adrenal tumour
M: 2mg dexamethasone p.p. at 2300 hrs
(3mgif>70kg)
A: The following morning (0800-0900 hrs)
for 1. <5 Ug/dl Cortisol
for 2. 44 DHEA, testosterone Abbreviations:
I Indication, question to be answered

Synacthen test
M Method
A Time of phlebotomy
1. Suspicion of adrenal insufficiency Required assay
2. Suspicion of adrenogenital syndrome XYZ Result to be considered normal
(poss. heterozygote) (*2) Normal response is a doubling
250 mg Synacthen Optional assay (increases sensitivity in individual
i.v. cases)
Cortisol 17a- DD, differential diagnosis
(for 1. and 2.) hydroxyprogesterone
Omin (for 2.)
Blood samples:
60 min >20ug/dl <260ng/dl 5 ml heparinized blood/hormone assay
120min 5 ml EDTA blood on ice/ACTH assay

238
 ENDOCRINOLOGY
Thyrotoxicosis and hypothyroidism

Thyrotoxicosis Hypothyroidism

Aetiology and Autoimmune thyroid disease Autoimmune thyroid disease,

differential (e.g. Graves' disease), toxic thyroidectomy, radioiodine
diagnosis nodular goitre (multinodular therapy, iodine deficiency,
or single toxic adenoma), anterior pituitary insufficiency
thyroxine intoxication
Rarely: TSH-secreting anterior
pituitary adenoma, carcinoma
of thyroid

Symptoms (older patients oftenmonosymptomatic)

General Metabolism T Metabolism i
Weight i, appetite T, heat Weight T, appetite i, cold
intolerance, sweating intolerance, hypothermia
Skin Warm, moist Cool, dry, bloated faces,
swollen tongue, pretibial
myxoedema
Hair Fine, hair loss Coarse, rough
Eyes Possibly ophthalmopathy with Swollen lids
lid lag, lid retraction and (Ophthalmopathy also possible!)
exophthalmos
Neurology and Fine tremor Carpal tunnel syndrome
psychiatry Reflexes T, hyperactivity, Reflexes I, delayed relaxation
insomnia, restlessness, anxiety, phase, activity I, marked
psychosis somnolence, apathy, lethargy
Circulation Palpitation, supraventricular Bradycardia, heart failure,
tachycardia, atrial fibrillation, pericardial effusion
RR T (RR amplitude T) RRi
Respiration Possibly tachypnoea Respiratory insufficiency
Gastrointestinal Diarrhoea Constipation
Breasts Cf Gynaecomastia
: 9: Galactorrhoea
Gonads $: Oligomenorrhoea 9: Menorrhagia, subfertility

Laboratory t: T T FT
4, 3, 4 I: T T* FT
4, 4

I: TSH (except in secondary T: TSH (except in secondary

form) form)
TRH test: negative TRH test: excessive response

For DD History, measurement of History, measurement of TAb,

TAb, MAb, TRAb, thyroid MAb, TRAb
scintigram, thyroid ultrasound

Therapy Antithyroid drugs Thyroxine (T4 ) replacement

Radioiodine therapy
Thyroid surgery

Abbreviations:
TAb Thyroglobulin antibodies TSH Thyroid-stimulating hormone
TRAb TSH receptor antibodies T3 Triiodothyronine
TRH Thyrotrophin-releasing hormone FT4 Free thyroxine (not bound to
T 4 Thyroxine thyroxine-binding globulin)
MAb Microsomal antibodies DD Differential diagnosis

239
MEMORIX CLINICAL MEDICINE

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240
 ENDOCRINOLOGY
Cushing's syndrome
Step 1: Clinical suspicion
Procedure: Search for typical somatic symptoms

History: Exclusion of an iatrogenic Cushing's syndrome

Step 2: Confirmation of the diagnosis of Cushing's syndrome

Tests: 1. Urinary Cortisol T (> 100 ug/24h)
2. Morning plasma Cortisol T (>5ug/dl) after taking 2mg
dexamethasone orally the previous evening

Step 3: Differential diagnosis of Cushing's syndrome

A ACTH-secreting pituitary adenoma (Cushing's disease)
Tests: 1. Plasma ACTH (collect sample on ice) normal - T
2. ACTH and Cortisol response obtained in CRH test
3. Suppression of urinary Cortisol into normal range after
administration of 2mg dexamethasone 6-hourly over 48 h
(Liddle test)
4. MRI scan demonstration of pituitary adenoma (positive in only
50-70%)
5. ACTH gradient > 1.4 between inferior petrosal sinus and
peripheral vein (reserve diagnostic test)

B Cortisol-secreting adrenal adenoma or carcinoma

Tests: 1. ACTH (collection on ice) normal - i
Plasma
2. No ACTH or Cortisol response in CRH test
3. Negative Liddle test
4. Demonstration of an adrenal tumour by ultrasound or CT.
Carcinomas are usually large (>>4cm), adenomas are small
(<4cm). Note: the demonstration of an adrenal tumour does not
exclude a pituitary tumour!
C Cushing's syndrome with paraneoplastic ACTH secretion
Tests: 1. Plasma ACTH (collection on ice) T - TT
2. No ACTH or Cortisol response in CRH
test
3. Negative Liddle test
4. Demonstration of a carcinoid, bronchial carcinoma,
phaeochromocytoma or medullary thyroid carcinoma, e.g. with
ultrasound, CT, etc.
5. ACTH gradient < 1.4 between inferior petrosal sinus and
peripheral vein (reserve diagnostic test)

Stage 4: Therapy
for A: Transsphenoidal ablation of the pituitary adenoma
forB: Unilateral adrenalectomy, for metastasizing carcinoma o,p'-DDD
therapy
for C: Operative removal of the tumour, possibly chemotherapy, possibly
palliative bilateral adrenalectomy

241
MEMORIX CLINICAL MEDICINE

Replacement therapy

Deficient Replacement therapy Preparation Aim of treatment,

hormone control parameters

ACTH Hydrocortisone Provides complete

25-30mg/day substitution
STH (GH) Recombinant human GH Only in children by
specialists
TSH L-thyroxine Dose according to
50-150ug/day clinical picture
LH, FSH $: hMG, then hCG, hMG therapy
hCG, until by specialists
pregnancy Only if fertility

required, otherwise
Cf : hCG plus hMG, ca. Cf: testosterone,
3-6 months 9: oestrogens and
progestogens
ADH (AVP) Desmopressin 5-20ug Dose adjusted
once or twice daily according to fluid
intranasally intake and urine
volume
Prolactin - No substitution

Thyroxine l-thyroxine 50-150ug/day TSH should be within

normal range
Parathormone Dihydrotachysterol Plasma calcium should
0.5-1.5mg/day or be at lower end of
1.25-hydroxy-D, normal range
0.5-1.0ug/day
Calcitonin - No substitution

Cortisol Hydrocortisone No control by ACTH

25-30 mg/day or Cortisol
Aldosterone Fludrocortisone Control by BP and
0.1-0.3 mg/day renin activity
Adrenal - No substitution
androgens
Catecholamines - No substitution

Testosterone Testosterone proprionate No control by LH, FSH

(oily) 250 mg i.m. or testosterone
every 3-6 weeks necessary
Oestrogens Conjugated oestrogens Always replace
0.6-1 .25 mg/day oestrogens in
combination with
progestogens
Progestogens e.g. Medroxyprogesterone (otherwise T risk of
acetate 5 mg/day carcinoma)
(days 15-24)

Abbreviations: hCG human chorionic gonadotrophin; hMG human menopausal

gonadotrophin

242
 ENDOCRINOLOGY
Endocrine crises

Thyrotoxic crisis 1. Fluid and electrolyte correction

2. Nutrition (glucose)
3. Temperature lowering (physical), antipyretics
(no salicylates)
4. <D 2
5. Betablockers: propranolol 1-5 mg i.v. or 20-80 mg
6-hourly p.o.
6. Hydrocortisone, 300 mg i.v. initially, then 100 mg i.v.
8-hourly
7. Antithyroid drugs: 60-1 20 mg carbimazole or 600-
1200 mg propylthiouracil p.o., if necessary by nasogastric
tube

Myxoedema coma 1. Correction of hypoventilation, if necessary intubation

and ventilation
2. Treatment of hypothermia with blankets (beware
peripheral vasodilatation, avoid active warming)
3. T3 lOOug i.v./12h, then 25ug/12h
,

4. Hydrocortisone 100 mg i.v. 6-hourly

5. Careful fluid and electrolyte correction (hyponatraemia,
beware fluid overload)
6. Dobutamine if heart failure

7. If necessary, antibiotic cover

Addisonian crisis 1. Hydrocortisone lOOmg i.v. as bolus, then 100 mg

8-hourly i.v.

2. Rehydration with 0.9% NaCl and glucose i.v.; ca. 20%

of extracellular volume on first day
Beware heart failure

Hypercalcaemic 1. Infusion of 200-300 ml 0.9% NaCl per hour

crisis 2. Frusemide 80-200 mg/1 2 h after diuresis
3. Electrolyte replacement
4. Salcatonin 5-10 units/kg daily to 400 units every 8h
according to clinical and biochemical response s.c. or
i.m.; by slow i.v. infusion 5-10 units over at least 6h
(avoid phosphate or EDTA administration)
5. If due to hyperparathyroidism: surgery
6. If resistant to therapy, consider haemodialysis

Hypocalcaemic 1. Calcium gluconate 20ml 10% solution i.v., if necessary

crisis followed by 50ml in 500ml 0.9% NaCl as infusion
2. Later oral calcium therapy and/or vitamin D
Hypertensive 1. Nifedipine, glyceryl trinitrate or sodium nitroprusside
crisis i.v. (dose according to effect) if cause unclear

2. Phentolamine 0.25-1 mg/min i.v. continuously if

phaeochromocytoma confirmed
3. Usual therapy for cardiac arrhythmias

243
 MEMORIX CLINICAL MEDICINE
Corticosteroids
Generic name Biological Relative potency Equivalent doses in mg>
half life
Anti-inflammatory Sodium retention
Glucocorticoid Mineralocorticoid
activity activity

Cortisone Short 0.8 0.8 25 50 100 200 500

8-12h 40
Cortisol 1 1 20 80 160 400
(Hydrocortisone)

Fludrocortisone 10 125 5 10 20 40 100

Prednisone/ Medium 4 0.8 5 10 20 40 100

Prednisolone 12-36

Methyl- 5 0.5 4 8 16 32 80
prednisolone

Triamcinolone 5 4 8 16 32 80
_
Dexamethasone Long 20 1 2 4

Betamethasone
36-72h 25 0.75 1.5 3 6 15

Sources: Haynes and Murad (1985) Kaiser (1977)

• With reference to the indicated biological half life, i.e. 1 mg dexamethasone/48h is approximately- equivalent to 4 x 25 mg hydrocortisone/
48 h or 2 x 5mg prednisolone/48 h.

Classification of renal osteodystrophy

Type Morphology Cause

I Osteitis fibrosa Secondary hyperparathyroidism

II Osteomalacia Mineralization defect
III Osteitis fibrosa and osteomalacia Secondary hyperparathyroidism and mineralization defect
a Reduced bone turnover
b Normal or increased bone turnover Activity
c Greatly increased bone turnover

Osteoporosis
+ Osteosclerosis

Types of multiple endocrine neoplasia (MEN)

(Identification of one of the disorders requires exclusion of the others)

Type Affected organ illness

I Parathyroid adenoma Primary hyperparathyroidism

and pancreatic tumours Gastrinoma, insulinoma, vipoma, etc.
and pituitary adenomas Acromegaly, prolactinoma, Cushing's disease
Ha Thyroid carcinoma (medullary) C-cell carcinoma
and adrenal medullary tumours (bilateral) Phaeochromocytomas
and parathyroid adenomas Primary hyperparathyroidism

lib Thyroid carcinoma (medullary) C-cell carcinoma

and adrenal medullary tumours Phaeochromocytomas
(bilateral)
and mucosal neuromas Ganglion neuromatosis
(intestinal)
(Megacolon in Hirschsprung's disease)

244
 DIABETOLOGY
Classification of diabetes mellitus
A Manifest diabetes Mellitus
• Type I: insulin-dependent diabetes (IDDM)
• Type II: non-insulin-dependent diabetes (NIDDM)
Type Ila: without obesity
Type lib: with obesity
• MODY (NIDDY): Maturity onset diabetes of young patients
B Gestational diabetes
C Abnormal glucose tolerance
D Secondary diabetes
• In pancreatic disorders (pancreatitis, postoperative, etc.)
• With endocrinopathies (Cortisol excess, acromegaly, etc.)
• Due to toxic influences (drugs, etc.)
• With genetic syndromes (insulin receptor abnormalities, etc.)

Normal values
mmol/1 i i mg %
15.0
-
-270 Diabetes
- -252
14.0

13.0
- -234
Diabetes
" -216
12.0
11.1 - " 11.0 - - 198
200 w
W
- -180
10.0
- -162 Reduced glucose tolerance
9.0

7.7 8J)_- z L44 _ _ _14_0_ w

^
^
^ 6.7 _ 13- -_L26. _ _- 120
No diabetes
--
No diabetes 6.0 108
w
W A 0.18
Fasting xO.Of
~- ^ Oral glucose tolerance
2h
test
after 75 g (lOOg) glucose

Gestational diabetes Data after:

National Diabetes Data Group
Glucose tolerance Screening
(1979)
fasting: >90mg/dl lh after 50 g glucose
American Diabetes Association
>5.0mmol/l independent of time (1985)
and of day or meals
WHO Expert Committee on
lh >190mg/dl Diabetes Mellitus (1980)
>140mg/dl
> 10.6 mmol/1 > 7.8 mmol/1 Mehnert (1990)
= diagnostic
2h >160mg/dl suspicion
> 8.9 mmol/1

245
 .

MEMORIX CLINICAL MEDICINE

Diabetic therapy

Type I Insulin Diet

Adjustment of diet Well-balanced energy provision,
slimming diet if overweight
Type II 1. Dietary treatment 1 Distribution of carbohydrate
If necessary, weight reduction intake over several (5-7)
(possibly with absorption retarders for meals throughout the day
postprandial blood sugar peaks) 2. Avoidance of rapidly absorbable
2. Diet + sulphonylureas carbohydrate
3. Diet + sulphonylureas + biguanide (CHO) (sugar-free diet, etc.)
(especially for obese patients, 3. Calculation of carbohydrate
biguanide monotherapy?) consumption and exchange according
4. Diet + combined therapy to
(sulphonylureas and insulin) Bread Units (1 BU = 12 g CHO)
or if necessary with reference to the

Diet and insulin monotherapy glycaemic index (blood sugar

(especially for patient of normal effectiveness of the CHO)
weight)
Gestational diabetes:
Insulin treatment if postprandial
BS is not below 140mg/dl
(7.7mmol/l) after dietary
treatment for 2 weeks

Oral hypoglycaemics
Sulphonylureas
Main action: liberation of insulin from P cells

Product Usual dose (adjusted Half life (h) Side effects

(selection) according to response)

Gliquidone 45-60mg in 2-3 doses/day ca. 1.4 Blood disorders. Skin changes
Glipizide Up to 40 mg daily in 2-3 doses ca. 3.5 (allergy,photodermatosis)
Tolbutamide 500 mg 1-2 times/day ca. 4 Rarely gastrointestinal
symptoms
Gliclazide Up to 320 mg daily in 2 doses ca. 10-12 Prolonged hypoglycaemia
Glibenclamide 5-15mg ca. 8-16 (especially glibenclamide)

Biguanide
Main action: enhancement of peripheral glucose utilization
Contraindications: impaired renal function, chronic renal disease, hypoxic conditions (operations,
heart failure, etc.), chronic liver disease, pregnancy

Product Usual dose Half life Side effects

Metformin 500mg 1-3 times daily ca. 2h (possible lactic acidosis)

Gastrointestinal symptoms

Absorption retardant
(a-glucosidase inhibitor)
Main action: retardation of carbohydrate absorption; possible addition to dietary treatment

Product Usual dose Half life Side effects

Acarbose 50mg 1-3 times daily Practically no Gastrointestinal symptoms

absorption
 DIABETOLOGY
Insulin therapy

Soluble insulin
i.v. and s.c.
Injection-meal interval 15min

1 1 1
I
*"

5 6 7 8 9 10 11 12 13 t/h

Time after s.c. insulin injection

Insulin preparations
All 100 units/ml Hypui
,
purin Neutral CP
(H) Human insulin Velos
Velosulin Novo Nordisk, Wellcome
(P) Porcine insulin Human Actrapid Novo Nordisk
(B) Bovine insulin Human Velosulin Novo Nordisk, Wellcome
Humulin S Lilly
Pur-In Neutral CP

Intermediate- and long-acting insulins

Only s.c. Injection-meal interval: 30min (absorption profile after s.c. administration
dependent on injection amount, insulin type, etc.)

*-*».
>2r^^-.
3 4 9 10 11 12 13 14 t/h

Time after s.c. insulin injection

Insulin preparations Isophane insulin

All 100 units/ml Hypurin Isophane (B) CP
(H) Human insulin Insulatard
(
p) Novo Nordisk, Wellcome
(P) Porcine insulin Human Insulatard H) Novo Nordisk, Wellcome
(B) Bovine insulin Human Protaphane (H) Novo Nordisk
Humulin (H) Lilly
Pur-In Isophane (H) CP
Insulin Zinc Suspension (mixed)
Hypurin Lente (B) CP
Lentard MC (B,P) Novo Nordisk
Human Monotard (
H )
Novo Nordisk
Humulin Lente H Lilly
Insulin Zinc Suspension (amorphous)
Semitard MC (P) Novo Nordisk
Insulin Zinc Suspension (crystalline)
Human Ultratard (H) Novo Nordisk
Humulin Zn (H) Lilly

247
MEMORIX CLINICAL MEDICINE

Biphasic insulins

Fixed combinations of soluble insulin +

delayed-action insulin, injection-meal
interval 15-30min (e.g. 30% soluble +
70% isophane insulin)

9 10 11 12 13 t/h

Time after s.c. insulin injection

i
Activity of normal insulin

Activity of delayed-action insulin

Total activity

Insulin preparations 10% soluble insulin + 90% isophane insulin

All 100 units/ml Humulin Ml (H) Lilly
(H) Human insulin PenMix 10/90 (H) Novo Nordisk
(P) Porcine insulin
15% soluble insulin + 85% isophane insulin
(B) Bovine insulin
Pur-In Mix 15/85 (H) CP
20% soluble insulin + 80% isophane insulin
Humulin M2 (H) Lilly
PenMix 20/80 (H) Novo Nordisk
25% soluble insulin + 75% isophane insulin
Pur-In Mix 25/75 (H) CP
30% soluble insulin + 70% isophane insulin
Mixtard 30/70 (P) Novo Nordisk, Wellcome
Humulin M3 (H) Lilly
PenMix 30/70 (H) Novo Nordisk
Human Actraphane (H) Novo Nordisk
Human Mixtard (H) Novo Nordisk, Wellcome
40% soluble insulin + 60% isophane insulin
Humulin M4 (H) Lilly
PenMix 40/60 (H) Novo Nordisk
50% soluble insulin + 50% isophane insulin
Initard 50/50 (P) Novo Nordisk, Wellcome
PenMix 50/50 (H) Novo Nordisk
Pur-In Mix 50/50 (H) CP
Human Initard 50/50 (H) Novo Nordisk, Wellcome

Crystalline bovine in soluble porcine insulin

Rapitard MC (B + P) Novo Nordisk
248
 DIABETOLOGY

Delayed-action insulin in
morning + delayed-action
insulin in evening

Biphasic insulin in morning

+ delayed-action insulin in
evening

Soluble insulin in morning

+ soluble insulin midday +
delayed-action insulin in

evening

Soluble insulin in morning

+ soluble insulin midday +
soluble insulin in evening +
delayed-action insulin late

Soluble + delayed-action
morning + soluble
insulin in
+ delayed-action insulin
midday + soluble insulin in
evening + delayed-action
insulin late

Insulin pump
Continuous subcutaneous
insulin injection + 3 bolus
doses of soluble insulin

Activity of soluble insulin

Activity of delayed-action insulin
1
Total activity

249
MEMORIX CLINICAL MEDICINE

Diabetic coma
Incidence: ca. 3-5 cases/1000 diabetics/year
Association with type not always clear-cut

Hyperglycaemic Hyperglycaemic
ketoacidotic coma hyperosmolar coma

Clinical Mostly < 60 years Mostly > 60 years

Commonly type I diabetes Commonly type II diabetes

known known
Rapid development Protracted development

Dehydration + Dehydration + +

Intestinal symptoms
(diabetic pseudoperitonitis)

Kussmaul respiration
Fetor of acetone

Clouding of consciousness + Clouding of consciousness + +

Often few symptoms (picture
of cerebrovascular accident)

BP i Heart rate T BP U Heart rate T

Precipitating Infections (> 40%) Severe coexisting illness

factors (cardiovascular, etc.)

First manifestation of insulin- Diabetes not previously

deficient diabetes (ca. 20%) recognized (>20%)

Treatment failure type I diabetes Drugs (diuretics)

(including 'technical defects',
pump failure, etc.) Infections

Typical
laboratory findings

17-45 mmol/1 BS > 33 mmol/1

<7.2 PH >7.2
310-330 Osmc >lality > 330, often >400
Approximate calculation:

2 x (Na + K) + BS (mmol) + urea (mmol/1)

++ Acetone in urine ( +)
< 10 mmol/1 Bicarbonate >10mmol/l
Normal to i Na Normal to T

Normal to T K Normal to i

250
 DIABETOLOGY

Hyperglycaemic ketoacidotic coma Hyperglycaemic hyperosmolar coma

Treatment
1. Correction of fluid deficit
(Total deficit ca. 10-15% of body weight)

Initial 1000ml 0.9% NaCl/hour 1000ml 0.9% NaCl/hour

(Na > 155mmol/l = NaCl 0.45%)

Subsequently 500ml 0.9% NaCl/hour I 500ml 0.9% NaCl/hour

or according to CVP: <0 = 1500ml/hour
0-3 = lOOOml/hour
4-8 = 500 ml/hour

2. Insulin dosage
(soluble insulin i.v.)

Initial (Bolus 10 units) No bolus

+ continuous infusion + continuous infusion
6-10 units/hour 3-6 units/hour

Course Aim: Fall of blood glucose (initially hourly) 2.5-5 mmol/hour;

More rapid reduction —> danger of cerebral oedema!

3. Correction of acidosis
Consider if signs of acidotic heart failure, i.e. hypotension with raised central
venous pressure, are present

(only if pH < 7.0; stop when pH > 7.2)

1/3 of calculated base deficit = 0.1 base deficit x body weight (kg) as sodium
bicarbonate 8.4%

4. Electrolyte replacement
Potassium >5.5mmol/l: no replacement, monitor
4.0-5.5 mmol/1: 10-20mmol/h
<4.0mmol/l: 20-40 mmol/h

Sodium > 1 55 mmol/1: 1/2 electrolyte solution

Phosphate < 0.40 mmol/1: 4- 10 mmol/h

Differential diagnosis
Other causes of disturbed consciousness (coma)

Hypoglycaemia: Rapid diagnosis by quick blood glucose determination -» glucose i.v.

Lactic acidosis: Kussmaul respiration, but no acetone fetor

Anion gap: Na + - (Cl~ + HC0 3 ) > 30 mmol/1

Modified after: Krebs and Otto (1986)

Haslbeck (1989)

251
 RHEUMATOLOGY/LOCOMOTOR SYSTEM
Check-up of the rheumatological patient
1. Family history
Arthropathies (polyarthritis, ankylosing spondylitis), metabolic disorders (gout),
allergies, skin diseases (psoriasis), osteoporosis.

2. Past history
Previous joint inflammations and other disorders of the locomotor system (course),
skin and mucous membrane conditions (psoriasis, aphthous ulcers, balanitis),
ophthalmic conditions (conjunctivitis, iritis, iridocyclitis).

Infections (TB, throat infections, urethritis, gonorrhoea, syphilis, tick bites (Borrelia
infection)).
Gastrointestinal tract: peptic ulcer, ulcerative colitis, Crohn's disease.
Occupational history: dependence on activity, accidents.
Psychosocial history (including pension).

3. Present complaint

• Pain

Localization:
Joints: mono-, polyarticular, small or large joints, symmetrical or asymmetrical.
Joint involvement in sequence.
Pain in tendon insertions, musculature, adipose tissue.
Backache (especially cervical and small of back), radiation.

Temporal relation:
Onset acute or gradual, pain progressive, diminishing or recurrent. Maximum
intensity: nocturnal pain, morning pain, continuous pain. Morning stiffness.

Relation to exertion:
Spontaneous pain: pain on movement (at onset or on exercise), rest pain. Pain on
coughing or sneezing. Pain in certain postures (lying, sitting, standing).
Combination of the pain with other symptoms (paresthesia, swelling, redness,
heat).

• General symptoms

Therapy
Previous physiotherapeutic, medicinal (especially corticosteroids and NSAIDs),
orthopaedic and surgical treatments.

253
MEMORIX CLINICAL MEDICINE

Rheumatological status
1. Axial skeleton

Inspection:
Posture, gait (limping), asymmetry of pelvis and shoulders (oblique pelvis:
shortening of leg?), scoliosis (torsion of spine?), muscular atrophy, foot deformities,
obesity. Height (especially with osteoporosis).

Palpation:
Pain on percussion or pressure, pain on agitation of individual vertebrae, Mennel
manoeuvre (painful in sacroiliitis). Muscle spasm.

Functional examination:
Mobility test in three planes (finger-ground distance, Schober measurement
(lumbar spine), thoracic spine rotation, sideways flexion and backward extension
(blockages? laxity? harmonic flexion?)).
Thoracic circumference inspiration/expiration, examination of muscle function.

2. Joints

Inspection:
Redness, swelling, deformity, abnormal position, muscular atrophy.

Palpation:
Heat, swelling (differential dignosis: intra-articular effusion, synovial swelling,
osteophytes, periarticular swelling, extra-articular swelling (ganglion, tenosynovitis,
bursitis, exostosis)). Pressure pain of the joints and its localization. Periarticular
pressure pain with insertion tendinitis/tendinosis. Crepitus.

Functional examination:
Measurement of active and passive excursion angle for flexion/extension, abduction/
adduction, internal/external rotation, pronation/supination (neutral-null method).
Movement and end-phase pain. Crepitus. Instability. Combination movements. At
the shoulder joints: C7-thumb distance; at the hand: fist closure and dynamometer
values.

General medical examination

Skin (psoriasis, erythema, tophi, signs of vasculitis, peau d'orange). Mucous

membranes (aphthous ulcers, ulcers, balanitis). Eyes: iritis, conjunctivitis, keratitis.
Rheumatic nodules. Scleroderma.

Neurological status

Motor system (power and coordination), sensation (superficial and deep), reflexes,
Lasegue's sign (sciatic stretch test).

254
 RHEUMATOLOGY/LOCOMOTOR SYSTEM
Examination of the range of joint mobility
(neutral-null method)
(After recommendations of the German and Swiss Orthopaedic Society)

i (erect, feet parallel, arms extended at side of body, thumbs to front)

Sagittal plane: Flexion = bending, extension = straightening (plantar flexion =

lowering of tip of foot, dorsal extension = elevation of tip of foot)

Frontal plane: Abduction = inclination away from midline, adduction =

inclination towards midline

Transverse plane: Outward rotation = turning outwards, inward rotation =

turning inwards (shoulder, hip), supination = palm towards front, sole inwards,
pronation = palm towards back, lateral border of foot upwards/outwards.

Frontal plane

Sagittal plane

Recording by the null-point transit method

1st Number: Movement towards body (flexion, adduction, inward rotation, anteversion)
2nd Number 0-position (if not attained, 1st or 3rd number)
3rd Number: Movement away from body (extension, abduction, outward rotation, retroversion)

Normal values shoulder joint Inward/outward rotation with forearm against

Anteversion/retroversion 150-170/0/40 body 40-60/0/
Adduction/abduction 20-40/0/180 Inward/outward rotation with upper arm elevated
sideways to 90 degrees 70/0/70

150-170° 180°

Normal values elbow joint

Flexion/extension 150/0/5-10
Forearm rotation
inwards/outwards 80-90/0/80-90

-0°
80-90°- 80-90°
,o

255
MEMORIX CLINICAL MEDICINE
Normal values wrist joint Fingers
35-60° Metacarpophalangeal
joint of thumb
abduction/adduction
or\_ a r\o m palmar plane 70/0

Abduction/adduction
at right angle to
palmar plane 70/0

50-60°
Palmar flexion/dorsiflexion 50-60/0/35-60 Terminal joint of thumb
Radial abduction/ulnar abduction 25-30/0/30-40 Flexion/extension 80/0
0°_

Normal values hip joint

Flexion/extension 130-140/0/10
Inward/outward rotation with
hip flexed to 90 degrees
Inward/outward rotation with
extended hip joint
Adduction/abduction

130-140°

30-

10° <

Normal values ankle/foot joints 0°

Plantar flexion/dorsiflexion 40-50/0/20-30
Normal values knee joint Pronation/supination (with fixed calcaneum) 15/0/35
Flexion/extension 120-150/0/5-10 Eversion/inversion (total) 30/0/60

120-150° 40-50°
256
 RHEUMATOLOGY/LOCOMOTOR SYSTEM
Classification of inflammatory illnesses
Chronic polyarthritis (cP)
• Felty's syndrome (seropositive cP with splenomegaly and leucopenia)
• Caplan's syndrome (pneumoconiosis and cP)
Juvenile chronic arthritis (types: systemic (Still's disease), mono- or polyarticular ± iridocyclitis, polyarticular)
Still's disease of adults

Palindromic rheumatism
Chronic atrophic polychondritis
Giant cell arteritis (temporal arteritis/polymyalgia rheumatica)
Behcet's syndrome
Eosinophilic fasciitis (Shulman's syndrome)
Eosinophilic myalgic syndrome (with L-tryptophan)
Sarcoidosis (Lofgren's syndrome: arthritis in acute sarcoidosis)
Amyloidosis; vasculitides
Collagenoses (in the strict sense)
Systemic lupus erythematosus (SLE)
• Drug-induced lupus
• Antiphospholipid syndrome (lupus anticoagulant - anticardiolipin antibody with arterial and venous

thromboses, abortion, thrombopenia)

Mixed connective tissue disease (MCTD), Sharp's syndrome
Systemic sclerosis (progressive systemic scleroderma (PSS)
• CREST syndrome (calcinosis, Raynaud's syndrome, oesophageal dysfunction, sclerodactyly, telangiectasia)
Dermato-/polymyositis
nodosa
Polyarteritis
Wegener's granulomatosis, Churg-Strauss syndrome
Sjogren's syndrome

Reactive arthritides and seronegative spondylarthritides in

Ankylosing spondylitis (Pierre-Marie-Strumpell-Bechterew disease)
Psoriatic arthropathy
Enterogenous arthritides (with ulcerative colitis, Crohn's disease, Whipple's disease (probably through
Corynebacterium-'mduccd jejunitis)) post-bypass syndrome
Reiter's syndrome (urethro-oculo-synovial syndrome)
Reactive arthritides: after enteral (Yersinia, Shigella, Salmonella, Campylobacter, Clostridium difficile), urogenital
(Chlamydia), pharyngeal (streptococci, rheumatic fever) infections
SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis)

Infective arthritides/spondylitis/spondylodiscitis
Pyogenic (bacterial arthritis, with Staphylococcus aureus, Strept. pneumoniae, streptococci, Haemophilus
influenzae, Neisseria gonorrhoeae), Brucella spondylodiscitis
Lyme disease (Borrelia burgdorferi)
Tuberculous (Mycobacterium tuberculosis, atypical mycobacteria)
Viral(AIDS, rubella, mumps, measles, hepatitis B, parvovirus)
Mycoses (Actinomyces, Candida albicans. Sporotrichosis)

Crystal-induced arthritides
Gouty arthritis (uric acid arthritis)
Pseudogout with chondrocalcinosis (calcium pyrophosphate hydrate crystals), idiopathic or secondary, especially
in Wilson's disease, haemochromatosis, hyperparathyroidism
Hydroxyapatite-induced arthritis
• Milwaukee shoulder (rapidly destructive shoulder arthropathy)
• With dialysis, milk-alkali syndrome, chondrocalcinosis
Corticosteroid injection

Arthropathies with endocrine and metabolic disturbances

Acromegaly, diabetes mellitus, hyper/hypoparathyroidism, renal osteodystrophy, thyroid disorders, Cushing's
syndrome
Haemochromatosis, ochronosis

Neuropathic arthropathies (Charcot joint) in

Diabetes mellitus, tabes dorsalis, syringomyelia, hemiplegia

Arthropathies with haematological illnesses

Haemoblastoses, coagulopathies, haemolytic anaemias, haemochromatosis, reticuloses

Arthropathies with tumours

Paraneoplastic syndrome, villonodular synovitis, benign and malignant tumours, tumour metastases

257
MEMORIX CLINICAL MEDICINE

Classification of degenerative illnesses

Osteoarthritis (arthrosis deformans)
Polyarthrosis of fingers (Heberden's nodes) (involvement of distal interphalangeal joints). Bouchard's arthrosis
(involvement of proximal interphalangeal joints), rhizarthrosis (involvement of the basal thumb joint)
Osteoarthritis of shoulder, hip, knee. etc.

Degenerative diseases of the vertebral column

(± associated with malformations and abnormal posture (static disturbances, scoliosis, juvenile kyphosis.
Scheuermann's disease))
(Osteo-)chondrosis, spondylosis, spondylarthrosis
Disc prolapse ± root compression (including cauda equina syndrome, spinal stenosis (neurogenic intermittent
claudication))
DISH (diffuse idiopathic skeletal hyperostosis; Forestier's disease)

Classification of extra-articular illnesses

(Soft-tissue rheumatism)
Fibromyalgia (generalized tendon myopathy)
Diseases of the subcutaneous connective tissue
• Panniculosis ('cellulitis')
• Panniculitis nodularis (Pfeifer-Weber-Christian disease)
• Panniculitis with pancreatic diseases
• Lipomatosis; erythema nodosum

Diseases of the tendons, tendon sheaths, ligaments, fasciae, bursae

• (Insertion) tendinitis, (insertion) tendinosis, tendomyositis, tendoperiostitsis, tenosynovitis
• Progressive hardening and contracture of the palmar aponeurosis (Dupuytren's disease), or of the plantar
fascia (Ledderhose's disease)
• Bursitis

Diseases of the musculature

• Functional myalgic syndrome (with overload, abnormal posture and static disturbances (spine))
• Myopathies of various causes
• Infectious myositis
• Polymyositis with collagenoses

Periarthropathies
• Hip periarthropathy (insertion tendinosis, possibly with bursitis of greater trochanter), periarthropathy of knee
• Humeroscapular periarthropathy (HSP) as collective term for periarticular pain and functional disturbances in
the shoulder region:
- HSP simplex
Supraspinatus syndrome (with calcium deposits)
Biceps tendinopathies
- Acute HSP (acute inflammation in region of a calcium or hydroxyapatite deposit with shoulder mobility
limited by pain
- Pseudoparalytic/pseudoparetic HSP with rotator cuff injury (supraspinatus and long biceps tendon)
- Ankylosing HSP (frozen shoulder) with capsule contracture following trauma, reflex (after cardiac infarct),
with degenerative changes, diabetes mellitus

Peripheral nerve entrapment syndromes

Carpal tunnel syndrome (median nerve)
Ulnar compression syndrome (in ulnar groove at elbow)
Meralgia paraesthetica (lateral cutaneous nerve of thigh)
Tarsal tunnel syndrome (tibial nerve or its branches (medial or lateral plantar nerves) between medial malleolus
and calcaneum)
Morton's metatarsalgia (digital branches of plantar nerves)
Neurodystrophic disturbances
Algoneurodystrophy (Sudeck's atrophy) at various sites

Classification of illnesses of bone (including osteogenic

arthropathies)
Osteoporosis, osteomalacia
Paget's disease of bone (osteodystrophy deformans)
Fibrous osteodystrophy, osteosclerosis, osteonecrosis, (juvenile) osteochondritis dissecans, other osteopathies
(such as osteomyelitis, benign and malignant tumours)

258
 RHEUMATOLOGY/LOCOMOTOR SYSTEM
Laboratory investigations
Tests 1 Interpretation (selection)

Humoral inflammation parameters

Sedimentation rate (ESR) Important parameter for differentiation inflammatory/

non-inflammatory rheumatic illness, indicator for activity

Others:
C-reactive protein (CRP) Reacts more quickly than ESR in inflammatory conditions
Acute-phase proteins ot,-glycoprotein, a,-antitrypsin, c^-ceruloplasmin,
o^-haptoglobin, fibrinogen and others

Electrophoresis p. 201

Blood count Microcytic anaemia as parameter of inflammatory activity

(DD: haemorrhagic complications of NSAIDs, steroids;
autoimmune haemolytic anaemia in SLE, gold therapy)
Leucocytosis/thrombocytosis in acute inflammatory illnesses
Leucopenia/thrombocytopenia in SLE, Felty's syndrome

Clinical chemical laboratory findings

Uric acid Gout. Diuretics (hydrochlorothiazide, chlorthalidone,

frusemide, ethacrynic acid)
Myeloproliferative syndrome (p. 211)

Creatine kinase (CK) Raised in (poly)myositis, dermatomyositis, inflammatory muscle

Aldolase involvement in SLE, rheumatoid arthritis, Sjogren's syndrome
Lactate dehydrogenase Drug-induced myopathy (triamcinolone, chloroquine,
penicillamine)

Alkaline phosphatase Metabolic bone diseases (hyperparathyroidism, osteomalacia,

Calcium, inorganic phosphate Paget's disease), see p. 264

Serological-immunological investigations

Rheumatoid factors Occurrence: Rheumatoid arthritis (RA) 70-80%. Note: patients

(Latextest, Rose-Waaler test) with juvenile RA are often seronegative. Collagenoses ca. 30%.
Non-rheumatoid illnesses: often positive; also in subacute
bacterial endocarditis, liver diseases, TB, syphilis, acute viral
infections

Antinuclear factors/antibodies Collagenoses (especially SLE, systemic sclerosis, mixed

(ANF/ANA) connective tissue disease (MCTD))
Special antibody patterns

Complement tests Serum complement as total haemolytic activity (CH50),

individual complement components (C3, C4). Reduced in active
SLE. Raised in acute-phase reaction

Circulating immune complexes Measurements of progression and activity criteria in various

(CIC), Clq binding inflammatory illnesses

Arthritis serology, bacterial Demonstration of antibodies against: Salmonellae, shigellae,

antibodies in reactive yersiniae, Campylobacter, gonococci, borreliae,chlamydias
arthritides HIV, etc., antistreptolysin O titre (clearly positive in ca. 80% of
patients with rheumatic fever); measurement of progression

Immunogenetic investigations

Histocompatibility antigen HLA-B27 - ankylosing spondylitis, Reiter's syndrome, etc.

(HLA typing)

259
MEMORIX CLINICAL MEDICINE
Joint aspirates
Basic aspirate Normal Non-inflammatory Inflammatory Septic Haemorrhagic
characteristics values (Group I) (Group II) (Group III) (Group IV)

Volume < 3.5 ml > 3.5 mi > 3.5 ml > 3.5 ml

(knee joint)
Turbidity Transparent Transparent Cloudy Cloudy Cloudy/bloody
Colour Colourless Pale yellow Yellow/white to Yellow to Reddish
xanthochromic greenish
Viscosity High High Reduced Reduced/ Increased
variable
Leucocytes (per ul) <20 200-2000 2000-100000 > 100 000* Erythrocytes
Polymorphonuclear <25% <25% 50% and more 75% and more Corresponding
leucocytes to blood count
Cultures Negative Negative Negative Often positive Negative
Mucin coagulation Firm Firm Deficient to Fragile
absent coagulum
Glucose Almost as Almost as More than 25% Mostly Almost as
blood blood lower than considerably blood
glucose* glucose* blood glucose" lower than glucose'
blood glucose'

Possible aetiology Degenerative Rheumatoid Bacterial Trauma

(osteoarthritis) arthritis infections
Haemorrhagic
Trauma (also Reiter's syndrome diathesis
haemorrhagic)
Acute crystal Neuropathic
Osteochondritis sinovitis (gout and joint illnesses
dissecans pseudogout) (also Group I)

Ankylosing
Osteochondroma tosis spondylitis Neoplasms
(Bechterew's
disease)
Neuropathic joint Psoriatic arthritis Haemangioma.
illnesses synovioma
(also Group IV) Arthritis with
ulcerative colitis and Pigmented
Hypertrophic regional enteritis villonodular
osteoarthropathy (Crohn's disease) synovitis (also
Group I or II)

Rheumatic fever
Group I)
(also
SLE (also Group I)

Progressive systemic
sclerosis (scleroderma)
(also Group I)

b
' Simultaneously collected serum. Fewer on treatment or with organisms of low virulence.

Viscosity: normal (drop from syringe with tail longer than 6 cm); reduced (shorter or
completely absent tail)
Turbidity: transparent (print can be read through synovial fluid in test tube); cloudy (print
cannot be read through synovial fluid in test tube)

Further investigations: Demonstration of crystals (uric acid crystals, negative birefringence:

gout)
Demonstration of phagocytes
Sediment -» Cytology
,
Centrifuge s
k

Supernatant -» Immunological/biochemical examination

(After Rodman (1973))

260
 RHEUMATOLOGY/LOCOMOTOR SYSTEM
Revised (1987) ARA criteria for the classification of
rheumatoid arthritis (RA)
(American Rheumatism Association, 1988)
1. Morning stiffness > 1 h
2. Simultaneous swelling of > 3 joint regions
and left PIP, MCP,
(Joint regions: right wrist joints, elbow, knee, ankle joints or MTP joints)
3. Swelling of MCP, PIP or wrist joint
4. Symmetrical swelling
5. Rheumatoid nodules
6. Positive rheumatoid factor (any method is suitable which has a specificity >95%)
7. Typical radiological changes (definite osteoporosis near affected joints, periarticular erosions)
in the P-A film of the hands and/or wrist joints

At least 4 of these 7 criteria must be fulfilled for the diagnosis of rheumatoid arthritis. Criteria 1

to 4 must be present for > 6 weeks.

Abbreviations: PIP proximal interphalangeal joint
MCP metacarpophalangeal joint
MTP metatarsophalangeal joint

ARA criteria (1982) for systemic lupus erythematosus (SLE)

(Tan et ai, 1982)

1. Butterfly erythema of face

2. Discoid lupus
3. Photosensitivity
4. Mucous ulceration in mouth and nasopharynx
5. Non-erosive arthritis
6. Pleurisy and/or pericarditis
7. Renal involvement: proteinuria > 0.5 g/day or urinary casts
8. CNS involvement: psychosis or fits
9. Haemolytic anaemia or leucopenia (< 4000/ul) (on at least 2 occasions) or lymphopenia
(< 1500/ul (on at least 2 occasions)) or thrombocytopenia (< 100 000)
10. LE cells or anti-DNA antibodies or anti-Sm antibodies or false-positive serological tests for
syphilis (twice within 6 months)
11. High antinuclear antibody (ANA) titre

Revised Jones criteria for diagnosis of rheumatic fever (RF)

(Stollermann et al., 1965)
Main criteria
Carditis, polyarthritis, Sydenham's chorea, erythema (marginatum), subcutaneous nodules
Secondary criteria
Clinical
Previous rheumatic fever or rheumatic carditis, arthralgia, fever
Investigations:
Acute-phase reactions (raised sedimentation rate, raised C-reactive protein, leucocytosis, pro-
longed PQ interval (ECG))
plus
Indication of preceding streptococcal infection (raised antistreptolysin titre or otherO
streptococcal antibodies, throat swab positive for streptococci Lancefield Group A, preceding
scarlet fever)

Rheumatic fever very probable:

2 main criteria or 1 main criterion and 2 secondary criteria, when preceding streptococcal
infection confirmed

261
MEMORIX CLINICAL MEDICINE

ARC criteria for fibromyalgia 1990

(Wolfe etaL, 1990)

1. History of widespread pains

Definition:
Pains are considered as widespread if they are present in both sides of the body above
and below the waist. Axial skeletal pains (cervical, thoracic or lumbar spine or anterior
chest wall) must also be present.

2. Pains in at least 11 of the 18 examined pressure pain points

Definition:
Pain on palpation must be present in at least 11 of the following examined pressure
pain points:

Occiput: bilateral, at the insertion of the sub-occipital muscles.

Lower cervical spine: bilateral, on the anterior aspect between the transverse processes
C5-C7.
Trapezius: bilateral, middle of upper border of
trapezius.
Supraspinatus: bilateral, at origin, near the middle of
the border, above the spine of the scapula.

2nd rib: bilateral, level of the 2nd chondrosternal

junction.

Lateral epicondyle of humerus: bilateral, 2 cm distal

to the epicondyles.

Gluteal: bilateral, in upper outer quadrant of buttock.

Greater trochanter: bilateral, dorsal to the

trochanteric prominence.

Knee: bilateral, over the medial fat pad proximal to

the joint cleft.

Finger pressure should be applied at about 4 kg. For a

pressure point to be designated positive the patient
must describe it as painful.
'Pressure sensitive' is not regarded as 'painful'.

The diagnosis of fibromyalgia can be made if both criteria are fulfilled. The pains
must be present for at least 3 months. The presence of another illness does not
exclude the diagnosis of fibromyalgia.

262
 RHEUMATOLOGY/LOCOMOTOR SYSTEM
Diagnostic criteria for the spondylarthropathies
(Dougadosefa/., 1991)

Pains from the spine with Synovitis

Cinflammatory characteristics asymmetric

preferentially in the lower
extremities
and

one or more of the following criteria:

Positive family history:

Presence of the following conditions in first or second degree relatives:
(a) Ankylosing spondylitis, (b) psoriasis, (c) acute uveitis, (d) reactive arthritis,
(e) inflammatory bowel disease

Psoriasis:
Previously diagnosed by a physician or present at the time of examination

Inflammatory bowel disease:

Crohn's disease or ulcerative colitis, previously diagnosed by a physician or present at the
time of examination, and confirmed by endoscopy or radiology

Non-specific urethritis, cervicitis or acute diarrhoea:

Within 1 month of the appearance of the arthritis

Buttock pain, alternating between left and right gluteal region:

Previous, or present at the time of examination

Heel pain:
Spontaneously volunteered pain or tenderness at the insertion of the achilles tendon or
the plantar fascia, previous or present at the time of examination

Sacroiliitis:
Bilateral grade 2-4 or unilateral grade 3-4 (grade radiologically normal; grade 1
sacroiliitis possible; grade 2 minimal inflammatory changes; grade 3 moderately severe
definite sacroiliitis; grade 4 ankylosis)

Principal symptoms of syndromes of vertebral origin

1. Soft-tissue rheumatic affections (including tendinoses, tendomyoses, e.g. chain
tendinoses)

2. Pseudoradicular syndromes
3. Neurogenic syndromes (medullary, radicular, vegetative compression syndromes)
4. Vascular syndromes (intermittent circulatory disturbances)
5. Circumscribed postural changes (with kyphosis, lordosis, scoliosis, contracture)

6. Segmental disturbance of function (movement restriction with blockage, fixation;

abnormal laxity)

263
 '

MEMORIX CLINICAL MEDICINE

Osteoporosis
I. Etiology: primary osteoporosis
(idiopathic, juvenile, postmenopausal, presenile and senile osteoporosis)

II. Etiology: secondary osteoporosis

1. Genetic (osteogenesis imperfecta; women > men, positive family history, slim configu-
ration)

2. Endocrine (e.g. hyperthyroidism, Cushing's syndrome, gonadal insufficiency)

3. Gastrointestinal (e.g. after total or subtotal gastrectomy and small bowel resection,
malabsorption*; liver, gall bladder, pancreatic diseases)
4. Dietary (malnutrition*, calcium deficiency)
5. Metabolic (e.g. diabetes mellitus; chronic alcoholism*)
6. Renal (e.g. with glomerular or tubular insufficiency)
7. Iatrogenic (e.g. steroids, heparin therapy)
8. Immobilization

*
' Osteoporomalacia

The radiologist's 'osteoporosis tree'

(After Haas (1983))

Hyperparathyroidism Osteoporoses Osteo malacia

Ca T P i APH n T ; Ca n P n
! APH n
fill Ca ^ pJ -

Baph t

Subperiosteal
erosions Renal
osteo-
dystrophy
Ca i P T APH T

localized pain
i
/ /

V (Deformity —»)
Stre ss pain
-> < Generalized

Ca Calcium n normal
P Phosphate T raised
APH Alkaline phosphatase
1 Radiological
i reduced

osteoporosis Bk

264
 J '

RHEUMATOLOGY/LOCOMOTOR SYSTEM

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 1

NEUROLOGY
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267
MEMORIX CLINICAL MEDICINE

Visual pathway lesions and visual field defects

Nasal Nasal Temporal Left Right

ght

1 Left amaurosis

Bitemporal
hemianopia

(J (J
Right homonymous
hemianopia

Upper quadrantic

Od
anopia

5 Right homonymous
hemianopia with
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Trigeminal nerve distribution Eliciting the corneal reflex

Sensory
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trigeminal nerve

V, ophthalmic division, V2 maxillary division

V 3 mandibular division Correct test area

268
 NEUROLOGY
Neurological examination
Upper limb Lower limb Trunk/Stature/Gait

General Left/right handed, Lasegue's sign, muscle Posture, configuration of

muscle tone, tone, muscular atrophy, spinal column, spinal
muscular atrophy, strength, mobility, pain, standing normally
strength, mobility, position test and on one leg, walking
position test normally, on heels or
toes, walking in a
straight line

Pyramidal Mayer reflex, Babinski's plantar sign, Spastic gait

tract signs Wartenberg's sign Gordon's sign,
Oppenheim's reflex
persistent clonus

Pyramidal tract signs/reflexes

Gordon's

Chaddock

Superficial Touch, pain, Touch, pain, temperature Walking with eyes shut
sensation temperature, two- two-point discrimination, (sensory ataxia?)
point discrimination figure writing appreciation

Deep Vibration sense, Vibration sense, position

sensation position sense of sense of toes (passive)
fingers (passive),
astereognosis

Coordin- Finger-nose test, Heel-knee test, rebound Walking in straight line,

ation diadochokinesia, phenomenon truncal ataxia,
rebound Romberg's sign,
phenomenon, Unterberger's step test,
fine finger walking with eyes shut
movements
Proprio- Brachioradialis jerk Knee jerk L, 4
ceptive
reflexes Biceps jerk C 5 C 6
, , Ankle jerk L,, S,
Triceps jerk Q, C7,
Tromner's sign C 8-T,
Cutaneous Plantar response L -S
5 2
Abdominal reflex T 5 l2

reflexes Cremaster reflex L,, L :

Anal reflex S,-S<

269
 -

MEMORIX CLINICAL MEDICINE

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270
 1

NEUROLOGY
lid

in isolation
isolation

and
cerebral

Bell's paresis
ischaemia

of
involved
paresis
with
in in
with
paresis central
with
facial
reversible
complete. pareses
involved
not affected
vertigo

facial
n.
and
vertebrobasilar

phenomenon
haemorrhage
peripheral
Ipsilateral

Forehead
Central accessory Central

E central
closure Seldom Seldom infarct rapidly

zoster,
paralysis
lesion

o
trapezius),
borreliosis, lateral after
metastases,

neuroma, paresis,
syndrome,

otic vestibulitis,
glossopharyngeal

vestibular

Melkersson-Rosenthal
vertigo
neuroma,
skull,
craniocervical
(recurrent in
otolith)
syndrome, tumour,

(only pressure
perioperative
syndrome,
meningitis,

acoustic
of bulbar
base,
diphtheria,
neuroma),

u
petrous,
of Wallenberg's
biopsy
clivus,

(Garcin's
(idiopathic),

base neck
deafness,
positional
jugulare of nerve) skull
of
fracture,

of surgery
node
surgery

of of
of
2S «
glossopharyngeal

c
(degeneration
poliomyelitis, poliomyelitis,
hypoglossal
Guillain-Barr6

Wallenberg's Anomalies tuberculous

tonsillectomy,

neuropathy, syndrome, Tumours

syndrome, neuralgia chordoma
junction, laryngeal
fractures tumours, petrous
glomus fracture thyroid
Cooling Sudden Lymph triangle lesions carotid
benign

6«3

s * a a
tests
S S S 3
t *
tests),

teeth),
.1
reflex
(tear examination
soft larynx,
(including
shoulder
reflex,

§
wrinkling tongue
sensation
dysarthria

(frowning, stapedius

of
*f
Rinne function towards
facial
head 'i
test nystagmus,

c showing
examination

salivary
gag of
tongue
of
speech,

of taste
test

and
of side),
5 I m <
c
oculovestibular
closure,
Examination
pharyngeal

expression for vegetative (deviation

1 Muscles
nose, Schirmer's

secretion),

reflex,
Hearing Weber
Taste
(bitter),
secretion,

palate, Turning
Elevation
Protrude
affected
inspection

(atrophy),

eye test
of

part),
taste secretion
sensation
m., tongue posterior
deglutition
pharynx, laryngeal

to
(in m.
musculature
innervation

of balance

innervation, salivary stapedius ••)

2/3 tongue), to palate m.
sensation of ear,
(p. tongue, parasympathetic

sternomastoid

and 8 (swallowing),
of saliva
Vegetative
innervation,

Muscles (middle sensation

of muscles,
soft
Trapezius

c
anterior
glands, Hearing, Tongue
Facial

3 tear
taste
organ
root 1/3
of of

n.
n.
n. n.

n. n. Hypoglossal

>
<u Auditory
vestibular
pharyngeal

Accessory
c « * ?.
c Facial Glosso-
Vagus

g VIII
VII XII
XI
IX X

271
MEMORIX CLINICAL MEDICINE

Symptoms of autonomic involvement

in polyneuropathies
(Occurrence in: diabetes mellitus, Guillain-Barre syndrome, porphyria, amyloidosis,
toxic causes, e.g. alcohol, isoniazid, lead, quinoline, uraemia, hereditary illnesses)

Symptom Diagnostic tests

Cardio- Tachycardia at rest i Variability of heart frequency

vascular Silent myocardial infarct with hyperventilation, Valsalva
test, drugs (atropine, betablocker)
Orthostatic dysregulation Schellong test

Gastro- Nocturnal diarrhoea Small bowel biopsy (exclusion of

intestinal coeliac disease)
Bloating, heartburn, dysphagia Barium meal and follow-through
Unrecognized hypoglycaemia Absence of insulin tachycardia
Exocrine pancreatic insufficiency Secretin-pancreozymin test

Gall bladder enlargement, Ultrasound, palpation

gallstones, salivary gland
inflammation

Urogenital Erectile impotence Testicular analgesia

Retrograde ejaculation Urinalysis
Residual urine with bladder Ultrasound
dysfunction

Trophic Hypo-/anhydrosis of feet Sweat test

Vasomotor paresis Histamine test (with

noradrenaline)
Trophic oedema, alopecia Sympathetic skin response with
Painless ulcer external stimulus (EMG lead)
Disturbed nail growth
Osteoarthropathy Plain X-ray

The principal neurological signs of polyneuritis (reduced vibration sense, stocking

hypoaesthesia/-algesia and reduced ankle jerk) may be absent.

Red = Basic or screening test

272
 NEUROLOGY
Sensory dermatomes

Level of the vertebral Level of the

spines (roman spinal segments
numerals) (arabic numerals)

Coccygeal vertebrae

273
MEMORIX CLINICAL MEDICINE

Cervical root compression syndromes

Level Pain Hypoaesthesia Pareses Reflexes

Deltoid m

cy 4 Normal
CV5

Biceps and
brachioradialis
reflexes i
c fi

CV5
CV 6

Triceps Triceps
reflex I

c 7

CV6
CVJ

Hand Hoffmann's
muscles sign

CVJ

CV = cervical vertebra
(Modified after Stohr and Riffel (1988))
274
 NEUROLOGY
Lumbosacral root compression syndromes
Pain Disturbance
Level Paraesthesiae of sensation Pareses Reflexes

(Modified after Stohr and Riffel (1988))

275
MEMORIX CLINICAL MEDICINE

Muscle function testing

Lateral J T Patient m Doctor • Muscle

Arm abduction
rotation ol

Tested
muscle Infraspinatus Biceps Deltoid

Associated
Suprascapular Musculocutaneous Circumflex (axillary)
nerve
Associated
nerve root
c 5 -c 6 c5 -c 6 c5 - c 6
Associated
reflex
Biceps

Finger extension Flexion of distal Abduction of

'

thumb joint j j extended thumb

^Sptt
Extensor digitorum Flexor pollicis longus Abductor pollicis brevis
mifsde
Associated
nerve Radial Median
Associated c 7 -c 8 c7 -c8 'C-T,
nerve root
Associated
reflex Triceps

Hip flexion Extension of leg Dorsiflexion of foot

Tested
muscle Iliopsoas Quadriceps Tibialis anterior

Associated
nerve Femoral Deep peroneal
Associated
nerve root Li-L 2 La-U L4 U
Associated
reflex Knee jerk

276
NEUROLOGY
MEMORIX CLINICAL MEDICINE

Glasgow coma scale

(For prognosis in skull/brain trauma and secondary brain injury)
(Teasdale and Jennet, 1976)
Points Points

Eye opening Motor response

Spontaneous 4 On command 6
To speech 3 Localized pain response 5
To pain stimulus 2 Flexion to pain 4
None 1 Abnormal flexion response 3
Extensor response 2
Verbal response None 1

Orientated 5
Confused conversation 4
Single words 3
Incomprehensible sounds 2 Maximal point count 15
None Minimal point count 3

Definition of coma Eyes closed

Verbal response incomprehensible sounds 2 or fewer
Motor response localized pain response 5 or fewer

Coma

Scale for assessment of pupil size (mm)

2 3 4 5 6 7

Staging of subarachnoid haemorrhage

(preoperative clinical grading)

Symptoms and signs

Grade State of Neurological deficits Headache Meningism Others

consciousness

A A a
: none Minimal Slight
I B Alert B*: present

A A a
: none
II B Alert Bb : cranial nerve deficits Moderate Definitely
(e.g. photophobia) to severe present

A A': none
III B Somnolent B h mild
: focal deficits (mild
Disorientated paresis and/or dysphasia)

IV Soporific to Marked focal deficits Pupil reactions

comatose (moderate to severe present
hemiparesis and/or dysphasia),
early symptoms of decerebration

V Deep coma Decerebration, possibly signs of No pupil

coning reactions,
moribund
A 1
without focal neurological deficits, Bb with focal neurological deficits.

Early operation within 72 h with grades I to III.

Somnolent Patient wakes only on stimulation, but is completely orientated

Soporific Patient can only be brought to consciousness briefly by strong stimuli

278
 NEUROLOGY

attacks

subdural

haemorrhage,

hallucination
porphyria

thyrotoxicosis

Korsakow psychomotor

amnesia
psychosis,

c
c infarct,
encephalopathy,

disturbances,
drugs

.3 alcoholic

1= global
tremens,

3 after states,
Hypo/hyperthermia,

metals,

M) Hyperglycaemia,

C Post-traumatic

Encephalitis

dehydration
CO haematoma
Wernicke's
Electrolyte
Dementias

OJ Oedema Oedema transitory

syndrome,
Twilight
Anaemia

delirium

U Heavy
B

massive haemorrhage

haemorrhage,

abscess,

K),
'faint' pulmonary
contusion
drugs
callosum
with
(Na,
1)
B hypertonic

cerebral

a myelinolysis,
lobe
CO,
impaction,
subarachnoid

'o oedema corpus

c/i hydrocephalus

c with
pressure, syndrome,

o haematoma,
temporal
disturbances

hypnotics,

infarct, or
of faint

c lower (meningo)encephalitis
pontine
arrhythmia,

3 pressure

sinus
_o mal, Hypoglycaemia
blood

or stem

B
Degeneration

u Extradural obstructive
haemorrhage, haemorrhage

Electrolyte
porphyria
in
Psychogenic

3
Sedatives,
embolus
Central
Upper
cardiac carotid
Brain Grand
Brain
3 Fall

CO

myelinolysis,
heavy
CO
c infarct(s),

haemorrhage

encephalopathy

disturbances acidosis/alkalosis
failure
CO,
'6 hypnotics,

haematoma
meningitis,

c
c pontine

liver

'c Hyperglycaemia,
hypopituitarism hypoventilation
hypothyroidism,
loss,
Space-occupying antidepressants, anticonvulsants,

8 intracerebral
encephalitis

K),
c Subdural
Oedema
Bacterial
Wernicke's
Electrolyte
Catatonia
Sedatives,

CO Central
uraemia, anaemia,
metals
Blood
(Na,
3
o ~
M

c lungs:

CO
U Heart/cardio-

y
c Vascular:
Infective:
Metabolic: Hormonal:
Psychiatric:

Tumour:
Epilepsy: vascular,
Trauma:
Toxic: Toxic:

%
g
|BIUBJ3BJ|UI |BIUKJJRJ|X^

279
 MEMORIX CLINICAL MEDICINE
Anatomy of the cerebral arteries

Carotid system

Middle cerebral a.

Posterior communicating a

Posterior cerebral a

Superior cerebellar a.

Basilar a

Anterior inferior cerebellar a

Vertebral a

Posterior inferior cerebellar a

Anterior spinal a.

Spinal cord
Vertebro-
basilar
Cerebellum system
(Circle of Willis)

280
 NEUROLOGY
Classification of cerebral is< :haemia
By temporal a spects By angiological aspects

* I
History, CT Doppler ultrasound, angiography, laboratory investigation
TIA (symptoms for not more than 24 h) Macroangiopathy:
RIA (symptoms for not more than 1 week) extracranial vessels Plaque
Infarct (persistent symptoms) intracranial vessels Stenosis

By localizing aspects Collateralization

] Occlusion
Dissection
Examination, CT, MRI
Dysplasia
I Anterior cerebral z .

Arteritis
Anterior circulation (carotid) Middle cerebral a.

1 Posterior cerebral a. Microangiopathy in hypertension

Diabetes mellitus

Posterior circulation Medulla oblongata Other angiopathies

(arteritis of peripheral vessels)
(vertebrobasilar) I Cerebellum

By pathological aspects By cardiolo gical aspects

1 *
CT, MRI ECG, echocardiography
Possible cardiac source of Endocarditis
Macroangiopathy: emboli: Valvular defect
Territorial infarct Embolic, thrombotic Arrhythmia
Capillary infarct haemodynamic Cardiomyopathy
Border zone infarct Mitral valve prolapse
Myocardial infarct
Microangiopathy: Paradoxic emboli
Lacunar infarcts (perhaps transoesophageal
Medullary dystrophy echocardiography)
(Binswanger's encephalopathy) Accompanying cardiac illness:

Coronary arteriosclerosis, arrhythmia

Risk factors, accompanying illnesses and findings that

increase the risk of cerebral infarction
Risk factors Cerebral infarct risk

Hypertension 6-fold increase, rising with age

Diabetes mellitus 3-fold increase
Smoking 3-fold increase, with cigarette smoking
Hyperlipidaemia 2-fold increase
Oral contraceptives 2- to 3-fold increase
Alcohol abuse 2-fold increase (in young patients)

Accompanying illnesses
Coronary artery disease 6-fold increase, with simultaneous arrhythmia up to
10-fold increase
Occlusive vascular disease of legs 2-fold increase
Migraine Potentiated by existing risk factors (oral contraceptives,
smoking)
Obesity No definite effect

Findings
History of TIA 4% per year
Extracranial asymptomatic carotid stenosis of 70% 2% per year
>80% 4-8% per year
Ulcerated plaque 4-8% per year
Polycythaemia Up to 2-fold increase
Hyperuricaemia No definite effect

281
 MEMORIX CLINICAL MEDICINE

Doppler ultrasonography of the extracranial cerebral arteries

(After Ries (1987))
Anterior circulation Posterior circulation

Supratrochlear a

Internal carotid a.

External carotid a

Carotid bifurcation

Common carotid a Proximal subclavian a

Possibilities of ultrasound investigation of supra-aortic vessels

Continuous ultrasound emission Pulsed ultrasound
CW (continuous wave) emission

I Doppler sonography Pulse echo technique

|

A mode amplitude
Extracranial Duplex sonography B mode brightness
Transcranial Duplex scan C mode - 2-D image
(Tomography)

Analysis of flow pulse Analysis of B picture

(Doppler signal)
Picture quality
Analogue pulse curve (Curve amplitude,
now direction,
pulsality,
resistance flow) • Edge reflectivity
(hyper/hypoechoic)
Frequency-time spectrum (Frequency analysis)
Plaque

• Stenosis surface
(Extent, surface characteristics)
* Frequency-density spectrum (Power spectrum)
• Stenosis internal echo
(Density, structure, pattern)

282
 NEUROLOGY
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283
MEMORIX CLINICAL MEDICINE
International classification of epileptic seizures
(International League against Epilepy, 1981, 1989)

I Focal (partial) seizures (local onset, focal cerebral lesion)

A Simple focal seizures (without disturbance of consciousness):
1. with motor symptoms (e.g. Jacksonian fit: circumscribed muscle twitching with generalized

evolution - march; adversive attack with turning of head/trunk, epilepsia partialis continua
without march);
2. with sensory symptoms (e.g. sensory Jacksonian fit: circumscribed wandering
paraesthesiae) or other sensations (e.g. flashes of light, acoustic sensation, olfactory or
gustatory hallucinations);
3. with vegetative symptoms (pallor, nausea, sweating, isolated aura);
4. with psychic symptoms (memory disturbance, cognitive or affective symptoms, e.g. d6ja-vu
experience, dreamy state, terror).
B Complex focal seizures (with disturbance of consciousness)
(psychomotor seizures)
1. Simple focal seizure followed by loss of consciousness

2. Disturbance of consciousness at onset (often with automatism such as fidgeting, lip

smacking, chewing)
C Focal seizures with secondary generalization
(e.g. grand mal with focal onset)

II Generalized seizures (convulsive or non-convulsive)

(often idiopathic, certain forms also residual or symptomatic)
A 1. Absences (brief disturbances of consciousness with spike-and-wave complexes in EEG)
2. Atypical absences (with clonic, atonic or tonic components or automatism)
B Myoclonic seizures (e.g. impulsive petit mal - brief twitching of proximal muscle groups with
poly-spike-wave EEG)
C Clonic seizures
D Tonic seizures
E Tonic-dome seizures (grand mal)
F Atonic seizures (including myoclonic-akinetic seizures)

III Unclassifiable seizures (because of insufficient data, or unclassifiable seizures of infants)

Locality determined (focal) epilepsies

A Idiopathic
Benign focal epilepsy in childhood
B Symptomatic
Chronic progressive epilepsia partialis continua
Temporal lobe epilepsy
Extratemporal epilepsy

Generalized epilepsies
A Idiopathic
Benign seizures of newborn
Absence epilepsy of childhood
Juvenile epilepsy with myoclonus (impulsive petit mal)
Others
B Cryptogenic or symptomatic
West syndrome (infantile spasms)
Early myoclonic encephalopathy
Lennox-Gastaut syndrome
Progressive myoclonic epilepsy

Special syndromes (occasional seizures)

Febrile convulsions
Metabolic or toxic causes (e.g. alcohol)
Single seizure or status epilepticus

Status epilepticus: Frequent epileptic seizures without intervening recovery: generalized (absence
status,grand mal status) or focal (Jacksonian status, epilepsia partialis continua)

284
 ' '

NEUROLOGY
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285
MEMORIX CLINICAL MEDICINE

Syncope
Aetiology Supportive investigations

Inadequate vasoconstriction
Vasovagal Retake history
Orthostatic Posture test (Schellong test, cf. p. 93).

Treatment with diuretics, vasodilators

Autonomic insufficiency Diabetes, sympathectomy, look for primary

forms

Reduced venous return

Valsalva (cough, micturition) Repeat Valsalva manoeuvre under controlled
conditions

Late pregnancy
Atrial myxoma Echocardiogram

Disturbances of rhythm
Carotid sinus syndrome Monitored carotid sinus massage
SA, AV blocks (Stokes-Adams) Long-term ECG monitoring
Sinus bradycardia
Asystole, fibrillation
Ventricular/supraventricular
ECG
tachycardia

Reduced cardiac output

Aortic stenosis, hypertrophic
obstructive cardiomyopathy 1 Auscultation, echocardiogram (< :f. pp. 62, 63)
Pulmonary stenosis

Pulmonary embolus Isotope lung scan

Cardiac infarct with heart failure ECG
Pericardiac tamponade Echocardiogram

Cerebrovascular
TIA
Carotid stenosis Doppler ultrasonogram
Vertebrobasilar stenosis Angiography (cf. p. 282)
Subclavian steal syndrome

Others
Epilepsy EEG
Hypovolaemia Neck veins, CVP, diuretics?
Hyperventilation, fear Allow patient to hyperventilate under control
Hypoxaemia Blood gas analysis
Anaemia Blood count
Hypoglycaemia Blood glucose, extended glucose tolerance test
i

Hysteria History

Note: In up to 50% of patients no cause can be found.

286
 NEUROLOGY

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 1

MEMORIX CLINICAL MEDICINE

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288
 NEUROLOGY
Differential diagnosis of vertigo

Type Peripheral labyrinthine Central vestibular

Positional vertigo
Latent time to onset Up to 20 s None
Duration of nystagmus Up to 30 s Longer than 30s
Vertigo symptoms Strong, directional Less strong, non-directional
Direction of nystagmus Towards lower-lying ear Variable
Critical head position Often single Mostly several
Clinical syndromes Benign positional vertigo Acoustic neuroma (late)
Alcoholic vertigo Vertebrobasilar ischaemia
Perilymph fistula Multiple sclerosis

Persistent vertigo
Nystagmus Horizontal rotating Variable, also downbeat, upbeat
Accompanying Sometimes hearing loss, Often vestibular vertigo.
symptoms tinnitus pendular nystagmus, other
focal signs
Clinical syndromes Meniere's syndrome Postmedullary brain stem
Acute labyrinthine lesion lesion - ischaemic.
Vestibular neuronitis tumour, inflammatory,
(no hearing loss!) malformation
Acoustic neuroma (early -
little vertigo!)

Neurological syndromes of malignancy

(From Berlit (1989))

Occurrence in

Brain
Encephalomyelitis: limbic encephalitis, Small cell carcinoma of bronchus
bulbar encephalitis, Rarely: carcinoma of breast, ovary, colon
spinocerebellar degeneration,
myoclonus-opsoclonus syndrome
Progressive multifocal leucoencephalopathy (PML) Lymphoma, leukaemias
Isolated angiitis of the CNS Hodgkin's disease
Subacute cerebellar atrophy Carcinoma of ovary, breast

Spinal cord
Subacute necrotizing myelopathy Small cell carcinoma of bronchus
Amyotrophic lateral sclerosis Lymphomas, carcinoma of bronchus, breast,
stomach, bowel

Peripheral nerve
Subacute sensory neuropathy (often Small cell carcinoma of bronchus
simultaneous encephalomyelitis)
Paraproteinaemic polyneuropathy Plasmacytoma, lymphomas
Sensorimotor polyneuropathy Carcinoma of bronchus
Neuromuscular synapse
Eaton-Lambert syndrome Small cell carcinoma of bronchus
Myasthenia gravis Thymoma
Muscle
Polymyositis-dermatomyositis Carcinoma of breast, bronchus, stomach,
bowel, uterus, ovary

289
 CLINICAL PHARMACOLOGY
Pharmacokinetic formulae
1. Loading

(a) Loading dos^ v = (Clargel - C actual )

x Vd x BW Qrger desired plasma concentration
(mg/l) C,ctuai : actual plasma concentration (mg/l)
Vd : distribution volume (1/kg)
(see table pp. 298 to 326)
(Cw C actual )
x Vd X BW F: bioavailability
(b) Loading dose ora =
(100% absorption =
,

1.0)
BW: body weight (kg)

(c) Rapid estimation of loading dose from nomogram

1. Choose target concentration on left ordinate.

(If loading does not proceed from zero, the target concentration is the difference between
the desired and the actual concentration.)

2. Choose the corresponding distribution volume on the right ordinate.

3. The intersection of the line joining the two points with the central ordinate gives the
desired loading dose (mg/kg).

4. This is multiplied by the body weight.

(5. Divide by bioavailability for oral administration.)

2. Dose adjustment

_ F x dose^ F: bioavailability (i.v. administration =

100% absorption 1.0)
Dose^,^: bolus dose (mg/kg)
Vd : distribution volume (1/kg)

3. Peak concentration after bolus administration

Dose Dr ,
x CU1 desired plasma concentration (mg/l)
Dose ne : actual plasma concentration (mg/l)

(This formula must not be used for drugs with non-linear kinetics. In these cases small dose increases
can lead to disproportionate increases in the plasma concentration; beware toxicity.)

4. Time to achievement of steady-state concentration

Elapsed time since % Steady-state concentration Further increase in plasma

start of therapy achieved concentration to be expected

Alternatively:

Drug elimination

Elapsed time since Amount of drug Amount of drug

last dose remaining in body excreted

1 half life 50% 50%

2 half lives 75% 25%
3 half lives 88% 12%
4 half lives 94% 6%
4.3 half lives 95% 5%
5 half lives 97% 3%

291
MEMORIX CLINICAL MEDICINE

Nomogram for calculation of loading dose

Target O Distribution
1 concentration volume (l/kg)

1000 1000000 1000

j
--
700 500000 700
500 500

300 100000 -r 300

200 50000 - 200

-'7
100 10000 100
]
- -
70 5000 70
50 50
-'7
30 1000 30
20 500 -- 20

10 100 - 10
7 50 " 7
5 5
-'7
3 10 3
5 --
2 2

1 1
" 1

0.7 0.5
" 0.7

0.5 0.5

0.3 0.1
" 0.3

0.2 0.05
"
0.2

- -*-
0.1 0.01 0.1

Loading dose
per kg

A Multiplication by
body weight
 1 1 1 1 1 1 1 1 1 1 1 1

CLINICAL PHARMACOLOGY
5. Estimation of individual half life (cf. illustration)

..-
v
0301 rfinal , nitial : interval between C ini(ial
and C final
(1 " — 'finai-iniiiai
x C initial concentration
- logC
'

logC initial
jnitial fin
C fina .: final concentration
0.693
= 'lta
lnC ini
lnC fir

Nomogram for estimation of half life

Concentration

100 r "^
£-'—
70
50

HL T 30
°1r- 0% 20
G
1
-- 50% 10
7
2- -75%
5

3- - 88% 3
kC2
2
4- -94%
1

5^ - 97% 0.7
0.5

0.3

0.2

°-1

01
I
1
I 1
I I
I
1
I 1
I I

23456789
I
1
I 1
I I
I
1
I 1
I I
I 1
I 1
I I
I
1
I 1
I I

Time
I
1
I 1
I I
I
1
I 1
I I
I 1
I I
1 I I 1
I 1
I I

10
I 1
I 1
I I I

11
1
I 1
I I
I

12
x

Graphic determination of elimination half (HLT) using two plasma life time
concentrations
1. Enter the initial (greater) concentration at time (i.e. on the y-axis) of the graph (CI)
2. Enter the second concentration at the correct time interval (C2)
3. Connect the two points with a straight line (G)
4. The HLT can now be determined using the enclosed plastic measure:
Lay the measure on the graph parallel to the jc-axis so that the upper line ('CI')
comes to lie on the initial concentration (CI).
5. Determine the intersection of the joining line (G) with the line '1 HLT'.
6. Slide the measure parallel to the x-axis until the arrow comes to lie on the
intersection of G
and '1 HLT'.
7. The arrow now points at the HLT of the drug under examination on the jc-axis.
8. Similarly the duration of 2 (line '2 HLT') 3 or 4 HLT can be read off. Alternatively,
the time required to attain a given concentration can also be estimated.

293
MEMORIX CLINICAL MEDICINE
Drugs with variable HLT
• Drugs with non-linear kinetics (HLT dependent on concentration) (see below)
• Drugs with self-induction (induction of own metabolism)
• Hepatic, renal, cardiac failure, combination therapy (cf. table pp. 298-326)

6. Estimation of HLT in anuria

The following formula permits the approximate estimation of HLT in anuria. With prolonged
renal insufficiency, however, the elimination can be modified by additional changes in
distribution volume and plasma protein binding.

HLT norma ,
HLTnormal HLT with
: normal renal function
HLT anuria = — Q : fraction of drug eliminated by extrarenal mechanisms

7. Dose adjustment in renal failure

(a) Determination of the individual elmination fraction (Q):

The elimination fraction with normal renal function (Q cf. table pp. 298-326) is entered ,

on the left vertical axis and joined to the right upper corner of the nomogram. The
intersection of the line with the individual creatinine clearance (measured or estimated) is
read off on the left vertical axis. This value corresponds to the individual elimination
fraction Q.

(b) Determination of the individual renal function (creatinine clearance; Clcreatjnine ):

_ (150 - age) x weight Men: +10%

Clcreatrinine ~ "7.
Women: — 10%
creatinine
C creatinine : creatinine serum concentration (umol/1)

(c) Determination of the individual HLT:

HLT norma |
HLT norna)
HLT with normal renal function
,
:

HLT individual = — ta bie pp. 298-326)

( cf
Q: individual elimination fraction

(d) Determination of the individual dose:

The initial loading dose of a drug is independent of its elimination and is not influenced
by the renal function of the patient. Its calculation is therefore the same as in a patient
with normal creatinine clearance. The maintenance dose, however, must be modified.

General rule
For most drugs:
Maintenance dose = Q x Maintenance dose hea thy |
.

The dose reduction can be achieved by increasing the dose interval or reducing the individual
doses.

Exceptions
For many antibiotics (aminoglycosides, many cephalosporins and penicillins):
Maintenance dose = d x Maintenance dose neallhy where d is decay fraction ,

The decay quotient can also be determined from the nomogram: the intersection of the
relevant dose interval (dose interval/HLT individual ) with the dotted curve indicates the decay
fraction d on the right vertical axis.

294
 CLINICAL PHARMACOLOGY
Removal of drugs by dialysis Upper abscissa
C cr
or
in (umol/1
Nomogram mg/dl) - creatinine
ooo o concentration

Lower abscissa
CI (in ml/min) -
creatinine clearance

c - relative dose
interval

0.4 Left ordinate

Q - individual
1/p elimination fraction
Q, - minimal
6 elimination fraction

r - residual fraction

Right ordinate
R - cumulation
factor

c - decay fraction/
C/(ml/min) decay quotient

8. Estimation of the dialysing ability of a drug

(a) Dialysing ability: Principles: The smaller the distribution volume, the smaller the
binding to plasma protein and the lower the molecular weight (factor in the table
> 2, i.e. molecular weight < 500), the more readily can the elimination of a drug be
expected during a dialysis procedure.
(b) Clearance during a dialysis:

Cl di = VX (Car J drug concentration in arterial

limb (mg/1)
r drug concentration in venous
^venous*
limb (mg/1)
V: blood flow through dialyser (ml/min)
Clearance total = CL + CL
9. Distribution volume (cf. table)

HLT Distribution volume

Clearance^,-,,
Distribution volume:
51 (=0.071/kg): Distribution in practice exclusively in blood
10-201 (=0.15-0.3 1/kg): Distribution in total extracellular fluid
401 (« 0.61/kg): Distribution in total body water
>401 (>0.61/kg): Concentration outside the body water (e.g. in adipose
tissue)

295
MEMORIX CLINICAL MEDICINE

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296
 1

CLINICAL PHARMACOLOGY

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297
MEMORIX CLINICAL MEDICINE
Pharmacokinetic and toxicological data
Drug Factor Plasma concentration (mg/l) HLT v4
Therap. Toxic Lethal l/kg

Acebutolol 2.97 0.5-2 2.9/11 2.9

Acemetacin 2.35 4.5/6 1

Acetazolamide 4.5 5-20 Nlin(6,3) 0.2

Acetylcysteine 6.13 1.5

Acetylsalicylic acid 5.55 20-100 > 450 > 1200 Nlin(0.25)/Nlin(4) 0.25

Acyclovir 4.44 0.7-2 2.4 (Nt,lT) 0.7

Acipimox 6.49 2
Adenosine 3.74 0.008
Alfentanil 2.4 0.1-0.3 7t: 2min, a: lOmin
Allopurinol 7.35 10 0.8/40 0.6

Alprazolam 3.24 10-50 >75 ll(At,CiT)/l,5 0.9

Alteplase (t-PA) 0.017 0.05 0.1

Amantadine 5.33 0.2-0.9 >1 11.8 12(AT) 3.5

Amikacin 1.71 Peak: 20-25 >30 2.5(Ci = ) 0.21

trough: 1-4 >8

Amiloride 4.35 10(At) 5

Aminoglutethimide 4.31 12

Amiodarone 1.55 0.8-2.5 (>2.5) 14-1300/700 66

Amitriptyline 3.61 0.05-0.2 > 0.5 10-20 17(At)/27 15

Amlodipine 2.45 40-60(At,Cit) 21.4

Amoxapine 3.19 0.2-0.4 >0.5 3 8/30

Amoxicillin 2.74 2-8 1.2 0.47

Amphetamine 7.4 0.02-0.03 0.5 >2 12.2 4

Amphotericin B 1.08 0.2-2 >6-10 360 4
Ampicillin 2.86 2-8 0.9(Nt,ST,AT,CiT) 0.52

Amylobarbitone 4.42 1-8 10-30 > 30 8-42 (IT) 1.1

Anistreplase (APSAC) - 1.5

Aprotinin 0.154 0.7

Arsenic 13.35 <0.02 >1 >9

Ascorbic acid 5.68 6-10 6(Si) 0.5

Astemizole 2.18 0.00013 20/50 250

Atenolol 3.75 0.2-1.3 6.1(At,Ci = ) 1

Atracurium 0.8 0.65 >1.1 0.33/? 0.15

298
 CLINICAL PHARMACOLOGY

Go Active metabolites Extra dose Clinical

Name Potency after dialysis application

0.6 Diacetolol X 1 nH P, -antagonist, type II

anti-arrhythmic
0.6 Indomethacin ? Indole NSAID
0.1 ? (unlikely) Carbonic anhydrase
inhibitor

0.99 Mucolytic
0.99 Salicylic acid <xl H,P Salicylate

0.23 H Antiviral drug (herpes)

0.01 - ? Lipid-lowering drug
0.99 ? Anti-arrhythmic
0.99 ? Opiate analgesic
0.85 Oxypurinol Potent H,Itx:H Xanthine oxidase
inhibitor
0.89 (OH-alprazolam) X0.5 ? (unlikely) Benzodiazepine
? (unlikely) Thrombolytic
0.1 nH,nP,Itx:H Antiviral drug (influenza)
0.06 - H,P Aminoglycoside
antibiotic
0.25 ? Potassium-sparing
diuretic
0.9 ? Corticoid synthesis
inhibitor
0.99 yV-monodesethyl nH.nP Type III anti-arrhythmic
amiodarone
0.95 Nortriptyline > xl nH,nP,Itx:kP Tricyclic antidepressant
0.9 ? (unlikely) Type II calcium-channel
blocker
0.95 8-OH-A, 7-OH- ? Tricyclic antidepressant
amoxapine
0.06 RnP Aminopenicillin
pHi (0.79- -0.45) ltx:H,Itx:P CNS stimulant
0.99 nH,nP Antifungal
0.1 H,nP Aminopenicillin
0.99 7 Barbiturate hypnotic
7 Thrombolytic
0.99 7 Kallikrein inhibitor
Itx:H Heavy metal
0.3-0.98 . H Vitamin C
0.99 Demethyl-astemizole x 1 ? (unlikely) Non-sedative
antihistamine
0.06 - H.nP [^-antagonist
0.99 Laudanosid nH Non-depolarizing muscle
relaxant

299
MEMORIX CLINICAL MEDICINE

Drug Factor Plasma concentration (mg/1) HLT v4

Therap. Toxic Lethal Vk*

Atropine 3.46 0.035-0.2 >0.2 2.5(lT,AT) 2

Auranofin 1.47 600 0.05

Azapropazone 3.33 13 0.16

Azathioprine 3.61 - 0.2/0.9 0.8

Azlocillin 2.17 50-500 Nlin(l)(lT) 0.2

Aztreonam 2.3 0.01-20 1.6(Cit) 0.82

BacampiciUin 2.15 -/0.9 0.25

Baclofen 4.68 0.08-0.4 3.5 0.85

Beclomethasone 2.45 15

Bendrofluazide 2.37 3.5 1.5

Betamethasone 2.55 5.6 1.4

Betaxolol 3.25 18(NT,AT) 7

Bezafibrate 2.76 1.7 0.3

Bisoprolol 3.07 12 (Cit) 32

Bleomycin - 3.1 0.27

Boric acid 16.17 <7 > 20 > 200 21 0.3

Bretylium 2.41 0.8-2.4 8.9 5.9

Bromazepam 3.16 0.08-0.17 16(At)/? 1

Bromide 12.52 <100 >500 >2000 24 >40

Bromocriptine 1.53 3 3.4

Brompheniramine 3.13 0.008-0.015 25 11.7

Budesonide 2.32 2.7 4.4

Bumetanide 2.74 1.5(Ci=,HFt) 0.3

Bupivacaine 2.92 1-4 >1.6 2.4 0.9

Buprenorphine 2.14 2.5 2

Buspirone 2.59 2.4(CiT)/2 5.3

Busulphan 4.06 2.6 0.99

Butobarbitone 4.27 1-5 10-30 > 30 37.5 0.8

Cadmium 8.9 < 0.005 >0.05

Caffeine 5.15 5-10 >100 Nlin(5) 0.61

Captopril 4.6 <0.05 1.9 0.7

Carbamazepine 4.23 4-10 >8 >15 16-37(Ni)/7 1.2

Carbenicillin 2.64 10-125 0.8(NT,lT,CiT) 0.15

Carbenoxolone 1.75 - 16.3(AT) 0.1

Carbimazole 5.37 0.5

Carisoprodol 3.84 10-30 >30 > 110 8 0.6

Carmustine 4.67 0.3 3.3

Carnitine 6.2 <12 2-15 0.25

300
 CLINICAL PHARMACOLOGY

Q. Active metabolites Extra dose Clinical

Name Potency after dialysis application

0.6 nH,nP Anticholinergic

0.9 nH Antirheumatic
0.4 ? NSAID
0.99 6-Mercaptopurine (H) Immunosuppressant
0.35 ~ H,nP Antipseudomonal
penicillin

0.33 - H,(P) Monobactam antibiotic

0.99 Ampicillin Prodrug H,nP Aminopenicillin

0.2 - ? Skeletal muscle relaxant

0.99 ? Glucocorticoid
0.7 ? Thiazide diuretic
0.95 ? Glucocorticoid
0.85 - nH (J, -antagonist

0.15 nP Lipid-lowering drug

0.5 - ? (unlilkely) P, -antagonist

0.32 nH DNA synthesis inhibitor

? Disinfectant
0.2 - nH III- Anti-arrhythmic

0.99 3-OH-bromazepam ? (unlikely) Benzodiazepine

Itx:H
0.99 ? Central dopamine agonist
0.95 Sedative antihistamine
? Glucocorticoid
0.5 ? Loop diuretic
0.98 ? Local anaesthetic
0.99 ? Opioid analgesic
0.99 l-(2-pyrimidiny)- x 0.2 nH Anxiolytic
piperazine
0.99 ? Alkylating drug
0.92 ? Barbiturate hypnotic
- ? Heavy metal
0.99 Itx:kP Analeptic
0.5 - H ACE inhibitor
0.99 Carb. 10,11 epoxide (XI) (H),Itx:H Anticonvulsant
0.2 H,P Penicillin active against

Pseudomonas
0.99 ? Ulcer-healing drug,
mineralocorticoid
0.99 ? Antithyroid drug
0.99 ? Skeletal muscle relaxant

? Alkylating drug
0.2 - H Vitamin

301
MEMORIX CLINICAL MEDICINE

Drug Factor Plasma concentration (mg/1) HLT V4

Therap. Toxic Lethal l/kg

Cefaclor 2.72 - 0.8 0.24

Cefadroxil 2.75 <35 1.3 0.15

Cefotaxime 2.2 0.2-8 1.2(At,CiT)/ 0.38

2.5(AT)
Cefoxitin 2.34 1-10 0.7(lT) 0.15

Cefsoludin 1.88 1.5 0.35

Ceftazidime 1.83 - 1.8(lt,AT) 0.25

Ceftizoxime 2.61 2-64 1.2 0.25

Ceftriaxone 1.8 0.2-8 8(Ci,Ci = ) 0.15

Cefuroxime 2.36 1-50 1.4(lT,Cii) 0.28

Cephalexin 2.88 6-50 0.9 0.26

Cephamandole 2.16 0.5-5 0.8(lt) 0.16

Cephazolin 2.2 <200 1.6(lT) 0.17

Cephradine 2.86 0.5-12 0.76 0.32

Celiprolol 2.64 0.2-0.8 5

Chloral hydrate 6.05 2-10(-20) >100 >250 -/8 0.6

Chlorambucil 3.29 1/2 0.86

Chloramphenicol 3.09 5-20 >25 >100 2.7(lT,CiT) 0.57

Chlordiazepoxide 3.34 0.7-3 >5 >20 15(At,CiT)/ 0.3

80(At)

Chlormethiazole 6.19 4.1(At,Cit) 5.4

Chloroform 8.38 20-230 >70 >390

Chloroquine 3.13 0.01-0.28 >3 1000/360 115

Chlorothiazide 3.38 6 1.5 0.2

Chlorpheniramine 3.64 0.005-0.04 20/? 4.3

302
 CLINICAL PHARMACOLOGY
Co Active metabolites Extra dose Clinical

Name Potency after dialysis application

0.4 H,P Oral second generation

cephalosporin
0.05 ~ H,nP Oral second generation
cephalosporin
0.35 Desacetyl-cefotaxime H,nP i.v. third generation

cephalosporin
0.15 H,nP i.v. second generation
cephalosporin
0.2 H i.v. 3rd generation
antipseudomonal
cephalosporin
0.12 H,nP i.v. 3rd generation
antipseudomonal
cephalosporin
0.05 H,nP i.v. third generation

cephalosporin
0.4 nH,nP i.v. third generation

cephalosporin
0.05 H,nP Second generation
cephalosporin
0.1 H,nP Oral first generation
cephalosporin
0.05 H,nP i.v. second generation
cephalosporin
0.15 H,nP i.v. first generation
cephalosporin
0.1 " H,P First generation

cephalosporin
0.6 ? a^pVantagonist,
pYagonist
0.99 Trichloroethanol x 1, H,nP:Itx:H,KP Sedative
Prodrug
0.99 nH,nP Alkylating agent
0.95 - nH,nP Antibiotic
0.99 Demethyl-chlordiazapine nH Benzodiazepine
-»demoxipam -» nordazepam
-* oxazepam

? (unlikely) Hypnotic
? (unlikely) Inhalation anaesthetic
pH i (0.4) Desethyl-chloroquine nH,nP Antimalarial
0.05 ? Thiazide diuretic
0.77 H,nP H, -antagonist

303
MEMORIX CLINICAL MEDICINE

Drag Factor Plasma concentration (m g/1) HLT v*

Therap. Toxic Lethal |/kg

Chlorpromazine 3.14 0.05-0.5 >0.75 >3 30(Cl)/25 21

Chlorpropamide 3.61 50-150 >200 32/? 0.15

Chlorthalidone 2.95 0.02-7.7 53(At) 4.1

Chlortetracycline 2.09 0.5-6 5.6 1.74

Cholestyramine Not absorbed

Cilastatin 2.8 0.8 0.2

Cimetidine 3.96 0.5-4 > 1.25(i ninimum 2(At,Ci = ) 1.8

value)

Cinnarizine 2.71 5

Cinoxacin 3.81 <30 2.1 0.33

Ciprofloxacin 3.02 5/? 2.1

Cisapride 2.15 0.01-0.1 10(AT) 1.9

Cisplatin 3.33 0.5 0.51

Clavulanic acid 5.02 0.9(lt) 0.3

Clindamycin 2.35 <4 2.8(CiT)/? 1.1

Clobazam 3.33 ll-77(At)/50 1.4

Clofazimine 2.11 0.5-1.5 240

Clofibrate 4.12 80-150 -/15-54(Ci=)
Clomipramine 3.18 0.05-0.4 24/50 17

Clonazepam 3.17 0.02-0.07 20-60 3.2

Clonidine 4.35 < 0.0005 > 0.001 Nlin(8) 3.5

Clorazepate 3.01 <0.02 2/80(AT) 0.33

Cloxacillin 2.29 7-14 0.6/? 0.35

Clozapine 3.06 0.1-0.7 10

CO 35.7 <6% > 15% > 50%
Cocaine 3.3 0.05-0.15 0.9 >l-20 0.71 2.1

Codeine 3.34 0.01-0.12 >0.2 >0.6 3.3/2.3 3.5

Colchicine 2.5 0.0003-0.03 19.4 10

Colestipol Not absorbed
Colistin 0.86 1-5 3 0.55

Copper 15-74 0.1-1.5 >2.5

Cortisone 2.77 0.5/1.75

Cyclophosphamide 3.83 - 7.6/?(C>l) 0.8

Cycloserine 9.8 10
Cyclosporin 0.83 0.2-0.5 6(Cl,CiT) 3.5

304
 CLINICAL PHARMACOLOGY
Go Active metabolites Extra dose Clinical

Name Potency after dialysis application

0.99 7-OH-chlorpromazine, (x 0.5) nH,nP Phenothiazine sedative

N-desmethyl chlorpromazine
PHT(0.05-0.85) (3 Metab.) nP,Itx:H Sulphonylurea
0.35 - ? Diuretic

0.82 ? (unlikely) Short-acting tetracycline

nH,nP Resin
0.3 H Dihydropeptidase
inhibitor

0.3 - (H),(P) H r antagonist

0.99 ? Vasodilator
0.2 ? Urinary antiseptic
0.5 nP,Itx:H 4-Ouinolone antibiotic
0.99 ? Gastric motility stimulant
0.75 (H) Cytotoxic drug
0.55 H ^-lactamase inhibitor
0.9 yV-demethyl- >xl Macrolide antibiotic
clindamycin
Desmethyl-clobazam ? (unlikely) Benzodiazepine
0.99 ? (unlikely) Antileprotic drug
0.85 Clofibrinic acid Prodrug nH Lipid-lowering drug
0.99 Desmethyl clomipramine nH,nP Tricyclic antidepressant

0.99 7-amino-cl., 7-acetamino-cl. ?(unlikely) Benzodiazepine

0.4 nH Central aj-agonist
antihypertensive
0.99 Nordazepam -» Prodrug nH Benzodiazepine
Oxazepam
0.25 nH Penicillinase-resistant

penicillin

0.99 (N-desmethyl-cl.) nH Antipsychotic

Carbon monoxide
0.99 7 Local anaesthetic
0.99 Morphine X5 7 Opiate analgesic
0.99 nH,Itx:H,P Gout treatment
nH,nP Bile acid binder
0.2 nH.(P) Polymyxin antibiotic
- ? Trace element
Hydrocortisone xl.25 nH Glucocorticoid
0.9 Phosphoramide- Prodrug H Alkylating agent
nornitrogen mustard
0.4 H Antitubercular agent
0.99 ? nH,nP Immunosuppressant

305
MEMORIX CLINICAL MEDICINE

Drug Factor Plasma concentration (mg/1) HLT V4

Therap. Toxic Lethal 1/kg

Cytarabine 4.11 0.01-0.1 2.3 2.2

Dacarbazine 5.49 0.7 0.63

Dactinomycin 0.8 - 36
Danazol 2.96 0.1-0.15 29
Dantrolene 3.18 0.3-3 9/?

Dapsone 4.03 1-7 29 1.9

Demeclocycline 2.15 0.5-3 13.6 1.8

Desferrioxamine 1.68 <100 6

Desipramine 3.75 0.15-0.3 > 0.5 10-20 Nlin(17)(At)/? 41.9

Desmopressin 0.94 0.5-2

Dexamethasone 2.55 3 0.82

Dexfenfluramine 4.32 18
Dextromethorphan 3.68 2.7/6.5 1.1

Diamorphine 2.71 0.05

Diazepam 3.51 0.1-1 >5 >20 33(lT,At,CiT) 2

/80(AT)
Diazoxide 4.33 15-35 >100 30 0.2

Diclofenac 3.54 1.5 0.2

Didanosine 4.23 0.63 1

Diethylcarbamazine 5.02 12 2.5

Diflunisal 4.0 9-90 >600 11 0.1

Digitoxin 1.31 0.01-0.03 > 0.04 > 0.3 164(Ci = )/43(Ci = ) 0.6

Digoxin 1.28 0.0008-0.002 > 0.002 > 0.015 43/(nT,U,aT, 6.3

Ci=,HF=)
Diltiazem 2.41 0.03-0.4 4(At)/8 5.3

Diphenhydramine 3.92 0.01-1 >5 >10 5.2(Cit) 3.7

Diphenoxylate 2.21 0.01 - 2.5/13 4.6

Dipyridamole 1.98 <1.5 0.8

Disopyramide 2.95 2-5(-8) >9 >26 7.8(HF=)/9 0.8

Disulfiram 3.37 2.5 7.3 8.2

Dobutamine 3.32 0.04-0.17 0.033(HF=) 0.2

Domperidone 2.35 8
Dopamine 6.53 0.01-0.1 0.15(Cl)/0.03 0.93

Dothiepin 3.38 - 22 45
Doxapram 2.64 2.7-5.2 7 3.5

Doxazosin 2.21 13 1.3

Doxepin 3.58 0.01-0.25 > 0.5-2 10-20 18/35 20

306
 CLINICAL PHARMACOLOGY
Q* Active metabolites Extra dose Clinical

Name Potency after dialysis application

0.9 ? Antimetabolite
0.3 ? DNA/RNA synthesis
inhibitor

? (unlikely) mRNA synthesis inhibitor

? Gonadotrophin inhibitor
0.96 5-OH-dantrolene (X0.5) ? Skeletal muscle relaxant

0.85 Monoacetyl-dapsone Itx:H Antileprotic drug

0.6 H,nP Medium-duration
tetracycline

Itx:H Chelating agent

0.99 5-OH-desipramine nH,nP Tricyclic antidepressant

0.99 ? Vasopressin analogue

0.97 ? Glucocorticoid
0.9 ? (unlikely) Appetite suppressant
0.8 Dextrophan ? Opiate analgesic
0.99 ? Opiate analgesic
0.99 Nordiazepam -> XI nH Benzodiazepine
oxazepam (temazepam) ? (unlikely) Benzodiazepine
0.6 H,P Antihypertensive
0.99 - ? (unlikely) Acetoacetate NSAID
0.6 ? Antiviral (HIV)
0.15 ? Antihelminthic
PHt (0.94) - nH,nP Salicylate

0.68 Digoxin nH,nP Digitalis alkaloid

0.24 nH,nP Digitalis alkaloid

0.96 Desacetyl-diltiazem X0.4 nH,nP Type I calcium-channel

blocker,

Type IV anti-arrhythmic
0.97 ? H,-antagonist
0.99 Diphenolic acid X5 ? Antidiarrhoeal
nH Antiplatelet drug
0.45 Nordisopyramide (X0.25) (H?) Type la anti-arrhythmic

0.5 ? Alcohol-deterrent
compound
0.99 ? P, -agonist
'
0.99 >
Antiemetic
0.97 Noradrenaline )
P, -agonist
0.99 ? I (unlikely) Tricyclic antidepressant
0.99 >
Analeptic
0.91 ? nH a, -antagonist
0.99 Desmethyldoxepin nH,nP Tricyclic antidepressant

307
MEMORIX CLINICAL MEDICINE

Drug Factor Plasma concentration (mg/l) HLT Vt

Therap. Toxic Lethal l/kg

Doxorubicin 1.84 36/? 25

Doxycycline 2.26 1-2 20 1.5

Droperidol 2.64 - 2.2 1.75

Fdrophonium 4.06 <0.15 1.8 1.1

Enalapril 2.66/2.6 0.02-0.08 (Enalaprilat) 1.3/1 l(HFt) l;7

Enflurane 5.42 50-100

Enoximone 4.03 1-20/2.2-25 2.5

Ephedrine 6.05 0.1 6

Epirubicin 1.84 39/s£39 50
Epoetin - 6 0.03

Ergotamine 1.72 1.9 1.8

Erythromycin 1.36 0.5-2.5 Nlin(2)(CiT) 0.6

Esmolol 3.39 0.2 0.15(Ci = ) 3.4

Estramustine 2.27 1.3/15

Ethacrynic acid 3.3 1 0.1

Ethambutol 4.89 2-5 3.5 2.3

Ethanol 21.7 >1800 >3500 Nlin(0.25) 0.54

Ether 13.49 500-1500 >1400

Ethinyloestradiol 3.37 13 2.9

Ethosuximide 7.08 40-100 > 150 >250 50(d) 0.67

Etidronate disodium 4.85 6 1400

Etomidate 4.09 0.5-4.6 45

Etoposide 1.7 7 0.35

Etretinate 2.82 0.2-0.8 8(-2900)/50 2

Famotidine 2.% 2.2(At) 1.3

Felodipine 2.6 10.2(At) 9.7

Fenbufen 3.93 10/? 3

Fenfluramine 4.32 0.04-0.12 >0.2 >6 19/? 14

Fenofibrate 2.77 5-15 (Fenofibricacide) -/22 0.9

Fenoprofen 4.13 20-65 >700 2.2 0.09

Fentanyl 2.97 0.001-0.003 3.7 n: 2min. a: lOmin

4(At,Ci = ) 4

Flecainide 2.41 0.2-1 > 1 9-20(C4.aT,HFT) 7.5

Flucloxacillin 2.2 0.4 0.8/? 0.12

Fluconazole 3.26 30 0.8

Flucytosine 7.75 35-70 > 100 4.8/0.25 0.6

308
 CLINICAL PHARMACOLOGY

Q. Active metabolites Extra dose Clinical

Name Potency after dialysis application

0.85 Doxorubicinol ? (unlikely) DNA synthesis inhibitor

pHT(0.45) nH,nP Long-acting tetracycline
0.99 ? ? (unlikely) Hypnotic
0.2 ? Cholinesterase inhibitor
0.1 Enalaprilat Prodrug H ACE inhibitor

? (unlikely) Inhalation anaesthetic

0.99 Enoximone ( +) ? Phosphodiesterase

sulphoxide inhibitor

0.3 ? (3, -antagonist

0.99 13-OH-epirubicin ? (unlikely) Cytotoxic antibiotic

0.9 nH Erythropoietic hormone
0.5 Itx:H Antimigraine drug
0.85 nH,nP Macrolide antibiotic
0.99 - ? P, -antagonist, Type II

anti-arrhythmic
0.99 ? Alkylating oestrogen
0.35 nH Loop diuretic

0.15 - H,P Antituberculous drug

0.97 Itx:H Hypnotic
? (unlikely) Inhalation anaestheic

? (unlikely) Sex hormone

0.7 ~ H Anticonvulsant
? (unlikely) Chelating agent
0.99 ~ ? Intravenous anaesthetic
agent
0.6 ? Antimetabolite
0.99 Etretin ? (unlikely) Oral retinoid for psoriasis
0.3 f nH H ;
-antagonist
0.99 ? (unlikely) Type II calcium-channel
blocker
0.95 Biphenyl acetate, ? (unlikely) Propionic acid NSAID
OH-biphenylacetate Prodrug
0.6 Norfenfluramine ? Appetite suppressant
0.2 Fenofibrinic acid Prodrug nH Lipid-lowering drug
0.95 - nH Propionic acid NSAID
0.92 - Opioid analgesic

pHi(0.75) - nH Type Ic anti-arrhythmic

0.45 OH-flucloxacillin nH Penicillinase-resistant

penicillin

0.2 H,P Antifungal drug

0.02 5-Fluorouracil H,P Antifungal drug

309
MEMORIX CLINICAL MEDICINE

Drug Factor Plasma concentration (mg/l) HLT y4

Therap. Toxic Lethal l/kg

Flumazenil 3.3 0.9 0.95

Flunisolide 2.3 1.8/? 1.8

Flunitrazepam 3.19 0.003-0.006 30(At)/28 4.5

Fluoride 52.66 4.3

Fluouracil 7.69 0.2/70 0.25

Fluoxetine 3.23 24-170/170 35

Flupenthixol 2.3 30 15

Fluphenazine 2.29 < 0.002 >2 36/?

Fluphenazine deconate 1.76 < 0.001 180-340

Flurazepam 2.58 0.01-0.1 > 0.2 > 0.5 2(AT)/40-100 22

Flurbiprofen 4.09 3.5 0.1

Flutamide 3.62 0.5-3 (2-OH-Flutamide) 7.8/Nlin(4-22)

Fluvoxamine 3.14 17.5

Folic acid 2.27 0.75

Folinic acid 1.95 9.3 3.2

Foscarnet 5.21 fi: 3,3,v: 18 1.3

Fosfestrol 2.33 0.08/?

Fosfomycin 7.24 <400 2 0.3

Frusemide 3.02 0.1-0.3 >25 1.5(lT,AT,Ci = , 0.2

HF=)
Fusidic acid 1.94 6
Gallamine 1.12 2.5 0.15

Ganciclovir 3.92 0.6-25 2.9 0.6

Gemfibrozil 3.99 1.5

Gentamicin ca. 2.1 peak: 6-10 >12 2(NTjT) 0.25

trough: <2 >2

Glibenclamide 2.02 (< 0.007) 10 0.1

Gliclazide 3.09 12(At) 0.2

Glipizide 2.24 - 3 0.16

Gliquidone 1.9 17/?

Glycerol 10.86 0.5

Glyceryl trinitrate 4.4 0.001-0.01 0.04/0.8 3.3

0.04/0.8

Griseofulvin 2.83 0.3-1.3

Guanethidine 5.04 > 0.008 43-150/?

Haloperidol 2.66 0.002-0.02 > 0.025 - 20(Cl)/? 18

Halothane 5.07 80-260 >200

Heparin - Nlin(0.5)(CiT) 0.06

310
 CLINICAL PHARMACOLOGY
Qo Active metabolites Extra dose Clinical

Name Potency after dialysis application

0.99 - ? Benzodiazepine
antagonist

0.95 (6-P-OH-flunisolide) ? Glucocorticoid

0.99 Desmethyl-flunitrazepair nH Benzodiazepine

0.96 Dihydro-fluouracil H Antimetabolite

0.98 Desmethyl-fluoxetin nH Antidepressant
- ? (unlikely) Antidepressant
0.99 7-OH-fluphenazine (X0.7) nH Antipsychotic
0.99 nH Antipsychotic
0.99 Desalkyl -flurazepam nH Benzodiazepine
OH-ethyl-flurazepam
0.9 - ? (unlikely) Propionic acid NSAID
0.99 2-OH-flutamide ? Anti-androgen
0.99 - ? (unlikely) Antidepressant
H Vitamin
0.7 ? (unlikely) Antidote against folate
antagonist
0.2 ? Antiviral (HIV)
0.95 Diethylstiboestrol Prodrug ? Mitosis inhibitor
0.01 - H,P Antibiotic
0.25 nH Loop diuretic

0.99 nH Antibiotic
0.05 H,P Non-depolarzing muscle
relaxant
0.1 Ganciclovir triphosphate H Antiviral (CMV)
0.99 ? Lipid-lowering drug
0.1 " H,P Aminoglycoside
antibiotic

0.99 - ? Sulphonylurea
0.99 7 Sulphonylurea
0.95 - 7 Sulphonylurea
0.99 p-OH-gliquidone 7 Sulphonylurea
0.8 7 Osmotic diuretic

1,3-Glyceryl dinitrate ? (unlikely) Vasodilator

1,2-Glyceryl dinitrate
0.99 7 Antifungal agent
0.5 Guanethidine-/V-oxide (<0.1) ? Antihypertensive
0.99 (reduced haloperidol) X0.1 nH, nP Antipsychotic
? (unlikely) Inhalation anaesthetic
0.99 nH,nP Parenteral anticoagulant
MEMORIX CLINICAL MEDICINE

Drug Factor Plasma concentration (mg/l) HLT v4

Therap. Toxic Lethal V*t

Hexamine 7.13 20 20 0.6

Hydralazine 6.24 0.1-1.5 2.5(HFT) 5

Fast acetylator 1 IJ
Slow acetylator 1 1.5

Hydrochorothiazide 3.36 0.07-0.45 10.2(AT) 3

Hydrocortisone 2.76 0.05-0.25 Nlin(1.8) 0.3

Hydroflumethiazide 3.02 - 16.6 6.4

Hydroxychloroquine 2.98 0.01-0.02 >60 72 50

Hydroxyurea 13.15 ^6 0.5

Hydroxyzine 2.67 14(At)/^14 22.5

Hyoscine 3.3 0.00004 2.9 1.4

Ibuproten 4.85 0.5-50 >100 - 2.2(AT) 0.1

Ifosfamide 3.83 Nlin(7)/?

Imipenem 3.34 -80 1.0(lT) 0.3

Imipramine 3.57 0.05-0.25 > 0.3-1 .5 >2 7-18(At)/17 15

Indapamide 2.73 18 1.6

Indomethacin 2.79 0.5-3 >5 6(lt) 0.9

Indoramin 2.88 4/?(AT) 7.4

Insulin 7.18 10-20 mU/1 0.25-2 0.6

Interferon o^, 0.0052 5.1 0.4

Interferon c^,, 0.0052 2

Ipatropium bromide 2.42 1.6

Iron 17.91 0.65-1.75 5-6 20-50

Isocarboxazid 4.32 <0.5 2

Isoniazid 7.29 0.5-15 >20 2.3(lT,CiT) 0.6

Fast acetylator 1.1 0.6

Slow acetylator 3.6 0.6

Isoprenaline 4.73 5/?

Isosorbide dintrate 4.23 0.003-0.2 1.3/2 1.5

1.3/5(Ci=)
Isotretinoin 3.33 14 7

Isradipine 2.69 3.2(At) 4

Kanamycin 2.06 peak: 20-25 >30 2(NTjT) 0.25

trough: 1-4 >8

Ketamine 4.21 0.1-0.15 a : 0.2, p: 3.6/? 2.9

Ketoconazole 1.88 8 0.36

Ketoprofen 3.93 1.5(At) 0.11

Ketorolac 3.92 4.5(At) 0.1

Ketotifen 3.23 1-4 4-20/?

312
 CLINICAL PHARMACOLOGY
Active metabolites Extra dose Clinical

Name Potency after dialysis application

Formaldehyde Prodrug Urinary antiseptic

0.9 nH,nP Vasodilator
0.98

0.9

0.05 ? Thiazide diuretic

0.99 ? Glucocorticoid
0.5 ? Thiazide diuretic
pHi(0.33) ? (unlikely) Antimalarial
0.5 - 9 DNA synthesis inhibitor
Cetirizine Potent ? (unlikely) H, -antagonist
0.95 9 Anticholinergic
0.99 - nH Propionic acid NSAID
0.8 4-OH-ifosfamide ? Alkylating agent
0.3 H Carbapenem antibiotic

0.98 Desipramine -> nH,nP Tricyclic antidepressant

2-OH-desipramine
0.95 nH Diuretic
0.85 - nH Indole NSAID
0.9 6-OH-indoramin ? (unlikely) a, -antagonist

0.95 nH Hormone
0.99 nH Immunostimulant
0.99 nH Immunostimulant
0.4 _ ? Anticholinergic
nH Trace element
? Irreversible MAO
inhibitor
pHt(0.7) H,P Antituberculous drug
0.93

0.7

0.5 3-O-methyl-isoprenaline ? P, +2 -agonist

0.99 2-mononitrate nH Nitrate vasodilator
5-mononitrate Nitrate vasodilator
0.99 ? Oral retinoid for acne
0.99 _ ? Type II calcium-channel
blocker
H,P Aminoglycoside
antibiotic
0.97 Norketamine X0.3 ? (unlikely) Intravenous anaesthetic
0.97 nH,nP Antifungal drug
0.99 Itx:H NSAID
0.4 ? NSAID
0.99 ? Mast cell stabilizer

313
MEMORIX CLINICAL MEDICINE

Drag Factor Plasma concentration (m g/l) HLT v*

Therap. Toxic Lethal l/kg

Labetalol 3.04 _ 4(Ci = ) 9

Lead 4.83 <0.03 >0.9 >1.1

Levodopa 5.07 0.2-4 1.4 12.7

Levonorgestrel 3.2 28 2.9

Lignocaine 4.27 2-5 >8 >25 1.8(lT,At,Cit, 1.5

HFt)/2.1
Lisinopril 2.26 7(At)
Lithium (mmol/1) 144.07 0.5-1.2 >2 >3 pH (22)(At) 0.79

Lofepramine 2.39 - 4.5/1 7( At)

Loperamide 2.1 < 0.003 11

Loprazolam 2.15 6<AT)

Loratadine 2.61 14.4

Lorazepam 3.11 0.02-0.24 >0.3 13(lt,Cit) 1.5

Lormetazepam 2.98 12/8

Loxapine 3.05 0.002-0.03 >0.2 >7.7 1.5-3.5

Lysergide (LSD) 3.09 - 0.001- - 3

0.004
Lysuride 2.95 2
Magnesium (mmol/1) 41.14 1.6-3.3 >7 >15
Mannitol 5.49 0.25-1.5 0.18

Maprotiline 3.61 0.2-0.3 >0.5 >2 43/? 51.7

Mebendazole 3.39 - 1.1 2

Medroxyprogesterone 2.9 36 0.6

Mefenamic acid 4.14 2-20 >25 4(Ci=)

Mefloquine 2.41 530 19

Melphalan 3.28 1.4/? 0.45

Meprobamate 4.58 5-30 60-100 140-350 12(Cit) 0.7

Mercaptopurine 6.57 0.9/? 0.56

Mercury 4.99 <0.08 >0.2 >6

Metformin 7.74 0.5-4 >45 1.5 3.1

Methadone 2,89 0.1-1.1 >2 >4 25(CiT) 3.9

Methanol 31.2 - 200-800 >800 3 0.7

Methicillin 2.63 1-6 l(Nt,lt) 0.3

Methocarbamol 4.15 _ 1.2 0.5

Methohexitone 3.52 5 K 5.5 min,

a: 60 min
3.9(Ci =) 2.2

Methotrexate 2.2 - 8.4(Cl) 0.75

Methotrimeprazine 3.04 0.02-0.14 21 29.8

314
 CLINICAL PHARMACOLOGY
Go Active metabolites Extra dose Clinical

Name Potency after dialysis application

0.95 nH,nP a,-|3 1+2 -antagonist

? Heavy metal
0.99 ? (unlikely) Antiparkinsonian drug
? Progestogen
0.95 MEGX, GX XI, X0.25 nH lb anti-arrhythmic. Local

anaesthetic
0.2 nH,nP ACE inhibitor

0.05 - H,P,Itx:H Antipsychotic

0.99 Desipramine —> 2-OH-d ? (unlikely) Tricyclic antidepressant

0.99 ? Anti-diarrhoeal

? (unlikely) Benzodiazepine
0.99 Descarboethoxy-L. ? H, -antagonist
0.99 - nH Benzodiazepine
0.99 ? (unlikely) Benzodiazepine
0.99 8-OH-loxapine ? (unlikely) Antipsychotic
8-OH-amoxapine
? CNS stimulant
0.99 ? Prolactin inhibitor
0.01 - Itx:H,P Anticonvulsant
0.05 Itx:H,P Osmotic diuretic

0.98 ? (unlikely) Tetracyclic antidepressant

0.99 nH Antihelminthic
0.55 ? Progestogen
0.95 - nH NSAID
0.9 ? (unlikely) Antimalarial
0.88 ? Alkylating agent
0.9 H,P,Ttx:H,KP Anxiolytic
0.78 TIMP, MTIMP nH,nP Antimetabolite
- ? (unlikely) Heavy metal
0.01 " Itx:H Biguanide oral
antidiabetic drug
pHt(0.7) nH.nP Opiate analgesic
Itx:H Solvent
0.25 nH,nP Penicillinase-resistant

penicillin

0.99 - ? Skeletal muscle relaxant

0.99 ? (unlikely) Intravenous barbiturate
anaesthetic

pHt(0.15-0.5) (H),nP,Itx:KP Dihydrofolate reducatase

inhibitor
0.99 ? (unlikely) Analgesic, hypnotic
MEMORIX CLINICAL MEDICINE

Drug Factor Plasma concentration (mg/l) HLT vt

Therap. Toxic Lethal Kg

Methyldopa 4.73 1-5 >7 1.4(lt)/? 0.4

Methylprednisolone 2.67 2.5 0.84

Methysergide 2.83 0.75

Metoclopramide 3.34 - 2.7 2.4

Metolazone 2.73 20 1.6

Metoprolol 3.74 0.025-0.3 3-6(Cit)/? 4.2

Metronidazole 5.84 1-2.5 8(CiT)/15 0.75

Metyrapone 4.42 0.5-4 0.4/?

Mexilitine 5.58 0.8-2 >2 10(Cit,HFt) 5.3

Mianserin 3.78 0.02-0.07 >0.1 Nlin(23)(AT)/*£ 23 6

Miconazole 2.4 0.001-10 22.5 21

Midazolam 3.07 0.2-0.5 2.5(Cit)/l 0.7

Milrinone 4.73 0.05-0.3 1.5(HFT) 0.3

Minocycline 2.19 0.5-3 12 0.43

Minoxidil 4.78 3.1/? 2.7

Misoprostol 2.61 -/157

Mitomycin 2.99 Nlin(0.25)

Moclobemide 3.72 0.2 2 1.1

Moracizine 2.34 _ 2-8 12

Morphine 3.5 0.01-0.1 0.1-1 > (0.05)-4 Jt:1.5 min, a: 15 min
2.3(Ci = )/4 3.5

Nadolol 3.23 0.025-0.275 14.1 2.1

Nafarelin 0.76 2.7

Nalbuphine 2.8 3.5(d)/? 3.8

Nalidixic acid 4.31 5-50 6(lT,At)/? 1

Naloxone 3.05 0.01 1 2.8

Naltrexone 2.93 3.9/12.9 19

Naproxen 4.34 >50 14 0.09

Neomycin 1.63 5-10 2.5 0.2

Neostigmine 3.3 1.3 0.7

Netilmicin 2.1 peak: 6-10 >12 2.2 0.25

trough: < 2 >2

Nicardipine 2.09 5(CiT) 1.1

Nickel 17.04 0.001-0.004 5

Nicotine 6.16 >10 50-500 2(5i) 2.6

316
 CLINICAL PHARMACOLOGY
Q. Active metabolites Extra dose Clinical

Name Potency after dialysis application

0.72 Dopamine H,P Central a r agonist

0.95 H Glucocorticoid
0.9 ? Migraine prophylactic
0.83 nH,nP Antiemetic
0.2 nH Thiazide diuretic
0.9 a-OH-meoprolol <X0.1 (H) P r antagonist
0.92 OH-metronidazole H,nP Antibiotic

0.99 Metyrapol ? Corticoid synthesis

inhibitor

pHi(0.9) - nH,nP Type lb anti-arrhythmic

0.95 Desmethyl-mianserin (-XI) ? (unlikely) Tetracyclic antidepressant

0.99 nH,nP Antifungal antibiotic

0.99 a-OH-midazolam XI ? Benzodiazepine
0.2 ? Phosphodiesterase
inhibitor

0.9 nH,nP Long-acting tetracycline

0.88 Min.-N-O-sulphate Prodrug nH Vasodilator
0.99 Misoprostol ic acid x 1 ? Prostaglandin-E,
analogue
0.9 ? DNA synthesis inhibitor

0.99 ? ? Reversible MAO

inhibitor

0.99 ? ? (unlikely) Type I anti-arrhythmic

Mo.-6-glucuronide Opiate analgesic

0.3 - H P lo -antagonist
0.95 ? Gonadotrophin RH
antagonist
0.95 ? (unlikely) Analgesic
0.95 OH-nalidixic acid X16 ? Urinary antiseptic
0.99 ? Opiate antagonist
0.99 6-|J-naltrexol (< x 0.08) ? (unlikely) Opiate antagonist
0.99 - nH Propionic acid NSAID
0.5 " H Aminoglycoside
antibiotic
0.33 ? Cholinesterase inhibitor
0.05 - H,P Aminoglycoside
antibiotic
0.99 nH Type II calcium-channel
blocker
- ? Trace element
pHi(0.83) ? (unlikely) CNS stimulant

317
MEMORIX CLINICAL MEDICINE

Drug Factor Plasma concentration (mg/l) HLT vt

Therap. Toxic Lethal l/kg

Nicotinic acid 8.12 0.75

Nifedipine 2.89 0.015-0.1 1.7(CiT,HF=) 1.1

Nimodipine 2.39 1.5 1.5

Nitrazepam 3.56 0.03-0.18 22(AT,Ci = ) 2.1

Nitrofurantoin 4.2 1.8 0.33 0.8

Nitroprusside 3.82 6-29 0.1

Nizatidine 3.02 0.07-0.7 1.3/4 1.2

N 2
(nitrous oxide) 22.72 17-22 >350
Noradrenaline 5.91 0.03

Norethisterone 3.35 10 4
Norfloxacin 3.13 <5 4(Ci = )/? 3.2

Nortriptyline 3.8 0.05-0.4 > 0.5 > 13 27(Tt)/> 27 20

Ofloxacin 2.77 4(Cit) 1

Omeprazole 2.9 1/1 0.35

Orciprenaline 4.73 2.1 7.6

Orphenadrine 3.71 0.4-1 >1 4-8 18/25 6

Ouabain 1.71 0.0002 22'? 15.7

Oxatomide 2.34 0.1 14

Oxazepam 3.49 0.2-2 >2 12(Ci = ) 1.2

Oxpentifylline 3.59 0.8/1 4.2

Oxprenolol 3.77 0.04-0.1 1.9 1.2

Oxytetracycline 2.17 0.05-3 9.2 1.9

Pancuronium 1.36 0.25-0.5 >1.6 2.3(AT, CiT)/l.l 0.26

Papaverine 2.95 0.1-4 1.6 0.2

Paracetamol 6.62 5-20 120-300 > 1500 2.5(lT,At,Si,CiT, 1.1

HF=)
Paraldehyde 7.57 10-100 > 200 > 500 6
Paraquat 5.37 - >1 >2 2.8

PAS 6.53 0.6-4 1.5(Ci = ) 0.11

Pemoline 5.68 11

Penicillamine 6.7 2.5

Penicillin G 2.69 1.5-16 0.7(NT,lT) 0.5

(Benzylpenicillin)

Penicillin V 2.85 3-5 0.6 0.4

(Phenoxymethylpenicillin)
Pentamidine 2.94 6.2 16

Pentazocine 3.5 0.1-0.6 2-5 >(l-)5 2.5(Si,CiT) 4

Perindopril 2.71 0.003 (Perindoprilat) 2.9(Ci = )/ll

Perphenazine 2.48 0.005 > 1 - 10/? 25

318
 CLINICAL PHARMACOLOGY
Q. Active metabolites Extra dose Clinical

Name Potency after dialysis application

0.1 ? Lipid-lowering agent

0.98 nH,nP Type II calcium-channel
blocker
0.9 - ? (unlikely) Type II calcium-channel
blocker
0.99 ? (unlikely) Benzodiazepine
pHt(0.6) H Urinary antiseptic
0.99 nH,CN-Itx:H Vasodilator
0.4 (A/2-monodesmethyl-N.) nH, Itx:H H 2 -antagonist

0.99 ? (unlikely) Inhalation anaesthetic

0.99 ? a P,- agonist
? Progestogen
0.35 6 different metabolites nH 4-Quinolone antibiotic
0.98 1 0-OH-nortripty line nH,nP,Itx:KP Tricyclic antidepressant

0.25 ? 4-Quinolone antibiotic

0.99 Omeprazole-sulphone ? (unlikely) Proton pump inhibitor

0.9 - ? (unlikely) pVagonist

0.92 nH Skeletal muscle relaxant
0.63 nH,nP Cardiac glycoside
0.99 ? ? H, -antagonist
0.98 - nH Benzodiazepine
0.99 5-OH-pentoxifylline ? (unlikely) Vasodilator
0.95 - ? Pi +r antagonist
0.5 nP Short-acting tetracycline
0.33 3-OH-pancuronium X 0.5 ? Non-depolarizing muscle
relaxant
0.99 (H) Vasodilator
0.95 (H),nP,Itx: Analgesic
H,KP
0.99 ? Anticonvulsant
Paraoxone Itx:KP Herbicide
0.9 H Antituberculous drug
0.6 ? CNS stimulant
0.85 ? Antirheumatic
0.2 H,nP Natural penicillin

0.74 H,nP Acid-resistant penicillin

0.95 ? (unlikely) Antiprotozoal

0.95 H Opiate agonist/antagonist
0.9 Perindoprilat Prodrug ? ACE inhibitor
(7- )H-perphenazine nH Antipsychotic

319
MEMORIX CLINICAL MEDICINE

Drug Factor Plasma concentration (rng/l> HLT v*

Therap. Toxic Lethal i*g

Pethidine 4.04 0.3-1 >5 10-30 a: lOmin

6(NT.AT.CiT)/? 4.7

Phenelzine 7.34 0.001-0.002 >4 Nlin( 1.5-4)

Phenobarbitone 4.31 15-40 >50 >100 100(lT,Cl,AT.CiT) 0.7

Phenylbutazone 3.24 40-150 >200 >400 72(At,Si)/48 0.1

Phenylephrine 4.91 0.03 2.5

Phenytoin 3.% 10-20 >20 >40 Nlin(20)(lT,C\t) 0.65

Physostigmine 3.63 1.5

Phytomenadione 2.22 2
Pimozide 2.17 53-111 24
Pindolol 4.03 0.05-0.15 2.2 2
Piperacillin 1.93 <400 0.93 0.18
Pirenzepine 2.85 10

Piretanide 2.76 1.4 0.3

Piroxicam 3.02 0.85-13.5 48 0.15

Pivampicillin 2.16 0.2/0.9

Platinum 5.13 <0.7 58-73

Polymyxin B - 0.5-4 4.4

Polythiazide 2.27 2-7 26

Pralidoxime 5.79 1.25

Praziquantel 3.2 1.5

Prazosin 2.61 2.9(HFT) 0.6

Prednisolone 2.77 2.2(Ci =) 0.65

Prednisone 2.79 3.6(Ci = ) 0.97
Prilocaine 4.54 1-5 >8 2.1

Primaquine 3.86 7
Primidone 4.58 4-12 >12 >100 6.5/1 00(CiT) 0.8

Probenecid 3.87 100-200 Nlin(5)/? 0.15

Probucol 1.93 15-80 550
Procainamide 4.25 4-10 >16 3(Cl,HF=)/6 2

Procarbazine 4.52 0.17

Prochlorperazine 2.67 - >1 >5 23
Promethazine 3.52 0.2-11 3-13 2

Propafenone 2.93 0.2-0.9 >0.9 Nlin(7)/10 4.4

Propantheline 2.23 1.8

Propofol 5.61 1-10 p: 0.8, y: 10(AT) 5

320
 CLINICAL PHARMACOLOGY
Q. Active metabolites Extra dose Clinical

Name Potency after dialysis application

Normeperidine Opiate analgesic

0.99 ? ? (unlikely) Irreversible MAO

inhibitor

pHt(0.75) - H,P,Itx:KP Barbiturate hypnotic

0.99 Oxyphenbutazone x 1 nH,Itx:KP NSAID
T-OH-phenylbutazone ? NSAID
0.85 ? a-agonist
0.95 ~ nH,nP,Itx:KP Anticonvulsant,
Ib-anti-arrhythmic
0.99 ? Cholinesterase inhibitor
0.95 ? Vitamin K,
0.99 - ? (unlikely) Antipsychotic
0.63 - ? (3, +2 -an tagonist

0.29 H,nP Broad-spectrum penicillin

0.8 ~ ? Gastric secretion

inhibitor

0.55 ? Loop diuretic

0.95 - ? (unlikely) Oxicam NSAID

0.99 Ampicillin Prodrug H,nP Aminopenicillin
? Heavy metal
0.4 nH,P Polymyxin antibiotic
0.75 ? Thiazide diuretic
0.2 ? Cholinesterase
reactivator
0.99 - ? Antihelminthic
0.99 nH,nP a, -agonist

0.75 Prednisone nH,nP Glucocorticoid

0.97 Prednisolone XI H Glucocorticoid
? Local anaesthetic
0.95 ? ? Antimalarial
0.9 Phenobarbitone XI H Anticonvulsant
Phenylethylmalonamide Anticonvulsant?
0.98 ? Uricosuric
0.99 ? nH,nP Lipid-lowering drug
0.5 NAPA H,nP Ia-anti-arrhythmic
0.95 ? Cytostatic
nH Antipsychotic
0.98 nH H, -antagonist
0.99 5-OH-propafenone ca.x 1 ? (Unlikely) Ic-anti-arrhythmic
0.85 ? Anticholinergic
0.99 ? ? Intravenous anaesthetic

321
MEMORIX CLINICAL MEDICINE

Drug Factor Plasma concentration (mg/1) HLT v 4

Therap. Toxic Lethal l*g

Propranolol 3.86 0.02-0.4 >2 8-12 3.8(AT,GT)/? 4

Propylthiouracil 5.87 1.4 0.36

Protriptyline 3.8 0.1-0.2 >0.5 >1 78 22

Pseudoephedrine 4.96 0.5-0.8 >19 6.9 2.8

Pyrazinamide 8.12 20-30 10

Pyridostigmine 3.83 0.05-0.1 1.9 1.1

Pyrimethamine 4.02 0.07-0.2 96 2.2

Quinalbarbitone 3.84 1-5 >3.5 28 1.5

Quinidine 3.08 2-5 >10 30-50 6.3(AT,CiT)/12 33

Quinine 3.08 7-17 >10 16.4 1.2

Ramipril 2.4 0.001-0.01 -/3.5

Ranitidine 3.18 0.1-0.2 2.3(AT,CiT) 1.6

Rifampicin 1.22 0.5-10 3(Cit)/? 1

Salicylic acid 7.24 20-300 >300 >1200 Nlin(4)(lT,AT) 0.14

Sodium aurothiomalate 1-5 ^600 0.26

Sodium cromoglycate 2.14 0.1

Sotalol 3.67 0.5-4 7-14 1.85

Spectinomycin 3.01 7.5-20 1 0.12

Spironolactone 2.4 1.6(Ci = )/19 14

Streptokinase - 1.4 0.016
Streptomycin 1.72 peak: 20-25 >30 2.4 0.26

trough: 1-4 >8

Sulfadoxine 3.22 100 184
Sulindac 2.81 7/16 2
Sulphadiazine 4.0 100-150 7-17 0.9

Sulphamethoxazole 3.95 50-200 10(Ci = ) 0.3

Sulphinpyrazone 2.47 - 4/18 0.74

Sulpiride 2.93 <0.5 5.5 0.9

Tamoxifen 2.69 - 170/310
Teicoplanin 0.53 30-100 0.6

Temazepam 3.33 0.4-0.9 13(Ci = >/12(Ci = ) 1.1

Temocillin 2.41 50-250 5 0.27

Tenoxicam 2.96 10-15 70

Terazosin 2.58 11 0.8

Terbutaline 4.43 0.003-0.007 >0.04 16 1.4

Terfenadine 2.12 -/17

Tetracycline 2.25 0.5-2 6.8 1.3

Thallium 4.89 < 0.005 >0.1

322
 CLINICAL PHARMACOLOGY
0. Active metabolites Extra dose Clinical

Name Potency after dialysis application

0.99 4-OH-propranolol x 1 ? (unlikely) P, +2 -antagonist,

II-anti-arrhythmic

0.9 ? (unlikely) Antithyroid drug

0.99 nH,nP Tricyclic antidepressant

0.04 ? Sympathomimetic
0.99 ? Antituberculous drug
•
0.15 ? Cholinesterase inhibitor
0.99 ? ? (unlikley) Antimalarial
0.95 nH,nP Barbiturate hypnotic
pHi(0.8) 3-OH-quinidine xO.6 (H),(P),Itx:H Ia-anti-arrhythmic
pHl(0.85) H.nP Antimalarial
0.99 Ramiprilat Prodrug ? ACE inhibitor

0.3 H,p H 2 -antagonist

0.9 Desacetyl-rifampicin XI nH,nP,Itx:H Antituberculous drug
pHt(0.98-0.7) H,Itx:H Salicylate

0.3 nH Antirheumatic
0.6 ? Mast cell stabilizer

0.25 - H,P + III

P, +2 -antagonist, 11

anti-arrhythmic
0.1 H Antibiotic
0.99 Canrenone ? Aldosterone antagonist
0.99 ? Thrombolytic
0.5 ~ H,P Aminoglycoside
antibiotic

0.6 ? (unlikely) Antimalarial

0.99 Sulindac sulphide Prodrug ? (unlikely) Indole NSAID
0.4 7 Short-acting sulphonamide
0.65 H,nP Medium-duration
sulphonamide
0.6 N-OH-phenyl-S. Active nH Uricosuric
0.12 - 7 Antipsychotic
0.99 N-desmethyl-tamox. X 1.9 ? (unlikely) Anti-oestrogen
0.05 - nH,nP Antibiotic
0.98 (Oxazepam) nH,nP Benzodiazepine
0.3 H,nP (i-lactamase-resistant

penicillin

0.99 - 7 Oxicam NSAID

0.9 ? (unlikely) a,-antagonist
0.43 - ? (3 r agonist
0.99 (X0.3) ? (unlikley) H,-antagonist
0.4 nH,nP Short-acting tetracycline
- Itx:H Heavy metal

323
MEMORIX CLINICAL MEDICINE

Drug Factor Plasma concentration (mg/l) HLT V,

Therap. Toxic Lethal l/kg

Theophylline 5.55 10-20 >20 >30 Nlin(9)(NT,U,Gl, 0.5

Sl,Cit,HFt)
Thiopentone 4.13 7-130 10-400 It 3 min, a: 47 min
Nlin(9)AT)/22 2.3

Thioridazine 2.7 0.2-2.6 >10 >(1-)13 20/?

Thyroxine 1.29 0.04-0.13 110 0.15

Ticarcillin 2.6 50-350 1.2 0.21

Timolol 3.16 0.005-0.01 4-8 2.1

Tinidazole 4.04 <25 15 0.75

Tobramycin 2.14 peak:6-10 >12 2(Nt) 0.25

trough: < 2 >2

Tocainide 5.2 4-10 >10 12.5(CiT,HF=) 3
Tolazamide 3.21 in.

Tolbutamide 3.7 50-250 >640 7(Nt,lT) 0.12

Tolmetin 3.89 37 >60 5 0.09

Tramadol 3.8 7/9 3.3

Tranexamic acid 6.36 2.3

Tranylcypromine 7.51 0.01-0.04 2

Trazodone 2.69 0.07-1.7 >2 5(AT) 1

Triamcinolone 2.54 1.4 1.8

Triamterene 3.95 4.2(Cit)/3 2.5

Tribavarin 4.09 p:l,T27 8.7

Trifluoperazine 2.45 <0.8 > 1.2-3 >3-8

Triiodothyronine 1.54 ^48 0.5

Trimethoprim 3.44 0.5-12 8.8(C>l,Ci = ) 2

Trimipramine 3.4 24 31

Tubocurarine 1.47 0.5-1.2 3.8 0.3

Urea 16.65

Urokinase - 0.3

Ursodeoxycholic acid 2.55 100

Valproate 6.93 50-100 >200 12.2(CiT) 0.14

Vancomycin 0.67 peak: 30-40 >80 6(CiT) 0.47

trough: 5-10 >20

Vecuronium 1.57 0.2-0.4 1.5 0.21

Verapamil 2.2 0.02-0.8 >2 Nlin(4.8)(CiT)/10 5.3

324
 CLINICAL PHARMACOLOGY
Q. Active metabolites Extra dose Clinical

Name Potency after dialysis application

0.87 H,(P),Itx:KP Bronchodilator

0.99 (Pentobarbitone) ? (unlikely) Intravenous barbiturate

anaesthetic

0.99 Mesoridazine x2 ? (unlikley) Antipsychotic

0.99 Triiodothyronine x4 ? Thyroid hormone
0.14 H,(P) Penicillin active against

Pseudomonas
0.8 - nH P, + .-antagonist

0.8 H Antiprotozoal,
anti-anaerobic

0.02 - H,P Aminoglycoside

antibiotic

pHi(0.6) - H Ib-anti-arrhythmic
0.85 3 weakly active ? Sulphonylurea
0.99 OH-tolb., Carboxy-tol. nH Sulphonylurea
0.89 - ? (unlikley) Indole NSAID
0.7 ? (unlikely) Opiate analgesic
0.03 ? Plasmin inhibitor
0.95 ? Irreversible MAO
inhibitor

0.99 ? Antidepressant
0.99 ? Glucocorticoid
0.95 OH-triamterene ? K + -sparing diuretic
0.65 ? (unlikely) Antiviral (RSV)
nH Antipsychotic
0.99 ? Thyroid hormone
0.4 H,nP,Itx:H Antibacterial
0.99 ? (unlikley) Tricyclic antidepressant

0.37 H Non-depolarizing muscle

relaxant

H,P Osmotic diuretic

nP Thrombolytic
0.99 ? (unlikely) Cholesterol gallstone
dissolvant
0.99 ? (H),nP Anticonvulsant
0.05 - nH,(P?) Antibiotic

0.8 (3a-deacetyl-vecuronium) ? Non-depolarizing muscle

relaxant
0.97 Norverapamil (X0.2) nH,nP Type I calcium-channel
blocker

325
MEMORIX CLINICAL MEDICINE

Drug Factor Plasma concentration (mg/1) HLT v<

Therap. Toxic Lethal l/kg

Vigabatrin 7.74 7(At) 0.8

Vinblastine 1.23 25 27
Vincristine 1.21 85 8.4

Vindesine 1.33 24 8.8

Vitamin K 2.22 0.0004-0.0012 1.7/?

Warfarin 3.24 1-10 46 0.11

Zidovudine (AZT) 3.74 0.27-1.5 l.l(Cit) 1.4

Zinc 15.3 0.5-1.5

Zolpidem 3.25 <0.2 1.7(AT) 0.5

Zopiclone 2.57 5(AT, CiT)/?

Abbreviations:
A Alteration of HLT in old age.
Ci Alteration of HLT in cirrhosis.
HF Alteration of HLT in heart failure.
H, P During haemo- or peritoneal dialysis, the clearance of the substance increases by
more than 30%; an additional dose after the dialysis is necessary; the administration

of the substance after the dialysis is advisable.

HLT Elimination half life; (J-half life (if not stated otherwise).
Itx:H, Itx:P, In intoxication with the relevant product the elimination can be substantially

Itx:KP accelerated by haemo- or peritoneal dialysis or by charcoal perfusion.

C Alteration of the HLT in children.

nH,nP During a haemo- or peritoneal dialysis the clearance of the product increases by less

than 30%; an additional dose after the dialysis is not necessary.

N Alteration of the HLT in neonates.
Nlin The kinetics of the substance are non-linear; doubling of the dose can therefore lead

to a prolonged HLT and a disproportionate increase in the serum concentration. A

typical 'HLT is given in brackets.
NSAID Non-steroidal anti-inflammatory drug.

PH The pH reference in the Q column indicates a pH-dependent renal excretion of the

product. Basic substances are generally eliminated better in an acid, and acid
substances better in an alkaline urine. The arrow indicates the alteration of pH which
leads to increased excretion.

Prodrug Inactive substance that is metabolized in the body to the active substance.

Go Fraction eliminated by non-renal mechanisms.

s Alteration of the HLT in smokers.
Alteration of the HLT in infants.

T,i,= Increase, decrease, unchanged.

Initial (rapid) distribution HLT.

Distribution HLT.
Data after the oblique stroke refer to the active metabolites.

326
 CLINICAL PHARMACOLOGY
G. Active metabolites Extra dose Clinical

Name Potency after dialysis application

0.35 ? Anticonvulsant
0.95 ? (unlikely) Antimetabolite
0.95 nH Antimetabolite
? (unlikley) Antimetabolite
0.99 Vit.K-2,3,-epoxide ? (unlikely) Coumarin antagonist
0.99 4 different ones ( +) nH,nP Oral anticoagulant
0.81 - ? Antiviral (HIV)
- 7 Trace element
0.99 - nH Hypnotic
0.95 < X 1 nH Hypnotic

Note:
1. The column marked 'Factor' gives the conversion factor from metric to SI units (conversion from
mg/1 to umol/1). The calculation is derived from the following formula: 1000 (mg/l)/molecular weight
(g/mol) = umol/1. In combined preparations the factors vary for the individual components.
Reversal of the formula permits the calculation of the molecular weight and thus gives an indication
of the ability to remove the relevant substance by dialysis.
2. The data in general refer to healthy subjects.

3. Plasma concentrations are indicated as therapeutic, toxic and potentially life threatening ('lethal').

Values in the first column represent either clearly defined limits (for trough values = blood
collection at lowest level) of an optimal effect (bold print) or concentrations found with
conventional doses (normal print).
4 Known active metabolites are shown in the relevant column; their HLT, if known, is given after the
HLT of the primary substance (cf. 5). The metabolite is given in brackets if under clinical

conditions only small amounts of metabolite are present, or if the inactivation of the metabolite is

so rapid that it does not have any clinical effect.

5. The column 'Potency' indicates the relative potency of the active metabolites compared with the
primary substance; the value is given in brackets if the only data are from animal experiments.
Irrelevant, weak activity is indicated by ( + ).

327
MEMORIX CLINICAL MEDICINE

Drugs in pregnancy
The following list should not invalidate the general principle that drug administration
during pregnancy should be kept to the absolute minimum.

Group A: Clinical studies have shown no evidence of an increased risk of fetal

malformation in the first trimester. Similarly there is no evidence of any
increased risk in the subsequent months of the pregnancy.

Digoxin, magnesium sulphate, nystatin (vaginal), pyridoxin (vitamin B 6 ), thiamin

(vitamin B,), thyroxine

Group B: No risk in animal studies, but adequate clinical studies not available; or no
risk in clinical studies, but an increased risk has been demonstrated in
animal studies.

Acebutolol, albumin, amiloride, azatadine, aztreonam, brompheniramine, buspirone,

carnitine, cephalosporins, chlorhexidine, chlorpheniramine, cinoxacin, clemastine,
clindamycin (topical), cromoglycate, cyclizine, desmopressin, dimenhydrinate,
diphenhydramine, dipyridamole, doxapram, erythromycin, ethacrynic acid, etidronate,
famotidine, fluoxetine, gemfibrozil, glibenclamide, gonadorelin, indapamide, insulin,
ipratropium bromide, iron, ketoprofen, lindane (topical), lignocaine, maprotiline,
metoclopramide, metolazone, metoprolol, mupirocin (topical), naloxone, naproxen,
penicillins, permethrin (topical), pindolol, praziquantel, prilocaine, probucol,
ranitidine, ritrodine, terbutaline, tranexamic acid, tretinoin (topical), triamterene,
triprolidine, urokinase

Drugs and breast feeding

(not excreted in breast milk or not absorbed by the infant)

Ascorbic acid, antacids, antihistamines, barbiturates(in low dose), benzodiazepines (in

low dose), bisacodyl, cephalosporins, clindamycin, clonidine, codeine, corticosteroids
(in low dose), dextropropoxyphene, dichloralphenazone, digoxin, erythromycin, folic
acid, heparin, ibuprofen, iron, ketoprofen, mefenamic acid, methyldopa,
metronidazole, monoamine oxidase inhibitors, nitrofurantoin, paracetamol, penicillins,
pentazocine, pethidine, phenothiazines (in low dose), rifampicin, salicylate (in low
dose), tricyclics, B-vitamins

328
 CLINICAL PHARMACOLOGY
Drug metabolism

1. Genetic polymorphisms

Acetylator status

Enzyme: Hepatic yV-acetyltransferase

Inheritance: Autosomal recessive
Test: Sulphadimidine test

Drugs affected: Aminoglutethimide, clonazepam, caffeine, dapsone,

hydralazine, isoniazid, nitrazepam, phenelzine,
procainamide, sulphadimidine, sulphasalazine,
thymoxamine
% slow metabolizers: Egyptians 83%, Americans (white) 58%, Americans
(black) 50%, Canadian Eskimos 0-5%, Chinese 20%,
Swiss 61%, Orientals 15%, South Africans (black)
41%

Hydroxylator status:

Enzyme: Debrisoquine-4-hydroxylase (cytochrome P450dfc,;

cytochrome P450 IID 6 )
Inheritance: Autosomal recessive
Test: Dextromethorphan test
Drugs affected: (Amitriptyline), (clomipramine), codeine,
debrisoquine, desipramine, dextromethorphan,
diltiazem, flecainide, (imipramine), indoramin,
metoprolol, nortriptyline, phenformin, propafenone,
propranolol, timolol

Pure inhibitors: Cimetidine, diphenhydramine, methotrimeprazine,

orphenadrine, quinidine, thioridazine

% slow metabolizers: Egyptians 1%, Chinese 0.7%, Japanese 0%, Nigerians

0%, Saudi Arabians 1%, whites 3-10%

Mephenytoinpolymorphism

Enzyme: 5-mephenytoin-hydroxylase
Inheritance: Autosomal recessive
Test: Mephenytoin test
Drugs affected: (Hexobarbitone), mephobarbitone, mephenytoin

Pure inhibitors: Ketoconazole

% slow metabolizers: White 5%, Japanese 20%, Cuna-Indians (Panama) 0%

329
MEMORIX CLINICAL MEDICINE
Cholinesterase deficiency

Enzyme: Serum cholinesterase (pseudocholinesterase)

Inheritance: Autosomal recessive
Test: Dibucaine inhibition test

Affected drugs: Suxamethonium

% slow metabolizers: Thais 0%, Japanese 0%, Koreans 0%, Indians 0%,
blacks rarely, whites frequently

Glucose-6-phosphate dehydrogenase deficiency:

Enzyme: G-6-P-D

Inheritance: X-chromosomal, incomplete dominant

Haemolysis-inducing drugs: Acetylsalicylic acid, chloramphenicol, dimercaprol,

naphthalene, nitrofurantoin, primaquine, probenecid,
quinidine, quinine, sulphonamides, vitamin K,
analgesics, antimalarials

% slow metabolizers: Africans 20%, Mediterraneans 35%, Chinese 20-30%,

Thais 20%

2. Enzyme inducers

Enzyme inducers produce an increase in the amount and activity of a specific,

generally hepatic, enzyme. They are usually lipophilic, often substrates of the induced
enzyme, and commonly have a long half life. Enzyme induction usually appears after a
few days and usually persists for 2-3 weeks, depending on the half life of the enzyme
concerned. Increased enzyme activity frequently leads to a clinically significant
reduction of the half life of the relevant substrate, necessitating dosage adjustments.

Substances that induce the metabolism of other substances:

a) Foodstuffs, etc.: Alcohol, grilled meat (barbecue), cabbage, cauliflower, tobacco

b) Drugs: Aminoglutethimide, amylobarbitone, ascorbic acid, carbamazepine, chloral

hydrate, chlorpromazine, clofibrate, DDT, diazepam, diphenhydramine, fenofibrate,
griseofulvin,meprobamate, nicotine, orphenadrine, phenobarbitone, phenylbutazone,
phenytoin, progesterone, quinalbarbitone, rifampicin, spironolactone, testosterone,
theophylline, tolbutamide, warfarin

Substances that induce their own metabolism (auto-inducers):

Carbamazepine, meprobamate, glyceryl trinitrate, phenobarbitone, phenylbutazone,

phenytoin, probenecid, tolbutamide

330
 CLINICAL PHARMACOLOGY
Side effects of drugs: central nervous system

Drug-induced coma:
Antihistamines, barbiturates, benzodiazepines, betablockers, chloral hydrate,
lignocaine, lithium, opiates, phenothiazines, salicylates, tricyclics, vitamin D
Hallucinations:
Amphetamine, anticholinergics, antihistamines, atropine, bromocriptine, cyclosporin,
LSD, mescaline, mexiletine, PCP, salicylates, tricyclics, yohimbine
cocaine,

Ophthalmic changes:
Mydriasis: Amphetamine, anticholinergics, (atropine, hyoscine), antihistamines,
baclofen, barbiturates (in coma), cocaine, LSD, mescaline, methanol, neuroleptics,
pethidine, phenylpropanolamine, sympathomimetics, tricyclics, yohimbine, withdrawal
syndromes

Miosis: Baclofen, cholinergics (physostigmine), clonidine, (neuroleptics), opiates

(except pethidine), organophosphates

Nystagmus: Alcohol, baclofen, barbiturates, carbamazepine, hydroxychloroquine,

lithium, mexiletine, pemoline, phenytoin, vitamin A intoxication

Sweating (Poisoning):
Acetylcholinesterase inhibitors, amphetamine, barbiturates, cocaine, caffeine, LSD,
mescaline, nicotine, organophosphates, phenylpropanolamine, mushroom poisoning,
salicylates, sympathomimetics, withdrawal, hypoglycaemia

Drug-induced aseptic meningitis:

Azathioprine, carbamazepine, cytarabine, immunoglobulin, isoniazid, NSAID
(ibuprofen, naproxen, sulindac, tolmetin), penicillin, sulphonamides (sulphamethizole,
co-trimoxazole)

Promotion of convulsive phenomena:

Drug-induced epileptic attacks and epileptiform manifestations with therapeutic doses in
non-epileptic patients:

Drug group In therapeutic concentrations In toxic doses

Anaesthetics Enfluran, etomidate, ketamine

Anti-asthmatics Theophylline
Antibiotics Ciprofloxacin, cycloserine, Cephalosporins, nalidixic acid, (rifampicin)
imipenem/cilastatin, isoniazid,
penicillins
Anticholinergics Hyoscine Anticholinergics
Antidepressants
Tricyclics Amitriptyline, amoxapine,
clomipramine, desipramine,
(doxepin), nortriptyline, imipramine
Non-tricyclics Amoxapine, (fluoxetine), (lithium), Lithium (monoamine oxidase inhibitors)
maprotiline, mianserin
Antiepileptics Phenytoin (in high doses)
Antihistamines Dimenhydrinate, diphenhydramine
Antimalarial drugs Chloroquine Chloroquine, hydroxychloroquine, quinine
Antipyretics, NSAID Mefenamic acid, ibuprofen, indomethacin,
salicylates
Antiviral drugs Acyclovir, amantadine
P-blockers Metoprolol
Cytostatic drugs Busulphan, chlorambucil, Vinca alkaloids
methotrexate

331
MEMORIX CLINICAL MEDICINE

Drug group

Illegaldrugs Amphetamine, cocaine, 'crack', pemoline

Local anaesthetics Buvicaine, lignocaine, procaine
Opiates Alfentanil, fentanyl, pethidine Morphine
Phenothiazines Chlorpromazine, clozapine,
promazine
Others Bismuth salts Camphor, clonidine, CO, cyanide,
dantrolene, lead, quinidine, strychnine,
thiamin

Smaller risk of convulsive attacks: Doxepin, fluphenazine, haloperidol, pimozide, thioridazine, trazodone

Side effects of drugs: gastrointestinal tract

Drug-induced pancreatitis:
(Asymptomatic elevation of serum amylase and/or pancreatitis)
The prevalence of acute drug-induced very low.
pancreatitis is

(Exceptions: azathioprine/mercaptopurine)
Incubation period: As a rule, days to weeks, occasionally years
Course: mostly benign, occasionally, however, fatal
Diagnosis: by exclusion. Note: Re-exposure can be dangerous

Drug Symptom-free interval

Established relationship:
Azathioprine 2-3 weeks
Chlorothiazide 1-4 months (rarely years)
Frusemide 3-5 weeks
Hydrochlorothiazide 1-4 months (rarely years)
Mercaptopurine 1-5 weeks
Methyldopa 1-7 days
Oestrogens <3 months
Sulphonamides 1-2 weeks
Sulindac 1month to 5 years
Tetracycline <3 weeks
Valproate Days to years

Probable relationship:
Asparaginase, cimetidine, cisplatin, cytarabine, glucocorticoids, pentamidine,
rifampicin

Hiccups:
Drugs that can precipitate hiccup:
Chlordiazipoxide, dexamethasone, diazepam, fluconazole, methohexitonc, methyldopa,
methylprednisolone, mexiletine, midazolam, nicotine, nikethamide, phenobarbitone,
propofol, thiopentone

Disturbances of temperature:
Drug fever
Definition: Development of raised body temperature related in time to administration
of a specific drug and normalization of temperature after withdrawal of the drug.
Rechallenge with the same substance produces recurrence of fever.
Clinical picture: Often rigors, often indistinguishable from bacterial infection.
Pulse usually > 100/min (no relative bradycardia); hypotension infrequent.

332
 CLINICAL PHARMACOLOGY
Accompanying symptoms: Myalgia >
leucocytosis (mild) eosinophilia > rash >
>
headache > others. Lag time: short with antineoplastic substances (on average 0.5
days); days to weeks for other substances
Resolution: as a rule within 48 h

Rule of thumb: Withdrawal syndromes lead to elevation of temperature, intoxications

more commonly to hypothermia.

Elevation of temperature
Frequently:
Amphotericin B, ampicillin, asparaginase, carboprost, dinoprost (prostaglandin E 2 ),

methyldopa, penicillin and derivatives, procainamide,

isoniazid, iodide, lisinopril,
prostaglandin E, (alprostadil), quinidine, sulphonamides, co-trimoxazole

Occasionally:
Acetylsalicylic acid, adriamycin, allopurinol, antihistamines, azathioprine,
barbiturates, bleomycin, carbamazepine, cephalosporins, chlorambucil,
chlorpromazine, cimetidine, cisplatin, clofibrate, clozapine, colistin, cytarabine,
dacarbazine, dactinomycin, dantrolene, diazoxide, folic acid, haloperidol,
hydralazine, hydroxyurea, ibuprofen, interferon, levamisole, mebendazole,
mercaptopurine, methotrexate, metoclopramide, nifedipine, nitrofurantoin,
oxprenolol, PAS, penicillamine, pentazocine, plicamycin, prazosin, procarbazine,
propylthiouracil, ritodrine, streptokinase, streptomycin, sulindac, tetracycline,
terazosin, thioridazine, tolmetin, triamterine, vancomycin, vinblastine, vincristine

In intoxications with:
Amitriptyline, amphetamine, anticholinergics, atropine, cocaine, crack, doxepin,
LSD, MAO inhibitors, metal vapours, phenothiazines, salicylates,
sympathomimetics, thallium, thyroxine

Practically never:
Choramphenicol, digitalis glycosides, insulins

Temperature reduction
Intoxication:
Barbiturates, chloral hydrate, glutethimide, haloperidol, tricyclic antidepressants

Side effects of drugs: cardiac

Torsade de pointes
(polymorphic ventricular tachycardia with widening of QTc)
Anti-arrhythmics Psychotropic drugs Antibiotics
Quinidine Thioridazine Erythromycin
Mexiletine Tricyclics Pentamidine
Disopyramide Co-trimoxazole
Procainamide Others
Tocainide Frusemide Intoxications
Propafenone Prednisolone Chloral hydrate
Sotalol Astemizole
Bretylium

333
MEMORIX CLINICAL MEDICINE

Side effects of drugs: genitourinary system

Discoloration of urine by drugs
Drug Colour
Amitriptyline Blue-green
Desferoxamine Reddish
Doxorubicin Red
Doxycycline Yellow
Methyldopa Darkens on standing
Methylene blue Dark green-blue
Metronidazole Darkens on standing
Mitozantrone Blue-green
Nitrofurantoin Darkens on standing
Phenothiazine Darkens on standing
Riboflavin (vitamin B2) Yellow-green
Rifampicin Red
Sulphasalazine Red
Triamterene Blue-green

Precipitation of drugs in urine

Procedure with appearance of unusual crystalluria:
Obtain history of drug intake over preceding 48 h, consider change of drug therapy,
infrared spectrophotometry of the urinary crystals.
Drug Crystal appearance
Acetazolamide
Acyclovir
Allopurinol Xanthine crystals
Amiloride
Amoxicillin Long colourless needle-formed rods of different lengths
Ampicillin Fine rods with square cross-section
Co-trimoxazole Rhomboid, hexagonal, greyish
Methotrexate
Nitrofurantoin Purple, irregular
Norfloxacin
Sulphadiazine Sea-urchin-shaped aggregation of fine rods (wheat sheaves)
Sulphasalazine
Triamterene Large aggregates: centrifuged deposit: yellow

Intoxications
Ethylene glycol Needles and envelopes
Primidone

334
 .

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colloid volume substitutes. Lancet, I, 466.

Rodman, G.P. (ed.) (1973) Primer on the rheumatic diseases. JAMA, 224, 662.

Sandoz, P. (1988) Abklarung der Hamaturie Heute. Schweiz. Rundsch. Med. Prax., 77,
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Sanford, J.P. (1991) Guide to Antimicrobial Therapy. Antimicrobial Therapy, West

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Schaad, U.B. (1986) Treatment of bacterial meningitis. Eur. J. Clin. Microbiol., 5, 492.

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Schulze-Werninghaus, G. and Debelic, M. (eds) (1988) Asthma. Grundlagen,

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Schupbach, J. (1991) Retroviren und AIDS, Part II. DIA-GM, 3, 228.

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Stamm, W.E. et al. (1989) Urinary tract infections: from pathogenesis to treatment. J.

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Stohr,M. and Riffel, B. (1988) Nerven- und Nervernwurzellasionen, Edition Medizin,

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Stollermann, G.H. et al. (1965) Jones criteria (revised) for guidance in the diagnosis of
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339
MEMORIX CLINICAL MEDICINE
WHO/ISFC (1981) Task Force on definition and classification of cardiac myopathies.
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Zimmerli, W. et al. (1991) Blood, 77, 393.

340
 1

INDEX
Index

Abdomen, acute 138-9 Antiemetics 234 206

Abdominal arteries 88 Anti-inflammatory drugs, blood-CSF barrier
Abducens nerve 270 non -steroid 265 disturbances 267
Accessory nerve 271 Antituberculous drugs coagulation
Acid-base disturbances 114,196 coagulation factors
126 Antiviral agents 182 219
estimation of 128 Aortic dissections 86 drugs affecting 219
Acid-base nomogram Arteries oral anticoagulants
127 abdominal 88 222-3
Acidosis 126 aortic dissections 86 process of 217
Activated charcoal carotid 280, 283 tests 218
administration 120 cerebral 280,282 thrombolytics 220
Acute abdomen 138-9 coronary 59 thromboplastins 221
Addison's disease 240 leg 90 Coombs' test 208
Addisonian crisis 243 pelvic 89 gas analysis 128
ADH (antidiuretic peripheral vascular haemorrhagic
hormone): syndrome of disease 86 diatheses 216
inappropriate ADH ultrasonography of hyperlipidaemias 100
secretion 131 282-3 lipid-lowering drugs
Adrenal glands 240 Arthritis 101
ultrasound of 137 osteoarthritis 33 treatment of 102-3
Adrenogenital syndrome rheumatoid arthritis iron metabolism 204
240 261 leukaemia 211
AIDS/HIV Asbestosis 116 myelodysplastic
definition and Ascites 147, 178 syndrome 211
classification of Aspirates, interpretation normal chemical values
184-5 of 178 10
investigation of 186 Asthma normal enzyme values
therapy for bronchial 108 11
opportunistic chronic, management normal haematological
infections in 187-8 of 109 values 204
Alcohol Auditory vestibular nerve polycythaemia vera 207
blood/plasma 11 271 protein electrophoresis
intoxication 11 Auscultation areas 51 201
Alkalosis 126 sedimentation
Allen test 86 Bacterial meningitis 178, rates 201
Allergic reactions 193 transfusion of 224
anaphylaxis 214, 215 Bacteriological stains 177 uraemia 167
types of 214 Balloon catheter 76 see also Haemorrhage
Anaemia Basilar arteries 280 Blood vessels
investigation of 207 Beta-adrenergic blocking abdominal arteries 88
renal 163 agents 84 aortic dissections 86
Anaphylaxis 214,215 Bleeding, see carotid arteries 280,
Antabuse reaction 1 Haemorrhage 283
Anti-arrhythmic agents Blood central venous pressure
82-3 alcohol levels 11 50
Anti-asthmatic drugs 109 anaemia 207 cerebral arteries 280,
Anticoagulants 222-3 blood cells 202-3 282
Anticonvulsant drugs 285 formation of 205 coronary arteries 59
Antidepressants 122 red cell morphology leg arteries 90

341
INDEX
Blood vessels contd Cardiomyopathies 77 Glasgow coma scale 278
leg veins 91-2 Cardiopulmonary Computed tomography
pelvic arteries 89 resuscitation 117 (CT) scanning
peripheral vascular Carotid arteries 280, 283 bronchopulmonary
disease 86 Catheter(s) segments 25
thromboembolism 220 balloon 76 cross-sectional
ultrasonography of sizes 6 topography 39-42
282-3 Central nervous system pelvic 43
Body surface area, (CNS) Consciousness
determination of 1 infection of 179, 193-4, disturbances of 279
Body temperature 267 syncope 286
disturbances: as drug see also Brain; see also Coma
side effect 332-3 Nerve(s); Spine Conversion scales 12-15
Bone Central venous pressure imperial/US-metric
magnetic resonance 50 16-18
imaging of 46-7 Cerebral arteries 280, 282 radiological units 19
metastases in 35 Cerebral infarction 281 Convulsions, see Epileptic
osteoporosis 32, 264 Cerebral ischaemia 281 seizures
skeletal X-rays 32-5 Cerebrospinal fluid (CSF) Coombs' test 208
skull CT scanning 44 blood-CSF barrier Corneal reflex 268
skull X-rays 36-8 disturbances 267 Coronary arteries 59
Bone marrow cells 202-3 interpretation of Corticosteroids 244
Brain aspirates 178 Cranial nerves 270-1
abscess 193, 194 Charcoal, activated, trigeminal nerve 268,
cerebral arteries 280 administration of 120 270
cerebral function test Chemotherapy 225 Creatinine clearance 162
124 antiemetics and 234 Crohn's disease 142-3
cerebral infarction 281 dose reduction of 233 Crystalluria 334
cerebral ischaemia 281 mode of action of 231 Cushing's syndrome 241
CT scanning of 44 side effects of 232 Cytostatic drugs, see
magnetic resonance Chest Chemotherapy
imaging of 46-7 CT cross-sectional
Brain death, confirmation topography 39-42 Death, confirmation of
of 173 X-rays 21-31 173
Breast feeding, drugs and Cholesterol, see Delivery, determination
328 Hyperlipidaemias of expected date of 2
Bronchial asthma 108 Cigarette consumption, Demographic
Bronchial carcinoma estimation of 105 parameters 8
diagnosis of 110 Cirrhosis 145-6 Dentition, chart of 5
histology of 112 Coagulation Diabetes mellitus
staging of 110-11 coagulation factors 219 classification of 245
surgery of 113 drugs affecting 219 coma 250-1
oral anticoagulants therapy of 246
Calcium 130 222-3 insulin 247-9
Calcium antagonists, process of 217 oral hypoglycaemics
WHO classification tests 218 246
of 80 thrombolytics 220 Dialysis 172
Carcinoma thromboplastins 221 removal of drugs by 295
bronchial 110-13 Colorectal carcinoma 158 Diuretics 171
colorectal 158 Coma Drugs
gallbladder 150 diabetic 250-1 anti-arrhythmic agents
stomach 157, 158 drug-induced 331 82-3

342
 INDEX
anti-asthmatic 109 electrode positions 52 syndrome of
anticoagulants 222-3 emergency 118 inappropriate ADH
anticonvulsants 285 infarct changes in 64-5 secretion (SIADH)
antidepressants 122 left ventricular 131
antiemetics 234 hypertrophy points tests of 238
antihypertensive system 56 thyroid 239, 243
therapy 95, 98, 99, long-term 52 see also Diabetes
243 normal values 53 mellitus
antituberculous drugs pacemaker testing 85 Endoscopy: of
114, 196 right ventricular gastrointestinal system
antiviral agents 182 hypertrophy points 157-8
beta-adrenergic system 57 Enzyme inducers 330
blocking agents 84 ruler 54 Epidemiological
calcium antagonists 81 systolic and diastolic parameters 8
chemotherapy 225, flow rates 72 Epileptic seizures
231-4 Electrolytes anticonvulsant drugs
corticosteroids 244 calcium 130 285
diabetes therapy 246-9 magnesium 131 284
classification of
diuretics 171 phosphorus 130 drug-induced 331-2
hormone replacement potassium 129 Erythrocytes 202-3
therapy 242 sodium 129 formation 205
infection therapy Emergencies iron metabolism 204
187-8, 189-95 acid-base disturbances morphology 206
interactions of 296-7 126 red urine 169
lipid-lowering 101, cardiopulmonary Erythropoietin, renal
102-3 resuscitation 117 anaemia and 163
metabolism of 329-30 cerebral function test Eye(s)
neuroleptic 123 124 corneal reflex 268
non-steroidal anti- electrocardiograms 118 drug side effects in
inflammatory drugs poisoning 119-21, 331
265 122-3 eye test chart 4
Parkinsonism therapy substance abuse 125 hypertensive
287 suicide risk estimation retinopathy 94
pharmacokinetic 122 pupil size assessment
formulae 291-4 Encephalitis 193, 194 278
pharmacokinetic/ Endocarditis visual field defects 268
toxological data prevention of 73
298-327 therapy of 190 Facial nerve 271
poisoning 119-21 Endocrine system 235-6 Fever (pyrexia) 175-6,
pregnancy and 328 adrenal cortex 240 195
prophylactic 73 corticosteroids 244 Fibromyalgia 262
psychotropic 123 crises in 243
renal failure and 166 Cushing's syndrome Gall bladder
side effects of 99, 122, 241 gallstones 150-1
149, 232,331-4 hormone replacement ultrasound of 136
substance abuse 125 therapy 242 Gastritis 159
multiple endocrine Gastrointestinal system
Ears: hearing tests 5 neoplasia (MEN) acute abdomen 138-9
Echocardiography 62-3 244 anatomy of 133
Electrocardiography normal values 237 ascites 147
(ECG) renal osteodystrophy bleeding 141, 157
axes 55 244 Crohn's disease 142-3
INDEX
Gastrointestinal system non-cardiac Hypercalcaemia 130, 243
contd operation 49 Hypercortisolism 240
endoscopic staging of conducting system of Hyperglycaemic coma
disorders 157-8 79 250-1
function tests 159 diastolic flow rates 72 Hyperkalaemia 129
gallstones 150-1 ECG 52-5, 64, 72 Hyperlipidaemias 100
gastritis 159 echocardiography 62-3 lipid-lowering drugs
ileus 140 endocarditis 73, 190 101
intra-abdominal enlargement of 28-9 treatment of 102-3
infection 192 infarct 64-5 Hypermagnesaemia 131
pancreatitis 144, 157, left ventricular Hypernatraemia 129
332 hypertrophy points Hyperparathyroidism 32
side effects of drugs in system 56 Hyperphosphataemia 130
332-3 normal cardiovascular Hypertension
stomach ulcers 159 values 72, 75 classification of 94
tumours in 157, 158 NYHA criteria 49 investigation of 96-7
ultrasound of 134-7 pacemakers 85 mild 98
Genetic polymorphisms, right ventricular portal 148
drug metabolism and hypertrophy points pulmonary 31
329-30 system 57 treatment of 95, 98,
Glossopharyngeal nerve side effects of drugs in 243
271 333 unwanted effects of
Gram stain preparations sounds 51 99
177 stress testing 58 Hyperventilation 126
Swan-Ganz balloon Hypocalcaemia 130, 243
Haematuria 168, 174 catheter 76 Hypoglossal nerve 271
Haemodialysis 172 systolic flow rates 72 Hypokalaemia 129
Haemorrhage transplantation 78 Hypomagnesaemia 131
gastrointestinal 141, valve abnormalities Hyponatraemia 129
157 66-9 Hypophosphataemia 130
oesophageal varices valve prostheses 70-1 Hypotension
145-6 ventricular orthostatic 93
subarachnoid 278 extrasystoles (VES) syncope 286
Haemorrhagic diatheses 81 Hypothyroidism 239
216 X-rays of 27-9, 60, 61 Hypoventilation 126
Hallucinations, drug- Hepatitis 179
induced 331 chronic active 155 Ileus 140
Headache, differential immunization against Immune system
diagnosis of 288 152 allergic reactions 214,
Hearing tests 5 markers 154 215
Heart serological course of illnesses, assessment of
anti-arrhythmic agents 153 214
82-3 types of 152 immunocompromised
auscultation areas 51 Hepatojugular reflux 50 patients 183
beta-adrenergic Hiccup: as drug side AIDS 184-8
blocking agents 84 effect 332 Immunization 198
block 80 Hip, arthritis of 33 adult 152,200
cardiac cycle 74 HIV, see AIDS/HIV childhood 199
cardiomyopathies 77 Hodgkin's lymphoma 212 Infarction
cardiothoracic ratio 28 Hormones, see Endocrine cardiac 64-5
cardiovascular risk system cerebral 281
assessment before Hyperaldosteronism 240 Infection(s)

344
 1

INDEX
AIDS/HIV 184-8 tubular syndromes 164 pelvis 47
aspirate interpretation ultrasound of 136 retroperitoneal space
178 Knee 47
bacteriological stain arthritis of 33 Measurement
preparations 177 magnetic resonance conversion scales 12-19
central nervous system imaging of 47 SI units of 9
(CNS) 179, 193-4, Kussmaul respiration 126 Medication, see Drugs
267 Meningitis
fever (pyrexia) 175-6, Leg bacterial 178, 193
195 arteries of 90 drug-induced 331
immunization against veins of 91-2 viral 178
152, 198-200 Leukaemia 211 Metabolic acidosis/
immunocompromised Liver alkalosis 126
patients and 183-8 cirrhosis 145-6 Metastases 229
therapy of 187-8, hepatitis 152-5, 179 bone 35
189-95 transplantation of 156 Muscle function testing
antituberculous drugs ultrasound 135 276-7
196 Lung(s) Myelodysplastic
antiviral agents 182 carcinoma of 110-13 syndrome 211
viral 178, 179-82 CT scanning of 25 Myocardial scintigram 60
see also individual function test 107 Myxoedema 243
infections pleural effusion 106,
Inflammatory arthritis 33 178 Needle sizes 6
Infusions, drip rate of 7 pneumoconiosis 116 Nephritis 164
Insulin 247-9 pneumonia therapy Nephrolithiasis 164, 168
Iron metabolism 204 190-1 Nephrological formulae
Ischaemia, cerebral 281 pulmonary 162
hypertension 31 Nephrotic syndrome 164
Jaundice 149 pulmonary venous Nerve(s)
Joint(s) congestion 30-1 cervical root
aspirates 260 tuberculosis compression
hip 33 testing for 115 syndromes 274
knee 33, 47 treatment of 114, cranial 268, 270-1
mobility examination 196 lumbosacral root
255-6 X-rays of 23, 26, 30-1 compression
spondylarthropathies 263 Lymph nodes syndromes 275
distribution of 1 1 muscle function
Kidney enlargement of 209 testing 276-7
anatomy of 161 Hodgkin's lymphoma neurological
calculi (nephrolithiasis) 212 examination 269
164, 168 non-Hodgkin's polyneuropathies 272
dialysis 172 lymphoma 213 sensory dermatomes
failure 164, 165 X-rays of 24 273
management of 166 Lymphadenopathy 179 Neuroleptic drugs 123
nephritis 164 Neutropenia 195
nephrotic syndrome 164 Magnesium 131 Neutrophilia 210
obstruction 164 Magnetic resonance Non-Hodgkin's
pyelonephritis 164 imaging (MRI) lymphoma 213
renal anaemia 163 head 46-7 Non-steroidal anti-
renal osteodystrophy image planes 47 inflammatory drugs 265
244 indications for 45
transplantation of 174 knee joint 47 Oculomotor nerve 270

345
INDEX
Oesophagus vesicle formation 120 inflammatory drugs
oesophageal varices Polycythaemia vera 207 265
157 Polyneuropathies 272 rheumatological status
haemorrhage 145-6 Portal hypertension 148 254
reflux oesophagitis 157 Potassium 129 Rinne hearing test 5
Olfactory nerve 270 Pregnancy
Optic nerve 270 determination of Scintigram 60
Organ transplantation, see expected date of Seizures, see Epileptic
Transplantation delivery 2 seizures
Osteoarthritis 33 drugs and 328 SI units 9
Osteodystrophy, renal Protein electrophoresis Silicosis 116
244 201 Skeletal X-rays 32-5
Osteolysis 32 Proteinuria 168 Skin
Osteomalacia 32 Psychotropic drugs 123 alterations in 3
Osteonecrosis 32 Pyelonephritis 164 lesions of, classification
Osteopenia 32 Pyrexia 175 of 3
Osteoporosis 32, 264 with neutropenia 195 Skull
Osteosclerosis 32 of undetermined origin CT scanning of 44
176 magnetic resonance
Pacemakers 85 imaging of 46
Pancreas Radiology X-rays of 36-8
pancreatitis 144, 157 CT scanning 25, 39-44 Sodium 129
drug-induced 332 magnetic resonance Spine
ultrasound 136 imaging 45-7 cervical root
Parkinsonism, therapy radiological unit compression
for 287 conversion scales 19 syndromes 274
Pelvis radio-opaque drugs 120 lumbosacral root
CT scanning of 43 X-rays 20-39,60,61, compression
pelvic arteries 89 139 syndromes 275
Peripheral vascular Renal disorders, see magnetic resonance
disease 86 Kidney imaging of 46
Peritoneal dialysis 172 Respiratory acidosis/ non-inflammatory
Pharmacology, see Drugs alkalosis 126 changes in 34
Phosphorus 130 Resuscitation rheumatological
Plasmacytoma 213 cardiopulmonary 117 syndromes 263
Pleural effusion cardiac arrest 118 sensory dermatomes
differential diagnosis of Retinopathy, and 273
106 hypertension and 94 Spleen
interpretation of Rheumatic fever 261 splenomegaly,
aspirates 178 Rheumatoid arthritis 261 differential diagnosis
Pneumoconiosis, Rheumatology of 209
classification of 116 check-up of ultrasound of 137
Pneumonia, therapy of rheumatological Spondylarthropathies 263
190-1 patient 253 Stomach
Poisoning classification of carcinoma of 157, 158
activated charcoal illnesses 257-8, gastritis 159
administration 120 261-4 ulcers 159
antidotes 119 joint mobility Stress testing 58
fetor 120 examination 255-6 Subarachnoid
information centres laboratory haemorrhage 278
121 investigations 259-60 Substance abuse 125
radio-opaque drugs 120 non-steroidal anti- Suicide: risk estimation

346
 INDEX
122 early warning proteinuria 168
Sweating: as drug side symptoms of 227 red, tests of 169
effect 331 gallbladder 150
Syncope 286 Hodgkin's lymphoma Vaccination, see
Syndrome of 212 Immunization
inappropriate ADH markers of 227 Vagus nerve 271
secretion (SI ADH) 131 metastases 229 Varicose veins 92
Syphilis 197 bone 35 Veins
Systemic lupus multiple endocrine central venous pressure
erythematosus 261 neoplasia (MEN) 50
244 leg 91-2
Teeth: chart of dentition neurological syndromes Ventriculogram 61
5 of 289 Vertebral arteries 280
Temperature non-Hodgkin's Vertigo, differential
disturbances: as drug lymphoma 213 diagnosis of 289
side effect 332-3 plasmacytoma 213 Viral infections 179
Tetracyclics 122 prognoses 226 AIDS/HIV 184-8
Thromboembolism 220 staging of 110-11,228 antiviral agents 182
Thrombolytics 220 stomach 157, 158 hepatitis 152-5, 179
Thromboplastins 221 therapy of 225 laboratory diagnosis
Thyroid gland cytostatic drugs 225, methods 180
hypothyroidism 239 231-4 collection and
thyrotoxicosis 239, 243 despatch of
Transplantation Ulcer(s), stomach 159 material for 181
heart 78 Ulcerative colitis 142-3 meningitis 178
kidney 174 Ultrasound 134 Vision
liver 156 adrenal glands 137 drug side effects and
organ donation carotid stenoses 283 331
guidelines 173 cerebral arteries 282 eye test chart 4
Tricyclic antidepressants gallbladder 136 hypertensive
122 kidney 136 retinopathy 94
Trigeminal nerve 270 liver 135 visual field defects 268
distribution 268 pancreas 136 visual pathway
Trochlear nerve 270 spleen 137 lesions 268
Tuberculosis supra-aortic blood
testing for 115 vessels 282 Weber hearing test 5
treatment of 114, 196 Uraemia 167
Tuberculous meningitis Urinary sepsis 164, 192 X-rays
178 Urinary tract infection for acute abdomen 139
Tumour(s) 164, 170 chest 21-31
assessment of physical Urine heart 27-9, 60, 61
condition of crystalluria 334 patient positions for 20
patients 230 diuretics 171 skeletal 32-5
bronchial carcinoma drug side effects 334 skull 36-9
110-13 haematuria 168, 174
colorectal carcinoma kidney failure and 165 Ziehl-Neelsen stain
158 normal values 163 preparations 177

347
Memorix Clinical Medicine
Conrad Droste and Martin von Planta
Translated and adapted by
Dennis Guttmann ma, bm BCh, bsc, frcp

The Memorix series consists of easy-to-use pocket books

in a number of different medical and surgical specialties.
They contain a vast amount of practical information in
very concise form through the extensive use of tables
and charts, lists and hundreds of clear line diagrams,
often in two colours.
Memorix Clinical Medicine covers radiology,
cardiology, chest medicine, emergency medicine,
gastroenterology, nephrology, infectious diseases,
hematology, oncology, endocrinology and diabetes,
rheumatology, neurology and clinical pharmacology.
Within these sections the text is concerned with
international classifications, differential diagnoses and
treatment plans. There is also a full colour section on
blood cell types.

Other titles in the series inc^d^bstetrics, gynecology,

neurology, emergency me'
with others to follow.

/ON Si'

CHAPMAN & HALL

London •
Weinheim •
New York
Melbourne •
Madras