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Preface & Acknowledgment
I’d like to start by quoting my friend Dr Ahmed Elmotaz, who told me that “when
preparing for the MRCP, study MRCP! Don’t study medicine!”. This book helps
you to prepare for both written parts of the exam. I also used it to refresh my
knowledge when I was preparing for the PACES and it was quite useful. I must
admit this was many years ago.
“The Only MRCP Notes You Will Ever Need” has been a favourite for many
around the world. I hope this edition, with the most up to date diagnosis and
management guidelines, will come handy to those preparing for the
membership exam.
The study pattern I recommend for the written exam is:
1. Study one chapter of your choice from this book
2. Solve the same chapter’s questions on your online question bank of choice,
there are many now.
3. Study another chapter and go online to solve its question, continue until you
finish all the chapters in the book and questions on your website of choice.
4. Revise the whole book.
5. Start solving questions randomly from another website (other than the
website you have chosen to solve chapter by chapter)
6. By this time you’d probably have solved around 3000‐4000 BOF questions,
and you’d have seen all the question patterns in MRCP.
7. I think the most important step is to revise this book again just before the
exam, this should be the last thing you do in the days ahead of your exam.
Solving question till the last moment is not recommended, you have probably
gathered enough information in your study, try to consolidate the information
by revising this book once more.
I would like thank my parents, Abuelgasim and Bothaina who have always
supported me by all possible and impossible means. My wife, Ahlam and the
two little ones; Yousif and Yasmin who have been very kind and patient during
my life journeys, I can’t thank them enough. I have two friends, both are called
Wael, each of them has been a blessing to have as a friend, I must thank them
both.
Hani Abuelgasim
Preface & Acknowledgment 1
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Contents
Preface & Acknowledgment ............................................................................... 1
Contents ......................................................................................................... 2
BASIC SCIENCES .............................................................................................. 7
CELLULAR & MOLECULAR ANATOMY ................................................................. 8
GROSS ANATOMY .............................................................................................. 12
IMMUNOLOGY .................................................................................................. 14
ELECTROLYTES AND ITS IMBALANCE ................................................................ 22
BODY & DISEASES MARKERS.............................................................................29
VITAMINS & ESSENTIAL MINERALS DEFICIENCY .............................................. 37
GENETICS & HEREDITARY DISORDERS .............................................................. 42
STATISTICS & EVIDENCE BASED MEDICINE ....................................................59
BASICS OF STATISTICS ........................................................................................ 60
EVIDENCE BASED MEDICINE ............................................................................. 71
GENERAL MEDICINE .....................................................................................75
ESSENTIAL TO KNOW ........................................................................................ 76
GENERAL ONCOLOGY .......................................................................................84
HEREDITARY MULTISYSTEM DISORDERS........................................................... 86
ENT RELATED CONDITIONS ............................................................................... 91
CARDIOVASCULAR SYSTEM ........................................................................... 95
PHYSIOLOGY & BASICS ...................................................................................... 96
ECGs ................................................................................................................ 101
GENERAL CARDIOLOGY ................................................................................... 104
CORONARY ARTERY DISEASES ........................................................................ 119
CARDIAC ARRHYTHMIA ................................................................................... 129
VALVULAR ABNORMALITIES ............................................................................ 148
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MAJOR VESSELS ABNORMALITIES .................................................................. 159
CONGENITAL HEART DISEASES ....................................................................... 163
RESPIRATORY SYSTEM ................................................................................ 171
PHYSIOLOGY & BASICS .................................................................................... 172
GENERAL RESPIRATORY MEDICINE ................................................................. 179
RESPIRATORY INFECTIONS .............................................................................. 192
AIRWAY DISEASE ............................................................................................. 197
ALVEOLAR & INTERSTITIAL LUNG DISEASES ................................................... 213
PULMONARY CANCERS ................................................................................... 219
GASTROINTESTINAL SYSTEM ...................................................................... 225
PHYSIOLOGY & BASICS .................................................................................... 226
GENERAL GI INFECTIONS ................................................................................ 229
UPPER GI DISORDERS ...................................................................................... 236
LOWER GI DISORDERS .................................................................................... 247
PANCREATIC DISORDERS ................................................................................. 263
HEPATOLOGY ................................................................................................... 269
COMMON GI SURGICAL PROBLEMS IN MRCP................................................ 289
RENAL SYSTEM ........................................................................................... 293
PHYSIOLOGY & BASICS .................................................................................... 294
RENAL DISORDERS .......................................................................................... 302
INHERITED RENAL DISORDERS ........................................................................ 314
COMMON UROLOGICAL PROBLEMS .............................................................. 319
NERVOUS SYSTEM ...................................................................................... 325
NEUROLOGY BASICS ........................................................................................ 326
NEURO‐OPHTHALMOLOGY ............................................................................. 328
GENERAL NEUROLOGY .................................................................................... 333
HEADACHE & PAIN .......................................................................................... 349
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IMMUNE‐MEDIATED NEURO. DISORDER ....................................................... 356
NEURODEGENERATIVE DISORDERS ................................................................ 363
CEREBROVASCULAR DISEASES ........................................................................ 370
INHERITED NEUROLOGICAL DISORDERS ........................................................ 379
SPINAL CORD ABNORMALITIES ...................................................................... 382
PERIPHERAL NEUROLOGICAL ABNORMALITIES............................................. 387
NEUROLOGICAL INFECTIONS .......................................................................... 389
COMMON INTRACRANIAL TUMOURS IN MRCP ............................................. 395
MUSCULOSKELETAL SYSTEM ....................................................................... 397
ANATOMY & BASICS ........................................................................................ 398
MUSCULAR DISORDERS .................................................................................. 403
COMMON UPPER LIMB PROBLEMS IN MRCP ................................................408
COMMON LOWER LIMB PROBLEMS IN MRCP ...............................................411
BONE DISORDERS............................................................................................ 413
RHEUMATOLOGY ........................................................................................ 421
JOINTS DISEASES ............................................................................................. 422
Seronegative Spondyloarthropathies ......................................................... 433
AUTOIMMUNE CONNECTIVE TISSUE DISEASES .............................................437
VASCULITIDES .................................................................................................. 447
HAEMATOLOGY .......................................................................................... 455
GENERAL HAEMATOLOGY ............................................................................... 456
HAEMOGLOBIN ABNORMALITIES ................................................................... 467
Inherited Anaemia ...................................................................................... 480
HAEMATO‐ONCOLOGY .................................................................................... 485
COAGULOPATHIES & BLEEDING DISORDERS .................................................. 509
ENDOCRINOLOGY ....................................................................................... 519
PITUITARY GLAND ........................................................................................... 520
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THYROID & PARATHYROID GLANDS ................................................................ 528
DIABETES & PANCREAS ................................................................................... 542
ADRENAL & ENDOCRINE‐ELECTROLYTES ........................................................ 563
METABOLISM, OBESITY & LIPID ...................................................................... 573
ENDOCRINE SYNDROMES & NEOPLASIA ........................................................ 583
INFECTIOUS DISEASES................................................................................. 587
BACTERIAL CLASSIFICATION ............................................................................ 588
VACCINATION & PROPHYLAXIS ....................................................................... 592
BACTERIAL INFECTIONS .................................................................................. 595
Mycobacteria .............................................................................................. 606
VIRAL INFECTIONS .......................................................................................... 611
PARASITIC INFECTIONS ...................................................................................621
STI & HIV .........................................................................................................628
GYNAECOLOGY & OBSTETRICS .................................................................... 645
GYNAECOLOGY................................................................................................646
OBSTETRICS ..................................................................................................... 653
DERMATOLOGY .......................................................................................... 661
DISEASES‐RELATED SKIN CONDITIONS ...........................................................662
DERMATOLOGICAL CONDITIONS .................................................................... 664
PSYCHIATRY ................................................................................................ 695
COMMON PSYCHIATRIC DISEASES IN MRCP .................................................. 696
COMMON PSYCHIATRIC TREATMENTS ........................................................... 707
OPHTHALMOLOGY ..................................................................................... 713
EXTRA‐OCULAR DISEASES ............................................................................... 714
INTRA‐OCULAR DISEASES ............................................................................... 718
PROBLEMS RELATED TO SYSTEMIC DISEASES ................................................. 729
PHARMACOLOGY & TOXICOLOGY ............................................................... 735
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GENERAL PHARMACOLOGY ............................................................................ 736
TOXICOLOGY .................................................................................................... 748
NERVOUS SYSTEM MEDICATIONS .................................................................. 759
CARDIOVASCULAR MEDIATIONS ..................................................................... 764
OTHER MEDICATIONS ..................................................................................... 780
ANTIMICROBIAL .............................................................................................. 791
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BASIC SCIENCES
Many MRCP candidates do not
realise the importance of basic
sciences until they go into the
exam hall and get surprised by
the amount of basic science
knowledge required, either
directly or through questions
related to clinical scenarios.
When faced with a long
scenario, it might be wise to
check the question at the
bottom of the scenario; this is a
common theme of basic science
questions.
BASIC SCIENCES : 7
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CELLULAR & MOLECULAR ANATOMY
Cell Organelles:
Endoplasmic reticulum Mitochondrion
Translation and folding of new Energy production. Contains
proteins (rough endoplasmic mitochondrial genome as circular
reticulum), expression of lipids double stranded DNA
(smooth endoplasmic reticulum)
Golgi apparatus Nucleus
Sorting and modification of DNA maintenance and RNA
proteins transcription
Lysosome Nucleolus
Breakdown of large molecules Ribosome production
such as proteins and
polysaccharides
Ribosome Peroxisome
Translation of RNA into proteins Breakdown of metabolic hydrogen
peroxide
Proteasome
Along with lysosome pathway: degradation of large protein molecules
M: Mitosis ‐ cell division
G1: Gap phase 1,
determines length of
cell cycle under
influence of p53
S: DNA Synthesis
G2: Gap phase
BASIC SCIENCES : Cellular & Molecular Anatomy 8
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Hyponatraemia: may be caused by water excess or sodium depletion.
Causes of pseudohyponatremia include ↑ lipids or ↑ proteins (↑ in serum
volume) or a taking blood from a drip arm. Urinary sodium and osmolarity
levels aid making a diagnosis. It is important to note that every 100mg/dL
increase of blood glucose will lower the Na as much as 1.6 meq.
Urinary sodium > 20 mmol/L Urinary sodium < 20 mmol/L
Na+ depletion, renal loss Na+ depletion, extra‐renal loss
(patient often hypovolaemic)
(patient often hypovolaemic) Diarrhoea, vomiting, sweating
Diuretics Burns, adenoma of rectum
Diuretic stage of renal failure
Addison's Water excess (patient often
hypervolaemic and oedematous)
Patient often euvolaemic Secondary hyperaldosteronism:
SIADH (urine osmolality > 500
CCF, cirrhosis
mmol/kg) ↓ GFR: renal failure with
Hypothyroidism
volume overload
IV dextrose, psychogenic
polydipsia
BASIC SCIENCES : Electrolytes and its Imbalance 23
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STATISTICS &
EVIDENCE BASED
MEDICINE
Statistics and evidence‐based
medicine questions keep
occurring in MRCP exams, these
are usually easy scoring
questions.
STATISTICS & EVIDENCE BASED MEDICINE : 59
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2 measurements, or variables, may be plotted on a scatter plot. For example,
age may be marked along the x axis and systolic BP along the y axis
Correlation
The correlation coefficient
(sometimes referred to as
Pearson's product‐moment
coefficient) indicates how closely
the points lie to a line drawn
through the plotted data. It is
denoted by the value R which may
lie anywhere between ‐1 and 1.
For example
R = 1 ‐ strong positive correlation (e.g. systolic BP always ↑ with age)
R = 0 ‐ no correlation (e.g. There is no correlation between systolic BP and
age)
R = ‐ 1 ‐ strong negative correlation (e.g. systolic BP always ↓ with age)
Whilst correlation coefficients give information about how one variable may ↑
or ↓ as another variable ↑ they do not give informa on about how much the
variable will change. They also do not provide information on cause and effect.
Linear Regression
In contrast to the correlation
coefficient, linear regression may
be used to predict how much one
variable changes when a second
variable is changed. A regression
equation may be formed:
Y = bX + a
Y = the variable being
calculated
a = the intercept value, when x
= 0
b = the slope of the line or
regression coefficient. Simply
put, how much y changes for a
given change in x
X = the second variable
STATISTICS & EVIDENCE BASED MEDICINE : Basics of Statistics 62
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GENERAL MEDICINE
Variety of topics that cannot be
classified under a certain
specialty.
GENERAL MEDICINE : 75
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GENERAL ONCOLOGY
Cancers in UK: (excludes non‐melanoma skin cancer):
Most common causes of cancer Most common causes of DEATH
Breast Lung
Lung Colorectal
Colorectal Breast
Prostate Prostate
Bladder Oesophagus
Non‐Hodgkin's lymphoma Stomach
Melanoma Bladder
Stomach Non‐Hodgkin's lymphoma
Oesophagus Ovarian
Pancreas Leukaemia
Tumour markers: May be divided into:
Monoclonal antibodies against carbohydrate or glycoprotein tumour
antigens
Tumour antigens
Enzymes (alkaline phosphatase, neuron specific enolase)
Hormones (e.g. calcitonin, ADH)
It should be noted that tumour markers usually have a low specificity
Monoclonal antibodies:
Tumour marker Association
CA 125 Ovarian cancer
CA 19‐9 Pancreatic cancer
CA 15‐3 Breast cancer
Tumour antigens:
Tumour marker Association
Prostate specific antigen (PSA) Prostatic carcinoma
α ‐feto protein (AFP) Hepatocellular carcinoma, teratoma
Carcinoembryonic antigen (CEA) Colorectal cancer
GENERAL MEDICINE : General Oncology 84
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Alpha‐1 Antitrypsin (A1AT) Deficiency: a common inherited
condition caused by a lack of a protease inhibitor (Pi) normally produced by the
liver.
Genetics
Located on chromosome 14
A1AT deficiency is inherited in an autosomal recessive /co‐dominant
fashion
Alleles classified by their electrophoretic mobility ‐ M: normal, S: slow,
and Z: very slow
Normal = PiMM
Homozygous PiSS (50% normal A1AT levels)
Homozygous PiZZ (10% normal A1AT levels)
Features
Patients who manifest disease usually have PiZZ genotype
Lungs: pan‐acinar emphysema, most marked in lower lobes
Liver: cirrhosis and hepatocellular carcinoma in adults, cholestasis in
children
By Mikael Häggström, used with permission 89
GENERAL MEDICINE : Hereditary Multisystem Disorders
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CARDIOVASCULAR
SYSTEM
Cardiology is often a feared
topic by many doctors who do
not have good cardiology
experience. Cardiology is simple
if you understand the basics of
its physiology and dynamics.
Understanding of ECG, rhythm
recognition and life‐threatening
ECG changes is an essential
knowledge for every doctor.
In this section our aim is to focus
on cardiology from exam point
of view to highlight the most
tested facts with a quick review
of basics.
CARDIOVASCULAR SYSTEM : 95
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Causes of ST depression:
Can be normal if
up‐sloping
Ischaemia
Digoxin
Hypokalaemia
Syndrome X
ECG changes may be seen in hypothermia:
Bradycardia
'J' wave ‐ small hump at the end of the QRS complex
First degree heart block
Long QT interval
Atrial and ventricular arrhythmias
J waves are seen in hypothermia whilst delta waves are associated with
WPW
Digoxin ECG Features:
Down‐sloping ST 102
depression
('reverse tick')
Flattened /
inverted T waves
Short QT interval
Arrhythmias e.g.
AV block,
bradycardia
CARDIOVASCULAR SYSTEM : ECGs
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Features suggesting VT rather than SVT with aberrant conduction
AV dissociation History of IHD
Fusion or capture beats Lack of response to
Positive QRS in chest leads adenosine or carotid sinus
Marked left axis deviation massage
QRS > 160 ms
AV Dissociation: when P waves (atrial activity) is not driving the ventricular
activity. Here in this rhythm strip, note the P waves come after the wide QRS.
Capture Beats: when SA node (P wave) successfully produces a narrow QRS
(ventricular contraction).
Fusion Beats: when SA node will appear like it produced a wide QRS, in fact this
is the SA node and ventricular contraction coinciding to come in correct
sequence rather than truly conducted beat.
Drug therapy
Amiodarone: ideally administered through a central line
Lidocaine: use with caution in severe left ventricular impairment
Procainamide
VERAPAMIL SHOULD NOT BE USED IN WIDE QRS TACHYCARDIA
Verapamil should never be given to a patient with a broad complex
tachycardia as it may precipitate ventricular fibrillation in patients with VT. If
you are not sure if its VT or SVT with wide QRS, Adenosine is sometimes given
in this situation as a ‘trial’, it may slow the rhythm to a degree that you can
detect the underlying rhythm (unmask).
CARDIOVASCULAR SYSTEM : Cardiac Arrhythmia 137
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Ostium Primum
Present earlier than ostium Secundum defects
Associated with abnormal Atrio‐Ventricular (AV) valves, note the
location of Primum ASD and its proximity to AV valves
ECG: RBBB with LAD, prolonged PR interval
Patent Ductus Arteriosus (PDA)
Overview
Acyanotic congenital
heart defect
Connection between the
pulmonary trunk and
descending aorta
More common in
premature babies, born at
high altitude or maternal
rubella infection in the
first trimester
Features Management
Left sub‐clavicular thrill Indomethacin closes the
Continuous ‘machinery’ connection in the majority of
murmur cases
Large volume, collapsing pulse If associated with another
Wide pulse pressure congenital heart defect
Heaving apex beat amenable to surgery, then
Dilated LV prostaglandin E1 is useful to
keep the duct open until after
surgical repair
CARDIOVASCULAR SYSTEM : Congenital Heart Diseases 165
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RESPIRATORY SYSTEM
Did you know?
In the United Kingdom, Ireland,
South Africa, and Australia the
term "respiratory physician" is
used to distinguish a physician
that practices pulmonology or
respiratory medicine. In
Canada, respirology and
respirologist are used while in
the States, pulmonologist is
widely used.
RESPIRATORY SYSTEM : 171
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Oral Therapy:
Theophylline:
o NICE only recommends theophylline after trials of short and long‐
acting bronchodilators or to if cannot use inhaled therapy.
o The dose should be reduced if macrolide or fluroquinolone
antibiotics are co‐prescribed.
Oral corticosteroids:
o Long‐term use of steroid in COPD is not normally recommended.
Advanced COPD may need long‐term steroids when these cannot be
withdrawn following an exacerbation. In these cases, the dose of
oral corticosteroids should be kept as low as possible.
o Monitor for osteoporosis. Give prophylaxis without monitoring if >
65 years.
Mucolytics:
o Should be ‘considered’ in patients with a chronic productive cough
and continued if symptoms improve but do not give routinely to
prevent exacerbations.
RESPIRATORY SYSTEM : Airway disease 199
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Phosphodiesterase‐4 Inhibitors:
o Roflumilast, as an add‐on to bronchodilator therapy, is
recommended as an option for treating severe COPD (FEV1 <50% or
≥2 exacerbations/year despite inhaled treatment).
Complications: Emphysema, Pulmonary hypertension and Cor Pulmonale.
Emphysema is an irreversible degenerative condition:
↑ Residual Volume (RV)
↑ Total Lung Capacity (TLC)
Giving typical obstructive
pathology
Flattening of diaphragms: ↑ lung
volumes
Enlarged left pulmonary artery
Attenuation of vessels
Diffuse hyperlucency
Types:
Panacinar (panlobular): entire
respiratory acinus, from
respiratory bronchiole to alveoli,
is expanded. > In lower lobes.
Centriacinar (centrilobular):
respiratory bronchiole (proximal
and central part of the acinus) is
expanded. The distal acinus or
alveoli are unchanged. > In upper
lobes.
Paraseptal Emphysema: involves the alveolar ducts and sacs at the lung
periphery. It may be an incidental finding in young adults and may be
associated with spontaneous pneumothorax. It may also be seen in older
patients with centrilobular emphysema. Both centrilobular and paraseptal
emphysema may progress to bullous emphysema.
Emphysematous Bulla is defined as being at least 1 cm in diameter, and with
a wall less than 1mm thick. Bullae are thought to arise by air trapping in
emphysematous spaces, causing local expansion.
RESPIRATORY SYSTEM : Airway disease 200
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RESPIRATORY SYSTEM : Airway disease 206
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GASTROINTESTINAL
SYSTEM
10% of GP visits in the UK are
related to indigestion. GI
cancers are the 4th most
common cancers in the UK;
after breast, prostate and lung.
While lung cancers are the
leading cause of cancer death
(21%), GI cancers come right
next with 10% of cancer deaths.
Currently, GI consultants are
commonly divided by their main
practice into hepatologists,
luminal gastroenterologists and
academics; but the specialty is
developing rapidly, and it is now
possible to sub‐specialise in
advanced endoscopy and
nutrition.
GASTROINTESTINAL SYSTEM : 225
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Causes:
Vomiting (against a closed glottis) in eating disorders such as bulimia
Rarely: extremely forceful coughing ‐ Obstruction by food
Diagnosis:
CXR show mediastinal gas, effusion, and later pneumothorax.
Oesophagram is used to confirm leak, first with water‐soluble contrast,
then barium if no leak demonstrated.
Management: Early operation after appropriate resuscitation offers the best
chance of survival.
Iatrogenic perforation, accounts for 85‐90% of cases of oesophageal
rupture, typically as a complication of an endoscopic procedure, feeding
tube, or unrelated surgery.
Peutz‐Jeghers Syndrome: autosomal dominant condition
characterized by numerous hamartomatous polyps in the gastrointestinal tract.
It is also associated with pigmented freckles on the lips, face, palms and soles.
Around 50% of patients will have died from a gastrointestinal tract cancer by
the age of 60. It is unusual to find cases in young adults without the
characteristic peristomal hyperpigmentation.
Genetics
Autosomal dominant
Responsible gene encodes
serine threonine kinase LKB1
or STK11
Features
Hamartomatous polyps in GI
tract (mainly small bowel)
Pigmented lesions on lips, oral
mucosa, face, palms and soles
classical histological
appearance of smooth muscle
“arborisation”
Intestinal obstruction e.g.
Intussusception
Gastrointestinal bleeding
Management: Conservative unless complications develop
GASTROINTESTINAL SYSTEM : Upper GI Disorders 244
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Although a relatively new test, faecal calprotectin is regularly used as indicator
for IBD during treatment and as diagnostic marker.
Ulcerative Colitis
Treatment can be divided into inducing and maintaining remission
Inducing remission
Treatment depends on the extent and severity of disease
Rectal aminosalicylates or steroids: for distal colitis. Rectal Mesalazine is
superior to rectal steroids
Oral aminosalicylates or steroids
Severe colitis should be treated in hospital
Maintaining remission
Oral aminosalicylates e.g Mesalazine
In severe UC, patients should be treated with IV steroids, fluids, subcutaneous
heparin and elemental diet. The patient should have daily examination and
monitoring including review by surgeons, blood tests, stool chart, heart rate,
temperature and abdominal X‐rays.
GASTROINTESTINAL SYSTEM : Lower GI Disorders 253
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RENAL SYSTEM
CKD progresses to kidney failure
in around 2% of patients.
Patients with CKD, even if it's
mild, are at an increased risk of
developing cardiovascular
disease. Majority of mortalities
in CKD are caused by
cardiovascular complications.
RENAL SYSTEM : 293
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Glomerulonephritis: generally classified according to histopathology.
The histopathologic appearance can be categorized according to presentation:
1. Nephrotic presentation
2. Mild glomerulonephritic presentation
3. Rapidly progressive glomerulonephritis presentation
Post‐Transplant recurrence of original renal disease
IgA > FSGS > Membranous > Membranoproliferative
Nephrotic presentation
1. Minimal change disease
Typically, a child with nephrotic syndrome (accounts for 80%)
Causes: Hodgkin's, NSAIDs
Good response to steroids
2. Focal segmental glomerulosclerosis
May be idiopathic (primary):
o presentation: proteinuria / nephrotic syndrome / CRF
o less responsive to steroids.
o can occur after transplantation.
o high recurrence rate in renal transplants
Secondary to HIV, heroin, Alport’s syndrome, sickle cell anaemia,
morbid obesity or chronic hypertension
o presents with variable proteinuria and outcome
3. Membranous glomerulonephritis
Common cause of adult idiopathic nephrotic syndrome
Presentation: proteinuria / nephrotic syndrome / CRF
Cause:
o infections: Hepa B.
o rheumatoid drugs: Penicillamine, NSAIDs.
o malignancy
Immune deposit: granular subepithelial IgG
1/3 resolve, 1/3 respond to cytotoxics, 1/3 develop CRF
RENAL SYSTEM : Renal Disorders 303
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Mild glomerulonephritic presentation
1. IgA nephropathy ‐ AKA Berger's disease, mesangioproliferative GN
Typically young adult with haematuria following an URTI, liver disease
or coeliac disease.
Associated with Henoch‐Schonlein Purpura (HSP)
Mesangial hypercellularity (mesangioproliferative)
Immune deposit: mesangial IgA (and C3)
2. Mesangiocapillary glomerulonephritis (membranoproliferative) (MPGN)
Immunoglobulin type:
o most common pattern found in association with subacute
bacterial infection, but also with cryoglobulinaemia
(monoclonal gammopathies) ± Hepa C.
o associated with low C4.
Complement type:
o partial lipodystrophy
o associated with low C3.
Rapidly progressive glomerulonephritis presentation
1. Diffuse proliferative glomerulonephritis
Classical post‐streptococcal glomerulonephritis in child
Presents as nephritic syndrome / ARF: severe sodium and fluid
retention, hypertension, haematuria and oliguria.
Most common form of renal disease in SLE (IV)
2. Rapidly progressive glomerulonephritis (RPGN):
Focal necrotising glomerulonephritis.
Rapid onset, often presenting as ARF.
Immune deposit: typically, negative or (pauciimmune)
Causes include Goodpasture's, ANCA positive vasculitis (e.g.
Wegener's granulomatosis)
Responds well to steroids and immunosuppressants.
3. Anti‐glomerular basement membrane disease
Crescentic glomerulonephritis
Immune deposit: Linear IgG along GBM.
Associated with lung haemorrhage but renal or lung disease may
occur alone
Treatment: steroids, cyclophosphamide and plasma exchange.
RENAL SYSTEM : Renal Disorders 304
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Disorders associated with glomerulonephritis and low serum C3 levels:
Post‐streptococcal glomerulonephritis
Subacute bacterial endocarditis
Systemic lupus erythematosus
Mesangiocapillary glomerulonephritis
Minimal Change Glomerulonephritis: nearly always presents as
nephrotic syndrome, accounting for 75% of cases in children and 25% in adults
Minimal change glomerulonephritis → prednisolone
ACE inhibitors may be used to ↓ proteinuria in pa ents with heavy proteinuria or who have a
slow response to rednisolone
Features Causes
Nephrotic syndrome Majority of cases are
Normotension ‐ hypertension idiopathic, but in around 10‐
is rare 20% a cause is found:
Haematuria is very rare Drugs: NSAIDs, rifampicin
Highly selective proteinuria* Hodgkin's lymphoma, NHL and
Renal biopsy: electron thymoma
microscopy shows fusion of Infectious mononucleosis
podocytes
Podocyte fusion is seen in minimal change glomerulonephritis but may
occasionally be a feature of focal segmental glomerulosclerosis as well.
Minimal change however is far more common
Management:
Majority of cases (80%) are steroid responsive
Cyclophosphamide is the next step for steroid resistant cases
Prognosis is overall good, although relapse is common. Roughly:
1/3 have just one episode
2/3 have relapses:
o 1/3 have infrequent relapses
o 1/3 have frequent relapses which stop before adulthood
*only intermediate‐sized proteins such as albumin and transferrin leak through the glomerulus
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NERVOUS SYSTEM
Every 15 minutes someone
suffers AF‐related stroke in the
UK, this equals 35000 AF‐
related stroke a year. It’s
estimated that 1.5 million
people have AF in the UK.
Source: 2018 ‐ AF Association UK ‐ Heart
Rhythm Alliance UK
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NEURO‐OPHTHALMOLOGY
Visual Field Defects:
Homonymous Hemianopia:
Incongruous defects = optic tract lesion (5)
Congruous defects (defect is
approximately the same in each eye): optic
radiation lesion or occipital cortex (8)
Macula sparing: lesion of occipital cortex
(9) Left homonymous
Rt homonymous hemianopia means visual hemianopia
field defect to the Rt, i.e. lesion of Rt optic
tract (5)
Homonymous Quadrantanopia:
Superior: lesion of temporal lobe (6)
Inferior: lesion of parietal lobe (7)
Mnemonic = PITS (Parietal‐Inferior, Temporal‐Superior) (7,6)
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Bitemporal Hemianopia:
Lesion of optic chiasm (3)
Upper quadrant defect > lower quadrant
defect = inferior chiasmal compression,
commonly a pituitary tumour
Lower quadrant defect > upper quadrant
defect = superior chiasmal compression,
commonly a craniopharyngioma
Nystagmus: is involuntary oscillations of the eyes. This may be pendular
when the oscillations are equal in rate and amplitude or jerking when there are
quick and slow phases. (The quicker phase is used to define the direction.)
Types Causes
Nystagmus which changes with Visual disturbances
the direction of gaze → Lesions of the labyrinth
involvement of vestibular nuclei. The central vestibular
Pendular: mostly due to loss of connections
macular vision but could be in Brain stem or cerebellar lesions.
diffuse brain stem lesions.
Jerking regardless of the Medial Longitudinal Bundle →
direction of gaze → labyrinthine coordinates lateral rectus of one
or cerebellar lesion. side with medial rectus of the
Jerking on lateral gaze, and fast other
in the direction of gaze → brain
stem or cerebellum lesion. Upbeat nystagmus → Cerebellar
Nystagmus confined to one eye vermis lesions
→ nerve or muscle lesion, or
medial longitudinal bundle Downbeat nystagmus ‐ foramen
lesion. magnum lesions → Arnold‐Chiari
Nystagmus restricted to the malformation
abducting eye on lateral gaze
(ataxic nystagmus) is due to a
lesion of the medial longitudinal
bundle between the pons and
mid‐brain as in multiple
sclerosis.
Wernicke's or thiamine
deficiency is a rare cause of
downbeat nystagmus
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HEADACHE & PAIN
Cluster Headache: are more common in men (5:1) and smokers
Episodic eye pain, lacrimation, nasal stuffiness occurring daily ‐ cluster
headache
Features
Pain typical occurs once or twice a day,
each episode lasting 15 mins ‐ 2 hours
Clusters typically last 4‐12 weeks
Intense pain around one eye (recurrent
attacks 'always' affect same side)
Patient is restless during an attack
Accompanied by redness, lacrimation,
lid swelling
Nasal stuffiness
Miosis and ptosis in a minority
Management
Acute: 100% oxygen, subcutaneous sumatriptan (5‐HT1D receptor
agonist), nasal lidocaine
Prophylaxis: verapamil, prednisolone
Consider specialist referral
some neurologists use the term trigeminal autonomic cephalgia to group a
number of conditions including cluster headache, paroxysmal hemicrania and
short‐lived unilateral neuralgiform headache with conjunctival injection and
tearing (SUNCT). It is recommended such patients are referred for specialist
assessment as specific treatment may be required, for example it is known
paroxysmal hemicrania responds very well to indomethacin.
Chronic Paroxysmal Hemicrania (CPH): characterized by:
Unilateral pain which is generally oculofrontotemporal in location.
Can occur at any time, and patients often describe a throbbing, boring,
pulsating or claw‐like pain
Frequency of attacks is usually 10–20 per day. Episodes usually last 2–25
min, but may last up to 60 min
Patients may also complain of ipsilateral conjunctival injection, ptosis
and lid swelling, lacrimation and rhinorrhoea, occasionally photophobia
The most effective treatment is with indomethacin
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The most important differential diagnosis is from cluster headache (CH) and
from other headache syndromes characterized by autonomic dysfunction such
as SUNCT (short‐lasting unilateral neuralgiform headache with conjunctival
injection and tearing). CH has male preponderance, unlike CPH, which is more
common in ♀. In CPH, frequency of attacks is higher, usually more than 15 in 24
hours, whereas CH has an attack frequency of 1‐4 (maximum 8) in 24 hours. The
duration of headaches is shorter in CPH (2‐25 min) than in CH (15‐60 min).
Migraine: The International Headache Society has produced the following
diagnostic criteria for migraine without aura:
A At least 5 attacks fulfilling criteria B‐D
B Headache attacks lasting 4‐72 hours* (untreated or unsuccessfully treated)
C Headache has at least two of the following characteristics:
1. Unilateral location*
2. Pulsating quality (i.e., varying with the heartbeat)
3. Moderate or severe pain intensity
4. Aggravation by or causing avoidance of routine physical activity (e.g.,
walking or climbing stairs)
D During headache at least one of the following:
1. Nausea and/or vomiting*
2. Photophobia and phonophobia
E Not attributed to another disorder (history and examination do not suggest
a secondary headache disorder or, if they do, it is ruled out by appropriate
investigations or headache attacks do not occur for the first time in close
temporal relation to the other disorder)
*In children, attacks may be shorter‐lasting, headache is more commonly bilateral, and
gastrointestinal disturbance is more prominent.
Migraine with aura (around 1 in 3 migraine patients) tends to be easier to
diagnose with a typical aura being progressive in nature and may occur hours
prior to the headache. Typical aura includes a transient hemianopic disturbance
or spreading scintillating scotoma ('jagged crescent'). Sensory symptoms may
also occur
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CEREBROVASCULAR DISEASES
TIA: NICE issued updated guidelines relating to stroke and transient ischemic
attack (TIA) in 2017. They continued advocating the use of the ABCD2 prognostic
score for risk stratifying patients who've had a suspected TIA:
ABCD2 score of ≥4: Criteria points
Aspirin (300 mg daily) started A Age ≥ 60 years 1
immediately
Blood pressure ≥ 140/90
Specialist assessment and B mmHg 1
investigation within 24 hours of
onset of symptoms Clinical features
2
Measures for secondary C ‐ Unilateral weakness 1
prevention introduced as soon as ‐ Speech disturbance, no
the diagnosis is confirmed, weakness
including discussion of individual Duration of symptoms
risk factors 2
D ‐ > 60 minutes 1
‐ 10‐59 minutes
ABCD2 risk score ≤ 3:
Specialist assessment within 1 D Patient has diabetes 1
week of symptom onset,
including decision on brain maximum points 7
imaging
Measures for secondary prevention introduced as soon as the
diagnosis is confirmed, including discussion of individual risk factors
People with crescendo TIA (two or more TIAs in a week) should be treated as
being at high risk of stroke, even though they may have an ABCD2 score of 3 or
below. People who have had a TIA but who present late (more than 1 week after
their last symptom has resolved) should be treated as though they are at lower
risk of stroke.
Recommendations from NICE (2017) include:
Aspirin 300mg immediately; orally if not dysphagic, rectal or enteral tube
if dysphagic.
Anterior circulatory TIAs, after specialist assessment, if considered as
candidates for carotid endarterectomy should have carotid imaging
within 1 week of onset of symptoms. (consideration depends largely on
patient’s fitness for surgery)
Consider dual antiplatelets (Aspirin 75mg+Clopidogrel 75mg) for 3 weeks
if ABCD2 Score ≥4*
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RHEUMATOLOGY
Around 400,000 adults have
rheumatoid arthritis in the UK,
there are 20,000 new cases of
rheumatoid arthritis every year
while 286,000 people every
year consult their GP about gout
and there are 4.11 million
people in England have
osteoarthritis of the knee.
Arthritis Research UK
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JOINTS DISEASES
Gout is a form of microcrystal synovitis caused by the deposition of
monosodium urate monohydrate in the synovium. It is caused by chronic
hyperuricemia (uric acid > 450 µmol/l) mostly due to ↓ renal excre on of UA
(90%). ↑ Produc on of uric acid
↓Excre on of uric acid
Drugs: diuretics Myeloproliferative and
Chronic kidney disease lymphoproliferative disorders
Lead toxicity Cytotoxic drugs
Severe psoriasis
Presentations:
Tophaceous gout Lesch‐Nyhan syndrome
Associated with renal Hypoxanthine‐guanine
impairment and prolonged phosphoribosyl transferase
diuretics use. deficiency
Affected joints are hot swollen Inheritance = X‐linked
and knobby appearance. recessive
Due to deposition of Na+ urate Features: gout, renal failure,
in skin and joint. learning difficulties, head‐
X‐ray: punched out bony cyst. banging
Patients with Lesch‐Nyhan
syndrome often take
allopurinol for life
Life style and drugs causes:
Lifestyle modifications Drugs causing gout
↓ alcohol intake and avoid Thiazides, furosemide
during an acute attack Alcohol
Lose weight if obese Cytotoxic agents
Avoid food high in purines e.g. Pyrazinamide
Liver, kidneys, seafood, oily fish
(mackerel, sardines) and yeast
products
Lithium was used to treat gout in the 19th century
it does NOT cause gout
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AUTOIMMUNE CONNECTIVE TISSUE DISEASES
Systemic Lupus Erythematosus (SLE)
Epidemiology Pathophysiology
Much more common in ♀s Associated with HLA B8, DR2,
(F:M = 9:1) DR3
More common in Afro‐ Thought to be caused by
Caribbeans and Asian immune system dysregulation
communities leading to immune complex
Onset is usually 20‐40 years formation
Incidence has risen Immune complex deposition
substantially during the past 50 can affect any organ; skin,
years (3 fold using American joints, kidneys and brain most
College of Rheumatology commonly affected
criteria)
Clinical Features:
Fatigue, headache and poor
concentration.
Arthritis: arthralgia is
common (90% of patients),
often associated with early
morning stiffness.
Tenosynovitis may also
occur but clinically apparent
synovitis with joint swelling
is rare. Joint erosion is not a
feature.
Raynaud’s phenomenon
Skin:
o Photosensitivity
By Mikael Häggström, used with permission
o Malar rash: butterfly‐shaped rash across cheeks and nose with
sparing of the nasolabial folds.
o Discoid rash characterised by hyperkeratosis and follicular
plugging, with scarring alopecia if it occurs on the scalp
o Livedo reticularis: which is also a feature of antiphospholipid
syndrome.
Lupus Nephritis
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HAEMATOLOGY
Around 30% of the total world
population is anaemic and half
of these, some 600 million
people, have iron deficiency.
The classification of anaemia by
the size of the red cells (MCV)
indicates the likely cause.
Blood cancer is the fifth most
common type of cancer in the
UK, with someone being
diagnosed every 20 minutes.
There are more than 240,000
people living with blood cancer
in the UK and 38,000 people are
diagnosed with blood cancer
each year.
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Blood Film Finding
Condition
G6PD Deficiency Heinz bodies
Myelofibrosis 'Tear‐drop' poikilocytes
Intravascular haemolysis Schistocytes
Megaloblastic anaemia Hypersegmented neutrophils
CLL Smudge or smear cells
Splenic lymphoma with villous Lymphocytes with polar villi
lymphocytes
Follicular lymphoma Lymphocytes (mature) with cleaved
nuclei
ALL Lymphocytes (immature) with prominent
nuclei
Tear‐drop' poikilocytes Smudge cells Schistocytes
Stains & Reagents used in Haematology:
Condition
Stain/Reagent
Tartrate‐Resistant Acid Phosphatase Always +ve in hairy cell
TRAP leukaemia
Sudan black B stain and acute myeloblastic leukaemia
myeloperoxidase
Terminal Deoxynucleotidyl Transferase acute lymphoblastic leukaemia
Stain (TDT)
↑ in polycythaemia RV and
Leukocyte Alkaline Phosphatase (LAP) myelofibrosis
↓ in chronic myeloid leukaemia
Drug causes of pancytopenia
Cytotoxics
Antibiotics: trimethoprim, chloramphenicol
Anti‐rheumatoid: gold, penicillamine
Carbimazole (causes both agranulocytosis and pancytopenia)
Anti‐epileptics: carbamazepine
Sulphonylureas: tolbutamide
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Aplastic Anaemia: Aplastic anaemia is a rare condition characterised by
↓Hb, ↓WC and ↓PLT with a hypocellular or acellular marrow. It’s usually
acquired though congenital forms do exist, e.g. Fanconi's. The underlying cause
is identified in less than 30% of cases despite extensive investigation.
Management:
Supportive with
o Blood products
o Prevention and treatment of infection
Anti‐thymocyte globulin (ATG) and anti‐lymphocyte globulin (ALG)
o Prepared in animals (e.g. Rabbits or horses) by injecting human
lymphocytes
o Highly allergenic and may cause serum sickness (fever, rash,
arthralgia), therefore steroid cover usually given,
immunosuppression using agents such as Cyclosporin may also
be given
Stem cell transplantation:
o Allogeneic transplants have a success rate of up to 80%
Fanconi’s Anaemia: (chromosomal breakage or fragility disorder)
Autosomal recessive Neurological manifestation
Aplastic anaemia; bone Skeletal abnormalities
marrow failure Skin pigmentation (café‐au‐
Developmental abnormalities lait spots)
Cancer susceptibility; ↑ risk Fatal with life expectancy of
of AML 16 years
image credit: Rationabilis ‐ Wikimedia 474
HAEMATOLOGY : Haemoglobin abnormalities
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Monoclonal Gammopathy of Undetermined Significance
(MGUS) also known as benign paraproteinemia and monoclonal
gammopathy) is a common condition that causes paraproteinemia and is often
mistaken for myeloma. Differentiating features are listed below. Around 10% of
patients eventually develop myeloma at 5 years, with 50% at 15 years
One of the key differentiating features between (MGUS) and myeloma is
the absence of complications such as immune paresis, hypercalcemia and
bone pain
Features Management
Usually asymptomatic Serum paraprotein <30 g/L
No bone pain or ↑ risk of AND
infections Clonal plasma cells <10% on
Around 10‐30% of patients bone marrow biopsy AND
have a demyelinating NO myeloma‐related organ or
neuropathy tissue impairment
M protein level < 30gm/l
No end‐organ damage.
Multiple Myeloma: is a neoplasm of the bone marrow plasma cells. The
peak incidence is patients aged 60‐70 years.
Features Diagnosis
Bone pain, osteoporosis + Monoclonal proteins in the
pathological fractures (typically serum and urine (Bence Jones
vertebral), osteolytic lesions proteins)
Lethargy ↑ plasma cells in the bone
Infection marrow
Hypercalcemia (see below) Bone lesions on the skeletal
Renal failure survey
Other features: amyloidosis Other findings on
e.g. Macroglossia, carpal tunnel investigations:
o Rouleaux formation of
syndrome; neuropathy;
hyperviscosity RBCs on blood film
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Definition of active multiple myeloma: clonal bone marrow plasma
cells >10% or biopsy‐proven bony or extramedullary plasmacytoma and
any one or more of the following CRAB features and myeloma‐defining
events:
Evidence of end organ damage that can be attributed to the
underlying plasma cell proliferative disorder, specifically:
o HyperCalcemia:
o Renal insufficiency: creatinine clearance <40 mL per minute or
serum creatinine >177µmol/L (>2mg/dL)
o Anaemia: haemoglobin <100g/L
o Bone lesions: ≥ 1 osteolytic lesion on skeletal radiography, CT,
or PET/CT. (If bone marrow has <10% clonal plasma cells, more
than one bone lesion is required to distinguish from solitary
plasmacytoma with minimal marrow involvement)
Any of the following biomarkers of malignancy (MDEs):
o ≥ 60% clonal plasma cells on bone marrow examination
o Serum involved / uninvolved free light chain ratio ≥ 100,
provided the absolute level of the involved light chain is at least
Part II 100mg/L (involved free light chain [either kappa or lambda] >
normal range. Uninvolved free light chain is the one that is
typically ≤ normal range)
o >1 focal lesion on MRI that is at ≥ 5mm.
Classification of MRCP important Plasma Cells Disorder:
Pre‐Cancer Cancer
Classification MGUS Smoldering Multiple
Multiple Myeloma
Myeloma
Plasma cells in < 10% 10‐60% > 10%
bone marrow
Myeloma
Defining Event
(MDE)
Chance of 1% 10% Cancer
progression to per year per year
cancer
Yes, for high‐
Treatment No = risk
Observation No, for other
groups
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High‐Risk Criteria for Smoldering MM:
o Plasma cells > 10% If all criteria is met → high
o M protein > 3g/dl risk
o Free light chain ration > 8 If 2 only → intermediate
or < 0.125 risk
If 1 only → low risk
Part II
B2‐microglobulin is a useful marker of prognosis ‐ raised levels imply poor
prognosis. Low levels of albumin are also associated with a poor prognosis
International prognostic index
Stage Criteria Median survival (months)
I B2 microglobulin < 3.5 mg/l 62
Albumin > 35 g/l
II Not I or III 45
III B2 microglobulin > 5.5 mg/l 29
Initial treatment depends on the patient’s age and comorbidities:
< 65 years of age:
High‐dose chemotherapy with hematopoietic stem‐cell
transplantation
Prior to stem‐cell transplantation, these patients receive an
Part II initial course of induction chemotherapy (thalidomide–
dexamethasone, bortezomiband lenalidomide–
dexamethasone.
Autologous stem cell transplantation (ASCT), (patient’s own
stem cells after chemotherapy), is the most common type of
stem cell transplantation for multiple myeloma. It is not
curative but does prolong overall survival.
Allogeneic stem cell transplantation, (transplantation of a
healthy person’s stem cells into the affected patient), has the
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ENDOCRINOLOGY
90% of diabetics have type 2
diabetes and around 8% have
type 1. About 2% have rarer
types of diabetes. Someone is
diagnosed with diabetes every
two minutes. 4.7 million people
in the UK have diabetes. At least
10,350 people in the UK have
end stage kidney failure
because of DM.
Diabetes UK 2019
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SIADH: criteria
Inappropriately ↑ urine
Normal Renal, Normal Adrenal and
Normal Thyroid and No Diuretics. osmolality >100
Hyponatraemia<135 mEq/L Urine Sodium >20 mEq/L
Hypotonic plasma – Osm<270 (inappropriate natriuresis)
Causes:
1. Malignancy 2. Infections
Especially small cell lung cancer TB
Also: pancreas, prostate Pneumonia
3. Neurological 4. Drugs
Stroke Sulfonylureas
Subarachnoid haemorrhage SSRIs, tricyclics
Subdural haemorrhage Carbamazepine
Meningitis/encephalitis/abscess Vincristine
Cyclophosphamide
5. Other causes
Positive end‐expiratory
pressure (PEEP)
Porphyria’s
ENDOCRINOLOGY : Pituitary Gland
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Primary Hyperparathyroidism: in postgraduate exams, primary
hyperparathyroidism is stereotypically seen in elderly ♀s with an unquenchable
thirst and an inappropriately normal or raised parathyroid hormone level. It is
most commonly due to a solitary adenoma
The PTH level in primary hyperparathyroidism may be normal
Features
Causes
'Bones, stones, abdominal groans 80%: solitary adenoma
and psychic moans' 15%: hyperplasia
Polydipsia, polyuria 4%: multiple adenoma
Peptic ulceration 1%: carcinoma
/constipation/pancreatitis
Bone pain/fracture
Renal stones
Depression
Hypertension
Associations
Hypertension
Multiple endocrine neoplasia: MEN I and II
Investigations Treatment
Raised calcium, low IV Fluids
phosphate Total parathyroidectomy
PTH may be raised or normal Bisphosphonates
Technetium‐MIBI subtraction
scan
ENDOCRINOLOGY : Thyroid & Parathyroid Glands 539
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