Unlock-The Only MRCP Notes You Will Ever Need 4ed

The Only MRCP Notes You’ll Ever Need

Hani Abuelgasim M.
1Hussam
/ 546
www.sudamedica.com
A. Albanna


MRCP, The Only Notes You Will Ever Need, 4th edition © January 2012
3rd edition © October 2010
2nd edition © January 2010
1st edition © September 2009

Copyright © 2012 SudaMediCa Publications
ISBN: pending issuance
All rights reserved. No part of this publication may be reproduced or distributed in any form or by any
means, or stored in a database or retrieval system, without the prior written permission of the publisher.

The Only MRCP Notes You’ll Ever Need

2 / 546

www.sudamedica.com


PREFACE
These notes intended to target those who are appearing in MRCP exam. The idea behind it was
collecting the most commonly tested topics and facts in the exam for my personal revision. The data
has been collected from many sources.
This book was not prepared to be the primary studying source but it can help you after finishing your

primary reading by arranging the thoughts in your mind and making every topic as short as possible by
highlighting the most important points about it. You may use it just before going through your favorite
MCQs book or internet site.
A friend of mine appeared in part one for couple of times, he reached to a conclusion and gave me a
valuable advice that said ‘when preparing for MRCP, study MRCP! Don’t study medicine!’ this book
helps you to study MRCP rather than studying medicine. But at the end, you have to be a good
physician otherwise MRCP will be a less valuable recognition, this is why I would advise to study
medicine before you study MRCP and for sure before you say that you are a member of the Royal
College you have to be upto the expectations.
This edition contains the latest guidelines including 2011 guidelines and recommendations. It is more
organized than ever.
In the 4th edition we have added topics that matters for part two, we have added many pictures, we
claim that it’s just enough to get you through the second part comfortably.
The study pattern we recommend is:
1. Study one chapter of your choice from this book
2. Solve the same chapter’s questions either on www.passmedicine.com, www.onexamination.com
or www.pastest.co.uk
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. Now you have probably solved at least 4000 BOF questions, you have seen all the question
patterns in MRCP, now you need to stabilize the information you have gained through your
journey
7. The most important step is to revise this book again just before the exam, this should be the
last thing you do just before going to the exam. Solving question till the last moment is not
recommended, you have probably gathered enough amount of information in your study, try to
fix the information by reading this book.
All candidates who followed this pattern have passed comfortably and no single one gave us a negative

feedback in both parts.
Hani Abuelgasim M., MD
Author

The Only MRCP Notes You’ll Ever Need

3 / 546

www.sudamedica.com


DEDICATION
To Mehiara, my late daughter who stole my heart and left
To my lovely Ahlam, who kept being patient and kind while I was studying
To my parents who always supported me
Hani Abuelgasim M.

The Only MRCP Notes You’ll Ever Need

4 / 546

www.sudamedica.com


CONTRIBUTORS
Dr.Hussam Albanna
Cardiology Registrar
MBBS, MRCP UK

Dr.Ahmed Ali Abuzaid

Medicine Specialist
MBBS, MRCP UK, MRCP Ireland

Dr.Salma Othman
Senior Cardiology Resident
MBBS, MRCP Part 1

Dr.Ahmed Elmotaz Mahgoub
Nephrology Specialist
MBBS, MRCP, Nephrology Diploma (Sheffield, UK)

To contribute to the


next

The Only MRCP Notes You’ll Ever Need

edition,

please

5 / 546

send

your

contributions

www.sudamedica.com

to


ALL BOXES WITH THIS COLOR
ARE FOR
MRCP PART II WRITTEN EXAM

The Only MRCP Notes You’ll Ever Need

6 / 546

www.sudamedica.com


Contents
……………...…………………………….
……………...…………………………….
……………...…………………………….
……………...…………………………….
……………...…………………………….
……………...…………………………….
……………...…………………………….
……………...…………………………….
……………...…………………………….
……………...…………………………….
……………...…………………………….
……………...…………………………….
Infectious & STD Diseases ……………...…………………………….

……………...…………………………….
Gyne & Obs
……………...…………………………….
Dermatology
……………...…………………………….
Psychiatry
……………...…………………………….
Ophthalmology

Basic Medical Science
Biostatistics & EBM
Miscellaneous
Neurology
Hematology
Endocrinology
GIT
Nephrology
Locomotor System
Rhematology
Cardiovascular System
Respiratory Sytem

Pharmacology
• General Pharma
• Nervous Pharma
• Cardiac Pharma

• Other Medications
• Antibiotics
Commonly tested facts in MRCP

……………...…………………………….
……………...…………………………….
……………...…………………………….
……………...…………………………….
……………...…………………………….
……………...…………………………….

The Only MRCP Notes You’ll Ever Need

7 / 546

9
53
65
83
131
167
203
245
269
287
309
357
389
425
437
459
475
491

492
509
515
523
535
541

www.sudamedica.com


The Only MRCP Notes You’ll Ever Need

8 / 546

www.sudamedica.com


BASIC SCIENCES

The Only MRCP Notes You’ll Ever Need

9 / 546

www.sudamedica.com


HLAs: are encoded for by genes on chromosome 6. HLA A, B and C are class I antigens whilst DP,
DQ, DR are class II antigens. Questions are often based around which diseases have strong HLA
associations. The most important associations are listed below
HLA and autoimmune diseases

Ankylosing spondylitis
Postgonococcal arthritis
HLA-B27
Acute anterior uveitis
Reiter's syndrome (reactive arthritis)
Narcolepsy
HLA-DR2
Goodpasture's
Autoimmune hepatitis
Primary biliary cirrhosis
Diabetes mellitus type 1
HLA-DR3
Dermatitis herpetiformis
Coeliac disease (95% associated with HLA-DQ2)
Primary Sjögren syndrome
Rheumatoid arthritis
HLA-DR4
Diabetes mellitus type 1 (> DR3)
HLA-DR3 + DR4 combined
Diabetes mellitus type 1
HLA-B47
21-hydroxylase deficiency
HLA-A3
Hemochromatosis
HLA-B5
Behcet's disease HLA B51 is a split of B5

Around 70% of patients with rheumatoid arthritis are HLA-DR4. Patients with Felty's syndrome
(a triad of rheumatoid arthritis, splenomegaly and neutropaenia) are even more strongly
associated with 90% being HLA-DR4

Clusters of Differentiation (CD): The table below lists the major clusters of differentiation
(CD) molecules
CD1 HLA molecule that presents lipid molecules
Found on thymocytes, T cells, and some natural killer cells that acts as a ligand for CD58 and
CD2
CD59 and is involved in signal transduction and cell adhesion
CD3 The signalling component of the T cell receptor (TCR) complex
CD4 Co-receptor for HLA class II; also a receptor used by HIV to enter T cells
CD8 Co-receptor for HLA class I; also found on a subset of myeloid dendritic cells

The Only MRCP Notes You’ll Ever Need

10 / 546

www.sudamedica.com


Hypersensitivity
The Gell and Coombs classification divides hypersensitivity reactions into 4 types
Type I - Anaphylactic
• Antigen reacts with IgE bound to mast cells
• Anaphylaxis, atopy
Type II - Cell bound
• IgG or IgM binds to antigen on cell surface
• Autoimmune hemolytic anemia, ITP, Goodpasture's
Type III - Immune complex
• Free antigen and antibody (IgG, IgA) combine
• Serum sickness, SLE, post-streptococcal glomerulonephritis, extrinsic allergic alveolitis
(especially acute phase)

Type IV - Delayed hypersensitivity
• T cell mediated
• Tuberculosis, Tuberculin skin reaction, grafT versus hosT disease, allergic conTacT
dermaTiTis, scabies, exTrinsic allergic alveoliTis (especially chronic phase)
In recent times a further category has been added:
Type V - Stimulated hypersensitivity
• IgG antibodies stimulate cells they are directed against
• Graves', myasthenia Gravis
Allergy Tests

Skin prick test

Most commonly used test as easy to perform and inexpensive. Drops of
diluted allergen are placed on the skin after which the skin is pierced using a
needle. A large number of allergens can be tested in one session. Normally
includes a histamine (positive) and sterile water (negative) control. A
wheal will typically develop if a patient has an allergy. Can be interpreted
after 15 minutes
Useful for food allergies and also pollen and wasp/bee venom
Determines the amount of IgE that reacts specifically with suspected or
known allergens, for example IgE to egg protein. Results are given in grades
from 0 (negative) to 6 (strongly positive)

Radioallergosorbent
test (RAST)

Skin patch testing

Useful for food allergies inhaled allergens (e.g. pollen) and wasp/bee venom
Blood tests may be used when skin prick tests are not suitable, for example

if there is extensive eczema or if the patient is taking antihistamines.
Useful for contact dermatitis. Around 30-40 allergens are placed on the
back. Irritants may also be tested for. The results are read 48 hours later by a
dermatologist

The Only MRCP Notes You’ll Ever Need

11 / 546

www.sudamedica.com


Immunoglobulins
IgG
IgA
IgM
IgD
IgE

75%
15%
10%
1%
0.1%

Monomer
Mono+Dimer
Pentamer
Monomer
Monomer

Enhance phaGocytosis of bacteria and viruses.
Found in secretions, provide localized protection on mucous membranes
first to be secreted, anti-A, B blood antibodies → Blood Transfusion
Involved in activation of B cells
Involved in allergic reactions

Each day an average adult produces approximately 3gm of antibodies, about two-thirds of this IgA
1. IgG
•
•
•
•
•
•
•

IgG makes up approximately 75% of the serum antibodies.
IgG has a half-life of 7-23 days depending on the subclass.
IgG is a monomer and has 2 epitope-binding sites
The Fc portion of IgG can activate the classical complement pathway.
The Fc portion of IgG can bind to macrophage and neutrophils for enhanced phaGocytosis.
The Fc portion of IgG can bind to NK cells for antibody-dependent cytotoxicity (ADCC).
The Fc portion of IgG enables it to cross the placenta. (IgG is the only class of antibody that
can cross the placenta and enter the fetal circulation).

2. IgA
• IgA makes up approximately 15% of the serum antibodies, it has a half-life of ≈ 5 days.
• IgA is found mainly in body secretions (saliva, mucous, tears, colostrum and milk) as
secretory IgA (sIgA) where it protects internal body surfaces exposed to the environment

by blocking the attachment of bacteria and viruses to mucous membranes.
• Secretory IgA is the most immunoglobulin produced.
• IgA is made primarily in the mucosal-associated lymphoid tissues (MALT).
• IgA appears as a dimer of 2 "Y"-shaped molecules and has 4 epitope-binding sites and a
secretory component to protect it from digestive enzymes in the secretions
• The Fc portion of secretory IgA binds to components of mucous and contributes to the
ability of mucous to trap microbes.
• IgA can activate the alternative complement pathway. (IgA ≈ Alternate)
3. IgM
• IgM makes up approximately 10% of the serum antibodies and is the first antibody produced
during an immune response.
• IgM has a half-life of about 5 days.
• IgM is a pentamer and has 10 epitope-binding sites
• The Fc portions of IgM are able to activate the classical complement pathway (most efficient)
• Monomeric forms of IgM are found on the surface of B-lymphocytes as B-cell receptors or sIg.
4. IgD
• IgD makes up approximately 1% of the serum antibodies.
• IgD is a monomer and has 2 epitope-binding sites.
• IgD is found on the surface of B-lymphocytes (along with monomeric IgM) as a B-cell
receptor or sIg where it may control of B-lymphocyte activation and suppression.
• IgD may play a role in eliminating B-lymphocytes generating self-reactive autoantibodies.

The Only MRCP Notes You’ll Ever Need

12 / 546

www.sudamedica.com


5. IgE

•
•
•
•
•
•

•

IgE makes up about 0.002% of the serum antibodies with a half-life of 2 days.
Most IgE is tightly bound to basophils and mast cells via its Fc region.
IgE is a monomer and has 2 epitope-binding sites.
IgE is made in response to parasitic worms (helminths) and arthropods. It is also often made in
response to allergens.
IgE may protect external mucosal surfaces by promoting inflammation, enabling IgG,
complement proteins, and leucocytes to enter the tissues.
The Fc portion of IgE can bind to mast cells and basophils where it mediates many allergic
reactions. Cross linking of cell-bound IgE by antigen triggers the release of vasodilators for an
inflammatory response.
The Fc portion of IgE made against parasitic worms and arthropods can bind to
eosinophils enabling opsonization. This is a major defense against parasitic worms and
arthropods.

Primary Immunodeficiency

disorders may be classified according to which component of

the immune system they affect
Neutrophil disorders
• Chronic granulomatous disease

• Chediak-higashi syndrome
• Leukocyte adhesion deficiency
B-cell disorders
• IgA deficiency
• Bruton's congenital agammaglobulinemia
• Common variable immunodeficiency
T-cell disorders = DiGeorge
• DiGeorge syndrome is an example of a microdeletion syndrome. Patients are consequently at ↑
risk of viral and fungal infections.
Combined B- and T-cell disorders
• Severe combined immunodeficiency
• Ataxic telangiectasia (Autosomal recessive - 10% risk of developing malignancy, lymphoma or
leukaemia, but also non-lymphoid tumours - recurrent chest infections)
• Wiskott-Aldrich syndrome inherited in an X-linked recessive fashion and is thought to be
caused by mutation in the WASP gene. Features include recurrent bacterial infections (e.g.
chest), eczema and thrombocytopenia with low IgG.

ANCA
There are two main types of anti-neutrophil cytoplasmic antibodies (ANCA) - cytoplasmic (cANCA)
and perinuclear (pANCA)
For the exam, remember:
• cANCA - Wegener's Granulomatosis
• pANCA - Churg-Strauss syndrome + others (see below)
The Only MRCP Notes You’ll Ever Need

13 / 546

www.sudamedica.com

cANCA
• Most common target serine proteinase 3 (PR3)
• Some correlation between cANCA levels and disease activity
• Wegener's granulomatosis, positive in > 90%
• Microscopic polyangiitis, positive in 40%
pANCA
• Most common target is myeloperoxidase (MPO)
• Cannot use level of pANCA to monitor disease activity
• Associated with immune crescentic glomerulonephritis (positive in c. 80% of patients)
• Microscopic polyangiitis, positive in 50-75%
• Churg-Strauss syndrome, positive in 60%
• Wegener's granulomatosis, positive in 25%
Other causes of positive ANCA (usually pANCA)
• Inflammatory bowel disease (UC > Crohn's)
• Connective tissue disorders: RA, SLE, Sjogren's
• Autoimmune hepatitis
Whilst C3 deficiency is associated with recurrent bacterial infections, C5 deficiency is more
characteristically associated with disseminated meningococcal infection

Complement Deficiencies
Complement is a series of proteins that circulate in plasma and are involved in the inflammatory and
immune reaction of the body. Complement proteins are involved in chemotaxis, cell lysis and
opsonisation
C1 inhibitor (C1-INH) protein deficiency
• Causes hereditary angiedema
• C1-INH is a multifunctional serine protease inhibitor
• Probable mechanism is uncontrolled release of bradykinin resulting in edema of tissues
C1q, C1rs, C2, C4 deficiency (classical pathway components)
• Predisposes to immune complex disease
• E.g. SLE, Henoch-Schonlein Purpura

C3 deficiency
• Causes recurrent bacterial infections
C5 deficiency
• Predisposes to Leiner disease
• Recurrent diarrhea, wasting and seborrhoeic dermatitis
• Disseminated meningococcal infection.
C5-9 deficiency
• Encodes the membrane attack complex (MAC)
• Particularly prone to Neisseria meningitidis infection
The Only MRCP Notes You’ll Ever Need

14 / 546

www.sudamedica.com


Electrolytes and Its Imbalance
Metabolic Acidosis is commonly classified according to the anion gap. This can be calculated
by: (Na+ + K+) - (Cl- + HCO-3). If a question supplies the chloride level then this is often a clue that
the anion gap should be calculated. The normal range = 10-18 mmol/L
Normal anion gap (hyperchloraemic metabolic acidosis)
• Gastrointestinal bicarbonate loss: diarrhea, ureterosigmoidostomy, fistula
• Renal tubular acidosis
• Drugs: e.g. Acetazolamide
• Ammonium chloride injection
• Addison's disease
Renal tubular acidosis (RTA) causes a normal anion gap
Raised anion gap
• Lactate: shock, hypoxia
• Ketones: DKA, alcohol

• Urate: renal failure
• Acid poisoning: salicylates, methanol
Metabolic acidosis secondary to high lactate levels may be subdivided into two types:
• Lactic acidosis type A: shock, hypoxia, burns
• Lactic acidosis type B: metformin

Metabolic Alkalosis may be caused by a loss of hydrogen ions or a gain of bicarbonate. It is
due mainly to problems of the kidney or gastrointestinal tract
Causes
• Vomiting / aspiration (e.g. Peptic ulcer leading to pyloric stenosis, nasogastric suction)
• Diuretics
• Liquorice, carbenoxolone
• Hypokalemia
• Primary hyperaldosteronism
• Congenital adrenal hyperplasia
• Cushing's syndrome
• Bartter's syndrome
Mechanism of metabolic alkalosis
• Activation of renin-angiotensin II-aldosterone (RAA) system is a key factor
• Aldosterone causes reabsorption of Na+ in exchange for H+ in the distal convoluted tubule
• ECF depletion (vomiting, diuretics) → Na+ and Cl- loss → activation of RAA system → raised
aldosterone levels
• In Hypokalemia, K+ shift from cells → ECF. Alkalosis is caused by shift of H+ into cells to
maintain neutrality

The Only MRCP Notes You’ll Ever Need

15 / 546

www.sudamedica.com

Hyponatremia

may be caused by water excess or sodium depletion. Causes of
pseudohyponatremia include hyperlipidemia (↑ 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.

Plasma Osmolality

Hypertonic
> 290

↑ Volemic

Isotonic
290-275

Hypotonic
< 275

↓ Volemic

↔ Volemic

Urinary sodium > 20 mmol/L
Urinary sodium < 20 mmol/L
Sodium depletion, renal loss (patient often Sodium depletion, extra-renal loss
hypovolaemic)

• Diarrhea, vomiting, sweating
• Diuretics
• Burns, adenoma of rectum
• Diuretic stage of renal failure
Water excess (patient often hypervolaemic and
• Addison's
edematous)
Patient often euvolaemic
• Secondary hyperaldosteronism: CCF,
cirrhosis
• SIADH (urine osmolality > 500 mmol/kg)
• ↓ GFR: renal failure with volume overload
• Hypothyroidism
• IV dextrose, psychogenic polydipsia

The Only MRCP Notes You’ll Ever Need

16 / 546

www.sudamedica.com


Hypernatremia: Causes
•
•
•
•

Dehydration
Osmotic diuresis e.g. Hyperosmolar non-ketotic diabetic coma

Diabetes insipidus
Excess IV saline

Hyperkalemia:

Plasma potassium levels are regulated by a number of factors including
aldosterone, acid-base balance and insulin levels. Metabolic acidosis is associated with Hyperkalemia
as hydrogen and potassium ions compete with each other for exchange with sodium ions across cell
membranes and in the distal tubule. ECG changes seen in Hyperkalemia include Tall-Tented T Waves,
small P waves, widened QRS leading to a sinusoidal pattern and asystole
Causes of Hyperkalemia:
• Acute renal failure
• Drugs*: potassium sparing diuretics, ACE
inhibitors, Cyclosporin
• Metabolic acidosis
• Addison's
• Rhabdomyolysis
• Massive blood transfusion
*β-blockers interfere with potassium transport
into cells and can potentially cause Hyperkalemia
in renal failure patients - remember β-agonists,
e.g. salbutamol, are sometimes used as
emergency treatment for hyperkalemia.
Untreated hyperkalaemia may cause lifethreatening arrhythmias. Precipitating factors
should be addressed (e.g. acute renal failure) and
aggravating drugs stopped (e.g. ACE inhibitors).
Management may be categorised by the aims of
treatment
Stabilisation of the cardiac membrane
• intravenous calcium gluconate

Short-term shift in potassium from extracellular
to intracellular fluid compartment
• combined insulin/dextrose infusion
• nebulised salbutamol
Removal of potassium from the body
• calcium resonium (orally or enema)
• loop diuretics
• dialysis

The Only MRCP Notes You’ll Ever Need

17 / 546

www.sudamedica.com


Hypokalemia
Potassium and hydrogen can be thought of as competitors. Hyperkalemia tends to be associated with
acidosis because as potassium levels rise fewer hydrogen ions can enter the cells
Hypokalemia with alkalosis
• Vomiting
• Diuretics
• Cushing's syndrome
• Conn's syndrome (primary hyperaldosteronism)
Hypokalemia with acidosis:
• Diarrhea
• Renal tubular acidosis
• Acetazolamide
• Partially treated DKA
ECG features of hypokalemia:

• U waves
• Small or absent T waves (occasionally inversion)
• Prolong PR interval
• ST depression
• Long QT
In Hypokalemia, U have no Pot and no T, but a long PR and a long QT!

Hypomagnesemia:
Cause of low magnesium
• Diuretics
• Total Parenteral Nutrition (TPN)
• Diarrhea
• Alcohol
• Hypokalemia, hypocalcemia
Features
• Paraesthesia
• Tetany
• Seizures
• Arrhythmias
• ↓ PTH secretion → hypocalcemia
• ECG features similar to those of Hypokalemia
• Exacerbates digoxin toxicity

The Only MRCP Notes You’ll Ever Need

18 / 546

www.sudamedica.com

Hypophosphatemia
Causes
• Alcohol excess
• Acute liver failure
• Diabetic ketoacidosis
• Refeeding syndrome (like in anorexia nervosa management)
• Primary hyperparathyroidism
• Osteomalacia
Consequences
• Red blood cell hemolysis
• White blood cell and platelet dysfunction
• Muscle weakness and rhabdomyolysis
• Central nervous system dysfunction

Calcium Metabolism
Vitamin D ↑ plasma calcium and plasma phosphate levels by promoting renal tubular absorption
and gut absorption of calcium and increasing renal phosphate reabsorption
The two hormones which primarily control calcium metabolism are:
• parathyroid hormone (PTH)
• vitamin D
Other hormones include
• Calcitonin: secreted from the C cells of the thyroid gland
• Thyroxine
• Growth hormone
Actions of parathyroid hormone (↑ plasma Ca from bones and kidneys and activation of Vit-D)
• ↑ plasma calcium, ↓ plasma phosphate
• ↑ renal tubular reabsorption of calcium
• ↑ osteoclastic activity
• ↑ renal conversion of 25-hydroxy vitamin D to 1,25 dihydroxy vitamin D
• ↓ renal phosphate reabsorption

Actions of vitamin D (↑ plasma Ca from bones and kidneys and GIT)
• ↑ plasma calcium and ↑ plasma phosphate
• ↑ renal tubular reabsorption and gut absorption of calcium
• ↑ osteoclastic activity
• ↑ renal phosphate reabsorption
FYI

Corrected Ca+ = measures Ca+ (mmol/l) + [40 - S.Albumin (g/dl)] x 0.027

The Only MRCP Notes You’ll Ever Need

19 / 546

www.sudamedica.com


Hypocalcemia
The clinical history combined with parathyroid hormone levels will reveal the cause of
hypocalcemia in the majority of cases
Causes
• Vitamin D deficiency (osteomalacia)
• Chronic renal failure
• Hypoparathyroidism (e.g. Post thyroid/parathyroid surgery)
• Pseudohypoparathyroidism (target cells insensitive to PTH)
• Rhabdomyolysis (initial stages)
• Magnesium deficiency (due to end organ PTH resistance)
Acute pancreatitis may also cause hypocalcemia. Contamination of blood samples with EDTA may
also give falsely low calcium levels
Hypocalcemia causes Prolonged QT in ECG
Osteomalacia causes hypocalcemia associated with a low serum phosphate

Cisplatin, often used in the management of non-small cell lung cancer, is a well known cause of
magnesium deficiency. Without first correcting magnesium levels it is difficult to reverse hypocalcemia
As extracellular calcium concentrations are important for muscle and nerve function many of the
features seen in hypocalcemia seen a result of neuromuscular excitability
Features
• Tetany: muscle twitching and spasm
• Perioral paraesthesia
• If chronic: depression, cataracts
• ECG: prolonged QT interval
Hypocalcemia: Trousseau's sign is more sensitive and specific than Chvostek's sign
Trousseau's sign
• Carpal spasm if the brachial artery occluded by inflating the blood pressure cuff and
maintaining pressure above systolic
• Wrist flexion and fingers drawn together
• Seen in around 95% of patients with hypocalcemia and around 1% of normocalcaemic people
Chvostek's sign
• Tapping over parotid causes facial muscles to twitch
• Seen in around 70% of patients with hypocalcemia and around 10% of normocalcaemic people
Management
• Acute management of severe hypocalcemia is with intravenous replacement. The preferred
method is with intravenous calcium gluconate, 10ml of 10% solution over 10 minutes
• Intravenous calcium chloride is more likely to cause local irritation
• ECG monitoring is recommended
• Further management depends on the underlying cause
The Only MRCP Notes You’ll Ever Need

20 / 546

www.sudamedica.com

Hypercalcemia
The most common causes of hypercalcemia are malignancy (bone metastases, myeloma, PTHrP from
squamous cell lung cancer) and primary hyperparathyroidism
One of the key differentiating features between monoclonal gammopathy of uncertain
significance (MGUS) and myeloma is the absence of complications such as immune paresis,
hypercalcemia and bone pain
Other causes include
• Sarcoidosis*
• Vitamin D intoxication
• Acromegaly
• Thyrotoxicosis
• Milk-alkali syndrome
• Drugs: thiazides, Ca++ containing antacids
• Dehydration
• Addison's disease
• Paget's disease of the bone**

Parathyroid hormone levels are useful, as malignancy and primary hyperparathyroidism are the
two most common causes of hypercalcemia. A parathyroid hormone that is normal or raised
suggests primary hyperparathyroidism.
Hypercalemia causes short QT in ECG
*other causes of granulomas may lead to hypercalcemia e.g. tuberculosis and histoplasmosis
**usually normal in this condition but hypercalcemia may occur with prolonged immobilization
Management
The initial management of hypercalcemia is rehydration with normal saline, typically 3-4 litres/day.
Following rehydration bisphosphonates may be used. They typically take 2-3 days to work with
maximal effect being seen at 7 days
Other options include:
• Calcitonin - quicker effect than bisphosphonates

• Steroids in sarcoidosis
There is a limited role for the use of furosemide in hypercalcemia. It may be useful in patients who
cannot tolerate aggressive fluid rehydration

The Only MRCP Notes You’ll Ever Need

21 / 546

www.sudamedica.com


Hyperuricemia ↑ levels of uric acid may be seen secondary to either ↑ cell turnover or ↓ renal
excretion of uric acid. Hyperuricemia may be found in asymptomatic patients who have not
experienced attacks of gout
Hyperuricemia may be associated with both hyperlipidemia and hypertension. It may also be
seen in conjunction with the metabolic syndrome

↑ Synthesis:
• Lesch-Nyhan disease
• Myeloproliferative disorders
• Diet rich in purines
• Exercise
• Psoriasis
• Cytotoxics
↓ Excretion:
• Drugs: low-dose aspirin, diuretics, pyrazinamide
• Pre-eclampsia
• Alcohol
• Renal failure
• Lead

The Only MRCP Notes You’ll Ever Need

22 / 546

www.sudamedica.com


Body & Diseases Markers
Acute Phase Proteins:
The following proteins ↑:
•
•
•
•
•
•
•
•
•

CRP
ferritin
fibrinogen
α-1 antitrypsin
caeruloplasmin
serum amyloid A
serum amyloid P component
haptoglobin
complement

During the acute phase response the liver ↓ the production of other proteins (sometimes referred to as
negative acute phase proteins).

The following proteins ↓:
•
•
•
•
•

albumin
transthyretin (formerly known as prealbumin)
transferrin
retinol binding protein
cortisol binding protein

Rheumatoid factor is an IgM antibody against IgG

Rheumatoid Factor (RF) is a circulatinjg antibody (usually IgM) which reacts with antigenic
sites on the Fc portion of the patients own IgG
RF can be detected by:
• Rose-Waaler test: sheep red cell agglutination
• Latex agglutination test (less specific)
RF is positive in 70-80% of patients with rheumatoid arthritis; high titre levels are associated with
severe progressive disease (prognosis but NOT a marker of disease activity)
Other conditions associated with a positive RF include:
• Sjogren's syndrome (around 100%)
• Felty's syndrome (around 100%)
• Infective endocarditis (= 50%)

• SLE (= 20-30%)
• Systemic sclerosis (= 30%)
• General population (= 5%)
• Rarely: TB, HBV, EBV, leprosy
The Only MRCP Notes You’ll Ever Need

23 / 546

www.sudamedica.com


Nitric Oxide: vasodilation+inhibits platelet aggregation

Nitric Oxide previously known as endothelium derived relaxation factor, nitric oxide (NO) has
emerged as a molecule which is integral to many physiological and pathological processes. It is formed
from L-arginine and oxygen by nitric oxide synthetase (NOS). An inducible form of NOS has been
shown to be present in macrophages. Nitric oxide has a very short half-life (seconds), being inactivated
by oxygen free radicals
Effects
• Acts on guanylate cyclase leading to raised intracellular cGMP levels and therefore decreasing
Ca++ levels
• Vasodilation, mainly venodilation
• Inhibits platelet aggregation
Clinical relevance
• Underproduction of NO is implicated in hypertrophic pyloric stenosis
• Lack of NO is thought to promote atherosclerosis
• In sepsis ↑ levels of NO contribute to septic shock
• Organic nitrates (metabolism produces NO) is widely used to treat cardiovascular disease (e.g.
Angina, heart failure)
• Sildenafil is thought to potentiate the action of NO on penile smooth muscle and is used in the

treatment of erectile dysfunctions

Atrial Natriuretic Peptide (ANP) is a powerful vasodilator, and a protein (polypeptide)
hormone secreted by heart muscle cells. It is involved in the homeostatic control of body water,
sodium, potassium and fat (adipose tissue). ANP acts to ↓ the water, sodium and adipose loads on the
circulatory system, thereby reducing blood pressure
Basics
•
•
•
•

Secreted mainly from myocytes of right atrium and ventricle in response to ↑ blood volume
Secreted by both the right and left atria (right >> left)
28 amino acid peptide hormone, which acts via cGMP
Degraded by endopeptidases

Actions
• Natriuretic, i.e. Promotes excretion of sodium
• Lowers BP
• Antagonises actions of angiotensin II, aldosterone

The Only MRCP Notes You’ll Ever Need

24 / 546

www.sudamedica.com


BNP - actions:

• Vasodilator
• Diuretic and natriuretic
• Suppresses both sympathetic tone and the renin-angiotensin-aldosterone system

B-type Natriuretic Peptide (BNP)

hormone produced mainly by the left ventricular

myocardium in response to strain
Whilst heart failure is the most obvious cause of raised BNP levels any cause of left ventricular
dysfunction such as myocardial ischemia or valvular disease may raise levels. Raised levels may also
be seen due to ↓ excretion in patients with chronic kidney disease. Factors which ↓ BNP levels include:
treatment with ACE inhibitors, angiotensin-2 receptor blockers and diuretics.

Clinical uses of BNP
Diagnosing patients with acute dyspnea
• A low concentration of BNP(< 100pg/ml) makes a diagnosis of heart failure unlikely, but raised
levels should prompt further investigation to confirm the diagnosis
• NICE currently recommends BNP as a helpful test to rule out a diagnosis of heart failure
Prognosis in patients with chronic heart failure
• Initial evidence suggests BNP is an extremely useful marker of prognosis
Guiding treatment in patients with chronic heart failure
• Effective treatment lowers BNP levels
Screening for cardiac dysfunction
• Not currently recommended for population screening

Endothelin is a potent, long-acting vasoconstrictor and bronchoconstrictor. It is secreted initially
as a prohormone by the vascular endothelium and later converted to ET-1 by the action of endothelin
converting enzyme. It acts via interaction with a G-protein linked to phospholipase C leading to
calcium release. Endothelin is thought to be important in the pathogenesis of many diseases including

primary pulmonary hypertension (endothelin antagonists are now used), cardiac failure, hepatorenal
syndrome and Raynaud's
Promotes release
• Angiotensin II
• ADH
• Hypoxia
• Mechanical shearing forces
Inhibits release
• Nitric oxide
• Prostacyclin
The Only MRCP Notes You’ll Ever Need

25 / 546

www.sudamedica.com