MRCP revision battle 28.1: Haemochromatosis

I feel like I'm possibly starting to make some inroads into this MRCP revision thing, and my chocolate dependency level has decreased a little.  Today is another random assortment of gems:


MRCP revision battle 28.1: Haemochromatosis
MRCP revision battle 28.2: Syphilis
MRCP revision battle 28.3: Third nerve palsy
MRCP revision battle 28.4: G6PD deficiency
MRCP revision battle 28.5: Kaposi's sarcoma
MRCP revision battle 28.6: Chronic Myeloid Leukaemia
MRCP revision battle 28.7: Gerstmann's Syndrome



MRCP revision battle 28.1: Haemochromatosis


Haemochromatosis is an excessive accumulation of iron.
There is increased intestinal absorption leading to deposition in joints, skin, the heart, liver, pancreas, adrenals and pituitary.


It is an autosomal recessive disorder, inherited on chromosome 6.



Presentation is initially with tiredness and arthralgia

Later problems include:

• diabetes mellitus (bronze diabetes)
• slate-grey skin
• liver disease/cirrhosis
• cardiac failure/cardiomegaly
• pseudogout
• hypopituitism
• >30% develop hepatocellular carcinoma

Males are affected earlier and more severely than females.



Diagnosis is by:

• transferrin saturation >50%
• ferritin >300-500micrograms/l (depending on guidelines)
• liver biopsy  - Perls stain to show hepatic iron >180micromol/g

Treatment is regular venesection and ?chelation with desferrioxamine



Haemosiderosis is secondary haemochromatosis.  


Causes of haemosiderosis include:

• beta thalassemia
• sideroblastic anaemia
• aplastic anaemia
• transfusions
• alcoholic cirrhosis
• chronic viral hepatitis
• porphyria cutanea tarda

Thats enough iron for one day... onwards to some syphilis...

MRCP revision battle 28.2: Syphillis

Syphilis is another of those conditions which is a common differential in MRCP questions.



Syphilis is caused by the spirochaete treponema pallidum.



There are 4 stages of syphilis:


1) Primary

• painless genital ulcer
• known as a chancre
• highly infectious

2) Secondary

• occurs 4-8 weeks after the chancre
• rash, malaise, lymphadenopathy, temperature
• condylomata lata

3) Tertiary syphilis

• >2yrs after secondary
• gummas (=granulomas) form in skin, mucosa and viscera

4) Quaternary syphilis

• cardiovascular
• aortic aneurysm
• aortic regurgitation
• neurosyphilis
• cranial nerve palsies
• general paralysis of the insane
• tabes dorsalis
• sensory ataxia
• numb legs
• lightening pains
• upgoing plantars
• argyll robertson pupil

Tests:

• cardiolipin antibody = VDRL, RPR
• not syphilis specific
• insensitive in late syphillis
• becomes negative after treatment
• false +ives in pregnancy, SLE, TB, leprosy, malaria, HIV
• treponeme-specific antibody = TPHA
• remains positive after treatment
• dark ground microscopy

Treatment:

• IM penicillin or PO doxcycline

Random eponymous warning - Jarisch-Herxheimer reaction:

• raised pulse, temp and vasodilation
• occurs hours after 1st dose of antibiotics
• due to release of endotoxin

Occurs in around 90% of patients with secondary syphilis.




Now on for a bit of third nerve palsy....

MRCP revision battle 28.3: Third nerve palsy

Cranial nerve III = oculomotor nerve arises in the rostral midbrain at the level of the superior colliculus.


It has 2 adjacent nuclei:

• oculomotor nucleus - somatic fibres (eye movements)
• edinger-westphal nucleus - visceral fibres (pupillary constriction)

The oculomotor nerve passes between the posterior cerebral and superior cerebellar arteries, then on through the cavernous sinus and out through the superior orbital fissure.


In the orbit it splits into:

• superior branch - supplies levator palpebrae
• inferior branch - supplies medial rectus, inferior rectus and inferior oblique muscles and carries the visceral fibres

Complete 3rd nerve palsies tend to be peripheral rather than central in origin as the nucleus is big.



Classic 3rd nerve palsy:

• ptosis
• 'down and out' pupil
• dilated pupil

If the pupil is spared it is sometimes referred to as a 'medical' third nerve palsy, whereas if it is fixed and dilated it is a 'surgical' third nerve palsy.

The reasoning behind this is that the visceral constrictive fibres run on the outside of the nerve so are spared in vascular aetiologies.



Causes of third nerve palsy:

• diabetes (75% pupil-sparing)
• temporal arteritis
• SLE
• MS
• cavernous sinus thrombosis
• amyloid
• posterior communicating artery aneurysm (usually painful)
• tumour

Webers syndrome: ipsilateral third nerve palsy with contralateral hemiplegia --> signifies a midbrain stroke.



After that pleasant forray into the world of neurology on to something completely different - G6PD deficiency...

MRCP revision battle 28.4: G6PD deficiency

Glucose-6-phosphate dehydrogenase deficiency is the commonest RBC enzyme defect.

It is x-linked recessive.


It causes intravascular haemolysis.


Generally patients are asymptomatic unless a crisis is precipitated, in which case they become anaemic and jaundiced.

Precipitants of crisis include:

• drugs
• primaquine
• sulfonamides
• ciprofloxacin
• aspirin
• broad/fava beans
• illness

During a crisis a blood film will show:

• bite cells
• heinz bodies (=inclusions within RBCs of denatured haemoglobin)

 click here for a whole page of images of Heinz bodies



 Management is to avoid precipitants and transfuse if necessary.


On to Kaposi's sarcoma...

MRCP revision battle 28.5: Kaposi's sarcoma

Kaposi's sarcoma is a red, brown, purple or blue plaque on the skin or mucosa

Kaposi's sarcoma is derived from capillary endothelial cells or fibrous tissue.


It is associated with HHV-8.


It may be secondary to immunosupression, or a diagnosing feature of HIV infection.



Next up - CML....

MRCP revision battle 28.6: Chronic Myeloid leukaemia

Chronic myeloid leukaemia is an uncontrolled clonal proliferation of myeloid cells.

It tends to affect middle aged people (40 to 60 years)


Classical presentation is with:

• decreased weight
• tiredness
• sweating

Possible additional presentations are:

• gout due to increased purine breakdown
• abdo pain due to splenomegaly
• bleeding due to platelet dysfunction

Approximately 30% are detected by chance.



Features include:

• elevated WCC - often 100-500
• massive neutrophilia with left shift
• low neutrophil alkaline phosphatase
• splenomegaly in >75%

The philadelphia chromosome is present in >80% of cases

The philadelphia chromosome:

• is a hybrid chromosome formed by t(9;22)
• forms a gene BCR-ABL which results in excess tyrosine kinase activity
• found in 80% CML, 5% children with ALL, 25% of adult ALL and 1% adult AML.
• is associated with a good prognosis in CML but a poor prognosis in all other leukaemias

Treatment for CML is:

• hydroxyurea
• imatimib = glivec = specific BCR-ABL tyrosine kinase inhibitor
• bone marrow transplant

CML transforms to AML in 80% of cases and ALL in 20%




Last battle of the day is Gertmann's Syndrome...

MRCP revision battle 28.7: Gerstmann's Syndrome

Gerstmann's Syndrome is a condition characteristed by:

1. dysgraphia
2. dyscalculia
3. finger agnosia
4. left-right disorientation

Gerstmann's Syndrome is associated with lesions in the dominant brain hemisphere in the region of the angular gyrus of the parietal lobe.



On that esoteric note, see you tomorrow!

MRCP revision battle 27.1: Heparin induced thrombocytopenia (HIT)

Today we have an epic set of battles with some real hard-hitters hidden amongst them, including sarcoidosis which is a differential for around 110% of MRCP questions (or at least thats what it feels like)   But if you get to the last battle you will be rewarded with lots of pictures (the joys of poikilocytosis) and then a link to look at some interesting non-medical pictures...


So the carrot is dangled, and here are the sticks:

MRCP revision battle 27.1: Heparin induced thrombocytopenia (HIT)
MRCP revision battle 27.2: Sarcoidosis
MRCP revision battle 27.3: Lofgren's syndrome
MRCP revision battle 27.4: Pancreatitis
MRCP revision battle 27.5: Visual field defects
MRCP revision battle 27.6: Paroxysmal nocturnal haemoglobinuria
MRCP revision battle 27.7: Poikilocytosis



MRCP revision battle 27.1: Heparin induced thrombocytopenia (HIT)

Heparin induced thrombocytopenia is one of those fabulous conditions whose name explains it all: low platelets, caused by heparin.  It is often abbreviated to HIT, which confused me greatly when I first had a patient affected by it and my consultant declared "ah, he's got HIT" which made me wonder who he was suspecting of abuse on the ward...


Technically there are 2 types of HIT:

• Type 1 - occurs in first 2 days, is non-immune and the platelet count spontaneously recovers 
• Type 2 - occurs 4 to 10 days after starting heparin, is immune-mediated and potentially life-threatening.

However, when HIT is mentioned, people generally mean type 2.



HIT is caused by antibodies against the heparin-platelet factor 4 complex.  These antibodies can be found in 90% of patients with HIT... but may also be present in unaffected patients taking heparin.



Ironically, although HIT is characterised by low platelets it is an incredibly pro-thrombotic condition.  As a result patients are likely to get PEs/DVTs and warfarin must absolutely not be started (since warfarin is initially prothrombotic too).  As you can see HIT causes something of a management problem - thrombosis due to the treatment you would give for thrombosis...



Management of HIT will involve specialist haematological input but in terms of MRCP question answers think:

• stop heparin
• stop/reverse warfarin
• give lepirudin (=highly specific direct inhibitor of thrombin)

Note that HIT is more likely with unfractionated than LMW heparin.



Onwards to sarcoidosis...

MRCP revision battle 27.2: Sarcoidosis

Sarcoidosis is a multi-system granulomatous disorder of unknown cause.


It is asymptomatic in up to 40% of cases, being discovered incidentally on a routine CXR.


Features of sarcoidosis may be divided into pulmonary and non-pulmonary:

Pulmonary features of sarcoidosis:

• dry cough
• progressive dyspnoea
• chest pain

Non-pulmonary features of sarcoidosis include:

• lymphadenopathy (commonest in non-whites)
• erythema nodosum (commonest in white females)
• polyarthralgia
• hepatomegaly
• splenomegaly (around 25%)
• anterior uveitis (around 25%)
• glaucoma
• Bells palsy
• lupus pernio
• hypercalcaemia
• renal stones
• pituitary dysfunction
• cardiomyopathy...

90% of patients with sarcoid will have an abnormal CXR.
Staging of CXR in sarcoid is:

• 0 = clear CXR
• 1 = bilateral hilar lymphadenopathy
• 2 = bilateral hilar lymphadenopathy plus pulmonary infiltration
• 3 = pulmonary infiltration only
• 4 = fibrosis, honeycombing, pleural involvement

Investigations:

• raised ESR
• lymphopenia
• raised LFTs
• raised serum ACE
• raised calcium (5%)
• tuberculin skin test is positive in around a third

Management:

• BHL alone doesn't need treatment
• acute sarcoidosis : NSAIDs and bed rest
• prednisolone ( 40mg OD for 4-6 weeks then reducing dose over one year) is indicated if:
• parachymal lung disease
• uveitis
• hypercalcaemia
• neurological/cardiac involvement

Lets move on to briefly consider lofgrens syndrome...

MRCP revision battle 27.3: Lofgren's syndrome

Lofgrens syndrome is a subtype of sarcoidosis, characterised by:

• erythema nodosum
• bilateral hilar lymphadenopathy
• fever
• athralgia

It affects females more than males (85:15)


It carries a good prognosis - unlike sarcoidosis is unlikely to become chronic and most cases resolve in 6 months to 2 years.


On to something which often doesn't have a good prognosis... pancreatitis...

MRCP revision battle 27.4: Pancreatitis

Acute pancreatitis tends to present as epigastric/central abdominal pain radiating to the back with vomiting.  The pain may be improved by sitting forward.

Signs may be few; periumbilical discoloration (Cullen's sign) or flank discoloration (Grey Turner's sign) are rare.


Causes of pancreatitis can be remembered by I GET SMASHED:

• idiopathic
• gallstones
• ethanol
• trauma
• steroids
• mump
• autoimmune
• scorpion venom
• hyperlipidaemia, hypercalcaemia, hypothermia
• ERCP
• drugs (steroids, ocreotide, sulphonamides, tetracyclines, azathioprine, sodium valproate)

Investigations:

• bloods including amylase 
• note amylase normalises in 24-48hrs; serum lipase is more sensitive and specific
• AXR: ?sentinel loop ?loss of psoas shadow
• CT abdo is the investigation of choice
• score using the Modified Glasgow criteria.

Modified Glasgow criteria (helpfully spells out 'pancreas'):

• Pa O2 <8
• Age >55
• Neurophils: WCC >15
• Calcium: <2
• Renal function: urea >16
• enzymes: LDH >600; AST >200
• Albumin: <32
• Sugars: glucose >10

3 or more suggests severe pancreatitis.



Management of acute pancreatitis is:

• lots of IV fluid, catheter for fluid balance
• analgesia
• close observation
• treat cause

Complications of pancreatitis include:

• early
• sepsis
• shock
• ARDS
• renal failure
• DIC
• hypocalcaemia
• hyperglycaemia - 5% need insulin
• late
• necrosis and pseudocyst (=fluid in lesser sac)
• abscess
• fistulae
• chronic pancreatitis

Now for something completely different, visual field defects...

MRCP revision battle 27.5: Visual field defects

Visual fields pop up frequently in MRCP questions so it pays to learn this well!

The basic anatomy is illustrated below:

Armed this this anatomy lets look at the various patterns of field defect...




1: Bitemporal hemianopia

• caused by compression of the optic chiasm
• upper affected more than lower = due to pituitary tumour
• lower affected more than upper = due to craniopharyngioma
• I personally remember this as UP  London City

2: Homonymous quadrantanopia

• superior homonymous quadrantanopia is a lesion in the temporal lobe
• inferior homonymous quadrantanopia is a lesion in the parietal lobe
• this can be remembered by thinking PITS - parietal inferior temporal superior
• if the defect is incongruous it is in the optic tract
• if the defect is congruous it is in the optic radiation/cortex

3: Homonymous hemianopia

• injury to the brain (eg bleed, tumour) on the opposite side to the field defect

4: Central scotoma

• usually caused by optic neuritis

5: Binasal hemianopia

 

• rare
• ?calcification of carotids

Note that the fovea is supplied by both the PCA and MCA so may be spared in a PCA CVA.


In the calcarine sulcus peripheral regions are processed anteriorly while central regions are processed posteriorly.



Finally remember cortical blindness:

• caused by bilateral occipital infarcts
• pupillary responses are preserved
• possibly small macular sparing
• patient may deny they have vision loss (=Anton's syndrome)

Wow, that was lots for one battle... lets move on to some urine for light relief...

MRCP revision battle 27.6: Paroxysmal nocturnal haemoglobinuria

Paroxysmal nocturnal haemoglobinuria is a condition in which blood cells are sensitive to complement-mediated lysis due to an inherited lack of surface glucosylphosphatidylinositol (GPI)



Features of paroxysmal nocturnal haemoglobinuria include:

• cola coloured/red urine in morning due to increase in RBC lysis overnight
• intravascular haemolysis
• pancytopenia
• thrombosis

Diagnosis is by urinary haemosiderin or + Ham's test (rarely done now)


Treatment is anticoagulation, transfusions when needed and possibly the smart new monoclonal antibody called eculizimab.



Now on to the last battle and some pretty pictures...

MRCP revision battle 27.7: Poikilocytosis

Poikilocytosis = abnormality of red blood cell shape.

Here's a quick crash course of the various shapes and their causes.  Blood slides are all from wiki commons.



1. Teardrop cells - myelofibrosis

2. Helmet cells - microangiopathic haemolytic anaemias

click here to link to an image covered by copyright


3. Elliptocytes = Pencil cells - seen in hereditary elliptocytosis and iron deficiency

4. Sickle cells - seen in sickle cell disease

5. Spherocytes - seen in any haemolysis and in hereditary spherocytosis

6. Target cells - seen in liver disease, post splenectomy, iron deficieny, thalassaemia, haemoglobinopathies


click here to link to an image covered by copyright



7. Acanthocyte/burr cell - acanthocytes are seen in liver disease.  Burr cells (=slightly less spikey than acanthocytes) appear in uraemia.

 

8. Schistocyte  = shredded red blood cells, seen in DIC, mechanical heart valves, microangiopathic diseases, haemolytic anaemias

Thats all the battles for today; as promised at the beginning  click here if you want to see some interesting pictures of what your workplace might look like if abandoned for a few years...

MRCP revision battle 26.1: Parkinson's disease

I'm back on the revision bandwagon and am ready for another 7 battles...


MRCP revision battle 26.1: Parkinson's disease
MRCP revision battle 26.2: Lewy Body Dementia
MRCP revision battle 26.3: Malignant hyperthermia
MRCP revision battle 26.4: Benign intracranial hypertension
MRCP revision battle 26.5: Coarctation of the aorta
MRCP revision battle 26.6: Heparin
MRCP revision battle 26.7: Essential tremor



MRCP revision battle 26.1: Parkinson's disease/Parkinsonism


Parkinsonism is a triad of:

• resting tremor (3 to 5 Hz)
• rigidity
• bradykinesia

 There is also loss of postural reflexes.


It is Parkinson's disease if there is degeneration of the substantia nigra dopaminergic neurones with Lewy bodies.


There are a whole list of associated features that I'm sure you're familiar with, but if you fancy a brief recap read the list below...

• expressionless, mask-like face
• dribbling
• festinant gait = short shuffling steps with flexed trunk)
• micrographia

Management of Parkinsons is by a multidisciplinary team and the pharmacological management of it is notoriously tricky, with multiple drugs which often decrease in efficacy with use and may result in 'on-off' symptoms.


Even the NICE guidelines recognise the challenge in drug prescription, stating that "it is not possible to identify a universal first-line drug choice".  They single out the following as possible first line options:

• levodopa
• use lowest dose possible
• give with carbidopa to prevent peripheral breakdown
• is of no use in neuroleptic induced Parkinsons
• dopamine agonists
• bromocriptine*, cabergoline*, ropinole
• if an argot-derived agonist is used (*) ESR, UEs and CXR should be done before starting and annually while on treatment
• MAO-B inhibitors
• selegiline
• decreases dopamine breakdown

Second line treatment is combining the above options, or one of the above with:

• COMT inhibitors
• entacapone
• inhibit dopamine breakdown

Other medications which may be useful for specific effects include:

• amantidine
• apomorphine
• antimuscarinics
• procyclidine
• more useful for drug-induced Parkinsons

A couple of other key points from the NICE guidelines on Parkinsons are:

• 'drug holidays' should not be undertaken due to risk of neuroleptic malignant syndrome on restarting
• clinicians should be aware of dopamine dysregulation syndrome, which is an uncommon disorder in which misuse of dopaminergic medication is associated with behaviours such as hypersexuality, pathological gambling and sterotypic motor acts

For the really keen:

Link to list of NICE guidelines on Parkinsons

For everyone else, lets move on to Lewy body dementia.

MRCP revision battle 26.2: Lewy Body Dementia

Lewy Body Dementia accounts for around 20% of cases of dementia.


The key feature is Lewy Bodies (=intracytoplasmic neuronal inclusion bodies) in substantia nigra, paralimbic and neocortical areas.


Since this would obviously only be confirmed post-mortem diagnosis is made clinically:

• Parkinsonian features
• fluctuating cognitive loss
• visual hallucinations

Neuroleptics must be avoided as their use would risk inducing irreversible Parkinsonism.



Treatments which may help include donepezil and rivastigmine.


Next up - malignant hyperthermia

MRCP revision battle 26.3: Malignant hyperthermia

Malignant hyperthermia is a rare, life-threatening condition in which there is a huge increase in the body's skeletal muscle oxidative metabolism, resulting in:

• hypercapnia
• increased oxygen consumption
• hyperthermia (T>38C)

Secondary problems which may develop from malignant hyperthermia include:

• renal failure
• arrhythmias
• DIC

Malignat hyperthermia may be caused by:

• any inhaled anaesthetic agent
• Succinylcholine  

It is often inherited in an autosomal dominant fashion.



Treatment is with dantrolene.



Onwards to benign intracranial hypertension...

MRCP revision battle 26.4: Benign intracranial hypertension

Benign intracranial hypertension classically affects overweight young females.

It presents like there should be a mass in the brain, but none can be found.


Features include:

• headache
• blurred vision
• dizziness
• horizontal diplopia
• papilloedema

Benign intracranial hypertension is associated with:

• COC
• steroids
• tetracyclines
• vitamin A
• nitrofurantoin
• isontertinoin
• danazol

Management is:

• weight loss
• acetazolamide
• loop diuretics
• prednisolone
• therapeutic lumbar puncture
• shunt

Note that up to 10% of patients have permanent significant vision loss - so its name of 'benign' is a little misleading!  Optic nerve sheath fenestration can help prevent this.


Onwards for a spot of coarctation of the aorta...

MRCP revision battle 26.5: Coarctation of the aorta

Coarctation of the aorta (=narrowing of the aorta) classically occurs just distal to the left subclavian artery.

It may present at birth with heart failure, or be discovered later in life, eg during investigation for hypertension.


Most adults with coarctation of the aorta are asymptomatic.  Occasionally they may complain of:

• headache
• recurrent epistaxis
• claudication of the calf muscles

Clinical examination may reveal:

• radio-femoral delay
• midsystolic murmur

Complications of coarctation include:

• hypertension
• LVF
• endocarditis

Conditions associated with coarctation include:

• bicuspid aortic valve (10-20%)
• PDA
• VSD
• Berry aneurysms
• Turners syndrome
• renal abnormalities

CXR may show rib notching due to formation of collaterals


Management is stenting/surgery.



Now for the penultimate battle of the day, heparin...

MRCP revision battle 26.6: Heparin

Heparin comes in 2 'flavours':

1. low molecular weight heparin (AKA dalteparin/fragmin, enoxaparin/clexane, tinzaparin) 
2. unfractionated (AKA 'heparin')

So what are the differences?

• molecular weight
• LMW heparin, as the name suggests, has a lower molecular weight - 5000 compared to unfractionated heparin's 13000
•  half life
• LMW heparin has a longer half life than unfractionated heparin
•  mechanism of action
• LMW heparin inhibits factor Xa but has little effect on antithrombin
• unfractionated heparin binds antithrombin
• affect on aPTT
• LMW heparin has little effect on aPTT
• unfractionated heparin prolongs aPTT
• side effects
• both can cause osteoporosis and thrombocytopenia but the risks are greatest with unfractionated heparin
• reversibility
• unfractionated heparin can be fully reversed by protamine
• LMW heparin cannot be fully reversed by protamine

A side effect of protamine to be aware of is hypotension.


HIT (=heparin induced thrombocytopenia) is a potentially serious side effect of heparin use which will be covered tomorrow.


With that to look forward to lets shake on to the last battle of the day, essential tremor...

MRCP revision battle 26.7: Essential tremor

Essential tremor can be sporadic or inherited; if inherited its inheritance pattern is believed to be autosomal dominant with incomplete penetrance.

35% of patients with essential tremor will have no family history.


It tends to be worse when the arms are outstretched.


Essential tremor improves with alcohol (not advised as a treatment option!)


Treatment tends to be:

• propranolol
• primidone if propranolol contra-indicated (eg in asthma)

Congratulations on surviving another day's battles!

MRCP revision battle 25.1: Neuroleptic Malignant Syndrome

Having been blessed by a set of on-calls with some nice interesting cases I'm full of enthusiasm for today's battles, so lets get on with it!


MRCP revision battle 25.1: Neuroleptic malignant syndrome
MRCP revision battle 25.2: Behcets disease
MRCP revision battle 25.3: Subarachnoid haemorrhage
MRCP revision battle 25.4: Normal pressure hydrocephalus
MRCP revision battle 25.5: Gas gangrene
MRCP revision battle 25.6: Methaemoglobinaemia
MRCP revision battle 25.7: The weeverfish




MRCP revision battle 25.1: Neuroleptic malignant syndrome


A nice straightfoward battle to begin with...


Neuroleptic malignant syndrome is a life-threatening condition associated with use of antipsychotic drugs.


Symptoms and signs include:

• hyperthermia
• rigidity/muscle cramps
• extrapyramidal signs
• autonomic dysfunction (labile BP, sweating, urinary incontinence
• confusion

Investigations show:

• raised CK
• raised WCC

Treatment is:

• cooling
• dantrolene (a muscle relaxant; note dantrolene is also used in malignant hyperthermia, which will be one of tomorrows battles)

Now on to a slightly less straightforward battle, Behcets disease...

MRCP revision battle 25.2: Behcets disease

Behcet's disease is a systemic vasculitis of unknown cause.


The classic triad of Behcet's disease is:

• oral ulcers
• genital ulcers
• anterior uveitus

which I remember as GOA, like the place in India.



Other possible features include:

• thrombophlebitis
• DVT
• erythema nodosum
• pathergy reaction (=needle prick leads to pustule formation)
• arthritis
• aseptic meningitis
• ataxia
• diarrhoea

Males are more commonly affected than females.
It is commonest in Turkey and Japan.
30% of patients have a positive family history.


HLA B5 is associated with anterior uveitis and HLA B12 is associated with recurrent ulceration.


Severe disease requires steroids/ciclosporin/azathioprine.


Next up - SAH...

MRCP revision battle 25.3: Subarachnoid haemorrhage

Subarachnoid haemorrhage is bleeding into the space between the subarachnoid membrane and the pia mater.

It accounts for 5-10% of all strokes.


Causes:

• ruptured berry aneurysm (80%)
• malformations (15%)
• post trauma

Common sites of berry aneurysms are:

• junction of the posterior communicating artery with the internal carotid
• junction of the anterior communicating artery with the anterior cerebral artery
• the bifurcation of the middle cerebral artery

If (like me) your anatomy of the circle of willis is a little rusty the wiki commons image below might help refresh your memory:

15% of berry aneurysms are multiple.




Subarachnoid haemorrhages are associated with:

• polycystic kidneys
• coarctation of the aorta
• Ehlers-Danlos syndrome
• PAN

Classical presentation is a thunderclap occipital headache "as if kicked in head" with vomiting and neck stiffness.
Around 6% of patients will have had a sentinel headache before.



Investigation is:

• CT - >90% of bleeds detected
• LP - done >12hrs after onset looking for xanthochromia

Management:

• neurosurgical referral
• prompt angiography if surgery likely
• nimodipine

On to another neuro topic - normal pressure hydrocephalus

MRCP revision battle 25.4: Normal pressure hydrocephalus

Normal pressure hydrocephalus is a triad of:

1. dementia
2. gait abnormality
3. urinary incontinence

(remember as DUG!)


It is caused by a defect in the absorption of CSF.
Causes include: meningitis, head injury, subarachnoid haemorrhage.


Note that there is NO headache and NO papilloedema.


Investigations:

• CT head (predictably) - enlarged ventricles
• large volume lumbar puncture - ? high opening pressure, ? improvement of symptoms
• lumbar infusion test

Treatment is a shunt.



Next up... gas gangrene!

MRCP revision battle 25.5: Gas gangrene

Gas gangrene is a life threatening bacterial infection.

It is characterised by muscle necrosis, gas production and sepsis.

A typical appearance is shown below:

                                       From Wiki Commons, taken by Engelbert Schröpfer, Stephan Rauthe and Thomas Meyer.






Most cases are caused by trauma innoculation with bacteria, for example a farmer standing on a pitchfork.
Very rarely it may occur spontaneously, for example in the context of neutropenia.


The commonest causative organism is clostridium perfringens.


Management is:

• urgent surgical debridement
• IV Abx 
• hyperbaric oxygen if available

Next up - methaemoglobinaemia

MRCP revision battle 25.6: Methaemoglobinaemia

Methaemoglobin (MetHb) is formed when the iron in haemoglobin is oxidised from the ferrous state (Fe2+) to the ferric state (Fe3+) 


Methaemoglobinaemia means raised MetHb levels, and as MetHb has a far higher affinity for oxygen than normal haemoglobin this results in tissue hypoxia as the oxygen being carried in the blood is not given up to the tissues.



Clinical features depend on the % of MetHb:

• 15-20% - cyanosis
• 20-45% - impaired consciousness
• >55% - seizures, arrhythmias, coma
• >70% - lethal

Pulse oximetry will show low oxygen sats, as will the printout from blood gas analysis - but the PaO2 will be high.



Causes of methaemoglobinaemia:

• congenital
• pyruvate kinase deficiency
• G6PD deficiency
• abnormal haemoglobin - HbH or HbM
• diaphorase 1 deficiency
• acquired - accelerated rate of oxidised formation due to meds
• antibiotics - sulphonamides, trimethoprim, dapsone
• drugs used in anaesthetics - lidocaine, procaine
• others -primaquine

Management:

• 1% solution of methylene blue
• hyperbaric oxygen
• exchange transfusion
• dialysis
• asorbic acid in patients with G6PD deficiency

So to the final battle of the day - weeverfish!

MRCP revision battle 25.7: The weeverfish

Just very briefly...

The weeverfish (AKA trachinus vipera) is found in shallow waters around the coast of the UK.

It is small and sandy-coloured, with sharp dorsal spines.


If you are unfortunate enough to stand on it you will get intense pain.

Happily the toxin produced by the weeverfish is denatured above 40C - so dunk the foot in hot water and the pain should stop.


On that most random of MRCP revision notes, lets end for the day!

MRCP questions: War 24

 I now have a co-conspirator for MRCP revision on the go... lets call her Dr Biscuit and she is now writing all the wars!  How hard they are will probably reflect how bad her day has been... good luck!


As with previous 'wars' after 'battles' these are just a few quick questions to see if your brain cells have retained the information provided in battles 24:1 to 24:6.

The answers are available here


Question 1:
You are referred a patient who was diagnosed with Primary Biliary Cirrhosis 2 years ago. Name 3 signs you might find on clinical examination?

Question 2:
What blood test would you do to confirm the diagnosis of PBC?


Question 3:
A 22 year old female patient presents with DIC and hepatosplenomegaly.  Blood film shows cells which are strongly sudan black/peroxidase positive. What is the diagnosis and what is the gene translocation?



Question 4:
Name 3 drugs which can be used to treat AML?


Question 5:
Name 3 conditions associated with angioid retinal streaks?


Question 6:
List 3 drugs/groups of drugs which can cause SIADH?


Question 7:
Your patient is hyponatraemic with a sodium of 120.  On examination they appear clinically dehydrated. What investigation would you request next to help you elucidate the cause of the hyponatraemia?


Question 8:
Your patient is hyponatraemic with a sodium of 118.  Name four signs or symptoms they might display?


Question 9:
A patient is admitted with confusion. You are unable to obtain a history from her family but she takes no medications.  Her sodium is 119.  On examination she appears euvolaemic.  The admitting doctor has sent a urine sample which shows a urinary na of 34, and urine osmolality of 750. What is the likely diagnosis?


Question 10:
What are the 2 main effects of ADH?



The answers are available here

MRCP revision battle 24.1: Primary biliary cirrhosis

All this working and revising is leaving me with little internet-publishable material to put into my daily intros.  Looking for inspiration I ended up stumbling accross an utterly brilliant set of articles written back in the early 2000's by a (then) junior doctor called Michael Foxton in the Guardian.  Hopefully this link will take you to a list of his articles to soothe you after some revision.... but I warn you not to start looking before you've finished revising for the day because otherwise there is a real danger you will get no revision done!!



So today's battles are:

MRCP revision battle 24.1: Primary biliary cirrhosis
MRCP revision battle 24.2: Acute Myeloid Leukaemia
MRCP revision battle 24.3: Acute Promyelocytic Leukaemia
MRCP revision battle 24.4: Angioid retinal streaks
MRCP revision battle 24.5: SIADH
MRCP revision battle 24.6: Hyponatraemia
MRCP revision battle 24.7: Neutropenia and neutrophillia




MRCP revision battle 24.1: Primary biliary cirrhosis



I've never bonded well with this topic so this battle is a personal Waterloo for me...


Primary biliary cirrhosis is thought to be an autoimmune condition in which the interlobular bile ducts are damanged by chronic granulomatous inflammation. 


The result of this is:

• progressive cholestasis
• cirrhosis
• portal hypertension

Females are more affected than males (9:1) and it tends to present in middle age.

It is associated with many other autoimmune conditions, including sjogrens, RA, systemic sclerosis, thyroid disease...


Primary biliary cirrhosis is often found incidentally by a raised alk phos on LFTs.Initially other LFTs may be normal but as the disease progresses bilirubin rises and PT may increase.


Associated signs (in late disease) include:

• jaundice
• xanthelasma
• hepatosplenomegaly
• clubbing

Complications include:

• osteoporosis
• portal hypertension
• variceal haemorrhage

Diagnosis includes antibodies:

• AMA M2 is highly specific and is positive in 98% of cases
• SMA is positive in 30%
• raised IgM

Treatment is:

• cholestyramine for itching
• osteoporosis prophylaxis
• transplant

Once jaundice develops, without transplant the survival is < 2yrs.


On to AML...

MRCP revision battle 24.2: AML

Acute myeloid leukaemia is cancer of the myeloid line of blood cells.
Myeloid cells are essentially all blood cells that are not leukocytes.


It is the commonest leukaemia in adults.


Presentation may be by:

• complications of marrow failure
• anaemia
• infection
• bleeding
• evidence of marrow infiltration
• hepato/splenomegaly
• gum hypertrophy

CNS involvement is rare in AML (contrasted with ALL, where it is common)


Diagnosis is by bone marrow biopsy.
Immunophenotyping/cytogenetic analysis is important to guide treatment and indicate prognosis.


The key feature on microsopy is the auer rod - note the small rod in the cytoplasm of the central cell:

 

Classification was traditionally done by the FAB (French-American-British) classification, which ran from M0 to M7.  The important random facts I remember from this is that M2 is associated with t(8;21) and M3 (aka acute promyelocytic leukaemia, the topic of the next battle) is associated with t(15;17).  Both of these translocations are associated with a good prognosis.

Now the WHO classification is more commonly used.  It is rather complex and includes catagories such as 'AML with characteristic abnormalities' and 'AML therapy-related'  If you are interested the further reading link at the bottom will tell you more.

Treatment is supportive care and intensive chemotherapy, usually with cytosine arabinoside and daunorubicin, or bone marrow transplant.

Survival with no treatment is around 2 months; with chemo there is around 20% 3 yr survival.

For the really keen:

Further information on WHO classification of AML

Now lets briefly look at acute promyelocytic leukaemia...

MRCP revision battle 24.3: Acute Promyelocytic Leukaemia

Acute Promyelocytic Leukaemia is the M3 subtype of AML.

It is associated with the t(15;17) translocation and the RARA gene.


On microscopy you look for faggots (=collections of auer rods):

 

The cells are strongly sudan black/peroxidase positive.

Acute promyelocytic leukaemia tends to present in young adults (average approx 25 yrs) and the presentation is often DIC.

Despite this sounding bad, acute promyelocytic leukaemia actually has a good prognosis.

Remission can be induce with all-trans retinoic acid.

Thats enough heavy-going haematology for one day... lets move on to angioid retinal streaks...

MRCP revision battle 24.4: Angioid retinal streaks

Angioid retinal streaks are caused by breaks in Bruch's membrane. 


They look like dark red lines under the retina - almost like blood vessels.  I'd recommend using google to search for a selection of images to look at.


They are associated with SLAPPERS:

• Sickle cell disease
• Lead poisoning
• Acromegaly
• Pagets disease
• Pseudoxanthoma elasticum
• Ehlers-Danlos
• Raised calicum/phosphate
• Short people

 Onwards to SIADH...

MRCP revision battle 24.5: SIADH

SIADH = syndrome of inappropriate antidiuretic hormone secretion is a condition whose name really says it all: it is ADH being produced and released when it shouldn't be.


Quick bit of physiological background:

• ADH is made in the magnocellular neurones in the supraoptic and paraventricular nuclei of the hypothalmus
• ADH is stored in the posterior pituitary
• it is released in response to raised plasma osmolality (osmoreceptors in hypothalamus) or decreased volume (baroreceptors in carotids, atria)
• its effect is to increase the insertion of aquaporin 2 channels in the collecting ducts of the kidney, hence increasing water reabsorption.
• it also increases peripheral vascular resistance

SIADH is diagnosed in the presence of:

• concentrated urine ( sodium >20mmol/l and osmolality >500mosmol/kg) AND
• hyponaturaemia (<125) or low plasma osmolality (<260mosmol/kg) AND
• the absence of hypovolaemia, oedema or diuretics.

Causes of SIADH include:

• malignancy: small cell lung cancer, pancreas, prostate, lymphoma
• lung pathology: TB, pneumonia, aspergillosis
• CNS pathology: injury, GBS, fits, subarachnoid/subdural haemorrhage, abscess, stroke
• metabolic: porphyria
• drugs: opiates, carbamazepine, SSRIs, TCA

So lets now finish todays battles by widening this topic out to hyponatraemia...

MRCP revision battle 24.6: Hyponatraemia

Hyponatraemia is low blood sodium.  The effect of this will depend on how low and for how long.

Possible signs and symptoms include:

• confusion
• seizures
• hypertension
• cardiac failrue
• anorexia
• nausea
• muscle weakness
• oedema

(=CASH MON)


My personal way of dealing with hyponatraemia is to begin by asking 2 cynical questions:

1. is it actually just dilutional? - ?hyperglycaemia 
2. is it actually just pseudo? - ?high protein ?high triglycerides

Once I've got negatives to my cynicism, I move on to ask:

1. are they dehydrated or not?

The divisions from this question onwards are summarised in the diagram below:

If the low sodium is chronic, you treat by:

• treating cause
• giving cautious N.saline if dehydrated
• fluid restricting if not dehydrated.

Occasionally demeclocycline might be needed; this is an antibiotic which has the side effect of inducing nephrogenic diabetes inspidus and hence helps treat SIADH.


Now on to neutrophils...

MRCP revision battle 24.7: Neutropenia and neutrophilia

Your humble neutrophil makes up 40-75% of your white blood cells.
It lives for a mere 5 days.
It migrates towards the 'bad guys' by following the signals of substances including IL-8.
It valiantly phagocytoses bacteria.

MRCP examiners enjoy asking questions about low and high levels of neutrophils...


Neutropenia = low neutrophil count

Causes:

• viral infection
• severe sepsis
• bone marrow failure
• neutrophil antibodies (eg SLE, haemolytic anaemia)
• drugs - chemotherapy, carbimazole

Neutrophilia = raised neutrophil count.

Causes:

• bacterial infection
• MI
• steroids
• pregnancy
• uraemia
• acidosis
• gout
• myeloproliferative disorders

That's all the hard work done for today; for some light relief click this link

MRCP revision battle 23.1: Henoch Schonlein purpura

No energy for an interesting introduction today... lets dive straight into the battles...



MRCP revision battle 23.1: Henoch Schonlein purpura
MRCP revision battle 23.2: Parinaud's syndrome
MRCP revision battle 23.3: Polymyositis and Dermatomyositis
MRCP revision battle 23.4: Trichomonas vaginalis
MRCP revision battle 23.5: Atrial septal defects
MRCP revision battle 23.6: Pyoderma gangrenosum



MRCP revision battle 23.1: Henoch Schonlein purpura


Henoch Schonlein Purpura (HSP) is a an IgA mediated small vessel vasculitis.

Classically it affects mainly children post infection.


Features include:

• symmetrical macular rash over buttocks and extensor surfaces of legs
• abdominal pain +/- blood diarrhoea
• arthralgia

Complications of HSP include:

• renal failure (look for microhaematuria)
• intussusception

Management is supportive.


Now for a very quick battle, Parinaud's Syndrome...

MRCP revision battle 23.2: Parinaud's syndrome

Parinaud's syndrome refers to the combination of:

• upward gaze palsy
• pseudo Argyll-Robertson pupils

Causes include:

• hydrocephalus
• pineal tumours
• stroke
• multiple sclerosis

Onwards to the longer 'buy-one-get-one-free' battle of dermatomyositis and polymyositis...

MRCP revision battle 23.3: Polymyositis and Dermatomyositis

Polymyositis is an idiopathic inflammatory disorder of skeletal muscle.  When it is associated with cutaneous lesions it is dermatomyositis.


Features:

• progressive proximal muscle weakness
• dysphagia
• interstitial lung disease
• oesophageal dysfunction
• weight loss 
• fever
• myocarditis
• arthralgia

To try and remember this list I think of the condition starting in the proximal muscles of the arm then creeping to the joint (causing arthralgia) and onwards to the oesophagus, causing dysphagia and oesphageal dysfunction.  I then imagine it seeping into the lungs (interstitial lung disease) and then onwards into the heart (myocarditis).



Skin signs include:

• heliotrope (liliac-purple) rash around eyelids/cheeks
• macular rash over back and shoulders (=shawl sign)
• Gottrons papules = scaly plaques on MCP/PIP joints
• Gottrons sign = erythema over knees/elbows
• periungal telangectasia
• nail fold infarcts
• photosensitivity

There is a higher prevalence of malignancy with dermatomyositis.


Investigations show:

• raised CK/AST/LDH
• abnormal EMG - shows fibrillation potentials
• anti-Jo antibodies associated with a systemic form of disease

Treatment is:

• prednisolone
• methotrexate
• screen for maligancy.

NB: juvenile dermatomyositis is different - it is more aggressive and includes a vasculitis and ectopic calcification.



Now onwards for our first expedition into the world of sexually transmitted diseases...

MRCP revision battle 23.4: Trichomonas vaginalis

Trichomonas vaginalis is an anaerobic protozoan that is transmitted sexually.

It needs an alkaline pH to thrive.


It can cause:

• thin, grey, fishy discharge
• itchiness
• dysparenia
• dysuria

As it inflames the endothelium it increases an individual's susceptibility to other sexually transmitted infections.


Treatment is with metronidazole.



Now on to atrial septal defects...

MRCP revision battle 23.5: Atrial septal defects

Atrial septal defects may present as:

• dyspnoea on exertion
• finding after AF diagnosed
• finding after CVA
• finding after heart failure

Clinical signs include:

• fixed splitting S2
• ejection systolic murmur
• left parasternal heave

A cardiac echo may show paradoxical ventricular septal motion due to right sided overload.



There are 3 main atrial septal defects to be aware of:


1: Ostium secundum defect

• Ostium secundum defects account for 70% of atrial septal defects
• caused by an enlarged foramen ovale
• ECG shows RBBB with right axis deviation and a long PR
• 10-20% of cases will be associated with mitral valve prolapse
• it tends to present in adulthood

2: Ostium primum defect

• ostium primum defects account for 15% of atrial septal defects
• ECG shows RBBB with left axis deviation and a long PR
• it tends to present earlier, in childhood
• it is associated with Downs, Klinefelters and Noonans
• some feel it should be classified as a atrioventricular septal defect as it is so low down in the atria, on the endocardial cushions
• often associated with TR/MR.

3: Sinus venous atrial septal defect

• up to 15% of cases

Treatment is closure.



A very small atrial septal defect is patent foramen ovale.  This is different from the others as as it is so small it does not allow equilisation of atrial pressures.  It occurs in 25% of the population and can allow paradoxical emboli (see below) and is associated with migraine.



Complications of ASDs include:

• Eisenmengers Syndrome
• left-to-right shunt causes increased blood flow through pulmonary vasculature and so pulmonary hypertension, which increases the pressure in the right side of the heart leading to reversal of the shun to right-to-left = eisenmnegers syndrome.
• paradoxical emboli 
• venous emboli ending up in arterial rather than venous system
• --> strokes, intestinal infarcts, splenic infarcts 
• ? migraines - controversial area of research - google if you are interested.

Finally for ASDs a brief eponymous syndrome that occasionally appears in MRCP answer options: Holt-Oram.  Holt Oram is an inherited condition characterised by abnormalities of the heart and upper limb.  It is inherited in an autosomal dominant manner with incomplete penetrance.

Now skip straight to last battle of the day

MRCP revision battle 23.6: Pyoderma gangrenosum

Pyoderma gangrenosum is a nodulo-pustular ulcer, with a purulent surface and a tender bluish overhanging edge.

Below is a picture from Wiki Commons showing pyoderma gangrenosum:

In 50% of cases it is idiopathic.


Associations with pyoderma gangrenosum include:

• inflammatory bowel disease
• RA/SLE/ank spond
• lymphoma/leukaemia/myeloproliferative disorders
• primary biliary sclerosis/sclerosing chloangitis
• sarcoid
• thyroid problems
• diabetes
• Wegeners granulomatosis

Treatment includes high dose oral steroids.


Another day's battling complete.  Congratulations!

MRCP revision battle 22.1: Goodpasture's Syndrome

Today's battles cover a lot of the random conditions that frequently appear as differentials in MRCP questions but rarely feature in your day-to-day life.  As well as being random, or possibly as a consequence of them being random, their exact causes are often unknown, their treatments are debated and they are just downright complex.  Can you tell from this opening gambit how much fun I've had preparing today's battles?!  Hopefully I've whittled them down to digestible forms and have tried to give links if I've whittled away too much.  I've also thrown in aortic regurgitation for some light relief... when aortic regurgitation is light relief you know its going to be a bad day....

So here goes, and good luck!!



MRCP revision battle 22.1: Goodpasture's Syndrome
MRCP revision battle 22.2: Neurofibromatosis
MRCP revision battle 22.3: Tuberous sclerosis
MRCP revision battle 22.4: Fanconi anaemia
MRCP revision battle 22.5: Fanconi syndrome
MRCP revision battle 22.6: Aortic regurgitation
MRCP revision battle 22.7: Argyll Robertson Pupil




MRCP revision battle 22.1: Goodpasture's Syndrome 


Goodpasture's syndrome is a rare condition caused by anti GBM antibodies and is characterised by pulmonary haemorrhage and renal failure.


There is less than 1 case per million people per year.
Cases may be triggered by inhaled hydrocarbons, paraquat or viral infections.


Pulmonary haemorrhage is treated by plasma exchange
Renal involvement is treated by steroids, cyclophosphamide and plasma exchange.


Renal biopsy would show:

• IgG on basement membrane
• crescent formation

For the really keen:

Patient plus article on Goodpasture's syndrome

1 random battle down, several more to go...

MRCP revision battle 22.2: Neurofibromatosis

Neurofibromatosis is an autosomal dominant condition which causes lesions in the skin, nervous system and skeleton.

It is quite complex so below are just a few key points to learn for MRCP:


There are 2 types:


Neurofibromatosis 1 = von Recklinghausen's disease

• chromosome 17, 1:2500
• features include:
• cafe au lait spots
• axillary/inguinal freckling
• lisch nodules in iris (seen in >90%)
• perpheral neurofibromas
• optic gliomas (2%)
• osseous lesions
• may have low IQ or renal artery stenosis

Neurofibromatosis 2

• chromosome 22, rarer than NF 1
• Features:
• bilateral acoustic neuromas - sensorineural hearing loss is first sign
• cafe au lait spots
• juvenile posterior subcapsular lenticular opacity = a form of cataract

For the really keen:

Further information from the neurological institute

So having got one complex, rare and unsatisfying battle out of the way lets jump straight into another...

MRCP revision battle 22.3: Tuberous sclerosis

This is going to be a very unsatisfying battle because tuberous sclerosis is rare and complex and essentially to grasp it properly goes far beyond what is required for MRCP, so please excuse my poor attempt at summarising some of the details which may be MRCP-relevant, particularly the skin manifestations...



Tuberous sclerosis is a rare, complex autosomal dominant condition which causes multiple benign tumours.


Features include:

1. cutaneous features
• ash leaf spots (appear under UV light)
• shagreen patches
• adenoma sebaceum
• subungal fibromata
• cafe au lait spots
2. neurological features
• epiplesy
• low IQ
3. other features
• retinal haematoma
• gliomas
• renal cysts

For the really keen:

Information sheet from the Institute of Neurological Disorders

Now lets go on to the thankfully less complex topic of Fanconi anaemia...

MRCP revision battle 22.4: Fanconi anaemia

Fanconi anaemia is an autosomal recessive disorder which is characterised by:

• pancytopenia secondary to bone marrow failure
• dysmorphic features
• short stature
• microcephaly
• absent radii
• cafe au lait spots
• susceptibility to cancers
• AML
• squamous cell cancers of head and neck
• gynaecological  cancers

Most patients die by 30.

For the really keen:

emedicine article on Faconi anaemia 

For the rest of us lets move on to look at the similarly named, but completely different, Fanconi Syndrome

MRCP revision battle 22.5: Fanconi Syndrome

Fanconi syndrome is disturbance of proximal renal tubule function, resulting in defective reabsorption of:

• amino acids
• phosphate
• potassium
• glucose
• bicarbonate

It can cause vitamin D resistant rickets.

Causes of Fanconi syndrome include:

• idiopathic
• inherited
• cystinosis
• Wilson's disease
• acquired
• heavy metal poisoning
• light chains
• amyloid
• myloma

Treatment is:

• treat cause
• replace losses (potassium, bicarb, phosphate, vit D supplements)

Lets now move back mainstream with a revision battle with aortic regurgitation...

MRCP revision battle 22.6: Aortic regurgitation

Aortic regurgitation produces a fiendishly difficult to hear early diastolic murmur; I've heard it once and embarked on a most unprofessional victory dance once out of sight of the patient (even more embarrassingly it wasn't even me picking up the murmur, I had been sent to listen to the patient knowing they had the murmur...)


Possibly because its so hard to hear there are a whole troop of eponymous signs that can suggest aortic regurgitation, and MRCP exams love throwing them into questions to excite you:

• Corrigan's sign: visible carotid pulsation 
• de Mussets sign: the head bobs with each pulse
• Duroziez's sign: femoral artery is compressed and auscultated proximally and a diastolic murmur is heard as blood flows backwards during diastole
• Millers sign: pulsation of uvula
• Quincke's sign: capillary pulsations in nail be
• Traube's sign: pistol shot sound over femoral arteries

The less exciting but probably more important points to remember are:

• the pulse is collapsing (=waterhammer)
• wide pulse pressure
• the apex is thrusting

As well as the classic early diastolic murmur best heard down the left sternal edge which is loudest when the patient is leaning forward and in expiration, you need to be aware of the Austin Flint murmur.



Austin Flint murmur only occurs in severe aortic incompetence.  It is a mid diastolic murmur and is probably due to the regurgitant jet interfering with the opening of the mitral valve.



Symptoms of AR are:

• dyspnoea
• palpitations
• heart failure

Causes of AR include:

• valve inflammation
• rheumatic fever
• IE
• RA
• SLE
• appetite supressants
• aortic root disease
• hypertension
• syphillis
• aortic dissection
• ankylosing spondylitis
• psoriasis
• collagen diseases
• hurlers syndrome
• marfans
• psuedoxanthoma elasticum

One way to remember these causes is SIR AA SHARP  plus collagen.


Management: the aim is to replace the valve before significant LV dysfunction.  Indications for surgery are increasing symptoms, enlarging heart (CXR/echo), worsening ECG (TWI laterally)


Onwards to the brief final battle - the Argyll Robertson Pupil

MRCP revision battle 22.7: Argyll Robertson Pupil

I love the Argyll Robertson pupil, and have done ever since a very serious elderly consultant intoned to us that "the Argyll Robertson pupil is like a prostitute... it will accommodate but will not react."


Essentially the Argyll Roberston pupil is a pupil that:

• will not react to light
• will accommodate

It is a sign of neurosyphillis, but a similar phenomenon occurs in diabetes.
They are also seen in Parinaud's syndrome, which will be covered tomorrow.


And on that teaser, adieu!

MRCP revision battle 21.1: Erythema nodosum

I'm feeling a rather keen bean today so I've decided to slightly modify the way I serve your daily MRCP battles to you.  From now on, as well as battles and wars, I'll try to add 'further reading' links to some of the battles as a form of desert wine for the really keen/anally retentive. 

On that motivated note, today's battles will be:


MRCP revision battle 21.1: Erythema nodosum
MRCP revision battle 21.2: Glucagon and glucagonoma
MRCP revision battle 21.3: Wegener's Granulomatosis
MRCP revision battle 21.4: Rapidly progressive glomerulonephritis
MRCP revision battle 21.5: Achalasia
MRCP revision battle 21.6: Scabies
MRCP revision battle 21.7: Pre eclampsia and HELLP syndrome
MRCP revision battle 21.8: Cafe au lait spots




MRCP revision battle 21.1: Erythema nodosum


Erythema nodosum is inflammation of subcutaneous fat resulting in tender erythematous nodules, typically on the shins.

It usually resolves without scars in around 6 weeks.


It is associated with multiple conditions; below is a list of just a few that you really should remember:

• infection
• TB
• streptococcus
• viral infections
• systemic
• sarcoid
• IBD
• Behcets
• malignancy
• drugs
• OCP
• penicillin
• sulphonamides
• dapsone
• tetracycline
• pregnancy

Treatment is to treat the underlying condition and give NSAIDs for the pain of the nodules.

For the really keen:

Paper from the Dermatology Journal Online  

For everyone else, lets go to to battle 21.2!

MRCP revision battle 21.2: Glucagon and glucagonoma

Lets quickly recap glucagon from our med school days before we move on to the more exotic beast of glucagonoma...


Glucagon is a peptide hormone secreaed from the alpha cells of the islets of langerhans.


It results in raised blood glucose by:

• increasing gluconeogenesis in the liver
• increasing lipolysis

Glucagon is secreted in response to low blood glucose, raised catecholamines and raised plasma amino acids.
Glucagon secretion is inhibited by insulin, ketones in the blood, somatostatin and free fatty acids in the blood



A glucagonoma is a very rare tumour of the alpha cells of the islets of langerhans which secretes glucagon.


It results in:

• massively raised levels of glucagon
• diabetes mellitus
• hypoaminoacidaemia (as GNG is using up protein)
• anaemia
• necrolytic migratory erythema

Necrolytic migratory erythema is a red, blistering rash which is the presenting feature of a glucagonoma in 70% of cases.


Glucagonomas can be associated with MEN 1.


Treatment of a glucagonoma is ocreotide and surgery; prognosis is poor

For the really keen:

Link to the PDF of an article from the European Journal of Endocrinology 

For the rest of us, its onwards to battle 21.3!

MRCP revision battle 21.3: Wegener's Granulomatosis

Wegener's Granulomatosis is a small/medium vessel necrotising granulomatous vasculitis which tends to affect the upper respiratory tract, lungs and kidneys.


90% of cases present with respiratory symptoms.


Associated features to be aware of include:

• blood nasal discharge
• haemoptysis
• saddle-shaped nose

75% get crescentic glomerulonephritis.


cANCA is positive in 90%, pANCA is positive in 25%


CXR may show large shadows.  Pulmonary haemorrhage is also possible.


Treatment is with steroids, cyclophosphamide and possibly co-trimaoxazole to try and reduce risk of PCP.


I guess this is a good opportunity to reconfront a personal demon in the form of a renal battle...

MRCP revision battle 21.4: Rapidly progressive glomerulonephritis

Rapidly progressive glomerulonephritis, AKA crescentic glomerulonephritis (don't you just love the way that in renal medicine everything has multiple names just to make it even more complicated than it already is?!) is, as the name suggests, a particularly aggressive form of glomerulonephritis.  It often presents with acute renal failure, and can progress to end stage renal failure in a matter of days.


It causes crescent-shaped scarring of the glomeruli, hence its name.



Causes of rapidly progressive glomerulonephritis include:

• Wegeners 
• microscopic polyangiitis
• Goodpastures (a topic to be tackled tomorrow)
• transformation from other glomerulonephritis'

Treatment is with high dose steroids.


The prognosis is poor, especially if the initial creatinine is higher than 600.



Since I find anything renal hard to swallow, achalasia seemed an appropriate next battle...

MRCP revision battle 21.5: Achalasia

Achalasia is abnormal peristalsis and failure of relaxation of the lower oesophageal sphincter.


It causes dysphagia, regurgitation, chest pain and weight loss.


Females aged 30-50 are most commonly affected.


Investigation is with oesophageal manometry and barium swallow.
The barium swallow should show a characteristic 'birds beak' appearance (image below is from wiki commons):

Treatment is with balloon dilation or hellers cardiomyotomy.    Nifedipine may be temporarily helpful.


A rare and late complication of achalsia can be squamous carcinoma.


Now on to battle 21.6, which is short but sure to make you itch...

MRCP revision battle 21.6: Scabies

Scabies is an intensely itchy condition caused by sarcoptes scabei, an arachnid which burrows into skin.


In terms of MRCP the follow facts need to be committed to memory:

• first line treatment is 5% permethrin which must be applied over whole body, face and scalp and washed off after 8 to 12 hrs and repeated after 7 days
• second line treatment is 0.5% malatrion
• pruritus persists for up to 6 weeks post erradication.
• look out for pictures of lines (burrows) between web spaces of hands

Now you're itching nicely, lets attack the penultimate battle of the day, pre-eclampsia and HELLP syndrome.

MRCP revision battle 21.7: Pre eclampsia and HELLP syndrome

Pre-eclampsia is defined as:

• gestational hypertension
• proteinuria
• occurring after 20 weeks gestation

Oedema is often a feature.
Possible symptoms include blurred vision, headache and abdominal pain.


Treatment is to lower blood pressure but ultimately the only way to treat pre-eclampsia which is advancing towards eclampsia (=fit) is to deliver the baby.




HELLP syndrome is a severe form of pre-eclampsia characterised by:

• haemolysis
• elevated liver enzymes
• low platelets

It complicates 10-15% of cases of pre-eclapsia.
Mortality is 20-25%


The treatment for eclampsia is IV magnesium sulphate


Now to the final battle of the day

MRCP revision battle 21.8: Cafe au lait spots

Cafe au lait spots are light brown patches on the skin (see picture below from wiki commons):

Cafe au lait spots are associated with several conditions. 
The top 4 associations I remember for MRCP are:

• neurofibromatosis types I and II
• tuberous sclerosis
• Fanconi anaemia
• Mc Cure-Albright syndrome

Which serves as a teaser for conditions I will be covering tomorrow!  See you then.