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.

MRCP revision battle 20.1: MEN

Yet another sunny day to try and tempt me outside (who am I kidding, it worked, I've been outside had some sunshine, beer and am now back inside trying to settle)

Todays battles are going to be:

MRCP revision battle 20.1: MEN
MRCP revision battle 20.2: Folate
MRCP revision battle 20.3: Subacute combined degeneration of the spinal cord
MRCP revision battle 20.4: Vitamin B12
MRCP revision battle 20.5: Pernicious anaemia
MRCP revision battle 20.6: Churg Strauss
MRCP revision battle 20.7: ANCA





MRCP revision battle 20.1: MEN

As any of my friends will tell you MEN have frequently been a problem in my life and the condition MEN (=multiple endocrine neoplasia) has been no less troublesome.  Yes, I get that they are genetic syndromes in which there are functioning hormone-producing tumours in multiple organs.  My problem lies in managing to associate the different patterns to the different classes of MEN, which MRCP seems to require you to do rather a lot.


Firstly, 2 key facts to grasp:

1. all MEN can be inherited or sporadic; if inherited they are autosomal dominant
2. all are associated with hypercalcaemia, especially MEN 1

So, to try and learn the subtypes... I've settled on learning "Para pits against the pan men, for which Phaeo gives a medal to the para"  (= parathyroid, pituitary, pancreas (men gene), phaechromocytoma, medullary thyroid, parathyroid)


Which, in more conventional terms:

MEN1

• parathyroid (95%), pituitary (70%) and pancreas (50%)
• caused by mutation of Menin gene (a tumour supressor) on chromosome 10

MEN 2a

• phaechromocytoma (95%), medullary thyroid cancer (70%) and parathyroid (60%)
• ret gene on chromosome 11

MEN 2b

• MEN 2a but without the parathyroid tumours and with a Marfarnoid appearence and mucosal neuromas
• also caused by the ret gene on chromosome 11

Note that the medullary thyroid cancer in MEN is in general less aggressive than the sporadic forms but prophylactic thyroidectomy should still be considered.


As a random aside it might be worth learning that in MEN the mutation in the ret gene is activating, whereas in Hirschsprung's disease, which is also caused by a ret gene mutation, the mutation is inactivating.


So, have you got Para pits against the pan men, for which phaeo gives a medul to the para... not ideal but its the best I've come up with....




Lets move on for a brief encounter with folate....

MRCP revision battle 20.2: Folate

Have you ever been confused by the seemingly random use of either 'folate' or 'folic acid' and wondered what the difference is?  Well, just in case you have, here is the answer: folate is naturally occurring vitamin B9, while folic acid is the artificial form of vitamin B9.   With that cleared up, lets briefly look at folate.


Folate is important in DNA synthesis.  It is also vital in the remethylation of homocysteine, which is a current area of research I'll touch on at the end.


Low folate levels result in a macrocytic anaemia.  In pregnancy they also predispose to neural tube defects.


Good sources of folate include liver, green vegetables and nuts.


Drugs that decrease absorption of folate include phenytoin
Drugs that decrease its metabolism to its active form include trimethoprim, methotrexate and pyrimethamine


If a patient has low folate you should never give folic acid without B12 as doing so may precipitate, or worsen, subacute combined degeneration of the spinal cord (wait for the next battle...)



So just to round up by speaking about folate and homocysteine.  Raised homocysteine levels are associated with increased risk of cardiovascular events, cerebrovascular events and fractures.  Folate lowers homocysteine levels.  Unfortunately, despite this seemingly simple way to decrease risk trials so far have not shown lowering levels to decrease risk.




On that wet blanket of an observation lets progress to subacute combined degeneration of the spinal cord...

MRCP revision battle 20.3: Subacute combined degeneration of the spinal cord

Subacute combined degeneration of the spinal cord is one of those conditions which does exactly what it says on the tin:

• subacute - it's onset is insidious
• combined degeneration - both dorsal and lateral columns affected
• of the spinal cord

The loss of dorsal columns causes sensory and LMN signs, while the lateral (corticospinal) column loss cause motor and UMN signs.


Clinically the classical triad is:

• extensor plantars (UMN)
• absent knee jerks (LMN)
• absent ankle jerks (LMN)

Pain and temperature sensation are preserved as the spinothalamic tracts are preserved.


Subacute combined degeneration of the spinal cord is caused by B12 deficiency.   Treatment is with B12, with varying levels of success.


Now it seems only sensible to have a quick recap of B12....

MRCP revision battle 20.4: Vitamin B12

Vitamin B12 is essential in DNA synthesis.  The body has approximately 4 yrs worth of B12 stored, 'just in case.'

B12 is found in meat and dairy, so other than vegans most people should get enough.


Absorption of B12 is specific; it requires intrinsic factor (which is released from parietal cells in the stomach) to bind to it and it is then absorbed as a complex uniquely in the terminal ileum.


Deficiency of B12 causes a variety of symptoms and signs:

• anaemia
• glossitis
• dementia/depression
• peripheral neuropathy
• subacute combined degeneration of the spinal cord

Investigations will show a macrocytic anaemia, and in severe cases WCC and platelets may also be decreased.


Causes of B12 deficiency can be split into:

• insufficient intake
• vegans
• alcoholics
• anorexics
• lack of absorption
• lack of intrinsic factor
• pernicious anaemia (see next battle)
• gastrectomy
• lack of terminal ileum/absorption space
• crohns
• resection
• giardiasis
• fish tapeworm, Diphyllobothrium 
• drugs interfering with absorption, eg metformin
  

Treatment is to treat the cause/give B12.









  
Lets have a quick look at pernicious anaemia...

MRCP revision battle 20.5: Pernicious anaemia

Pernicious anaemia is an autoimmune atrophic gastritis which leads to achlorhydria and lack of intrinsic factor.


It affects 1:1000 and is commonest in blood group A


Diagnosis may be by:

• parietal cell antibodies - present in 90% of patients with PA - but also 3-10% of people without
• intrinsic factor antibodies - less common but more specific
• the schilling test - click here if it wasn't drummed into you ad nauseum at med school!

Treatment of pernicious anaemia is by B12 injections.


Note gastric cancer is 3x more common in people with PA.



Now for some diversification into the exciting area of small to medium vessel vasculitis...

MRCP revision battle 20.6: Churg Strauss

Churg Strauss is a rare vasculitic disease of unknown aetiology.


The classic triad associated with it is:

• asthma
• eosinophilia
• vasculitis of small and medium vessels

The vasculitis usually affects the lungs, peripheral nerves and skin.


Glomerulonephritis may occur with Churg Strauss but renal failure is rare.


It is pANCA positive.


Treatment is with high-dose steroids.


Now to the final battle of the day, a bit about ANCA...

MRCP revision battle 20.7: ANCA

I had never heard of ANCA until I started my MRCP revision then it seemed to pop up everywhere!


ANCA stands for anti-neutrophil cytoplasmic antibodies.  They are mainly IgG.  They are subdivided into 2 groups based on the patterns produced when they are stained:


1. cANCA

• cytoplasmic, anti PR3
• found in Wegeners (90%), mircroscopic polyangiitis (40%)
• some correlation between level and disease activity

2. pANCA

• perinuclear, anti MPO
• found in churg strauss (60%), crescentic glomerulonephritis (80%), microscopic polyangiitis (60%), Wegeners (60%)
• may also be seen in IBD, RA, SLE, sjogrens, autoimmune hepatitis

Thats it for today, no war at present but I'll try and post one later

MRCP revision battle 19.1: Myelofibrosis

I have more time than usual to revise this week and am actually finding it harder to sit down and get on with it... must have a quiet word with the motivational centres of my brain (which I believe are the mesolimbic areas... anyone care to correct me?)  Anyway, today's battles will be:

MRCP revision battle 19.1: Myelofibrosis
MRCP revision battle 19.2: Hepatitis
MRCP revision battle 19.3: Peutz Jegher Syndrome
MRCP revision battle 19.4: Familial Adenomatous Polyposis
MRCP revision battle 19.5: Hereditary Non-Polyposis Colorectal Cancer
MRCP revision battle 19.6: LTOT
MRCP revision battle 19.7: Exercise tolerance tests
MRCP revision battle 19.8: Lead poisoning




MRCP revision battle 19.1: Myelofibrosis


Myelofibrosis has always been a secret 'sweet-spot' of mine - I think because of its 'teardrop cells' - so its a good battle to start this unmotivated day on...


Myelofibrosis is fundamentally fibrosis of the bone marrow.  There is hyperplasia of megakaryocytes which produce platelet-derived growth factor, leading to:

1. marrow fibrosis
2. haemopoesis being forced to move to the spleen and liver.

Features of myelofibrosis include:

• lethargy
• weight loss
• night sweats
• massive hepato/splenomegaly

Investigations show:

• raised WCC, low Hb
• teardrop pokilocytes
• leucoerythroblastic cells (=nucleated red cells)
• raised LDH and urate as increased cell turnover
• bone marrow may produced a 'dry tap'

Image below shows teardrop cells.

Treatment is ?allogenic stem cell transplant.

Prognosis is poor with a median survival of 4 to 5 yrs.



Onwards to hepatitis.... 

MRCP revision battle 19.2: Hepatitis

There are 5 'flavours' of viral hepatitis, labeled A to E.  Important general points to learn are:

• all are caused by RNA virus' except hepatitis B, which is a DNA virus
• B and C are spread by blood/sexual contact
• A and E are spread by the faecal-oral route
• Hepatitis D essentially is only ever found as a co-infection, never alone.

So to explore the 3 most popular MRCP 'flavours' in more depth....


Hepatitis A:

• spread faeco-orally, so look out for questions featuring backpackers returning home
• incubation period is 2-6 weeks
• presents as fever, malaise, nausea
• patient likely to be jaundiced and may have hepato/splenomegaly
• treatment is supportive
• patients generally make a full recovery

Hepatitis B:

• symptoms are similar to hep A
• incubation period is longer at 1 - 6 months
• spread is blood/bodily fluids - questions likely to hint at male business traveller or other innuendo
• important to fully grasp the various antigens and their meanings:
• HBsAg: present for 1-6 months after exposure; if present for >6 months patient is a carrier
• HBeAg: present for 1.5-3 months after exposure and is marker of high infectivity
• anti HBC IgM - signifies acute infection/carrier
• anti HBC IgG - may be acute infection, carrier or cleared infection
• anti HBS - if present with anti HBC suggests recovered from hep B and naturally immune; if present alone suggests hep B vaccination
• complications of hepatitis B include:
• 5-10% chronic hepatitis
• glomerulonephritis
• increased risk hepatocellular carcinoma
• cryoglobulinaemia

Hepatitis C:

• is spread by blood/sexual contact
• blood pre 1991 wasn't screened for hep C
• <20% get an acute hepatitis but 80% get chronic hepatitis
• breast feeding is NOT contraindicated (a common MRCP fascination for some reason)
• complications:
• 80% chronic hepatitis
• 20% cirrhosis
• increased risk hepatocellular carcinoma
• Treatment: IFN alpha and ribavirin

After that wizz through some high-yield viral hepatitis facts lets move on to Peutz Jegher Syndrome

MRCP revision battle 19.3: Peutz Jegher Syndrome

Peutz Jegher Syndrome is a condition characterised by:

• pigmented 'freckles' (macules) on lips, face, palms and soles
• hamartomatous polyps in gastrointestinal tract

It is an autosomal dominant condition caused by a mutation of gene LKB1


Complications of PJS include:

• obstruction/intususception
• GI haemorrhage
• iron deficiency
• colicky abdo pain
• malignant transformation - around 50% of sufferers will have died from a cancer by the age of 60.

There is no specific treatment.



 
So lets move on from a relatively benign cause of multiple colonic polyps to a less benign one....

MRCP revision battle 19.4: Familial Adenomatous Polyposis

Familial adenomatous polyposis is an inherited condition in which patients develop literally thousands of polyps in the GI tract.  Virtually all sufferers will get cancer, usually in their 30s or 40s.


It is caused by a mutation in the tumour supressor gene APC on chromosome 5.


The appearance of the colon is:

Treatment tends to be a colectomy before cancer develops.



As an aside, a variation of FAP called 'Gardners Syndrome' exists.  This is FAP plus osteomas, epidermal cysts, fibromas and retinal pigmentation.



So after 2 conditions which are defined by polyps, lets look at one which defines itself by not having polyps - Hereditary Non-Polyposis Colorectal Cancer

MRCP revision battle 19.5: Hereditary Non-Polyposis Colorectal Cancer

Hereditary Non-Polyposis Colorectal Cancer is an autosomal dominant condition associated with an increased risk of colorectal cancer.


90% of patients with HNPCC develop cancers, usually in the proximal colon and often poorly differentiated/highly aggressive cancers.


There is also an increased risk of breast, ovary and endometrial cancers.


HNPCC is defined by the Amsterdam criteria:

• at least 3 family members with colon cancer (one a 1st degree relative)
• at least 2 generations affected
• at least 1 diagnosed under 50 yrs of age

Thats quite enough bowels for one day, lets come up for some oxygen...

MRCP revision battle 19.6: LTOT

LTOT = long term oxygen therapy = 15 or more hours of oxygen per day.


This is the only treatment to increase survival in COPD.


NICE recommends it if:

• PaO2 <7.3kPa OR
• PaO2 <8kPa if
• secondary polycythaemia
• nocturnal hypoxia (questions may note 'morning headaches;
• peripheral oedema
• pulmonary hypertension

How about now trying our exercise tolerance...

MRCP revision battle 19.7: Exercise tolerance tests

Exercise tolerance tests are starting to go out of fashion but are still currently a mainstay of assessment of angina. 

I'd recommend this BMJ article for a comprehensive discussion; what follows below are just a few salient MRCP points.


ETTs are carried out according to the Bruce protocol, which is 7 sections each 3 minutes long so a maximum of 21 minutes of exercise.  A modified bruce can be used in higher risk/frailer patients.


Beta blockers must be stopped the day before an ETT
Digoxin should be stopped a week before.



The test is deemed to be positive if:

• anginal symptoms
• BP decreases by 15mmHg or fails to increase on exercise
• arrhythmia
• ST depression
• failure to achieve target heartrate (220-age in men, 210-age in women)
• ST elevation

Now for the last battle of the day, lead poisoning

MRCP revision battle 19.8: Lead poisoning

Lead poisoning is a good topic as it has 2 nice distinctive features (blue lines on nail growth margins and basophillic stippling of red blood cells.)


A more comprehensive list of lead poisoning features is:

• abdominal pain
• constipation
• peripheral neuropathy
• fatigue

Blue lines on the growth margin of nails affect 20% adults with lead poisoning but are rare in children.


Investigations should show:

• microcytic anaemia
• basophillic stippling of red blood cells
• raised aminolevulinic acid levels (a haem precursor)

 The image below shows basophillic stippling of red blood cells (right and left arrows)

Treatment is by chelation with either EDTA, d-penicillamine or dimercaprol.



Thats today wrapped up; questions on yesterday's battles can be found here

MRCP questions: War 18

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 18.1 to 18.8.

Grab a piece of paper, jot down your answers then compare them to my answers here


Question 1:
Which 4 clotting cascade factors is vitamin K a cofactor for?


Question 2:
Your patient has an INR of 7 but no evidence of bleeding.  What would you do?


Question 3:
A 20 year old comes to you with a rash across their back of teardrop-shaped lesions topped with some silver scales.  They note they had a sore throat a week or 2 ago.  What is the rash?



Question 4:
State the classical triad of symptoms for aortic stenosis.



Question 5:
A patient tells you their cardiologist said the pressure gradient across their aortic valve was 52mmHg.  What grade of severity is their stenosis?



Question 6:
Your houseofficer has diagnosed PMR and wants to know how to treat it.  What would you prescribe?




Question 7:
A mum brings her 16 year old son who has learning difficulties to you, saying he has been itching his bottom a lot recently.  You think he has threadworms.  How would you treat them?





Question 8:
Your consultant states he is admitting someone with pseudopseudohypoparathyroidism.  What blood results would you expect?


The answers are here

MRCP revision battle 18.1: Warfarin

Today is another 'octopus' day with 8 battles to embrace (three of which are mercifully brief)

So the topics are:

MRCP revision battle 18.1: Warfarin
MRCP revision battle 18.2: Psoriasis
MRCP revision battle 18.3: Beau's lines
MRCP revision battle 18.4: Elliptocytosis
MRCP revision battle 18.5: Aortic stenosis
MRCP revision battle 18.6: Polymyalgia rheumatica
MRCP revision battle 18.7: Threadworm
MRCP revision battle 18.8: Pseudohypoparathyroidism






MRCP revision battle 18.1: Warfarin


Ah, warfarin... everyone's favourite out-of-hours bleep as a houseofficer.  Originally made as a rat poison, it quickly became a favourite in the UK for the treatment of DVTs, PEs and prevention of clots associated with mechanical heart valves.


Warfarin works by inhibiting vitamin K epoxide reductase, which prevents vitamin K being recycled.  Since vitamin K is a cofactor for factors II, VII, IX and X it decreases coagulation.


Note however that vitamin K is also a cofactor for protein C and protein S, which help inhibit the clotting cascade.  As protein C is initially affected more than the clotting factors by lack of vitamin K warfarin is initially a procoagulant and when started therefore increases the risk of thrombosis.


Warfarin is monitored by INR.  The targets are:

• PE/DVT: INR 2-3
• metallic valve: INR 3-4

The duration of anticoagulation depends on the cause of the clot:

• below knee DVT after surgery: 6 weeks
• above knee DVT/PE after surgery: 3 months
• DVT/PE without precipitating factor identified: 6 months

1-2% of patients on warfarin have a haemorrhage per year.

Other complications of warfarin treatment include:

• increased risk of osteoporosis
• purple toe syndrome - toes turn purple ?secondary to cholesterol deposits 3 to 8 weeks after starting warfarin

Warfarin levels are notoriously difficult to regulate.

Things which increase the effect of warfarin include:

• erythromycine/clarithromycin
• metronidazole
• hyperthyroidism
• cranberry juice
• alcohol
• amiodarone
• propranolol
• fluconazole
• isoniazod
• cimetidine
• omeprazole

Things which decrease the effect of warfarin include:

• rifampacin
• carbamazepine
• chlordiazepoxide
• avocado in excess!

Management of INR outside the desired range depends both on the level and if there is bleeding:

• major bleed
• stop warfarin
• give vit K 5-10mg IV
• give prothrombin complex (II, VII, IX, X) or FFP if this is not available
• INR>8 but no/minimal bleeding
• stop warfarin
• give vit K 2.5-5mg PO/0.5-1mg IV
• restart warfarin when INR<5
• INR 5-8, no bleeding
• stop warfarin
• restart when INR<5
• INR 5-8 minor bleeding
• stop warfarin
• give 1-2.5mg vitamin K PO
• restart when INR<5

As an aside, with an eye on the future, a new drug called dabigatran is looking to usurp warfarin as king of the anticoagulants.  Trials such as RELY and RECOVER have shown dabigatran to be non-inferior to warfarin in preventing thrombosis, to cause fewer bleeding adverse effects and even better not require regular blood tests to check levels.  Of course its expensive and so not yet approved...



On to the second battle of the day, psoriasis...