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...

MRCP revision battle 18.2: Psoriasis

Psoriasis is an autoimmune disease that classically causes a silver-scale topped rash on the skin.

It affects 1-2% of the population.

The cause is believed to be abnormal activity of the type 1 T helper cells.
It is associated wtih HLA CW6, B13, B17 and B27.


Females tend to be affected at a younger age than males.


The main 'types' of psoriasis are:

1. chronic plaque
2. generalised pustular
3. palmo-plantar pustulosis
• strong association with smoking
• tends to affect middle-aged females
4. guttate
• usually young adults/teenagers
• is often preceded by a strep infection 2-4 weeks before
• resolves spontaneously in 2-3 weeks
5. nail
6. flexural

Athropathy is a feature in 8% and may be in the form of :

• symmetric arthritis - appears rheumatoid-like; 50%
• asymmetric arthrtitis - 35% - dactylitis
• arthritis mutilans - <5%
• spondylitis
• distal interphalangeal predominant

Psoriasis can be worsened by multiple factors, including:

• trauma
• infection
• post-partum
• beta blockers
• lithium
• stress
• alcohol
• NSAIDs

Management for skin psoriasis is by a host of lotions and potions - coal tar, dithranol, topical vitamin D.... if these haven't already been drummed into you a brief visit to the BAD website (british association of dermatologists, trying to sound cool) to recap might be a good idea.



Now for a brief skirmish with Beau's lines

MRCP revision battle 18.3: Beau's lines

Beau's lines are transverse depressions in nails due to temporary arrest in their growth.

They are associated with:

• psoriasis
• diabetes
• metabolic disturbances

Now onwards to another very brief battle, elliptocytosis

MRCP revision battle 18.4: Elliptocytosis

Elliptocytosis is an autosomal dominant condition which results in cigar-shaped elliptocytes:

In severe cases they can cause haemolytic anaemia; happily the majority of people with elliptocytosis have no ill effects from it at all.


Now on to a more substantial battle again: aortic stenosis

MRCP revision battle 18.5: Aortic stenosis

Aortic stenosis may be detected incidentally (keen houseofficer noticing the classical ejection systolic murmur radiating to the carotids) or may present with its classical triad of symptoms that can be remembered as 'DAD':

• exertional dyspnoea
• etertional angina
• exertional dizziness

Signs of aortic stenosis include:

• ejection systolic murmur radiating to carotids
• slow rising pulse
• narrow pulse pressure
• heaving apex beat

Things which suggest severe aortic stenosis include:

• LVF
• soft S2
• paradoxically split A2
• S4

 The formal divisions of severity are as follows:

• mild: area >1.5cm, gradient <25
• moderate: area 1-1.5cm, gradient 25-50
• severe: area <1cm, gradient >50
• critical: area <0.7cm, gradient >80

The main causes of aortic stenosis are:

• calcification of the valve
• bicuspid aortic valve

ECG changes which may be associated with aortic stenosis include:

• p mitrale
• LVH
• LAD
• poor R wave progression
• complete heart block if calcification involves the conduction tissue.

Treatment is surgical.  The operative mortality is around 20-25% if there is LVF, 2-8% if not.



So from the very factual aortic stenosis on to the slightly touchy-feeling PMR...

MRCP revision battle 18.6: Polymyalgia rheumatica

Polymyalgia rheumatica (PMR) is a slightly nebulous condition which the Oxford handbook defines as 'symmetrical aching, tenderness and morning stiffness in shoulders and proximal limb muscles, +/- systemic features'.  These systemic features can include anything from fatigue to anorexia...


It generally affects over 70s and is rare in under 60s.


Bloods tend to show a raised ESR


Treatment is with prednisolone (15mg PO OD) which tends to produce a dramatic improvement in days.  This should be decreased by 1mg per month, and of course anti-OP treatment should be given concurrently.

If symptoms recur on decreasing the dose and you have a lovely little old lady stuck on >10mg OD for over a year, it is worth considering methotrexate or azothioprine to try and allow you to decrease the steroid.


As a random aside, 10% of patients with PMR will suffer from carpal tunnel syndrome.



Now get ready to itch as we move on to the penultimate battle of the day, threadworm....

MRCP revision battle 18.7: threadworm

Threadworm, AKA enterobius vernicularis, appears frequently in MRCP questions, usually in relation to patients in institutions.

They tend to present with perianal itching.

Treatment is mebendazole 100mg (or piperazine if the patient happens to be under 2 yrs of age)



On that pleasant note, on to the last battle of the day, pseudohypoparathyroidism

MRCP revision battle 18.8: Pseudohypoparathyroidism

Pseudohypoparathyroidism is an autosomal dominant condition that occurs when a person is insensitive to PTH.


Features include:

• short metacarpals (esp 4th and 5th)
• short stature
• round face
• obese
• low IQ
• dental hypoplasia

It can be diagnosed by a failure of cAMP to increase after injection of parathyroid hormone.  More traditionally, the clinical picture of low calcium, high PTH and normal/raised alk phos is enough.


Treatment is with alfacalcidol.

It is worth noting it is associated with slipped femoral epiphysis.



To end today's battles on an almost comic note (and the fact I find this comic is a reflection that I really should get out more) there also exists a pseudopseudohypoparathyroidism, which is essentially the morphological features of pseudohypoparathyroidism but with normal biochemistry.  Hopefully that'll make you smile if it comes up!


A few questions on yesterday's battles are now online here, otherwise see you tomorrow!

MRCP questions: War 17

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 11.1 to 11.4.

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


Question 1:
What haematological picture do you get in DIC?


Question 2:
What symptoms are associated with jugular foramen syndrome?


Question 3:
Name the commonest form of thyroid cancer.



Question 4:
List 3 causes of unilateral pleural calcification



Question 5:
What condition is associated with a 'plucked chicken skin' appearence?



Question 6:
Legionella is a gram positive bacteria.  True or false?




Question 7:
Which biochemical disturbance is classically associated with legionella?


The answers are here

MRCP revision battle 17.1: DIC

Lots of short battles from a variety of specialities today so buckle up for a ride through some haematology, neurology, endocrinology, respiratory and dermatology.  Yeee-hhaaaa!

MRCP revision battle 17.1: DIC
MRCP revision battle 17.2: Jugular foramen syndrome
MRCP revision battle 17.3: Thyroid cancer
MRCP revision battle 17.4: Legionella infection
MRCP revision battle 17.5: Pleural calcification
MRCP revision battle 17.6: Pseudoxathoma elasticum






MRCP revision battle 17.1: DIC


Disseminated intravascular coagulation (=DIC) is the pathalogical widespread activation of coagulation.


Blood tests will show:

• prolonged PT
• prolonged aPTT
• massively raised d-dimer levels
• low platelets
• low fibrinogen
• schistocytes

Of these, it is the level of fibrinogen which best correlates to the severity.


Causes of DIC include:

• obstetric
• crush injury
• septicaemia
• malignancy
• transfusion reaction

The treatment is:

• treat the cause
• give platelets if platelets <50
• cryoprecipitate
• FFP
• activated protein C if septic.

Now lets canter onwards to jugular foramen syndrome....

MRCP revision battle 17.2: Jugular foramen syndrome

Jugular foramen syndrome, also known as Vermet's Syndrome, is a condition arising from the compression of the cranial nerves that run through the jugular foramen.


Now just in case they aren't quite on the tip of your tongue, the nerves that run through the jugular foramen are IX, X and XI.


The syndrome is therefore characterised by:

• loss of taste to posterior 1/3 of tongue (CN IX)
• dysphagia (CN X)
• sternocleidomastoid and trapezius paralysis (CN XI)

Anything that compresses the jugular foramen can cause this syndrome.  The commonest cause is a paraganglioma.



Now we've acquired a bit more esoteric MRCP knowledge, lets gallop on to discover some details about thyroid cancer...