MRCP revision battle 36.1: Wilson's disease

Another set of battles written before commencing the joy of a 10 hour shift... and to think we all used to think revising for finals was hard!



MRCP revision battle 36.1: Wilson's disease
MRCP revision battle 36.2: Drugs causing impaired glucose tolerance
MRCP revision battle 36.3: Acromegaly
MRCP revision battle 36.4: Vitamin C
MRCP revision battle 36.5: Insulinoma
MRCP revision battle 36.6: Metabolic syndrome
MRCP revision battle 36.7: Phaeochromocytoma





MRCP revision battle 36.1: Wilson's disease


Wilson's disease is an autosomal recessive condition inherited on chromosome 13.
Approximately 1 in 400 people carry the gene, giving the disease an incidence of around 1 in 200 000


Wilson's disease is due to a mutation in the gene coding for a copper transporting ATPase, ATP7B.   This results in the failure of biliary copper excretion, causing raised urinary copper and raised tissue copper with accumulation of copper especially in the liver and basal ganglia.


Features include:

• liver disease - hepatitis, cirrhosis
• CNS  signs - tremor, ataxia, dementia, emotional lability
• hypoparathyroidism
• haemolysis
• Kayser-Fleischer rings - copper deposits in descemet's membrane - pathognomonic
• blue nails
• hypermobile joints
• arthritis

Diagnosis:

• low serum caeruloplasmin
• raised urinary copper

Treatment: penicillamine - remember this can cause low platelets and white cells so patients should be warned to report bruising/fever/sore throat to their doctor.


Note that the liver aspects of Wilson's tend to be reversible while the neuro problems have limited reversibility on treating.



Now on for a short battle about drugs causing impaired insulin tolerance...

MRCP revision battle 36.2: Drugs causing impaired glucose tolerance

Drugs associated with impaired glucose tolerance include:

• thiazide diuretics
• furosemide
• steroids
• tacrolimus
• ciclosporin
• IFN alpha
• nicotinic acid

I'm afraid I can't think of any clever way to remember this list... if anyone can think of one please email me... marietreasure7 followed by at gmail .com.


Next up: acromegaly

MRCP revision battle 36.3: Acromegaly

Acromegaly is caused by excess growth hormone.  99% of cases are due to a pituitary tumour.  5% of cases are associated with MEN 1 (now might be a good time to re-revise battle 20.1 which covers MEN...)


For the purposes of revision I'll divide features into 'classical' and 'MRCP smaller print'


Classical features:

• soft tissue growth
• large tongue
• large hands
• big ears
• coarsening facial features
• widening of gaps between teeth
• impaired glucose tolerance (40%)/diabetes (20%)
• raised blood pressure
• horse voice

MRCP features:

• raised phosphate
• raised triglycerides
• pseudogout
• colonic polyps
• proximal muscle weakness
• arthralgia

Diagnosis:

• failure of GH to decrease (to a lab-specific level) after oral glucose tolerance test
• false positives to this test may occur in puberty, pregnancy, DM, renal/liver impairment
• serum IGF-1 is a screening test only

Treatment:

• transphenoidal surgery (40-70% cure)
• ocreotide = somatostatin analogue
• bromocriptine (<20% effective)
• pegvisomant = GH receptor antagonist, conclusive data on effectiveness still awaited

Now for a little vitamin C....

MRCP revision battle 36.4: Vitamin C

Vitamin C is an antioxidant.  It is found in many fruits, vegetables and in liver. 


A deficiency in vitamin C leads to scruvy:

• gingivitis
• loose teeth
• malaise
• poor wound healing
• bleeding

Causes of deficiency include poor diet and pregnancy.


Now for another short battle, insulinoma...

MRCP revision battle 36.5: Insulinoma

Insulinoma is the commonest pancreatic endocrine tumour.

10% are malignant, 10% are multiple.
If multiple, 50% are associated with MEN-1.


Presentation tends to be with the symptoms of hypoglycaemia (revise battle 29.1 if you need to be reminded of these)


Diagnosis is by supervised prolonged fasting.


Treatment is surgical excision.



Onwards for a quick tour of metabolic syndrome...

MRCP revision battle 36.6: Metabolic syndrome

Metabolic syndrome (AKA syndrome X) is a combination of disorders that increase a patient's risk of cardiovascular disease/diabetes.



It is defined as:

• central obesity (= waist >94cm in europeans) OR BMI >30 
• PLUS 2 of the following 4:
• triglycerides >1.7
• low HDL
• BP >130/85
• fasting glucose >5.6 or type 2 DM

Metabolic syndrome is associated with:

• raised uric acid levels
• non-alcoholic fatty liver
• PCOS

Now for the final battle of the day, phaeochromocytoma...

MRCP revision battle 36.7: Phaeochromocytoma

Phaeochromocytomas are rare, catecholamine (=adrenaline, noradrenaline, dopamine ) producing tumours.


Presentations are variable and can include:

• headaches
• visual disturbances
• chest tightness
• palpitations
• hypertension (70% persistent, 30% episodic)
• hypotension/postural hypotension is also possible
• faints
• abdominal pain

The triad of headache, sweating and palpitations is 90% predictive.



Lots of facts to remember about phaeochromocytomas follow the rule of 10%:
10% are familial (= MEN II, neurofibrosis, Von Hippel Lindau)
10% are bilateral, 10% are malignant and10% are extraadrenal


The commonest extraadrenal site is the organ of Zuckerkandl, which is adjacent to the bifurcation of the aorta.



Diagnosis is by VMA in urine and CT/MRI (show up bright white on T2 weighted MRI)



Treatment is surgery with pre-op alpha and beta blockade (alpha blocker of choice = phenoxybenzamine)



Recurrence is possible so these patients should be followed up lifelong.



Thats all for today, hopefully more tomorrow!

MRCP revision battle 35.1: Graves' disease

Today is going to be a bit of a thyroid binge with a little gap to end on...


MRCP revision battle 35.1: Graves' disease
MRCP revision battle 35.2: Subacute (de Quervain's) thyroiditis
MRCP revision battle 35.3: Hashimoto's thyroiditis
MRCP revision battle 35.4: Drugs causing hypothyoidism
MRCP revision battle 35.5: Thyroid storm
MRCP revision battle 35.6: Anion gap




MRCP revision battle 35.1: Graves' disease


Graves' disease is an autoimmune condition which causes hyperthyroidism.  Autoantibodies against the thyroid gland are present.  This may be antithyroid peroxidase antibodies or antithyroglobulin antibodies (neither are specific as they may also found in Hashimotos)  or TSH receptor antibody (specific)


Features of Graves' disease include:

• eye disease (see revision battle 29.2 to recap which features are Graves' disease specific)
• pretibial myxoedema - only found in Graves
• thyroid acropachy = clubbing, painful toe and finger swelling - also only in Graves
• diffuse thyroid enlargement

Associated with Graves' disease include:

• diabetes 
• vitiligo
• Addisons

Treatment options for Graves are:

1. titrate antithyroid drugs
• start at 40mg carbimazole
• continue for 12-18 months
• less side effects
2. block and replace
• start at 40mg carbimazole, levothyroxine once euthyroid
• treat for 6 to 9 months
• more side effects
3. radioiodine

on to battle 35.2...

MRCP revision battle 35.2: Subacute (de Quervain's) thyroiditis

Subacute (de Quervain's) thyroiditis is the label given to a viral infection which causes a painful goitre and potentially transient hyper or hypo thyroidism.


In addition to a painful goitre the patient may have a fever and dysphagia.


Classically it occurs following a upper respiratory tract infection but it may occur after any viral illness (mumps, adenovirus) and also post-partum.


Histology would show multi-nucleated giant cells.
Radioiodine uptake is typically less than 1% at 24 hrs.


Treatment is with NSAIDs.  It resolves spontaneously.


Onwards to Hashimotos...

MRCP revision battle 35.3: Hashimoto's thyroiditis

Hashimoto's thyroiditis is an autoimmune condition causing hypothyroidism.


It is associated with high titres of antithyroid peroxidase antibodies or antithyroglobulin antibodies (neither are specific as they may also found in Graves' disease)


Patients with Hashimotos have a goitre due to lymphocytic and plasma cell infiltration.  The gotire is firm and non-tender.


Clinically patients' with Hashimotos may be hypothyroid, euthyroid or occasionally initially even hyperthyroid!



So lets move away from this autoimmune cause of hypothyroidism to look at drugs causing hypothyroidism...

MRCP revision battle 35.4: Drugs causing hypothyoidism

Drugs which can cause hypothyroidism include:

• lithium
• interferon
• amiodarone
• phenytoin
• aspirin
• oestrogens
• furosemide

 On  to the final bit of thyroid for the day: thyroid storm

MRCP revision battle 35.5: Thyroid storm

Thyroid storms may be precipitated by:

• recent thyroid surgery
• radioiodine
• infection
• MI
• trauma

Iatrogenic thyroxine excess doesn't usually cause a storm.


Features of a thyroid storm include:

• fever >38.5C
• tachycardia
• confusion
• nausea and vomiting
• hypertension
• heart failure

Treatment:

• treat precipitating event
• propranolol
• antithyroid drugs eg propylthiouracil or carbimazole
• dexamethasone/hydrocortisone - blocks T4 to T3 
• Lugol's solution
• ?digoxin to slow heart.

Thats the end of the thyroid binge - now to 'mind the gap..'

MRCP revision battle 35.6: Anion gap

If you have a patient with metabolic acidosis you need to calculate their anion gap.  This is very simple to do, so long as you can remember the following formula (which unfortunately I never can):

Anion gap = (Na + K) - (Cl + HCO3)

A 'normal' anion gap is 10 to 18mmol/l (which can be recalled as roughly the ages you attend secondary school for)


Causes of a raised anion gap may be recalled as LUKES:

• lactic acid (shock, infection, hypoxia)
• urate (renal failure)
• ketones (diabetes, alcohol)
• ethylene glycol/methanol
• salicylate

A more comprehensive list can be recalled by 'cute dimples' = cyanide, urate, toulene, ethylene glycol, diabetic ketoacidosis, isoniazid, methanol, propylene glycol, lactic acid, salicylates




Causes of a metabolic acidosis with a normal anion gap can be recalled as FUSEDCARS:

• fistula (pancreatic)
• uretogastric conduits
• saline administration
• endocrine (hyperparathyroidism)
• diarrhoea
• carbonic anhydrase inhibitors (acetazolamide)
• ammonium chloride
• renal tubular acidosis
• spironolactone

Hopefully thats demystified the anion gap for you.

MRCP revision battle 34.1: The first heart sound

I've just had a whole week off revising.  Very bad from a passing MRCP point of view.  Very good from a remaining sane, keeping friends and staying up-to-date with all the other bits of paper medicine in the UK requires.  Since the exam is now under a month away however I'd better buckle down to it...


MRCP revision battle 34.1: The first heart sound
MRCP revision battle 34.2: The second heart sound
MRCP revision battle 34.3: The third and fourth heart sounds
MRCP revision battle 34.4: Sodium Valproate
MRCP revision battle 34.5: Salicylate overdose
MRCP revision battle 34.6: Haemodialysis in overdose
MRCP revision battle 34.7: Cyanide poisoning
MRCP revision battle 34.8: Phentolamine





MRCP revision battle 34.1: The first heart sound



The first heart sound is made by the closure of the mitral and tricuspid valves.



A loud S1 may be due to:

• mitral stenosis
• hyperdynamic states
• short PR

A soft S1 may be due to:

• long PR
• mitral regurgitation

A    s p l i t  S1 is caused by:

• RBBB
• LBBB
• VT 
• inspiration
• Ebsteins abnormality

A variable S1 is caused by:

• complete heart block
• AF

On to the second heart sound....

MRCP revision battle 34.2: The second heart sound

The second heart sound comprises of the closure of the aortic and pulmonary valves.They usually close <0.05secs apart and in alphabetical order, with the aortic valve closing first.



A loud S2 may be due to:

• systemic hypertension (=loud A2)
• pulmonary hypertension (=loud P2)
• tachycardia

A soft S2 may be due to aortic stenosis.



A  w i d e l y   s p l i t  second heart sound occurs in:

• RBBB
• deep inspiration
• mitral regurgitation
• pulmonary stenosis

A reverse split (=paradoxical split) second heart sound occurs in:

• LBBB
• severe aortic stenosis
• right ventricular pacing
• WPW type 2
• patent ductus arteriosus

Onwards for the third and fourth heart sounds...

MRCP revision battle 34.3: The third and fourth heart sounds

Third heart sound

Third heart sound, AKA gallop rhythm, can be perfectly normal in children and young adults.

It is due to passive filling of the ventricles when the atrioventricular valves open.


In the over 40s it is pathological and may indicate:

• mitral regurgitation
• VSD
• CCF
• constrictive pericarditis

S1          S2  S3

The sound of the 3rd heart sound may be remembered as 'Kentucky' or 'SLOSH-ing in'




Fourth heart sound

A 4th heart sound is caused by atrial contraction against stiff ventricles.

It occurs in:

• aortic stenosis
• HOCM
• hypertension

S4  S1     S2

It can be remembered as 'Tennessee' or  'a STIFF wall'




I thoroughly recommend this website to listen to them http://www.wilkes.med.ucla.edu/Rubintro.htm



Now away from cardiology and to a bit of pharmacology - sodium valproate....

MRCP revision battle 34.4: Sodium valproate

Sodium valproate is a drug used in epilepsy.


It is a P450 inhibitor.


It has the highest risk of birth defects of any of the anti-epileptic drugs.


Sodium valproate also has an impressive plethora of unfortunate side effects which often appear in MRCP questions:

• alopecia
• nausea
• gynaecomastia
• weight gain
• tremor
• hepatitis
• pancreatitis
• tetratrogenic
• ataxia
• thrombocytopenia

As always with long lists of side effects its probable best to try and imprint on your mind a cartoon image of an unfortunate patient who is suffering from all of these side effects.   Personally I have a bald man who has big breasts and a fat, pregnant stomach, who is walking along in an ataxic way, covered in bruises (from his thrombocytopenia and crashing into things with his ataxic gait) while also vomiting and pointing with his trembling fingers to his liver and pancreas.



On that pretty image, lets move on to battle 33.5...

MRCP revision battle 34.5: Salicylate overdose

Patients who have taken a salicylate overdose are potentially more interesting than those who have taken a paracetamol overdose as salicylate poisoning actually has early clinical features you can look out for,  such as:

• sweating
• tinnitus
• dizziness
• pyrexia
• hyperventilation

A blood gas should show a mixed respiratory alkalosis and metabolic acidosis, and potentially a low potassium.


The sweating and pyrexia are due to uncoupling of oxidative phosphorylation.




The effects of salicylate are dose related:

• 150mg/kg: mild
• 250mg/kg: moderate
• >500mg/kg: severe

Later features of salicylate poisoning include:

• renal failure
• hypo or hyperglycaemia
• seizures
• acidosis

Treatment:

• activated charcoal if within 1 hr
• correct acidosis with 1.26% sodium bicarb
• haemodialysis if:
• conc >700mg/l
• metabolic acidosis resistant to treatment
• acute renal failure
• pulmonary oedema
• seizures
• urinary alkalinization is rarely used and is contra-indicated in cerebral or pulmonary oedema

Lets move on to consider use of haemodialysis in overdoses in general...

MRCP revision battle 34.6: Haemodialysis in overdose

Haemodialysis is not helpful in removing a drug if:

• the drug has a large volume of distribution (eg amiodarone, paraquat)
• the drug is highly protein-bound (digoxin, phenytoin)

The drugs that are appropriate for haemodialysis can be remembered as BLAST:

• Barbituates
• Lithium
• Alcohol (methanol/ethanol)
• Salicylate
• Theophylline

Charcoal haemoperfusion may be considered for:

• paracetamol
• theophylline

Now for a touch of cyanide poisoning....

MRCP revision battle 34.7: Cyanide poisoning

Cyanide is used in insecticides, photography and found in some metals.


It's toxicity comes from inhibition of oxidising enzymes, which happily is reversible.


The classical features of cyanide poisoning are:

• brick red skin
• smell of bitter almonds

Acute signs of cyanide poisoning include:

• hypotension
• hypoxia
• headache
• confusion

Chronic signs of cyanide poisoning include:

• ataxia
• peripheral neuropathy
• dermatitis

Treatment is with 100% oxygen and IV dicolbalt edetate



Onwards for a very brief final battle of the day: phentolamine