MRCP revision battle 52.1: Zollinger-Ellison Syndrome

Finally I have a topic to put under the 'z' catagory in my A to Z index!

Today we have:

MRCP revision battle 52.1: Zollinger-Ellison Syndrome
MRCP revision battle 52.2: Congential Hyperbilinrubinaemia
MRCP revision battle 52.3: Metformin
MRCP revision battle 52.4: Flecainide
MRCP revision battle 52.5: Arrhythmogenic right ventricular cardiomyopathy
MRCP revision battle 52.6: Pulmonary hypertension and cor pulmonale
MRCP revision battle 52.7: Scromboid poisoning




MRCP revision battle 52.1: Zollinger-Ellison Syndrome


Zollinger-Ellison syndrome is a rare condition in which there are multiple gastric and duodenal ulcers in association with gastrin-secreting adenoma. 

The adenoma is usually pancreatic in origin but may be found in the stomach or duodenum.



50-60% of the adenomas in Zollinger-Ellison syndrome are malignant.
10-30% are associated with MEN-1.
(quick recap: MEN 1 = pancreatic tumours, parathyroid tumours and pituitary tumours)


Presentation:

• epigastric pain from the ulcers
• diarrhoea
• malabsorption/steatorrhoea from inactivation of pancreatic enzymes

Diagnosis is by a raised fasting gastrin level.
Note gastrin levels will also be raised in achlorhydria - this differential can be eliminated by doing a secretin stimulation test which will cause a raised gastrin level in Zollinger-Ellison syndrome but no rise with achlorhydria.


Treatment is with high dose PPI (eg 60mg/day).
Ocreotide (somatostatin analogue) may help with symptom relief.


On to consider some congenital causes of jaundice...

MRCP revision battle 52.2: Congential Hyperbilinrubinaemia

This battle will briefly run through 4 conditions associated with congenital hyperbilinrubinaemia....


1. Gilberts


This is the absolute classic.  Gilberts is inherted in an autosomal recessive fashion and affects 1-2% of the population.


Gilberts is due to low levels of UDP glucuronosyltransferase.
It results in a rise in unconjugated bilirubin.

Gilberts is entirely benign and many sufferers only take on a yellow tinge when they have a concurrent illness.



2. Crigler Najjar

There are 2 types of Crigler Najjar - type 1, which is autosomal recessive, and type 2, which is autosomal dominant.


It is due to there being no UDP glucuronosyltransferase
This results in a catastophic rise in unconjugated bilirubin.


Unless the sufferer has a liver transplant they are likely to die as a baby.




3. Dubin Johnson

Dubin Johnson is an autosomal recessive condition in which there is a mutation in the cMOAT transport protein resulting in a defect of hepatic excretion of bilirubin and a rise in conjugated bilirubin.


This manifests as intermittent jaundice with RUQ pain.


Tests to confirm Dubin Johnson include:

• coproporphyrin I levels being 3-4x higher than coproporphyrin III- in normal subjects this is reversed
• normal levels of urine coproporphyrin  but 80% being the I isomer, when normally this would be 25%
• at postmortem: liver has black pigmentation

Happily Dubin-Johnson is a benign condition



4. Rotor syndrome

Rotor syndrome is an autosomal recessive disorder which is similar to Dubin-Johnson and is also due to a defective mechanism of excretion of conjugated bilirubin.

It is also benign.

Rotor syndrome can be differentiated from Dubin-Johnson as:

• Dubin-Johnson has normal levels of urinary coproporphyrin while Rotor syndrome has high levels
• liver in Dubin-Johnson has black pigmentation whereas in Rotor syndrome it is normal

Now on to metformin...

MRCP revision battle 52.3: Metformin

Metformin's mechanism of action is:

• increasing gluconeogenesis
• increasing insulin sensitivity and therefore increasing peripheral utilisation of glucose
• possibly by decreasing GI absorption of carbohydrates

Metformin works only in the presence of endogenous insulin and is therefore only effective if there is residual functioning pancreatic islet cells.


Adverse effects of metformin include:

• GI upset - to an intolerable degree in up to 20% of subjects
• decreased B12 absorption - rarely clinically relevant but popular in MRCP questions
• rarely it may provoke lactic acidosis - usually only if there is also renal impairment.

Contra-indications to metformin include:

• eGFR <30 
• IV contrast
• stop of morning of general anaesthesia
• pregnancy
• breast feeding

Now on to a cardiac drug as we enter the cardiology section of today's battles...

MRCP revision battle 52.4: Flecainide

Flecainide is a class Ic antiarrhythmic which works by blocking the sodium channels.

Flecainide causes a wider QRS and longer PR.


Indications for flecainide are:

• AF
• SVT with accessory pathway

Its half life is 16 hrs.


Flecainide is contraindicated post MI.
It should be used with caution in those with pacemakers as it can raise the potential needed for stimulation.


Adverse effects of flecainide include:

• negatively inotropic
• bradycardic
• proarrhythmic
• oral parasthesia
• visual disturbances
• rarely: pneumonitis

Next - Arrhythmogenic right ventricular cardiomyopathy

MRCP revision battle 52.5: Arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy is the second most common cause of sudden cardiac death in young people after HCM.

It is characterised by fatty and fibrofatty tissue infiltrating predominantly the right ventricle.

It may be inherited in an autosomal dominant fashion with variable penetrance.


Presentation may be:

• palpitations
• syncope
• sudden death

ECG may be normal, or:

• T wave inversion V1-V3
• epsilon wave = terminal notch in QRS

The investigation of choice is MRI.


Treatment includes:

• sotolol
• ablation
• ICD

An MRCP-gem to remember is Naxos disease, which is the association of arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratosis and wooley hair.



Now for some pulmonary hypertension...

MRCP revision battle 52.6: Pulmonary hypertension and cor pulmonale

Definition of pulmonary hypertension

Normal pulmonary artery pressure is 12 to 16 mmHg.

Pulmonary hypertension is defined as pulmonary artery pressure:

• >25mmHg at rest OR
• >30mmHg on exercising

Note that technically a Swan-Ganz catheter/cardiac catherisation is needed to diagnose pulmonary hypertension; however, cardiac echo is often used.  Echo reports tend to quote systolic pulmonary artery pressure rather than mean - to convert to mean multiply by 0.61 and add 2.


Cor pulmonale is right heart failure caused by pulmonary hypertension.



Features of pulmonary hypertension


Tends to present with progressive shortness of breath.


On examination look for signs of right heart failure:

• right ventricular heave
• raised JVP, a waves
• loud P2
• pansystolic murmur - tricuspid regurgitation

Types of pulmonary hypertension


Primary - accounts for <1% pulmonary hypertension
10% of cases are familial and inherited in an autosomal dominant fashion


Secondary  - commonest cause is COPD
Other secondary causes of pulmonary hypertension include:

• IHD
• MV disease
• left to right shunts
• chronic hypoxia

Treatment of pulmonary hypertension

• If secondary, treat cause
• Give diuretics
• anticoagulate
• vasodilators:
• calcium channel blockers
• IV prostaglandins
• bosentan = endothelial antagonist
• sildenafil = PDE-5 inhibitor
• transplant

5 yr survival is less than 50%



On to a fishy battle...

MRCP revision battle 52.7: Scromboid poisoning

Scromboid poisoning is caused by the ingestion of amines, mainly histamines, which are produced by bacterial decarboxylation of histadine in fish meat (mainly tuna, mackeral, sardines, anchoives, marlin)

The commonest cause of scromboid poisoning is ingestion of spoiled fish following improper refridgeration.  Cooking well will not inactivate the hisatmines that have been produced.

Degree of symptoms correlates to amount of fish consumed.

Symptoms include:

• nausea
• abdo pain
• diarrhoea
• flushing
• rash
• headache 
• palpitations
• hypo or hypertension

Onset of symptoms tends to be within 10 to 30 mins but may take up to 2 hours
Symptoms tend to settle within 36 hours

Treatment is with antihistamine; corticosteroids are not indicated.


People with asthma or on isoniazid may be more severely affected.