MRCP revision battle 28.1: Haemochromatosis

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


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



MRCP revision battle 28.1: Haemochromatosis


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


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



Presentation is initially with tiredness and arthralgia

Later problems include:

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

Males are affected earlier and more severely than females.



Diagnosis is by:

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

Treatment is regular venesection and ?chelation with desferrioxamine



Haemosiderosis is secondary haemochromatosis.  


Causes of haemosiderosis include:

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

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

MRCP revision battle 28.2: Syphillis

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



Syphilis is caused by the spirochaete treponema pallidum.



There are 4 stages of syphilis:


1) Primary

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

2) Secondary

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

3) Tertiary syphilis

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

4) Quaternary syphilis

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

Tests:

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

Treatment:

• IM penicillin or PO doxcycline

Random eponymous warning - Jarisch-Herxheimer reaction:

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

Occurs in around 90% of patients with secondary syphilis.




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

MRCP revision battle 28.3: Third nerve palsy

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


It has 2 adjacent nuclei:

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

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


In the orbit it splits into:

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

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



Classic 3rd nerve palsy:

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

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

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



Causes of third nerve palsy:

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

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



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

MRCP revision battle 28.4: G6PD deficiency

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

It is x-linked recessive.


It causes intravascular haemolysis.


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

Precipitants of crisis include:

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

During a crisis a blood film will show:

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

 click here for a whole page of images of Heinz bodies



 Management is to avoid precipitants and transfuse if necessary.


On to Kaposi's sarcoma...

MRCP revision battle 28.5: Kaposi's sarcoma

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

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


It is associated with HHV-8.


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



Next up - CML....

MRCP revision battle 28.6: Chronic Myeloid leukaemia

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

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


Classical presentation is with:

• decreased weight
• tiredness
• sweating

Possible additional presentations are:

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

Approximately 30% are detected by chance.



Features include:

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

The philadelphia chromosome is present in >80% of cases

The philadelphia chromosome:

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

Treatment for CML is:

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

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




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

MRCP revision battle 28.7: Gerstmann's Syndrome

Gerstmann's Syndrome is a condition characteristed by:

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

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



On that esoteric note, see you tomorrow!