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