MRCP revision battle 54.1: Primary sclerosing cholangitis

Today is in pairs: a pair of gastro battles, a pair of cardiology battles, a pair of haematology battles then a strange inherted disorder to finish on....


MRCP revision battle 54.1: Primary sclerosing cholangitis
MRCP revision battle 54.2: Jaundice
MRCP revision battle 54.3: Patent ductus arteriosus
MRCP revision battle 54.4: Cardiac axis
MRCP revision battle 54.5: Haemolysis
MRCP revision battle 54.6: Leukoerythroblastic change
MRCP revision battle 54.7: Gaucher's disease



MRCP revision battle 54.1: Primary sclerosing cholangitis

Primary sclerosing cholangitis is a condition of unknown aetiology in which there is inflammation and fibrosis of bile ducts.


Presentation:

• patients may be asymptomatic with an incidental finding of raised ALP
• may present as:
• jaundice
• pruritus
• abdo pain
• fatigue

Diseases associated with primary sclerosing cholangitis include:

• IBD (UC>crohns; 70% of patients with PSC have UC but only 5% of patients with UC have PSC)
• HIV
• HLA A1, B8, DR3

Males are more frequently affected than females.


Diagnosis is by:

• ERCP - shows strictures of the biliary tree and a 'beaded' appearence
• liver biopsy - fibrous, obliterative cholangitis
• ANA, SMA and ANCA may be positive

Treatment is:

• colestyramine for pruritis
• ursodeoxycholic acid to improve cholestatis
• ?stenting of strictures 
• ?liver transplant

Complications include:

• decreased absorption of fat-soluble vitamins A,D,E and K
• clotting abnormalities and easy bruising
• osteoporosis
• cholangiocarcinoma (10-30%)
• bacterial cholangitis
• liver cirrhosis
• portal hypertension

Survival tends to be around 10 yrs


As an aside, the other 2 conditions associated with cholangiocarcinoma are:

• liver flukes
• Caroli's disease = dilation of hepatic ducts

Into the yellow...

MRCP revision battle 54.2: Jaundice

Jaundice is yellow pigmentation of the skin caused by raised bilirubin.

It is generally clinically visible above 35micromol/l.


The 'story' of bilirubin is illustrated in the diaphragm below:

• phagocytes break haemoglobin down into unconjugated (=insoluble) bilirubin
• unconjugated bilirubin is joined with glucoronic acid in the liver, making it conjugated (=soluble)
• conjugatde bilirubin passes into the gallbladder and on to the small intestine, where it is converted into urobilinogen and excreted in urine by the kidneys or to stercobilinogen and excreted in faeces

The types of jaundice are:

1. Pre-hepatic = unconjugated

• caused by:
• haemolysis
• lack of UDP: Gilberts, Crigler Najjar
• urine/faeces colours normal

2. Hepatic = both conjugated and unconjugated

• caused by:
• infection: HBV, HCV, EBV
• Wilsons
• Budd-Chiari
• Dubin-Johnson/Rotor syndromes
• cirrhosis
• drugs:
• anti-TB meds
• statins
• sodium valproate
• MAOIs
• halothane
• paracetamol OD
• urine dark, faeces normal

3. Post-hepatic = conjugated = obstructive/cholestatic

• gallstones
• pancreatic cancer
• cholangiocarcinoma
• primary bilary sclerosis
• sclerosing cholangitis
• Mirrizi's syndrome = obstructive jaundice secondary to compression of the common hepatic duct by a gallstone impacted in the cystic duct
• Drugs
• antibiotics - co-amoxiclav, nitrofurantoin, flucloxacillin
• OCP
• chlorperazine
• sulphonylureas
• anabolic steroids
• urine pale and faeces pale

Now for something different... PDA...

MRCP revision battle 54.3: Patent ductus arteriosus

The ductus arteriosus is a connection between the pulmonary trunk and the descending aortic arch allowing blood flow in the fetus to avoid the fluid-filled lungs.

It should close shortly after birth, being mostly closed within 48 hrs and fully closed within 3 weeks, leaving the ligamentum arteriosum in its place.


Closure is due to 2 mechanisms:

1. exposure of infants lungs to oxygen promotes bradykinin production which promotes PDA closure
2. loss of maternal prostaglandins encourages closure

Closure is more likely to fail (=patent ductus arteriosus) in:

• premature infants
• infants exposed to rubella in 1st trimester
• infants at high altitude

Features of patent ductus arteriosus include:

• machinery murmur
• wide, collapsing pusle
• apical heave

If it does not close the infant may fail to thrive or develop heart failure.
Many cases however will be asymptomatic.
5% of patients with PDA go to develop pulmonary hypertension and Eisenmengers.


Treatment:

• indomethacin (a prostaglandin antagonist) causes closure in 90%
• surgical treatment is also an option

In some cases (eg transposition of the great vessels) keeping the ductus arteriosus open may be beneficial to the infant, in which case IV prostaglandin E1 is given.


On to the cardiac axis...

MRCP revision battle 54.4: Cardiac axis

The normal cardiac axis is -30 to +90 degrees.

More negative = left axis deviation
More positive = right axis deviation.


Causes of left axis deviation:

• LBBB
• LVH
• ASD
• cardiomyopathies
• aortic stenosis
• can be normal in:
• ascites
• pregnancy
• obesity

Causes of right axis deviation:

• RBBB
• RVH --> lung disease
• PE
• can be normal in:
• infancy
• thin people

Next: haemolysis

MRCP revision battle 54.5: Haemolysis

Haemolysis (=breakdown of red blood cells) may be intravascular or extravascular.
It causes a microcytic anaemia and raised reticulocyte count.


Intravascular haemolysis

Intravascular haemolysis is characterised by:

• low haptoglobin (as all used up trying to 'recycle' the broken down red cells)
• raised free plasma haemoglobin
• haemoglobuinuria: red-brown urine
• haemosiderinuria: once haptoglobin binding capacity is surpassed free Hb is filtered by the kidneys and can be detected in the urine in sloughed tubular cells using Prussian blue staining

Causes of intravascular haemolysis include:

• cold AIHA
• transfusion reaction
• G6PD (recall battle 28.4?)
• paroxysmal nocturnal haematuria (recall battle 27.6?)
• microangiopathic haemolytic anaemia (recall battle 38.6?)
• DIC
• TTP
• mechanical heart valves

Extravascular haemolysis

Extravascular haemolysis may cause splenomegaly.

Causes of extravascular haemolysis include:

• warm AIHA (remember battle 39.7?)
• cold haemagglutination disease
• spherocytosis
• haemoglobinopathies
• haemolytic disease of the newborn

Now to the second haem battle of the day...

MRCP revision battle 54.6: Leukoerythroblastic change

Leukoerythroblastic change is the term used to describe nucleated red cells and primative white cells in the peripheral blood.


Causes of leukoertythroblastic change can be split into 2 catagories:

1. Invasion of bone marrow space

• metastatic carcinoma
• leukaemia
• myeloma
• lymphoma
• myelofibrosis
• Gaucher's disease (covered in next battle)

2. Severe illness


Leukoerythroblastic change may be indicated by:

• high leucocyte alkaline phosphatase
• Dohle bodies = blue leucocyte inclusions in peripheral cytoplasm of neutrophils
• left shift of neutrophils = younger neutrophils than normal -->less nuclei

As an aside, Dohle bodies are also seen in burns, infection and trauma.


Now for the final short skirmish, Gaucher's disease...

MRCP revision battle 54.7: Gaucher's disease

Gaucher's disease is the most common of the lysosomal storage disorders.

It is a recessive inherited disorder on chromosome 1 in which lipid accumulates in organs (spleen, liver, brain, kidneys, lungs) and bone marrow due to lack of an enzyme.

Ashkenazi Jews are more affected.


Possible features include:

• splenomegaly
• hepatomegaly
• yellow-brown skin pigmentation
• seizures
• low IQ
• osteoporosis

Treatment can include splenectomy and replacement of the missing enzyme.