Inherited liver disease Flashcards
Which are the more common of the inherited liver diseases and how are they inherited? (what pattern of inheritance?)
The four most common conditions are haemochromatosis (carrier 1:14), alpha-1-antitrypsin deficiency (carrier 1:20), cystic fibrosis (1:25) and Wilson’s disease (1:85)
What is Wilson’s disease?
This is a condition associated with a block in the excretion of copper into the cannuliculi. Therefore the tissue copper is elevated, but the bile and serum copper is decreased.
Which chromosome is Wilson’s disease located on?
I just can’t believe that they would want us to learn this.
Chromosome 13
What is the mechanism of Wilson’s disease
It is an abnormality in the copper-transporting ATPase, but there are like >200 mutations recognised.
What are the blood test and urinary findings in this disease?
Firstly, there is decreased copper in the serum, and decreased caeruloplasmin.
Secondly there is increased urinary copper
Don’t forget good ol’ KF rings in the eye
How do we screen family members for Wilson’s disease?
This is important - because there are so many mutations, there is no single DNA test.
Instead, the screening relies on “microsatellite (flanking) markers”
If you already have a high level of suspicion you could just do a urine sample or serum copper/caeruloplasmin
What is the primary change in cystic fibrosis? (the underlying mechanism)
There is a mutation in the chloride transport channel.
IT IS ON CHROMOSOME 7
What are the more common manifestations of cystic fibrosis?
paranasal sinus opacification (90-100%)
bronchiectasis (80%)
the most common GI manifestation is pancreatic insufficiency (85%)
about 20% get liver disease
Infertility is the most common manifestation for men with 95% males suffering, and almost 100% absence of the vas deferens
What is the most common mutation for CF? Which chromosome?
Once again, it’s chromosome 7
the most common mutation is deletion F508
What is alpha 1 antitrypsin deficiency?
This is an autosomal recessive condition from chromosome 14.
In the liver it is the failure of formation and excretion of alpha1 antitrypsin
In the lungs, the pathophysiology is different. Here the defective (or insufficient enzyme) fails to protect from the action of neutrophil elastase
What is haemochromatosis and which chromosome is it on?
CHROMOSOME 6!
It is an iron accumulation disorder
It is associated with many many problems including heart disease, diabetes, M-C joint arthritis and infertility. There is skin colour change (associated with pituitary deposition, leading to MSH release) and cirrhosis and HCC development
What is the characteristic arthritic changes with haemochromatosis?
Metacarpo-phalyngeal joint arthritis - JOINT SPACE NARROWING
there is also a propensity for pseudogout
Why do haemochromatosis suffers get testicular atrophy?
This is most likely related to pituitary deposition, rather than testicular iron deposition.
How do we make the diagnosis of haemochromatosis?
This is interesting and a developing field.
Firstly, there is a genetic diagnosis of the predisposition for the condition, and this is confirmed by testing for C282Y and H63D.
HOWEVER:
established haemochromatosis is defined as:
- stainable hepatic iron grade 3 or 4
- hepatic iron concentration of >80 micromol/gram
- hepatic iron index > 1.9
- > 5g iron removed by phlebotomy
What is hepcidin? What is ferroportin?
Interesting question!
Hepcidin’s overall role is to inhibit iron absorption.
It binds to ferroportin and inhibits enterocyte iron release at the basolateral membrane.
How would you screen for haemochromatosis?
The first thing would be to perform a transferrin saturation.
If this is >45%, then repeat when fasting.
If still >45%, then perform HFE gene testing.
If these come back as C282Y +/+ or C282Y/H63D +/+, then do LFTs and ferritin.
Biopsy is essential for diagnosis.
If you’ve just diagnosed someone with haemochromatosis, what do we have to warn them about not getting?
Don’t drink heavily.
Don’t get fat (NASH)
Don’t get hepatitis.
Also, be aware of porphyria cutanea tarda
Usually we should be doing 6 monthly USS and AFP
What is Gilbert’s syndrome?
this is a benign condition of mild unconjugated hyperbilirubinaemia.
Basically in times of increased stress, there is an inability of the liver to increase its metabolism of the bilirubin
This condition is A. Recessive
What is Dubin-Johnson syndrome?
This is familial hyper-conjugated bilirubinaemia
It is autosomal recessive.
The ALP is normal. The process is about excretion.
There are a few familial cholestatic syndromes. Do you know their names at least?
First up is benign recurrent intra-hepatic cholestasis.
This autosomal recessive condition is all about a defect in the biliary canalicular transporters
Next is progressive familial intra-hepatic cholestasis.
These are also autosomal recessive and are all treated with OLT
Have you heard of Crigler-Najjar syndrome?
this is a SEVERE unconjugated hyperbilirubinaemia.
it is treated with phototherapy and OLT
How does vitamin C help with the absorption of iron?
And where does iron get absorbed?
Ascorbic acid helps to change iron from Fe3+ (ferric) to Fe2+ (ferrous). It also helps to keep iron soluble
it’s absorbed at the proximal duodenum
With respect to HBV infection, what is the YMDD mutant?
Found different answers on this, but Lawrie Powell has said that this occurs following lamovudine treatment.
UTD says it is a mutation associated with reverse transcriptase.
What are the best tests of liver synthetic function?
albumin and prothrombin time (following vitamin K administration)
