Metabolic causes of liver disease Flashcards
Examples of metabolic causes of liver disease
Haemochromatosis
Wilson’s disease
Alpha-1-antitrypsin deficiency
What is haemochromatosis
Deficiency of the iron regulatory hormone hepcidin -> iron overload
*What mutations cause haemochromatosis
HFE mutations - 2 types/genes:
C282Y
H63D
Haemochromatosis clinical presentation
Often asymptomatic until later stags.
Usually presents between 40-60.
Fatigue, weakness, arthropathy, heart problems.
Clinical presentation of advancing haemochromatosis
Also Bronzing of the skin,
Diabetes,
Hepatomegaly,
Arthropathy
Haemochromatosis pathophysiology
Depends on the aetiology
In hereditary; increased intestinal absorption of iron causes accumulation in tissues, particularly in the liver, leading to fibrosis and functional organ failure
Aetiology of haemochromatosis
Often hereditary in autosomal recessive pattern of HFE gene (responsible for regulating iron uptake).
Epidemiology of haemochromatosis
C282Y is more common in white populations
Diagnosis of haemochromatosis
Screening not advised;
penetrance very low.
Consider genetic analysis in unexplained chronic liver disease.
Total Iron Binding capacity reduced, serum iron raised.
LFTs can be normal
Treatment of haemochromatosis
Phlebotomy; removing 400-500ml of blood every 2 weeks.
Tends to require insulin
Complications of haemochromatosis
Liver fibrosis Liver failure Cirrhosis Hepatocellular carcinoma Diabetes is deposition in the pancreas
What is Wilson’s disease
Disorder of copper metabolism -> Copper build up in the liver
Wilson’s disease clinical presentation
Hepatic = acute liver failure; chronic hepatitis Psychological = behavioural problems common, might lead to diagnosis Eyes = Kayser-Fleischer ring and/or sunflower cataracts on examination with a slit lamp
Wilsons disease pathophysiology
ATP7B codes for a P type ATPase, which acts in hepatocytes to move copper across intracellular membranes.
Copper transporting action directly supports production of ferroxidase caeruloplasmin, as well as excretion of copper into bile.
Serum levels of copper are low.
Hepatic retention of copper develops, which causes liver injury (cirrhosis, failure)
Wilsons disease, what gene codes for which protein that allows copper to move into hepatocytes
ATP7B codes for P type ATPase
What are the purposes of copper once undergone transporting action into hepatocytes
Supports production of Ferroxidase Caeruloplasmin.
Excretion of copper into bile.
Wilsons disease aetiology
Mutation in ATP7B - over 500 identified.
Autosomal recessive
Wilsons disease epidemiology
Rare -difficult to diagnose.
Affects 1/30,000 to 1/100,000
Wilsons disease diagnosis
Slit lamp analysis of eyes
Detect Kayser-Fleischer rings (bronze rings of the cornea)
Low serum caeruloplasmin.
Wilsons disease treatment
Avoid alcohol.
Prevent intestinal copper absorption - Chelation agents such as Zinc (lifelong)
Hepatic = about 5% of patients with liver failure will need a transplant
Neuro = deep brain stimulation
Wilsons disease complications
Cirrhosis -> liver failure.
Fatal if untreated
What is Alpha-1-antitrypsin deficiency
Deficiency of serine protease inhibitor alpha-1-antitrypsin
Clinical presentation of Alpha-1-antitrypsin deficiency
Lung symptoms present between 30-50 (this is earlier in smokers). COPD life symptoms, early onset emphysema
Liver: Not always present here. Neonates may present jaundice and hepatitis. Possibly cirrhosis and liver failure
Pathophysiology of Alpha-1-antitrypsin deficiency
A1AT inhibits the action of neutrophil-protease enzymes in the lung, produced in presences of inflammation, infection or smoking.
In deficiency, elastase can break down elastin without inhibition, so destroys alveolar walls and causes emphysematous change
What is the function of Alpha-1-antitrypsin
Inhibits the action of neutrophil-protease enzymes in the lung, produced in presences of inflammation, infection or smoking
Aetiology of Alpha-1-antitrypsin deficiency
Mutation in the SERPINA1 gene
Autosomal recessive
Relatively low penetrance
Many possible mutations
Epidemiology of Alpha-1-antitrypsin deficiency
Commonest amongst white people.
1/4000 present
Underdiagnosed since not always exhibits problems
Diagnosis of Alpha-1-antitrypsin deficiency
A1AT serum levels
Treatment of Alpha-1-antitrypsin deficiency
Lung = (as COPD) cessate smoking, corticosteroids, bronchodilators, treat infection. Liver = cessate drinking. In liver failure, possibly transplant
Complications of Alpha-1-antitrypsin deficiency
Variable prognosis.
Untreated can lead to liver failre
