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Flashcards in Metabolic causes of liver disease Deck (30)
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1
Q

Examples of metabolic causes of liver disease

A

Haemochromatosis
Wilson’s disease
Alpha-1-antitrypsin deficiency

2
Q

What is haemochromatosis

A

Deficiency of the iron regulatory hormone hepcidin -> iron overload

3
Q

*What mutations cause haemochromatosis

A

HFE mutations - 2 types/genes:
C282Y
H63D

4
Q

Haemochromatosis clinical presentation

A

Often asymptomatic until later stags.
Usually presents between 40-60.
Fatigue, weakness, arthropathy, heart problems.

5
Q

Clinical presentation of advancing haemochromatosis

A

Also Bronzing of the skin,
Diabetes,
Hepatomegaly,
Arthropathy

6
Q

Haemochromatosis pathophysiology

A

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

7
Q

Aetiology of haemochromatosis

A

Often hereditary in autosomal recessive pattern of HFE gene (responsible for regulating iron uptake).

8
Q

Epidemiology of haemochromatosis

A

C282Y is more common in white populations

9
Q

Diagnosis of haemochromatosis

A

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

10
Q

Treatment of haemochromatosis

A

Phlebotomy; removing 400-500ml of blood every 2 weeks.

Tends to require insulin

11
Q

Complications of haemochromatosis

A
Liver fibrosis
Liver failure
Cirrhosis
Hepatocellular carcinoma
Diabetes is deposition in the pancreas
12
Q

What is Wilson’s disease

A

Disorder of copper metabolism -> Copper build up in the liver

13
Q

Wilson’s disease clinical presentation

A
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
14
Q

Wilsons disease pathophysiology

A

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)

15
Q

Wilsons disease, what gene codes for which protein that allows copper to move into hepatocytes

A

ATP7B codes for P type ATPase

16
Q

What are the purposes of copper once undergone transporting action into hepatocytes

A

Supports production of Ferroxidase Caeruloplasmin.

Excretion of copper into bile.

17
Q

Wilsons disease aetiology

A

Mutation in ATP7B - over 500 identified.

Autosomal recessive

18
Q

Wilsons disease epidemiology

A

Rare -difficult to diagnose.

Affects 1/30,000 to 1/100,000

19
Q

Wilsons disease diagnosis

A

Slit lamp analysis of eyes
Detect Kayser-Fleischer rings (bronze rings of the cornea)
Low serum caeruloplasmin.

20
Q

Wilsons disease treatment

A

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

21
Q

Wilsons disease complications

A

Cirrhosis -> liver failure.

Fatal if untreated

22
Q

What is Alpha-1-antitrypsin deficiency

A

Deficiency of serine protease inhibitor alpha-1-antitrypsin

23
Q

Clinical presentation of Alpha-1-antitrypsin deficiency

A

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

24
Q

Pathophysiology of Alpha-1-antitrypsin deficiency

A

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

25
Q

What is the function of Alpha-1-antitrypsin

A

Inhibits the action of neutrophil-protease enzymes in the lung, produced in presences of inflammation, infection or smoking

26
Q

Aetiology of Alpha-1-antitrypsin deficiency

A

Mutation in the SERPINA1 gene
Autosomal recessive
Relatively low penetrance
Many possible mutations

27
Q

Epidemiology of Alpha-1-antitrypsin deficiency

A

Commonest amongst white people.
1/4000 present
Underdiagnosed since not always exhibits problems

28
Q

Diagnosis of Alpha-1-antitrypsin deficiency

A

A1AT serum levels

29
Q

Treatment of Alpha-1-antitrypsin deficiency

A
Lung = (as COPD) cessate smoking, corticosteroids, bronchodilators, treat infection.
Liver = cessate drinking. In liver failure, possibly transplant
30
Q

Complications of Alpha-1-antitrypsin deficiency

A

Variable prognosis.

Untreated can lead to liver failre