Metabolic Causes of Liver Disease

Question 1

Hereditary haemochromatosis

Answer 1

inherited autosomal recessive disorder of Fe metabolism

Increase Fe absorption –> iron loading in joints, liver, heart and pancreas

Question 2

What gene is responsible for HH?

Answer 2

HFE

human haemochromatosis gene

Question 3

epidemiology of HH

Answer 3

middle aged men more frequently + severely effected

menstrual blood loss is protective

Question 4

Early clinical presentation of HH

Answer 4

Early: none. arthralgia, decreased erections

Question 5

Late clinical presentation of HH

Answer 5

slate-grey skin pigmentation
signs of CLD
hepatomegaly
cirrhosis
endocrinopathies

Question 6

Bloods for HH

Answer 6

LFT often normal even with cirrhosis

elevated serum iron
reduced total iron-binding capacity

greatly elevated serum ferritin

Question 7

other Ix for HH - apart from bloods

Answer 7

genotyping for mutant HFE
phlebotomy
liver biopsies

Question 8

Tx HH

Answer 8

venesection

screening 1st degree relatives for serum ferritin and genotype

Question 9

Cause of Wilson’s disease (hepatolenticular degeneration)

Answer 9

Rare inherited autosomal recessive disorder

mutations in a gene on c13 that codes for a copper transporting ATPase

treatable

Question 10

what is the major copper-carrying protein in the blood?

Answer 10

ceruloplasmin

Question 11

what happens in wilsons?

2 things intact, 2 things impaired

Answer 11

absorption + transport of copper are intact but incorporation into caeruloplasmin in hepatocytes and excretion into bile are impaired

so it accumulates in the liver, - and, later on, other organs

Question 12

what does copper accumulation in the liver lead to?

Answer 12

fulminant hepatic failure and cirrhosis

Question 13

what does copper accumulation in the basal ganglia lead to?

Answer 13

parkinsonism and eventual dementia

Question 14

what are Kayser-Fleischer rings?

Answer 14

greenish-brown rings caused by copper accumulation in the cornea

Question 15

Diagnosis Wilson’s disease

Answer 15

low total serum copper and caruloplasmin

increased 24-hour urinary copper excretion

increased copper in a liver biopsy specimen

Question 16

Tx Wilson’s disease

Answer 16

Penicillamine or trientene - to chelate copper
- penicillamine SEs: nausea, rash

or zinc - reduces copper absorption

liver transplant

screen 1st degree relatives

Question 17

A1AT deficiency stands for what and is caused by what

Answer 17

alpha-1 antitrypsin deficiency

mutations in alpha-1 antitrypsin gene on chromosome 14

Question 18

What happens in A1AT deficiency

Answer 18

reduced hepatic production of A1AT, which normally inhibits the proteolytic enzyme, neutrophil elastase

A1AT is trapped in the liver, causing liver damage

neutrophil elastase is uninhibited, causing lung damage –> emphysema

Question 19

function of A1AT in the lungs

Answer 19

it coats the lungs, protecting them from neutrophil elastase

Question 20

neutrophil elastase

Answer 20

produced by WBCs to break down harmful bacteria, potentially damaging the lungs if they are exposed to it

Question 21

Serpinopathy

Answer 21

deficiency in one of a family of serine protease inhibitors made in the liver that control the inflammatory cascade

(A1AT is a glycoprotein and also one of these)

Question 22

Symptoms A1AT

Answer 22

Usually homozygote for Z (PiZZ if symptomatic

dyspnea from emphysema
cirrhosis
cholestatic jaundice

Question 23

Diagnosis A1AT

Answer 23

low serum levels of A1AT
genotype assessment

A1-AT containing globules seen in hepatocytes

Question 24

Tx A1AT

Answer 24

for chronic lung and liver disease

stop smoking!