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Flashcards in Metabolic Causes of Liver Disease Deck (24):
1

Hereditary haemochromatosis

inherited autosomal recessive disorder of Fe metabolism

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

2

What gene is responsible for HH?

HFE

(human haemochromatosis gene)

3

epidemiology of HH

middle aged men more frequently + severely effected

menstrual blood loss is protective

4

Early clinical presentation of HH

Early: none. arthralgia, decreased erections

5

Late clinical presentation of HH

slate-grey skin pigmentation
signs of CLD
hepatomegaly
cirrhosis
endocrinopathies

6

Bloods for HH

LFT often normal even with cirrhosis

elevated serum iron
reduced total iron-binding capacity

greatly elevated serum ferritin

7

other Ix for HH - apart from bloods

genotyping for mutant HFE
phlebotomy
liver biopsies

8

Tx HH

venesection

screening 1st degree relatives for serum ferritin and genotype

9

Cause of Wilson's disease (hepatolenticular degeneration)

Rare inherited autosomal recessive disorder

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

treatable

10

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

ceruloplasmin

11

what happens in wilsons?

(2 things intact, 2 things impaired)

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

12

what does copper accumulation in the liver lead to?

fulminant hepatic failure and cirrhosis

13

what does copper accumulation in the basal ganglia lead to?

parkinsonism and eventual dementia

14

what are Kayser-Fleischer rings?

greenish-brown rings caused by copper accumulation in the cornea

15

Diagnosis Wilson's disease

low total serum copper and caruloplasmin

increased 24-hour urinary copper excretion

increased copper in a liver biopsy specimen

16

Tx Wilson's disease

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

or zinc - reduces copper absorption

liver transplant

screen 1st degree relatives

17

A1AT deficiency stands for what and is caused by what

alpha-1 antitrypsin deficiency

mutations in alpha-1 antitrypsin gene on chromosome 14

18

What happens in A1AT deficiency

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

19

function of A1AT in the lungs

it coats the lungs, protecting them from neutrophil elastase

20

neutrophil elastase

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

21

Serpinopathy

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)

22

Symptoms A1AT

Usually homozygote for Z (PiZZ if symptomatic


dyspnea from emphysema
cirrhosis
cholestatic jaundice

23

Diagnosis A1AT

low serum levels of A1AT
genotype assessment

A1-AT containing globules seen in hepatocytes

24

Tx A1AT

for chronic lung and liver disease

stop smoking!