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Flashcards in Metabolic causes of Liver Disease Deck (33):
1

What is meant by 'metabolic disease'?

A disease involving enzymes that play a key role in certain chemical processes in the body

2

What are the most important metabolic liver diseases?

Haemochromatosis
Wilson's disease
Alpha1-anti-trypsin deficiency

3

What is Haemochromatosis?

An autosomal recessive disorder

Excessive absorption of iron from the diet

Leads to excess iron deposition in organs.

This leads to fibrosis of that organ and functional organ failure

4

Which organs are most often targeted in Haemochromatosis?

Liver
Adrenal glands
Heart
Skin
Gonads
Joints

5

What is the pathogenesis of Haemochromatosis?

Unknown exactly what causes it, one cause is:

A genetic mutation in the HFE (human haemochromatosis protein) gene

Puts intestinal absorption of iron into overdrive

If HFE is mutated it interprets that the body is deficient so it absorbs loads of iron from the food

But there are many different genes that regulate iron absorption that could play a part

6

What are the clinical features of Haemochromatosis?

Often an incidental finding from routine blood tests

Or diagnosed from screening due to a close relative being diagnosed

Fatigue
Malaise
Joint + bone pain

Hyperpigmentation of the skin

Liver cirrhosis, hepatomegaly due to liver damage

Diabetes mellitus due to pancreas damage

Heart problems: cardiomegaly, heart failure

7

Who gets Haemochromatosis?

Europeans of Celtic descent

People are usually diagnosed between age 30-50

8

Why is presentation of symptoms in haemochromatosis in women often delayed?

The symptoms are caused by high iron levels

Women menstruate so lose iron then, it takes longer for the levels to get as high

9

Investigations of Haemochromatosis?

Bloods:
- Serum transferrin raised
- Serum ferritin raised
- Liver function tests low

Liver biopsy:
- Look for evidence of cirrhosis

10

What is transferrin?

A protein that transfers iron around the body in the blood stream

The higher transferrin levels are the more iron in bloodstream

11

What is ferritin?

A protein involved in iron storage within cells and tissues

The higher ferritin levels are the more iron in bloodstream

12

Management of Haemochromatosis?

Phlebotomy: removal of blood from the body on a regular basis helps to keep iron levels at bay

Chelation therapy: desferrioxamine, medication that works by locking on to the iron molecules, before releasing them through urine or stools

Low iron diet

13

What is Wilson's disease?

An autosomal recessive disorder

Results in accumulation of copper in the tissues and organs

This causes them to become damaged and scarred

14

Which organs are most often targeted in Wilson's disease?

Liver
Kidneys
Eyes
Brain

15

What is the pathophysiology of Wilson's disease?

Genetic mutation results in:

Copper being unable to bind to caeruloplasmin or be excreted into the bile

Copper therefore builds up in the hepatocytes

It produces free radicals which damage the cells

In time, copper escapes the cells and goes via the bloodstream to the brain, eyes etc.

16

What is caeruloplasmin?

The protein that carries copper in the blood

17

How is excess copper usually excreted from the body?

Either into the bile and then into the faeces

Or into the urine

18

What normally happens to copper when it is eaten in food?

It is absorbed from the small intestine into enterocytes

Then goes into the liver via portal veins

In hepatocytes it is either bound to caeruloplasmin or exocytosed into the bile (egested)

Once bound to caeruloplasmin it travels round the body in the blood

19

What are the clinical features of Wilson's disease?

When do these symptoms present?

In childhoods: liver failure
- jaundice
- cirrhosis

In young adults: CNS damage
- ataxia
- personality change
- dysarthria: difficulty speaking
- dementia

Any age:
- Kayser fleishcer rings - copper deposit (gold) ring around iris
- Haemolysis
- Blue nails
- Grey skin

20

What is haemolysis?

The rupture or destruction of red blood cells

21

Investigations of Wilson's disease?

Urine: 24 hours copper excretion will be high

Liver function test: will show some degree of failure

Serum copper + caeruloplasmin levels low

Liver biopsy: shows copper deposits + damage/scarring

MRI: show basal ganglia degeneration

22

What would you see on a liver biopsy of someone with Wilson's disease?

Copper deposits
Hepatitis: damage, inflammation
Cirrhosis: scarring, fibrosis

23

Management of Wilson's disease?

Low copper diet

Penicilllamine: a copper chelation drug

Liver transplant

24

What do you need to discuss with a patient and their family after diagnosing someone with Wilson's disease?

Screening of the family
It is a genetic disorder so some of them could be affected

25

What are high-copper foods?

Liver
Chocolate
Nuts
Mushrooms
Legumes
Shellfish

26

What is alpha1-antitrypsin deficiency?

A mutation in the alpha1-antitrypsin gene means less production of alpha1-antitrypsin in the lungs

And excessive deposition of alpha1-antitrypsin in the liver

This causes damage to the liver and lungs

27

What is the effect of alpha1-antitrypsin deficiency on the liver? How does it do it?

Excess deposition of abnormal alpha1-antitrypsin protein in the liver cells

Causing damage - cirrhosis and dysfunction

28

What is the effect of alpha1-antitrypsin deficiency on the lung? How does it do it?

Normally alpha1-antitrypsin inhibits the activity of neutrophil elastase - which digests elastin in the alveoli

Without alpha1-antitrypsin, the N. elastase is allowed to digest the elastin causing emphysema

29

What are the clinical features of alpha1-antitrypsin deficiency?

SOB
Wheezing
Early onset, non-smoking emphysema

Cirrhosis
Liver failure
Jaundice

30

Investigations for alpha1-antitrypsin deficiency?

Blood:
Serum alpha1-antitrypsin levels will be low

Liver biopsy:
Look for damage + scarring, and abnormal protein deposits

Symptomatic

31

Management of alpha1-antitrypsin deficiency?

Treat lung and liver problems

Quit smoking

Rarely: IV infusion of alpha1-antitrypsin derived from donated human plasma

Transplant

32

What do you need to discuss with the patient and their family after diagnosing someone with alpha1-antitrypsin deficiency?

Screening

Familial disease so other family members could be affected

33

What most often causes death in alpha1-antitrypsin deficiency ?

Emphysema