Flashcards in Metabolic causes of Liver Disease Deck (33):
What is meant by 'metabolic disease'?
A disease involving enzymes that play a key role in certain chemical processes in the body
What are the most important metabolic liver diseases?
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
Which organs are most often targeted in Haemochromatosis?
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
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
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
Who gets Haemochromatosis?
Europeans of Celtic descent
People are usually diagnosed between age 30-50
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
Investigations of Haemochromatosis?
- Serum transferrin raised
- Serum ferritin raised
- Liver function tests low
- Look for evidence of cirrhosis
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
What is ferritin?
A protein involved in iron storage within cells and tissues
The higher ferritin levels are the more iron in bloodstream
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
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
Which organs are most often targeted in Wilson's disease?
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.
What is caeruloplasmin?
The protein that carries copper in the blood
How is excess copper usually excreted from the body?
Either into the bile and then into the faeces
Or into the urine
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
What are the clinical features of Wilson's disease?
When do these symptoms present?
In childhoods: liver failure
In young adults: CNS damage
- personality change
- dysarthria: difficulty speaking
- Kayser fleishcer rings - copper deposit (gold) ring around iris
- Blue nails
- Grey skin
What is haemolysis?
The rupture or destruction of red blood cells
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
What would you see on a liver biopsy of someone with Wilson's disease?
Hepatitis: damage, inflammation
Cirrhosis: scarring, fibrosis
Management of Wilson's disease?
Low copper diet
Penicilllamine: a copper chelation drug
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
What are high-copper foods?
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
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
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
What are the clinical features of alpha1-antitrypsin deficiency?
Early onset, non-smoking emphysema
Investigations for alpha1-antitrypsin deficiency?
Serum alpha1-antitrypsin levels will be low
Look for damage + scarring, and abnormal protein deposits
Management of alpha1-antitrypsin deficiency?
Treat lung and liver problems
Rarely: IV infusion of alpha1-antitrypsin derived from donated human plasma
What do you need to discuss with the patient and their family after diagnosing someone with alpha1-antitrypsin deficiency?
Familial disease so other family members could be affected