metabolic liver disease Flashcards
define haemochromatosis
Multi-system disorder of dysregulated dietary iron absorption and
increased Iron release from macrophages
aetiology of haemochromatosis
- Autosomal recessive
- High intake of iron and chelating agents e.g. ascorbic acid
- Alcoholics may have iron overload
- Chronic transfusions
Risk factors for Haemochromatossi
- white
- male
- middle age
- fx
Where is the mutation in haemochromatosis
- chromosome 6 of the HFE gene
What is acquired HH due to?
frequent transfusions of red blood cells or excessive intake of iron
What are the 2 missense mutations in hereditary HH
C282Y and H63D
Pathophysiology of HH
HFE gene protein interacts with transferrin receptor 1 > iron taken up by mucosal cells of SI inappropriately
Hepcidin (Protein synthesised in liver) is underexpressed in HH leading to iron overload
In duodenum unregulated absorption of iron resulting in iron overload
presentation of HH
- after the age of 40 for men but after menopause for women
- chronic fatigue
- arthralgias
- bronze discoloration
investigations for HH
- serum ferritin
- transerrin saturation - GS
- genetic testing
- Diagnostic is liver biopsy.
treatment of HH
Venesection
- weekly
Lifestyle:
- Patients should be advised to avoid alcohol and have a low iron diet
Iron chelation:
- Desferrioxamine can be used for patients with a contraindication to phlebotomy, such as severe anaemia
Complications of HH
Liver cirrhosis
Hepatocellular carcinoma
DM
Dilated cardiomyopathy
Pseudogout
DEFINE WILSONS DISEASE
Wilson’s disease is an autosomal-recessive disease of copper accumulation and copper toxicity caused by mutations in the ATP7B gene, which is part of the biliary excretion of copper pathway.
aetiology of wilsons disease
Autosomal recessive
Normal role of atp7b
1- bind cu to apoceruloplasmin to make ceruplasmin
2- package excess cu into veseicles for removal via exocytosis in BILE
pathophysiology of wilsons disease
- Cu+ accumulates in the liver and can deposit elsewhere
- produces free radicals
- free radicals can damage liver and brain
What is Wilsons characterised by?
increased copper absorption from the small intestine and decreased hepatic copper excretion
presentation of wilsons disease if brain affected
- Behavioural and psychiatric issues: such as depression and delusions, often the first presentation. Also, loss of libido and bad memory.
- Parkinsonism: half of patients present with a tremor
- Asterixis
- Chorea
- Dysarthria
- Dystonia
- Dementia
Presentation of wilsons if eyes affected
- descemets membrane
- corneal ring around eye is brown
Wilsons effects
- Hepatosplenomegaly
- Jaundice+ ascites
- Renal tubular acidocis
- Blue nails
- Grey skin
investigation for wilsons disease
LFTs
24-hour urinary copper
slit-lamp examination
serum ceruloplasmin
Definitive diagnosis for wilsons is made through ?
Liver biopsy
Treatment for wilsons
- Copper chelation
- penicillinamine
- trientine hydrochloride
Complications of Wilsons
- Liver failure:patients can present with acute liver failure or decompensation of pre-existing chronic liver disease. This may necessitate transplantation
- Renal stones: secondary to hypercalciuria
- Renal failure: often due to D-penicillamine therapy, rather than the disease itself
what is alpha 1- antitrypsin deficiency
rare autosomal recessive disorder that causes liver and pulmonary disease.
A1AT is a type of serine protease inhibitor. Deficiency is called serinopathy.
Epidemiology of A1AT
- A1AT deficiency is most common in people of European ancestry and is uncommon in people of Asian descent.
- Worldwide, there are > 3 million people affected by AATD.
- Equal sex prevalence.
- FH is RF
what does alpha 1 anti trypsin deficiency lead to
- excess of protease enzymes
- liver cirrhosis
- pulmonary basal emphysema
pathophysiology of A1AT
Alpha-1 antitrypsin (A1AT) is aprotease inhibitormade in the liver which predominantly acts to protect the lungs from neutrophil elastase.
A1AT deficiency is a common inherited condition caused by a deficiency in A1AT, resulting inprotease-mediated damage, particularly in the lungs
Autosomal recessive/ co-dominant
Symptoms of A1AT
- Resp: Dyspnoea, weight loss, productive cough
- Liver: Jaundice, hepatomegaly, ascites
diagnosis for A1AT is made via
- Low serum A1AT
- liver biopsy shows cirrhosis
- genetic testing for the A1AT gene
- high resolution CT thorax
- LFTs
- Chest x-ray
What type of mutation occurs in the liver for a1at
pi z mutation
misfolding of the protein
What does pi z mutation lead to
misfolded protein aggregates in hepatocyte’s endoplasmic reticulum causing those cells to die
presentation of a1at d
- SOB
- inability to make coagulation factors- bruise easily
- cirrhosis sx
tx for A1AT D
- smoking cessation
- avoid alcohol
- COPD treatment
- Hep A and B vaccinations
Complications of A1AT
Resp failure
Cirrhosis
Cholestasis
