Metabolic liver conditions Flashcards
What is Wilsons disease
Inherited disorder characterised by toxic accumuation o fcopper in the liver, brain and other organs
Autosomal inheritience pattern
characterised by decreased hepatic excretion of copper into bile
What are the indications for testing for Wilsons disease
- Liver disease in children and young adults
- Neurologic disease in adolescents and young adults
- Hemolysis with liver disease
- Presence of Fanconi’s syndrome
- Presence of hypouricemia
- Kayser-Fleischer rings discovered
- Siblings of affected patient
What are the characteristic laboratory findings of wilsons disease
Serum copper, μg/dL:
- Normal values: 80-140
- <80
Urine copper, μg/24 h:
- Normal values: <40
- >100
Serum ceruloplasmin, mg/dL:
- Normal values: 20-40
- <20
Hepatic copper, μg/g dry wt
- Normal values: 15-50
- 250-3000
Serum-free copper μg/dl)
- Normal values: 8-12
- >25
How is Wilsons disease treated
- D-Penicillamine
- Trientine
- Zinc supplementation
- Ammonium tetrathiomolybdate
What is haemochromatosis
- An inherited disorder of iron metabolism in which increased intestinal iron absorption leads to its deposition in multiple organs.
- Organs most commonly involved are joints, skin, heart, liver, pancreas and pituitary
Explain the molecular reguation of iron haemostasis
- This is maintained by Hepcidin, a peptide released by hepatocytes into the circulation under stimulatory control of a common pathway involving HFE(high iron) gene, Hemojuvelin and transferrin receptor 2.
- Hepcidin normally inhibits iron export from enterocytes and macrophages via its interaction with Ferroportin (Fpn).
- Mutations in ‘haemochromatosis’ genes reduce Hepcidin expression and allow excess iron to enter the plasma compartment and bind to transferrin (Tf) with consequent tissue iron loading.
List the different iron overload conditions
**Hereditary haemochromatosis **
- HFE-related (HFE 1)
* C282Y/C282Y
* C282Y/H63D
* Other HFE mutations
- Non-HFE-related
* Juvenile hemochromatosis (HFE 2)
* Transferrin receptor-2 mutations (HFE 3)
* Ferroportin-1 mutations (HFE 4)
* African iron overload
Secondary iron overload
* Iron-loading anemias
* Parenteral iron overload
* Chronic liver disease
* Dysmetabolic iron overload syndrome
Miscellaneous
* Neonatal iron overload
* Aceruloplasminemia
* Congenital atransferrinemia
What is the treatment for haemochromatosis
- 1-U Phlebotomy = 250 mg iron
- Weekly phlebotomy until:
- Hematocrit <0.5
- Ferritin < 50 ng/mL
- Transferrin saturation < 50%
- Maintenance usually consists of a 1-U phlebotomy every 2 to 4 months.
What is alpha1-antitrypsin deficiency
- Alpha1-antitrypsine is one of a family of protease inhibitors controlling inflammatory cascades.
- It is synthesized in the liver
- Is the commonest genetic cause of liver disease in children
- In adult it is associated with emphysema, chronic liver disease and hepatocellular carcinoma.
What is metabolic syndrome
Any patients meeting three of the following five criteria:
*Glucose >= 5.6mmol/L or drug treatment for elevated blood glucose
*HDL cholesterol <1.0mmol/L in men and <1.3mmol/L in women or drug treatment for low HDL-C
- Triglyceride >= 1.7 mmol/L or drug treatment for elevated triglycerides
- Obesity Waist 102 cm (men) or 88 cm (women)
- Hypertension 130/85 mmHg or drug treatment for hypertension
NB: -metabolic syndrome is related to obesity and insulin resistance and can result in fatty liver, steatohepatitis and cirrhosis
What is required for the diagnosis NALFD
- Liver biopsy showing steatosis, hepatocyte ballooning degeneration, mild diffuse lobular mixed acute and chronic inflammation, and perisinusoidal collagen deposition
- Alcohol consumption of less than 20g (equivalent units is 2.5units) of ethanol per week
- Absence of serologic evidence of hepatitis B or C or other aetiology e.g. autoimmune serology etc.
