Biochemical Investigation of Liver Function Flashcards
What is the functional unit of the liver?
A liver lobule
How are liver lobules arranged?
Hexagonal shape composed of: hepatocytes (parenchymal cells) arranged in plates, in contact with bloodstream on one side and bile canaliculi (little canals) on the other
What are between the plates of liver lobules?
Vascular spaces (sinusoids) containing Kupffer cells (phagocytic macrophages)
What are the functions of the liver?
- Metabolic - carbohydrates, hormones, lipids, drugs and proteins
- Storage - glycogen, vitamins, iron
- Protective - detoxification and elimination of toxic compounds, Kupffer cells ingest bacteria and other foreign material from blood
- Bile production - formed in biliary canaliculi, emulsifies fats and provides route for waste removal
What are the classifications of liver disease?
- Infection - viral (HepA-E, CMV), bacterial, parasitic
- Toxic / drug induced
- Autoimmune
- Biliary tract obstruction - tumours, gallstones
- Vascular
- Metabolic - haemochromatosis, Wilson’s, hereditory hyperbilliruninaemias
- Neoplastic
What can the causes be of acute hepatitis?
- Poisoning (paracetamol)
- Infection (Hep A-C)
- Inadequate perfusion
What cacn the outcome be of acute hepatitis?
- Resolution - majority of cases
- Progression to acute hepatic failure
- Progression to chronic hepatic damage
What are the common causes of chronic liver disease?
- Alcoholic fatty liver
- Chronic active hepatitis
- Primary biliary cirrhosis
What are some unusual causes of chronic liver disease?
- alph-1 AT deficiency
- Haemochromatosis
- Wilson’s disease
What is cholestasis?
Failure to produce or excrete bile - result is accumulation of (conjugated) billirubin in the blood leading to jaundice
What can cause jaundice other than hepatic causes?
Excessive haemolysis - bilirubin is unconjugated and does not appear in the urine
What does liver failure lead to?
- Inadequate synthesis of albumin leading to oedema and ascites
- Inadequate synthesis of clotting factors resulting in bruising
- Inability to eliminate bilirubin causing jaundice
- Inability to eliminate nitrogenous waste e.g amonia, giving rise to hepatic encephalopathy, a poorly defined neuro-psychiatric disorder
What are the 4 current liver function tests?
- Albumin: for synthetic function
- ALT: (&AST) aminotransferases for hepatocellular damage
- ALP: (& gama-GT) for biliary epithelial damage and obstruction
- Billirubin: for cholestasis (bile flow blockage)
What are advantages of LFTs?
- Cheap, widely available, interpretable
- \direct subsequent investigation (e.g imaging)
What are the disadvantages of LFTs?
- Do not assess liver “function”
- Lack of complete organ specificity
- Lack of disease specificity
- May be “over-sensitive”
- > 40 years old, many newly discovered diseases for which they have no diagnostic value
What can albumin be used as an assessment of?
Liver synthetic function
What can low albumin also be found in?
- Post-surgical/ITU patients due to redistribution
- Significant malnutrition
- Nephrotic syndrome
What are ALT and AST markers of?
- Sensitive, non specific markers of acute damage to hepatocytes
- Cytoplasmic enzymes also found in cardiac muscle and erythrocytes
What is ALP a marker of?
- Increased liver disease due to increased synthesis in response to cholestasis
- Biliary epithelial damage and obstruction
- Also present in bone, gut and placenta
What can y-GT be a marker of?
- Raised in cholestasis, also affected by ingestion of alcohol and drugs such as phenytoin
- Also present in bone, biliary tract, pancreas and kidney
What is bilirubin a breakdown product of?
Haemoglobin
Explain how bilirubin is excreted
- Breakdown product of haemoglobin
- Unconjugated bilirubin taken up by liver and conjugated
- Conjugated bilirubin excreted in bile
- Attacked by bacteria in colon and excreted in faeces
- Small amounts reabsorbed and excreted in urine as urobilinogen
What is cholestasis?
- The consequences of failure to produce and excrete bile
What is intrahepatic cholestasis?
Failure by hepatocytes
What is extrahepatic obstruction?
Obstruction to bile flow
What does cholestasis result in?
Accumulation of bilirubin in circulation and jaundice
Why is mild jaundice extremely dangerous in children?
- Weak blood brain barrier
- Billirubin can penetrate into brain more easily and therefore cause death
What is the likely cause of hyperbilirubin, normal ALT and ALP but increased conjugated billirubin?
Dubin Johnson Roctor syndrome
What is the likely cause of hyperbilirubin, normal ALT and ALP and normal levels of conjugated billirubin?
Haemolysis Gilberts Crigler-Najjar syndrome
What can increased bilirubin in an asysmptomatic patient be due to?
Haemolysis, Gilberts syndrome
What can increased ALP be due to in an asymptomatic patient?
Physiological e.g pregancy, childhood
What cna increased ALT be due to in an asymptomatic patient?
Skeletal muscle disorders, MI
What can increased y-GT be due to in an asymptomatic patient?
- Alcohol, drugs
What are the other lab tests should be done after LFTs?
- Hepatitis serology
- alp-1 antitrypsin deficiency
- alph-fetoprotein - tumour marker (hepatocellular carcinoma)
- Caeruloplasmin / copper studies - Wilson’s disease
- Iron studies - Haemochromatosis (genetic)
- Autoantibodies - chronic active hepatitis, PBC
- Radiology - obstruction, hepatomegaly
- Liver biopsy
When can LFTs be normally or mildly increased even when the patient is quite unwell?
Chronic disease e.g. cirrhosis
Where does liver disease rank in terms of causes of death in men?
- 3rd < 65 yrs
- Likely to rise further due to alcohol consumption and obesity
What is iLFT?
- Intelligent Liver Function Test
- Patients with abnormal LFTs in whom the cause is unclear (patients with jaundice excluded)
- A combination of biochemistry, haematology and serology in conjunction with liver ultrasound
What are the elemants included in the iLFT?
- Patient specific data
- LFT and FBC performed
- ALT, ALP and yGT all normal: no further tests
- Any of ALT, ALP and yGT abnormal:
- Aetiology screen - Hepatitis serology, liver immunology, ferritin, alph-1 antitrypsin, caeruloplasmin, AST, yGT, platelet count and
- Fibrosis staging - FIB4 score
- NAFLD fibrosis score
What percentage of the population have Gilbert’s syndrome?
7%
What is Gilbert’s disease?
- Fluctuating hyperbilirubinaemia
- Characterised by intermittent mild jaundice evident during periods of fasting and illness
- Due to conjugating defect in liver
