Liver Flashcards
What are some of the livers functions and what is looked at in liver function tests
- Waste elimination
- Storage- glycogen
- Synthesis- protein
- Metabolism- detoxification, drug metabolism, protein breakdown to NH3
LFTs
Bilirubin, AST, ALT, ALP, GGT and albumin
How is bilirubin produced in the body
- Produced from haemoglobin and Haem products in RBC breakdown- Haem breaks down into biliverdin first and is reduced to bilirubin
- Bilirubin binds to albumin to be transported to the liver- it is unconjugated at this point
- Bilirubin is bound to albumin at the liver and is transported into hepatocytes via ligandin
- In the liver endoplasmic reticulum the bilirubin is conjugated UDP glycuronosyltransferase to form conjugated bilirubin (bilirubin diglycuronide)
How is bilirubin excreted from the body
- Excreted as urobilinogen and stercobilin
- Conjugated bilirubin goes into bile via the gall bladder and bile duct
- Conjugated bilirubin and bile pass into the small intestine and are degraded to urobilinogen by intestinal bacterial or to stercobilin
- Not all bilirubin and uronilinogen is excreted, some is reabsorbed via the portal vein and passes back into the liver into systemic circulation- enterohepatic circulation
- Some urobilinogen will go into urine via kidneys to make pee yellow
How do we measure plasma bilirubin
- Conjugated bilirubin can be directly measured
- Unconjugated needs to be separated from albumin first
-When bilirubin is over 50 umol/L it is detectable as jaundice
What are the causes of unconjugated hyperbilirubinaemia and what results would be present on investigation
Bilirubin has not made it to the liver to be conjugated yet- so prehepatic cause
-Increased level of haemoglobin break down
Causes: Physiological neonatal jaundice (babies are born with increased RCC and increased erythrocyte load- neonatal liver has less ligandin)
-Haemolysis
-Gilbert syndrome- autosomal dominant, bilirubin>100 micromoles/L, decreased glucuronosyltransferase
-Crigler-Najaar syndrome - autosomal recessive, severe glycuronosyl transferase deficiency
Investigation results
- Mild AST and LDH
- Decreased haptoglobin (In haemolysis)
- Increased reticulocyte count
What are the causes of conjugated hyperbilirubinaemia
Causes:
Hepatic- hepatitis (drug, virus, autoimmune) -Cirrhosis -Primary biliary cirrhosis
-Infiltrations: Lymphoma, amyloid, haemochromatosis
Post-hepatic: Anything obstructing bile flow -Gallstones in bile -Biliary structure -Sclerosing cholangitis -Cancer, head of pancreas/ biliary tree
Conjugated bilirubin is water soluble so excreted in urine making it dark leaked into systemic circulation- can’t go through intestine for excretion
If there is obstruction to bile flow stools will be pale- no stercobilin as bile can’t get into intestine
- Discuss what liver enzymes give a hepatic picture
- What other investigations would you do due to this
- AST and ALT
- AST- increases in muscle damage and cell breakdown (haemolytic)
- ALT= more liver specific
If hepatic dysfunction look for specific cause
- Glucose/ HbA1c for T2DM
- Lipids- triglycerides
- Viral screen- Hep ABCDE CMV EBV
- Autoantibodies- anti smooth antibodies (autoimmune hep) and anti mitochondrial antibodies- primary biliary cirrhosis
- Copper- Wilsons
- US Abdominal
- Lipids- triglycerides
- Iron studies- haemochromatosis
Discuss what liver enzymes indicate cholestasis
- ALP and GGT
- ALP- can be in bone, placenta and intestine (fractures pregnancy and growth spurts)
- GGT can be induced by some drugs and alcohol
Discuss the biological features of non alcoholic fatty liver disease
- Elevated GGT
- Associated with T2DM and high triglycerides and obesity
- ALT more raised than AST
- Decreased alcohol intake and give metformin
What do these investigation results indicate?
- Increase in all liver enzymes
- Increased GGT
- Increased ALP
- Increased AST and ALT
- Increased in all liver enzymes - acutely unwell, sepsis, congestive heart failure (hepatic vein congestion)
- Increased GGT- alcohol, drugs
- Increased ALP- bone source - Vit D deficiency, fracture, Paget’s
- Increase AST and ALT- early hep, NAFLD, drugs and toxins
