Liver I and II Flashcards
what is the main function of the liver
- synthesis and metabolism of carbohydrate, lipid, protein, drugs
- metabolism and excretion of bilirubin and bile acids
what kind of blood supply does the liver have
dual supply
what is the liver vulnerable to
wide variety of insults (metabolic, toxic, microbial, circulatory & neoplastic)
what are thr 4 primary liver diseases
- viral hepatitis
- alcohol liver disease
- nonalcoholic fatty liver disease
- hepatocellular carcinoma
what are the major causes of liver disease in West and elsewhere
- West: alcohol and hepatitis C virus
- Elsewhere: hepatitis B virus, but the incidence is decreasing (vaccination)
what is the importance of bilirubin levels
- used to diagnose and differentiate between different diseases
- abnormal Haemoglobin in RBC O it needs to be destroyed
- destroyed in the SPLEEN; haemoglobin –> haem and globin
- haem –> bilirubin (unconjugated/protein bound) yellow colour. unconjugated bilirubin is toxic to the brain, it is not water soluble O if it crosses BBB it can damage the brain
- if there is a LARGE DEGREE of RBC destruction- haemolysis, this will lead to suddenly HIGH LEVELS of unconjugated bilirubin in the blood stream
- bilirubin is bound by ALBUMIN and transported to the liver
- in the liver the bilirubin is CONJUGATED with glucose residues
- it is now water soluble and is no longer toxic
- O small amount enters blood stream (but it isn’t toxic so this is fine), some goes to gut where it will go through enterohepatic circulation, bile duct cont conjugated bilirubin
- if there is liver cell hepatocyte damage- the liver will release both conjugated and unconjugated into blood
- O conjugated and unconjugated will be released into blood
- we measure both levels for diagnosis
what is jaundice (icterus)
what are the types
- Yellow sclerae and skin; serum bilirubin > 50μmole/L
Types: - Haemolytic jaundice (pre-hepatic)
- Congenital hyperbilirubinaemias (non-haemolytic)
- Cholestatic jaundice
describe haemolytic jaundice (pre hepatic)
- INC RBC BREAKDOWN
Investigations: - haemolysis
- INC serum UNCONJUGATED bilirubin
- normal alkaline phosphatase (ALP) and transferase
- Bile duct obstruction results in increased synthesis of ALP by bile duct epithelial cells but as the bile duct is unaffected by haemolytic anaemia there are no high levels
- transferase is released from hepatocytes if they are damaged, but since there is no liver damage in haemolytic anaemia there is no high transferase
describe Congenital hyperbilirubinaemia
- most common - Gilbert’s syndrome:
- LOW UDP-glucuronyl transferase activity LOW conjugation of bilirubin with glucuronic acid
- O INC in UNCOJUGATED BILIRUBIN
- other tests normal
describe cholestatic jaundice
1) INTRAHEPATIC CHOLESTASIS:
- Abnormal bile excretion
- Bile channel obstruction
2) EXTRAHEPATIC CHOLESTASIS:
- bile flow obstruction that is distal to bile canaliculi (tubes in the liver that collect bile secretions)
Investigation:
- serum liver biochemistry
- jaundice (due to HIGH LEVELS OF CONJUGATED BILIRIRUBIN- as the bilirubin has been conjugated
- jaundice ( if there is HEPATOCYTE DAMAGE AS WELL there will be HIGH UNCONJUGATED BILIRUBIN AS WELL)
- if there is hepatitis, early in hepatitis: HIGH ALT AND AST and maybe high ALP (but less likely as cholestatic jaundice is caused by hepatocyte damge not bile duct damage)
- if there is EXTRAHEPATIC OBSTRUCTION: HIGH ALP (bile duct damage) and high (but not as high) ALT and AST
- ultrasound (dilated bile ducts in extrahepatic cholestasis ) and find the LEVEL of obstruction
- serum hepatitis markers: acute hepatitis A or B or antibodies for Hepatitis C
OTHER TESTS:
- cholestasis –> LOW VITAMIN K (it cannot be absorbed) –> INCREASED PROTHROMBIN TIME (inc time taken to clot due to less vitamin K which is req for prothrombin and other clotting factor synthesis)
- DEC liver synthetic function –> INC prothrombin time + DEC albumin production (albumin is synthesised in liver)
- autoimmune liver disease –> test serum antibodies
what is high ALP a marker for
bile duct damage
what is the pathology of hepatitis
what are the types
- liver cell necrosis and inflammatory infiltration
- can be acute or chronic
how does hepatitis present
- enlarged and tender liver (may or may not be obvious)
- jaundice (may or may not be obvious)
what investigations can be done for hepatitis
- SERUM TRANSFERASE IS INCREASED
either ALT (much more specific) or AST
what are the causes of acute hepatitis
- Viruses: hepatitis viruses (most common)
- Non-viral infection: toxoplasma gondii , etc
- Alcohol
Drugs: anti-TB (isoniazid), etc - Others: pregnancy, etc
what are the clinical features of acute hepatitis
- Usually (viral) self-limiting, return to normal structure & function
- Occasionally progression to massive liver necrosis, even death
what investigations are used for hepatitis
- HIGH SERUM ALT (best indicator of acute hepatic injury) (indicates specificity to liver)
- prothrombin time and bilirubin conjugated and unconjugated (reflects disease severity)
what is chronic hepatitis
A sustained inflammatory disease Causes: any cause -Viral -Chemical -Autoimmune
describe hepatitis A
- acute viral hepatitis (no chronic form)
- caused by virus HAV
- spread: faecal-oral
- mechanism of liver damage: cytopathic (viruses damage cells) and immunity mediated (by T cells)
