Liver disease

Liver disease

Bilirubin
1. Metabolism
  1. Occurs in hepatocytes
  2. UDP glucuronyl transferase adds 2 glucuronic acid to bilirubin to form bilirubin diglucuronide
  3. Haem is broken down into bilirubin
    1. Removed from blood by liver
      1. Conjugated into glucuronide to faciliate excretion
        Further metabolism by gut bacteria into urobilinogen
        Oxidised into urobilin
        Proportion of products are reabsorbed and excreted in urine
2. Causes of hyperbilirubinaemia
  1. Pre-hepatic
    1. Increased bilirubin production
      1. Increased haem breakdown
      2. Impaired removal by hepatocytes
      3. Obstruction of biliary system
        Increased levels of bilirubin
        Biliary calculi (gall stones) cause build-up and reabsorption of conjugated bilirubin
        Intrahepatic
        Hepatocellular damage
        Intrahepatic carcinoma
        Primary biliary cirrhosis
        Drug-induced
        Extrahepatic
        Gall stones
        Extrahepatic carcinoma
  2. Hepatic
    1. Decreased uptake into liver cells
    2. Impaired conjugation
  3. Post-hepatic
    1. Interference with secretion of conjuagtion bilirubin
Liver functions
1. Protein, carbohydrate and lipid homeostatis
2. Reticuloendothelial system
3. Metabolism, detoxification and excretion of exogenous and endogenous compunds
4. Excretion of water-soluble endproducts
5. Synthesis of plasma proteins
Causes of acute liver disease
1. Poisoning e.g. paracetamol
  1. Metabolised by sulphation
    1. At high conc. sulphation is depleted and glucuronidation occurs
      1. If glucuronidation is depleted paracetamol is oxidised by P450 and conjugated to glutathione
  2. Redox imbalance and hepatocyte damage occurs
  3. Oxidised intermediate causes cell damage
2. Infection e.g. hepatitis
  1. Hep A = usually mild
  2. Hep B = 10% go on to develop chronic liver disease or cancer
  3. Hep C = 80% go on to develop chronic liver disease or cancer
3. Inadequate perfusion
  1. Failure of blood supply to liver
    1. Heart failure
    2. Low blood volume
  2. Can lead to Ischaemia
  3. Can lead to liver damage
Cirrhosis
1. Causes
  1. Chronic alcohol ingestion
  2. Viral hepatitis
  3. Autoimmune disease
2. Symptoms
  1. Fat intolerance
  2. Itchy skin
    1. Accumulation of bile acids
  3. Reduced ability to metabolise drugs
  4. Susceptibility to infections
3. Terminal features
  1. Jaundice
  2. Encephalopathy
  3. Acites due to low albumin
  4. Bleeding tendencies
  5. Terminal liver failure
Associated conditions
1. Crigler-Najjar syndrome
  1. Impaired conjugation
    1. Bilirubin is retained by body
  2. Decreased concentration of UDP-glucuronyl transferase
  3. Severe in neonates
    1. Early death
2. Dubin-Johnson syndrome
  1. Inability of hepatocytes to secrete conjugated bilirubin
  2. Conjuagted bilirubin returns to blood
  3. Increased bilirubin in urine
3. Gilbert's Disease
  1. Inability of hepatocytes to take up bilirubin from blood
    1. Accumulation of unconjugated bilirubin
  2. Autosomal dominant
  3. Usually asymptomatic
  4. Decreased expression of UDP-glucuronyl transferase
4. Jaundice
  1. Yellow discolouration os skin / sclera of eye
  2. Increased bilirubin in plasma (>40umol/L)
  3. Stool colour
    1. Pale = obstructive jaundice
    2. Dark = excessive breakdown of haem
  4. Causes of hepatic jaundice
    1. Decreased hepatic blood flow
    2. May be due to fasting
    3. Decreased number of hepatocytes
    4. Defects in uptake or conjugation
  5. Causes of haemolytic jaundice
    1. Haemolytic anaemia
    2. Rhabdomyoloysis
    3. Haemolytic disease of newborn
    4. Ineffective erythropoeisis
Causes of chronic liver disease
1. Chronic toxin exposure
2. Chronic hepatitis
3. Cholestatic disease
Liver function tests
1. Cholestatic damage
  1. High conjuagted bilirubin
  2. High ALP
  3. High GG
2. Hepatocellular damage
  1. High unconjuagted bilirubin
  2. High AST
  3. High ALT
3. Tests carried out
  1. Aspartate transaminase
  2. Alanine transaminase
  3. Alkaline phosphotase
  4. Albumin
  5. Total protein
  6. Bilirubin
  7. Gamma-glutamyl transferase
4. Haemolytic damage
  1. High unconjuagted bilirubin
  2. Low haptoglobins
Disease processes associated with liver damage
1. Portosystemic shunt
2. Hepatic necrosis
3. Focal lesions
4. Hepatic lipidosis
5. End stage liver disease
6. Steroid hepatopathy
7. Biliary abnormalities
8. Chronic progressive liver disease
Effects of acute hepatic failure
1. Electrolyte imbalance
2. Hypoglycaemia
3. Metabolic acid-base disturbances
4. Increased blood anaemia
5. Clotting disturbances
6. Oedema / ascities

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