Liver function
Location:
o URQ
o Dome of liver lies against inferior diaphragm surface
o Gall bladder on inferior surface
Structure:
o 60 % of cells are hepatocytes
o 30 % are Kupffer cells
o 10 % vascular and supporting tissue cells
Function:
o Detoxification & drug metabolism:
Synthesis of waste products
Conjugation of hormones and bilirubin to water-soluble forms
Conversion of drugs to metabolites for excretion in urine/stool
Bile:
o Secreted by liver
o Bile salts made of cholic acid and chenodeoxycholic stored in gall bladder
o Bile composed of water, ions, bile acids, organic molecules (cholesterol, phospholipids, bilirubin)
o Body produces 3L of bile/ day, excretes 1L of what is produced
o Gallstones are mostly cholesterol
Contain waste products from RBC breakdown and other metabolic processing
Bilirubin metabolism:
o Hydrophobic & cytotoxic
o Insoluble in aqueous solutions at pH <8.0
o Soluble in organic solvents and dissolves in lipids diffuses across membranes
o Production:
80% heme from Hb
20 % myoglobin
Bilirubin fractions in blood:
Unconjugated: complexed with albumin
Conjugated: bilirubin monoglucuronides
, Conjugated: bilirubin diglucuronides
Conjugated bilirubin bound to albumin
α- bilirubin - unconjugated
β – bilirubin - monoconjugated
γ – bilirubin - diconjugated
δ – bilirubin – bound to albumin
Most common diseases affecting liver:
Hepatitis: damage to liver cells
Cirrhosis
o Increased fibrous tissue formation, leads to shrinkage of
liver
o Decreased hepatocellular function and obstruction of bile flow (cholestasis)
Tumors
Jaundice- icterus:
Due to hyperbilirubinemia
o Can be acquired or inherited
CLINICAL JAUNDICE bilirubin > 50mmol/L (3mg/dL)
Activity of hepatic conjugating enzymes is low at birth but
increases rapidly after
o Transient physiological jaundice of new born reflects this
Physiological jaundice:
o Immaturity in bilirubin metabolism at multiple steps results in hyperbilirubinemia in first few days of
life:
Increased bilirubin load on hepatic cell
Defective uptake from plasma into liver cell
Defective conjugation
Decreased excretion
Increased entero-hepatic circulation
o Characteristics:
Appears 24-72hrs of age
Max intensity 4-5th day in term, 7th day preterm neonates
Does not exceed 15mg/dL
Undetectable after 14 days
o Pathological jaundice
Presence of any of the following:
Rise in serum bilirubin by more than 5mg/dL/day
Serum bilirubin more than 15mg/dL
Clinical jaundice persisting beyond 14 days of life
Clay/white stool and dark urine
Direct bilirubin >2mg/dL
Exchange blood transfusion or phototherapy
Hyperbilirubinemia:
Causes of jaundice:
Accumulation of bilirubin
Increased bilirubin production
Impaired metabolism
Decreased excretion or combination
Classification of jaundice based on site od disorder:
Location:
o URQ
o Dome of liver lies against inferior diaphragm surface
o Gall bladder on inferior surface
Structure:
o 60 % of cells are hepatocytes
o 30 % are Kupffer cells
o 10 % vascular and supporting tissue cells
Function:
o Detoxification & drug metabolism:
Synthesis of waste products
Conjugation of hormones and bilirubin to water-soluble forms
Conversion of drugs to metabolites for excretion in urine/stool
Bile:
o Secreted by liver
o Bile salts made of cholic acid and chenodeoxycholic stored in gall bladder
o Bile composed of water, ions, bile acids, organic molecules (cholesterol, phospholipids, bilirubin)
o Body produces 3L of bile/ day, excretes 1L of what is produced
o Gallstones are mostly cholesterol
Contain waste products from RBC breakdown and other metabolic processing
Bilirubin metabolism:
o Hydrophobic & cytotoxic
o Insoluble in aqueous solutions at pH <8.0
o Soluble in organic solvents and dissolves in lipids diffuses across membranes
o Production:
80% heme from Hb
20 % myoglobin
Bilirubin fractions in blood:
Unconjugated: complexed with albumin
Conjugated: bilirubin monoglucuronides
, Conjugated: bilirubin diglucuronides
Conjugated bilirubin bound to albumin
α- bilirubin - unconjugated
β – bilirubin - monoconjugated
γ – bilirubin - diconjugated
δ – bilirubin – bound to albumin
Most common diseases affecting liver:
Hepatitis: damage to liver cells
Cirrhosis
o Increased fibrous tissue formation, leads to shrinkage of
liver
o Decreased hepatocellular function and obstruction of bile flow (cholestasis)
Tumors
Jaundice- icterus:
Due to hyperbilirubinemia
o Can be acquired or inherited
CLINICAL JAUNDICE bilirubin > 50mmol/L (3mg/dL)
Activity of hepatic conjugating enzymes is low at birth but
increases rapidly after
o Transient physiological jaundice of new born reflects this
Physiological jaundice:
o Immaturity in bilirubin metabolism at multiple steps results in hyperbilirubinemia in first few days of
life:
Increased bilirubin load on hepatic cell
Defective uptake from plasma into liver cell
Defective conjugation
Decreased excretion
Increased entero-hepatic circulation
o Characteristics:
Appears 24-72hrs of age
Max intensity 4-5th day in term, 7th day preterm neonates
Does not exceed 15mg/dL
Undetectable after 14 days
o Pathological jaundice
Presence of any of the following:
Rise in serum bilirubin by more than 5mg/dL/day
Serum bilirubin more than 15mg/dL
Clinical jaundice persisting beyond 14 days of life
Clay/white stool and dark urine
Direct bilirubin >2mg/dL
Exchange blood transfusion or phototherapy
Hyperbilirubinemia:
Causes of jaundice:
Accumulation of bilirubin
Increased bilirubin production
Impaired metabolism
Decreased excretion or combination
Classification of jaundice based on site od disorder:
