Bilirubin and liver enzymes Flashcards
Bilirubin
a bile pigment accumulation results in jaundice metabolized by the liver and excreted into bile ducts a waste product hydrophobic, nonpolar has a high affinity for albumin
Jaundice
a defect in bilirubin metabolism
Reticuloendothelial cell hemoglobin is broken down into
heme and globin
heme oxygenase oxidizes
heme to hydroxyheme to biliverdin-Fe
biliverdin-Fe is converted to bilirubin by
biliverdin reductase
Clearance in the liver and conjugation of bilirubin
Bilirubin dissociates from albumin
Combines with ligandin
Ligandin facilitates its transfer to the SER
UDPGT-1 forms bilirubin monoglucurnoide (BMG)
BMG is converted to BDG (a water-soluble conjugated form)
Stool coloration
BDG –> reduction to urobilinogen –> oxidation to stercobilin
Entero-hepatic circulation
10-30% of urobilinogen is reabsorbed into portal circulation
90% is carried to the liver for re-excretion
remaining 10% gets into systemic circulation and is excreted by urine
7 Steps of bilirubin metabolism
- Haem breakdown
- Transport of unconjugated bilirubin to the liver
- Hepatic uptake of unconjugated bilirubin
- Conjugation
- Secretion of conjugated bilirubin into bile
- Gut breakdown of conjugated bilirubin to urobilinogen
- Faecal and urinary excretion of urobilinogen and stercobilin
Hyperbilirubinemia
balance broken between production and excretion
Causes of hyperbilirubinemia
- overproduction of bilirubin - hemolysis
- Impairment of uptake, conjugation, and excretoin
- Obstruction in liver cells or bile duct
Total bilirubin
All bilirubin, conjugated and unconjugated
Direct bilirubin
conjugated bilirubin (Bc)
Indirect bilirubin
Unconjugated bilirubin (Bu), cannot react with activator (ex. caffeine)
3 liver enzymes of diagnostic value
Aminotransferases
Alkaline Phosphatase (ALP)
y-Glutamyl Transferase (GGT)
Aminotransferase
found in the liver
AST and ALT
AST is abuntant in liver, heart, skeletal muscle, and exists as a cytoplasmic and mt enzyme
ALT is restricted to cytoplasmic fraction and high concentration in hepatocyte
AST/ALT may also be elevated in other non-hepatic/non-biliary diseases
Hepatocellular disease
high levels of aminotransferase
aminotransferases are released into the liver upon liver cell necrosis/abnormal membrane permeability
ALT wil increase most as it is exclusively cytoplasmic
ALT is more diagnostically sensitive
AST is a better marker in alcoholic liver disease
Alkaline phosphatase (ALP)
low substrate specificity
catalyzes hydrolysis of many phosphate esters at alkaline pH
located in brush borders of both proximal convoluted tubule of kidney and small intestinal mucosa
located at sinusoidal surface and in microvilli in hepatocyte
role in bone mineralization
serum ALP activity is age dependent
higher values in men before menopause, then this switches
Liver disease (ALP)
biliary tract obstruction (cholestasis) cuases high levels of ALP
compared w/ hepatocellular and obstructive jaundic: increased activity compared to normal, levels not necessarily high
Bone disease
High serum ALP
GGT
nonspecific, good sensitivity
highest activity located in kidney, followed by pancreas, liver, spleen, and placenta
reabsorption of amino acids from glomerular filtrate
present in hepatocyte ER
GGT levels tend to parallel those shown by ALP
Liver disease (GGT)
highest activity of GGT in obstructive liver diseases
GGT levels tend to parallel those shown by ALP, also a marker for biliary obstruction
GGT is not present in bone so higher specificitiy
Acute Viral hepatitis (type B)
disease affecting liver cells
flu like symptoms
ALT/AST rise in prodromal phase, AST declines faster than ALT
AST/ALT ratio is less than 1
if these levels remain elevated this may indicate the onset of chronic hepatitis or cirrhosis
ALP remains normal, may raise slightly due to mechanical intrahepatic obstruction or inflamed hepatocytes
IMPORTANT EARLY MONITORING OF LIVER ENZYMES
3 Stages of AVH
- Prodromal stage
- Clinical jaundice
- Recovery phase
