Bilirubin and liver enzymes

Question 1

Bilirubin

Answer 1

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

Question 2

Jaundice

Answer 2

a defect in bilirubin metabolism

Question 3

Reticuloendothelial cell hemoglobin is broken down into

Answer 3

heme and globin

Question 4

heme oxygenase oxidizes

Answer 4

heme to hydroxyheme to biliverdin-Fe

Question 5

biliverdin-Fe is converted to bilirubin by

Answer 5

biliverdin reductase

Question 6

Clearance in the liver and conjugation of bilirubin

Answer 6

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)

Question 7

Stool coloration

Answer 7

BDG –> reduction to urobilinogen –> oxidation to stercobilin

Question 8

Entero-hepatic circulation

Answer 8

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

Question 9

7 Steps of bilirubin metabolism

Answer 9

1. Haem breakdown
2. Transport of unconjugated bilirubin to the liver
3. Hepatic uptake of unconjugated bilirubin
4. Conjugation
5. Secretion of conjugated bilirubin into bile
6. Gut breakdown of conjugated bilirubin to urobilinogen
7. Faecal and urinary excretion of urobilinogen and stercobilin

Question 10

Hyperbilirubinemia

Answer 10

balance broken between production and excretion

Question 11

Causes of hyperbilirubinemia

Answer 11

1. overproduction of bilirubin - hemolysis
2. Impairment of uptake, conjugation, and excretoin
3. Obstruction in liver cells or bile duct

Question 12

Total bilirubin

Answer 12

All bilirubin, conjugated and unconjugated

Question 13

Direct bilirubin

Answer 13

conjugated bilirubin (Bc)

Question 14

Indirect bilirubin

Answer 14

Unconjugated bilirubin (Bu), cannot react with activator (ex. caffeine)

Question 15

3 liver enzymes of diagnostic value

Answer 15

Aminotransferases
Alkaline Phosphatase (ALP)
y-Glutamyl Transferase (GGT)

Question 16

Aminotransferase

Answer 16

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

Question 17

Hepatocellular disease

Answer 17

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

Question 18

Alkaline phosphatase (ALP)

Answer 18

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

Question 19

Liver disease (ALP)

Answer 19

biliary tract obstruction (cholestasis) cuases high levels of ALP
compared w/ hepatocellular and obstructive jaundic: increased activity compared to normal, levels not necessarily high

Question 20

Bone disease

Answer 20

High serum ALP

Question 21

GGT

Answer 21

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

Question 22

Liver disease (GGT)

Answer 22

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

Question 23

Acute Viral hepatitis (type B)

Answer 23

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

Question 24

3 Stages of AVH

Answer 24

1. Prodromal stage
2. Clinical jaundice
3. Recovery phase

Question 25

Extrahepatic cholestasis

Answer 25

due to intrahepatic or extrahepatic obstruction resulting in jaundice, pale faeces, dark urine, itching, and hepatomagaly
obstruction of common hepatic or common bile ducts by gallstone or stricture or neoplasm
ALP is elevated to 2x or 3x beyond upper reference limit
aminotransferase levels are modest