Download Clinical biochemistry (5) Liver

LIVER
Liver functions
Bile pigment metabolism
Degradation of hemoglobin
Disorders of bile pigment metabolism
Liver diagnostic enzymes
Liver functions
• Liver performs many important functions dealing
with or affecting metabolism, excretion of various
substance, protection, circulation and blood
coagulation.
 Metabolic functions:
- Carbohydrate metabolism (glycogenesis from
glucose and stored in liver, glycogenolysis).
- Protein synthesis (almost all of the plasma
proteins are synthesized in the liver), lipoproteins
blood coagulation factors: V, VII, X and IX.
- Lipid metabolism: plasma lipoproteins,
cholesterol, phospholipids, and triglycerides.
- Other synthesis or transformations: conversion of
keto acid to amino acid, production of ketone
bodies(acetoacetic acid and β–hydroxybutyric
acid) from acetyl-CoA, a.a from glucose, lactate
to glucose, synthesis fatty acids from acetyl-CoA.
Storage functions: liver is the primary storage site
for glycogen, vitamins A, D, and B12 , iron.
Excretory functions: liver excretes bile (bilirubin),
bile salts (cholic acid), some dyes, heavy metals,
enzymes and many waste products.
 Protective functions: liver protects the body
from foreign and dangerous materials by
- Phagocytic action. Liver contains many
phagocytic cells called Kupffer cells (remove
foreign materials from blood.
- Detoxification: involve esterification,
methylation, oxidation, reduction. Ammonia is
converted to urea.
Circulatory functions: liver play a role in
immunologic defense, helps to regulate blood
volume.
Bile pigment metabolism
Bilirubin
 Bilirubin is the principal pigment in the bile.
 It is derived from breakdown of hemoglobin.
 RBC lives only 120 days.
 The destruction of old RBC occur in
reticuloendothelial (RE) system by phagocyte cells.
 That destroy are located in spleen, liver and bone
marrow.
Degradation of hemoglobin
1- Splitting off of protein
globin, which hydrolyzed to
a.a. The porphyrin ring of
heme molecule is broken
open. The resulting open
chain of tetrapyrrol loses its
iron. The resulting pigment
is reduced to form bilirubin,
reddish yellow waste
product that must be
excreted.
2- Bilirubin leaves the
reticuloendothelial cell and bonds to
plasma albumin.
3- Bilirubin-albumin transferred into
liver cells by active process then
bilirubin is detached from albumin.
4- Esterification (conjugation) of
bilirubin to bilirubin diglucuronide
(BDG) by the of enzyme glucuronylbilirubin transferase.
5- BDG (conjugated bilirubin) is water
soluble and secreted from the liver.
6- BDG , with the rest of bile passes
into bile duct. Bile is produced
continuously by liver.
7- BDG reaches the colon and exposed
to the action of bacteria whose
enzymes cleave off BDG into
urobilinogen.
8- A portion of urobilinogen is
absorbed into liver and re-excreted it
into the bile. Small portion of
urobilinogen reaches the peripheral
circulation and excreted by kidney.
9- Urobilinogen in colon is partially
oxidized to urobilin and other
brownish pigments that are excreted
in the feces
Disorders of bile pigment metabolism
 A bout 250-300mg of bilirubin are produced daily in
normal healthy adult.
 Normal concentration of total bilirubin in serum
ranges from 0.1-1.0mg/dl.
 Normal concentration of esterified bilirubin
(conjugated)(direct) in serum may be up to
0.3mg/dl.
 When the bilirubin concentration in blood rises, the
pigment begins to be deposited in sclera of the eye
and in the skin. This yellowish pigmentation in the
skin or sclera is known as jaundice.
Disorders of bile pigment metabolism
Most liver diseases and several nonhepatic
disorders are companied by jaundice.
1) A excessive load of bilirubin (hemolytic diseases
, chronic hemolytic anemia)
2) Defective transport into the hepatocyte. This
transport defect is known as Gilberts disease.
3) Impairment in esterification of bilirubin.
A) physiologic jaundice of new born due to the
UDPG transferase enzyme is not fully developed.
B)Hemolytic disease of new born due to Rh and
ABO system incompatibility.
4) Congenital deficiency of UDPG transferase.
Known as the Crigler-Najjar syndrome .
Disorders of bile pigment metabolism
5) Disturbances in excretion of bilirubin.
(Cholestasis), hyperbilirubinemia.
6) Intrahepatic . Viral hepatitis, hepatitis produced
by toxic (drug, chemicals like phosphorus,
organic arsenicals, carbon tetrachloride and
chloroform), cirrhosis, hepatic edema.
7) Posthepatic. These include all type of extrahepatic
cholestasis or obstruction of the flow of bile into
intestine, may due to stones in the bile ducts or
gallbladder, by carcinoma of the head of pancreas, by
other tumors.
Liver diagnostic enzymes
• Number of enzymes are helpful in diagnosis of
liver function they are called diagnostic enzymes.
1. Alkaline phosphatase (ALP). The enzyme
distributed in many tissues including osteoblasts,
cells lining the sinusoids and bile canaliculi .
Normal range 2o-1o5u/L. The increase in ALP
activity is due to liver lesion such as, carcinoma,
amebic abscess, amyloidosis, granulomatous
lesion(sarcoidosis, tuberculosis of liver)
Liver diagnostic enzymes
2. Aspartate aminotransferase (AST) (GOT).
3. Alanine aminotransferase (ALT) (GPT).
The liver is a rich source of both enzymes GOT
and GPT,
Normal range : GOT male up to 37u/L
female up to 31u/L
GPT male up to 40u/L
female up to 31u/L