Jaundice and liver function tests

KVB

Normal Liver:

• The liver is the largest internal organ,measuring on an average 1500 g.

• The liver has a dual blood supply: 2/3rd by the portal circulation & 1/3rd of blood arriving from the hepatic artery.

• This dual blood supply accounts for the red colour of hepatic infarcts.

The hepatic acinus:

The three zones of the acinus:

• Zone 1: Bordering on the portal tract & first to receive blood from the branches of the portal vein & hepatic artery. Susceptible to toxin-mediated damage.

• Zone 3: Comprises hepatocytes around the THV,consequently the last to receive blood entering the acinus.This area is susceptible to ischemic injury during hypoperfusion of the liver.

• Zone 2 :Located between Zones 1 & 3.

FUNCTION OF THE LIVER

• The liver regulates most chemical levels in the blood and excretes bile, which helps carry away waste products from the liver.

• All the blood leaving the stomach and intestines passes through the liver.

• The liver processes this blood and breaks down the nutrients and drugs into forms that are easier to use for the rest of the body.

• More than 500 vital functions have been identified with the liver. Some of the more well-known functions include

the following:

Glucose metabolism

Ammonia conversion

Protein metabolism

Fat metabolism

Vitamin and iron storage

Drug metabolism

Bile formation

Main functions of the liver:

Metabolic functions: Processing nutrients. Removal of impurities and neutralizing various

toxins.

Storage functions: Storage of energy & metabolites,predominantly

in the form of lipids & carbohydrates. Vitamins A & B12,folate. Oligo-minerals like iron and copper.

Secretory functions:Most of the plasma proteins,Lipids in the form of lipoproteinsCarbohydrates that are being transported

to other organs for metabolic conversion into energy.

Excretory function:Excretes bile into the intestine.

Proteins secreted by the liver:

• Albumin.• Clotting factors.• Acute-phase reactants: C-RP,SAA protein.• Binding & carrier proteins, eg, transferrin,

ceruloplasmin, thyroid-binding protein.• Alpha-fetoprotein (AFP) is produced by fetal

liver cells. Levels rise in patients with hepatocellular carcinoma.

jaundice

The main forms of jaundice:

1) Prehepatic hemolytic jaundice: • Bilirubin is predominantly in an unconjugated form.

Seen in:• Autoimmune hemolytic anemia.• Transfusion reaction.• Malaria.• Erythroblastosis fetalis.• Resorption of bilirubin from internal hemorrhages

( massive hematoma, intestinal hemorrhage).• Inefficient hematopoiesis (pernicious anemia,

thalassemia).

2) Hepatic jaundice:

• Bilirubin is partially conjugated & partially in an unconjugated form.

• Results from liver cell injury.

The Hereditary Hyperbilirubinemias

• Inborn errors of bilirubin metabolism resulting in excessive amounts of bilirubin in the circulating blood, either because of increased bilirubin production or because of delayed clearance of bilirubin from the blood.

• Hereditary hyperbilirubinemias can be divided into conjugated forms and unconjugated forms.

Congenital hyperbilirubinemias

Unconjugated Conjugated

1. Gilbert’s syndrome

2. Crigler-Najjar syndrome

1. Rotor syndrome

2. Dubin-Johnson syndrome

• Both types of conjugated hyperbilirubinemias have a relatively benign course, but establishing the diagnosis is important to spare patients from undergoing multiple unnecessary procedures and to exclude other more serious causes of hyperbilirubinemia.

Rotor syndrome

• Rotor syndrome is a rare, relatively benign autosomal recessive bilirubin disorder of unknown origin.

• It has many things in common with Dubin-Johnson syndrome except that in Rotor Syndrome, the liver cells are not pigmented. The main symptom is a non-itching jaundice.

• There is a rise in bilirubin in the patient's serum, mainly of the conjugated type.

3) Post-hepatic obstructive jaundice:

• Bilirubin is mostly in conjugated form.

• Results from the obstruction of major extrahepatic biliary ducts.

Bilirubinuria:

• Unconjugated bilirubin, typically found in hemolytic jaundice, circulates bound to albumin.

• Conjugated bilirubin typically found in the blood of patients suffering from hepatocellular or obstructive jaundice is water soluble & will readily pass into the urine.

Kernicterus:

• The deposition of bilirubin in basal ganglia of the brain.

• Occurs typically in infants affected by the massive hemolysis of eryhthroblastosis fetalis.

• High levels of unconjugated bilirubin enable it to cross blood-brain barrier.

• Deposition of bilirubin causes brain injury.

Causes of neo-natal jaundice:

• sepsis

• hypoxia

• hypoglycemia

• hypothyroidism

• hypertrophic pyloric stenosis

• galactosemia

• fructosemia

Evaluation of liver function:The liver function tests(LFTs)

These tests monitor:

1) Liver cell integrity (known as necroinflammatory indices):

AST,ALT,which can rise 50 times over normal values in massive liver necrosis.In viral hepatitis, levels of AST & ALT are 4-6 times above the normal values.

2) Hepatic secretory function: Albumin:Normal values are 3.5-5

g/dL.Reduced to < 3g/dL in chronic liver injury.

Coagulation proteins: Measure prothrombin time(PT).Prolonged PT is a very sensitive index of liver function loss.

Serum protein electrophoresis:• This is an evaluation of the types of proteins that are

present with in a patient's serum.• By using an electrophoretic gel, major proteins can be

separated out. • This results in four major types of proteins. These are: 1) Albumin, 2) Alpha globulins 3) Beta globulins 4) Gamma globulins

Serum Electrophoresis

• Serum protein electrophoresis is useful for evaluation of patients who have abnormal liver function tests since it allows a direct quantification of multiple different serum proteins.

• If the gamma globulin fraction is elevated, autoimmune hepatitis may be present.

• In addition a deficiency in the alpha globulin fraction can result in the diagnosis, or a clinical clue, to alpha-1 antitrypsin deficiency. This is a simple blood test that is commonly performed by hepatologists.

Coagulation tests (e.g. INR)

• The liver is responsible for the production of coagulation factors.

• The international normalized ratio (INR) measures the speed of a particular pathway of coagulation, comparing it to normal.

• If the INR is increased, it means it is taking longer than usual for blood to clot.

• The INR will only be increased if the liver is so damaged that synthesis of vitamin K-dependent coagulation factors has been impaired: it is not a sensitive measure of liver function.

Serum glucose

• The liver's ability to produce glucose (gluconeogenesis) is usually the last function to be lost in the setting of fulminant liver failure.

3) Biliary excretory function: Bilirubin:Conjugated bilirubin that cannot be

excreted into the intestine can be readily measured as direct bilirubin.

Alkaline phosphatase: Elevated levels are typical of obstructive jaundice.

Gamma-glutamyl transferase(GGT): Primarily a hepatic enzyme and its rise is a reliable sign of biliary obstruction.Is also induced in liver cells in alcohol or phenobarbital injury to the p450 system.GGT is thus a marker of liver-cell injury,especially alcohol-induced injury.

4) Hepatic catabolic function: include the detoxification of many metabolites.

In practice,only the capacity of the liver to remove ammonia is measured.

Elevation of blood ammonia is a good marker of severe liver injury.

Other tests commonly requested alongside LFTs:

• 5' nucleotidase (5'NTD) :

• 5' nucleotidase is another test specific for cholestasis or damage to the intra or extrahepatic biliary system, and in some laboratories, is used as a substitute for GGT for ascertaining whether an elevated ALP is of biliary or extra-biliary origin.

Lactate dehydrogenase (LDH)

• Lactate dehydrogenase is an enzyme found in many body tissues, including the liver.

• Elevated levels of LDH may indicate liver damage

Why is it important to fractionate bilirubin in the serum?

• Fractionation of bilirubin is important for elucidating the causes & pathogenesis of jaundice.

• Normally,blood contains <1.2 mg/dL of bilirubin,most of it being in an unconjugated (indirect) form-95%.

• According to laboratory analysis, hyperbilirubinemia can be classified as the following:

Predominantly unconjugated(<20%). Mixed (CB 20-50%). Predominantly conjugated (>50%).

Thank you