DEFINITION:• Icterus

• A yellowish tint to the body tissues; yellowness of the skin and deep tissues

• 0.5 mg/dl of plasma

• Above 1.5mg/dl- jaundice appears

Heme Anabolism & Heme Catabolism

Bilirubin metabolism (RES)

Conjugation of bilirubin (liver)

Disposal of bilirubin (GIT)

Unconjugated Conjugated

Also known asBilirubin Bilirubin Diglucuronide

Indirect Bilirubin Direct Bilirubin

Solubility Lipid Soluble Water Soluble

Normal Amount in blood 1mg/dl Well below 1/2mg/dl

Accumulation Increased Hgb to salvageMalfunction in hepatocyte/

biliary tree

Diagnostic tests Not detected in urine Detected in urine

Causes of JaundiceCauses of Jaundice

• Predominantly Unconjugated hyperbilirubinemiaPredominantly Unconjugated hyperbilirubinemia:I. Excess production of bilirubinII. Reduced hepatic uptakeIII. Impaired bilirubin conjugation

1.1. Deficiency of canalicular membrane transportersDeficiency of canalicular membrane transporters• Dubin-Johnson syndrome, Rotor syndrome

2. Impaired bile flow.2. Impaired bile flow.• UGT, uridine diphosphate-glucuronyltransferase.

Predominantly Conjugated Predominantly Conjugated HyperbilirubinemiaHyperbilirubinemia

Predominantly Conjugated Predominantly Conjugated HyperbilirubinemiaHyperbilirubinemia

• Conjugated Conjugated HyperbilirubinemiaHyperbilirubinemia

• Unconjugated Unconjugated HyperbilirubinemiaHyperbilirubinemia

• Water soluble and is seen in urine at low levels

• Urobilinogen will be absent in urine with cholestasis

• Abnormal liver laboratory• Elevated alkaline phosphatase and gamma-

glutamyl transpeptidase (GGTP) suggest intra/ extrahepatic obstruction

• Tightly bound to albumin and will not appear in the urine

• Should have normal liver laboratory, CBC and smear may show anemia and hemolysis

• Gilbert’s syndrome is most common cause– Increase bilirubin may be seen with fever,

exertion, fasting, surgery, and heavy alcohol use

• CHOLURIC – presence of bile derivatives in the urine– Occurs in regurgitation hyperbilirubinemia– Obstructive type

• ACHOLURIC – absence of bile derivatives in urine– presence of an excess unconjugated bilirubin– Retention hyperbilirubinemia– Hemolytic type

CLINICAL• Defect in uptake of bilirubin

by liver cells• Immature hepatic

conjugating system

BIOCHEMICAL• Slight change in liver cells• Severe increase of Alkaline

Phospholipase (APL)• Gilbert's syndrome is a

congenital disorder of bilirubin metabolism

CLINICAL• Presence of tumors,

structures

BIOCHEMICAL• Mild to severe increase

of APL

CLINICAL• Liver damage (hepatitis,

cirrhosis)

BIOCHEMICAL• With marked

biochemical change in liver cells

• Marked increase in APL

• Bilirubin is produced by the normal breakdown of red blood cells.

• Jaundice occurs when bilirubin builds up faster than a newborn's liver can break it down and pass it from the body.

Reasons for this:•Too large an amount of bilirubin is reabsorbed from the intestines before the baby gets rid of it in the stool.

•A newborn baby's still-developing liver may not yet be able to remove adequate bilirubin from the blood.

•Newborns make more bilirubin than adults do since they have more turnover of red blood cells.

• High levels of bilirubin — usually above 25 mg — can cause deafness, cerebral palsy, or other forms of brain damage in some babies.

• Jaundice may indicate the presence of another condition, such as an infection or a thyroid problem.

• Also called hematogenous jaundice.

• Massive lysis of red blood cells may produce bilirubin faster than it can be conjugated.

• Normally that liver produces 300 mg of bilirubin per day but has the capacity to excrete over 3 000 mg.

• Under these conditions there is an increase bilirubin is excreted into the bile, the amount of urobilinogen entering the enterohepatic circulation is increased, and urinary urobilinogen is increased.

• Hemolytic jaundice is the presentation of an increase in unconjugated bilirubin levels in the blood.

• The common causes of hemolytic jaundice include Rh hemolytic disease, ABO incompatibility, G-6-PD deficiency and minor blood group incompatibility.

• Rh hemolytic disease• A baby born to an Rh-negative mother

(and Rh-positive father) should have Rh typing and a Direct Coomb’s test (DCT) on cord blood.

• ABO Incompatibility• Babies born to women with O blood

group should be closely monitored for jaundice and discharged after 72 hours.

• Other hemolytic states•G6PD deficiency, hereditary spherocytosis, minor group incompatibilities should be managed similar to ABO incompatibility.

• also known as plethora.• A condition where there is an

increase in Red Blood Cells in relation to the blood volume.

• As the blood cells begin to breakdown after its normal lifespan, there will be increase of bilirubin production than normal due to the abnormally high amounts of red blood cells in the circulation.

• There will be increase of bilirubin production than normal due to the abnormally high amounts of red blood cells in the circulation.

• This will cause an accumulation of

bilirubin in the blood leading to jaundice.

• Leakage of blood from the blood vessels into the tissues.

• Does not cause an increase in neither conjugated nor unconjugated bilirubin in the blood.

• It causes local accumulation of bilirubin in the affected tissue and subsequently causes local jaundice in that area.

• This in turn will be phagocytosed by cell macrophages for further breakdown to biliverdin then to unconjugated bilirubin

• Conjugated hyperbilirubinemia commonly results from blockage of the hepatic or common bile ducts, most often due to a gallstone or to cancer of the head of the pancreas.

• Once biliburin sent to the liver, it will be conjugated to bind with glucoronic acid or sulfate before it is excreted into the bile and finally the intestines.

• The conversion of free bilirubin to the conjugated form requires a specific enzyme called UDP glucoronyltransferase.

Some disorders that is conjugated bilirubin: Dubin Johnson Syndrome, Cholestatic jaundice of pregnancy, and Alcoholic liver diseases.

• A condition wherein there is jaundice in an exclusively breast fed baby who is otherwise healthy.

• It develops after the first week of life and continues up to the sixth week of life.

• The presence of the progesterone called 3-alpha-20 beta pregnanediol in the breast milk of some women.

• 3 alpha 20 beta pregnanediol counteracts the effect of UDP- glucoronyltransferase, the enzyme responsible for conjugating free bilirubin in the liver.

• Caused by factors in the breast milk, which block certain proteins in the liver that break down bilirubin.

• Bile duct obstruction is a blockage in the tubes that carry bile from the liver to the gallbladder and small intestine.

• When the bile ducts become blocked bile builds up in the liver.

• Jaundice develops due to the increasing levels of bilirubin in the blood.

• Patients with Dubin-Johnson Syndrome, Hepatic tumor or common bile stones suffer from obstructive jaundice.

• http://www.gpnotebook.co.uk/simplepage.cfm?ID=-536477635&linkID=7340&cook=no

• DISORDERS OF BILIRUBIN METABOLISM• Namita Roy Chowdhur• Irwin M. Arias• Allan W. Wolkoff• Jayanta Roy Chowdhury• Color Atlas of Physiology by Stephan Silbernagl

and Agamemnon Despopoulos