Hematology 6 jaundice
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1. Hemoglobin is broken down through a series of steps after red blood cells are destroyed. This produces the yellow pigment bilirubin. 2. Jaundice occurs when bilirubin levels in the blood rise above normal. It can be caused by increased red blood cell breakdown, liver problems filtering bilirubin, or blockages in the bile ducts. 3. There are three main types of jaundice - pre-hepatic from too much red blood cell breakdown, hepatic from liver issues, and post-hepatic from bile duct blockages. They are distinguished by urine/stool pigments and liver function test results.
Hematology 6 jaundice
- 2. Learning objectives To understand: 1. Fate of Hb. 2. Jaundice: Definition, types, cause and differences between different types. 3. Physiologic jaundice
- 3. Catabolism of hemoglobin When senile red blood cells are destroyed in the reticulo endothelial system (RES), hemoglobin is liberated from the cells will be metabolized. The metabolic end product of Hb will be excreted from the body along with feces and urine as bilinogen.
- 4. Catabolism of Hb continued In the RES, during the catabolism of Hb, in the first step, the ring structure of Hb is removed. Now the pyrrole rings are arranged in a straight chain called choleglobin. From choleglobin, iron and globin are removed, stored and reutilized for synthesis of Hb.
- 5. Catabolism of Hb continued After removing iron and globin, the four pyrrole rings are converted to biliverdin. This compound is green in color. By the action of tissue enzymes, biliverdin is converted to bilirubin. This bilirubin is yellow in color and water insoluble. It is soluble in lipidssoluble in lipids and is toxic.
- 6. Catabolism of Hb continued The water insoluble bilirubin enters circulation. In circulation it is attached to plasma proteins and transported. One of the important plasma proteins which transports bilirubin is albumin. The unconjugated bilirubin that is in circulation now is known as hemobilirubin. Hemobilirubin is taken to liver. In liver it undergoes conjugation reaction with glucuronic acid. The enzyme involved is glucuronyl transferase. Due to this reaction bilirubin glucuronide is formed. This is a water soluble compound and is less toxic.
- 7. Catabolism of Hb continued Bilirubin glucuronides are secreted into biliary tract along with bile. These pigments reach small intestine. In intestine, bilirubin glucuronide is acted upon by the bacteria and will be converted into a series of colorless compounds known as bilinogens. Some amount of this bilinogen is excreted along with feces as stercobilinogen. In the terminal part of small intestine, a part of bilinogens are absorbed and pass through enterohepatic (portal) circulation and reach liver.
- 8. Catabolism of Hb continued The bilinogens that have entered portal circulation also reach systemic circulation. Along systemic circulation, bilinogens reach kidney. Kidney filters these compounds and bilinogen is excreted in urine. The bilinogens excreted in urine are known as urobilinogens. Whether it is uro or stercobilinogen, after excretion when exposed towhen exposed to atmosphere, are oxidized to form uro and stercobilinsatmosphere, are oxidized to form uro and stercobilins. The characteristic color of the feces is because of the presence of this compound. Along with feces about 80 to 240 mg of bilinogen is excreted per day and along with urine, only about 0.5 to 2.0 mg/day is excreted.
- 10. Jaundice Jaundice is yellow discoloration of: • Skin • Mucus membrane • Sclera of eyes. It occurs due to increase in serum bilirubin level in circulation. The normal serum bilirubin level is about 0.2 to 0.8 mg%. When bilirubin level exceeds 2.0 mg%, it results in clinical jaundice.
- 11. Jaundice continued The cause for jaundice varies. It can be due to increased hemolysis, or due to malfunctioning of liver or may be due to blockade in the biliary tract. Depending on the cause, jaundice is classified into: a. Hemolytic or pre-hepatic jaundice. b. Hepatic jaundice c. Obstructive or post hepatic jaundice.
- 12. Hemolytic or pre hepatic jaundice As the name indicates, in this condition, the cause is before liver. In pre hepatic jaundice, there will be increased hemolysis. Increased hemolysis occurs in some of the conditions like • Malaria • Sickle cell anemia • Incompatible blood transfusion • In erythroblastosis fetalis (blood group incompatibility between mother and fetus) etc.
- 13. Hepatic jaundice As the name suggests, in this type of jaundice, the problem is in liver. Liver converts water insoluble bilirubin (hemobilirubin) to water soluble bilirubin (cholebilirubin) by conjugation reaction. Bilirubin is excreted from the body in water soluble form only. In diseases like • Cirrhosis of liver • Viral hepatitis etc., the liver function suffers. Therefore severe liver disorders are usually accompanied with jaundice.
- 14. Obstructive or post hepatic jaundice Water soluble bilirubin that is secreted into bile by liver reaches intestine through biliary tract. If there is obstruction in biliary tract, flow of bile suffers. This also results in jaundice. The duration of obstruction and extent of obstruction matters in the onset of characteristic features of jaundice. In the initial phase, post hepatic jaundice is purely obstructive jaundice. But when bile starts accumulating behind the obstructed area, the back pressure built up in biliary tract, damages liver cells and the signs and symptoms seen may be of both obstructive and hepatic jaundice.
- 15. Differences between pre hepatic, hepatic and post hepatic jaundice Pre hepatic Hepatic Post hepatic Urine Urobilinogen content Increased Decreased Absent Bilirubin (bile pigments) Absent (acholuric) Present Present Bile salts Absent Present Present
- 16. Differences between pre hepatic, hepatic and post hepatic jaundice continued Pre hepatic Hepatic Post hepatic Stools Stercobilinogen content Increased Decreased Absent Quantity and nature of stools Normal More oily and foul smelling More oily and foul smelling
- 17. Differences between pre hepatic, hepatic and post hepatic jaundice continued Pre hepatic Hepatic Post hepatic Liver function tests Clotting time Normal Increased Increased Prothrombin time Normal Increased Increased Plasma protein level Normal Decreased Decreased Alkaline phosphatase level Normal Increased Markedly increased
- 18. Differences between pre hepatic, hepatic and post hepatic jaundice continued Pre hepatic Hepatic Post hepatic Others Vanden Bergh reaction Indirect Biphasic Direct Reticulocyte count in circulation Increased Normal Normal
- 19. Vanden Bergh test A mixture of sulphanilic acid, hydrochloric acid and sodium nitrate (diazo reagent) is added to serum containing excess of bilirubin glucuronide. A reddish color results in about 30 sec. This is known as direct reaction and post hepatic type of jaundice gives direct response. In hemolytic jaundice, in serum there is excess of bilirubin and not bilirubin glucuronide. This bilirubin is lipid soluble. After addition of diazo reagent, color will not appear. Reddish color appears only after addition of alcohol. The color appears because alcohol dissolves lipid soluble bilirubin. This is known as indirect reaction.
- 20. Physiologic jaundice Manifests in about 72 hours after birth. It is more common in premature births. Due to immaturity of the liver (less amount of glucuronyl transferase), liver is unable to cope with the demand and the unconjugated bilirubin accumulates in circulation. Treatment is to expose the infant to ultra violet rays which quickens bilirubin metabolism. In some cases phenobarbitone is administered to hasten the conjugation reaction.
- 21. Jaundiced at birth A newborn infant which is jaundiced at birth or develops jaundice within 24 hours after birth, is probably due to blood group incompatibility between mother and infant. This is may be due to Rh or ABO group incompatibility. This condition is known as erythroblastosis fetalis.
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Editor's Notes
- #7: Bilirubin is in the blood attached to albumin. Hence, the name, hemo bilirubin . It is insoluble in plasma and quite toxic , so it is transported to the liver by albumin to be conjugated with glucuronic acid. Conjugation makes hemobilirubin less toxic.
- #9: When stercobilinogen is exposed to the air, it is oxidized to bilin ; responsible for the characteristic color of feces.
- #10: Hemosiderin often forms after bleeding (hemorrhage). When blood leaves a ruptured blood vessel, the cell dies and the hemoglobin of the red blood cells is released into the extracellular space. White blood cells called macrophages engulf (phagocytose) the hemoglobin to degrade it, producing hemosiderin and porphyrin Choleglobin : A protein which is formed from the breakdown of haemoglobin (a protein that carries oxygen in the blood) and is a precursor to the bile pigment biliverdin.