Heme catabolism.pptx

This PPT is recommended for B.Sc nursing 2nd semester students which is highly benefited for students.

1. HEME DEGRADATION PATHWAY Red blood cells have limited lifespan of approximately 100-120 days. Degradation of red blood cell occurs in spleen, bone marrow, liver and lymph glands. Degradation of heme occurs mainly, in the liver. If degradation of red blood cells occurs in the tissues other than the liver, hemoglobin is transported to the liver by means of haptoglobulin .

2. After the aged red blood cells are recognized by macrophages, they are rapidly engulfed by the phagocytes and form phagosomes . They fuse with the primary lysosomes and form secondary lysosomes . Lysosomal cathepsin results in complete degradation of the cellular proteins, including globin of hemoglobin, to the constituent amino acids, which are utilized for general metabolic needs. Heme is degraded in the reticuloendothelial cells, to a linear tetrapyrrole ( biliverdin IXa ), by the microsomal enzyme system, which is designated as heme oxygenase . This enzyme requires molecular oxygen and NADPH, and is induced by heme . Heme oxygenase catalyzes the cleavage of a- methenyl bridge whichis quantitatively converted to carbon monoxide (CO) that is trapped by the hemoglobin and eventually exhaled. Biliverdin is reduced to bilirubin by the enzyme biliverdin reductase .

3. BILIRUBIN Bilirubin is an orange-yellow pigment, derived from the breakdown of red blood cells in the liver, spleen and bone marrow. Its daily production, in men, averages from 250 mg to 300 mg. Approximately , 85% of this is derived from the heme moiety of hemoglobin, which is released from the erythrocytes that are destroyed in the reticuloendothelial cells while rest of it is formed from catabolism of other heme containing proteins, such as myoglobin , cytochromes and other heme containing enzymes.

4. Metabolism of Bilirubin Bilirubin , normally present in the blood, is bound to albumin & transported to the liver. Hepatocytes trap bilirubin by means of a specific binding protein, called ligandin . In the heapatocytes , bilirubin gets conjugated with UDP Glucuronate , which is derived from the oxidation of UDP glucose. This reaction is catalysed by UDP- glucuronyltransferase . In the normal bile, bilirubin diglucuronide is the major form of excreted bilirubin with only a smal amount of the bilirubin monoglucuronide . As bilirubin diglucuronide is much more water soluble than free bilirubin , transferase thus facilitates the excretion of bilirubin , via bile duct, into the intestine

5. Metabolism of Billirubin

6. HYPERBILIRUBINEMIA AND JAUNDICE Normal serum contains total bilirubin up to 1 mg/ dL of which about two third or 70% is indirect or unconjugated form and about 30% or one-third is direct or conjugated bilirubin. Blood levels of more than 1 mg% are called hyperbilirubinemia. Jaundice refers to yellowish discoloration of the sclera of eye ball, mucous membranes and skin due to high levels of bilirubin in the blood. Usually this occurs when the serum bilirubin is 2 mg% or more.

7. Latent jaundice • It refers to the stateof hyperbilirubinemia when serum bilirubin level is between 1-2 mg%. Usually there is no yellowish discoloration of sclera or mucous membrane in this state. As the level increases, jaundice appears.

8. Types of Jaundice Three types of jaundice are seen depending on the cause of increased bilirubin in the blood . Hemolytic jaundice Hepatic jaundice Obstructive jaundice

9. Hemolytic Jaundice Haemolytic jaundice is also called retention or acholuric jaundice. In typical hemolytic jaundice, the basic abnormality is over production of bilirubin due to excessive heme catabolism.

10. Causes Abnormal shape of RBCs such as in sickle cell anaemia Deficiencies of some enzymes like pyruvate kinase, glucose-6-phosphate dehydrogenase, etc. Mismatched blood transfusion is the other common cause leading to hemolysis of RBCs. Abnormal RBCs are prone to undergo hemolysis. Excessive bilirubin goes to the hepatocytes which conjugate bilirubin to its maximum capacity. But the hemolysis is usually much more and so ultimately the unconjugated bilirubin dominates in blood. This is water insoluble and hence it is not excreted in urine.

11. Conjugated bilirubin is also more than the normal. It leads to excessive urobilinogen production and its excretion in urine and stools. This is because proportionately more urobilinogen is absorbed in enterohepatic circulation.

12. Hepatic Jaundice Hepatic jaundice is due to diminished hepatic function due to liver diseases. Commonly in typical hepatic jaundice there is deficiency or complete absence of glucuronosyl transferase enzyme. So the conjugation of bilirubin is absent or decreased. Causes Acute and chronic hepatitis caused by hepatitis viruses A, B, C, D and E; infection with B and C viruses is dangerous and should be treated early. Long term use of hepatotoxic drugs like antitubercular drugs etc. Congenital defects e.g. Gilbert syndrome, Crigler Najjar syndrome, etc.

13. Metabolic Abnormality Since bilirubin is not adequately conjugated, increase in unconjugated bilirubin is seen. Some conjugated bilirubin will also be present due to residual conjugation activity in the liver. Since in hepatitis there is usually narrowing of hepatic canaliculi due to swelling of hepatocytes, there is intrahepatic obstruction to bilirubin secretion into the bile. In such cases, the conjugated bilirubin is reabsorbed into blood circulation. It is then excreted in urine because this bilirubin is water soluble. So bilirubin may be seen in urine in hepatic jaundice due to hepatitis also in active phase of disease. Normally, no bilirubin is present in urine.

14. Obstructive Jaundice Obstructive jaundice is also called regurgitation or choluric jaundice. Conjugation occurs normally in the liver, but there is a defect in secretion. This type of jaundice occurs due to extrahepatic obstruction to the flow of bile. So the conjugated bilirubin is not secreted into the intestine.