1. Third lecture

2. Composition of the blood 1-RBCs (erythrocytes). 2-WBCs (leukocytes).  Granulocytes.  A granulocytes. 3-Thrombocytes (Platelets).

3. 1-Erythrocytes (RBCs)  8  m in diameter.  2.7  m thick.  volume ~ 90  m 3.  area ~ 160  m 2.  Biconcave disc.   surface area.   efficiency for diffusion of O2 & CO2.

4. 1-Erythrocytes Structure Structure  Plasma membrane  Cytoplasm  Hemoglobin  Binds O 2 & CO 2  No nucleus or organelles

5. 1-Erythrocytes Flexible. Flexible. Elastic. Elastic. Life span 100-120 day. Life span 100-120 day. Originate in bone marrow. Originate in bone marrow.

6. Erythroblasts Reticulocytes Become progressively smaller, form haemoglobin, lose nucleus Released into circulation, mature over following 24 hours - lose mitochondria and ability to synthesise protein (haemoglobin) Erythrocyte (RBCs) No mitochondria - utilise glycolytic pathway for energy Regulated by erythropoietin Formation of RBCs

7. Fate of red blood cells Life span in blood stream is ~120 days.   Senescent RBCs are phagocytosed and/or lysed.   Normally, lysis occurs extravascularly in the reticuloendothelial system subsequent to RBC phagocytosis.   Lysis can also occur intravascularly.

8. Extravascular Destruction of RBCs Liver, Bone marrow, & Spleen. Hemoglobin Globin Amino acids Amino acid pool Heme Bilirubin Fe 2+ Excreted Phagocytosis & Lysis Hemolysis

9.   In normal adults this results in a daily load of 250-300 mg of bilirubin.   Normal plasma concentrations are less then 1 mg/100ml.   Hydrophobic – transported by albumin to the liver for further metabolism prior to its excretion. Degradation of heme

10. Normal bilirubin metabolism Uptake of bilirubin by the liver is mediated by a carrier protein.   On the smooth ER, bilirubin is conjugated with glucoronic acid, xylose, or ribose. Glucoronic acid is the major conjugate - catalyzed by UDP glucuronyl tranferase. “Conjugated” bilirubin is water soluble and is secreted by the hepatocytes into the biliary canaliculi.

11. Normal bilirubin metabolism Converted to stercobilinogen (urobilinogen) (colorless) by bacteria in the gut. Oxidized to stercobilin which is colored. Excreted in feces. Some stercobilin may be re-adsorbed by the gut and re-excreted by either liver or kidney.

12. Hyperbilirubinemia  Increased plasma concentrations of bilirubin (> 3 mg/100mL) occurs when there is an imbalance between its production and excretion.  Recognized clinically as jaundice.

13. Handling of free Hemoglobin  Haptoglobin: hemoglobin-haptoglobin complex is readily metabolized in the liver and spleen forming an iron-globin complex and bilirubin. hemoglobin-haptoglobin complex is readily metabolized in the liver and spleen forming an iron-globin complex and bilirubin. This prevents loss of iron in urine. This prevents loss of iron in urine. Hemopexin: Hemopexin: binds free heme. The heme-hemopexin complex is taken up by the liver and the iron is stored bound to ferritin. binds free heme. The heme-hemopexin complex is taken up by the liver and the iron is stored bound to ferritin.

14. Methemalbumin: Methemalbumin: complex of oxidized heme and albumin. complex of oxidized heme and albumin.  Purposes: 1. Scavenge iron. 2. Prevent major iron losses. 3. Free heme is very toxic. Handling of free hemoglobin