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Learning Objectives of today’s

Learning Objectives of today’s. Revise Erythropoiesis Regulation of Erythropoiesis Fate of RBCs. Erythropoiesis. RBC Formation before birth. Mesoblastic stage Nucleated RBCs - Yolk sac Mesothelial layers of the placenta – 3 rd week Hepatic stage

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Learning Objectives of today’s

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  1. Learning Objectives of today’s • Revise • Erythropoiesis • Regulation of Erythropoiesis • Fate of RBCs

  2. Erythropoiesis

  3. RBC Formation before birth • Mesoblastic stage • Nucleated RBCs - Yolk sac Mesothelial layers of the placenta – 3rd week • Hepatic stage • At 6 weeks - Liver form blood cells • Spleen + lymphoid tissues form blood cells.

  4. RBC Formation before birth • Myeloid stage • From the third month on - the bone marrow gradually becomes the principal source of the RBCs • Last month – Bone marrow exclusively

  5. Relative rates of red blood cell production in the bone marrow of different bones at different ages.

  6. Bone marrow cells for Erythropoiesis • Pluripotential hematopoietic stem cell, PHSC • Colony-forming unit–erythrocyte, CFU-E Factors: • Growth inducers • Differentiation inducers.

  7. Features of a Mature RBC • Biconcave disc • Mean Diameter 7.8 um • Can deform easily. • Bag of fluid with dissolved substances and hemoglobin • No sub cellular particles • Metabolism • Anaerobic respiration- Glycolysis • Pentose phosphate pathway.

  8. RBC Count • Remains remarkably constant although there are some variations. • MALE: 5.2 ± 0.3 x 106 /uL. • FEMALE: 4.7 ± 0.3 x 106 /uL. • Life span :120 Days.

  9. Regulation of Erythropoiesis • Importance • Factors affecting Erythropoiesis • Tissue Oxygenation • Anemia, • Bone marrow destruction • High Altitudes, • Cardiac failure, • Respiratory problem

  10. ERYTHROPOITEN • Sites of production • If Erythropoiten production reduced • Stimulants of Erythropoiten production: • RENAL MECHANISM • NON RENAL MECHANISM • In Renal failure?

  11. Formation of Erythropoiten • Erythrogenin – Renal Erythropoitic factor • Erythropoitinogen • Stimulants for Erythrogenin • Role of Erythropoiten • Recombinant Erythropoiten

  12. Vit B12 & Folic acid • Essential for formation of thymidine triphosphate • Vitamin C • Potentiate the effect of Folic acid • Also helpful in Iron Absorption • Reducing Ferric to ferrous form • Pyridoxine: • Glycine and succinyl-CoA condensation • Riboflavin and Pantothenic acid • Heme formation • Cell growth and division

  13. Metals • Iron • Copper • Ceruloplasmin • Necessary for Iron transfer from storage sites • Bone marrow, Liver and Spleen • Cobalt • Forms a part of Vitamin B12 • Nickel and Manganese

  14. Proteins • Formation of Globin • Protein deficiency • Hormones • GH,Testosterone , TH, Cortisol, ACTH • Other factors………………..

  15. If  you complain about your transport system, What about them?

  16. FATE OF RBC's

  17. At 120 Days…. in RBC’s 1. No DNA,RNA 2. No protein synthesis 3. Enzymes exhausted 4. Decreased energy production 5 Increased rigidity of cells (memb lipids rearrangements) 6. Triggering of cell lysis

  18. RBCs after 120 days Fragile Membranes of RBC rupture Phagocytized by Reticulo endothelial system Tissue macrophages • Kupffer cells • Spleen

  19. Hemoglobin split Heme Globin Amino acid pool- reuse Free Iron Straight chain of 4 pyrrole nuclei Transported in blood by transferrin Reused

  20. HEME OXYGENASE Straight chain of 4 pyrrole nuclei Biliverdin Free Bilirubin (released by Macrophages into plasma) Combination with plasma Albumin BloodInterstitial fluids Liver kidney-- Nil Free Bilirubin BILIVERDIN REDUCTASE

  21. Within Hours Free Bilirubin in blood Absorption in hepatic cell membrane Released from Albumin Conjugated Glucoronic acidSulfates Other substances Bilirubin Glucoronide Bilirubin Sulfate

  22. Bilirubin Glucoronide Bilirubin Sulfate Excreted from hepatocytes Bile canaliculi Conjugated Bilirubin in intestines Urobilinogen ACTIVE TRANSPORT Bacterial Action

  23. Urobilinogen Reabsorbed by intestinal mucosa Blood Liver Kidneys UrobilinogenStercobilinogen Urine Feces UrobilinStercobilin 5% Reexcreted Into Gut Oxidation Oxidation

  24. Normal serum Bilirubin Conc Serum Bilirubin • Total: 0.3 to 1.0 mg/dl • Conjugated: 0.1 to 0.4 mg/dl • Unconjugated: 0.2 to 0.7 mg/dl

  25. RBCs after 120 days Fragile Membranes of RBC rupture Phagocytized by Reticulo endothelial system Tissue macrophages • Kupffer cells • Spleen

  26. Hemoglobin split Heme Globin Amino acid pool- reuse Free Iron Straight chain of 4 pyrrole nuclei Transported in blood by transferrin Reused

  27. HEME OXYGENASE Straight chain of 4 pyrrole nuclei Biliverdin Free Bilirubin (released by Macrophages into plasma) Combination with plasma Albumin BloodInterstitial fluids Liver kidney-- Nil Free Bilirubin BILIVERDIN REDUCTASE

  28. Within Hours Free Bilirubin in blood Absorption in hepatic cell membrane Released from Albumin Conjugated Glucoronic acidSulfates Other substances Bilirubin Glucoronide Bilirubin Sulfate

  29. Bilirubin Glucoronide Bilirubin Sulfate Excreted from hepatocytes Bile canaliculi Conjugated Bilirubin in intestines Urobilinogen ACTIVE TRANSPORT Bacterial Action

  30. Urobilinogen Reabsorbed by intestinal mucosa Blood Liver Kidneys UrobilinogenStercobilinogen Urine Feces UrobilinStercobilin 5% Reexcreted Into Gut Oxidation Oxidation

  31. When you were born you were crying and everyone around you was smiling. Live your life in such a way, so that when you die, you're the one smiling and everyone around you is crying..............

  32. T H A N K Y O U

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