Learning Objectives of today’s Revise –Erythropoiesis –Regulation of Erythropoiesis Fate of RBCs

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

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

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

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

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.

RBC Count Remains remarkably constant although there are some variations. MALE : 5.2 ± 0.3 x 10 6 /uL. FEMALE : 4.7 ± 0.3 x 10 6 /uL. Life span : 120 Days.

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

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

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

Vit B 12 & 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

Metals Iron Copper –Ceruloplasmin –Necessary for Iron transfer from storage sites Bone marrow, Liver and Spleen Cobalt –Forms a part of Vitamin B 12 Nickel and Manganese

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

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

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

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

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

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

Free Bilirubin in blood Absorption in hepatic cell membrane Released from Albumin Conjugated Glucoronic acid Sulfates Other substances Bilirubin Glucoronide Bilirubin Sulfate Within Hours

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

Urobilinogen Reabsorbed by intestinal mucosa Blood Liver Kidneys Urobilinogen Stercobilinogen Urine Feces Urobilin Stercobilin Reexcreted Into Gut 5% Oxidation

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

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

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

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

Free Bilirubin in blood Absorption in hepatic cell membrane Released from Albumin Conjugated Glucoronic acid Sulfates Other substances Bilirubin Glucoronide Bilirubin Sulfate Within Hours

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

Urobilinogen Reabsorbed by intestinal mucosa Blood Liver Kidneys Urobilinogen Stercobilinogen Urine Feces Urobilin Stercobilin Reexcreted Into Gut 5% Oxidation

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