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 –
3rd 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 106 /uL.
• FEMALE :
4.7 ± 0.3 x 106 /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 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
• 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
• 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
Free Iron
Globin
Straight chain of
4 pyrrole nuclei
Transported in
blood by transferrin
Reused
Amino acid
pool- reuse
Straight chain of 4 pyrrole nuclei
HEME OXYGENASE
Biliverdin
BILIVERDIN REDUCTASE
Free Bilirubin (released by Macrophages into plasma)
Combination with plasma Albumin
Blood
Liver
Interstitial fluids
kidney-- Nil
Free Bilirubin
Free Bilirubin in blood
Within Hours
Absorption in hepatic cell membrane
Released from Albumin
Conjugated
Glucoronic acid
Bilirubin Glucoronide
Sulfates
Other substances
Bilirubin Sulfate
Bilirubin Glucoronide
Bilirubin Sulfate
Excreted from hepatocytes
ACTIVE TRANSPORT
Bile canaliculi
Conjugated Bilirubin in intestines
Bacterial Action
Urobilinogen
Urobilinogen
Reabsorbed by intestinal mucosa
Blood
Liver
5%
Kidneys
Urobilinogen
Urine
Oxidation
Urobilin
Reexcreted
Into Gut
Stercobilinogen
Feces
Oxidation
Stercobilin
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
Free Iron
Globin
Straight chain of
4 pyrrole nuclei
Transported in
blood by transferrin
Reused
Amino acid
pool- reuse
Straight chain of 4 pyrrole nuclei
HEME OXYGENASE
Biliverdin
BILIVERDIN REDUCTASE
Free Bilirubin (released by Macrophages into plasma)
Combination with plasma Albumin
Blood
Liver
Interstitial fluids
kidney-- Nil
Free Bilirubin
Free Bilirubin in blood
Within Hours
Absorption in hepatic cell membrane
Released from Albumin
Conjugated
Glucoronic acid
Bilirubin Glucoronide
Sulfates
Other substances
Bilirubin Sulfate
Bilirubin Glucoronide
Bilirubin Sulfate
Excreted from hepatocytes
ACTIVE TRANSPORT
Bile canaliculi
Conjugated Bilirubin in intestines
Bacterial Action
Urobilinogen
Urobilinogen
Reabsorbed by intestinal mucosa
Blood
Liver
5%
Kidneys
Urobilinogen
Urine
Oxidation
Urobilin
Reexcreted
Into Gut
Stercobilinogen
Feces
Oxidation
Stercobilin
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..............