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 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 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 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..............