basic insights into process of erythropoiesis

2. Structure of RBC
Normal size
Normal structure
Hematopoiesis
Erythropoiesis
Definition
Site
Stages
Factors affecting
erythropoiesis
Fate of RBC
Recent advances
Bibliography

3. Side view
Top View
2.0μ
7.5μ
1μ

4. HEMO: Referring to Blood Cells
POIESIS:”The development of
production of”
The word HEMATOPOIESIS refers to
development and production of blood cells
•ERYTHROCYTES- erythropoiesis
•LEUKOCYTES- leukopoiesis
•THROMBOCYTES- thrombopoiesis
Begins in the 20th week of life in fetal
liver and spleen, continues in the bone
marrow till young adulthood & beyond!!!!

5.  MONOPHYLETIC
 DUALISTIC
 TRIALISTIC or
polyphylectic

6. AGE SITE OF HEMATOPOIESIS
EMBRYO • YOLK SAC THEN LIVER
3-7 MONTH • SPLEEN
• MARROW CAVITY SPECIALLY-GRANULOCYTES
AND PLATELETS
4TH & 5TH MONTH
7th MONTH • MARROW CAVITY-ERYTHROCYTES
• MOSTLY BONE MARROW;SPLEEN &
LIVER WHEN NEEDED
BIRTH
• NUMBER OF ACTIVE SITES IN
BONE MARROW DECREASES BUT
RETAIN ABILITYFOR
HEAMATOPOIESIS
BIRTH TO MATURITY
• BONE MARROW OF
SKULL,RIBS,STERNUM,VERTEBRAL
COLUMN,PELVIS,PROXIMAL ENDS OF
FEMUR
ADULT

8. “ERYTHROPOIESIS is the process of origin,
development and maturation of erythrocytes”

9. IN
FETAL
LIFE
MESOBLASTIC
STAGE
HEPATIC STAGE
MYELOID STAGE

10. IN NEW BORN
BABIES- Upto
age of 20 yrs
RBCs are produced
from red bone
marrow of all
bones(long bones
and all the flat
bones)
The shaft of long bones
becomes yellow bone
marrow because of fat
deposition and looses
the erythropoietic
function
After the age of 20
years: RBCs are
produced from
membranous bones
like vertebra,
sternum ,ribs and
ends of long bones
In adults ,
liver & spleen
may produce
blood cells if
bone marrow is
destroyed or
fibrosed

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

12. Primary cells that are capable of self-renewal
differentiating into specialized cells.
Hematopoietic stem cells are the primitive cells in the
bone marrow which give rise to blood cells.
Hematopoietic stem cells in the bone marrow are
called uncommitted pluripotent hematopoietic stem
cells(PHSC)
When the cells are designed to form a particular type
of blood cells, the uncommitted PHSCs are called
committed PHSCs.

13. Uncommitted pluripotent hemopoietic stem cell
Committed pluripotent hemopoietic stem cell
LYMPHOID STEM CELL COLONY FORMING
BLASTOCYTE
L
COLONY forming
unit-E
Colony forming unit-GM
R
Granulocytes
N
B
E
COLONY
forming unit-
M
M
MEGAKARYOCYTE
P
L=LYMPHOCYTE
R=RED BLOOD
CELL
N=NEUTROPHIL
B=BASOPHIL
E=EOSINOPHIL
M=MONOCYTE
P=PLATELET

15. •Reduction in size of the cell(from diameter of 25-7.2μ)
•Disappearance of nucleoli & nucleus
•Appearance of hemoglobin
•Change in the staining properties of cytoplasm

16. HEAMOCYTOBLAST PROERYTHROBLAST
EARLY
ERYTHROBLAST
LATE
ERYTHROBLAST
NORMOBLAST
RETICULOCYTE
ERYTHROCYTE
PLEURIPOTENT
STEM CELL
DERIVED FROM
MESENCHYME
COMMITTED CELL
DEVELOPMENT
PATHWAY
PHASE 1
RIBOSOME
SYNTHESIS
PHASE2
Hb
ACCUMULATION
PHASE 3
EJECTIO
N OF
NUCLEUS

24. FACTORS CLASSIFIED INTO 3 CATEGORIES
GENERAL
FACTORS
•ERYTHROPOEITIN
•THYROXINE
•HEMATOPOIETIC
GROWTH FACTORS
•VITAMINS
MATURATION
FACTORS
•Vit.B 12
•INTRINSIC
FACTOR OF CASTLE
•FOLIC ACID
FACTORS
NECESSARY
FOR Hb
FORMATION
•FIRST CLASS
PROTEINS &
AMINO ACIDS
•IRON
•COPPER
•COBALT &
NICKEL
•VITAMINS

25.  Principal factor that stimulates red blood cell
production
Glycoprotein with a molecular weight of 34,000
Hypoxia is a key factor in increased production of
erythropoietin

26. ROLE OF ERYTHROPOIETIN
HEMOPOIETIC stem cells
PROERYTHROBLASTS
RED BLOOD CELLS
Tissue Oxygenation
Erythropoietin
Increases
KIDNEY
Factors that decrease oxygenation
1. Low blood volume
2. Anemia
3. Low hemoglobin
4. Poor blood flow
5. Pulmonary disease
Function of the erythropoietin
mechanism to increase the
production of red blood cells
when various factors decrease
tissue oxygenation
Decreases

28. OTHER FACTORS
Hemopoietic growth factors-
•Interleukin-3
•Interleukin-6
•Interleukin-11
Vitamins
•Vit.B 12
•Folic acid
•Vit.C
•Vit.D
•Vit.E
Dietary factors
•Metal ions
Iron
Copper
Cobalt
•Proteins

29.  Especially important for the final maturation of red blood
cells are the two vitamins,Vitamin B12 and Folic acid
 Both are essential for synthesis of DNA
INTRINSIC FACTOR OF CASTLE
•Produced in gastric mucosa by parietal
cells
•Essential for absorption of Vit. B12

30. •The RBCs circulate an average of 120 days before being
destroyed
• The metabolic system of RBC’s becomes less active,
membrane of RBC’s becomes fragile
•Destroyed in the spleen

31. RBCs AFTER 120 DAYS
FRAGILE
MEMBRANES OF RBC RUPTURE
PHAGOCYTOSED BY RETICULOENDOTHELIAL
SYSTEM
TISSUE MACROPHAGES
KUPFFER CELLS
SPLEEN

32. Hemoglobin split
HEME
GLOBIN AMINO ACID
POOL-REUSE
Free Iron
TRANSPORTED IN
BLOOD BY
TRANSERRIN
REUSED
STRAIGHT CHAIN OF 4
PYRROLE NUCLEI

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

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

35. Urobilinogen
Reabsorbed by intestinal mucosa
Blood LIVER
Kidneys
Urobilinogen Stercobilinogen
Urine FEACES
STERCOBILIN
Reexcreted
Into Gut
Oxidation
Oxidation
Urobilin

36. Apoptotic mechanisms in control of
erythropoiesis (Ref. Leukemia (2008),1176-
1199 )
Erythropoiesis-stimulating agents & other
methods to enhance oxygen transport
(Ref.Br J Pharamacol;v 154(3)2008 jun )
Erythroblastic islands- niches for
erythropoiesis (Ref. Blood (2008),112;470-
478 )

37. BIBLIOGRAPHY
•TEXTBOOK OF MEDICAL PHYSIOLOGY – GUYTON &
HALL
•GANONG REVIEW OF MEDICAL PHYSIOLOGY
•ESSENTIALS OF MEDICAL PHYSIOLOGY-K
SEMBULINGAM
•GOOGLE SEARCH ENGINE