erythropoiesis

DR NILESH KATE

MBBS,MDASSOCIATE PROF

DEPT. OF PHYSIOLOGY

ERYTHROPOIESIS.

OBJECTIVES Sites of haemopoiesis. Blood cell precursors. Control of haemopoiesis. Stages of erythropoiesis. Regulation of erythropoiesis Factors necessary for erythropoiesis

Tuesday, May 2, 2023

HAEMOPOIESIS. Process of development

of blood cells. Erythropoiesis –

development of RBC Leucopoiesis –

Development of WBC Thrombopoiesis –

Development of platelets.


SITES OF HAEMOPOIESIS. First 2 months of

gestation – yolk sac. 3rd month onwards –

liver 7 spleen. 20th week onwards –

till birth - bone marrow.


SITES OF HAEMOPOIESIS. In Young Children – axial

skeleton & bones of extremities i.e. Red Bone marrow.

With fatty replacement it becomes Yellow Bone Marrow.

In Adults – axial skeleton & proximal extremities of long bones.

In Pathological conditions – extra medullary haemopoiesis i.e liver & spleen resumes .


BLOOD CELL PRECURSORS. The stem cells –

Monophyletic Theory. All originate from PHSC,

Pleuripotent Hamopoietic Stem Cell.

Fundamental properties Self replication. Differentiation &

commitment.


BLOOD CELL PRECURSORS. Progenitor cells. Pleuripotent progenitor

cells Lymphoid stem cell –

Lymphocytes. Myeloid stem cell.

Granulocyte – Monocyte progenitor.

Erythroid progenitor. Megakaryocyte Progenitor.


FEATURES OF PROGENITOR CELLS.

Progenitor cells form group of cells called Clones so also called CFU-colony forming units.

CFU-GEMM – Granulocyte, Erythroid, Megakaryocyte & Macrophages.

BFU-E – Burst forming units Erythroid.

CFU-E - Erythroid CFU-Ba – Basophil.


CONTROL OF HAEMOPOIESIS. Mainly by Hamopoietic

Growth Factors i.e. Cytokines.

These are called Colony Stimulating Factors (CSF) CSF-G CSF-M CSF-GM

Interleukins – for Lymphocyte precursor.

Erythropoietin


STAGES OF ERYTHROPOIESIS. Pronormoblast Early normoblast

(Basophilic) Intermediate

normoblast (Polychromatic)

Late normoblast (orthochromatic)

Reticulocyte.



STAGES OF ERYTHROPOIESIS.


CELLS/FEATURES SIZE CYTOPLASM NUCLEUSHAEMOGLOBIN

MITOSIS

PRONORMOBLAST

15-20 μm

BASOPHILICLARGE WITH RETICULAR FORMATION

ABSENT SEEN

EARLY12-16μm

BASOPHILIC

LARGE,NUCLEOLI DISAPPEARED.

ABSENT SEEN

INTERMEDIATE10-14μm

POLYCHROMATIC

CONDENSED APPEARS PRESENT

LATE8-10μm

ACIDOPHILIC

SMALL PYKNOTIC

INCREASES ABSENT

RETICULOCYTE7-7.5μm

RETICULUM LIKE

ABSENT INCREASES ABSENT

MATURATION OF RETICULOCYTE TO ERYTHROCYTES.

Reticulocyte – juvenile red cells without nucleus but contains ribosomal RNA so can synthesize Hb.

Mature Red cells maturation in spleen, lost Ribosomes, Mitochondria.

Reticulocyte in Infants -2-6%, Adults 0.5-2%.

Slightly basophilic hue in cytoplasm & can stain with new Methelene Blue or Brilliant Cresyl Blue


SUMMARY OF CHANGES.

Cell Duration Size NucleusHb synthesis

Cytoplasm staining

Mitosis

Reticulocyte

0-5 DAYS 7-7.5 μmCondenses, pyknotic

Present

Basophilic-polychromatic - acidophilic

Only upto intermediate normoblast

RBC 2 DAYS 7 μm Absent Absent acidophilic

Absent only cell matures.


REGULATION OF ERYTHROPOIESIS

Erythropoietin – Glycoprotein with molecular wt 34000.

Site of formation- 85% - epithelial linings of

peritubular capillaries. 15% - liver & cells of

tissue macrophage system.


ERYTHROPOIETIN Stimulus for secretion. Mainly hypoxia –

causes release of Renal Erythropoietic Factor – acts on Plasma alpha globulin Erythropoietinogen – form Erythropoietin


ERYTHROPOIETIN Actions

Main effect on stem cells – differentiation

Promote Hb synthesis Promotes every stage Promotes release of RBC

from Bone Marrow to Peripheral Circulation.


FACTORS AFFECTING ERYTHROPOIETIN

Increase secretion Hormones – Androgen ,

Thyroxine, GH, ACTH, Prolactin, Adrenocortical Steroids.

Haemolysates – products of RBC destruction.

Nucleotides – cAMP,NAD,NADP

Vasoconstrictor drugs – that causes renal hypoxia

Decrease secretion. Adenosine antagonists

– Theophylline. Oestrogen – decreases

synthesis of Globin & depressing erythropoietic response to hypoxia.


FACTORS NECESSARY FOR ERYTHROPOIESIS

General factors. Special maturation

factors. Haemoglobinization

factors.


GENERAL FACTORS. Optimum levels of

hormone Erythropoietin & efficient feedback mechanism controlling erythropoietin.


SPECIAL MATURATION FACTORS. Vit B 12

(extrinsic factor) Folic acid Intrinsic factor

of Castle.


VIT B 12 (EXTRINSIC FACTOR) Vit B12 –

Cyanocobalamin or extrinsic factor.

Daily need – 1-2 μg. Sources – Milk, Meat,

Liver of Animals Also synthesized by

bacterial Flora.


VIT B 12 (EXTRINSIC FACTOR) ABSORPTION – need

Intrinsic Factor Of Castle , a glycoprotein secreted by parietal cells of gastric mucosa.

With it form Intrinsic Factor- Cyanocobalamin complex

Bound to sp receptors in ileum & absorbed by Endocytosis.


VIT B 12 (EXTRINSIC FACTOR) TRANSPORT – in blood transported by combining

with Transcobalamin-II

STORAGE – In liver & Muscle

ROLE – required for synthesis of DNA & maturation of nucleus & cell.


FOLIC ACID Folic acid –

Pteroylglutamic acid. Daily requirement –

100 μg. Sources – leafy veg,

pulses, yeasts, liver. From breakdown of

Polyglutamate to Monoglutamates.


ROLE OF FOLIC ACID IN DNA SYNTHESIS.


Polyglutamates in food

Monoglutamates

Plasma Methyl tetrahydrofolate

TetraHydrofolate (THF)

Formyl THF(Folinic Acid)

5,10 methylene THF

Dihydrofolate

Uridine Monophosphate

D Thymidine Monophosphate

Dihydro reductase

INTRINSIC FACTOR OF CASTLE. Intrinsic factor of

Castle is formed by Gastric Cells.

Deficiency if intrinsic factor occurs in autoimmune cause of failure of secretion of IF. ( Addisonian Pernicious Anaemia)


Thank you.


erythropoiesis

Health & Medicine