ERYTHROPOIESI

BY DR.ABSAR ULLAH KHAN

 In adults, if liver and spleen produce RBCs if bone
marrow is destroyed or fibrosed.
 Bone marrow is equal to liver in size and weight.
 Involved in the production of cells.
 75% leukocytes are produced and 25%
erythrocytes.
 WBC-RBC ratio: 1:500
 Difference in life span.
Erythropoiesis:
 Process of origin, development and maturation of
red blood cells.
 Hemopoiesis or hematopoiesis:
 Process of origin, development and maturation of all
blood cells.
 PROCESS OF
ERYTHROPOIESIS:
 STEM CELLS:
 Blood cells are formed in the bone marrow from stem cells
called pluripotential haematopoietic stem cells.
 Also called uncommitted pluripotential haematopoietic stem
cells (PHSC).
 All the cells of circulation are derived from these cells.
 During reproduction, few PHSC remain like the cells of origin
to maintain the supply.
 When cells are differentiated to form particular types of blood
cells, uncommitted PHSC are converted to committed PHSC.
 These are the cells restricted to give rise to specific type of
blood cells.
 Two types of PHSCs:
 1. lymphoid stem cells:
 Lymphocytic cells.
 2. colony forming blastocytes:
 Myeloid cells.
 When grown in culture these cells form colonies.
Units of colony forming cells:
 A committed stem cell that forms erythrocytes is
called colony forming unit erythrocytes. CFU-E
 Colony forming units that form granulocytes and
monocytes have designation CFU-GM.
 These cells give rise to neutrophils, eosinophils and
basophils.
 Colony forming unit-megakaryocytes CFU-M.
 Platelets are developed from these cells.
Changes during erythropoiesis:
 CFU-E in the process of maturation pass through 4
stages:
 Reduction in size of cells:
 25 to 7.2 micrometer.
 Disappearance of nuclei and nucleus.
 Appearance of haemoglobin.
 Changes in the staining properties of cytoplasm.
STAGES OF ERYTHROPOIESIS:
 1. Proerythroblast.
 2. Early normoblast.
 3. Intermediate normoblast.
 4. Late normoblast.
 5. Reticulocyte.
 6. Matured erythrocyte.
1.PROERYTHROBLAST:
 Megaloblast
 First cell derived from CFU-E
 Large with 20 micrometer diameter.
 Cytoplasm is basophilic in nature.
 Large nucleus occupying the cell completely.
 Nucleus has 2 or more nucleoli and reticular
network.
 No haemoglobin.
 Multiplies several times to form early normoblasts.
2. EARLY NORMOBLAST:
 Synthesis of haemoglobin starts in this stage.
 Smaller than proerythroblasts.
 15 micrometer diameter.
 Cytoplasm is basophillic in nature.
 Cell is also called basophilic erythroblast.
 Nucleoli disappear.
 Chromatin network becomes dense.
 These cells develops into next stage called
intermediate normoblast.
3. INTERMEDIATE
NORMOBLAST:
 Haemoglobin appears in this stage.
 Cells have diameter of 1-0-12 micrometer.
 Nucleus is still present.
 Chromatin network is further condensed.
 Cytoplasm is basophilic. Due to haemoglobin it
stains both acidic and basic.
 Cells are also called polychromophilic or
polychromatic erythroblast.
 Develop into late normoblast.
4. LATE NORMOBLAST:
 8-10 micrometer diameter.
 Very small nucleus with condensed chromatin.
 Ink spot nucleus.
 Increased haemoglobin.
 Acidophilic cytoplasm.
 Orthochromatic erythroblast.
 Before passing to next stage, nucleus disappears.
 Pyknosis.
 Final remnants of nucleus are extruded from the cell.
5. RETICULOCYTE:
 Immature RBC.
 Slightly larger than mature RBC.
 Reticulum. Remnants of disintegrated organelles.
 Named because of reticular network.
 In newborns, reticulocyte count is 2% to 6% of RBCs.
 Number decreases in first week of birth.
 In mature life, its below 1%.
 Count increases when production and release of RBCs increases.
 Basophilic because of remnants of golgi apparatus., mitochondria
and other organelles
 Enter the blood through capillary membrane by diapedesis.
6. MATURED ERYTHROCYTES:
 Reticular network disappears.
 Cell becomes mature RBC.
 7.2 micrometer. Biconcave shape.
 Haemoglobin but no nucleus.
 7 days to convert to mature erythrocyte from
proerythroblasts.
 5 days to convert to reticulocytes from
proerythroblasts.
 2 days to convert to mature erythrocytes.
FACTORS NECESSARY FOR
ERYTHROPOIESIS:
 Factors are generally classified into three categories:
 General factors.
 Erythropoietin
 Thyroxine.
 Hemopoietic growth factors.
 Vitamins.
 Maturation factors
 Vitamin B12.
 Intrinsic factor of castle.
 Folic acid
 Factors necessary for haemoglobin formation.
ERYTHROPOIETIN:
 Hormone for erythropoiesis.
 Hematopoietin/ erythrocyte stimulating factor.
 Secreted by peritubular capillaries of kidney.
 Small quantity also secreted from brain and liver.
 Hypoxia is the stimulant of erythropoietin.
 Actions:
 Proerythroblasts from CFU-E.
 Proerythropoietin into mature RBCs.
 Release of matured erythrocytes and some reticulocytes into blood.
 Level of erythropoietin increases with anemia.
THYROXINE:
 General metabolic hormone.
 Accelerates the process of
erythropoiesis at many levels.
 Hyperthyroidism and polycythemia
are common.
Hemopoietic growth factor:
 Growth factors or growth inducers.
 E.g interleukins and stem cell factors
 Induce the proliferation of PHSCs.
 Interleukins involved in erythropoiesis:
 Interleukin 3 secreted by T cells.
 Interleukin 6 secreted by T cells,
endothelial cells and macrophages.
 Interleukin 11 secreted by ostoblasts.
VITAMINS:
 Some vitamins necessary for erythropoiesis.
 Deficiency will result in anemia along with
other disorders.
 Vitamin B deficiency causes anemia and
pellagra.
 Vitamin C deficiency causes anemia and
scurvy.
 Vitamin D deficiency causes anemia and
rickets.
 Vitamin E deficiency causes anemia and
malnutrition.
MATURATION FACTORS:
 1: VITAMIN B 12:
 Maturaion factor necessary for erythropoiesis.
 Obtained from diet. Its absorption requires intrinsic factor of castle.
Also by large intestine flora.
 Stored in liver and some in muscle.
 Transported to bone marrow when required for maturation of RBCs.
 Required for synthesis of DNA in RBCs.
 Deficiency results in failure of maturation and reduction in cell
division.
 Large cells with weak cell membrane.
 Pernicious anemia.
2. INTRINSIC FACTOR OF
CASTLE:
 Produced in gastric mucosa from parietal cells.
 Essential for absorption of vitamin B12 from
intestine.
 Deficiency of intrinsic factor occurs in
 Severe gatritis
 Ulcer
 Gastrectomy.
3. FOLIC ACID:
 Required for synthesis of DNA.
 Maturation factor.
 Absence causes decrease in DNA synthesis leading
to failure of maturation.
 This makes cells appear larger and in
Megaloblastic/ proerythroblastic stage.
 This anemia is called megaloblastic anemia.
FACTORS NECESSARY FOR
HEMOGLOBIN FORMATION:
 First class proteins and amino acids.
 Iron.
 Copper.
 Cobalt and nickel.
 Vitamins.
HEMOGLOBI


N AND IRON
METABOLISM
INTRODUCTION:
 Iron containing matter of RBCs.
 Chromoprotein.
 95% of dry weight of RBC
 30% to 34% net weight.
 Carries respiratory gases.
 Acts as buffer.
 Molecular weight is 68,000.
 Average Hb is 14-16 g/dL.
FUNCTIONS OF
HEMOGLOBIN:
 1.TRANSPORT OF GASES:
 Oxygen:
 O2 binds with hemoglobin.Oxyhemoglobin.
 Process is called oxygenation.
 Iron is in ferrous state.
 Its an unstable compound.Reversible.
 Release of oxygen from oxyhemoglobin results
in ferrohemoglobin or reduced hemoglobin.
 Carbon Dioxide:
 Binds with hemoglobin to form carbhemoglobin.
 Unstable and reversible.
 Affinity of Hb to combine with CO 2 is 20 times more than
that for O2
2.BUFFER ACTION:
 Important to maintain acid base balance.
STRUCTURE OF
HEMOGLOBIN:
 Conjugated protein.
 Protein combined with iron containing pigment.
 Also forms a part of structure of myoglobin and
neuroglobin.
 Iron is present in ferrous form.Fe+2
 Abnormally can convert to ferric form which is
stable. Fe+3.
 Globin:
 Contains four polypeptide chains.
 2 alpha chains and 2 beta chains.
TYPES OF NORMAL
HEMOGLOBIN:
 Two types:
 Adult Hb. HbA
 Fetal Hb. HbF
 HbF is replaced by HbA immediately after birth.
 Completes at 10th to 12th week after birth.
 HbF and HbA are different on basis of structure
and function.
 Structural difference:
 HbA contains 2 alpha chains and 2 beta chains.
 HbF contains 2 alpha chains and 2 gama chains.
 Functional difference:
 HbF has more affinity to O2 than adult Hb.
ABNORMAL HEMOGLOBIN:
 Pathologic mutant forms of Hb.
 Variations are due to structural changes in the
polypeptide chains.
 Due to mutation is the gene of globin chains.
 Categories:
 Hemoglobinopathies.
 Hemoglobin in thalassemia and related disorders
HEMOGLOBINOPATHIES:
 Caused by abnormal polypeptide chains.
 Hb-S:
 Sickel cell anemia. Alpha chains are normal. Beta
chains abnormal.
 Hb-C:
 Abnormal beta chains.mild hemolytic anemia and
splenomegaly.
 Hb-E:
 Abnormal beta chains. Mild hemolytic anemia and
splenomegaly.
 Hb-M:
 Abnormal Hb in form of methemoglobin.
 Mutation of genes in both alpha and beta chains.
 Present in babies in Hb M disease or blue baby
syndrome.
 Inherited disease characterised by
methemoglobinemia.
HEMOGLOBIN IN THALASSEMIA
AND RELATED DISORDERS:
 Different types of abnormal Hb.
 Polypeptide chains are decreased, absent or abnormal.
 Alpha thalassemia:
 Alpha chains are decreased, absent or abnormal.
 Beta thalassemia:
 Beta chains are decreased, absent or abnormal.
 Some abnormal Hb are; Hb G, H, I, Bart’s,
Kenya,Lepore and constant spring.