ERYTHROPOIESIS : ERYTHROPOIESIS Presented By
Dr.Kusum Khoiwal HEMOPOIESIS: INTRO : HEMOPOIESIS: INTRO Hemo: Referring to blood cells
Poiesis: “The development or production of”
The word Hemopoiesis refers to the production & development of all the blood cells:
Begins in the Yolk Sac 6-7 week of life, from 12th week upto 28th in the fetal liver & spleen,continues in the bone marrow till young adulthood & beyond! ERYTHROPOIESIS: SITES/PHASES : ERYTHROPOIESIS: SITES/PHASES INTRAUTERINE LIFE:
INTRAVASCULAR PHASE: Upto 3rd month of Intra Uterine Life.
Endothelial cells = = = RBCs
HEPATIC PHASE: 3rd to 5th month IUL
Liver & Spleen
MYELOID PHASE: From 5th month of IUL onwards. ERYTHROPOIESIS: SITES/PHASEScontd. : ERYTHROPOIESIS: SITES/PHASEScontd. POST NATAL LIFE:
Predominantly Red Bone Marrow of skeleton:
Red Bone Marrow of Axial Skeleton. CLONAL HEMOPOIESIS : CLONAL HEMOPOIESIS PLURIPOTENT STEM CELL STEM CELL MULTIPLICATION COMMITTMENT COMMITTED
STEM CELL COMMITTED
STEM CELL MULTIPLICATION PROGENITOR
CELL CFU: COLONY
FORMING UNIT CLONAL HEMOPOIESIS: (Contd) : CLONAL HEMOPOIESIS: (Contd) COLONY FORMING UNIT
BLAST CELLS MATURE BLOOD CELLS
END CELLS: FINITE LIFE SPAN MORPHOLOGICALLY
RECOGNIZABLE STEM CELL THEORY : STEM CELL THEORY All bloods cells come from a single class of primitive mother cells called as:
Pluripotent Stem cells:
Has a diameter of 18 – 23 μ.
Giving rise to: both Myeloid and Lymphoid series of cells
Capable of extensive self-renewal.
Myeloid Stem cells: Generate myeloid cells:
Granulocytes: PMNs, Eosinophils & Basophils.
Lymphoid Stem cells: Giving rise only to:
Lymphocytes: T type mainly. STEM CELLS : STEM CELLS These cells have extensive proliferative capacity and also the:
Ability to give rise to new stem cells (Self Renewal)
Ability to differentiate into any blood cells lines (Pluripotency)
They grow and develop in the bone marrow.
The bone marrow & spleen form a supporting system, called the
“hemopoietic microenvironment” PROGENITOR CELLS : PROGENITOR CELLS Committed stem cells lose their capacity for self-renewal.
They become irreversibly committed.
These cells are termed as “Progenitor cells”
They are regulated by certain hormones or substances so that they can:
Undergo Maturation. ERYTHROID PROGENITOR CELLS : ERYTHROID PROGENITOR CELLS BFU-E: Burst Forming Unit – Erythrocyte:
Give rise each to thousands of nucleated erythroid precursor cells, in vitro.
Undergo some changes to become the Colony Forming Units-Erythrocyte (CFU-E)
Regulator: Burst Promoting Activity (BPA) ERYTHROID PROGENITOR CELLS : ERYTHROID PROGENITOR CELLS CFU-E: Colony Forming Unit- Erythrocyte:
Well differentiated erythroid progenitor cell.
Present only in the Red Bone Marrow.
Can form upto 64 nucleated erythroid precursor cells.
Both these Progenitor cells cannot be distinguished except by in vitro culture methods. ERYTHROPOIESIS : ERYTHROPOIESIS Normoblastic Precursors : Normoblastic Precursors PROERYTHROBLAST:
Large cell: 14 – 20 Microns in diameter.
Cytoplasm is deep violet-blue staining
Has no Hemoglobin.
Large nucleus 12 Microns occupies 3/4th of the cell volume.
Nucleus has fine stippled reticulum & 2-5 nucleoli. Normoblastic Precursors : Normoblastic Precursors EARLY NORMOBLAST:
Smaller in size 12-16 microns.
Shows active Mitosis.
No nucleoli in the nucleus.
Fine chromatin network with few condensation nodes found.
Hemoglobin begins to form.
Cytoplasm still Basophilic. Normoblastic Precursors : Normoblastic Precursors INTERMEDIATE NORMOBLAST:
Has a diameter of 12 – 14 Microns.
Shows active Mitosis.
Increased Hemoglobin content in the cytoplasm
Cytoplasm is Polychromatophilic. Normoblastic Precursors : Normoblastic Precursors LATE NORMOBLAST:
Diameter is 8 – 12 Microns.
Nucleus shrinks with condensed chromatin.
Appears like a “Cartwheel”
Cytoplasm has a Eosinophilic appearance. Normoblastic Precursors : Normoblastic Precursors RETICULOCYTE:
The penultimate stage cell.
Has a fine network of reticulum like clumps of dots
This is the remnant of the basophilic cytoplasm, comprising RNA.
In the Neonates, Count is 2 – 6/Cu.mm.
Falls to <1 in the first week of life.
Reticulocytosis is the first change seen in patients treated with Vit B12 Normoblastic Precursors : Normoblastic Precursors MATURE ERYTHROCYTE:
About One-third filled with Hemoglobin.
Diameter is 7.5 micron Dyserythropoiesis : Dyserythropoiesis Abnormal red cells are produced
These cells are destroyed in the marrow before their release or enter circulation
They have shortened life span
Morphological abnormalities are :
Premature nuclear extrusion
Basophilic stippling of the cytoplasm
Howel jolly bodies in red cells eg. In megaloblastic anaemia congenital dyserythropoietic anaemias Ineffective erythropoiesis : Ineffective erythropoiesis Erythroid hyperplasia in the marrow, but patient is anaemic
Eg. Megaloblastic anaemias : Marked erythroid hyperplasia in marrow but these megaloblast die in marrow resulting in ineffective erythropoiesis
In such cases reticulocyte count is normal /low inspite of erythroid hyperplasia Slide 25: Production of Erythrocytes: Erythropoiesis Slide 26: Hematopoiesis Factors affecting erythropoiesis:-
A)-Oxygen supply of tissues:
Decreased oxygen supply (hypoxia) to tissues stimulates secretion of erythropoietin (EP) hormone.
Hypoxia stimulates kidney to release renal erythropoietic factor (REF).
Hypoxia stimulates liver to produce a special type of globulin.
Both REF & globulin unite in plasma and form EP.
EP then stimulates bone marrow to produce RBCs.
Erythropoietin accelerates nearly all stages of RBCs formation,
i.e. it stimulates proliferation & differentiation of progenitor stem cells to produce mature RBCs. Slide 27: Erythropoietin Mechanism Figure 17.6 Imbalance Reduces O2 levels in blood Erythropoietin stimulates red bone marrow Enhanced erythropoiesis increases RBC count Normal blood oxygen levels Stimulus: Hypoxia due to decreased RBC count, decreased availability of O2 to blood, or increased tissue demands for O2 Imbalance Start Kidney (and liver to a smaller extent) releases erythropoietin Increases O2-carrying ability of blood Regulation of Erythropoiesis : Regulation of Erythropoiesis CFU – E
Poor blood flow
Pulmonary Disease ERYTHROPOIETIN Decreases Stimulates An example of a
Negative feed back
mechanism Slide 29: Hematopoiesis Factors affecting erythropoiesis:-
B) Dietary factors:
i-Proteins: Proteins of high biological value are needed in the formation of RBCs.
Iron Fe: is essential for RBCs formation because it enters in the formation of the hem part.
Copper Cu: It is carried & transported by plasma protein ceruloplasmin. It catalyses the oxidation of Fe++ to Fe+++, a reaction that must occur before transferrin can combine and transport iron.
Cobalt Co: It stimulates EP release from kidney. So, excess Co may produce polycythaemia. Slide 30: Factors affecting erythropoiesis:-
B) Dietary factors:
Both vitamins B12 & folic acid are essential for final maturation of RBCs because they are needed in DNA synthesis.
Deficiency of either B12 or folic acid results in failure of nuclear maturation and causing maturation failure anemia.
Vitamin C is a strong reducing agent which is important in reducing the ferric form of iron to ferrous to facilitate its absorption and transport. Hematopoiesis Slide 31: Factors affecting erythropoiesis:-
C) Hormonal factors:
i-Androgens: increase erythropoiesis by stimulating the production of erythropoietin from kidney.
Stimulate the metabolism of all body cells including the bone marrow cells, thus, increasing erythropoiesis.
Hypothyroidism is associated with anemia while hyperthyroidism is associated with polycythaemia. Hematopoiesis Slide 32: Hematopoiesis Factors affecting erythropoiesis:-
C) Hormonal factors:
Stimulate the general metabolism and also stimulate the bone marrow to produce more RBCs.
In Addison’s disease (hypofunction of adrenal cortex) anemia present, while in Cushing’s disease (hyperfunction of adrenal cortex) polycythaemia present. Hematopoiesis : Hematopoiesis Factors affecting erythropoiesis:-
IV- Pituitary gland: Affects erythropoiesis both directly and indirectly through the action of several hormones.
V- Haematopoietic growth factors: Are secreted by lymphocytes, monocytes & macrophages to regulate the proliferation and differentiation of proginator stem cells to produce blood cells. Slide 34: Factors affecting erythropoiesis:-
D)-State of liver & bone marrow:
i-Liver: Healthy liver is essential for normal erythropoiesis because the liver is the main site for storage of vitamin B12 , folic acid, iron & copper. In chronic liver disease anemia occurs.
ii-Bone marrow: When bone marrow is destroyed by ionizing irradiation or drugs, aplastic anemia occurs. Hematopoiesis Slide 35: Thank you!