UG SEM-IV
CC-9T: Animal Physiology:Life Sustaining Systems

Unit 3: Physiology of Circulation

HAEMOPOIESIS

(Basic steps & its regulation)

SANJIB KR. DAS

ASST. PROFESSOR (WBES)

DEPT. OF ZOOLOGY

JHARGRAM RAJ COLLEGE

15 July 2020 sanjib.biology2012gmail.com 1

HAEMOPOIESIS

• General term for production of blood cells
from Haemopoietic stem cell.

• It includes

Erytropoiesis

Leucopoiesis

Thrombopoiesis

15 July 2020 sanjib.biology2012gmail.com 2

Sites of Haemopoiesis

3rd week of intra-uterine life –area
vasculosa of yolk

In liver & Spleen – 3rd month of
intra –uterine life

Bone marrow-5th month of intra-
uterine life & after birth

15 July 2020 sanjib.biology2012gmail.com 3

15 July 2020 sanjib.biology2012gmail.com 4

Bone Marrow

RED marrow – active, found inside all
bones till the age of 20 years, most of it
replaced by yellow marrow. adult pattern of
marrow distribution – cranial bones,
vertebrae, pelvic bones, ribs, sternum,
upper ends of femur & humerus.

YELLOW marrow – inactive, filled with fatty
tissue, on demand become active converted
into red marrow producing blood cells.

15 July 2020 sanjib.biology2012gmail.com 5

Haemopoetic stem cells

• The blood cells begin their lives in the bone marrow from a single type of cell
called the pluripotential hematopoietic stem cell, from which all the cells of
the circulating blood are eventually derived.

• As these cells reproduce, a small portion of them remains exactly like the
original pluripotential cells and is retained in the bone marrow to maintain a
supply of these, although their numbers diminish with age.

• Most of the reproduced cells, however, differentiate to form the other cell
types.

• The intermediate stage cells are very much like the pluripotential stem cells,
even though they have already become committed to a particular line of cells
and are called committed stem cells.

• The different committed stem cells, when grown in culture, will produce
colonies of specific types of blood cells. A committed stem cell that produces
erythrocytes is called a colony-forming unit–erythrocyte, and the
abbreviation CFU-E is used to designate this type of stem cell. Likewise,
colony-forming units that form granulocytes and monocytes have the
designation CFU-GM, and so forth.

15 July 2020 sanjib.biology2012gmail.com 6

• Growth and reproduction of the different stem cells are controlled by
multiple proteins called growth inducers.

• Four major growth inducers have been described, each having different
characteristics. One of these, interleukin-3, promotes growth and
reproduction of virtually all the different types of committed stem cells,
whereas the others induce growth of only specific types of cells.

• The growth inducers promote growth but not differentiation of the cells.

• This is the function of another set of proteins called differentiation
inducers. Each of these causes one type of committed stem cell to
differentiate one or more steps toward a final adult blood cell.

• Formation of the growth inducers and differentiation inducers is itself
controlled by factors outside the bone marrow. For instance, in the case of
erythrocytes (red blood cells), exposure of the blood to low oxygen for a
long time results in growth induction, differentiation, and production of
greatly increased numbers of erythrocytes.

• In the case of some of the white blood cells, infectious diseases cause
growth, differentiation, and eventual formation of specific types of white
blood cells that are needed to combat each infection.

15 July 2020 sanjib.biology2012gmail.com 7

Haemopoetic stem cells

Stem cell (pluripotent)

Stem cells
Stem cells

(committed to produce blood
(pluripotent)

cells)

Formation of

RBCs,Granulocytes,Monocytes
Formation of Lymphocytes

&

platelets

15 July 2020 sanjib.biology2012gmail.com 8

Formation of the multiple different blood cells from the original pluripotent
hematopoietic stem cell (PHSC) in the bone marrow.

15 July 2020 sanjib.biology2012gmail.com 9

Cell Renewal

 Progenitor cells – in between committed stem
cells & blast cells.

Eg. Progenitor of erythrocytic series

 Blast cells –immature cells found in the early
stages of development, normally not found in
peripheral blood but only in bone marrow

Eg. erythroblast, myeloblast,
megakaryoblast, lymphoblast, monoblast

15 July 2020 sanjib.biology2012gmail.com 10

15 July 2020 sanjib.biology2012gmail.com 11

Erythropoiesis: Genesis of RBC

• The first cell that can be identified as belonging to the red blood cell series is the
proerythroblast. Under appropriate stimulation, large numbers of these cells are
formed from the CFU-E stem cells.

• Once the proerythroblast has been formed, it divides multiple times, eventually forming
many mature red blood cells. The first-generation cells are called basophil erythroblasts
because they stain with basic dyes; the cell at this time has accumulated very little
hemoglobin.

• In the succeeding generations, the cells become filled with hemoglobin to a
concentration of about 34 per cent, the nucleus condenses to a small size, and its final
remnant is absorbed or extruded from the cell.

• At the same time, the endoplasmic reticulum is also reabsorbed. The cell at this stage is
called a reticulocyte because it still contains a small amount of basophilic material,
consisting of remnants of the Golgi apparatus, mitochondria, and a few other
cytoplasmic organelles.

• During this reticulocyte stage, the cells pass from the bone marrow into the blood
capillaries by diapedesis (squeezing through the pores of the capillary membrane).

• The remaining basophilic material in the reticulocyte normally disappears within 1 to 2
days, and the cell is then a mature erythrocyte. Because of the short life of the
reticulocytes, their concentration among all the red cells of the blood is normally
slightly less than 1 per cent.

15 July 2020 sanjib.biology2012gmail.com 12

15 July 2020 sanjib.biology2012gmail.com 13

Steps of Erythropoiesis:

Stem cell Committed stem cell
Progenitor cells BFU-E CFU-E
Proerythroblast (15-20u) Early
normoblast (10-17u) Intermediate
normoblast (10-14u) Late normoblast(7-
10u) Reticulocyte Erythrocyte (7.2u)

15 July 2020 sanjib.biology2012gmail.com 14

15 July 2020 sanjib.biology2012gmail.com 15

Regulation of Red Blood Cell Production—Role of
Erythropoietin

• The total mass of red blood cells in the circulatory system is regulated
within narrow limits, so that

(1) an adequate number of red cells is always available to provide
sufficient transport of oxygen from the lungs to the tissues, yet

(2) the cells do not become so numerous that they impede blood flow.

15 July 2020 sanjib.biology2012gmail.com 16

Tissue Oxygenation Is the Most Essential Regulator of Red Blood Cell
Production

• Any condition that causes the quantity of oxygen transported to the
tissues to decrease ordinarily increases the rate of red blood cell
production.

1.anemic condition due to hemorrhage or any other condition

2.destruction of major portions of the bone marrow by any means

3.At very high altitudes, where the quantity of oxygen in the air is greatly
decreased

4.Various diseases of the circulation that cause decreased blood flow
through the peripheral vessels, and particularly those that cause failure of
oxygen absorption by the blood as it passes through the lungs

Tissue hypoxia resulting from these above conditions
increases red cell production, with a resultant increase in hematocrit and
usually total blood volume as well.

15 July 2020 sanjib.biology2012gmail.com 17

Function of the erythropoietin mechanism to increase production of red
blood cells when tissue oxygenation decreases.

15 July 2020 sanjib.biology2012gmail.com 18

Erythropoietin Stimulates Red Cell Production,
and

Its Formation increases in Response to Hypoxia.

• In the absence of erythropoietin, hypoxia has little or no effect in
stimulating red blood cell production. But when the erythropoietin system
is functional, hypoxia causes a marked increase in erythropoietin
production, and the erythropoietin in turn enhances red blood cell
production until the hypoxia is relieved.

• Renal as well as nonrenal sensor sends signal to the kidneys (renal tubular
epithelial cells) to produce & secrete the erythropoietin under low oxygen
state.

• Erythropoietin a glycoprotein hormone with a molecular weight of about
34,000.

• In the normal person, about 90 per cent of all erythropoietin is formed in
the kidneys; the remainder is formed mainly in the liver.

• Both norepinephrine and epinephrine and prostaglandins stimulate
erythropoietin production.

15 July 2020 sanjib.biology2012gmail.com 19

Leucopoiesis: (Genesis of White Blood Cells)

15 July 2020 sanjib.biology2012gmail.com 20

Leukocytes:

• The leukocytes, also called white blood cells, are the mobile
units of the body’s protective system. They are formed
partially in the bone marrow (granulocytes and monocytes
and a few lymphocytes) and partially in the lymph tissue
(lymphocytes and plasma cells). After formation, they are
transported in the blood to different parts of the body where
they are needed.

15 July 2020 sanjib.biology2012gmail.com 21

15 July 2020 sanjib.biology2012gmail.com 22

Genesis of the White Blood Cells

• Apart from those cells committed to form red blood cells, two major
lineages of white blood cells are formed, the myelocytic and the
lymphocytic lineages.

• The granulocytes and monocytes are formed only in the bone marrow.

• Lymphocytes and plasma cells are produced mainly in the various
lymphogenous tissues—especially the lymph glands, spleen, thymus,
tonsils, and various pockets of lymphoid tissue.

• The white blood cells formed in the bone marrow are stored within the
marrow until they are needed in the circulatory system. Then, when the
need arises, various factors cause them to be released.

• The lymphocytes are mostly stored in the various lymphoid tissues, except
for a small number that are temporarily being transported in the blood.

15 July 2020 sanjib.biology2012gmail.com 23

1, myeloblast;
2,promyelocyte;
3, megakaryocyte;
4, neutrophil myelocyte;
5, young neutrophil metamyelocyte;
6,“band” neutrophil metamyelocyte;
7, polymorphonuclear neutrophil;
8, eosinophil myelocyte;
9,eosinophil metamyelocyte;
10,polymorphonuclear eosinophil;
11, basophil myelocyte;
12, polymorphonuclearbasophil;
13–16,stages of monocyte formation

Genesis of white blood cells. The different cells of the myelocyte series.

15 July 2020 sanjib.biology2012gmail.com 24

15 July 2020 sanjib.biology2012gmail.com 25

15 July 2020 sanjib.biology2012gmail.com 26

15 July 2020 sanjib.biology2012gmail.com 27

Control of White Blood Cell Production

• The cause of the increased production of granulocytes and monocytes by
the bone marrow is mainly the three colony-stimulating factors, one of
which, GM-CSF (granulocyte-monocyte colony-stimulating factor),
stimulates both granulocyte and monocyte production; the other two, G-
CSF (granulocyte colony-stimulating factor) and M-CSF (monocyte colony-
stimulating factor), stimulate granulocyte and monocyte production,
respectively.

• These factors are formed by activated macrophage cells in the inflamed
tissues

• This combination of TNF (tumor necrosis factor), IL-1 (interleukin-1) , and
colony-stimulating factors provides a powerful feedback mechanism that
begins with tissue inflammation and proceeds to formation of large
numbers of defensive white blood cells that help remove the cause of the
inflammation.

15 July 2020 sanjib.biology2012gmail.com 28

Control of bone marrow production of granulocytes and monocyte- macrophages in response
to multiple growth factors released from activated macrophages in an inflamed tissue.

15 July 2020 sanjib.biology2012gmail.com 29

15 July 2020 sanjib.biology2012gmail.com 30

Thrombopoiesis : Genesis of Platelets

15 July 2020 sanjib.biology2012gmail.com 31

Platelets

• Platelets (also called thrombocytes) are minute discs 1 to 4 micrometers in
diameter.

• They are formed in the bone marrow from megakaryocytes, which are
extremely large cells of the hematopoietic series in the marrow.

• The megakaryocytes fragment into the minute platelets either in the bone
marrow or soon after entering the blood, especially as they squeeze
through capillaries.

• The normal concentration of platelets in the blood is between 150,000
and 300,000 per microliter

15 July 2020 sanjib.biology2012gmail.com 32

15 July 2020 sanjib.biology2012gmail.com 33

Reference:

15 July 2020 sanjib.biology2012gmail.com 34