Haemopoiesis

It is the process by which blood cells are formed.

Site of haemopoiesis: varies with the age of individual. In adult, RBCs, WBCs and platelets are
formed in the bone marrow.

Erythropoiesis
Definition: It is the process of RBC formation.
Duration: 7- 10 days
Sites:
1. Intrauterine life (Fetal life)
up to 2nd month - yolk sac
2nd to 7th month – Liver and spleen
7th to 9th month – Bone marrow become the major site
2. After birth
Infancy - throughout skeleton
(up to 1 yr)
7 years - marrow becomes slightly fatty & activity begins to decline in the bones of the
extremities and to a certain extent in other bones
> 20 years - in red marrow upper ends of humerus & femur, flat bones (skull, ribs, sternum)
Extramedullary haemopoiesis - Diseases - bone marrow is destroyed or fibrosed
demand for RBCs > supply by bone marrow

Stages
The cell up to the intermediate normoblast show mitotic division. Cells up to reticulocyte stay in
the bone marrow while mature erythrocytes enter the circulation. Circulating reticulocyte
count: 0.5-1% of RBC).

Maturation of RBC is characterized by

1. Redcution in the cell size

2. Increase in the amount of haemoglobin

3. Disappearance of nucleus, and

4. Change in staining characteristics of cytoplasm: basophilic to eosinophilic due to a fall in

content of RNA.

Haemoglobin (red oxygen carrying pigment in RBC)

✓ Haemoglobin, the red oxygen-carrying pigment in the RBC, is made up of four subunits.
✓ Each subunit contains a haem moiety (an iron-containing porphyrin derivative)
conjugated to a polypeptide.
✓ The polypeptides are referred to as the globin portion of the Hb.

Types of Haemoglobin
▪ Hb A 2 and 2 polypeptide chains
▪ Hb A2 (2.5%) 2 and 2 polypeptide chains

Functions of Hb
Heme portion – carries O2 as oxyhaemoglobin
Globin portion – carries CO2 as carbaminohaemoglobin
Aminoacid in globin – regulate the blood pH by acting as buffers
 Control of Erythropoiesis
I. Nutritional factors
a. Proteins→ glycine for heme synthesis and other amino acids for globin synthesis
b. Vitamins→ vitamin B6 heme synthesis , vitamin C for intestinal absorption of iron(Fe2+) and
vitamin B12 and folic acid for maturation of RBC.
c. Minerals→ iron and copper for heme synthesis and cobalt salts as a constituent of vitamin
B12
d. Maturation factors (vitamin B12 and folic acid)
It plays an important role in DNA synthesis (replication). In the absence of either of these
vitamins, cell division slow down and result in formation of immature large cells.
Proerythroblasts give rise to megaloblasts which appear as large red cells called macrocytes.
These abnormal cells are destroyed by macrophages. This produces megaloblastic macrocytic
anaemia.

Anaemia due to Iron Deficiency Anaemia

Causes: dietary deficiency, absorption defect and blood loss. Common in tropical countries.
Iron is essential for heme synthesis.
Blood picture: Hypochromic microcytic anaemia
Anaemia due to folic acid deficiency
It is common in period of rapid growth. E.g. Pregnant and growing children
Anaemia due to vitamin B12 deficiency
i. Dietary deficiency eg. vegetarians
ii. After removal of stomach: Stomach secretes intrinsic factor of Castle which is essential for vit
B 12 absorption in terminal ileum.
iii. Gastric atrophy e.g. Pernicious anaemia

II. Factors influencing Bone marrow activity

a. Stimulating factors
i. Erythropoietin
Source: It is a glycoprotein hormone secreted by the kidney (85%) and the liver (15%).
Regulation: erythropoietin secretion is stimulated by androgen, alkalosis (high altitude), cobalt
salts, catecholamine and hypoxia.
Action: erythropoietin stimulates erythropoiesis by promoting the differentiation of committed
stem cells into proerythroblasts. It acts by stimulating mRNA synthesis.
Function: It is fundamental regulating factor.
ii. Colony stimulating factors
IL-1, 3, 6 and GM-CSF, G-CSF, stem cell factor (SCF) which are secreted by endothelial cells,
fibroblasts and macrophages (monocyte)
iii. Other hormones
Erythropoiesis is stimulated by thyroid hormones and androgen.

b. Inhibiting factors
Urea, bacteria toxins, radiation, cytotoxic drugs cause bone marrow depression.

Physiogical basis of Anaemia

Definition: Anaemia is defined as a reduction in the haemoglobin concentration of the
circulating blood below the normal for that age and sex of the individual.
Normal Values:
Western value Myanmar value
Male 16g∕dl (14-17 g/dl) 14.4g∕dl (14-16)
Female 14g∕dl (12-15.5 g/dl) 12.5g∕dl (11-14)
Causes of anaemia
I. Impaired red cell formation
a. Due to deficiency of nutritional factors:
Iron Deficiency Anaemia
Causes: dietary deficiency, absorption defect and blood loss. Common in tropical countries.
Iron is essential for heme synthesis.
Blood picture: Hypochromic microcytic anaemia

B12 deficiency anaemia

Causes: dietary deficiency, absorption defect (removal of stomach, Gastric atrophy e.g.
Pernicious anaemia) due to lack of intrinsic factor which is required for B12 absorption.
Common in vegetarians.
It plays an important role in DNA synthesis (replication). In the absence of either of these
vitamins, cell division slow down and result in formation of immature large cells.
Proerythroblasts give rise to megaloblasts which appear as large red cells called macrocytes.
These abnormal cells are destroyed by macrophages. This produces megaloblastic macrocytic
anaemia.
Blood picture: Megaloblastic macrocytic anaemia
Folic Acid Deficiency Anaemia
Causes: It is common in period of rapid growth. E.g. Pregnant and growing children
Folic acid is a maturation factor. It is also required for DNA synthesis.
Blood picture: Megaloblastic macrocytic anaemia

b. Due to lack of stimulating factors

i. Chronic Renal Failure
Decrease erythropoietin secretion →decrease RBC formation. Erythropoietin is secreted by
kidneys. Erythropoietin is the fundamental regulating factor for erythropoiesis. Erythropoietin
promotes differentiation of commitment stem cell to proerythroblast.
Blood picture: Normochromic normocytic anaemia
ii. Hypothyroidism
Hypothyroid patient may suffer anaemia because thyroid hormone stimulates erythropoiesis.

c. Due to bone marrow depression

Increase blood urea (renal failure), radiation, cytotoxic drugs and bacterial toxin→ depress
bone marrow →decrease RBC formation.

d. Due to infiltration of bone marrow by other cells

Tumour cells infiltrate the marrow → blood cells formation are impaired

II. Increased red cells destruction

G6PD deficiency, hereditary spherocytosis, sickle cell anaemia and erythroblastosis fetalis cause
haemolysis. This produces haemolytic anaemia.

III. Blood loss – Haemorrhage