Haemopoiesis

Composition of Whole Blood & its Components

Characteristics
1) Temperature: 38C
2) pH: Slightly alkaline (7.35-7.45)
3) Composition:
 78% water and 22% solids

Plasma 55 % (~ 3.5 L) Formed elements 45%

Liquid component of blood in which the cells are Red cells (erythrocytes) 99%
suspended Platelets < 1%
Complex aqueous solution containing gases, White cells (leukocytes) < 1%
salts, proteins, carbohydrates & lipids.

Functions of Blood

Carries TO the body tissues Carries AWAY from the tissues

• oxygen • waste matter
• nutrients • carbon dioxide
• hormones
• water
• solutes
• heat

Sites, Steps & Factors Involved in Haemopoiesis

Factors:

 Single stem cells grow and divide in bone marrow to produce >106 mature cells
 Lose Cell Adhesion Molecules (CAMs) (cells can leave marrow & enter circulation)
 Require Growth Factors
– Erythropoietin
– Colony Stimulating Factors
– Interleukins
– Thrombopoietin

Sites:

In developing embryos, blood formation occurs in the yolk sac.

As foetal development progresses, it beings in the liver (6th week ), spleen (2nd month), and lymph
nodes.
When bone marrow develops, it eventually assumes the task of forming most of the blood cells for
the entire organism. However, maturation, activation, and some proliferation of lymphoid cells still
occurs in the spleen and lymph nodes.

In children, it occurs in the marrow of the long bones such as the femur and tibia.
In adults, it occurs mainly in the pelvis, cranium, vertebrae, and sternum.
In some cases, the liver, thymus, and spleen may resume their haematopoietic function, if
necessary. This is called extramedullary haematopoiesis.

Erythropoiesis
 Foetus
– Yolk sac
– Liver
– Spleen
– Red Bone marrow
 Adult
– Red Bone marrow
– Extramedullary
One proerythroblast gives rise to about 16 mature red blood cells.
Erythropoiesis occurs in the bone marrow. Erythropoietin hormone is produced in the kidneys. It
circulates in the plasma and induces red cell production in the bone marrow, where it binds to
erythroid progenitor cells.

Essential Ingredients for Erythropoiesis

 Amino acids
 Vitamins - B12 & folate
 Iron - 60-70% of iron in body is in haemoglobin

Characteristics and Life Cycle of Erythrocytes

Red Blood Cell Haemoglobin

Biconcave disc (7.5 µm diameter)
No nucleus or organelles
Shape:
 Enhances the diffusion of gases
 Increases the surface area
 Increases flexibility
 Its thinness enables oxygen to diffuse
rapidly
Life span = 120 days
Senescent RBC’s removed by macrophages
Haemoglobin components are recycled:
 Globin into amino acids then reutilized
 Iron reutilised
 Haem excreted in bile
Only in RBC’s
Four folded globin polypeptide chains
Each binds one Fe2+containing haem moiety
 Adult (A) 2β2
 Foetus (F) 22
Affinity of haemoglobin for oxygen is affected
by:
pH, Temp, 2,3-diphosphoglycerate conc. and
changes in polypeptide subunits of globin.
White Blood Cells

Five types of leukocyte in the blood:

• neutrophils
• eosinophils
• basophils
• lymphocytes
• monocytes

Polymorphs - Neutrophils, eosinophils and basophils (multilobed nuclei).

Granulocytes - Neutrophils, eosinophils and basophils have granules in their cytoplasm.
Agranulocytes - Lymphocytes and monocytes have no cytoplasmic granules,

Neutrophils (40-75%)

• phagocytic - they consume bacteria.

• Some granules produce antibacterial proteins and some are lysosomes.

Eosinophils (2-4%)
• Basic Granules that take up acidic stains.
• Bilobed nuclei.
• Granules specialised for the removal of antigen-antibody complexes.

Basophil (<1%)
• Acidic granules that take up basic stains. Overshadow bilobed nuclei.
• Granules contain heparin and histamine (inflammatory response).

Lymphocytes (20-30%)
• Large nucleus with small ring of cytoplasm
• normal immune responses to foreign bodies such as bacteria and viruses.

Monocytes (5%)
• largest leukocytes
• small granules – lysosomes that stain for acid phosphatase
• exit circulation via capillary fenestrations. Subsequently called macrophages.
• Indented nucleus – plenty cytoplasm.
• Capable of cell division and manufacturing lysosomes.

Leukocyte Stains
Granulocytes
• Neutrophils: Granules neutral — stain poorly
• Eosinophils: Granules have affinity for acidic stains (like eosin)— stain red
• Basophils: Granules have affinity for basic stains (like haematoxylin) — stain blue
Agranulocytes (no granules)
• Lymphocytes: Affinity for basic stains — stain light blue, with darker blue nucleus
• Monocytes: Affinity for basic stains — stain light blue, with darker blue nucleus

Neutrophils and eosinophils constitute forward defence against microorganisms. Pus consists of
millions of dead and dying neutrophils and eosinophils. Eosinophilia suggests allergy or
hypersensitivity, and this may be found during an asthmatic attack, an allergic reaction or a parasitic
infestation. After an episode of heavy bleeding, the body tries to compensate for the loss of oxygen
carrying capacity by releasing red cells from the bone marrow into the circulation more quickly than
normal. This means that some red cells which are not fully developed (reticulocytes) are released.
The presence of many reticulocytes in the blood is evidence that bleeding has occurred.
Haematological Indic es

1) Full Blood Count (FBC)/Complete Blood Count (CBC)

Measures blood cell counts of red blood cells, white blood cells and platelets.

2) Red Cell Count (RCC) = 4.5 - 5.4 x 106/mL. 4.0-5.0 for women, 4.6-6.0 for men.

3) Packed Cell Volume = haematocrit = 45 %

Measures the fraction of blood occupied by red blood cells.

4) Haemoglobin = 14-18 g/dL male, 12-16 g/dL females

Amount of Hb in blood, indicator of iron binding capability

5) Mean Cell/Corpuscular Haemoglobin (MCH)

Concentration of Hb in average RBC
Hb concentration/red-cell count = 27-33 pg

6) Mean Cell Haemoglobin Concentration (MCHC)

Concentration of Hb per dL RBC
Hb concentration/haematocrit = 32-35 g/dL

7) Mean Cell Volume (MCV)

Size/Volume of the average RBC (80-90 fL)
Haematocrit/red cell count

8) Reticulocytes (%) = 0.2-2 %

Erythropoietic activity in the bone marrow.
If a patient is anaemic and the reticulocyte count is high, then it is most likely that
red cells are being destroyed in the periphery (haemolytic anaemia)

Polycythaemia
 Too many RBCs
 Increase in Hb / RBC / PCV above reference level for age & gender
 Occurs in hypoxic conditions, at high altitude

 Primary polycythaemia
– Tumour-like condition of the bone marrow in which erythropoiesis proceeds at an
excessive uncontrolled rate
– Polycythaemia Vera

 Secondary polycythaemia
– Appropriate erythropoietin-induced adaptive mechanism to improve the blood’s
oxygen-carrying capacity in response to a prolonged reduction in oxygen delivery to
the tissues
– Physiologic Polycythaemia

 Relative polycythaemia
– Body loses fluid but not erythrocytes

Because of increased viscosity, there is a tendency to thrombosis, particularly cerebral. The spleen
is frequently enlarged.
Anaemia
Deficiency of haemoglobin in the blood
1) Decreased RBC production
2) Increased Erythrocyte destruction/loss
3) Blood loss

Characteristics:
 decreased rate of erythropoiesis or a deficiency in the haemoglobin content of erythrocytes.
 decrease in Hb / RBC / PCV below reference level for age & gender.
 occurs in iron deficiency, blood loss, B12 or folate deficiency

Clinical Signs:
Pallor - an abnormal loss of skin or mucous membrane color.
Koilonychia - the nail curves upwards (becomes spoon-shaped)
Angular stomatitis - deep cracks and splits form at the corners of the mouth
Glossitis - inflammation or infection of the tongue

Types:
 Hypochromic-microcytic (cells are small due to less Fe2+ inside and thus less O2)
– Iron deficiency (most common)
– Anaemia of chronic disease
– Blood loss is the most common cause of iron deficiency in adults.
• Acute blood loss (trauma, postpartum bleeding)
• Chronic blood loss
– In men and postmenopausal women, iron deficiency usually indicates bleeding in
the digestive tract.
– In premenopausal women, menstrual bleeding is the most common cause of iron
deficiency.
– Iron deficiency may also result from too little iron in the diet.

 Normochromic macrocytic (Raised MCV)

– Folate deficiency
– Vitamin B12 deficiency
– Body normally stores 3 year’s supply of vitamin B12
• Onset is slow
– Vitamin B12 absorbed only when in complex with gastric intrinsic factor
• glycoprotein secreted by stomach parietal cells
• complex resistant to proteolysis
• binds specific receptor on cells in distal ileum
– Pernicious anaemia is specifically caused by malabsorption of vitamin B12 due to
lack of intrinsic factor.

 Polychromatophilic macrocytic
– Haemolytic
– Genetic disorders
• Haemoglobin – sickle cell anaemias
• RBC membrane – hereditary spherocytosis
– Acquired disorders
• Immune – ABO or Rh incompatibility

Clinical Evaluation
 Review of blood count, blood smear and RBC indices (MCV, MCH, MCHC)
 Reticulocyte index
 Determination of acuteness or chronicity
Hematocrit Under Various Conditions

Pancytopenia – suppressed CBC (decrease in all formed elements)

Thrombocytopenia – Decreased Thrombocytes
can result in many small bleeding episodes anywhere in the body. Symptoms vary depending on the
site of the mini-haemorrhages. For example, if the mini-haemorrhages are in the skin, the skin will
appear to have many tiny red dots (purpura) like a rash. Thrombocytopenia occurs most often in
children and young adults, and often follows a viral infection. It is thought to be an autoimmune
disease in which antibodies attack the platelets.

Leukopenia – Decreased WBC

Leucocytosis – Increased WBC
Erythrocyte Diseases

In spherocytosis, erythrocytes are small and spherical. This poses problems for oxygen
exchange because the central portions of the cell are farther away from the surface than in a
normal biconcave cell. The spleen recognises these erythrocytes as abnormal and destroys
them, further compounding the problems.

In sickle cell disease, erythrocytes contain an abnormal form of haemoglobin which causes
them to assume a sickle shape. As in spherocytosis, the spleen destroys these abnormal
cells.
People with sickle cell disease tend to be more resistant to malaria. Thus in a community
where malaria is prevalent, the person with sickle cell disease would have a good chance of
breeding and passing on their genes, so the gene for sickle cell haemoglobin may be
favoured in places where malaria is endemic.
Thalassaemia is caused by abnormal haemoglobin. Erythrocytes are smaller than normal
and their oxygen carrying capacity is reduced.

The term, leukaemia, includes several conditions, some more serious than others. In short,
you can think of them as being conditions in which haemopoietic tissues produce many
defective white cells, so that there are huge numbers of them in the bone marrow spilling
over into the blood. The problem is that they do not work properly, so the patient suffers
from a variety of problems which include anaemia, susceptibility to infections and
haemorrhage.