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Composition of
Blood and Hematopoiesis

Lesson Outcomes
• Describe the components of blood and outline the functions of blood

• Discuss the functions of plasma proteins

• Discuss the structure and functions of red blood cells and describe the different stages of
erythropoiesis

• Compare the different types of leucocytes and describe the different stages of leucopoiesis

• Discuss the functions of platelets

• State the site of production of blood cells in fetus and in adults

• Explain the role of erythropoietin in erythropoiesis

• Name the factors affecting hematopoiesis

Connective Tissue
• Connective tissue is found throughout the body; the most abundant and widely
distributed of primary tissues
• They provide support for all organs and have a dynamic function in development, growth
and homeostasis

Functions of CT:

• Binding and Support

• Protection
• Insulation
• Transportation

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Blood
• Blood is Connective tissue - Continuously circulating, transports materials in the circulation
• Blood Volume:
• Adult Male: 5 – 6 L,
• Female: 4 - 5 L
• New born baby - 250ml

• Blood Viscosity – 1.1 to 1.2 centipoise

• Inherent resistance of blood to flow – influenced by red cells and proteins
• Increased blood viscosity has been linked with all of the major cardiovascular risk factors (hypertension,
high cholesterol, diabetes, metabolic syndrome, obesity, smoking)
• The combination of a high hematocrit and a high fibrinogen level lead to extremely high viscosities

• pH: 7.4 [ 7.35 – 7.45 (slightly alkaline) ]

• Osmolarity : 285 -295 mOsm/L

Blood
• Represents about 8% of total body weight

• Makes one fourth of the ECF

• Blood in the Circulatory System

• Cessation of blood circulation will severely impair tissue
function, within a few minutes causes irreversible damage or
death of the highly susceptible brain cells

• Blood – Is complex of liquid plasma in which the cellular

elements erythrocytes, leukocytes and platelets are
suspended

• Constant motion of blood keeps its cellular elements

dispersed within the extracellular fluid (plasma)

Functions of Blood
Transport:
• Carry the nutrients to different parts of the body
• Transport of respiratory gases [oxygen and carbon dioxide]
• Waste products are carried to the excretory organs like kidney, skin and liver
• Transport of hormones and enzymes to different parts from the site of secretion
Regulation :
• Maintain homeostasis of body fluids
• Regulation of acid base balance (plasma proteins and hemoglobin)
• Regulation of water balance
• Regulation of body temperature
Protection:
• Hemostasis
• White blood cells
• Blood proteins – antibodies, interferons

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Components of Blood
Formed
• Organic substances are proteins, carbohydrates,
Plasma Elements
fats, amino acids, vitamins, non-protein
nitrogenous substances, bilirubin, hormones,
enzymes etc. • 46 - 63% • 37 – 54%
• Inorganic substances are Na+, Cl-, K+, Ca++, HCO3-
iron, iodide, copper, phosphates, zinc etc. • Water – 92% • Red Blood Cells [RBC]
• Liver cells (hepatocytes) synthesize most of the
proteins • Plasma Proteins – 7% • White Blood Cells
• There are three groups of plasma proteins –
albumin, globulin and fibrinogen • Other solutes – 1% [WBC]
• Platelets

Plasma – Anticoagulated blood from which cellular components have been removed by centrifugation
Plasma contains blood coagulation proteins

Serum – Liquid in blood that has been collected without an anticoagulant

Yellow in colour where many of the proteins have clotted

Plasma Proteins
• Albumin
• Most abundant (60%); major plasma protein
• Contribute to osmotic pressure of plasma (25 mmHg)
• Transport lipids, bilirubin, fatty acids and steroid hormones
• Has maximum buffering capacity amongst all proteins
• Albumin-free fatty acid complex can not cross blood brain barrier –
hence fatty acids can not be utilized by the brain
• Loosely bound bilirubin to albumin can be easily replaced by drugs
like aspirin (if newborn is given aspirin, that will release bilirubin,
which gets accumulated to cause Kernicterus)
• Hypoalbuminemia will result in tissue edema (malnutrition,
nephrotic syndrome, cirrhosis of liver)
Relative dimensions and approximate
• Albuminaemia – Albumin concentration is less than 1.0g/L molecular masses of protein molecules in the
blood

Plasma Proteins…
• Globulin
• Larger than albumin - Produced by liver and by plasma
cells [during immune response]
• Alpha-1, alpha-2, beta and gamma globulins
• Many of the blood clotting factors are  and  globulins
• Transport metal ions, hormones, lipids
• Gamma globulins – made by lymphoid tissue
• Are the immunoglobulins (antibodies) which are crucial to
the body’s defense mechanism - further fractionated as IgG,
IgA, IgM, IgB, and IgE
• Alpha 1 antitrypsin is the major component of alpha 1
fraction
• It inhibits trypsin, elastase and other proteases (protects
lung tissue from proteases)
• Alpha 1 antitrypsin deficiency – lung tissue destruction
(emphysema)
• Transferrin is a beta 1 globulin which transports iron
• Fibrinogen
• Clotting factor (Clotting factor 1); Large asymmetric
molecule
• Imparts maximum viscosity to blood
• Amino terminal end is highly negative

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Functions of Plasma Proteins

• Coagulation of blood
• Transport
• Plasma oncotic pressure/colloidal osmotic pressure
• The osmotic pressure exerted by proteins in the plasma is called colloidal osmotic pressure.
• It is about 25mmHg
• It has an important role in fluid exchange between blood and tissue fluids
• It is the primary force responsible for preventing excessive loss of plasma from the capillaries into the interstitial
fluid
• Viscosity of blood
• The viscosity of a protein solution depends far more on the shape of the protein molecule than on its size
• Hence fibrinogen exerts highest viscosity and albumin least
• But as albumin concentration is more its contribution for viscosity is more than any other plasma protein
• Acid base balance
• They accept or reject H+ depending on the conditions and thereby maintain blood pH at 7.4
• Their buffering capacity is 15% of the total buffering capacity of the blood
• Erythrocyte sedimentation rate (ESR)
• The rate at which Red Blood Cells (RBCs) sediment in a period of one hour (For males : 0-9 mm/hr; For females 0-20 mm/hr)
• Increase in fibrinogen increases ESR

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Clinical Significance of Plasma Proteins

Hyperproteinemia Hypoproteinemia

Increase in total plasma protein (> 8.0g/L) Decrease in total plasma protein

Caused by Dehydration induced Caused by hemodilution and

hemoconcentration hypoalbuminemia
•Excessive vomiting •Nephrotic syndrome
•Diabetes insipidus •Liver diseases
•Diuresis •Pregnancy
•Diarrhea •Extensive skin burns
•Malabsorption

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Formed Elements of Blood

Red Blood Cell (RBC) or Erythrocyte
Top view
• The red blood cell is simple in terms of its structure and function,
consisting principally of a concentrated solution of hemoglobin
surrounded by a membrane
7.8 micrometers
• It is a specialized, circular, biconcave, non-nucleated cell
• Each RBC is 7.5 micrometer in diameter and 2 micrometer in
thickness 2.5 micrometers

• The mature RBC has no nucleus, no mitochondria and no

Sectional view
ribosome
• Its normal life span is 120 days
• It has cytoplasmic enzymes for metabolizing glucose
• 90% of glucose metabolism occurs via anaerobic glycolysis
(ATP) and 10% via HMP pathway (NADPH)
• Cytoplasmic enzymes also maintain pliability of the cell
membrane, maintain membrane transport of ions, keep the iron
of Hb in ferrous form

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Erythrocytes
• Anucleated and flexible cell membrane → Red cell is able to bend to traverse through 2-3
M capillaries
• The shape of RBC is due to membrane skeleton (strong & flexible)
• Biconcave shape provides a larger surface area for diffusion of O2 and CO2 across the membrane than a
spherical cell of same volume
• Thinness of the cell enables O2 to diffuse rapidly between the exterior and inner most regions

• New red cell is bigger than old cells (more rigid and less deformed)
• RBC packages hemoglobin - Contains 29 picograms (pg) of Hb; 33% of the cell’s weight
• Cells also contain the enzyme carbonic anhydrase (CA), which plays important role in the
carriage of CO2
• The plasma membrane of erythrocytes contain specific polysaccharides and proteins
(form antigens) that differ from person to person

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Red Cell Membrane

• Red cell membrane is made up of three important structural
proteins - spectrin which is anchored to the transmembrane
protein band 3 by protein ankyrin

• Inherited abnormalities of any of these proteins result in

altered shape and flexibility (Deficiency of spectrin results in
hereditary spherocytosis - one of the most common causes of
hereditary hemolytic anemia)

• Red cell volume and ionic content are actively regulated by

energy (ATP) dependent pumps that traverse the membrane

• Defects in the ATP production → loss of cell volume, increased

rigidity and decreased cell survival

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RBC and G6PD

• The red cell contains a battery of cytosolic enzymes, such as superoxide
dismutase, catalase, and glutathione peroxidase, to dispose of powerful oxidants
generated during its metabolism
• Cytoplasmic enzymes also maintain pliability of cell membrane (red cell fragility is
maintained by NADPH), maintain membrane transport of ions, keep the iron of
Hb in ferrous form
• Glucose 6-phosphate dehydrogenase (mediates the generation of NADPH(via
HMP pathway), which in turn reduces glutathione) deficiency increases a normal peripheral blood smear showing
susceptibility of red cells to haemolysis normochromic, normocytic red blood cells

• G6PD deficiency (most common enzyme defect) may result in acute hemolysis
when red cell is exposed to oxidative stress
• Red cells do not have an insulin receptor and thus glucose uptake in RBC is not
regulated by insulin

The function of G6PD in RBC is to

generate NADPH which will
generate reduced glutathione
that protect the RBC’s from
oxidative damage by H2O2

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White Blood Cells (Leukocytes)

• Colorless, nucleated cells without hemoglobin Important for body defense
• Granulocytes and Agranulocytes (4-11X 109/L)
Granulocytes: Neutrophils, Eosinophils and Basophils
Agranulocytes: Lymphocytes and Monocytes
• Mobile units of body’s defense system
“Seek and Destroy” functions - Destroy invading microorganisms; destroy abnormal cells
Clean up cellular debris (phagocytosis) - assist in injury repair

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Leukocytes
Neutrophils
• Polymorphos/polymorphonuclear cells/polys/polymorphs; Size - 10 -12 microns
• Fine granules in cytoplasm, evenly distributed 2 - 5 lobes in the nucleus (segmented nucleus)
• As the cells age – nuclear lobes increases
Eosinophils
• Coarse granules; Stain bright red/orange; stain with acidic dyes
• 10 – 14 microns
• Bilobed nucleus [two lobes in the nucleus]
Basophils
• Dark, Bluish, coarse granules; Stain blue-purple with basic dyes
• Bilobed nucleus; Granules normally cover the nucleus
• 8 – 10 microns
Monocytes
• Agranular leukocyte; Largest leukocyte [14-18 microns]
• Oval or kidney shaped nucleus (mononucleated cell); Blue-grey cytoplasm
• Differentiated into macrophages once they leave circulation
• Fixed macrophages and Wandering macrophages
Lymphocytes
• Agranular - No granules; Cytoplasm forms a rim around the nucleus
• Kidney shaped nucleus; 7 – 12 microns
• Large and small lymphocytes (cell diameter)

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Leukocytes
Neutrophils – 62% Eosinophils – 2%
• Most abundant WBC (constitute 50-80% of the total count in • Increase in reaction to foreign protein
adults); Important in inflammatory response; Bacterial & viral • Parasitic worms, allergies – control inflammation and allergic
infections reactions – Respond to IgE to produce acute allergic response
• Contain lysozyme, oxidants, defensins for phagocytosis • Phagocytose antigen-antibody complexes
• Circulate ~10 to 12h, days in tissues –Functions: phagocytosis • Circulates for about 24 hours
and digest the bacteria and debris
Lymphocytes – 30.0%
Basophils – 0 to 1%
• T and B lymphocytes - major subset based on functions
• T-cells – cell mediated immune response - directly destroy virus • Granules contain histamine, heparin and hyaluronic acid
invaded cells and cancer cells • Histamine – important in allergic (hypersenisitivity) reactions; and
• B-cells – humoral immunity – produce antibodies Heparin - anticoagulant
• Circulate several hours in blood, live for months to years in
tissues
• Only 2% of the total population circulating in the blood – rest Neutrophils and Macrophages kill bacteria -
is in lymphatic organs by bactericidal agents - superoxide (O2–), hydrogen peroxide
Monocytes – 5%
(H2O2), hydrocloritine anion (OCl-)and hydroxyl ions (OH–),
• Spend 1-3 hrs in bone marrow and up to 72 hrs in circulation all of which are lethal to most bacteria, even in small quantities
• 10 –20 hours in blood, months to years in tissues (Tissue
Macrophages)
• Function: Phagocytosis, participate in inflammation and
immune response

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Characteristics of Leukocytes
• Amoeboid movements [neutrophils and monocytes]
Adhesion molecules- help in
• Diapedesis (neutrophils and monocytes can squeeze through adhering to the endothelium

the pores of the blood capillaries) in response to chemotactic

stimuli
• Emigration of white cells
• Chemotaxis (White Blood Cells are attracted to inflamed tissue
areas)
• Small peptide chemicals called chemokines are produced in
the inflamed tissue [kinins, colony stimulating factors
(CSF’s)]
Migration of neutrophil from the blood into inflamed tissue
• Phagocytosis [neutrophils and monocytes]
• Adhesion of neutrophils to endothelial cells employs specific adhesive
proteins (integrins) located on their surface and also specific receptor
proteins in the endothelial cells.

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Platelets
• Small, colorless, anucleated, irregular disc shaped cell fragment
• Bud off from the cytoplasm of bone marrow megakaryocytes
• Contain hemostatic cofactors, coagulation factors, glycoproteins,
phospholipids, actin, myosin, serotonin, histamine in their granules
High-powered view of a large platelet on the left
• The normal platelet count is 150,000 to 400,000/ µ L (150-400X109/L) and normal-sized platelets on the right

• Life span – 5 to 9 days

• Thrombocytosis – increased count
• Thrombocytopenia – decreased count

Functions of Platelets
 Hemostasis –Vasoconstriction and Platelet Plug
 Blood Coagulation – Phospholipids
 For Clot Retraction – Contractile Proteins

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Platelets
Platelet Factors:
• From two specific types of granules (α- and δ-granules)
• - granules -Fibrinogen, von Willebrand factor (vWF),
fibronectin, factors V and VIII, PDGF
• δ-granules (dense granules) - ADP and ATP, ionized calcium,
histamine, serotonin, and epinephrine
• Other platelet factors - Glycoproteins, phospholipids, Actin,
Myosin, Thrombasthenin, Thromboxane A2

Platelet Properties: Platelet production is controlled by

▪Adhesion – due to thromboxane A2, ADP, & von Willebrand thrombopoietin (TP)
factor Causes proliferation and maturation of
megakaryocytes
▪Aggregation – activated platelets become sticky due to ADP TP from - liver, kidney, smooth muscle,
and thromboxane A2 and bone marrow
▪Agglutination – clumping of platelets to form platelet plug

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Hematopoiesis
• Process development of blood cells

• Includes erythropoiesis, leukopoiesis and thrombopoiesis

• Begins early in embryonic life

• Most formed elements survive in the bloodstream only for a few days

• Most blood cells are renewed by cells in the bone marrow

• Mostly in the red bone marrow

• Each day an adult human produces 2 x 1011 erythrocytes, 1 x 1011 leukocytes, and
1 x 1011 platelets

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Sites of Hematopoiesis
• Hematopoiesis begins in yolk sac – 3rd week of embryonic life
• Erythrocytes – first cells
• By 2nd month - granulocyte and megakaryocyte production
• 4th month - lymphocytes production
• 5th month - monocytes produced

• 3rd to 7th month, stem cells migrate to liver and spleen

• At birth and into adulthood - red bone marrow is active

Yolk sac- 3rd to 10th wk
Liver- 6th to 32nd wk
Spleen- 10th to 25th wk
Bone marrow- 30th to 36th wk and also after birth

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Hematopoiesis Stages
Mesoblastic Stage
Hepatic Stage
Myeloid Stage

Mesoblastic Stage - Blood formation begins in mesoderm of the yolk sac – up to 3 months
of fetal life
Primitive blood cells appear in the 2nd to 3rd week of embryonic life

Hepatic Stage - After the third month up to fifth/seventh month of fetal life, liver (hepatic)
and spleen are the important sites of hematopoiesis

Myeloid Stage - After 5th month of fetal life, hemopoiesis occurs in the bone marrow
Hemopoiesis continues within all the bones until age of five

• Active regions of marrow decreases after 4-5 years and replaced by fat (yellow marrow)
• In adults - only the sternum, vertebrae, ribs, clavicles, skull, pelvis and proximal ends of long bones produce blood cells
(red bone marrow)
• Inactive regions of bone marrow, liver and spleen can resume blood cell production in times of need

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Bone Marrow
• Found in the medullary canals of long bones and in the cavities of
cancellous bones

• Red Bone marrow – Hematogenous bone marrow – active marrow

• Yellow bone marrow – Adipocytes; New born – all bone marrow is red
marrow
• Yellow marrow is replaced by red bone marrow – hypoxia, severe
bleeding

• Red marrow – Stroma, hematopoietic cords and sinusoidal capillaries

• Stromal matrix – microenvironment for stem cell survival
• Stromal cells → fibroblasts, macrophages, osteocytes, adipocytes etc.
• Red marrow – about 75% of the cells are immature white cells and 25% of the
cells are immature red cells
• Myeloid to erythroid ratio is 3:1 (in the peripheral blood white cells: red cells is
1:600)

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Hematopoetic Stem Cells

• Undifferentiated cells that give rise to all of the bone marrow cells
• All the cells of blood are descendants of a single precursor cell type known as the pluripotent
stem cell (pluripotent hematopoietic stem cell)
• 0.5% of all marrow nucleated cells
• Multipotential precursors – can produce all types of blood cells
• Have the remarkable ability to develop into committed stem cells and for self renewal
• Not morphologically distinguishable
• Gradually they become restricted to differentiation in a single cell line – unilineage or committed
progenitor cell

• Proliferate and form myeloid and lymphoid lineage of cells

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Hematopoiesis

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Colony Forming Units

• As the cells divide, they become committed – they can only
become one kind of cell – called as colony forming units (CFU)
• Colony forming units are the progenitor cells formed from
stem cells
• Stem cells form colonies of cells – described as colony forming
units (CFU)
• CFU-GEMM (granulocytic, erythrocytic, monocytic,
megakaryocytic)
• CFU-GM
• CFU-Mk or (CFU-Meg)

• Structural differentiation of CFU continues

• Survival and differentiation of progenitor cells influenced by
growth regulatory glycoproteins, called cytokines

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Cellular Maturation
• Changes when the cell matures during
hematopoiesis
• Cell size decreases
• Cytoplasmic:nulcear ratio increases
• Chromatin becomes thick, coarse, irregular
• RNA decreases
• Immature cell:
Intensely basophilic (blue) because of high RNA
content
• Loss of blue as cell matures
• Granules may appear as cell matures
• Initial granules are nonspecific
• Take on specific characteristics as they mature
• Relative amount of cytoplasm increases as
cell matures

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Different Stages of Erythropoiesis

Stage Size Nucleus Hb Staining Mitosis
(mM)
Hemocytoblast (CFU-E) 19 - 23 -Deep basophilic Absent Deep basophilic Present ++
-4-5 nucleoli

Proerythroblast 15 -20 -Large central nucleus Absent Scanty and deep ++

-Deep basophilic basophilic
-Fine reticular chromatin
• Pluripotent stem cells divide to -N:chromatin ratio is 8:1

Basophilic erythroblast 16-18 -Deep basophilic cytoplasm Absent Deep basophilic ++

form committed stem cells of RBC --Small nucleus, very coarse
-N:C ratio 6:1
type
Polychromatic 10 - 14 -Nucleus becomes Appears Acidophilic with +
• RBC’s form from CFU-E which are erythroblast condense, coarse, basophilic basophilic hue
-Nucleoli absent
derived from the committed -N:C ratio is 4:1

progenitor cells Orthochromatic 8 - 10 -Nucleus small, pyknotic, Increased Acidophilic Absent

erythroblast with dark chromatin in amount
-Nucleus is eccentric or
central
-Nucleoli absent

Reticulocyte 7 - 7-5 -Nucleus absent Increased Acidophilic Absent

(polychromatic -Remnants of RNA in the in amount
form of reticulum
erythrocyte)

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Erythropoiesis

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Erythropoiesis…
• Erythropoiesis requires 5 -9 days
• Reticulocytes circulates for 1-2 days in peripheral blood before maturing in the spleen
• Abnormal increase in reticulocytes in circulation – hemolytic anemia and following treatment of deficiency
anemias
• Nucleus is gradually pushed to periphery and then extruded out – nucleus is absent in reticulocyte

Key Features of Erythropoiesis

• Basophilic nature of cytoplasm is an indicator of immaturity
• Cell size reduces with maturity
• As hemoglobin develops, the cytoplasm becomes more magenta
• The N:C ratio decreases as the cell matures
• The cytoplasm of the red cell does not contain specific granulation
• Nuclear chromatin becomes more condensed with age
• Nucleated red cells (orthochromic normoblasts) are not a physiological
component of the normal peripheral smear

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Hematopoietic Growth Factors

• Hematopoiesis depends on:
• Favorable microenvironmental conditions
• Presence of growth factors
• Large number of protein hormones and paracrine agents
collectively termed as haematopoietic growth factors
• IL – 1
• GM-CSF
• IL-3
• TNF Characteristics of Growth Factors
• M-CSF
• G-CSF • Glycoproteins
• Produced by many cell types
• Erythropoietin
• Affect more than one lineage
• Thrombopoietin • Synergistic effect with other growth factors
• Multiple actions – Proliferation,
differentiation, maturation, prevention of
apoptosis, functional activation

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Erythropoietin
• Erythropoiesis is controlled by the glycoprotein erythropoietin
(and assisted by several other cytokines)
• Hemtopoietin/hemopoietin
• It is produced in the kidneys (interstitial fibroblasts of
peritubular capillaries and tubular epithelium)
• Perisinusoidal cells in the liver in fetus
• The stimulus for erythropoietin synthesis and release is
hypoxia, low oxygen levels in the tissues
• It stimulates RBC production by red bone marrow, increases
maturation and also release of matured RBC’s
• Erythropoietin speeds up the stages of development of
proerythroblasts into mature red cells

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Erythropoietin
• Promotes every stage of maturation from pronormoblast to the
mature red cells

• Exerts its chief effect on the stem cells causing them to

differentiate

• It promotes Hb synthesis by increasing globin synthesis

• Promotes release of red cells from bone marrow into the

circulation

• Hemolysates – products released following RBC destruction

increase erythropoietin

• Erythropoietin levels are lowered in chronic renal diseases - a case

of renal cell carcinoma may be associated with its increased
production and erythrocytosis
• Clinical use – Anemia of chronic disease, anemia associated with
chemotherapy, anemia due to chronic renal disease

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Other factors influencing Erythropoiesis

• Vitamins -
• Vitamin B12, folic acid, vitamin B complex (riboflavin, pyridoxine) and vitamin C
• Vitamin B12 – an extrinsic factor- present in meat, fish, liver, milk and eggs is essential for erythropoiesis
• The intrinsic factor, formed in the parietal cells of the stomach is essential for absorption of vitamin B 12

• Folic acid
• Folic acid present in spinach, green leafy vegetables, fruits and many plants
• Required for synthesis of the nucleotide base thymine
• Essential for the formation of DNA and thus for normal cell division
• Inadequate folic acid - impairment of cell division occurs through out the body, most strikingly in rapidly
proliferating cells including erythrocyte precursors
• Vitamin B12 is required for the action of folic acid

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Other Factors …
• Lack of vitamin B12 and folic acid
• Diminishes cell multiplication and cell number
• Cells formed become larger than normal with more fragile membrane
• Erythrocytes are irregular, large and oval instead of the usual biconcave disk
• Metals
• Iron, copper, manganese, cobalt, zinc and calcium are necessary for
erythropoiesis. Iron is essential for the formation of haem
• Hormones
• Erythropoietin, Thyroxin, Testosterone, ACTH, Cortisol, Growth hormone,
Parathyroid hormone are required for erythropoiesis
• Nutritional factors
• First class proteins are necessary as amino acids are essential for globin formation. Even
lipids and carbohydrates are required

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Hemoglobin
• Main erythrocyte compound – a red pigment/chromo protein
• It is formed by 4 subunits – each unit contains heme
• A hemoglobin molecule consists of two parts:
• The globin portion, a protein made up of highly folded polypeptide chains
• Four iron containing non protein groups known as heme groups, each of which is bound
to one of the polypeptides
• Heme is an iron-porphyrin complex

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Hemoglobin
• Each of the four iron atoms can combine reversibly with
one molecule of O2
• HbO2 – oxyhemoglobin – oxygenation of iron
The oxygenated and deoxygenated haemoglobin molecule.
• Each Hb can pick up four O2 molecules in the lungs α, β, globin chains of normal adult haemoglobin (Hb A).
2,3-DPG, 2,3-diphosphoglycerate

• A rise in red cell concentration of 2,3-BPG (2,3-DPG),

an intermediate product of Embden-Meyerhof
pathway, as occurs in anaemia and hypoxia, causes
decreased affinity of HbA for oxygen
• This, in turn, results in enhanced supply of oxygen to
the tissue

Carbamino-hemoglobin: Carboxyhemoglobin:
Oxyhemoglobin:

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Types of Haemoglobin
• Four different types of polypeptide chains - alpha, beta, gamma
and delta (α, β, , )
• HbA1: Normal adult haemoglobin - has 2 alpha and 2 beta
chains (It forms about 95%)
• Normal adult haemoglobin (HbA) has lower affinity for
oxygen than foetal haemoglobin and, therefore, releases
greater amount of bound oxygen at tissue capillaries
• HbA2: It has 2 α and 2  chains (5% of adult Hb)
The timeline of the expression of the human globin genes from early
• HbF: Predominant type in fetus and contains 2 and 2  chains stages of fetal development to the changes that occur at birth and in
the first year of life
- Has increased affinity for oxygen
• HbF appears on 9th wk in fetus
• For first 7-12 weeks, it is primitive hemoglobin in the fetus

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Hemoglobin Levels
• At birth 23gm% of Hb is present as RBC count is high

• In adults: males – 13 to 18 g% [135 to 180 g/L] and females 12 to 16 g% [115 to 160 g/L]
(international units - 8.1 - 11.2 mmoles/liter for men, 7.4 - 9.9 mmoles/liter for women)

• One gram of Hb can combine with 1.34ml of O2

• Blood contains 15g of Hb in 100ml of arterial blood - on an average 100ml of blood can carry
20ml of O2

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Erythrocyte Destruction
• Senile RBCs are destroyed by the tissue macrophage system
• Extravascular destruction: spleen, bone marrow, liver
• Conserves and recycles erythrocyte components (amino acids, iron)
• Heme is reduced to bilirubin and eventually degraded to urobilinogen and excreted in the feces
• Indirect indicators of erythrocyte destruction include blood bilirubin and urine urobilinogen

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Leukopoiesis

Essential Hematology, 6th Ed A. V. Hoffbrand, P. A. H. Moss,

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Leukopoiesis Granulocyte Colony Stimulating

Factor – used clinically to produce
a rise in Neutrophils
-Infections, post chemotherapy,
lymphomas, post stem cell
Increased transplantation
granulocyte and
monocyte
production in
response to an
infection is by Included in the
increased growth blood count
factors production
from stromal cells

Not included in the

blood count

Essential Hematology, 6th Ed A. V. Hoffbrand, P. A. H. Moss,

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