Hematology-

Hematopoiesis and
red blood cells

Mohamed Elsadig Mohamed

 Blood is a type of connective tissue.

 Like other types of connective tissue it consists of:

 Cells and intercellular substance.

 The cells:

 Red blood cells (RBCs) or erythrocytes.

 White blood cells (WBCs) or leukocytes.

 Platelets (PLs) or thrombocytes.

 The intercellular substance:

 Is called plasma.
 Volume of blood is about 5L in an average adult male (8% of

total body weight).

 Volume of plasma is about 3.5L (5% of total body weight).

 The cells in blood can be separated from plasma by

centrifugation.
 The percentage of cells in blood is called the packed cell

volume (PCV) or the hematocrit.

Functions of blood
1. Transport of:
 Gases (e.g. oxygen and carbon dioxide).

 Nutrients (e.g. glucose, amino acids and free fatty acids).

 Waste products (e.g. urea and uric acid).

 Hormones (e.g. catecholamines, insulin, cortisol and thyroid

hormones).
2. Defense by white blood cells(WBCs).
3. Control of temperature by distribution of heat by the blood.

4. Control of pH by buffers in the blood, e.g. HCO3-, proteins

and hemoglobin.
5. Hemostasis:
 Is prevention of blood loss and maintenance of blood in the

fluid state.
 Blood loss is prevented by arrest of bleeding by platelets and

clotting factors.
 Maintenance of blood in the fluid state occurs by the natural

anticoagulants.
Hematopoiesis
 Hematopoeisis: is the mechanism of blood cells formation

and stages of development.

 It Includes:

 Erythropoiesis: formation of RBCs.

 Leukopoiesis: formation of WBCs.

 Thrormbopoiesis: formation of PLs.

 Sites of hematopoiesis:

 During pregnancy, blood is formed at the following sites:

1. Yolk sac:
 Forms blood during the intrauterine life in the first trimester.

2. Liver, spleen and lymph nodes:

 Forms blood during the intrauterine life in the second trimester.

3. Bone marrow:
 Forms blood during the intrauterine life in the third trimester

and then continue 5 years after delivery.

 The bone marrow called red marrow (active marrow) which is

found in almost all bones during pregnancy.

 After delivery, blood is formed at the following sites:

 After 5 years from delivery, the red bone marrow starts to be

replaced gradually by yellow marrow(inactive marrow).

 At about the age of 20 years the red marrow is confined to:

1. Flat bones e.g. skull, sternum, ribs, scapula, vertebrae and

iliac bone.
2. Ends of long bones “epiphyses” not the shaft “diaphysis”

3. Small bones of hands and feet.

 NB:

 About 75% of the cells in the red bone marrow are WBC

precursors and only 25% are RBC precursors in spite of the

fact that RBC count is over 500 times more than the WBC
count, this indicates the longer life span of RBCs.
The red blood cells(RBCs)
 Characteristics of RBCs:

 Shape: Biconcave disks

 Diameter: 7.5 micrometer

 Thickness: 1 micrometer

(center), 2 micrometer
(edges)
 Contents:

 No nucleus, therefore no reproduction.

 No organelles, e.g. no mitochondria and therefore no aerobic

glycolysis, they use anaerobic glycolysis to generate small

amount of energy for maintenance of the integrity of the cell
membrane.
 Their life span is about 120 days
 Contain hemoglobin(Hb), a red pigment found within RBCs

 Hb constitutes 90% of solid material, and total solid material

inside RBC is about 40% and 60% is water.

 Important for transport of oxygen.

 The volume of a red blood cell is larger than its contents, this

allows it to squeeze itself through the narrow capillaries.

 Count of RBCs

 In males: 4.9 -5.5 million/mm3.

 In females: 4.4 -5 million/mm3.

 RBC count is higher in males than females of the same age because:

1. Males contain more muscle which is active tissue while in females

there is more fat tissue.
2. Female loss blood monthly in menstrual cycle.
 About 3 million RBCs are normally destroyed each second and same

number is replaced each second.

 Destruction and removal of RBCs take place in the reticuloendothelial

system.
 Functions of RBCs

1. Transport oxygen (bound to iron in hemoglobin).

2. Transport carbon dioxide (bound to globin in hemoglobin).

3. Buffer (a function of hemoglobin).

4. Contain antigens on its surface that determine the type of

blood group.
Stages of erythropoiesis
 Can be divided into:

1. Replication phase:
 The increase in number of RBCs.

2. Maturation phase:
 The decrease in size of RBC precursors.

 Loss of contents (nucleus and organelles).

 Acquisition of hemoglobin.
1. Stages in the bone marrow:

a. Pluripotent non-committed stem cells:

 Nucleated cells that divide to form two types of committed

stem cells:

i. Lymphoid.

ii. Non-lymphoid which has two types, myeloid and erythroid

cells.
b. Committed stem cells (or progenitor cells):

 Nucleated cells that divide to form only one type of blood cells

e.g.:
 The lymphoid forms lymphocytes.

 The erythroid forms RBCs.

 The myeloid forms other WBCs and platelets.

c. Proerythroblasts (or Normoblasts):
 They have three stages, early, intermediate and late

normoplast.
 These divide many times and start to form hemoglobin.

 The normoblasts lose the nucleus and other organelles to

become reticulocytes.
2. Stages in the blood:

a. Reticulocytes:
 The first non-nucleated red blood cell.

 They have no organelles.

 High reticulocyte count >2% indicates hyperactivity in the bone

marrow.
b. Erythrocytes:
 The mature red blood cells.
Control of erythropoiesis
 Normal erythropoiesis requires:

1. Normal bone marrow.

2. Cytokines and colony stimulating factors.

3. Erythropoietin and other hormones e.g. thyroid hormones.

4. Certain nutrients e.g. iron, vitamin B12 and folic acid.

1. Normal bone marrow:
 Normal bone marrow is essential for normal erythropoiesis.

 Diseases affecting the bone marrow usually results in abnormal

erythropoiesis
2. Cytokines and colony stimulating factors:
 Interleukins: IL-1, IL-3, IL-6 and GM-CSF (Granulocyte- Monocyte

Colony Stimulating Factors) stimulate proliferation and conversion

of pluripotent stem cells into committed stem cells.
 These growth factors are produced by bone marrow’s fibroblasts,

endothelial cells, activated T cells and macrophages.

3. Erythropoietin (the principal regulator of erythropoiesis):

 Erythropoietin is glycoprotein.

 Site of production:

 In adults: produced mainly in the kidneys (90%) and in the liver (10%).

 In fetal life: the liver is the main site of production.

 Stimulus:

 Hypoxia, which is low oxygen at the tissue level.

 Function:

 Stimulates replication of stem cells and formation of erythroblasts.

 Erythropoietin dose not influence the maturation stages of RBCs.

 Abnormalities of erythropoietin:

 Erythropoietin excess :

 It causes polycythemia.

 Causes of polycythemia:

a. High altitudes: people living at high altitudes have

physiological polycythemia due to the low oxygen tension at
these sites.
b. Renal problems: e.g. renal tumors or polycystic kidney disease.

c. Chronic respiratory problems: e.g. lung fibrosis.

 Erythropoietin deficiency:

 It causes anemia.

 Anemia caused by erythropoietin deficiency is characterized

by low count of RBCs but with normal shape and color

“normocytic normochromic anemia”.
 Other hormones needed for normal erythropoiesis:

a. Androgens (male hormones that increase bulk of muscles,

e.g. testosterone). Muscles are more active than fats, they
consume more oxygen.
b. Growth hormone
c. Cortisol
d. Thyroid hormones
4. Nutrients needed for erythropoiesis:
 Amino acids: for formation of globin of hemoglobin.

 Iron: for formation of heme of hemoglobin. It’s deficiency

causes microcytic hypochromic anemia.

 Vitamin B12 and folic acid: for DNA synthesis for cell

division. It’s deficiency causes macrocytic normochromic

anemia.
 Vitamin C: for iron absorption, it is a reducing factor that

maintains iron in the ferrous state.

 B vitamins: e.g. riboflavin, nicotinic acid and biotin for

metabolic reactions.
 Vitamin E: for maintenance of RBC membrane (an anti-

oxidant that protects the cell membrane from oxygen radicals).

It’s deficiency causes hemolytic anemia.
 Copper: promotes iron absorption.

 Cobalt: stimulate erythropoietin production.

 Iron metabolism:

 Distribution in the body:

 Total amount in the body is about 3 - 5 grams, distributed in:

 Heme of hemoglobin (65-75%).

 Storage (ferritin, hemosiderin) (15 -30%).

 Cellular enzymes e.g. catalase, cytochrome oxidase (3%).

 Plasma (transferrin) (< 1%).

 Dietary sources:

 Animal products: e.g. liver, meat and egg.

 Plant products: e.g. vegetables and beans.

 The average diet provides 10-20 mg/day.

 Daily requirements:

 About 1 mg/day in an adult man, 2 mg/day in an adult woman

 The daily requirements are increased during:

1. Pregnancy

2. Lactation

3. Infancy (the first year of life)

 Site of absorption:

 Duodenum.

 Mechanism of absorption:

 2ndary active transport (Fe2+/H+ symport).

 Factors that increase absorption:

1. Ferrous state (Fe2+).

2. Gastric acidity (HCl), maintains iron in the ferrous state.

3. Vitamin C, also maintains iron in the ferrous state.

 Factors that decrease absorption:

1. Achlorohydria (low hydrochloric acid due to gastric atrophy).

2. Diarrhea.

3. Clay.

4. Fever.

5. Tetracycline.
 Storage:

 Sites of storage: Intestinal mucosa, liver, spleen and bone

marrow.
 Forms of storage:

1. Ferritin, is the main form of storage, it stores 65% of stored

iron in a soluble form.
2. Hemosiderin, insoluble form 35%.
 Function of iron: formation of heme in Hb

 Iron found in ferrous (Fe2+) form.

 Each Hb molecule contains 4 (Fe2+).

 Each atom of iron binds 2 atoms of oxygen (Therefore each

Hb molecule carries 8 atoms of oxygen (or four molecules).

 Excretion:

 Total daily loss of iron= 1 mg/day in adult men, 2mg/day in

adult women (daily intake = daily loss).

 Routes for iron loss: Feces, skin, urine and menstruation.
 Abnormalities

 Iron deficiency anemia:

 Characterized by: Low Hb, small and pale RBCs (microcytic

hypochromic anemia).
 Iron overload:

 Hemochromatosis: is a common hereditary condition

characterized by excessive iron absorption resulting in abnormal

accumulation of iron in many organs causing damage.
 Hemosiderosis: describes iron overload secondary to certain

causes (e.g. repeated blood transfusions and excessive iron

therapy).
 Vitamin B12:

 Sources and requirement:

 Found in food of animal origin.

 Daily requirements are very low (about 1- 2 microgram/day).

 Site of absorption:

 Terminal ileum

 Functions:

1. DNA synthesis: (needed for red blood cell replication)

2. Myelination of nerves
 Deficiency causes:

1. Macrocytic normochromic anemia (megaloblastic anemia)

2. Sub-acute combined degeneration of the cord (demyelination)

 Folic acid:

 Sources and requirement:

 Found mainly in food of plant origin

 Daily requirement is about 100 microgram/day.

 Absorption:

 In the small intestine (especially the jejunum)

 Function:

 DNA synthesis (needed for red blood cell replication)

 Abnormalities:

 Deficiency causes: macrocytic normochromic anemia

Thank you