1. Blood Physiology Professor A. M. A Abdel Gader MD, PhD, FRCP (Lond
Blood Physiology Professor A.M.A Abdel Gader MD, PhD, FRCP (Lond., Edin), FRSH (London) DEpartment of Physiology College of Medicine & King Khalid University Hospital King Saud University Riyadh

2. BLOOD

3. Lecture # 1 & 2 Topic: Red Blood Cells (RBCs)
Composition & functions of the Blood
Morphological Features of RBCs.
Production of RBCs
Regulation of production of RBCs
Nutritional substances need for RBC production
Haemoglobin
(Iron metabolism)

5. Blood Film

6. Blood Composition

7. Blood Composition 2. Plasma Red Blood Cells White Blood Cells
1. Cellular components
Red Blood Cells
White Blood Cells
Platelets
2. Plasma
Consist of:
Water: 98%
Ions: Na, K, HCO3, PO4 ..etc
Plasma proteins (Albumin, globulin, Fibrinogen)
PlasmaSame ionic composition as interstitial fluid

8. Functions Of the blood Transport O2 from lungs to tissues
CO2 from tissues to lungs
Nutrients
Waste products to kidneys
Hormones from endocrine glands to tissues

9. Functions Of Blood Cont.
2. Homoeostasis
Regulation of body temperature
Regulation of ECF pH

10. Functions Of Blood Cont.
3. Protecting the body against infections
White Blood Cells
Antibodies
4. Blood clotting prevent blood loss

11. Formation of Blood Cells -Definitions
Formation of erythrocytes (RBC) >Erythropoiesis
Formation of leucocytes (WBC) >Leucopoiesis
Formation of thrombocytes (platelets)> Thrombopiesis
Formation of blood >Haemopoiesis.

12. The Red Blood cell

13. The Red Blood cell

14. Red Blood Cells Structure Cell membrane: phospholipid; semi-permeable
Flat Biconcave Disc
Non-nucleated
framework of protein (stromatin) + haemaglobin
Cell membrane: phospholipid; semi-permeable
Composition of RBCs
60% water
40% solids
90% of solids content is Hb
10% stromatin

15. Red Blood cells cont. Functions Metabolism Carry Haemoglobin
Transport of Oxygen
Transport of Carbon Dioxide
Buffer ( pH regulation)
Metabolism
Metabolically active cells uses glucose for energy

16. Red Blood Cells cont. Life span ………. 120 days
RBC Count (Practical Class):
In males million cells/mm3
In females million cells/mm3

17. Sites of blood formation
Adults………… Bone Marrow
(Flat bones)
Children …………. Bone Marrow
(Flat & long bones)
Before Birth: …. Bone Marrow
Liver & spleen
Fetus 1st 4 months …Yalk Sac

18. Production of RBC-cont.

19. Blood Formation in the bone marrow

20. Monophyletic theory of cell formation
Red blood cells

21. Hematopoiesis
(17.9)

22. Formation of RBC – cont.

23. Production of Erythrocytes: Erythropoiesis
Figure 17.5

24. Maturation Times

25. Erythropoiesis, (Formation/genesis of RBC)
Stages of RBC development
Pluripotential haemopoietic STEM CELL
Committed Stem cell
Proerthroblast
early, intermediate and late normoblast
Reticulocytes
Erythrocytes

26. Maturation Sequence

28. Features of the maturation process of RBC
Reduction in size
Disappearance of the nucleus
Acquisition of haemoglobin

29. Regulation of Erythropoiesis

30. Control of Erythropoiesis
Erythropoiesis is stimulated by erythropoietin (EPO) hormone
Secretion of EPO is stimulated by:
Hypoxia (low oxygen)
Anaemia
Hemorrhage
High altitude
Lung disease
Heart failure

31. Role of the kidneys in RBC formation

32. Tissue oxygenation and RBC formation

33. Control of erythropoiesis Cont.
Erythropoietin
glycoprotein
90% from renal cortex 10% liver
Stimulates the growth of:
early RBC-committed stem cells
Does not affect maturation process
Can be measured in plasma & urine
High level of erythropoietin
anemia
High altitude
Heart failure

34. Control of erythropoiesis cont.
Other hormones
Androgens, Thyroid, cortisol & growth hormones are essential for red cell formation
Deficiencies of any one of these hormones results in anaemia

35. Control of erythropoiesis

36. Erythropoitein- Mechanism of production of
Hypoxia, (blood loss) 
Blood O2 levels
Tissue (kidney) hypoxia
 Production of erythropoietin
 plasma erythropoietin
Stimulation of erythrocytes production
 Erythrocyte production

37. Nutritional requirements for RBC formation
Amino acid
HemoGlobin
Iron
Deficiency  small cells
(microcytic anaemia )

38. Nutritional requirements for RBC formation cont.
3. Vitamins
Vit B12 and Folic acid
Synthesis of nucleoprotein DNA
Deficiency  macrocytes
megaloblastic (large) anemia
Vit C
Iron absorption

39. Nutritional requirements for RBC formation-cont.
Vit B6
Riboflavin, nicotinic acid, pantothenic acid, biotin & thiamine (VB)
Deficiency  normochromic normocytic anaemia
Vit E
RBC membrane integrity
Deficiency  hemolytic anaemia

40. Nutritional requirements for RBC formation cont.
Essential elements
Copper, Cobalt, zinc, manganese, nickel
Cobalt  Erythropoietin

41. Vitamin B12 & Folic acid Important for cell division and maturation
Deficiency of Vit. B12 > Red cells are abnormally large (macrocytes)
Deficiency leads:
Macrocytic (megaloblastic) anaemia
Dietary source: meat, milk, liver, fat, green vegetables

42. Vitamin B12 Pernicious anaemia
Absorption of VB12 needs intrinsic factor secreted by parietal cells of stomach
VB12 + intrinsic factor is absorbed in the terminal ileum
Deficiency arise from
Inadequate intake
Deficient intrinsic factors
Pernicious anaemia

43. Hemoglobin Globin protein consisting of 4 polypeptide chains2 1 3 4
Globin protein consisting of 4 polypeptide chains
One heme pigment attached to each polypeptide chain
Each heme contains an iron ion (Fe+2) that can combine reversibly with one oxygen molecule

44. HAEMOGLOBIN 14g/dl---18g/dl Protein (Globin) + Heme
Each heme consist of:
porpharin ring + iron
The protein (Globin) consist of:
4 polypeptide chains:
2  and 2  chains

45. HB Structure

46. HAEMOGLOBIN

47. Types of normal hemaglobin
HAEMOGLOBIN
Types of normal hemaglobin
HbA: 98% of adult Hb its polypeptide chains (2 & 2)
HbA2: 2.5% of adult Hb (2 & 2)
HbF: 80-90% of fetal Hb at birth (2 & 2)
Abnormality in the polypeptide chain > abnormal Hb (hemoglobinopathies) e.g thalassemias, sickle cell

48. HAEMOGLOBIN cont. Functions of Hb Carriage of O2 and CO2 Buffer
(Bind CO Smokers)

49. BLOOD PHYSIOLOGY
Iron metabolism

50. Total Iron in the body = 3-5g
Iron metabolism
Total Iron in the body = 3-5g
Haemoglobin: ……… % (3g)
Stored iron………… %
Muscle Hb (myoglobin) ….. 4%
Enzymes (cytochrome) …….. 1%
Plasma iron: (transferrin) …. 0.1%
(Serum ferritin  indication of the amount of iron stores)

51. Iron intake: Iron metabolism cont. Diet provides 10-20 mg iron
Liver, beef, mutton, fish
Cereals, beans, lentils and
Green leafy vegetable

52. Iron in food mostly in the form of Ferric (F+++, oxidized)
Iron metabolism, cont.
Iron absorption
Iron in food mostly in the form of Ferric (F+++, oxidized)
Better absorbed in reduced form Ferrous (F++)
Iron in stomach is reduced by gastric acid, Vit. C.
Maximum iron absorption occurs in the duodenum

53. Intestinal mucosal cell
Iron absorption
Tissues
Plasma
Intestinal mucosal cell
intestinal
lumen
Storage
Pool
&
Erythropoietic
Apo-
Transferrin
Fe3+ +
Apoferritin
Ferritin
Ascorbic
Acid
Fe2+

54. Iron absorption cont. Rate of iron absorption depend on:
Amount of iron stored
Rate of erythropoiesis
When all the apoferritin is saturated the
rate of absorption of iron from intestine
is markedly reduced

55. Iron absorption cont. Iron in plasma:
Transporting protein: TRANSFERRIN
Normally saturated with Fe
(plasma iron ug/100ml)
When transferrin 100% saturated >> plasma iron: 300ug/100ml
(Total Iron Binding Capacity)

56. Iron stores Site: liver, spleen & bone marrow Storage forms:
Ferritin and haemosiderin
Apoferretin + iron = Ferritin
Ferritin + Ferritin = Haemosiderin

57. Iron excretion and daily requirement
Iron losses
feces: unabsorbed, dead epithelial cells
bile and saliva.
Skin: cell, hair, nail, in sweat.
Urine
Menstruation, pregnancy and child birth

58. Destruction of Erythrocytes
At the end of RBC life span is 120 days:
Cell membrane ruptures during passage in capillaries of the spleen, bone marrow & liver.
Haemoglobin
Polypeptide  amino acids  amino acid pool
Heme:
Iron  recycled  iron storage
porphryn  biliverdin  bilirubin (bile)

59. Jaundice Yellow coloration of skin, sclera
Deposition of bilrubin in tissues
If Bilrubin level in blood > 2 mg/ ml > jaundice
Causes of Jaundice
Excess breakdown of RBC (hemolysis)
Liver damage
Bile obstruction: stone, tumor

60. ANAEMIAS Definiation Decrease number of RBC Decrease Hb Symptoms:
Tired, Fatigue, short of breath,
(pallor, tachycardia)

61. Causes of anaemia 1. Blood Loss 2. Decrease RBC production
acute accident
Chronic  ulcer, worm
2. Decrease RBC production
Nutritional causes
Iron  microcytic anaemia
VB12 & Folic acid  megaloblastic anaemia
Bone marrow destruction by cancer, radiation, drugs  Aplastic anaemia.
3. Haemolytic  excessive destruction
Abnormal Hb (sickle cells)
Incompatible blood transfusion

62. Microytic hypochromic anaemia (Iron deficiency anaemia)
The most common cause of microcytic hypochromic anemia is iron deficiency.
The most common nutritional deficiency is lack of dietary iron.
Thus, iron deficiency anemia is common in children and in women in reproductive years (from menstrual blood loss and from pregnancy)

63. Microytic hypochromic anaemia (Iron deficiency anaemia)
The RBC's here are smaller than normal and have an increased zone of central pallor. This is indicative of a hypochromic (less hemoglobin in each RBC) microcytic (smaller size of each RBC) anemia. There is also increased anisocytosis (variation in size) and poikilocytosis (variation in shape).

64. Macrocytic anemia RBCs are almost as large as the lymphocyte.
Note fewer RBCs (and the hypersegmented neurotrophil)

65. Polycythemia Increased number of RBC Types: Relative True or absolute
Primary (polycythemia rubra vera): uncontrolled RBC production
Secondary to hypoxia: high altitude, chronic respiratory or cardiac disease
Relative
Haemoconcentration:
loss of body fluid in vomiting, diarrhea, sweating