Blood

1. BLOOD
Sreenu Thalla
Assistant Professor
Department of Pharmacology
4/3/2024 1

2. Primary Functions of the Circulatory System
1) Transportation
- Deliver life-supporting materials, i.e., O2, glucose,
amino acid, fatty acids, vitamins, minerals, etc.
- Deliver regulating signals, i.e., hormones to tissue
cells
- Collect waste products from tissue cells and
deliver to special organs (kidney, lung) for disposal
- Distribute heat throughout the body
4/3/2024 2
Sreenu Thalla, Department of
Pharmacology

3. Primary Functions of the Circulatory System
2) Protection
- Special components of the blood patrol the whole
body and fight against invaded microorganisms and
cancerous cells.
cell
cell
cell
cell
cell
cell
cell
H2O
Glucose
Lipids
Amino acids
Vitamins
Minerals
O2
pH 7.35-7.45
~38° C
290 mOsm
4/3/2024 3
Sreenu Thalla, Department of
Pharmacology

4. 4/3/2024 4
Sreenu Thalla, Department of
Pharmacology

5. 1) Plasma
2) The Formed Elements
(blood cells/cell fragments)
Composition of the Blood
4/3/2024 5
Sreenu Thalla, Department of
Pharmacology

6. General Properties of Whole Blood
- Fraction of body weight
- Volume
- temperature
- pH 7.35 - 7.45
- Viscosity (relative to water)
- Osmolarity
- Mean salinity (mainly NaCl)
8%
Female: 4-5 L
Male: 5-6 L
38 C (100.4 F)
Whole blood: 4.5-5.5
plasma: 2.0
280-300 mOsm/L
0.85%
4/3/2024 6
Sreenu Thalla, Department of
Pharmacology

7. Hematocrit
RBCs as percent of total blood
volume
- Female: 37%-48%
- male: 45%-52%
100%
4/3/2024 7
Sreenu Thalla, Department of
Pharmacology

8. Hemoglobin
Female: 12-16 g/100 ml
male: 13-18 g/100 ml
Mean RBC count
Female: 4.8 million/l
male: 5.4 million/l
Platelet counts 130,000-360,000/l
Total WBC counts 4,000-11,000/l
General Properties of Whole Blood (continued)
4/3/2024 8
Sreenu Thalla, Department of
Pharmacology

9. Plasma
4/3/2024 9
Sreenu Thalla, Department of
Pharmacology

10. Water 92% by weight
Proteins Total 6-9 g/100 ml
Albumin 60% of total plasma protein
Globulin 36% of total plasma protein
Fibrinogen 4% of total plasma protein
Enzymes of diagnostic value trace
Glucose (dextrose) 70-110 mg/100 ml
Amino acid 33-51 mg/100 ml
Lactic acid 6-16 mg/100 ml
Composition of Plasma
4/3/2024 10
Sreenu Thalla, Department of
Pharmacology

11. Total lipid 450-850 mg/100 ml
Cholesterol 120-220 mg/100 ml
Fatty acids 190-420 mg/100 ml
High-density lipoprotein (HDL) 30-80 mg/100 ml
Low-density lipoprotein (LDL) 62-185 mg/100 ml
Neutral Fats (triglycerides) 40-150 mg/100 ml
Phospholipids 6-12 mg/100 ml
Composition of Plasma (continued)
4/3/2024 11
Sreenu Thalla, Department of
Pharmacology

12. Iron 50-150 g/100 ml
Vitamins (A, B, C, D, E, K) Trace amount
Electrolytes
Sodium 135-145 mEq/L
Potassium 3.5-5.0 mEq/L
Magnesium 1.3-2.1 mEq/L
Calcium 9.2-10.4 mEq/L
Chloride 90-106 mEq/L
Bicarbonate 23.1-26.7 mEq/L
Phosphate 1.4-2.7 mEq/L
Sulfate 0.6-1.2 mEq/L
Composition of Plasma (continued)
4/3/2024 12
Sreenu Thalla, Department of
Pharmacology

13. Nitrogenous Wastes
Ammonia 0.02-0.09 mg/100 ml
Urea 8-25 mg/100 ml
Creatine 0.2-0.8 mg/100 ml
Creatinine 0.6-1.5 mg/100 ml
Uric acid 1.5-8.0 mg/100 ml
Bilirubin 0-1.0 mg/100 ml
Respiratory gases (O2, CO2, and N2)
Composition of Plasma (continued)
4/3/2024 13
Sreenu Thalla, Department of
Pharmacology

14. plasma serum
clotting proteins
(fibrin)
4/3/2024 14
Sreenu Thalla, Department of
Pharmacology

15. The Formed Elements
(Blood Cells)
4/3/2024 15
Sreenu Thalla, Department of
Pharmacology

16. Formed elements include:
Erythrocytes (red blood cells, RBCs)
Platelets (cellular fragments)
Leukocytes (white blood cells, WBCs)
Granulocytes
Agranulocytes
Neutrophils
Eosinophils
Basophils
Lymphocytes
Monocytes
4/3/2024 16
Sreenu Thalla, Department of
Pharmacology

17. 4/3/2024 17
Sreenu Thalla, Department of
Pharmacology

18. 4/3/2024 18
Sreenu Thalla, Department of
Pharmacology

19. Erythrocytes
(red blood cells)
4/3/2024 19
Sreenu Thalla, Department of
Pharmacology

20. Erythrocytes (Red Blood Cells, RBCs)
Appearance:
- biconcave disc shape,
which is suited for gas
exchange. The shape is
flexible so that RBCs can pass
though the smallest blood
vessels, i.e., capillaries.
4/3/2024 20
Sreenu Thalla, Department of
Pharmacology

21. Erythrocytes are smaller than Leukocytes.
4/3/2024 21
Sreenu Thalla, Department of
Pharmacology

22. Erythrocytes (Red Blood Cells, RBCs)
Structure:
-Primary cell
content is
hemoglobin,
the protein
that binds
oxygen and
carbon
dioxide.
- no nucleus
nor
mitochondria
4/3/2024 22
Sreenu Thalla, Department of
Pharmacology

23. Hemoglobin consists of :
globin and heme pigment
4/3/2024 23
Sreenu Thalla, Department of
Pharmacology

24. Globin
- Consists of two  and two  subunits
- Each subunit binds to a heme group
4/3/2024 24
Sreenu Thalla, Department of
Pharmacology

25. Heme Group Structure
Heme Groups
carry four molecules of oxygen
Each heme group bears an atom of iron, which binds
reversibly with one molecule of oxygen
4/3/2024 25
Sreenu Thalla, Department of
Pharmacology

26. Carbon monoxide competes with oxygen
for heme binding with a much higher
affinity.
Problem:
Treatment:
deoxygenate hemoglobin
hyperbaric oxygen chamber
4/3/2024 26
Sreenu Thalla, Department of
Pharmacology

27. Oxyhemoglobin
- bound with oxygen
- red
Deoxyhemoglobin
- free of oxygen
- dark red.
Carbaminohemoglobin
20% of carbon dioxide
in the blood binds to the
globin part of
hemoglobin, which is
called carbamino-
hemoglobin.
4/3/2024 27
Sreenu Thalla, Department of
Pharmacology

28. 1) Primary Function
Transport oxygen from the lung to tissue cells
and carbon dioxide from tissue cells to the lung
Functions of Erythrocytes
2) Buffer blood pH
4/3/2024 28
Sreenu Thalla, Department of
Pharmacology

29. Production of Erythrocytes
Hematopoiesis
refers to whole blood cell
production.
Erythropoiesis
refers specifically to red
blood cell production.
All blood cells, including red and white,
are produced in red bone marrow.
On average, one ounce, or 100 billion
blood cells, are made each day.
4/3/2024 29
Sreenu Thalla, Department of
Pharmacology

30. Hematopoiesis
The red bone marrow is a network of reticular connective
tissue that borders on wide blood capillaries called blood
sinusoids. As hemocytoblasts mature, they migrate
through the thin walls of the sinusoids to enter the blood.
4/3/2024 30
Sreenu Thalla, Department of
Pharmacology

31. All of blood cells
including red and
white arise from
the same type of
stem cell, the
hematopoietic
stem cell or
hemocytoblast
4/3/2024 31
Sreenu Thalla, Department of
Pharmacology

32. Erythropoiesis
Erythrocytes are produced throughout
whole life to replace dead cells.
4/3/2024 32
Sreenu Thalla, Department of
Pharmacology

33. - regulated by renal
oxygen content.
- Erythropoietin, a
glycoprotein hormone, is
produced by renal cells
in response to a
decreased renal blood
O2 content.
- Erythropoietin
stimulates erythrocyte
production in the red
bone marrow.
Feedback Regulation of Erythropoiesis
4/3/2024 33
Sreenu Thalla, Department of
Pharmacology

34. A drop in renal blood oxygen level can
result from:
1) reduced numbers of red blood cells due to
hemorrhage or excess RBC destruction.
2) reduced availability of oxygen to the blood,
as might occur at high altitudes or during
pneumonia.
3) increased demands for oxygen (common in
those who are engaged in aerobic exercise).
4/3/2024 34
Sreenu Thalla, Department of
Pharmacology

35. Dietary Requirements for Erythropoiesis
Iron
vitamin B12
folic acid
4/3/2024 35
Sreenu Thalla, Department of
Pharmacology

36. The average
life span of
erythrocytes
is 120 days.
4/3/2024 36
Sreenu Thalla, Department of
Pharmacology

37. Anemia
is a condition in which the blood has an
abnormally low oxygen-carrying capacity.
Erythrocyte Disorders
4/3/2024 37
Sreenu Thalla, Department of
Pharmacology

38. Common causes of anemia include:
1) an insufficient number of red blood cells
2) decreased hemoglobin content
3) abnormal hemoglobin
Two such examples are Thalassemias and
Sickle-cell anemia, which are caused by
genetic defects.
4/3/2024 38
Sreenu Thalla, Department of
Pharmacology

39. Common causes of polycythemia include:
1) Bone marrow cancer
2) A response to reduced availability of
oxygen as at high altitudes
Polycythemia
is an abnormal excess of erythrocytes that
increases the viscosity of the blood, causing it
to sludge or flow sluggishly.
Erythrocyte Disorders - 2
4/3/2024 39
Sreenu Thalla, Department of
Pharmacology

40. Human Blood Groups
4/3/2024 40
Sreenu Thalla, Department of
Pharmacology

41. Human Blood Groups
- were learned from tragedies (death) caused by
mismatch during transfusion in ancient time.
- ABO blood types were identified in 1900 by Karl
Landstein (1930 Nobel laureate).
- Other blood types were identified later.
4/3/2024 41
Sreenu Thalla, Department of
Pharmacology

42. Blood type is determined by
Agglutinogens
• are specific
glycoproteins on red
blood cell membranes.
• All RBCs in an
individual carry the same
specific type of
agglutinogens.
4/3/2024 42
Sreenu Thalla, Department of
Pharmacology

43. ABO Blood Groups
Type A: RBCs carry agglutinogen A.
Type B: RBCs carry agglutinogen B.
Type O: RBCs carry no A nor B agglutinogens.
Type AB: RBCs carry both A and B agglutinogens.
4/3/2024 43
Sreenu Thalla, Department of
Pharmacology

44. A
- RBCs carry type A
agglutinogens.
- Plasma contain
preformed antibodies,
Agglutinin B, against
B agglutinogens.
B
B
B
B
B
Type A blood
A
A A
A
A
A A
4/3/2024 44
Sreenu Thalla, Department of
Pharmacology

45. Agglutinins
- are preformed antibodies in plasma
- bind to agglutinogens that are not
carried by host RBCs
- cause agglutination --- aggregation
and lysis of incompatible RBCs.
B
B
B
B
B
B
B
B
B
B
B
B
B
B B
B
B
Agglutinin B
4/3/2024 45
Sreenu Thalla, Department of
Pharmacology

46. B
B
B
B
B
B
B
B
B
B
B
B
B
B
B B
B
B
B
B
B
B
B
B
B
B B
B
B
B
B
B
B
B
B
Mix Type A plasma with Type B RBCs
4/3/2024 46
Sreenu Thalla, Department of
Pharmacology

47. Type B recipient
4/3/2024 47
Sreenu Thalla, Department of
Pharmacology

48. -RBCs carry type B
agglutinogens.
- Plasma contain
agglutinin against A
agglutinogens.
Type B blood
A
A
A
A
A
A
B
B
B
B
B
B
B B
B
4/3/2024 48
Sreenu Thalla, Department of
Pharmacology

49. - RBCs carry neither
type A nor type B
agglutinogens.
- Plasma contain
agglutinin against
both A and B
agglutinogens.
- The person can
accept only type O
blood transfusion.
Type O blood
A
A
A
A
A
A
B
B
B
B
4/3/2024 49
Sreenu Thalla, Department of
Pharmacology

50. Type AB blood
Agglutinogen(s) ?
Agglutinin(s) ?
4/3/2024 50
Sreenu Thalla, Department of
Pharmacology

51. Type AB blood
Agglutinogen(s): A and B
No A nor B
B
A
Agglutinin(s) ?
4/3/2024 51
Sreenu Thalla, Department of
Pharmacology

52. Blood Type Agglutinogen
(on RBC)
Agglutinin
(in Plasma)
A A B
B B A
O A & B
AB A & B
Summary of ABO Blood Groups
4/3/2024 52
Sreenu Thalla, Department of
Pharmacology

53. Blood Type Match
A B O AB
A Yes No Yes? No
B No Yes Yes? No
O No No Yes No
AB Yes? Yes? Yes? Yes
R
D
4/3/2024 53
Sreenu Thalla, Department of
Pharmacology

54. Rh positive
- RBCs contain Rh agglutinogens.
Rh Blood Groups
Classify blood groups based on Rh agglutinogens
other than A/B agglutinogens
A
A
A
Rh
A
Rh
Rh
Rh
- The majority of human beings is Rh positive.
4/3/2024 54
Sreenu Thalla, Department of
Pharmacology

55. A
A A
A
B
A
A
A
A
Rh negative
- The RBCs contain no Rh agglutinogens.
- Agglutinins against Rh-positive RBCs are
produced after Rh-negative blood sees Rh-
positive RBCs.
Rh
Rh Rh
Rh
Rh
Rh
4/3/2024 55
Sreenu Thalla, Department of
Pharmacology

56. The problem with a Rh-negative
mother and her Rh-positive
fetus.
4/3/2024 56
Sreenu Thalla, Department of
Pharmacology

57. Protected by the placenta-blood
barrier, the mother is not exposed
to Rh agglutinogens until the time
of childbirth due to placental
tearing.
First Preganancy
no anti-Rh
no Rh
4/3/2024 57
Sreenu Thalla, Department of
Pharmacology

58. Second Pregnancy
4/3/2024 58
Sreenu Thalla, Department of
Pharmacology

59. Leukocytes (White Cells)
4/3/2024 59
Sreenu Thalla, Department of
Pharmacology

60. Leukocytes are grouped into two major categories:
Granulocytes
- contain specialized membrane-bound
cytoplasmic granules
- include neutrophils, eosinophils, and
basophils.
Agranulocytes
- lack obvious granules
- include lymphocytes and monocytes
4/3/2024 60
Sreenu Thalla, Department of
Pharmacology

61. 4/3/2024 61
Sreenu Thalla, Department of
Pharmacology

62. Leukocytes (WBCs) Count
4,000-11,000 / L
4/3/2024 62
Sreenu Thalla, Department of
Pharmacology

63. Function of Leukocytes: defense against diseases
Leukocytes form a mobile army that helps protect
the body from damage by bacteria, viruses,
parasites, toxins and tumor cells.
4/3/2024 63
Sreenu Thalla, Department of
Pharmacology

64. Primary Functions of the Circulatory System
2) Protection.
cell
cell
cell
cell
cell
cell
cell
H2O
Glucose
Lipids
Amino acids
Vitamins
Minerals
O2
pH 7.35-7.45
~38° C
290 mOsm
4/3/2024 64
Sreenu Thalla, Department of
Pharmacology

65. Life span
- several hours to
several days for
the majority
- many years for a
few memory cells
Leukocytes circulate in the blood for
various length of time.
4/3/2024 65
Sreenu Thalla, Department of
Pharmacology

66. Neutrophils
- 40%-70% WBCs
- Nucleus multilobed
- Duration of development: 6-9 days
- Life Span: 6 hours to a few days
- Function: phagocytize bacteria
4/3/2024 66
Sreenu Thalla, Department of
Pharmacology

67. 4/3/2024 67
Sreenu Thalla, Department of
Pharmacology

68. Eosinophils
- 1%-4% WBCs
- Nucleus bilobed
- Development:6-9 days
- Life Span: 8-12 days
- Function:
1) Kill parasitic worms
2) destroy antigen-antibody complexes
3) inactivate some inflammatory chemical of allergy
4/3/2024 68
Sreenu Thalla, Department of
Pharmacology

69. Basophils
- 0.5% WBCs
- Nucleus lobed
- Development: 3-7 days
- Life Span: a few hours to a few days
- Function:
1) Release histamine and other
mediators of inflammation
2) contain heparin, an anticoagulant
4/3/2024 69
Sreenu Thalla, Department of
Pharmacology

70. Lymphocytes
- T cells and B cells
- 20%-45% WBCs
- Nucleus spherical or indented
- Development: days to weeks
- Life Span: hours to years
- Function
Mount immune response by direct cell attack
(T cells) or via antibodies (B cells)
4/3/2024 70
Sreenu Thalla, Department of
Pharmacology

71. Monocytes
- 4%-8% WBCs
- Nucleus U-shaped
- Development: 2-3 days
- Life Span: months
- Function:
Phagocytosis
develop into macrophages in tissues
4/3/2024 71
Sreenu Thalla, Department of
Pharmacology

72. Blood Capillary
Leukocytes are deployed
in the infected areas
outside blood vessels via
3 steps.
1) Margination
2) Diapedesis
3) chemotaxis
4/3/2024 72
Sreenu Thalla, Department of
Pharmacology

73. Blood Capillary
slow down by cell
adhesion
molecules secreted
by endothelial cells
Leukocytes are deployed
in the infected areas
outside blood vessels via
3 steps.
1) Margination
4/3/2024 73
Sreenu Thalla, Department of
Pharmacology

74. Blood Capillary
2) Diapedesis:
Leukocytes slip
out of the
capillary blood
vessels.
4/3/2024 74
Sreenu Thalla, Department of
Pharmacology

75. Blood Capillary
3) Chemotaxis:
Gather in large
numbers at areas
of tissue damage
and infection by
following the
chemical trail of
molecules
released by
damaged cells or
other leukocytes
4/3/2024 75
Sreenu Thalla, Department of
Pharmacology

76. Blood Capillary
Phagocytosis
Destroy foreign
substances or
dead cells
4/3/2024 76
Sreenu Thalla, Department of
Pharmacology

77. Leukocyte Disorders
Normal Leukocyte Count: 4,000 – 11,000/l
Leukopenia: < 4,000/l normal leukocytes
Leukocytosis: > 11,000/l normal leukocytes
Leukopenia is one major side effect of chemotherapy.
4/3/2024 77
Sreenu Thalla, Department of
Pharmacology

78. - Cancerous cells grow fast, which distinguish
themselves from most of normal cells.
- Chemotherapy is designed to kill fast-growing
cells by interrupting mitotic cell division.
- Chemotherapy also kills a few normal fast-
growing cells including:
Why Leukopenia during chemotherapy?
intestinal epithelial cells
leukocytes
hair
4/3/2024 78
Sreenu Thalla, Department of
Pharmacology

79. Leukemia
- Leukemia refers to a group of cancerous
conditions of white blood cells.
- Descendants of a single stem cell in red
bone marrow tend to remain unspecialized
and mitotic, and suppress or impair normal
bone marrow function.
- extraordinarily high number of abnormal
(cancerous) leukocytes
4/3/2024 79
Sreenu Thalla, Department of
Pharmacology

80. HEMOSTASIS
4/3/2024 80
Sreenu Thalla, Department of
Pharmacology

81. - Hemostasis refers to the stoppage of
bleeding.
Hemostatsis = Homeostasis
Maintaining balance
Three phases occur in rapid sequence.
4/3/2024 81
Sreenu Thalla, Department of
Pharmacology

82. 1) vascular spasms
2) platelet plug formation
3) blood clotting /
coagulation
4/3/2024 82
Sreenu Thalla, Department of
Pharmacology

83. Platelets
Platelets are not cells but cytoplasmic fragments of
extraordinarily large (up to 60 m in diameter) cells
called megakaryocytes.
Normal Platelet Count: 130,000 – 400,000/l
4/3/2024 83
Sreenu Thalla, Department of
Pharmacology

84. Function of Platelets
1) Secrete vasoconstrictors that cause vascular
spasms in broken vessels
vascular spasms
4/3/2024 84
Sreenu Thalla, Department of
Pharmacology

85. 2) Form temporary platelet plugs to stop bleeding
4/3/2024 85
Sreenu Thalla, Department of
Pharmacology

86. 3) Secrete chemicals that attract neutrophils and
monocytes to sites of inflammation
4/3/2024 86
Sreenu Thalla, Department of
Pharmacology

87. 5) Dissolve blood clots that have outlast their usefulness
4) Secrete growth factors that stimulate mitosis in
fibroblasts and smooth muscle and help maintain the
linings of blood vessels
4/3/2024 87
Sreenu Thalla, Department of
Pharmacology

88. Coagulation (Clotting)
- Many clotting factors in
plasma are involved in
clotting.
- These factors are
inactive in the blood.
- They are activated when:
1) blood vessel is
broken, or
2) blood flow slows
down.
4/3/2024 88
Sreenu Thalla, Department of
Pharmacology

89. - The sequential
activation (reaction
cascade) of the clotting
factors finally leads to
the formation of fibrin
meshwork.
- Blood cells are
trapped in fibrin
meshwork to form a
hard clot.
4/3/2024 89
Sreenu Thalla, Department of
Pharmacology

90. Fibrinogen Fibrin Fibrin
Polymer
soluble monomer Insoluble filaments
4/3/2024 90
Sreenu Thalla, Department of
Pharmacology

91. 4/3/2024 91
Sreenu Thalla, Department of
Pharmacology

92. Coagulation Disorders
Thrombosis is the abnormal clotting of blood in
an unbroken vessel.
Thrombus is a clot that attaches to the wall of
blood vessel.
Embolus is a clot that comes off the wall of blood
vessel and travel in the blood stream.
Embolism is the blockage of blood flow by an
embolus that lodges in a small blood vessel.
Infarction refers to cell death that results from
embolism. Infarction is responsible for most
strokes and heart attacks.
4/3/2024 92
Sreenu Thalla, Department of
Pharmacology

93. 1) Thrombocytopenia
- the number of circulating platelets is deficient
(<50,000/l )
- causes spontaneous bleeding from small blood
vessels all over the body
2) Deficiency of clotting factors due to impaired liver
function
3) Hemophilias
Hereditary bleeding disorders due to deficiency of
clotting factors
Bleeding Disorders
4/3/2024 93
Sreenu Thalla, Department of
Pharmacology