Blood Physiology

For Regular Pharmacy Students-2015EC

BY ;
Adugnaw Ambelu(MSc)

University of Gondar

CMHS

Department of
Human Physiology
 Objectives
At the end of this chapter the students are expected to:
1. List functions of blood.

2. Explain the components of blood.

3. Discuss about blood typing.

4. Discuss the functional classification of lymphocytes with

its primary role

5. Enumerate the functions of the immune system.

2
 Introduction
• Blood, vital fluid that

– provides important nutrients to all body tissues &

– carries away waste materials.

• Blood is referred to as “river of life,”

• It is the only fluid connective tissue

• Formed elements are suspended in nonliving fluid matrix

called plasma

• An adult human has about 4 - 6 liters of blood, which is

roughly 7- 8% of total body weight.
3
 Overview of Blood Circulation
• Blood leaves the heart via arteries that branch repeatedly until
they become capillaries.

– O2 & nutrients diffuse across capillary walls & enter tissues

– CO2 & wastes move from tissues into the blood

• Oxygen deficient blood leaves the capillaries and flows in veins

to the heart.

• This blood flows to the lungs where it releases CO2 & picks up
O2

• The oxygen rich blood returns to the heart.

4
 Functions of Blood
1. Substance distribution.

2. Regulation of blood levels of particular substances.

3. Protection.

5
 Distribution

Blood transports:

1. Oxygen from the lungs and

nutrients from the digestive
tract.

2. Metabolic wastes from cells

to the lungs and to kidneys
for elimination.

3. Hormones from endocrine

glands to target organs.
6
Regulation Protection
Blood maintains: Blood prevents blood loss by:

1. Appropriate body 1. Activating plasma proteins &

temperature by platelets.
absorbing & distributing 2. Initiating clot formation when
heat. a vessel is broken.
2. Normal pH in body Blood prevents infection by:
tissues using buffer 1. Synthesizing & utilizing
systems. antibodies.
3. Adequate fluid volume 2. Activating WBCs to defend the
in the circulatory system. body against foreign invaders.
7
 Characteristics of blood
▪ pH of blood:

▪ 7.35 (venous) to 7.45 (arterial),which is slightly alkaline

▪ Venous blood normally has lower pH than arterial blood

▪ Viscosity: thickness/ stickiness of blood

• Measure of resistance of blood to flow

• Contributes to normal BP

– Blood is 3-5 times denser & more viscous than water &
feels slightly sticky

– Due to blood cells & plasma proteins

8
 Characteristics of blood…
▪ Osmolarity
✓ 300 mOsm, reflects concentration of solutes in plasma
▪ Salinity
✓ 0.9%, concentration of NaCl in blood
▪ Temperature:
✓ 38°C (100.4°F), about 1°c higher than oral or rectal body
temperature
▪ Specific gravity/relative density
• Depends on RBCs & Plasma proteins
• More influenced by RBCs
• Blood: 1.05 - 1.06g/ml 9
 Characteristics of blood….
• Color: oxygen content determines color

– Arterial blood is bright red (oxygen-rich)

– Venous blood is dark red (oxygen-poor)

• Drops much oxygen in tissues & thus has a darker, dull

red color

10
 Characteristics of blood….
• Blood Volume

– The amount of blood inside

circulatory system & stored in
certain organs like spleen

– It represents total blood of body

– Normal value

= 80 ml/kg

= 5 – 6 L / 70kg body weight

for males, 4–5 L for females
11
Blood volume…

12
 Blood volume…
• The volume of blood in an individual
fluctuates.
– During dehydration, blood volume
decreases. E.g., running a marathon
– Blood volume increases in pregnancy,
• when the mother’s blood needs to
carry extra oxygen & nutrients.
– Blood volume increases during
exercise, High altitude
– Blood volume is higher in males than
females(why?) 13
 Composition of Blood
• Blood is the body’s only fluid tissue composed of:

– Liquid Plasma (55%) &

– Formed Elements (45%)

• Formed elements include:

1. Erythrocytes = Red blood cells (RBCs)

2. Leukocytes = White blood cells (WBCs)

3. Thrombocytes = Platelets

14
Composition of Blood…

15
 Composition of Blood…

Plasma
(55% of whole blood)

Buffy coat:
leukocytes and
platelets
1 Withdraw blood 2 Centrifuge (<1% of whole blood) Formed
and place in tube elements
Erythrocytes
( 45% of whole blood)

16
Composition of Blood…

17
Composition of Blood…

18
Blood Plasma (liquid portion of blood)
• Clear straw colored fluid portion of
blood after cellular elements are
removed

– Nonliving part of blood

• Intravascular part of ECF

• Serum is plasma without

fibrinogen & clotting factors

19
 Blood Plasma…..
Blood plasma contains over 100 solutes, including:
❖ Proteins
- albumin, globulins, clotting proteins, …
❖ Non-protein nitrogenous substances
- lactic acid, urea, creatinine
❖ Organic nutrients
- Glucose, Carbohydrates, Amino Acids, Fats
❖ Electrolytes
- Sodium, Potassium, Calcium, Chloride, Bicarbonate
❖ Respiratory gases
20
- O & CO
 Formed Elements (Cells in Blood)
• Erythrocytes, leukocytes, & Thrombocyte make up the formed
elements

☞Only WBCs are complete cells

☞RBCs have no nuclei or organelles, &

☞Platelets are just cell fragments

• Most formed elements survive in the bloodstream for only a

few days

• Most blood cells do not divide but are renewed by cells in bone
marrow.
21
 Hematopoiesis/Hemopoiesis
• Production/synthesis of blood cells

• Blood cells begin their lives in bone marrow from single type

of cell called pluripotent hematopoietic stem cell (PHSC)

which is present in BM

• Intermediate stage cells become committed to particular line of

cells called Committed Stem Cells

22
23
Stages in blood cells development

25
 Haematopoiesis regulating factors
• Hemopoiesis is chemically regulated by

– Colony stimulating factors: GM-CSF,, M-CSF

– Interleukines (e.g. IL-3)

– Platelet derived growth factor (PDGF)

– Thrombopoietic stimulating factor (TSF)

– Erythropoietin, GH, thyroid hormones (T3/T4), androgen

(Testosterone)

26
LT-HSC- long-term hematopoietic stem cell; ST-HSC-short-term hematopoietic
stem cell. CLP, common lymphoid progenitor; CMP, common myeloid progenitor27
Erythrocytes and Blood Grouping
 Erythrocytes (RBCs)
• Biconcave discs, anucleate,
essentially no organelles.

• Filled with hemoglobin (Hgb), a

protein that functions in gas
transport.

• Plasma membrane of RBCs is

comprised of flexible proteins

– allow them to change shape as

necessary.
29
 Erythrocytes (RBCs)…
➢ Structural characteristics contribute to its gas transport function

✓ Biconcave shape that has a huge surface area relative to

volume.

✓ Discounting water content, erythrocytes are more than 97%

hemoglobin.

✓ ATP is generated anaerobically, so the erythrocytes do not

consume the oxygen they transport.

Men= 5,200,000 ±300,000

Women= 4,700,000 ±300,000
30
[Guyton and Hall, textbook of medical Physiology, 13th ed]
 Functions of RBC

1. Carries hemoglobin that in turn transports respiratory gases

(O2 & CO2)

2. Carbonic anhydrase (CA): enzyme located in RBC membrane

• CO2 + H2O CA H2CO3 CA HCO-3 + H+

• CA increases rate of this reaction 5000-fold

• Good to transport CO2 from tissues to lung very fast

31
 Erythropoiesis
• Process of RBC synthesis

• Yolk sac (3wk to 3 months)

• Middle trimester of gestation

– Liver, Spleen & lymph nodes

• Starting from last month of gestation onwards and after

birth
✓ Ribs
– Red bone marrow
✓ Sternum
✓ Vertebrae
✓ Pelvic bones
✓ Proximal ends of long bones
32
Erythropoiesis…

33
 Substances for erythropoiesis
A. Vitamin B12: requires Intrinsic factor (IF) for its absorption

– Used in DNA synthesis & thus cell division

– Insufficient IF causes , Maturation failure for Vit. B12 , called

pernicious anemia

B. Folic acid: important in DNA synthesis

C. Iron: Necessary for RBC formation

D. Trace elements like copper

34
 Regulation of erythropoiesis
➢ Erythropoiesis is hormonally controlled and depends on
adequate supplies of:
• Iron, proteins, lipids, carbohydrates , vitamin B12, and folic acid

• Hormones accelerating erythropoiesis:

– Erythropoietin from Juxta Glomerular( JG) cells and

hepatocytes

– GH from anterior pituitary gland

– T3/T4 from follicular cells of thyroid gland

– Androgens from adrenal gland and gonads

• Intrinsic factor (IF) from stomach 35

 Hormonal Control of Erythropoiesis
➢ Erythropoietin (EPO) release by the
kidneys is triggered by hypoxia due to:
1. Decreased RBCs count.
2. Decreased oxygen availability.
3. Increased tissue demand for
oxygen.
➢ Enhanced Erythropoiesis increases
the:
– RBC count in circulating blood
– Oxygen carrying ability of the blood.
36
Figure. Control of erythropoiesis 37
 Hematocrit(Hct)
• % volume of packed RBC’s from whole blood

• Accounts about;

• 42-48% (M)

• 38-43% (F)

▪ Hct increases in dehydration

▪ Thus knowing Hct value is important in

clinical practices to diagnose diseases

• Hematocrit= 3 times Hemoglobin

39
 Hemoglobin (Hb)
• Red protein molecule containing iron, responsible for O2
transport

• Normal concentration

➢ 15 g/dl or 15g% in Males

➢ 14 g/dl or 14g% in Females

• About 280 million Hb molecules per RBC

• Hb reversibly binds with O2 and most O2 transport is in this

form

40
 Hemoglobin…
• 4 non-protein O2 binding heme and 4
peptide chains (globin)

• Globin for adult hemoglobin

– Two alpha(α) & 2 beta(β) chains

• Heme: for each peptide chain &

contains iron that combines reversibly
with 1 O2

• 1 heme to one chain to 1 O2

41
 Hemoglobin…
• Iron is the site of O2 binding at heme

• 1 Hb molecule can bind with 4 O2

• 1g of Hb can bind with 1.34 ml O2

▪ 15g of Hb/dl x 1.34 ml O2 = 20.1 ml O2 /100 ml blood

42
 Structure of Hemoglobin

The body stores iron in :

✓ Hemoglobin (65%), liver, spleen & bone marrow.
43
 Destruction of RBCs
• The life span of an erythrocyte is 100–120 days.

• Old erythrocytes become rigid and fragile, and their

hemoglobin begins to degenerate.

• Dying erythrocytes are engulfed by macrophages.

• Heme & globin are separated & the iron is salvaged for reuse:

*Heme: broken down into iron and bilirubin

*Globin: a reusable protein

45
 Destruction of RBCs…
Steps in destruction of RBC:

• RBC =hemoglobin= Globin + Heme

• Globin = AA’s : used for protein synthesis

• Heme = Fe2+ + porphyrin rings

• Fe2+ = stored in liver: for new Hb synthesis

• Porphyrin oxidized to green pigment called biliverdin and

later reduced to bilirubin

46
 Destruction of RBCs…
• Bilirubin + serum albumin :reach to liver

– Bilirubin conjugates with glucuronic acid

• Liver releases bilirubin as bile to intestine

• Bacteria change bilirubin into:

– Stercobilinogen- stercobilin: feces (brown)

– Urobilinogen-Urobilin: Urine (yellow)

47
 Destruction of RBCs…

48
Formation and destruction of RBCs, and the recycling of hemoglobin components.
 Disorders related to RBCs
Anemia/erythropenia
• Deficiency of Hb in blood. Types
1. Deficiency anemia: caused by deficiency of vit-B12 , folic acid,
Iron, proteins
2. Aplastic anemia: depression of bone marrow due to
irradiation, drugs and leukemia
3. Hemolytic anemia: prematurely ruptured erythrocytes or
formation of fragile RBCs due to sickle cell, transfusion
reaction, snake venoms, malaria, erythroblastosis fetalis
4. Bleeding (blood loss anemia or hemorrhagic anemia): result
of acute or chronic loss of blood 49
 Polycythemia(Erythrocytosis)
• RBC count is more than normal
– Abnormal increase of RBC in circulation
– ↑RBC s count > 6 m illion/m m 3 or Hct of >55%
1. Polycythemia Vera
– Cancerous production causes excess RBCs
– Genetic mutation in hemocytoblast cell line that increases RBC
production
– Hematocrit values can reach 70%

2. Physiologic polycythemia
• Increase in RBC production due to hypoxic tissues
• A common type of 20 polycythemia, occurs in natives who live at high
altitudes, where atmospheric O2 is very low 50
 Human Blood Groups
• Blood types and transfusion compatibility are a matter of:

✓ Interactions between plasma proteins and erythrocytes.

• All cells have an inherited combination of proteins:

✓ Glycoproteins and glycolipids on their surfaces.

• These function as:

✓ Antigens that enable our immune system to distinguish our

own cells from foreign invaders.

✓ Production of γ globulins called antibodies to combat the

invader.
51
 Human Blood Groups…
• The clumping of red blood cells when testing blood

compatibility or resulting from a transfusion reaction is called

agglutination.

• In blood typing, the antigens on RBC surfaces are called

agglutinogens.

• The plasma antibodies that react against antigens are called

agglutinins.
52
 Human Blood Groups…
• Over 400 different blood group antigens have been found,
many of these being very rare.

• The two most important blood group systems used to describe

the blood type were:

– ABO group and

– Rhesus group

53
Prevalence of
ABO & Rh
blood groups
among different
ethnic groups

Frequency of blood groups (%)

Races
O A B AB Rh+
Whites 45 41 10 4 85
Blacks 48 27 21 4 88
Chinese 36 28 23 13 100
Ethiopians 47 28 20 5 97
54
 Importance of Knowing Blood groups:
• ABO blood grouping is clinically significant in:

➢ Transfusion during emergency conditions

➢ Transplantation

➢ Pregnancy (Rh incompatibility)

➢ Universal donor or recipient identification.

➢ Judicially purposes (parental disputes)

➢ Social relations

55
 Landsteiner’s Law
• If agglutinogen is present on RBC
surface corresponding agglutinin must
absent in plasma

• If agglutinogen is absent on RBC

surface corresponding agglutinins must
Karl Landsteiner( 1900)
present in plasma

56
 ABO Blood Group system…
• Based on the + of 2 agglutinogen (A and B), the ABO blood

group can be classified into 4 types of blood.

1. When agglutinogen A is present on RBCs, the blood is type-A

2. When agglutinogen B is present on RBCs, the blood is type-B

3. When both agglutinogen A & B exist together, the blood is

type-AB

4. When neither agglutinogen A nor B are present, type-O

57
 ABO Blood Group system…
• In the ABO blood grouping, plasma contains two genetically
determined agglutinins (antibodies):

➢ Anti-A antibodies (agglutinin-α)

➢ Anti-B antibodies (agglutinin-β)

• Persons with

➢ Type A blood have anti-B antibody in their plasma

➢ Type B blood have anti-A antibody

➢ Type AB blood have neither antibody

➢ Type O blood have both anti-A and anti-B.

58
Ag-Ab coexistence in the ABO Blood groups

59
ABO Blood Group system…

60
Observation of agglutination reactions

61
Observation of agglutination reactions

62
63
64
 Rh Factor
✓ It was first worked out on Rhesus monkey to the name Rh-
system.

✓ Grouped as Rh+ and Rh- based on the + of agglutinogen D on

the surface of RBCs:

➢ Presence of agglutinogen D on RBCs = Rh+

➢ Missing agglutinogen D on RBCs = Rh-

✓ Agglutinin (anti-D antibodies) are not normally present in the

serum, produced secondary to exposure of an Rh- blood to Rh+
blood (antigen-D).
65
 Erythroblastosis Fetalis
• Also called Hemolytic Disease of the Newborn (HDN)

• Disease that destroys red blood cells.

• A serious blood disease of fetuses & newborn babies,

– in which the antibodies produced by an RH- mother destroy

the RBCs of an RH+ fetus.

• Occurs when an Rh- mother marries an Rh+ father and

conceives an Rh+ fetus.

• During delivery, there could be a leakage of Rh+ blood from the

fetus to the circulation of the mother.
66
 Erythroblastosis Fetalis...
• Rh+ blood induces production of anti-D antibodies in the
circulation of the mother.

• During 2nd conception of Rh+ fetus, anti-D antibodies cross the

placenta and attack RBCs of the fetus.

• Treatment

– Rho Gam injection after 1st birth which blocks mother from
forming anti-Rh antibody

✓Limits risk for subsequent births

67
68
 Blood Transfusions
• Blood transfusion is giving of blood of one person to another
when there is a need.
• It can be:
1. Whole blood transfusion
– When blood loss is substantial.
– In treating thrombocytopenia.
• Often associated with hemorrhage.
2. Packed red cells transfusion
• Cells with plasma removed
• Are used to treat anemia.

69
 Transfusion Reactions
• Transfusion reactions occur when mismatched blood is infused.

• Donor blood cells are attacked by the recipient’s plasma:

– Diminished oxygen-carrying capacity.

– Clumped cells that impede blood flow.

– Ruptured RBCs that release free hemoglobin into the

bloodstream

• Circulating hemoglobin precipitates in the kidneys and

causes renal failure

70
 Compatibility between the Donor's Cells &
Recipient’s Serum
Recipients Serum
Donor's Cells
A B AB O
A ✓ Х ✓ Х
B Х ✓ ✓ Х
AB Х Х ✓ Х
O ✓ ✓ ✓ ✓

✓ No Agglutination Х Agglutination
AB = universal receiver O = universal donor
71
Compatibility between the Donor's Cells & Recipient’s Serum

Blood type Can donate blood to Can receive blood from

A+ A+, AB+ A+, A-, O+, O-

B+ B+, AB+ B+, B-, O+, O-

AB+ AB+ All types

O+ A+, B+, AB+, O+ O+, O-

A- A-, A+, AB-, AB+ A-, O-

B- B+, B-, AB+, AB- B-, O-

AB- AB+, AB- A-, B-, AB-, O-

O- All types O-
72
 Diagnostic Blood Tests
▪ Laboratory examination of blood can assess an individual’s
state of health
▪ Microscopic examination:
✓ Variations in size & shape of RBCs
o Predictions of anemias
✓ Type and number of WBCs
o Diagnostic of various diseases
▪ Chemical analysis can provide
▪ A comprehensive picture of one’s general health status in
relation to normal values.

73
 Platelets and Hemostasis
• Platelets are disk-shaped cell fragments produced in the
megakaryocytes

• The smallest cells in the blood

– designed for coagulation/ forming a clot, whenever a blood

vessel is broken.

75
 Platelets and Hemostasis…
• As soon as an artery or vein is injured,

– the platelets in the area of the injury begin to clump together

& stick to the edges of the cut.

• Platelets also release messengers into the blood that perform a

variety of functions:

1. Constricting the blood vessels to reduce bleeding.

2. Attracting more platelets to the area to enlarge the platelet

plug.

3. Initiating the work of plasma-based clotting factors, such

as fibrinogen. 76
 Platelets and Hemostasis…
• Through a complex mechanism involving many steps and

many clotting factors,

– the plasma protein fibrinogen is transformed into long,

sticky threads of fibrin.

• Together, the platelets and the fibrin create an intertwined

meshwork that forms a stable clot.

• This self-sealing aspect of the blood is crucial to survival.

77
 Genesis of Platelets
• The stem cell for platelets is the Hemocytoblast

78
 Platelets and Hemostasis…
• Platelets have many functional characteristics of whole cells:

– Actin and myosin

– Thrombosthenin,

– Residuals of both the ER and the Golgi apparatus

• that synthesize various enzymes & store calcium ions

– Mitochondria & enzyme systems

• Capable of forming ATP & ADP

– Enzyme systems that synthesize Prostaglandins

– Fibrin-stabilizing factor & growth factor

79
 Platelets and Hemostasis…
• On the platelet cell membrane surface

– There is a coat of glycoproteins

• that repulses adherence to normal endothelium

• Surface glycoprotein Ib and IIb/IIIa receptors

– Large amounts of phospholipids

• activate multiple stages in the blood clotting process

– Have two types of special organelles:

• α- granules and,

• less abundantly, dense-core (Delta) granules

80
Platelets and Hemostasis…

81
 Platelets…
α-Granules Dense (Delta) granule
• Have adhesion molecule P-selectin • Contain
• Contain – ADP & ATP,
– Fibrinogen – ionized calcium,
– Fibronectin, – Histamine,
– Factors V & VIII, – serotonin, &
– Platelet factor IV – epinephrine
– PDGF
– TGF-ß

82
 Hemostasis - Stoppage of bleeding
• A series of reactions designed to arrest bleeding from a broken
blood vessel.
• Hemo- means “blood”; -stasis means “standing”
• The process of hemostasis involves 3 components:
☞Blood vessels
☞Thrombocytes &
☞Coagulation factors/proteins
• During hemostasis, 3 phases occur in rapid sequence:
☞Vascular spasm
☞Platelet plug formation
☞Coagulation (blood clotting) 83
 Step 1 Vascular spasm
• Smooth muscle contracts, causing
vasoconstriction.

Step 2 Platelet plug formation

• Injury to lining of vessel exposes
collagen fibers; platelets adhere.
Collagen fibers

• Platelets release chemicals that make

nearby platelets sticky; platelet plug
Platelets forms.

Step 3 Coagulation
• Fibrin forms a mesh that traps red blood
cells and platelets, forming the clot.
Fibrin Fig Events of hemostasis.
84
Hemostasis…

85
86
 Hemostasis, 1st Vascular spasm
• Local vasoconstriction that is caused by:

• Reflex sympathetic discharge &

• Local myogenic contraction of the vascular wall

• Local autacoid factors

– From the traumatized tissues and blood platelets

• All reactions minimize rate of bleeding

– By narrowing the diameter of the hole (rupture) on the

wall of the blood vessels.

87
Hemostasis, Vascular spasm

88
 Hemostasis, 2nd Platelet Plug Formation
• Normally, platelets do not stick to each other or to the
endothelial lining of blood vessels.

• Upon damage to blood vessel endothelium (which exposes

collagen) platelets:

– Adhere & stick to exposed collagen fibers and form a

platelet plug

– Release serotonin and ADP, which attract additional

platelets

• Platelet plug is limited to the immediate area of injury.

89
 Hemostasis, Platelet Plug Formation
• Platelet plug involves the three successive steps

☞1st Adhesion

☞2nd Activation

☞3rd Aggregation

90
Hemostasis, Platelet Plug Formation

COLLAGEN

THROMBIN
ADP
GpIIb/IIIa
GpIIb/IIIa
GpIIb/IIIa Aggregation

Adrenaline Platelet
Adhesion
vWF

Endothelium
Exposed Collagen 91
 Hemostasis, Platelet Plug Formation
 Adhesion
◼ Platelets adhere to damaged vessel wall indirectly via von
Willebrand factor- vWF
 Activation
◼ Excitatory agonists (collagen, thromboxaneA2, etc.) cause a
conformational change in platelet to expose Glycoprotein
IIb/IIIa binding sites for fibrinogen
 Aggregation
◼ Platelets are laced together through fibrinogen bridges
 Fibrin formation
◼ Locally thrombin converts the fibrinogen to fibrin
stabilizing the platelet plug 92
Fig. Fibrin clot. Scanning electron micrograph of red blood
cells trapped in a mesh of fibrin threads.
93
Hemostasis, Platelet Plug Formation

94
Hemostasis, Platelet Plug Formation

95
 Hemostasis…3rd Coagulation
• A set of reactions in which blood is transformed from a liquid
to a gel (clot).

• It is slow, but the body’s most powerful hemostatic

mechanism to stop bleeding.

• Activator substances from

☞Traumatized vascular wall,

☞Platelets, and

☞Blood proteins

96
 Hemostasis… Coagulation
• More than 50 important substances that affect blood
coagulation have been found

– Procoagulant

– Anticoagulants

• When a vessel is ruptured,

– Procoagulants become “activated” and override the

anticoagulants,

97
 Blood Clotting Factors
1. Factor-I: Fibrinogen
2. Factor-II: Prothrombin. α1- globulin
3. Factor-III: Tissue factor, tissue thromboplastin,
4. Factor-IV: Calcium ion, essential for clotting
5. Factor-V: Labile factor, β-globulin.
6. Factor-VII: Stable factor, α1-glubulin
7. Factor -VIII: Antihemophilic factor-A, β2-globulin
8. Factor -IX: Christmas factor, AHF-B, α1- globulin
9. Factor -X: Stauter-power factor
10. Factor-XI: AHF-C, γ-globulin
11. Factor-XII: Contact factor, Hagen factor, glass factor
12. Factor-XIII: Fibrin stabilizing factor, β-globulin 98
 Vitamin-K and blood clotting
• Almost all the blood clotting factors are formed by the liver

• Vitamin K is an essential factor to a liver for production of

clotting factors

– prothrombin, Factor VII, IX, X, and protein C

• Depressed formation of clotting factors by liver results from

– Diseases of the liver &

– Vitamin K deficiency as a result of

• Poor absorption of fats from the GIT

• Failure of the liver to secrete bile

99
 Hemostasis… Coagulation
• Coagulation undergoes three steps of reactions:

1. Formation of prothrombin activators through

• The intrinsic pathway

• The extrinsic pathways

2. Conversion of prothrombin into thrombin by the action of

prothrombin activators (Prothrombinase)

3. Conversion of fibrinogen into fibrin thread by the action of

thrombin

100
101
 Injury to the Blood vessel

Damage to the endothelium &

Local smooth
Exposure of Collagen fibrinogen
muscle
contraction
Adherence of Platelets
or
Release of Activation of Platelets Fibrin thread
Vasoconstrictor
Serotonin by Secretion of ADP, & Thromboxane A2
the platelets
Aggregation of more & more Platelets Blood
Formation of loose Platelet plug clotting
Vasoconstriction
Formation of tight
Hemostatic plug 102
Formation of prothrombin activators

F-III

103
The coagulation cascade

104
 Hemostasis…
• Coagulation is formed primarily of fibrin threads (or
polymers),

– but also including blood cells and platelets.

• Blood clots:

– in the right places prevent the loss of blood from ruptured

vessels,

– but in the wrong place can cause problems such as a stroke .

107
 Clot Retraction & Repair
• Clot retraction

– Stabilization of the clot by squeezing serum from the fibrin

strands

• Vessel Repair: is vessel healing mediated by:

– Platelet-derived growth factor (PDGF) stimulates division of

• Smooth muscle cells and

• Fibroblasts to rebuilding blood vessel wall

– Vascular endothelial growth factor (VEGF) stimulates

•Endothelial cells to multiply & restore the endothelial lining

108
 Dissolution
• Clot usually is dissolved within a few days after clot formation
by a process called

– fibrinolysis

• It involves the activity of plasmin

• Plasmin is formed when inactive plasminogen is activated by

– Thrombin,

– Factor XII,

– Tissue plasminogen activator (t-PA),

– Streptokinase, and Lysosomal enzymes

109
Fibrinolysis

110
 Prevention of unwanted intravascular clotting
1. Endothelial Surface Factors
– Smoothness of the endothelial cell surface
• prevents contact activation of the intrinsic clotting system
– A layer of glycocalyx on the endothelium
• repels clotting factors and platelets
– Thrombomodulin which binds thrombin,
– this binding(thrombomodulin-thrombin complex )
• slow the clotting process by removing thrombin
• activates protein C
– that in turn inactivates activated Factors V and VIII
111
Fibrinolytic system and its regulation by protein C.

112
 Prevention of unwanted intravascular clotting

2. The presence of intravascular anti-platelet aggregating agents

and anticoagulants
– Produced by endothelial cells, platelets and WBCs.
• Prostacyclin
• Nitric oxide
• Adenosine diphosphatase
• Heparin
• Anti-thrombin-III
• Prostaglandin-I2
• Oral anticoagulant drugs
113
114
Leukocytes and Immune system

115
 Leukocytes (WBCs)…
• The only blood components that are complete cells.
– contain nucleus, and other organelles
• Less numerous than RBCs and platelets.
• WBC count :
– Normal (4,000-11,000/mm3)
• Average (7,000/mm3)
– Decrease in WBC count = Leukopenia
– Increase in WBC count = Leukemia
* normal response to bacterial or viral invasion
• Function = defense/protection against disease. 116
 Leukocytes (WBCs)…
• WBCs only make up about 1% of blood,

– but their small number belies their immense importance.

• Play a vital role in the body’s immune system.

– the primary defense mechanism against invading bacteria,

viruses, fungi, and parasites.

• Often accomplish this goal through direct attack,

– which usually involves identifying the invading organism as

foreign, attaching to it, and then destroying it.

➢This process is referred to as phagocytosis.

117
 Leukocytes (WBCs)…
• WBCs also produce antibodies,
– which are released into the circulating blood to target and
attach to foreign organisms.
– after attachment, the antibody may neutralize the organism,
or
– it may elicit help from other immune system cells to destroy
the foreign substance.
• There are several varieties of WBCs,
– including neutrophils, monocytes & lymphocytes,
– all of which interact with one another & with plasma
proteins & other cell types to form the complex & highly
effective immune system.
118
 Types of WBCs
Granular leukocytes Agranular leukocytes
PMN-cells:
Neutrophils Monocytes
Eosinophils Lymphocytes
Basophils
WBC differential count
❖ Neutrophils: 50-60% (60%), 3000-7000/mm3
❖ Eosinophils: 1-4% (2.4%), 100-440/mm3
❖ Basophils: 0.3-0.5% (0.4%), 20-50/mm3
❖ Monocytes: 2-8% (5.3%), 100-700/mm3
❖ Lymphocytes: 20-40% (30%), 1500-3500/mm3

mnemonic = (Never Let Monkeys Eat Banana) 119

 Primary Functions of WBCs
1. Neutrophils

– The most abundant WBC & the first line of defense.

– Phagocytic cells (ingest bacteria)

2. Monocytes

– The largest WBCs & highly phagocytic cells.

– Leave the circulation, enter tissue & differentiate into

macrophages:

120
 The tissue macrophage system
(Reticuloendothelial System)
Monocytes are formed in the bone marrow

enter the circulation

leave the circulation & enter the tissue

↑size,↑lysosom alactivities

become tissue macrophages

Lungs
Skin Liver Brain Bone Spleen
Alveolar Histocyti Kupffer Microglia Lymph nodes
Osteoclastes
macrophage c cells cells l cells reticular cells
121
 Primary Functions of WBCs...
3. Basophils
– Liberate heparin, histamine & serotonin in allergic
reactions that intensify the overall inflammatory response.
– Increases in allergic reactions, leukemia, cancers,
4. Eosinophils
– Absorb histamine during allergic conditions so that lessen
the severity of allergies
– Produce hydrolytic enzymes to kill big parasites.
– Increase in number during parasitic infection
• Eosinophilia 122
 Primary Functions of WBCs...
5. Lymphocytes

– Are responsible for acquired immunity.

– Of 2 types; B and T lymphocytes.

– An important cell class in the immune system that produces

antibodies:

• to attack infected & cancerous cells, and

• to reject foreign tissue.

123
 The Immune System
• A complex system that is responsible for protecting us against
infections & foreign substances.
• There are three lines of defense:
1. Keep invaders out (skin, mucus membranes).
2. Non-specific ways to defend against pathogens that have
broken through the first line of defense (inflammatory
response & fever).
3. Mounted against specific pathogens that are causing
disease.
• B cells produce antibodies against bacteria or viruses in
the ECF,
• T cells kill cells that have become infected.
124
 The Immune System …
• The immune system is closely tied to the lymphatic system,
with B & T lymphocytes being found primarily within lymph
nodes.

– Tonsils & thymus gland are also considered lymph organs

& are involved in immunity.

• We often don't realize how effective the immune system is until

it fails or malfunctions, such as when the lymphocytes are
attacked by HIV in an AIDS patient.

125
 The Immune System …
• Body's ability to resist or eliminate potentially harmful foreign
materials or abnormal cells consists of the following activities:

1. Defence against invading pathogens (viruses & bacteria).

2. Removal of 'worn-out' cells (old RBCs) & tissue

debris (from injury or disease).

3. Identification & destruction of abnormal or mutant cells -

primary defence against cancer.

4. Rejection of 'foreign' cells (organ transplant ).

126
 Types of Immunity
A. Innate / Natural / Non-specific immunity
✓ HCl in the stomach
✓ Phagocytosis
✓ Skin barrier
✓ Lysozymes in saliva
B. Acquired/ Adaptive / Specific immunity
Features:
✓ Specific
✓ Memory
✓ Recognition of self and non-self
127
 Innate Immunity
• It is also known as Natural / Nonspecific immunity.

• It is present since from the birth & it is the inborn capability of

the body to resist the entry of microorganisms into the body.

• This type of immunity represents the first line of defense

against any pathogens.

• Therefore, it is called NonSpecific Immunity.

128
 Innate Immunity…
• The mechanisms involved in Innate Immunity are:

1. Destruction of bacteria by gastric HCl.

2. Protective function of ciliated epithelium in the respiratory

tract.

3. Reflex mechanisms like sneezing, coughing, & vomiting.

4. Protective function of keratinised stratum corneum of skin,

a physical barrier against entry of microorganisms.

5. Presence of proteolytic enzymes & lysosomes in secretions

like sweat, saliva, sebum etc. destroys or inactivate the
bacteria. 129
 Acquired Immunity
• It is the resistance developed in the body against any specific
foreign body like bacteria, viruses, toxins.

• It is the most powerful immune mechanism that protects the

body from the invading organisms or toxic substances.

• Of two types:

1. Passive Immunity

2. Active Immunity

➢ Active immunity is the function of Lymphocytes.

130
 Acquired Immunity…
1. Passive Immunity:

– Immunity developed in a nonimmune individual by

transfer of blood, serum, lymphocytes/antibodies from an
immune individual.

2. Active Immunity:

• Immunity developed by the production of antibodies in

response to the specific foreign antigen or

• Immunity developed by the production of antibodies by

injecting antigen into the body through vaccination.
131
 Active Immunity
• Active Immunity is of 2 types:

1. Cell Mediated Immunity (Cellular Immunity)

2. Antibody Mediated Immunity (Humoral Immunity)

1. Cell Mediated Immunity:

• It is provided by the activation of T lymphocytes.

• It is particularly effective against intracellular pathogens

that reside within host cells primarily fungi, parasites, &
viruses.

132
 Active Immunity …
2. Antibody Mediated Immunity

• It is provided by the activation of B lymphocytes.

• B lymphocytes fight against the invading organisms by

secreting antibodies into the blood & lymph.

• It is particularly effective against extracellular pathogens that

multiply in body fluids, mostly the bacteria.

133
 Development & Processing of Lymphocytes:
Lymphoid stem cell
Lymphocyte
From bone marrow

Thymus processing [Maturation]

Thymopoietin
Mature B lymphocyte
Mature T lymphocyte
Antigen
Sensitised T cell Sensitised B cell
Memory cells

Helper T Memory Suppressor Cytotoxic T Plasma cells

cells cells T cells cells
Antibodies
Cell mediated immunity Antibody mediated immunity 134
Development of Cell Mediated Immunity:
• To develop cell mediated immunity, T cells must be
activated by exposure to an antigen
• Antigenic materials are released from invading
organisms & presented particularly to helper T- cells
❖ Done via a special type of cells called Antigen
Presenting Cells (APC).
• Antigen Presenting Cells, Helper T Cells,
Cytotoxic T Cells, Suppressor T Cells & Memory T
Cells have their own roles.

1/13/2023 Blood Physiology 135

 1. Role of Antigen Presenting cells:
•Only Macrophages & B lymphocytes function as
APCs & synthesize class II MHC proteins.
•Helper T cells require class II MHCs to function.
•Foreign organisms invade the body the APCs engulf
them by phagocytosis.
• Later the antigen from the engulfed organism is
partially digested into smaller peptide fragments by
the proteolytic enzymes of macrophage.

1/13/2023 Blood Physiology 136

▪ The resulting
digested
.
fragmented
then bind to
class II MHC
proteins of
macrophage. IL 1 & TNF

1/13/2023 Blood Physiology 137

 2. Role of helper T cells:
•Binding b/n helper T cell receptor & antigen bound
to class II MHC is an essential event for the activation of
helper T cells.
• Finally antigenic binding of the APC to the helper T cell
causes the APC to secrete interleukin – 1 ( IL-1 ) & Tumor
necrosis factor ( TNF ),which facilitates the activation of
helper T cells.
• Activated helper T cell now secretes various cytokines like
• IL-2 which inturn activates the same helper T cell &
as well as the nearby cytotoxic T cells.
• IL-4 & IL-5 which activates the B lymphocytes & causing
the production of antibodies.

1/13/2023 Blood Physiology 138

 3. Role of Cytotoxic Cells:
• Activated cytotoxic T cells circulate through blood & lymph
& destroy the invading organisms by attacking them directly
in the following way –
1. Binding b/n cytotoxic T cell receptor & antigen causes the
release of cytotoxic substances like lysosomal enzymes
which destroys large number of microorganisms.
2. Cytotoxic T cells destroy even body’s own tissues which are
affected by the foreign bodies particularly the viruses. Many
viruses are entrapped in the membrane of affected cells.
• Virus antigens attract the T cell , the cytotoxic cells kill the
affected cells also along with viruses b/c of this cytotoxic T cell
is called Killer cell (Natural Killer cells ).

1/13/2023 Blood Physiology 139

 4. Role of Suppressor T- Cells:
•Suppressor T cells are also called as Regulatory T cells.

• These T cells suppress the activities of Cytotoxic T cells &

play important roles in preventing the cytotoxic T cells
from destroying the body’s own tissues along with invaded
organisms.

•Suppressor T cells also suppress the activities of helper T cells.

1/13/2023 Blood Physiology 140

 5. Role of Memory T Cells:
• Some of the T cells activated by an antigen do not enter the
circulation but remain in Lymphoid Tissue.
• These T cells are called Memory T Cells.
• In later periods, the memory cells migrate to various
lymphoid tissues throughout the body.
• When the body is exposed to the same antigen for the 2nd
time, the memory cells identify the organism & immediately
activates the other T cells. So, the invading organism will
be destroyed very instantly.
•Response of T cells is also more powerful at this time.

1/13/2023 Blood Physiology 141

Development of Antibody Mediated Immunity

• Antibody Mediated Immunity is developed by the

antibodies, which are circulating in the blood.
•Antibodies are produced by the B lymphocytes.
– These antibodies fight against the invading organisms.
• Antibody Mediated Immunity is the major
defensive mechanism against bacterial infection.
• As in the case of Cell Mediated Immunity,
macrophages & other APC play an important roles
in the development of Antibody Mediated
Immunity.

1/13/2023 Blood Physiology 142

 1. Role of Antigen Presenting cells.
• Antigen Presenting Cells (Macrophages) present the
antigen bound to class II MHC to B cells in addition
to presenting to T cells.

• The B cell receptor recognizes the antigen bound to

MHC which is displayed on the surface of the APC.

• The antigenic products activate B cells.

• Macrophages also secrete a cytokine called IL-1.
•This causes the activation & proliferation of lymphocytes.

• B cells proliferated & transformed into 2 types of cells.

1. Plasma Cells
2. Memory Cells
1/13/2023 Blood Physiology 143
 2. Role of Plasma Cells:
• Plasma Cells produce antibodies which are globulin in nature.
• The antibodies are called Immunoglobulin's.
• The rate of antibody production is very high & are released
into lymph & then transported into the circulation.

3. Role of Memory B cells:

• Occupy the lymphoid tissues throughout the body.
• Are in inactive condition until the body is exposed to the
same antigen for the second time.
•Antibodies produced during the 2nd exposure to the
foreign antigen are also more potent than those produced
during 1st exposure.
1/13/2023 Blood Physiology 144
 4. Role of Helper T cells:

▪ The activated helper T cells in response to antigen

secrete two substances called :
➢ IL – 2 &
➢ B cell growth factor which promote;
• Activation of more number of B lymphocytes.
• Proliferation of Lymphocytes.
• Production of Antibodies.

1/13/2023 Blood Physiology 145

 Antibodies (Immunoglobulin’s)-Igs
• Are produced by plasma cells in response to antigen.
• The antibodies produced by B lymphocytes are found in almost
all the tissues of the body.
• Among these antibodies, Ig G forms 75%-80%of the antibodies
in the body Types:
1.IgG =80%
2.IgA =10-15%
3.IgM =5-10%
4.Ig D =0.2%
5.Ig E =0.1%

Mnemonic= 146
(Give Additional Money During Exams)
Immunoglobulin's)

1/13/2023 Blood Physiology 147

Mechanism of Action of Antibodies

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THANK YOU!!!

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