Chapter Five

Blood Physiology

1
Objectives:
• Understand the principal functions of blood

• Know the components of blood

• Appreciate the cellular components of blood and their

functions
• Understand blood grouping and its clinical significance

• Analyze hemostasis and the role of platelets

2
• Blood is a type of connective tissue, consisting of cells
and cell fragments surrounded by a liquid matrix.
• Blood makes up about 7 % of the total weight of the body.
• Cells require constant nutrition and waste removal
because they are metabolically active.
The heart pumps blood through blood vessels, and the
blood delivers nutrients and picks up waste products.

3
 Functions of the Blood

1. For transport of
• Oxygen from the lungs and nutrients from the
digestive tract to the tissues .
• Metabolic wastes from cells to the lungs and
kidneys for elimination.
• Hormones from endocrine glands to target organs.

4
 Function (continued)

2. Regulations
 Appropriate body temperature by absorbing and
distributing heat to other parts of the body.
 Acid-base balance-Hemoglobin acting as a
buffer.
3. Defense against infections by means of phagocytosis
and antibody formation.
4. Platelets prevent from bleeding.

5
 Characteristics of Blood

a.Color:
Bright red (arterial blood, oxygenated blood)
Dark red (venous blood, deoxygenated blood)
b.Viscosity: Blood is three to four times thicker and
denser than pure water.
c.pH range: from 7.35 to 7.45 (blood is slightly alkaline).

6
d. Volume of blood :
 Adult male: 5-6 liters
 Adult female: 4-5 liters
e. Specific gravity
– Refers to the weight of blood compared to
that of water.
 Male: 1.052- 1.063
 Female: 1.050 – 1.058

7
 Components of Blood

1. Formed elements (45%) - the actual cellular components of blood

a. Erythrocytes (Red blood cells)
b. Leukocytes (White blood cells)
c. Thrombocytes (Platelets )

2. Plasma (55%) - is the fluid portion of the blood.

8
 Components of Blood (continued)

Three layers after centrifugation of blood:

1. Upper suspension: is the blood plasma that
accounts to 55% of the blood volume.
2. Buffy coat located at the middle. Accounts to <
1% of the volume. It consists of WBC & platelets.
3. Lower portion : is a reddish mass of RBC that
settles at the bottom of the test tube. Accounts to
45% of the whole blood.

9
 Components of Whole Blood

Plasma (55% of
whole blood)
Buffy coat:
leukocyctes and platelets
(<1% of whole blood)

1 Withdraw blood 2 Centrifuge Erythrocytes

and place in tube
(45% of whole
blood)

10
11
 Plasma and it’s composition
• Plasma is the liquid portion of the blood and
accounts to about 55% of the total blood volume.
• Plasma is composed of :
– Water (93%) , proteins (7%), gases (O2, CO2 ),
nutrients , electrolytes, hormones, metabolic
wastes etc.

12
 Serum vs. plasma
• Serum is the yellowish fluid that forms after blood is left
to clot.

• Serum has more or less similar composition to plasma

except that its fibrinogen and clotting factors (II,VI, VII)
have been removed .

13
• Plasma proteins
A. Albumins (~ 60% )
B. Globulins ( ~ 36%)
C. Fibrinogen (~ 4%)

14
A. Albumin:
– Is produced in the liver.
– Helps to maintain blood volume, b/s it can not
easily pass through the capillary membrane and
thus, exerts the so called plasma colloid osmotic
pressure (oncotic pressure).
– Albumin serves in transporting nutrients,
hormones…

15
B. Globulin:
i. Alpha globulin

ii. Beta globulin

iii. Gamma globulin

 The majority of the immunoglobulin (antibodies) are part

of gamma globulins.

 Globulins help as carriers to transport lipoproteins, Fe 2+,

hormones, enzymes, nutrients…

16
C. Fibrinogen:

Fibrinogen is synthesized in the liver.

Involved in blood clotting

17
 Genesis of Blood Cells (Hematopoiesis)
• The blood cells begin their lives in the red bone marrow
from a single type of cell called the pluripotential
hematopoietic stem cell.
– From which all the cells of the circulating blood are
eventually derived.
• The pluripotential hematopoietic stem cells, will divide
and differentiate in myeloid stem cell and lymphoid
stem cells.

18
• The myeloid stem cells will divide and differentiate
in to:
oRBCs
oGranulocytes
oMonocytes
oPlatelets and
• Lymphoid stem cells will differentiate to
lymphocytes.

19
Red Blood Cells (RBC’s)

20
• Physical features of RBCs:
 A flexible biconcave cell that is thinner at the center and

thicker at the ages.

 Diameter: ~ 7.5 um
 Mature RBCs, No nucleus, no mitochondria, no ribosomes
 Can bend and twist to pass through the narrow
capillaries very easily.
 Cytosol is 97% occupied by Hgb.
The cell generates its ATP exclusively by glycolysis.

21
22
• Red blood cells compose most of the formed elements.

• Hematocrit - the percentage of red blood cell volume to total blood

volume in a centrifuged blood sample.

• It is 36% to 46% in women and 41% to 53% in men.

• Average: RBC Number

• 5.5 million/ mm3 of blood in male.

• 4.7million/ mm3 in female.

• Life span of RBC – 120 days.

23
 Functions of RBC
1.Carrying of O2 from the lungs to the systemic tissues,
2. Carrying of CO2 from tissues to the lungs,
3.Assisting in the buffering of acids and bases.
They contain a large quantity of carbonic anhydrase.
Increasing the rate of reaction between CO 2 and water to form carbonic acid
by several thousand fold.
The rapidity of this reaction makes it possible for the blood to transport large
quantities of CO2 in the form of HCO3-.

The hemoglobin in the cells is also an excellent acid-base buffer.

24
 Haemoglobin
280 million hemoglobin molecules/cell!(15g/dl)
Has two parts: Globin and Heme.
 Globin
Two alpha(α) chain polypeptide
Two beta(β) chain polypeptides
• The polypeptide chain (the Globulin unit) determines the physical
characteristics of the Hb-molecule. Thus, there exists:

1. Adult Hb (Hb A): 2 alpha + 2 beta

2. Fetal Hb (Hb-F): 2 alpha + 2 gamma

3. Sickle cell anemia (Hb-S): with valine substituted for glutamic acid
at position six of the beta chain.
25
 Heme
Each polypeptide has one heme group, each heme with
Fe2+ carries one oxygen molecule.
A total of four oxygen molecules are carried with in
one hemoglobin molecule.
The Hb molecule combine maximally with 4 molecules
of O2 in a cascade manner (100% saturated).

26
27
 Production of Red Blood Cells

i. Areas of the body that produce red blood cells

 In the early weeks of embryonic life primitive nucleated
RBCs are produced in the yolk sac.
 During the middle trimester of gestation, the liver is the
main organ for production of RBCs.
 Reasonable numbers are also produced in the spleen
and lymph nodes.
 During the last month of gestation and after birth, RBCs
are produced exclusively in the bone marrow.

28
• Until a person is 5 years old, the bone marrow of
essentially all bones produces RBCs.
• Except for the proximal portions of the humer and tibiae,
the marrow of the long bones becomes quite fatty and
produces no more RBCs after about age 20 years.
• After age of 20 most RBCs continue to be produced in the
marrow of the membranous bones, such as the vertebrae,
sternum, ribs, and ilia.

29
 Production of RBC (Erythropoiesis)
• Stem cells differentiate to produce committed stem cells
called hematocytoblasts that in turn produce :
1. Proerythroblast: where Hgb synthesis begins, big
nucleus
2. Basophile erythroblast: cell division continues.
3. Polychromatophil erythroblast: Hgb synthesis
increases and fills the cytoplasm, nucleus size
decreases.

30
4. Ortochromatic erythroblast: Nucleus decreases
5. Reticulocytes: contains Hgb, no nucleus and the
cell is expelled from the bone to circulation.
– They still contains remnants of the Golgi
apparatus, mitochondria, and a few other
cytoplasmic organelles.
– The remaining basophilic material in the
reticulocyte normally disappears within 1 to 2 days,
and the cell is then a mature erythrocyte.

31
32
 Regulation of Red Blood Cell Production
Tissue oxygenation is the most essential regulator
of red blood cell production:
1. When there is Hypoxia - that occurs also in the kidney
cells.
2. Kidney then produce a hormone called erythropoietin.
3. Erythropoietin is transported by the blood to bone
marrow.
4. Bone marrow produces and releases RBC .
5. Increased or adequate O2 then blocks the formation of
more RBC.
33
Erythropoiesis

34
35
Substances necessary for RBC maturation :

1. Vitamin B12
– Important for DNA synthesis and thus for cell
division.
2. Folic acid:
– Also important in DNA synthesis.
3. Iron:
– Necessary for RBC formation .

36
RBC destruction and fate of Hb
• The absence of nucleus in erythrocytes prevents them from
synthesizing proteins and other important substances necessary for
survival.
• Thus, the cells become weak and fragile and die after about 120 days.
• The older red cells are phagotizised by macrophage cells of the
reticuloendothelial system located in the liver, spleen, and bone
marrow cells.
• The macrophages release the Hb-molecule that is broken down into:
a. Its protein part (Globin) and,
b. Heme part ------ Bilirubin

37
 Anemia
• Defined as a decrease in the ability of the blood to carry
oxygen due to:

1. a decrease in the total number of erythrocytes, each

having a normal quantity of hemoglobin, or

2. a diminished concentration of hemoglobin per

erythrocyte, or

3. a combination of both.

38
 Major Causes of Anemia
1. Dietary deficiencies of iron (iron-deficiency anemia),
vitamin B12, or folic acid.

2. Bone marrow failure due to toxic drugs or cancer

3. Blood loss from the body (hemorrhage).

4. Inadequate secretion of erythropoietin in kidney disease.

5. Excessive destruction of erythrocytes (for example, sickle-

cell anemia).
39
 Types of anemias

1. Blood Loss anemia

After rapid hemorrhage
2. Aplastic anemia
It is due to lack of functioning bone marrow.
3. Megaloblastic anemia
Results from deficiency of vitamin B12 and folic acid
4. Hemolytic anemia
RBCs become fragile due to different reasons(sickle-cell
anemia).

40
 Effect of anemia on the Circulatory system

 Anemia decreases blood viscosity.

 The decrease in viscosity causes decreased resistance of blood
vessel to blood flow.
 Blood vessels dilate and allow increased return of blood
to the heart.
The work load of the heart increases and consumption
of O2 and nutrients by heart muscles raises.
The heart rate, respiratory rate etc. increase in response
to the tissue hypoxia produced by anemia.

41
 Polycethemia:
• Is abnormal increase of RBC in the circulation.
1. Polycethemia Vera:
- Cancerous production causes highly engorged blood.
2. Secondary Polycythemia: Is mostly physiologic, hypoxic
tissues..
• Effect:
- Increased viscosity causes sluggish blood movement
- Hct increases and so blood volume, blood pressure and work
of the heart increases.

42
 White blood cells(WBCs)

Normal number: 4,000-10,000 / mm3 of blood

WBCs fight infection by:
Direct destruction (e.g. Phagocytosis)
Producing antibodies & sensitized lymphocytes.
They are highly mobile and reach tissue fluids.
When infection occurs, WBCs increase in number.

43
 Types of WBCs

1. Granulocytes
They are also called polymorphonuclear WBCs.
I. Neutrophils (62%)
II. Eosinophil ( 2-3%)
III. Basophiles ( < 1%)
2. Agranulocytes
I. Lymphocytes (30%)
II. Monocytes (5 %)

44
 Life Span of WBC:
• Granulocytes: 4-8 Hrs in the circulating blood
4-5 days in the tissue
• Monocytes: 10-20 Hrs in the circ.
- become tissue macrophages and live
for months in the tissue.
• Lymphocytes: for months or even years
 Functions of WBCs
• Granulocytes and Monocytes destroy invading
organisms by Phagocytosis.

• Lymphocytes , to the contrary, attack infections through

the immune system by producing sensitized lymphocytic
cells and plasma cells that produce antibodies.

46
 Neutrophils:
• Phagocytize bacteria
• Their granules have enzymes to digest
bacteria
• Have 2-5 lobes and are the most
numerous
• Their numbers increase during
infection.
• They stay in circulation for 10 hrs.

47
 Eosinophils
• Are bi-lobed and weak phagocytes .
• Have granules in the cytoplasm .
• Phagocytize antigen-antibody complexes and destroy
them.
• Their number increases during asthma and other allergic
attacks.

48
 Basophils:
• Constitute < 1%
• Have granules
• Produce heparin, so act as natural inhibitors of blood
clotting.
• They also release histamine, serotonin, etc

49
Monocytes
• Have no granules
• When attach to tissues they become Macrophages
• Macrophages are highly phagocytic cells that can ingest
many bacteria's, parasites and debris etc.

50
Lymphocytes
• Have no granules and the nucleus is not lobed
I. T lymphocytes or T cells (70% to 80%)
• undergo maturation primarily in the thymus.
• are responsible for cell-mediated immunity.
II. B lymphocytes or B cells (10% to 15%)
• undergo maturation in bone marrow and peripheral lymphoid
tissue.
• Make and secrete antibodies that are directed against specific
antigens.
• Are responsible for humoral immunity.

51
Types of Lymphocytic cells

52
Mechanisms of WBC mobility through the tissues:
1. Diapedesis: WBC Squeeze out through the capillary pore
(e.g. Neutrophils, Monocytes).

2. Amoeboid motion: Produce pseudopodia and reach the

microbes in the tissues

3. Chemotaxis: WBC are attracted by chemicals or toxins

produced by the microbe or inflamed tissues.

4. Phagocytosis: engulfing and destroying e.g., Neutrophils,

macrophages.
53
Movement of neutrophils toward an area of tissue damage.

54
 Immunity

• Definition
– Immunity constitutes all the physiological
mechanism which allow the body to recognize
materials as foreign to itself and to neutralize or
eliminate them.
Function:
• Protection against
• microbes, viruses,bacteria,
• Elimination of worn out or damage body cell
• Immune surveillance (cancer)
• Involve in the process of aging
• Obstacle to successful transplantation of organ
Classification:
• Innate (Non-specific) defense mechanism
• Acquired (Specific) immune mechanism
I. Non- specific defense mechanism
• Phagocytes
• Skin resistance
• Gastric acid and digestive enzymes
• Certain chemical substances in the blood
• lysozymes
II. Specific immune mechanism:
1. Humoral immunity (antibodies)=
• B-cells, make up 15% of lymphocytes
2. Cell-mediated immunity
– (sensitized Lymphocytes) =
– T-cells, make up 70-80% of lymphocytes
– Depend upon prior exposure to the specific
foreign substances.
Terms :
1. Antigen:
– Any substance capable of provoking an immune
rxn.
– Antigens occurring in nature are substances of high
molecular weight and usually are proteins.
2. Antibodies:
• Plasma proteins synthesized in immune responses
which are capable of combining with the provoking
antigens.
– The antibodies are gamma globulins called
immunoglobulins (abbreviated as Ig).
59
 Functions of the immunoglobulin's (Ig)

1. IgG (>75%):
– The most plenty form of Ig in circulation.
– It crosses the placenta and provides passive
defense to the fetus and the new born.
– It activates the complement proteins that in turn
stimulates opsonins and enhances
phagocytosis.

60
2. IgA (~15%):
– It is the main antibody type found in body
secretions such as saliva, tears, milk, bronchus
and the GIT.

3. IgM (10%):
– The largest in size of the antibodies.
– It is the 1st antibody that appears in the
circulation soon after an infection occurs.
– It forms the natural antibodies of the ABO blood
antigens.
4. IgD (~0.2%):
– Antibody type found on B lymphocytes.
– It helps B-cells to recognize the antigen.

5. IgE (~0.004%):
– They are found as antigen receptors on basophiles
in blood and mast cells in tissues.
– It is responsible for immediate allergic responses
and protection against certain parasitic worms.
 Blood Groups
• Landsteiner (Austrian): is the 1st scientist to identify blood
group antigens.

• Blood typing is important because during transfusion of blood,

mismatching can take place and cause complications.
• Erythrocytes contain genetically determined surface
antigens(agglutinogens).
• Blood plasma contains antibodies(agglutinins) that react
with specific antigens.
• Blood is named according to surface antigens that are
present.

63
Blood groups on RBC

64
• In humans, there are two known blood groups that are
clinically important:
a. The ABO-blood groups,
b. The Rh- factors
• In the ABO system, blood is classified primarily on the
basis of the A and B antigens present on the surface of
red blood cell membranes.
• Secondly, blood is classified on the basis of the
naturally occurring antibodies in the serum.

65
• A person whose red cells possess the A -antigen has anti-
B antibody in his serum and is classified as blood group
A.
• If B antigen is present in the Red cell membranes, Anti-A
antibody is present in his serum and the person is
designated as blood group B.
• If both A and B antigens are present on red cells, then the
person has no antibody, so he has AB blood group.
• If No antigens are present on red cells, the person is O
Type and has both anti A and B antibody in his serum.

66
Relative Frequencies of the Different Blood Types.

67
• Universal donor
– Blood group “O” is called universal donor, because
people with this blood types have no antigens on their
cell-membrane surfaces and therefore can not
agglutinate if transfused to any blood types.
– Even though they lack antigens, they have anti- A &
anti-B antibodies in the plasma. So, they can receive
blood from persons with blood group “O” only.

68
• Universal recipient
– People with blood group AB can take (be transfused)
blood from any blood types, because they have no
antibodies in their blood to cause agglutination
reactions.
– AB can donate blood only to a person with blood
AB, not to other.

69
 Donators and Recipients
Donators
1. O can donate blood to group A, B, AB, and O
2. A “ A & AB only
3. B “ B & AB only
4. AB “ AB only

70
 Recipients
1. O can receive blood from group O only
2. A “ A & O only
3. B “ B & O only
4. AB “ A, B, O, & AB

71
 Rh Blood Group
• Named because it was first studied in rhesus monkeys.
• Consists of clinically significant antigens ; D,C,E,c and e.
• The type D antigen is more antigenic and widely prevalent in
the population.
• Therefore, any one who has this type of antigen (type D antigen)
is said to be RH positive (Rh+), and those who lack this antigen
is Rh negative(Rh-).

72
• 85% of the population is Rh+

• A person with Rh negative blood does not have Rh antibodies

naturally in the blood plasma.

• Antibodies against the Rh antigen do not develop unless an Rh-

negative person is exposed to Rh-positive blood.

This can occur through a transfusion or if blood

crosses the placenta to a mother from her fetus.

• When an Rh-negative person is exposed to Rh-positive blood, the

person can become sensitized to the Rh antigens and produce anti-
Rh antibodies.

73
 RH Incompatibility
E.g. Father Rh+ =Rh + means he has D-antigen on his RBC
membrane
Mother Rh- = No D-antigen , so it is depicted as Rh-
Marriage:
1. Rh + father X Rh- mother = Rh+ fetus
 During birth, through placenta , Rh+ blood of the
fetus leak to mother’s blood and sensitizes her.

74
2. Mother ‘s blood produces anti-Rh antibodies (anti-D antibodies )
against the Rh+ blood.

3. During the 2nd pregnancy and there after, the Anti-Rh+ antibodies
(agglutinins) enter into the fetus and agglutinate or hemolyze the
RBC of the fetus.

75
76
This type of hemolytic disease is called
hemolytic disease of the
newborn( Erythroblastosis fetalis).
If the baby is born alive from the incidence, then
there is a higher risk of being anemic and
jaundiced.

77
Prevention of Erythroblastosis Fetalis:
•Injection of a specific type of antibody preparation, called
Rho(D) immune globulin (RhoGAM).
•Contains antibodies against Rh antigens.
•Can be given during the pregnancy, before delivery, or
immediately after each delivery, miscarriage, or abortion.
•The injected antibodies bind to the Rh antigens of any fetal
red blood cells that may have entered the mother’s blood.
•This treatment inactivates the fetal Rh antigens and prevents
sensitization of the mother.
•However, if sensitization of the mother has already occurred,
the treatment is ineffective.

78
 Platelets and hemostasis
Platelets: General Characteristics:
– Are small fragments that emerge from
megakaryocytes in red bone marrow (2-4µm in
diameter)
– Range: 250,000 – 500,000/ mm3
– Involved in blood clotting processes.
– Life Span - 4-12 days
– Mostly have no nucleus.
– Release serotonin, thromboxane (cause
vasoconstriction)
79
 Hemostasis
• Refers to the stoppage/arresting of bleeding.
• It is a complex process depending on interaction
between vessel wall, platelets and coagulation factors.

• Actions that limit or prevent blood loss include:

• Blood vessel spasm(vasoconstriction)

• Platelet plug formation

• Blood coagulation

80
Rationale of hemostasis:

• Ensure that coagulation mechanisms are

• Activated when there is injury

• Not unnecessarily activated

• Restore tissue blood flow after repair of injury
(fibrinolysis).

81
82
Hemostatic mechanisms

83
84
III. Blood coagulation
• The clotting mechanism involves a cascade of reactions
in which clotting factors are activated.
• Most of clotting factors are plasma proteins
synthesized by the liver (vitamin K is needed for the
synthesis of factor II, VII, IX and X).
• They are always present in the plasma in an inactive
form.
• When activated they act as proteolytic enzymes which
activate other inactive enzymes.
• Several of these steps require Ca++ and platelet
phospholipids.
85
Clotting factors

86
• Blood coagulation is triggered by cellular damage and blood
contact with foreign surfaces.
•This coagulation forms a more permanent clot!
•Two pathways to achieve this:
– Intrinsic Pathway
• Exposed collagen activates the initiating factor of the
cascade event = factor XII
– Extrinsic Pathway
• Damaged tissues release tissue factor (factor III or tissue
thromboplastin)

87
88
A blood clot consists of fibrin fibers that trap red blood cells, platelets, and flui d.

89
 Why Circulating Blood Does Not Clot?

 Velocity of circulation.
 Surface effects of endothelium:
- Smoothness of the endothelial lining inhibits platelet
adhesion and thus prevents initiation of intrinsic
clotting mechanism.
 Circulatory anticoagulants

90
Conditions that Cause Bleeding:

1. Vitamin K deficiency
2. Liver disease
3. Hemophilia
4. Thrombocytopenia (platelet deficiency) <
50,000/mm3.

91