Blood Physiology

Blood physiology
Major Functions of the blood

• 1. Transport
a. Gases (O2 and CO2)
b. Nutrients (organic and inorganic like electrolytes)
c. Hormones and Waste products
• 2. Defense: against infections by means of
a. WBC (phagocytosis, antibody formation)
b. Platelets (prevention from bleeding)
• 3. Regulation
a. Temperature regulation
b. Acid-base balance, Hb-acting as a buffering
c. Blood volume regulation etc.
Characteristics and Properties of blood

 Color: bright red (Hb- oxygenated blood)

dark red (venous blood, deoxygenated)

 Viscosity:
 Refers to internal resistance of a liquid to flow.
 Blood is 3X thicker and denser than pure water.
 B/s of its thicker and sticky nature blood flows through blood
vessels with little difficulty

 pH range: from 7.3 to 7.4 (blood is slightly alkaline)

Major Components of Blood

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

the blood

a. Erythrocytes - (Red blood cells)

b. Leukocytes - (White blood cells)
c. Thrombocytes - (Platelets)

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

 Blood volume = accounts to ~ 8% of the body weight (about

5 Liters).
Blood: Hematocrit (Ht) or packed cell volume (PCV)

3-layers after centrifugation

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.
Blood, components
 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 (Plasma vs serum):
 > 90 % water , ~ 7 % proteins, gases (O2, CO2 in Small
amounts), nutrients , electrolytes, hormones, and metabolic
wastes etc.
 The major electrolyte that determine the osmolalrity of the
plasma is Na+ ion
 Parts of plasma proteins

• Plasma proteins
A. Albumin (~ 60% or
4.5 gm/dl)

B. Globulins ( ~ 40%, or
2.5 g/dl)

C. Fibrinogen (0.3 g/dl)

Determined by means of
Electrophoresis
 Characteristics of plasma proteins,
A. Albumin: - Is formed 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).
 i.e., causes re-absorption pressure of ~ 25 mm Hg. This force
helps to move plasma back into the blood
 During malnourished conditions (deficiency of protein intake),
blood volume decreases due to decreased albumin and this effect
results in edema development
 Albumin also serves in transporting nutrients (FFA, hormones,
bilirubin etc.)
 Plasma proteins, Globulin
2. Globulin: types (alpha1&2, beta, gamma)
 Are produced in the lymph tissues from B-cell line called plasma
cells
 The majority of the immunoglobulin (antibodies) are part of
gamma globulins
 Globulins help as carriers to transport lipoproteins, Fe 2+,
hormones, enzymes, nutrients, and others in the body.
3. Fibrinogen:
 Fibrinogen is synthesized in the liver
 It is mainly involved in blood clotting
Red Blood Cells (RBC’s)
 Red Blood cells (RBC)
Shape:
• RBC is a flexible biconcave cell that is
thinner at the center and thicker at the
ages

Diameter: ~ 7.5 um
• Mature, No nucleus
• Has greater surface area/volume ratio
• Therefore, can bend and twist to pass
through the narrow capillaries very
easily
 RBC, Function

Function:
1. Carries hemoglobin that in turn transports respiratory gases (O2
and CO2)
• Hb also helps as a buffer (pH balance)
2. Carbonic anhydrase (CA):
• An enzyme located in RBC membrane,
CO2 + H2O CA > H2CO3 = HCO-3 + H+
 CA increases the rate of this reaction 5000 fold.
 Good to transport CO2 from the tissues to the lung very fast
 RBC number

Average: RBC No
5 million/ mm3 blood

Average: Hb: 15 g/dl

Average Hct : 45%
 RBC fragility test (hemolysis)
1. In isotonic solution: (0.9% NaCl solution is isotonic to plasma.

 The size and shape of RBC remains normal

2. Hypertonic solution: Greater than 0.9% NaCl solution,

 RBC lose water and shrink

3. Hypotonic solution: Lower than normal (<0.9%) NaCl solution,

 RBC hemolyze or burst and lose their Hb to the plasma

Production of RBC in the body
A. Embryonic life:

 RBC are produced in the liver, spleen

and lymph nodes

B. Infants (5 years old):

 Red bone marrow of all cells

C. Adults (after age 20):

 Membranous bones like ribs,

sternum, vertebrae & pelvic bones

 But not in long bones like femur or

tibia (fat)
 Hemopoiesis, production (genesis) of blood cells

 RBC and other blood cells are produced in the bone marrow

 All cells emerge from undifferentiated (uncommitted ) stem

cells in the bone marrow

 When stimulated, the stem cells are committed or differentiated

and develop in to:-
•erythroid (RBC line),
•lymphoid (WBC line), or
•myeloid (megakaryocytic and granulocytic line) line of
blood cell formation
Genesis of RBC
Erythrocyte sedimentation rate (ESR)
 Erythrocyte sedimentation rate (ESR)

Def: ESR is the rate or speed at which un-coagulated blood (RBC)

settles down when allowed to stand in a tube.
 It is caused by rouleaux formation (pilling of RBC like coins
together).

Factors that affect ESR: Red cells & protein concentration

a. Polycethemia : Hct value is large, so ESR is low
b. Anemia: ESR is fast, so increases the ESR
Erythropoiesis
 Regulation of RBC-production

Erythropoiesis: Production of RBC in the body occurs by the

process of Erythropoiesis by negative feed back mechanism.
Physiological Mechanism
The stimulus for Erythropoiesis is Hypoxia (low O2) that occurs in the kidney
cells ----
 Kidney then releases an enzyme renal erythropoitic factor (REF) into the
blood ---
 This enzyme acts on a plasma protein (globulin) to produce a hormone
called erythropoietin ----
 Erythropoietin is transported by the blood to bone marrow ----
 Bone marrow produces and releases a increased RBC that in turn supply
O2 to hypoxic tissues.
 Increased or adequate O2 then blocks the formation of more RBC.
 Factors that enhance RBC production

 The rate of RBC production is controlled not by the number of

RBC’s, but primarily by the demand of body tissues for oxygen.
This is seen by the following facts:

 Some disturbances like for example:

- Low blood volume, - Low Hb concentration
- Lung diseases, - High altitude etc.

 cause insufficient oxygenation of tissues that necessities the

production of more RBC by the Erythropoiesis.
Erythropoietin
 Substances necessary for RBC maturation
a. Vitamin B12: (requires intrinsic factor for absorption)

 Important for DNA synthesis and thus for cell division.

Deficiency of Vit B12 causes macrocytic cells (big Hb in
cytoplasm)

 Because of their big size, the cells rupture when passing

through the capillary wall (so, cause megaloblastic anemia.
Maturation failure for Vit. B12 is call pernicious anemia.

b. Folic acid: Obtained from green vegetables, fruits, liver, meat.

 Also important in DNA synthesis.

c. Iron: Necessary for RBC formation (Vit. Copper etc)

 Hb structure and function
Function: HB functions in carrying O2 and CO2 gases
It is a buffer to maintains acid-base balances
Hemoglobin – is large molecule inside RBC. It has:
a. Globin part: protein with 4-polypeptides (2 alpha & 2 beta
polypeptides)
b. Heme group: Fe 2+ containing central part to which
oxygen binds.
 Each polypeptide has one heme group, each heme with Fe2+
carries one O2 molecule, total = 4-O2 molecules are carried
with in Hb molecule
 1g Hb binds with 1.34 ml O2
 15g Hb/dl x 1.34 ml O2 = 20.1 ml O2/100 ml blood
 Importance of HB and its types
Importance of Hb: (in O2-Hb saturation curve)
The most important advantage of Hb is that it combines loosely
and reversibly with O2-molecule. That means, it gives up O2
easily to tissues and takes up (loads) O2 easily from the lung
tissues.
Types of Globin Chains:
The polypeptide chain (the Globin unit) determines the physical
characteristics of the Hb-molecule. Thus, there exists:
a. Adult Hb (Hb A): 2 alpha + 2 beta
b. Fetal Hb (Hb-F): 2 alpha + 2 gamma
c. Sickle cell anemia (Hb-S): valine is replaced by glutamic acid at
Beta- chain so on.
Hemoglobin (Hb), structure
 RBC destruction
 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 that are 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
 Anemia

• Anemia: means deficiency of RBC production

• Causes:
a. Decreased RBC No
- Blood loss anemia: e.g, hemorrhage
- A plastic anemia: bone marrow destruction (X-ray)
- Maturation failure anemia: Nutritional Vit. B12 etc
- Hemolytic anemia: Sickle cell anemia etc
b. Slow production of RBC
c. Decreased Hb synthesis
 Effect of anemia on the circulatory system
A. Anemia decreases blood viscosity

B. The decrease in viscosity causes decreased resistance of blood

vessel to blood flow

C. Blood vessels dilate and allow increased return of blood to the

heart

D. The work load of the heart increases and consumption of O2

and nutrients by heart muscles raises

E. The heart rate, respiratory rate etc. increase in response to the

tissue hypoxia produced by anemia
 Polycethemia, High number of RBC
• Polycethemia is abnormal increase of RBC in the circulation.
• 2-types
1. Polycethemia Vera (8-9 million)
 Tumerous or cancerous production
 causes highly engorged blood
2. Secondary Polycethemia:
 Is mostly physiologic, hypoxic tissues (low O2)
 Effect of polycethemia on the circulatory system
 Increased viscosity causes sluggish blood movement
 Hct increases and so blood volume, blood pressure and work of
the heart increases
 White Blood Cells (Leukocytes)

Properties of WBC

a. Nucleus: Have nucleus all the time, but lack Hb

b. Normal number: 4000-10,000 / mm3 of blood
c. Defense: WBC’s fight infection by:
 by direct destruction (e.g., Phagocytosis)
 by producing antibodies & sensitized lymphocytes
d. Mobility: Are highly mobile and reach tissue fluids
e. When infection occurs, WBC increase in number e.g., Neutrophils
f. Life span: Many (not all) live only a few days, may be b/s of their
engagement with pathogens
 WBC Types
1.Granulocytes and their life span
Polymorphonuclear WBc’s (i.e. their nuclei have 3-5 lobes)
a. Neutrophils (~ 62%), life span 4-5 days
b. Eosinophils (~ 2-3%) “
c. Basophiles (~ 0.1-0.4%) “
2. Agranulocytes and their life span
d. Lymphocytes (~ 30%), weeks or months
e. Monocytes (~ 5 %), 20 hrs, circulate in blood
and change into macrophages that attach to tissues e.g.
alveolar macrophages in the lung, kuffer cells in the liver etc.

• Macrophages live longer times (Months).

types of WBC
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
 Phagocytes and immune cells

 Phagocytosis vs. immune development by WBC

 Granulocytes (Neutrophils, Eosinophils, basophiles) 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 that are produced in the bone marrow and
lymphogenous (spleen, thymus, tonsils , payer’s patches etc) organs.
 Neutrophils & Macrophages

 Neutrophils attach bacteria's by phagocytosis. Neutrophils can engulf

3-20 bacteria's at once.
 Macrophages: They can phagocytize >100 bacteria at once and even
engulf bigger ones like RBC’s, malaria parasites etc.
Mechanism of Phagocytosis
a. Presence of rough space facilitates phagocytosis
b. Dead tissues are easily phagotisized
c. Antibodies by Opsonization promote phagosytosis
d. Lysosomes, and oxidizing agents like lipases, peroxisomes, H2O2, etc.
produced from macrophages are lethal for bacterial membranes.
 Disturbances of WBC

• Leukemia (increased WBC • Leucopenia: (decreased

No): cancerous production of production of WBC)
WBC. • Bone marrow stops producing
• These occurs: them

a. in the bone marrow - Drug poison

b. in the lymph - X-rays

• Their increased production • Differential count is usually

takes the space of platelets & undertaken in the lab to know
RBC causing anemia + the proportions of WBC No
impaired blood clotting
 common effects of Leukemia

• Increased WBC causes

A. Metabolic starvation:
• The increased WBC consume too much metabolic substrates.
• Thus energy source is depleted and too much use of amino acids by
cancerous cells causes rapid deterioration of other body tissues.

B. Anemia and increased bleeding tendency can occur b/s of the

displacement of these cells from bone marrows by the tumor.
 Hemostasis
(blood clotting mechanisms)

Blood physiology, Platelets

General Characteristics
1. Are small fragments that emerge from Megakaryocytes in red bone
marrow (2-4 microns in diameter)
2. Range: 250,000 – 5000,000 mm3
3. Involved in blood clotting processes.
4. Life Span 4-12 days
5. Mostly have no nucleus
6. Release serotonin, thromboxane (cause vasoconstriction)
 Hemostasis, platelets and their function

• Def: Hemostasis or blood clotting refers to stopping or arrest of

bleeding.
• Blood cells involved in blood clotting processes are platelets
(Thrombocytes).
• Platelets are small, colorless, and non-nucleated blood cells that have
a life span of about 10 days.
• They emerge from fragments of big cytoplasm structures in the bone
marrow called megakaryocytes.
• The cytoplasm of platelets synthesizes chemicals like thromboxane
A2, serotonin, histamine, von Willbrand’s factor (important for
adherence of platelets) and minerals like Ca2+, Cu, Fe2+ etc involved
in clotting processes.
 Platelets and their properties

Properties of platelets (remember the 3-A’s)

Adhesiveness, Aggregation, and Agglutination

1. Adhesiveness : platelets stick when they come in contact with wet

and rough surfaces.
 Normally, their glycoprotein (structure in their cell membranes)
prevent adhesiveness to normal endothelium

2. Aggregation: When platelets are activated, they usually group

together.
 Their aggregation and stickiness is mainly due to ADP and
Thromboxane A2 found in their cytoplasm

3. Agglutination: Platelets clump together and form clots

 Hemostasis, Blood clotting

Five stages of hemostasis:

1. Vasoconstriction (vascular spasm)

2. Platelet plug

3. Clot (coagulation) formation

4. Fibrin clot formation (clot retraction)

5. Clot dissolution
 Bleeding disorders

Excessive bleeding can be caused due to 3-major factors:

1. Hemophilia:
 It is due to insufficiency of Factor VIII and IX
 bleeding occurs at big blood vessels

2. Vit. K deficiency: (liver diseases, hepatitis)

 important to synthesize Prothrombin in the liver

3. Thrombocytopenia (platelet deficiency)

 Bleeding at small vessels, capillaries and Venules.
 Platelets usually plug small blood vessels, so their absence causes
thrombocytopenic purpura ( small purplish blotches )
 Hemophilia continued
 Hemophilia is an “ X” linked inherited recessive bleeding disorder (i.e., the
person does not have enough clotting factors)

 Hemophilia is passed as a recessive trait on the X-chromosome

 Hemophilia-A- (classic hemophilia): is due to inadequate production of

Factor-VIII

 Hemophilia-B (charismas disease): is due to inadequate production of

Factor-IX

 When one or both of the above are absent, Factor-X can not be activated.

 Factor-X - is the main enzyme that converts Fibrinogen to Fibrin

 When Factor X is not activated , a good clot can not be formed and
excessive bleeding occurs.
 Hemophilia (von Willbrands factor)
 Von Willebrand’s disease is a hereditary problem seen mainly in
females where the subject has “long bleeding time” because of poor
platelet function, a possible deficit of Factor VIII.

 Factor VIII is a protein found on plasma wall of blood vessels and

platelets.

 If von Willbrand’s factor is missing, platelets won’t adhere to vessel

walls at the injury site.
 Therefore, bleeding won’t stop as quickly as it would.
 Hemophilia, continued

 Hemophilia is passed congenitally

as a recessive trait on the X- Female
chromosome carrier normal
+X X____
Female Male X +XX XX
X X__ Y +Xy Xy__
Male +X +XX +XX
Y Xy Xy__  +XX - carrier female
 +Xy - hemophilic male
 +XX - carrier female
 Xy - normal male  50% chance of a female who will be
 All females would be carriers b/s a carrier and a male with the
of the “X” –chromosome from hemophilic disease
being affected
Thrombus and emboli formation
 Thrombo-embolic conditions in humans

• Thrombus : is an abnormal clot that develops in a blood

vessels.
• Emboli: is a thrombus that is freely flowing through the
circulation. That is , the thrombi detaches , forced by flowing
blood and cause the clot to flow through the circulation.
• Causes:
1. Rough endothelial surfaces of a vessel
2. Slow stagnant flowing blood in blood vessels can initiate clotting
and emboli formation
 Blood types and blood transfusion

Blood Groups

 An adult human has about 4–6 liters of blood circulating in the body.

 Blood consists of several types of cells floating around in a fluid called

plasma.

 The red blood cells contain hemoglobin, a protein that binds oxygen.

 Red blood cells transport oxygen to, and remove carbon dioxide from,
the body tissues.

 The white blood cells fight infection.

 The platelets help the blood to clot, if you get a wound for example.

 The plasma contains salts and various kinds of proteins.

 Blood Groups
 Landsteiner: is the 1st scientist to identify blood group antigen.

 Blood group antigens are located at the cell membrane surface of

Erythrocytes (RBC’s).

 Blood typing is important because during transfusion of blood,

mismatching can take place and cause unwanted complications.

 For example: when people have hemorrhage, blood loss due to

several reasons, an immediate blood supply (transfusion) is
necessary.

 So, compatible blood types should be prepared and given to save

life.

 Otherwise, agglutination (clumping of RBC’s) or hemolysis

(rupture) of RBC can occur.
 Types of blood groups

 In humans, there are two known blood groups that are

clinically important:
a. The ABO-blood groups,
b. The Rh- blood group 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 (erythrocytes).
 Secondly, blood is classified on the basis of the naturally
occurring antibodies (agglutinins) in the serum
ABO blood grouping system

According to the ABO blood typing system there are four different
kinds of blood types: A, B, AB or O (null).
 ABO-blood groups

• 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 & B antigens are present on Red cells, then he

has no antibody, so is AB blood group.

• If No antigens are present on red cells, he is O Type and

has both anti A & B antibody in his serum.
 Blood group A
 If you belong to the blood group A, you have A antigens
on the surface of your red blood cells and B antibodies in
your blood plasma.
 Blood group B
 If you belong to the blood group B, you have B antigens
on the surface of your red blood cells and A antibodies in
your blood plasma.
 Blood group AB
 If you belong to the blood group AB, you have both A and
B antigens on the surface of your red blood cells and no
A or B antibodies at all in your blood plasma.
 Blood group 0
 If you belong to the blood group 0 (null), you have neither
A or B antigens on the surface of your red blood cells but
you have both A and B antibodies in your blood plasma.
ABO-blood group
ABO-blood group
 ABO- blood group

Universal donor: (Blood group O)

 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.
 ABO-blood group
Universal recipient (blood group AB)
• People with this blood group 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.
Method of Blood typing
 Method of blood typing

 On a slide at opposite ends , drops of anti- A antibody and Anti-

B antibody are added at opposite sides.
 2-3 drops of Blood (RBC’s) are added on the prepared
antibodies and changes for agglutination are observed after a
few minutes.
 If agglutination occurs on anti-A antibody, then the blood is group
A.
 If agglutination occurs on anti-B antibody , the blood is blood
group B.
 If no agglutination occurs, then it is blood group O.
 If there is agglutination in both A and B-antibodies, then it is
blood group AB.
Observation of agglutination reactions
 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

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
 Antibody formation in the new born

 Newborn infants have no antibodies. However, food and

some bacteria contain antigens similar to human
agglutinogens and can stimulate the production of antibodies
after about 3-8 months following birth.
 Blood groups can be used medico legally to prove that some
body is not the father of a certain child.
 Blood group identification is also useful to identify the right
child for the right mother when there is a mix up of babies
in maternity hospital.
 Nowadays DNA analysis gives the correct parenthood than
assessing blood group types
 Rh-factor
• How is it first identified: Blood of Rhesus monkey (antigen) is
transfused to Guinea Pigs or Rabbits (1940)
• The serum of Rabbits or Guinea Pigs agglutinated the
monkey’s RBC.
• These anti-Rehsus antibody was also found to a agglutinate the
majority (85%) of RBCs of Humans.
• Thus, people are classifies as Rh+, if their red cells possess the
Rh-antigen (called D antigen) or Rh- , if they do not posses the
D- antigen on their Red cells.
• Rh- subjects can however produce antibodies against that
antigen only when they are exposed to Rh+ blood.
• Though there are many kinds of Rh-antigens (e.g., C, D, E, c, d,
e), the most potent one is antigen D.
 Rh- blood typing
 In comparison to ABO blood group, the Rh-factor is slow
acting and is not found in other secretion like saliva etc.
 Rh- incompatibility: Usually causes serious problems

The Incompatibility:
 Father Rh + = Rh + means he has D-antigen on his RBC
membrane

 Mother Rh- = No Rh factor, so it is depicted as Rh-

Marriage:
1. Rh+ father X Rh- mother = Rh + fetus
2. During birth through placenta , Rh+ blood (antigens) of the
fetus leak (enter) to mothers blood and sensitizes her.
 Rh- incompatibility
3. Mother ‘s blood produces anti-Rh antibodies (anti-D antibodies )
against the Rh+ blood.

4. During the 2nd pregnancy and there after, the Anti-Rh+

antibodies (agglutinins) enter into the fetus and agglutinate or
hemolyze the RBC’s the fetus.

 This type of hemolytic disease is called Erythroblastosis fetalis.

 If the baby is born alive from the incidence, then there is a

higher risk of being anemic and jaundiced (Yellow coloration
on his skin, eyes, finger nails due to excess circulation of
bilirubin.

 Typing of blood for Rh-system is the same as for ABO system.

 That is, Rh+ RBC’s are agglutinated when exposed to

serum containing anti-D antibodies, but Rh- RBC’s are
not agglutinated.