Blood Physiology

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.

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 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
 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).
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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

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 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.

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 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.

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 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)

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 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 (O 2, CO2 ),
nutrients , electrolytes, hormones, metabolic
wastes and etc.
– The major electrolyte that determine the
osmolalrity of the plasma is Na+ ion.

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 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 .

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

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 Characteristics of plasma proteins
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, bilirubin etc.

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B. Globulin:
– Types : alpha1&2, beta, gamma
– The majority of the immunoglobulin
(antibodies) are part of gamma globulins.
– Globulins help as carriers to transport
lipoproteins, Fe 2+, hormones, enzymes,
nutrients…

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B. Fibrinogen:
– Fibrinogen is synthesized in the liver.
– It is mainly involved in blood clotting
Red Blood Cells (RBC’s)

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• 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.
 Red Blood Cells ( RBCs)

• RBCs are flexible biconcave cells thinner at the

center and thicker at the edges.
• Diameter: ~ 7.5µm
• They have a thickness of 2.5µm at the thickest
point and 1µm or less in the center.
• The shapes of RBCs can change remarkably as the
cells squeeze through capillaries.

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• Average: RBC Number
– 5.5 million/ mm3 (5.5 x 106/ μl ) of blood in
male.
– 4.7million/ mm3 (4.7 x 106/ μl ) in female.
• Life span of RBC – 120 days

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 Functions of RBC
•Carries hemoglobin that in turn transports respiratory
gases (O2 and CO2).
• 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.
 Haemoglobin
•Has two parts: globulin and heme.
Globulin
– Two alpha(α) chain polypeptide
– Two beta(β) chain polypeptides
Heme
– Each heme is present in one peptide chain and
contains an iron {Fe++} that combines reversibly
with one molecule of O2.
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• Each polypeptide has one heme group,
each heme with Fe2+ carries one oxygen
molecule.
– A total of four oxygen molecules are
carried within one hemoglobin molecule.

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 Types of Globulin Chains

• 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.

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 Production of Red Blood Cells

i. Areas of the body that produce red blood cells

– In the adult, RBCs, many WBCs, and platelets are
formed in the bone marrow.
– In the fetus, blood cells are also formed in the liver
and spleen.
– 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.
Fig. Relative rates of red blood cell production in the bone
marrow of different bones at different ages.
 Genesis of Blood Cells

• The blood cells begin their lives in the 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.

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

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Blood cell genesis
 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.
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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.

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 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.
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Figure: Function of the erythropoietin mechanism to increase
production of red blood cells when tissue oxygenation
decreases.
 Substances necessary for RBC maturation
1. Vitamin B12
– Important for DNA synthesis and thus for cell
division. Deficiency of Vitamin B12 causes macrocytic
cells (big Hgb in cytoplasm).
– Because of their big size, the cells rupture when
passing through the capillary wall.
2. Folic acid:
– Also important in DNA synthesis.
3. Iron:
– Necessary for RBC formation . 35
 Anemias
• Anemia means deficiency of hemoglobin in
the blood, which can be caused by either too
few red blood cells or too little hemoglobin in
the cells.
 Types of anemia

1. Blood Loss anemia

– After rapid hemorrhage the body replaces the fluid
portion of the plasma in 1 to 3 days.
• This leaves a low concentration of RBCs – the RBC
concentration usually returns to normal within 3
to 6 weeks.
2. Aplastic anemia
– It is due to lack of functioning bone marrow.
– Causes
• Exposure to high-dose radiation or
chemotherapy
• High exposure to insecticides or benzene in
gasoline
• Autoimmune disorders (lupus erythematosus)
– In about 50% cases the cause is unknown --
idiopathic aplastic anemia.
3. Megaloblastic anemia
– Results from deficiency of vitamin B12, folic acid, and
intrinsic factor from the stomach mucosa.
– Atrophy of the stomach mucosa or total gastrectomy
can lead to megaloblastic anemia.
– In these states the erythroblasts cannot proliferate
rapidly enough to form normal numbers of red blood
cells.
• RBCs formed are mostly oversized and have fragile
membranes.
4. Hemolytic anemia
– Due to different abnormalities of the RBCs the cells
become fragile.
– The life span of this fragile red cell is so short.
– Examples
• Hereditary spherocytosis
• Sickle cell anemia
• Erythroblastosis fetalis
 Polycythemia

1. Secondary (physiologic) polycythemia

– Occurs when the tissues become hypoxic.
• High altitudes
• In cardiac failure
– Red cell count commonly rises to 6 to 7
million/mm3.
2. Polycythemia vera (Erythremia)
– It is caused by a genetic abnormality in the
hemocytoblastic cells that produce the blood cells.
– The RBC count may be 7 to 8 million/mm3 and the
hematocrit may be 60 to 70%.
– It usually causes excess production of white blood
cells and platelets as well.
 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.
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 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 %)

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 Life span of the white blood cells

• Granulocytes - 4 to 8 hours circulating in the

blood and another 4 to 5 days in tissues.
• Monocytes - 10 to 20 hours in the blood, but in
the tissues they become tissue macrophages and
can live for months.
• Lymphocytes - have life spans of weeks or
months, depending on the body's need for these
cells.
 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 that are produced in the bone marrow and
lymphogenous organs (spleen, thymus, tonsils ,
payer’s patches)

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Neutrophils
• Attack bacterias by phagocytosis.
• Neutrophils squeeze through the pores of
the blood capillaries by diapedesis.
• Neutrophils move through the tissues by
ameboid motion.

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Eosinophil
– Are weak phagocytes .
– Their number increases during asthma, parasitic
infection and other allergic attacks
– Function:
– Kill parasitic worms
– Destroy antigen-antibody complexes
– Inactivate some inflammatory chemical of
allergy (histamine).
Basophils
– Constitute < 1%
– Produce heparin, so act as natural inhibitors of
blood clotting.
– They also release histamine, serotonin..
– They intensify inflammatory response

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Monocytes
– When attach to tissues they become
Macrophages.
– Macrophages: They can phagocytize >100
bacteria at once and even engulf bigger ones
like RBC’s, malaria parasites…

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 Clinical correlation

 Leukemia (increased WBC Number):

– cancerous production of WBC.
– These occurs:
a. In the bone marrow
b. In the lymph
– Their increased production takes the space of
platelets and RBC
• Causing anemia and impaired blood clotting
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Leucopenia: (decreased production of WBC)
- Bone marrow stops producing them
- Drug poison

- X-rays

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 Blood Groups

• 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.

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• 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.
• Secondly, blood is classified on the basis of the
naturally occurring antibodies (agglutinins) in the
serum.

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• 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 is 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.

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• 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
receive blood from persons with blood group
“O” only.

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• 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.

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 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
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RH Blood Group

• Named after Rhesus monkey.

• Consists of over 50 related antigens, the most
clinically significant is 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 (Rh-).

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 RH Blood Group
• Any one who has type D antigen is said to be RH positive
(Rh+), and those who lack this antigen are Rh negative
(Rh-).
• 85% of the population is Rh+, the other 15% of the
population is running around with Rh- .
• A person with Rh- blood does not have Rh antibodies
naturally in the blood plasma.
• If they receive blood that is Rh+, the they will produce
antibodies but not a problem.
• But for the second exposure, they can produce a
transfusion reaction.
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 RH Incompatibility

• Father Rh+ : Rh + means he has D-antigen on his RBC

membrane
• Mother Rh- : No D-antigen on the RBC membrane.
• Marriage: Rh + father X Rh- mother = Rh+ fetus
– During birth through placenta , Rh+ blood of
the fetus leak to mothers blood and sensitizes
her.

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

• 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.

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Bio 130 Human Biology
• 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.
Prevention of Erythroblastosis Fetalis
• An anti-D antibody that is administered to the
expectant mother starting at 28 to 30 weeks of
gestation.
• The anti-D antibody is also administered to Rh-
negative women who deliver Rh-positive babies.

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• One effect of the anti-D antibody is to inhibit
antigen-induced B lymphocyte antibody
production in the expectant mother.
• The administered anti-D antibody also attaches
to D-antigen sites on Rh-positive fetal RBCs that
may cross the placenta, thereby interfering with
the immune response to the D antigen.
 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)
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 Hemostasis
• Hemostasis is the process of forming clots in the walls
of damaged blood vessels and preventing blood loss
while maintaining blood in a fluid state within the
vascular system

• Response to Injury to limit blood loss

• Blood vessel spasm

• Platelet plug formation

• Blood coagulation

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 Blood vessel spasm
• Triggered by pain receptors, platelet release, or
serotonin
• Smooth muscle in blood vessel contracts.

 Platelet plug formation

• Triggered by exposure of platelets to collagen
• Platelets adhere to rough surface to form a plug

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 Blood coagulation
 Triggered by cellular damage and blood contact with
foreign surfaces.
• A blood clot forms
• This is a hemostatic mechanism which causes the
formation of clot via a series of reactions which
activates the next in a cascade
• Occurs extrinsically or intrinsically.

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 Extrinsic clotting mechanism

• Chemical outside of blood vessel triggers blood

coagulation.

• Triggered by tissue thromboplastin (factor III) (not found

in blood).

• A number of events occur that includes factor VII, factor

X, factor V, factor IV, and factor II (prothrombin).

• Triggered when blood contacts damaged blood vessel

walls or tissues.

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 Intrinsic clotting mechanism

• Chemical inside blood triggers blood coagulation

• Triggered by Hageman factor XII (found inside

blood)

• Factor XII activates factor XI which activates IX

which joins with factor VIII to activate factor X

• Triggered when blood contacts a foreign surface

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Figure: The clotting pathways