Blood Physiology

Objective
After Completing this chapter the students is able to:

 List functions of blood

 Describe RBC production and disorder

 Explain WBC production and disorders

 Describe platelet and associated disorder

 Explain blood group and Rh factor

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Introduction
 Blood is the only fluid connective tissue that consists of
blood plasma (liquid) plus formed elements: red blood
cells, white blood cells, and platelets.

 Hematology is the branch of science concerned with the

study of blood, blood-forming tissues, and the disorders
associated with them.

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Function of Blood
1. Protection 2. Regulation 3. Transportation

 Deliver O2

 Remove metabolic wastes

 Maintain temperature, pH, and fluid volume

 Protection from blood loss- platelets

 Prevent infection- antibodies and WBC

 Transport hormones

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Physical Characteristics of Blood
 Blood is a sticky, opaque fluid with a metallic taste
 Blood is denser and 3 times thicker(viscous) than water
 The pH of blood is 7.35–7.45 (slightly alkaline)
 Blood temperature is 38oc
 Blood accounts for approximately 8% of body weight
 Color of blood- ranges from bright red (arterial blood) to
dark red (venous blood)
 Average volume of blood is 5–6 L for males, and 4–5 L for
females 6
Composition of Blood

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Composition of Blood…

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Composition of Blood…

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Blood Serum & Plasma
 Serum is almost the same as that of plasma (55%).

 Serum contains all the other constituents of plasma except

fibrinogen.

 Fibrinogen is absent in serum because it is converted into

fibrin during blood clotting.

 Serum = Plasma – Fibrinogen

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Functions of plasma proteins

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Introduction to RBCs
 Size: Diameter - 7.5 µm

: Thickness - 1- 2 µm

 Shape: Biconcave disk

 Anucleate (have no nucleus) also

they lack mitochondria and other
organelles.

 Function- transport respiratory

gases
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Introduction to RBCs…
 Central portion is thinner and
periphery is thicker.

 This difference in thickness is because

of the biconcave shape
 ( ↑surface area for diffusion of gases).

 The extensive cytoskeleton of red

cells causes them to be extremely
pliable and allows them to pass
through the microcirculation. 14
Blood cell production (Hematopoiesis)

 Hematopoiesis– formation of blood cells from stem cells

 Before birth hematopoiesis occurs in liver, spleen & thymus

of the fetus.

 After birth hematopoiesis occurs in the red bone marrow.

 Within red bone marrow are stem cells called pluripotent

stem cells (hemocytoblasts) that differentiate in to blood
cells

 Hemocytoblasts undergo mitosis to produce all the kinds of

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blood cells many of which are RBCs
Blood cell production (Hematopoiesis)…

 In response to stimulation by specific hormones, pluripotent

stem cells generate two other types of stem cells:

1. Myeloid stem cells - begin their development in red bone

marrow and differentiate into several types of cells from which
red blood cells, platelets, eosinophils, basophils, neutrophils,
and monocytes develop.

2. Lymphoid stem cells - begin their development in red bone

marrow but complete it in lymphatic tissues. They differentiate
into cells from which the T and B lymphocytes develop. 16
Blood cell production (Hematopoiesis)…

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Regulation of Hematopoiesis
 Hemtopoiesis is controlled by cytokines.

 Cytokines are proteins released from one cell that affect the
growth or activity of other cell (induce cell division &
maturation of stem cell)

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Erythropoiesis (production of RBCs)

 Erythropoiesis is the process of RBC formation

 In the adults erythropoiesis occurs in the red bone marrow.

 Erythropoiesis is stimulated by hypoxia (deficiency of

oxygen) which stimulates release of erythropoietin by the
kidneys.

 Erythropoietin acts on red bone marrow and enhances the

production of red blood cells

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Erythropoiesis (production of RBCs)…

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Erythropoiesis (production of RBCs)

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Causes of Hypoxia (↓tissue oxygenation)

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Hemoglobin
 RBCs or erythrocytes contain the oxygen-carrying protein
hemoglobin, which is a pigment that gives whole blood its
red color.
 Normal concentration; 16 g/dl in M and 14 g/dl in F
Composition and synthesis of hemoglobin
 Composed of a protein globin and heme (4 heme + 4
globin)
 Each heme group bears an atom of iron, which can bind to
one oxygen molecule. 23
Hemoglobin…

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Hemoglobin…
 1 RBC contains 280 million hemoglobin molecules

 Men- 5 million cells/mm3

 Women- 4.5 million cells/mm3

 This difference reflects differences in body size

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Hemoglobin…
 Oxyhemoglobin – hemoglobin bound to oxygen

 Oxygen loading takes place in the lungs

 Deoxyhemoglobin – hemoglobin after oxygen diffuses into

tissues.

 Carbaminohemoglobin – hemoglobin bound to CO2

 Carbon dioxide loading takes place in the tissues and is

returned to lungs to be eliminated in expired air

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Hemoglobin synthesis

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Hematocrit
 Hematocrit -the percentage of red blood cells in whole blood
 M = 45%
 F = 42%
 Abnormal values: The test is used to diagnose anemia,
polycythemia (an increased percentage of RBC above 55%).
 Anemia may vary from mild anemia (hematocrit of 35%) to
severe anemia (hematocrit of less than 15%).
 Athletes often have a higher-than-average hematocrit, and
the average hematocrit of persons living at high altitude is
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greater than that of persons living at sea level.
Destruction of Erythrocytes
 The life span of an erythrocyte is 120 days (4 months)

 Old erythrocytes become rigid and fragile, and their

hemoglobin begins to degenerate.

 Dying erythrocytes are engulfed by macrophages

 Heme and globin are separated and the iron is salvaged for
reuse.

 The heme part is converted into bilirubin.

 Bilirubin is the main component of biliary secretion.

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Formation and destruction of RBCs

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Erythrocytes Disorder
 Jaundice- is a yellow discoloration of the skin & sclera
caused by an excessive accumulation of bilirubin in the
blood plasma.

 Normal plasma bilirubin level is 0.5 mg/dl

 In case of jaundice, bilirubin level is elevated up to 40 mg/dl

 The skin and the sclera look yellow when bilirubin level
rises >1.5 mg/dl

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Erythrocytes Disorder…
 Types of jaundice

1. Hemolytic jaundice: ↑RBC

destruction

2. Obstructive jaundice:
Obstruction of bile ducts by stone or
inflammation of the gallbladder

 Obstructive jaundice may be a sign

of liver disease such as hepatitis or
cirrhosis. 32
Erythrocytes Disorder…
 Anemia- is a deficiency of RBC, or insufficient Hb in RBC.

 Types of Anemia

A. Iron-deficiency anemia- is caused by a lack of dietary iron,

and there is not enough of this mineral to form Hb.
 A person with this type of anemia may have a normal RBC
count but the Hb level will be below normal.

B. Pernicious anemia - A deficiency of vitamin B12, which is

found only in animal foods, leads to pernicious anemia, in which
the RBCs are large, misshapen, and fragile. 33
Erythrocytes Disorder…
C. Sickle-cell anemia - It is a genetic disorder of hemoglobin,
which causes RBCs to have sickle shaped, clog capillaries, and
rupture.
D. Aplastic anemia - is destruction or suppression of the
RBM, which decreased production of blood cells.
This may be caused by exposure to radiation, certain
chemicals such as drugs
E. Hemolytic anemia - is any disorder that causes rupture of
RBCs before the end of their normal life span.
Sickle-cell anemia, transfusion reaction and Rh disease of the
newborn are examples of hemolytic anemia.
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Erythrocytes Disorder…
F. Hemorrhagic anemia - loss of a large amount of blood
from the vessels.

Polycythemia: ↑RBCs count > 6 million/mm3

 Effect: Polycythemia ↑ blood viscosity (> 55% Hct)= ↑

Resistance to blood flow

 Types of polycythemia

1. Physiologic polycythemia (altitude training)

2. Pathologic polycythemia (polycythemia vera)

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Effects of Anemia on Circulatory System

 In severe anemia, the blood viscosity may fall to as low as

1.5  decrease resistance to blood flow in the peripheral
blood vessels  increase in venous return  causes
increasing heart rate (tachycardia) & cardiac output.

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Leukocytes (White blood cells)
Introduction to WBCs
 Leukocytes are the only complete cells that contain nucleus,
and other organelles

 WBCs Make up 1% of the total blood volume

 Normal WBC count: 7000 – 11000/mm3

 Life span of most WBCs is only few hours or a few days.

 However, some B and T cells remain in the body for

years.

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Introduction to WBCs…
 Leukopenia (< 7000/mm3) - ↓in WBC count b/c of
radiation or chemicals.

 Leukocytosis (> 11000/mm3) - ↑in WBC count normal

response to bacterial or viral invasion
 Leukocytosis usually indicates an inflammation or
infection.

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Types of WBCs
 There are five types of circulating leukocytes - Neutrophils,
Eosinophils, Basophils, Monocytes, and Lymphocytes—
each with a characteristic structure and function.

Mononuclear Agranulocytes Polymorphonuclear Granulocytes

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Introduction

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Unique Properties of WBCs
 Leukocytes primarily function as defense agents outside the
blood.
 To carry out their functions, leukocytes largely use a “seek out
and attack” strategy; that is, they go to sites of invasion.
 The main reason WBCs are in the blood is for rapid transport
from their site of production or storage to wherever they are
needed.
 Unlike erythrocytes, leukocytes are able to exit the blood by
assuming amoeba-like behavior to wriggle through narrow
capillary pores and crawl to assaulted areas (affected area). 42
Differential white blood cell count
 Determining the percentage of each type in the blood assists
in diagnosing the disease condition.

 This test, called a differential white blood cell count,

measures the number of each kind of white cell in a sample
of 100 white blood cells.
 Neutrophils: 60% (3000-7000/mm3)
 Eosinophils: 2.4% (100-440/mm3)
 Basophils: 0.4% (20-50/mm3)
 Monocytes: 5.3% (100-700/mm3)
 Lymphocytes: 30% (1500-3500/mm3) 43
Differential white blood cell count…
 A high neutrophil count might result from bacterial
infections, burns, stress, or inflammation

 A high eosinophil count often indicates a parasitic

infection.

 A high Basophils often indicates allergic reactions.

 A high lymphocyte counts could indicate viral infections

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Leukopoiesis (WBCs Production)

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Leukopoiesis (WBCs Production)…
 All leukocytes ultimately originate
from common precursor stem
cells in the bone marrow.

 Granulocytes , monocytes & B-

lymphocytes are produced &
matured only in the bone
marrow.
 T-lymphocytes are originally
derived from precursor cells in
the bone marrow but matured in
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lymphoid tissues like thymus.
WBCs disorders
Leukemia - refers to a group of red bone marrow cancers in
which abnormal white blood cells multiply uncontrollably.

 The accumulation of the cancerous white blood cells in red

bone marrow interferes with the production of red blood
cells, white blood cells, and platelets

 All leukemia's produce the usual symptoms of anemia

(fatigue, intolerance to cold, and pale skin).

 In addition, weight loss, fever, night sweats and excessive

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bleeding.
WBCs disorders…
Leukopenia

 Abnormally low WBC count—drug induced

Mononucleosis

 Highly contagious viral disease caused by Epstein-Barr

virus; excessive # of agranulocytes; fatigue, sore throat,
recover in a few weeks

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Thrombocytes (Platelets)
Introduction to platelets
 Platelets are cell
fragments shed from
megakaryocytes

 Platelets are disc-shaped

cell fragments without
nuclei.

 A normal platelet count is

150,000 to 300,000/mm3
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Thrombocytosis (platelets Production)…

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Platelets function
 Platelets are necessary for
Hemostasis (stoppage of
hemorrhage)
 Hemostasis prevents blood loss from
damaged blood vessel by 3 steps
1. Vasoconstriction (Vascular spasm)
2. Platelet plug formation
3. Blood Coagulation (clot
formation)
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Vascular spasm
 In vascular spasm, the smooth muscle of a blood vessel wall
contracts.

 As platelets accumulate at the damaged site, they release

chemicals that enhance vasoconstriction (narrowing of a
blood vessel), thus maintaining the vascular spasm.

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Platelet plug formation
 Platelets normally do not stick to the smooth endothelial
surface of blood vessels, but when this lining is disrupted
because of vessel injury, platelets adhere to the exposed
collagen.

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Platelet plug formation…
 Why does the platelet plug not continue to develop and
expand over the surface of the adjacent normal vessel
lining?
 Activated platelets stimulate the release of Prostacyclin and
Nitric oxide from the adjacent normal endothelium.
 Both Prostacyclin & Nitric oxide inhibit platelet
aggregation.
 Thus, the platelet plug is limited to the defect and does not
spread to the nearby undamaged vascular tissue 55
Platelet plug formation…

+ve feed
back

56
Platelet plug formation…

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Blood Coagulation (Clotting)
 Blood coagulation (clotting) is the transformation of blood
from a liquid into a solid gel by chain of plasma clotting
factors.

 Formation of a clot on top of the platelet plug strengthens

and supports the plug, reinforcing the seal over a break in a
vessel.

 Clotting is the body’s most powerful hemostatic mechanism.

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Blood Coagulation (Clotting)…
 The ultimate step in clot formation is the conversion of
fibrinogen (soluble) into fibrin (insoluble) a threadlike
molecule catalyzed by the enzyme thrombin at the site of
the injury.

 Fibrin molecules adhere to the damaged vessel surface,

forming a loose, netlike meshwork that traps blood cells,
including aggregating platelets.

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Blood Coagulation (Clotting)…

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Blood Coagulation (Clotting)…

61
Blood Coagulation (Clotting)…

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Blood Coagulation (Clotting)…

RBC

Platelet

Fibrin

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Blood Coagulation (Clotting)…

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Blood Coagulation (Clotting)…

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Coagulation & Fibrinolysis
 A clot is not meant to be a
permanent solution to
vessel injury.
 It is a transient device to
stop bleeding until the
vessel can be repaired.
 Fibrinolysis-break down
of clot by plasmin
(enzyme) after the
damaged blood vessel is
healed or repaired (after
hemostasis).

66
Clotting Disorders
 Hemophilia: The most common cause of excessive bleeding
which is caused by a deficiency of one of the factors in the
clotting cascade.

67
Clotting Disorders…
 Inappropriate clotting produces thromboembolism.

 Thrombus: An abnormal intravascular clot attached to a

vessel wall.

 Embolus: freely floating clots.

 Both thrombus & embolus can completely occlude and

block blood flow to vital organs & may result in MI &
stroke.

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ABO Blood Types & Rh factors
ABO Blood Types
 The ABO blood groups were discovered in the early 1900s
by Karl Landsteiner, an Austrian-American scientist.

 The ABO group contains 4 blood types: A, B, AB, & O.

 The letters A and B represent antigens which are found on

the red blood cell membrane.

 Plasma contains antibodies termed anti-A and anti-B

antibodies.

70
ABO Blood Types…
 Antigen- protein on the surface of a RBC membrane

 Antibody- proteins made by lymphocytes in plasma which

are made in response to the presence of antigens.
 They attack foreign antigens, which result in clumping
(agglutination)
Blood type Antigen Antibody
A A anti-B
B B anti-A
A& B AB no anti body
Neither A or B No anti-A and anti-B
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ABO Blood group Cross Matching/Transfusion

Donors Recipients Blood Types

Blood
Types A B AB O
A ‒ + ‒ +
B + ‒ ‒ +
AB + + ‒ +
O ‒ ‒ ‒ ‒

(+) = Agglutination reaction

(‒) = No agglutination reaction 72
Transfusion Reaction (Blood incompatibility)

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Transfusion Reaction (Blood incompatibility)…

 Antibody interaction with an erythrocyte-bound antigen may

result in agglutination (clumping) or hemolysis (rupture) of
attacked RBCs.
 Agglutinated clumps of incoming donor cells can plug small
blood vessels which blocks oxygen and other nutrients to the
cells.
 The release of large amounts of hemoglobin from ruptured
donor erythrocytes will precipitate in the kidneys & block the
urine forming structures, leading to acute kidney shutdown.
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Rh Factor
 Rh blood group is so named because the Rh antigen or factor
was first found on the blood of Rhesus monkey.
 Grouped as Rh+ and Rh- based on the presence or absence of
antigen D on the surface of RBCs
The presence of antigen D on RBCs: Rh+
The absence of antigen D RBCs: Rh-
 Agglutinin (anti-D antibodies) are not normally present in the
serum but produced secondary to exposure of an Rh- blood to
Rh+ blood (antigen-D)
 Rh-negative people do not have natural antibodies but will
produce them if given Rh positive blood.
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Erythroblastosis Fetalis
 Resulted from of an Rh incompatibility between mother and
fetus.

 During a normal pregnancy, maternal blood and fetal blood

do not mix in the placenta.

 However, during delivery of the placenta (the “afterbirth” that

follows the birth of the baby), some fetal blood may enter
maternal circulation.

 If the woman is Rh negative and her baby is Rh positive, this

exposes the woman to Rh positive RBCs. 76
Erythroblastosis Fetalis…
 In response, her immune system will now produce anti-Rh
antibodies following this first delivery.

 In a subsequent pregnancy, these maternal antibodies will

cross the placenta and enter fetal circulation.

 If this next fetus is also Rh positive, the maternal antibodies

will cause destruction (hemolysis) of the fetal causing the
child to be born with serious anemia

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Erythroblastosis Fetalis…

 Rh+ mother w/Rh- baby– no problem

 Rh- mother w/Rh+ baby– problem
 Rh- mother w/Rh- baby - no problem
 Rh+ mother w/Rh- baby - no problem

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Treatment of Erythroblastosis Fetalis

 Erythroblastosis Fetalis (Hemolytic disease of the newborn) is

prevented by giving all Rh negative women an injection of
anti- Rh antibodies called anti-Rh gamma globulin
(RhoGAM) soon after every delivery, miscarriage, or abortion
or during pregnancy.

 These antibodies destroy any Rh antigens that are present so

the mother doesn’t produce her own antibodies to them.

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