Physiology of blood

Outline

1. Introduction
2. Hematopoeisis
3. Red blood cells
4. Disease of RBC
5. Hemostasis
6. White blood cells (WBC)
7. Immunity
 Introduction
• Blood is a connective tissue only because of
more than 2 cells
• Blood cells constitute:
a. Erythrocytes
b. Leukocytes
c. Thrombocytes
• Plasma is the liquid part of the blood and
contains
different organic and inorganic substances
(7% of the
body weight).
 cont’d

Functions of blood
▪ Transport: nutrients, gases, waste products
of metabolism
▪ Regulation: by transporting hormones,
regulation of temprature, ph, blood volume …
▪ Protection:
- Prevents blood loss
- Prevents infection through the activity of
WBC
 cont’d

Properties of blood
•The blood color: bright Vs. dark
• The red color comes from the Hgb…
• Blood viscosity
• Blood ph … 7.3-7.4
• ~ 60,000 miles of blood vessels throughout
the body
• The circulatory system works very closely
with the
other systems in the body …
 cont’d
Plasma:
• is the liquid portion of the blood
• 55% of the total blood volume.
• Composed of 92% water, 7% proteins, and
minute amounts of gases (O2, C02),
nutrients, metabolic wastes, and hormones.
Serum
• Is the fluid portion of the blood that remains
after blood has clotted.(It lacks fibrinogen
and clotting factors)
• Plasma proteins are divided into 3 groups
(albumin, globulin, and fibrinogen).
 Cont’d

Plasma protiens
1 . Albumin (60%):
- formed in the liver
- maintain blood
volume
- This prevents
edema.
 Cont’d

2. Globulin (36%):
• Divided into alpha, beta, and gamma
globulins.
• Gamma globulins serve as antibodies.
• Some other globulins help as carriers to
transport hormones, enzymes, nutrients
and other molecules in the body.
• Gamma globulinsCont’d
are produced in the
lymph tissues.
• Fibrinogen produced in the liver and
together with
other plasma proteins (e.g. prothrombin)
is involved in
blood clotting.
• When proteins involved in clotting
processes are
removed, the remaining liquid is known as
“serum”.
2. Hematopoeisis
 3.Red blood cells
• Red blood cells are relatively large
microscopic cells without nuclei.
• Accounts 40-50% of the total blood
volume.
• They transport oxygen from the lungs to
all of the living tissues of the body and
carry away carbon dioxide.
• Hemoglobin is the gas transporting
protein molecule that makes up 95% of a
red cell.
 con’d

• Each red cell has about 250 million iron-

rich hemoglobin molecules.
• The average is about 5 million cells/mm3.
• Although the numbers are important, it is
the amount of hemoglobin in the blood at
any time that really determines how well
oxygen is transported.
 con’d
• Hematocrit or packed
cell volume (PCV): If un
coagulated blood (blood
where Heparin is added)
is centrifuged, red blood
cells (RBCs) precipitate
down to the bottom of the
tube and account to about
45% of the measured
volume.
• This volume of
precipitated RBC is called
Hematocrit.
• Hematocrit means the
 cont’d

• PCV (Ht) increases in dehydration and

polycethemia and decreases in anemia,
thus Knowing Hct value is important in
clinical practices
• The white blood cells and platelets are
found between the precipitated RBCs’ and
the plasma layer forming a buffy coat.
 cont’d

✓ ESR is the rate or speed at which un-

coagulated blood (RBC) settles down when
allowed to stand in a tube.
✓ 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
Reading of ESR: Measure the depth of the
plasma layer in
 cont’d
Function of RBC
1. Carries hemoglobin that in turn transports

respiratory gases (O2 and CO2)

2. Carbonic anhydrase (CA):
An enzyme located in RBC membrane,
CO2 + H2O CA > H2CO3 = HCO-3
+ H+

• Average: Hb: 15 g/dl

• Average Hct : 45%
 cont’d
Production of RBC
A.Embryonic life:
produced in the liver, spleen and LN
B. Infants (5 years old):
Red bone marrow of all cells
B. Adults (after age 20):
Membranous bones like ribs, sternum,
vertebrae, and pelvic bones
B.But not in long bones like femur or tibia
(fat)
C.RBC production is controlled by tissue
hypoxia
 cont’d

✓ Substances necessary for formation and

maturation of RBC
- Iron
- Vitamin B12
- Folic acid
 cont’d

• Hemoglobin is a protein found inside RBCs

and functions in binding and transporting
O2 to tissues and also CO2 away from
tissues.
• Hb gives off O2 to tissues very easily when
tissues need for O2 increases as in
increased metabolism.
• Hb binds with O2 easily in the lungs (this
loose and reversible binding of Hb to O2 is
an important aspect of the Hb molecule to
supply O2 to body tissues).
 cont’d

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.
 cont’d

RBC destruction
• Steps in the destruction of RBC
1. RBC >Globin + Heme
2. Globin > Broken to AA’s > used for
protein synthesis
3. Heme > Fe2+ + poryphrine rings
4. Fe 2+ > stored in the liver > used for new
Hb synthesis
 cont’d

5. Pyrol rings > oxidation to green pigment

called Biliverdin and later
reduced to bilirubin
a. bilirubin + serum albumin > reach
liver
b. Bilirubin conjugates with glucuronic
acid in liver
c. Liver releases bilirubin as bile to
Small intestine
d. Bacterrias change bilirubin into:
Strrcobilinogen > stercobilin > feces
(brown color)
Effect of bilirubin
 4.Disease of RBC
Disease of RBCs
1. Anemia: 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:
i. Blood Loss Anemia.
ii. Aplastic Anemia functioning bone
marrow
iii. Megaloblastic Anemia
iv. Hemolytic Anemia
 Cont’d

2. 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)
 5. Types of blood group

• There are two known blood groups that

are clinically important:
a. The ABO-blood groups,
b. The Rh- blood group factors
cont’d
 cont’d

Rh factor
• 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.
 cont’d
Rh- incompatibility: Usually causes serious problems
- Father Rh + = Rh + means he has D-antigen on his
RBC membrane
- Mother Rh- = No Rh factor, so it is depicted as Rh-
ve
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.
 cont’d

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.
cont’d
 6. Hemostasis

• Hemostasis 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.
 cont’d
Properties of platelets (remember the 3-A’s)
1.Adhesiveness : platelets stick when they
come in -contact with wet and rough
surfaces.
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
 cont’d

Five stages of hemostasis:

1. Vasoconstriction (vascular spasm)→ decrease
blood flow to injured areas.
2. Platelet plug is Sealing the open injured blood
vessel holes
- The mechanism of platelet plug involves the
aggregation of platelets that stick to injured
vessels.
- ADP and Thromboxane A2 released from
cytoplasm of
platlets responsible for platlet aggregation
 cont’d
3. Clot (coagulation) formation
- This is a phase where blood loose its fluidity &
becomes a
jelly-solid mass.
- This cascade of reactions start by intrinsic and
extrinsic
mechanisms.
Extrinsic pathway:
- Begins with traumatized (injured) tissues that
release a
substance called tissue thromboplastin
Intrinsic mechanism
- Begins with trauma to the blood itself or exposure
of the
blood to collagen at injured blood vessel wall
 cont’d

4. Fibrin clot formation (clot retraction)

• Within a few minutes after a clot is formed,
it begins to contract and usually expresses
most of the fluid from the clot within 20-60
minutes.
• The fluid expressed is called serum
• failure of clot retraction is an indication that
the number of platelets in the circulating
blood might be low.
5. Clot dissolution
 cont’d
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) causes
thrombocytopenic purpura ( small
purplish blotches )
 cont’d
Anticoagulants
1.Heparin: has anti- Pro-coagulants
thrombin activity and
1. Thrombin
also inactivates factor
IX, X, XII 2. Snake venom
2.Warfarin and 3.
dicoumoaral: inhibit Thromboplasti
Vitamin K that is n
necessary to produce
factor X, IX and VII
3. EDTA (Ethylene
diamine tetra acetic
acid): Removes Ca2+
 7. White blood cells (WBC)
Types of WBC
1. Granulocytes and their life span
Polymorphonuclear
WBc’s (i.e. their nuclei have 3-5 lobes)
- Neutrophils (~ 62%), Eosinophils (~ 2-3%),
Basophiles (~ 0.1-0.4%) “
2. Agranulocytes and their life span
- Lymphocytes (~ 30%), weeks or months
- 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.
Mechanisms of WBC motility
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
 WBC cont’d
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
Mechanism of phagocytosis
1. Opsonization:
2. Attachment
3. Engulfment
4. Intracellular killing
by producing:
- Lysosomes, and
- oxidizing agents like
lipases,
peroxisomes, H2O2,
OH- ions are
produced from
macrophages that
are lethal for
bacterial cell
membranes.
 WBC cont’d
• 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
 WBC cont’d
• Are bi-lobed and
weak phagocytes .
• Have granules in the
cytoplasm that have
enzymes
• Phagocytize
antigen-antibody
complexes and
destroy them
• Their number
increases during
asthma and other
allergic attacks
 WBC cont’d
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.
 WBC cont’d
Basophils
• Constitute < 1%
• Have granules
• Produce heparin,
so act as natural
inhibitors of blood
clotting. They also
release
histamine,
serotonin, etc
 WBC cont’d
Lymphocytes
• Have no granules
and the nucleus is
not lobed
• Are responsible for
Specific immunity
that consists of:
a. Cellular
immunity
b. Humoral
immunity
 WBC cont’d

Diseases of WBC
1.Leukemia: Is a form of cancer in which WBCs
divide and increase their numbers above
normal.
The cancerous production can occur in the
bone marrow or lymph nodes.
2. Leucopenia: (decreased production of WBC)
- Bone marrow stops producing them
- Drug poison
- X-rays
 8. Immunity

• Immunity is the ability of the body to

specifically
protect itself against disease or
infectious agents.
• Immunology is the study of the bodies’
defense
mechanism against diseases.
• There are two types of immunity
1. Non-specific immunity (innate
immunity), you
are born with innate immunity
- These include the skin, hairs or cilia, and
 cont’d

2. Acquired (specific) immunity (develops

after exposure to foreign infectious agents).
• The type of WBCs directly involved in
specific immune responses is lymphocytes.
• During fetal development, lymphocytes are
produced from stem cells in the bone
marrow.
• Later before birth, one group moves to the
Thymus gland to be further differentiated or
preprocessed into cells called T-
Lymphocytes
 cont’d

Types of acquired immunity

1. Cellular immunity
Cellular immunity develops from T-
lymphocytic cells.
2. Humoral immunity
• Humoral immunity develops from B-
lymphocytic cells.
• The B-Lymphocyte cell after being
exposed in the spleen move to the
lymphoid tissues
• Activated Blymphocytes begin to multiply
 Cont’d
• Some of the clones differentiate into plasma cells,
which can then secrete large amounts of antibody.
• The other cells of the clone become B-memory cells
• Plasma cells have developed and extended
Endoplasmic R. which synthesize and secrete
antibody.
• Antibody cause destruction of antigen by
- Agglutination (clumping the pathogens
together)
- Lyses (rupturing the cell-membrane of the
invader).
- Neutralization (Blocking the toxic effects of
pathogens)
- Opsonization (making the agent susceptible for
Phagocytosis)
 Cont’d
The different types of T-cells include:
A.Killer (cytotoxic) T-cells: Kill pathogens
directly and stimulate other macrophages for
phagocytosis
B. T-memory cells: Remain as reserve in the
lymph node and protect when the same type
pathogen attacks the body again
C.Helper T- cells: Helper B-lymphocytes to
produce plasma cells for antibody production.
Are the most numerous than others.
D. Suppressor T-Cells: Regulate the
immunological
response of T-and B-cells.
 cont’d

B-lymphocytes
- Are pre-processed in fetal liver, spleen or
in bone marrow.
- They migrate to lymphoid tissues and
become sensitized by specific antigens.
After sensitization, they multiply forming
clones of identical cells
 Cont’d

- Some B-cells enlarge and change to

plasma cells that secrete different kinds
of antibodies (IgA, IgD, IgE, IgM, IgG).
- Other B-cells of the clone become B-
memory cells, which stay in the lymph
node as a reserve and fight back when
the same type of antigen comes into
contact in a 2nd exposure.
 cont’d

1. IgG (>75%):The most plenty form of Ig in

circulation. (>75%). It crosses the placenta
and provides passive defense to the fetus and
the new born.

2.IgM (10%): Are pentameres and 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 and activates the complement
system and clumps cells
 cont’d

3. IgE :Antibodies of this class are called

reagins
-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.

4. IgA :It is the main antibody type found in

body secretions such as saliva, tears,
milk, bronchus and the GIT