Blood

Physiology
1. Introduction
2. Basic function of cells
3. Blood
4. Circulatory system
5. Respiratory system
6. Digestive system
7. Energy metabolism and body temperature
8. Urinary system
9. Endocrine system
10. Nervous system
11. Sensory organ
Blood
Nutritive function
Transport function
Clot formation
Protective function
The function of blood
Regulation of osmosis
Homeostatic function
Maintenance of body
temperature
Storage function
Function of Blood
• Blood carries the nutritive substances like glucose,

Nutritive amino acids, fatty acids, vitamins, electrolytes and
others from the gut to the tissues where they are
function utilized.
• The various hormones produced by the endocrine

glands, the biological enzymes, antibodies, gases
(O2 &CO2 ) are transported by the blood to the
Transport target tissue to modulate metabolic process. Blood
transports various metabolic waste products, such
function as urea, uric acid and creatinine to excretory
organs (kidney, skin, intestine and lungs) for their
disposal.
Function of Blood
• Blood clotting protects against excessive
blood loss when blood vessels are damaged.
The blood clot that forms in damaged tissue is
Clot formation also the first step in tissue repair and the
restoration of normal function (positive
feedback mechanism)
• Neutrophils and monocytes engulf the

Protective microorganisms entering the body by
phagocytosis. Lymphocytes and γ globulins
function initiate immune response.
Regulation of • The osmotic composition of blood is also

critical for maintaining normal fluid and ion
osmosis balance.
Function of Blood
• Blood plays an important role in maintaining the
internal environment of the body (homeostatic
Homeostatic function): water and electrolyte balance of the body,
Plasma proteins and haemoglobin act as buffers and
function help in maintaining the acid–base balance and pH of
the body fluids.
Maintenance of • Blood plays an important role in regulation of the

body temperature, as described: Specific heat of
body blood is high, High heat conductivity of blood , high
temperature latent heat of evaporation of blood
• Blood serves as a ready-made source of substances

stored in it (such as glucose, water, proteins and
Storage function electrolytes for use in emergency conditions like
starvation, fluid loss and electrolyte loss).
Blood
• Composition and characteristics of blood

• Physiology of blood cells
• Physiological hemostasis, blood coagulation and fibrinolysis
• Blood group and blood transfusion
Composition and characteristics of blood
• The basic composition of blood and blood volume

– Haematocrit
– Plasma
– Blood volume
• Characteristics of blood
– The specific gravity of blood
– The viscosity of blood
– The osmotic pressure of plasma
– The pH of plasma
The basic composition of blood
• Blood is a liquid connective tissue that consists of

cells surrounded by a liquid extracellular matrix.
• blood plasma, a clear straw coloured watery liquid portion of
blood that contains dissolved substances
• formed elements, which are cells and cell fragments (red
blood cells, white blood cells, and platelets)
venipuncture
• Constituents of plasma protein
• Hematocrit：a percentage of erythrocytes (RBC) in the total

volume of a blood sample
• normal range：
adult male 40%50%
adult female 37%48%
newborn 55%
by spinning the capillary tubes which contain

the whole blood, the centrifuges can be used
to determine hematocrit value
• Plasma：a clear straw coloured watery

liquid portion of blood with
anticoagulant
• Serum：If the blood is drawn from the

body, it thickens and forms a gel (blood).
Serum is the straw-colored liquid
separates from the gel, it is simply
blood plasma minus the
clotting proteins
• blood volume： volume of blood (both red blood cells and

plasma) in the circulatory system of any individual
circulating blood volumes

blood volumes of storage pools
• Normal range：Volume of blood in an average adult is about

5–6 L (8% of the body weight or 80 mL/kg body weight, 100
mL/kg in neonates)
• Functions of plasma proteins

1. Transport function
2. Role as reserve proteins & nourishment of tissue cells
3. Exert osmotic pressure:The plasma proteins exert an oncotic
pressure of about 25 mm Hg.
4. Role in coagulation & fibrinolytic function of blood
5. Role in maintaining acid–base balance of the body: NH2+H+→
NH4; COOH→ COO−+H+
6. Role in defense mechanism of the body: antibodies
which play an important role in the immune system
Characteristics of blood
• Colour of the blood is opaque red due to the pigment
haemoglobin in the red blood cells (RBCs). The arterial blood is
bright red and venous blood is dark red in colour.
• Viscosity of blood is 4-5 times more than that of water (due to the
number of RBC).
• Viscosity of plasma is 1.6-2.4 times more than that of water (due
to the amount of protein).
• Specific gravity of blood is 1.050–1.060 (due to the number of
RBC).
• Specific gravity of RBC is 1.090-1.092 (due to the amount of
hemoglobin).
• Specific gravity of plasma is 1.025-1.030 (due to the amount of
protein).
• pH of blood is about 7.4 (ranges from 7.38 to 7.42), i.e. it is
alkaline in nature. In acidosis, pH of blood falls below 7.38 and in
alkalosis, pH is more than 7.42.
colloid osmotic pressure
of tissue fluid (0.8)
Tissue fluid

of plasma (1.6)
crystalloid
osmotic pressure crystalloid
of RBC osmotic pressure
of plasma
• Blood osmotic pressure

– Osmosis
– Osmotic pressure
– plasma osmotic pressure
– crystalloid osmotic pressure
– colloid osmotic pressure

– Osmosis：Osmosis is the diffusion of water (solvent) from
low concentration of solute to high concentration of solute
across a selectively permeable membrane
– Osmotic pressure is the minimum pressure which needs to
be applied to a solution to prevent the inward flow of
water across a semipermeable membrane.
– Osmole is the unit used in place of grams to express the
concentration in terms of number of osmotically active
particles in a given solution. One osmole is equal to the
molecular weight of a substance in grams divided by the
number of freely moving particles liberated in solution
by each molecule. Thus:
1. A molar solution of glucose contains 1 mole and
exerts osmotic pressure of 1 atm.
2. A molar solution of NaCl contains 2 osmoles (1 mole of
Na+ and 1 mole of Cl−) and exerts osmotic pressure of 2
atmospheres.
3. A molar solution of CaCl2 contains 3 osmoles (1 mole of
Ca2+ and 2 moles of Cl−) and thus exerts osmotic
pressure of 3 atm.
4. One milli osmole (mOsm) is 1/1000 of an osmole.

– Osmolality of a solution refers to the number of osmotically active
particles (osmoles) per kilogram (kg) of a solution
– Osmolarity refers to the number of osmoles per litre (L) of a
solution
– Osmolarity is affected by the volume of the various solutes in
the solution and the temperature, while the osmolality is not.
– The osmotic pressure is determined by the osmolality.
– In practice, osmolarity is more frequently used in
physiological studies, since it is far more easier to measure
osmolarity.
300 mmol/L
300 mOsm/Kg H2O
770 kPa
5800mmHg)

– plasma osmotic pressure
– The normal osmolality of the extracellular and intracellular
fluids is 290 milliosmoles per kilogram (mOsm/kg).
crystalloid osmotic pressure
– In the plasma of the total osmolality 270 mOsm are
contributed by Na+, Cl− and HCO3−. The remaining 20
mOsm are contributed by glucose and urea. Because of the
large molecular weight and hence lesser number of
particles, plasma proteins contribute 2 mOsm to the total
plasma osmolality.
– ～300 mmol/L (300 mOsm/Kg H2O)
Characteristics of blood crystalloid
of plasma

– crystalloid osmotic pressure：
• is the pressure generated by all crystal substances,
particularly electrolytes (mainly Na+ and Cl-).
• This pressure modulates water distribution between
inside and outside of cells. Hence, it is important in
maintaining fluid balance
Characteristics of blood crystalloid
of plasma

– crystalloid osmotic pressure
shrink swell & burst
Isosmotic solutions hyperosmotic solutions hyposmotic solutions

have the same have a greater have a lower
concentration of concentration of solute concentration of
solute particles particles solute particles.
of tissue fluid (0.8)
Tissue fluid
• Blood osmotic pressure colloid osmotic pressure

of plasma (1.6)
– colloid osmotic pressure/ oncotic pressure：
– Colloids = large molecular weight particles present in a solution.
– The plasma proteins, particularly albumin are the major colloids
present in plasma and they contribute to the total osmotic pressure of
the solution.
– most blood capillary walls are relatively impermeable to the plasma
proteins, and the proteins therefore exert an osmotic force of about
25 mm Hg across the capillary wall (oncotic pressure that pulls water
into the blood.)
– This pressure modulates water distribution between inside and
outside of blood capillaries. Hence, it is important in fluid transfer
across capillaries
• pH of plasma
– The pH of plasma is maintained within a narrow range of
7.35～7.45.
– Buffers system in blood (consist of mixtures of a weak acid
or base and its salt) can minimize the changes in pH.
most important potassium salt of Hb

bicarbonate/carbonic acid buffer
Physiology of blood cells
• Erythrocytes/red blood cells/RBC

• Leukocytes/white blood cells/WBC
• Platelets
• Erythrocytes
– The morphology & number of erythrocytes
– The physiological features of erythrocytes
– The functions of erythrocytes
– The erythropoiesis and its regulation
– The life span and destruction of erythrocytes
Erythrocytes
• Diameter of each RBC is 7.2 μm (range

6.9–7.4 μm)
• circular, biconcave discs (greater
surface area as compared to volume)
• non-nucleated and lacks the usual cell
organelles
• carry the blood group antigens like A
antigen, B antigen and Rh factor. This
helps in determination of blood group
• Contains a special pigmented protein
called the haemoglobin (Hb)
Erythrocytes
• Hemoglobin
male：120～160 g/L
female：110－150 g/L
• RBC count
female ： 3.8～4.6 X 1012 /L
male： 4.5～5.5 X 1012 /L
neonate： 6 X 1012 /L
• The number of red cells you have varies according to sex and
age. Women have lower levels than men and newborn babies
often will have more than adults.
• Persons living at high altitudes have greater numbers of RBCs.
Erythrocytes
Hemoglobin/Hb
• each of the four polypeptide chains of a hemoglobin molecule
has one heme group, which contains an iron ion (Fe2)
ferrous
Erythrocytes
The physiological features of erythrocytes

1. Permeability
2. plastic deformability
3. osmotic fragility
4. suspension stability
Erythrocytes

1. Permeability
• The red cell membrane is a semi-permeable membrane,
allowing some substances to pass through and preventing
some.
• Impermeable to sodium, calcium and barium ions, fats and
sugars.
• Slightly impermeable to amino acids.
• Freely permeable to all anions like Cl−, SO4− and HCO3− , and to
urea, ammonia, aldehyde, alcohol and bile salts.
During blood storage there is a slow but constant leakage

of potassium from cells into surrounding plasma. →K+
Erythrocytes
2. plastic deformability
• Their plasma membrane is both strong and
flexible, which allows them to deform without
rupturing as they squeeze through narrow
blood capillaries
Erythrocytes

3. Osmotic fragility
• The susceptibility of red cell membrane to get lysed due to
changes in the osmotic pressure of the solution in which they
are suspended
• The process of breaking of RBCs and release of Hb into the
plasma is called haemolysis.
Erythrocytes

3. Osmotic fragility
• Isotonic solution: 0.9% NaCl solution or 5% glucose solution
• Normal values (index of fragility)
– Onset of haemolysis (fragility) in normal RBCs occurs in
0.42% NaCl
– Completion of haemolysis (ending of fragility) occurs in
0.35% NaCl
isosmotic solutions
hyperosmotic hyposmotic
solutions solutions
Erythrocytes

• The property of red blood cells which remain suspended
uniformly in the blood is called the suspension stability of red
blood cells (resistance to sedimentation rate) , it can be
measured by ESR
• Erythrocyte sedimentation rate (ESR) ：It is the rate at which
the RBCs sediment (settle down) when the blood containing an
anticoagulant is allowed to stand in a vertically placed tube. It is
expressed in millimetre at the end of first hour.
Erythrocytes

• Rouleaux formation refers to the tendency of the RBCs to pile one
over the other like a pile of coins (reversible phenomenon).
• This causes a fall in the surface area exposed to the plasma and
decreases the stability of red cell suspension by reducing the
frictional interaction between cells and plasma, thus increase ESR
• fibrinogen, globulin and other products of tissue destruction
increase rouleaux formation
• Albumin and lecithin decrease () the rouleaux formation
• ESR values: Male：0～15mm/hr，female：0～20mm/hr
(normal range varies depending on the type of test tube used)
Erythrocytes
The functions of erythrocytes

1. Transport of O2 from the Lungs to the Tissues:
Hemoglobin in RBC combines with oxygen to form
oxyhemoglobin (HbO2). About 97% of oxygen is transported in
blood in the form of oxyhemoglobin.
2. Transport of CO2 from the Tissues to the Lungs:
Hemoglobin combines with carbon dioxide (30%) and form
carbaminohemoglobin /carboxyhaemoglobin /HbNHCOOH/
HbCO2). RBCs contain a large amount of carboxyhaemoglobin the
carbonic anhydrase. This enzyme is necessary for the formation of
bicarbonate (HCO3-) from water and carbon dioxide (63%) .
3. Buffering Action in Blood: Hemoglobin functions as a good
buffer and thereby plays a role in the maintenance of acid-base
balance.
Erythrocytes
The erythropoiesis
• The process by which the formed elements of blood develop
is called hemopoiesis or hematopoiesis.
• Erythropoiesis, i.e. development of RBCs.
Erythrocytes
The erythropoiesis
• Before birth, hemopoiesis first occurs in the yolk sac
of an embryo and later in the liver, spleen, thymus,
and lymph nodes of a fetus.
• Red bone marrow (bones) becomes the primary site of
hemopoiesis in the last 3 months before birth, and
continues as the source of blood cells after birth and
throughout life.
• In adults, therefore, haemopoietic (red) bone marrow is
confined to the axial skeleton (skull, vertebrae, sternum,
ribs, sacrum and pelvis) and the proximal ends of long
bones (humerus, femur and tibia).
Erythrocytes
• Erythropoiesis: the production of RBCs Mature RBC
Reticulocyte
Pronormoblast Early normoblast Late normoblast
/proerythroblast /Orthochromatic normoblast
Stem cells
Erythroid progenitors Intermediate normoblast

/polychromatic normoblast
Pluripotent progenitor cells
BFU-E (burst forming unit–erythroid)

CFU-E (colony forming unit–erythroid)
Erythrocytes
The erythropoiesis and its regulation

• The materials for erythropoiesis
– Vitamin B12 (cobalamin)：
– folic acid
– Iron
– Protein
– Amino acid
– Vitamin
– Trace elements
Erythrocytes

– Vitamin B12 (cobalamin) ：is required for the synthesis of DNA
(activation of folic acid) and maturation of nucleus and cell. The
intrinsic facator, which produced by gastric cells, can combine
with vitamin B12 in food and makes the B12 available for
absorption by the gut.
– Deficiency of vitamin B12 leads to:
• Failure of maturation of nucleus.
• Cells remain large (megaloblasts) and become more
fragile
• There occurs reduction in the cell division.
Erythrocytes

– folic acid: play an important role in the synthesis of DNA
along with vitamin B12. Folate deficiency causes
megaloblastic anaemia.
Erythrocytes

– Vitamin B12 (cobalamin)
– folic acid
Metabolic pathway showing interaction of

vitamin B12 and folate in the synthesis of DNA
Erythrocytes

– Iron：Iron is necessary for formation of the heme part of
haemoglobin. In addition to dietary iron, the iron released
by degradation of RBCs is also reused for the synthesis of
Hb. The lack of ion will cause iron deficiency anaemia,
which is microcytic hypochromic anemia.
Erythrocytes
• Hypoxia stimulates the kidneys to step up the release of
erythropoietin (EPO) which speeds the development of RBCs.
• Epo plays a unique role in erythropoiesis, stimulating
proliferation of immature BFU-E in addition to promoting
terminal differentiation of later erythroid progenitor cells.
Erythrocytes

• Hormones which increase erythropoietin secretion also involve
in increasing of RBCs
1. Androgens (male sex hormones) enhance erythropoietin
secretion. This explains the greater RBC count in males as
compared to females.
2. Thyroxine also promotes erythropoiesis. This explains the
occurrence of polycythaemia in hyperthyroidism.
3. Other hormones which increases erythropoietin secretion are
growth hormone, prolactin, ACTH and adrenocortical steroids.
Erythrocytes
The life span and destruction of erythrocytes

• The cell membrane of old RBCs becomes more fragile due to
decreased NADPH activity.
• Red blood cells live only about 120 days because of the wear
and tear their plasma membranes undergo as they squeeze
through blood capillaries.
• The destruction of red cells occurs mostly in the tissue
macrophage system (reticuloendothelial system) of bone
marrow, liver, spleen and lymph node. → extravascular
hemolysis
• The porphyrin portion of the hemoglobin is converted by the
macrophages, through a series of stages, into the bile pigment
bilirubin
Erythrocytes
reticuloendothelial system
(extravascular hemolysis)
Erythrocytes

• In intravascular hemolysis, RBCs lyse in the circulation
releasing hemoglobin into the plasma. Causes include
mechanical trauma, complement fixation, and other toxic
damage to the RBC.
• Intravascular hemolysis releases hemoglobin which is
immediately bound by haptoglobin.
• After haptoglobin is saturated, excess hemoglobin is filtered in
the kidney →Hemoglobinuria
Erythrocytes
(intravascular hemolysis)
Erythrocytes
RBC Life Cycle
https://www.youtube.com/watch?v=jRTt_2UWryk
• Leukocytes
– The number & classification of leukocytes
– The physiological features & functions of leukocytes
– The production & regulation of leukocytes
Leukocytes
White blood cells (leukocyte/WBC) are colourless nucleated cells

and play an important role in the defence mechanism of the
body.
• leucocyte count & its classification
– Adults：(4.0～10)×109/L
– neutrophil：50%～70%
eosinophil： 0.5%～5%
differential count
basophil：0%～1%
monocyte：3%～8%
lymphocyte：20%～40%
Leukocytes
• leucocyte count & its classification

– Variation in leukocyte count (physiological fluctuation)
1. higher in infants and children: More lymphocytes (40-60%
of TC) than Neutrophils.
2. After meals
3. Diurnal variation: Rises in afternoon and falls in early
morning.
4. In pregnancy and puerperium
5. In muscular exercise
6. In fear, pain and anoxia
Leukocytes
The physiological features of leukocytes

• diapedesis
• chemotaxis
• phagocytosis
Leukocytes

• diapedesis: a process by which the cells are emigrated from
the blood to the site of infection into the tissues by passing
through the junction between endothelial cells of the
blood vessels
Leukocytes

• chemotaxis:a process by which the cells are attracted towards
bacteria at the site of inflammation. The process is mediated
by the chemotactic agents called chemokines which are
released at the infected area.
Leukocytes
• phagocytosis: a process by which the cell engulf the foreign
particles or bacteria and digest them and ultimately may kill
them
Leukocytes
Neutrophil
• In the blood, they exist in two equal populations:
– The circulating pool comprises 50% cells which are
circulating in the blood at any instant
– The marginal pool is constituted by the rest of 50% of cells
which remain marginated or sidelined, i.e. sticking to the
endothelial cells of closed capillaries, venules, small
veins and sinusoids.
Leukocytes
Neutrophil
• engulfment and destruction of bacteria and dead cells by
bactericidal agents such as lysosomal hydrolases, defensins,
strong oxidants (the superoxide anion/O2-), hydrogen
peroxide/H2O2, and the hypochlorite anion/OCl-
• Neutrophils killed by the toxins released from the bacteria are

collected in the centre of infected area. These are called pus
cells and together with plasma leaked from the blood vessels,
liquefied tissue cells and red blood cells escaped from the
damaged capillaries constitute the pus.
Neutrophil
Leukocytes
eosinophil：
• Eosinophils are not very motile and thus have a very mild
phagocytic activity
• They play an important role in the defence mechanism of
body especially in parasitic infections. Eosinophils attach to
the worm and secrete substances that kill it.
• The eosinophils increase in number in allergic conditions like
bronchial asthma and hay fever.
• They are capable of detoxifying inflammation inducing
substances (released by mast cells and basophils) like
histamine—eg. Release histaminase (combat the effects of
histamine) or inhibit mast cell degranulation.
Leukocytes
basophil：
• similar structurally and functionally to mast cells
• Basophils release histamine, leukotriene and serotonin (5HT).
These substances, in turn, cause local vascular and tissue
reactions (contract bronchial smooth muscle and increase small
blood vessel permeability) that cause many allergic
manifestations.
• Basophils also release eosinophil chemotactic factor that causes
eosinophils to migrate toward the inflamed allergic tissue.
Eosinophils then phagocytose and destroy antigen–antibody
complexes and prevent spread of local inflammatory process.
• Basophils release heparin in the blood which prevents clotting of
the blood and activates the enzyme lipoprotein lipase which
removes fat particles from the blood after a fatty meal.
Leukocytes
monocyte
• On their arrival at the site of infection , monocytes enlarge
and differentiate into macrophages
• Their main function is phagocytosis (most powerful) -engulf
bacterial and large particles such as red blood cells
• They also play a role in antigen presentation
Leukocytes
monocyte
• Tissue macrophage can live for months or even years
Leukocytes
lymphocyte
• Based on their developmental background, life span and
functions, the small lymphocytes have been broadly classified
into three subtypes :
1. B lymphocytes which are processed in the bone marrow and
concerned with the humoral immunity
2. T lymphocytes which are processed in the thymus and
concerned with cellular immunity
3. Natural killer cells are lymphocyte-like cells that non-
specifically kill any cell that is coated with immunoglobulin
IgG.
Leukocytes
lymphocyte
• T lymphocytes do not produce circulating antibodies; instead,
they directly destroy their specific target cells by releasing
chemicals that punch holes in the victim cell, a process called
cell-mediated immunity. The target cells of T cells include body
cells invaded by viruses and cancer cells.
Leukocytes
lymphocyte
• The derivatives of B lymphocytes, the plasma cells produce
antibodies, which circulate in the blood. An antibody binds with
and marks for destruction (by phagocytosis or other means) the
specific kinds of foreign matter, such as bacteria, that induced
production of the antibody.
Leukocytes
The production & regulation of leukocytes

• The process of development and maturation of white blood cells
(leucocytes), called leucopoiesis.
• All the blood cells develop from the so-called pluripotent
hematopoietic stem cells (PHSCs). The stem cells after a series
of divisions differentiate into progenitor cells which are also
called colony forming units (CFU)
• The development of granulocytes through various stages is called
myeloid series and development of monocytes through various
stages is called monocyte–macrophage series.
• The development of lymphocytes through various stages is called
lymphoid series.
Leukocytes
• The production &

regulation of leukocytes
• The life span of leukocytes
Hematopoiesis regulation
factor:
1. Colony Stimulating factor
/CSF
2. Interleukin
n months/ 6-8h 6h >100 d 3～4d
n year
• Platelets
– The number of platelets
– The physiological features of platelets
– The functions of platelets
– The production & regulation of platelets
– The life span & destruction of platelets
Thrombocytes/platelets
• Platelets are the smallest blood cells varying in diameter from

2 to 4μm.
• They break off from the megakaryocytes in red bone marrow
and then enter the blood circulation.
• Platelets are colourless, spherical or oval discoid (plate)
structures at resting state
• when they are activated, they begin to swell and assume
irregular forms with large number of pseudopodia
protruding from the surface
• Nucleus is absent in the platelets
• central compact region (granulomere) that stains blue to purple

• periphery pale blue homogeneous region (hyalomere)
• Invagination of the surface membrane forms the so called open
canalicular system or the surface connecting system— discharge
of secretory products
• dense tubular system—an internal smooth endoplasmic
reticulum membrane system for the storage of Ca2+ & the
synthesize prostaglandin and thromboxane
• resting state
/5-hydroxytryptamine/5-HT
• activated state
The number of platelets

• Normal blood contains 100,000–300,000 platelets/μL.
• Critical values:
– <50  109/L ：severe thrombocytopenia →
bleeding/haemorrhage
– >1000 109/L：severe thrombocytosis →
thrombosis (clotting in an undamaged blood vessel)
The physiological features of platelets

• Adhesion
• Aggregation
• Secretion
• Absorption
• clot retraction

• Adhesion：Platelets possess the property of adhesiveness,
i.e. when they come in contact with any wet surface or rough
surface, these are activated and stick to the surface. The von
Willebrand factor which released from storage granules in
platelets and endothelial cells, mediates the adhesion of
platelets to collagen at the sites of vascular injury.
fibrinogen
von Willebrand factor


• Secretion ：Following adhesion, the platelets are stimulated
to release the contents of their granules such as ADP and
thromboxane A2, which act on the nearby platelets and cause
their activation.
Fibrinogen
thromboxane A2 von Willebrand factor
platelet-derived growth factor
platelet factors 1–7
beta-thromboglobulin
Thrombospondin
Fibronectin
P-selectin
Lysosomes: Acid hydrolases


• Aggregation：Platelets have the property to aggregate, i.e.
they stick to each other. Several mediators lead to activation
and subsequent aggregation of platelets.

• Absorption：The platelets also provide an extensive
phospholipid surface for the interaction and activation of
clotting factors in the coagulation pathway.

• clot retraction： Contraction of contractile proteins (actin,
myosin) presents in the platelets play an important role in clot
retraction, the process by which a blood clot becomes
smaller and draws the edges of a broken blood vessel
together and which involves the shortening of fibrin threads
and the squeezing out of excess serum.
The functions of platelets：

• Involve in hemostasis
• Promote coagulation
• The PDGF present in the cytoplasm of platelets plays an
important role in the repair of endothelium and other
structures of the injured or damaged blood vessels
• Primary hemostasis. A platelet plug is rapidly formed to stop
blood loss from an injured vessel. Adhesion of platelets to
subendothelial collagen is accompanied by the release of
platelet factors, resulting in recruitment and aggregation of
more platelets.
• Secondary hemostasis. A cascade of coagulation reactions

results in the formation of a stable fibrin mesh to prevent
bleeding from a site of injury.

• Involve in hemostasis
Aggregation
Secretion clot retraction
Adhesion Absorption

• Promote coagulation：
1. Release of platelet factors
i. platelet factor 1 is adsorbed coagulation factor V from the plasma
i. PF2/platelet factor 2 is an accelerator of the thrombin-
fibrinogen reaction
ii. PF3/platelet factor 3 is a lipoprotein with roles in the activation of
both coagulation factor X and prothrombin
iii. PF4 /platelet factor 4 is capable of inhibiting the activity of
heparin
iv. PF6 /Anti-fibrinolytic factor
2. Release of coagulation factors
The life span & destruction of platelets
• Formation or development of platelets is called thrombopoiesis
• Thrombopoiesis seems to be regulated by thrombopoietin,
megakaryocyte—colony stimulating activity (Meg-CSA)
• Life span of platelets varies from 8 to 12 days with an average of 10
days. Platelets are destroyed by tissue macrophage system in spleen.
• Each megakaryocyte may form up to 4000 platelets.
Blood
• Physiological hemostasis, blood coagulation and fibrinolysis
– Physiological hemostasis
– Blood coagulation and anticoagulant system
– Fibrinolysis and fibrinolysis inhibitors
Hemostasis
• Haemostasis refers to the spontaneous arrest or prevention of

bleeding from the injured/damaged vessels by the physiological
process.
1. Vasoconstriction
2. Formation of temporary haemostatic plug
3. Formation of the definitive haemostatic clot
4. Breakdown of the clot (fibrinolysis)
Hemostasis
Hemostasis
5-HT, Vascular
TXA2 constriction
Hemostasis
1. Vasoconstriction:At a site of injury, platelet activation and clot
formation result in the release of the vasoconstrictors. Platelets
release the vasoconstrictors serotonin and thromboxane A2; the
clotting protein thrombin stimulates endothelial cells to secrete
the highly potent vasoconstrictor endothelin-1.
2. Formation of temporary haemostatic plug: Platelet plug
formation occurs at the site of damage in capillaries, arterioles,
and venules. Plug formation is called primary hemostasis.
3. Formation of the definitive haemostatic clot: Clot formation
occurs in which a fibrin mesh forms together with platelets and
other trapped blood cells. Clot formation is called secondary
hemostasis.
4. The formation of a stable blood clot is followed by the orderly
breakdown of the clot (fibrinolysis) as wound healing proceeds.
Blood coagulation
• When the blood looses its fluidity and gets converted into a jelly-like
mass which is called clot. This phenomenon is called coagulation or
clotting of blood.
• The process of blood coagulation consists of a complex cascade of
reactions.
– Formation of prothrombin activator
• Extrinsic pathway
• Intrinsic pathway
– Conversion of prothrombin to thrombin
– Conversion of fibrinogen into fibrin
Blood coagulation
• Coagulation factor
Blood coagulation
Blood coagulation
• Majority of coagulation
factors are precursors
of proteolytic enzymes
known as zymogens
that circulate in an
inactive form.
Blood coagulation
• Coagulation cascade
(intrinsic coagulation pathway)
collagen/
HMWK
kallikrein
(extrinsic coagulation pathway)
PKK
组织因子
Ca2+
Ca2+
(common coagulation pathway)
Formation of
prothrombin activator
Conversion of prothrombin to thrombin
Conversion of fibrinogen to fibrin Ca2+

Blood coagulation
Blood coagulation
• The extrinsic pathway of formation of prothrombin activator begins
with trauma to the vascular wall or the tissues outside the blood
vessel.
• The intrinsic pathway of formation of prothrombin activator begins in
the blood itself following trauma to blood itself or exposure of blood
to collagen in a traumatized vascular wall.
• Common pathway
– Formation of prothrombin activator. The activated factor X along
with the phospholipids released by the activated platelets,
activated factor V and Ca2+ forms a complex which is called
prothrombin activator.
– Conversion of prothrombin to thrombin is caused by the
prothrombin activator in the presence of Ca2+. This occurs at the
surface of platelets which form the platelet plug at the site of
injury.
– Conversion of fibrinogen into fibrin by thrombin. Fibrin stabilizing
factor (factor XIII) causes formation of covalent cross-linkages
between fibrin threads to strengthen the fibrin meshwork.
Anticoagulant system
• Mechanisms preventing intravascular coagulation in the normal
human : (1) the fibrinolytic system ; (2) the antithrombin
system; (3) blood flow; (4) surface effects of endothelium
• Velocity of circulation. Blood is pumped into the vessels and
circulated at a constant velocity which contributes to its fluidity.
• Surface effects of endothelium
– Smoothness of the endothelial lining inhibits platelet
adhesion and thus prevents initiation of intrinsic clotting
mechanism.
– A layer of glycocalyx (mucopolysaccharide) adsorbed to the
inner surface of endothelium being negatively charged repels
clotting factors (anion proteins) and platelets and thereby
prevents clotting.
– Intact endothelium acts as a barrier between the
thrombogenic subendothelial collagenous tissue and the
blood.
– Prostacyclin is an endogenous factor which prevents platelet
aggregation by inhibiting the thromboxane A2 formation
(which promotes platelet aggregation).
• Circulatory anticoagulants or the so-called natural anti-

coagulants present in the blood which prevent clotting are:
– Tissue factor pathway inhibitor/TFPI
– Heparin
– Antithrombin III
– α2 macroglobulin
– ProteinC
• Fibrinolytic mechanism
• Removal of activated clotting factors. Liver plays a role in
preventing the intravascular clotting by removing activated
clotting factors in the event of onset of spontaneous clot
formation.
Tissue factor pathway inhibitor/TFPI

• TFPI is thought to be important in modulating TF-induced
thrombogenesis.
• TFPI is a dual inhibitor, binding to the TF/FVIIa complex to
prevent it from acting on its FIX and FX substrates, and by
directly inhibiting FXa as well.
protein C system
• protein-C is a naturally occurring anticoagulant which
inactivates factors V and VIII and also inactivates an inhibitor
of tissue plasminogen activator increasing the formation of
plasmin which acts as fibrinolytic system
• Protein S serves as cofactor for activated protein C.
• protein-C is activated by thrombin
• Antithrombin III inactivates a number of coagulation factors including

clotting factors IX, X, XI and XII
FIX, X, XI and XII
• Heparin：
– Facilitates the action of antithrombin III
– Reduced platelet aggregation
– induces synthesis and secretion of tissue factor pathway inhibitor
(TFPI) from endothelial cells
– Enhance induction of endothelial plasminogen activators
Fibrinolysis and fibrinolysis inhibitors
Fibrinolysis
• Fibrinolysis is the plasmin-mediated enzymatic breakdown of
fibrin.
• Plasmin is a protease formed from its precursor,
plasminogen. It lyses fibrin and fibrinogen into fragments
knowns as fibrin degradation products (FDP)
• Fibrinolysis is regulated by activator (plasminogen activators )
and inhibitors (antiplasmin or prevent the activation of
plasminogen)
Fibrinolysis and fibrinolysis inhibitors
Fibrinolysis
(endothelial cell) Kallikrein
(plasminogen activators, PAs)
(inhibitor)
(urokinase) (Prourokinase)
(tissue plasminogen activators)
(plasminogen activator inhibitor

, PAI)
plasminogen plasmin (fibrinolysis inhibitor)
(antithrombin)
XIIa、Xa、Kallikrein 、 (α2-macroglobulin)
Fibrin degradation
Fibrinogen/fibrin
product, FDP
Hemostasis
Blood
• Blood group and blood transfusion
– Blood group and agglutination of red blood cell
– Blood group of Red blood cell
– Blood transfusion
Blood group and agglutination of red blood cell
• Blood group：Classification of RBC based on the presence or

absent of specific antigen on the red cell membranes
• Agglutination：the clumping together in suspension of
antigen-bearing cells, microorganisms, or particles in the
presence of specific antibodies (agglutinins)
• Agglutinogens：refer to the antigens present on the cell
membranes of RBCs
• Agglutinin：refer to the antibodies against the agglutinogens.
These are present in the plasma.
• Depending upon the type of agglutinogen present or absent

on the red cell membranes, various blood grouping systems
are known: ABO blood grouping system and Rhesus (Rh,
CDE) blood grouping system.
• White blood cells also express human leukocyte antigen (HLA)
despite of ABO antigen. Human leucocyte antigens (HLA) are
polymorphisms in cell surface molecules that distinguish 'self'
from 'non-self'.
• Platelets express both platelet specific antigens such as
human platelet antigens (HPAs) and antigens which are
shared with other cells such as ABO and HLA class I antigens.
agglutination of red blood cell

Agglutinogens
Agglutinin
• Hemagglutination, or haemagglutination, is a specific form of

agglutination that involves red blood cells (RBCs). It has common
uses in the laboratory: blood typing.
• Blood transfusions between incompatible groups cause an immune
response. This can lead to a serious transfusion reaction.
Blood group of Red blood cell
There are at least 24 blood groups and more than 100 antigens
that can be detected on the surface of red blood cells.
• ABO blood group system
• Rh blood group system
• Kell, MNSS, P…
ABO blood group system

• The classical ABO blood grouping system is based on the presence
of A and B agglutinogens on the cell membrane of RBCs.
• The H antigen defines the O blood group and is the precursor for A
and B antigens.
• The A and B glycosyltransferases add either N-acetylgalactosamine
(GalNAc) or galactose (Gal), respectively, to the H antigen, resulting
in the A and B antigens, respectively.
• The antibodies that against the A, B or H antigen are large IgM-type
antibodies that do not cross the placenta, so ABO incompatibility
between a mother and her fetus rarely causes problems.
ABO blood group system /ABO血型系统

ABO blood group system

Rh blood group system

• The Rh blood group is so named because the Rh antigen,
called Rh factor, was first found in the blood of the Rhesus
monkey.
• The Rh system has more than 50 antigens, but those of
routine concern are D, C, c, E and e antigens.
• It is the presence or absence of the D antigen that confers the
Rh-positive or Rh-negative status.
D Positive Haplotypes D Negative Haplotypes

R1: DCe r': dCe
R2: DcE r": dcE
R0: Dce r: dce
Rz: DCE ry: dCE

• Most Rh antibodies are IgG and can cross the placenta.
• Normally, blood plasma does not contain anti-Rh antibodies.
• If an Rh person receives an Rh blood transfusion, however, the
immune system starts to make anti-Rh antibodies that will
remain in the blood.
• If a second transfusion of Rh blood is given later, the
previously formed anti-Rh antibodies will cause agglutination
and hemolysis of the RBCs in the donated blood, and a severe
reaction may occur.


• At birth, a small quantity of fetal blood usually leaks across
the placenta into the maternal bloodstream. A problem can
arise when the mother is Rh - and the baby is Rh+, having
inherited an allele for the Rh antigens from the father.
• On exposure to Rh antigen, the mother’s immune system
responds by making anti-Rh antibodies.
• During a subsequent pregnancy, the maternal antibodies cross
the placenta into the fetal blood. If the second fetus is Rh+,
the ensuing antigen–antibody reaction causes agglutination
and hemolysis of fetal RBCs. The result is hemolytic disease of
the newborn .
Blood transfusion
• Before blood is transfused, a donor’s and recipient’s blood is

typed
• Blood transfusion should be given at slow rate, especially
transfusion with an alternate group
• Before blood transfusion always crossmatching is done. The
objective of the crossmatch is to demonstrate compatibility
between antigens on the donor RBCs and the recipient’s
plasma antibodies.
Blood transfusion
crossmatching
• The major crossmatch involves testing the
patient’s serum with donor cells to
determine whether the patient has an
antibody which may cause a hemolytic
transfusion reaction or decreased cell
survival of donor cells. This is the most
important cross-match.
• The minor crossmatch involves testing the
patients cells with donor plasma to
determine whether there is an antibody in
the donor’s plasma directed against an
antigen on the patient’s cells.
Blood transfusion
crossmatching
• O type can receive

donor from O type
only
• A type can receive
donor from A and
O only
• B type can receive
from B and O only
• AB type can
receive all blood
type
Blood transfusion
transfusion of blood component
• Whole blood is now rarely

used for transfusion. Blood
component therapy makes
clinical sense as most patients
require a specific element of
blood.
• Apheresis is a medical
technology in which the blood
of a person is passed through
an apparatus that separates
out one particular constituent
and returns the remainder to
the circulation.
Blood transfusion
transfusion of blood
component

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Physiology

• Blood carries the nutritive substances like glucose,

• The various hormones produced by the endocrine

• Neutrophils and monocytes engulf the

Regulation of • The osmotic composition of blood is also

Maintenance of • Blood plays an important role in regulation of the

• Blood serves as a ready-made source of substances

• Composition and characteristics of blood

• The basic composition of blood and blood volume

• Blood is a liquid connective tissue that consists of

• Hematocrit：a percentage of erythrocytes (RBC) in the total

by spinning the capillary tubes which contain

• Plasma：a clear straw coloured watery

• Serum：If the blood is drawn from the

• blood volume： volume of blood (both red blood cells and

circulating blood volumes

• Normal range：Volume of blood in an average adult is about

• Functions of plasma proteins

colloid osmotic pressure

• Blood osmotic pressure

• Blood osmotic pressure

• Blood osmotic pressure

• Blood osmotic pressure

• Blood osmotic pressure

• Blood osmotic pressure

Isosmotic solutions hyperosmotic solutions hyposmotic solutions

• Blood osmotic pressure colloid osmotic pressure

most important potassium salt of Hb

• Erythrocytes/red blood cells/RBC

• Diameter of each RBC is 7.2 μm (range

The physiological features of erythrocytes

The physiological features of erythrocytes

During blood storage there is a slow but constant leakage

The physiological features of erythrocytes

The physiological features of erythrocytes

The physiological features of erythrocytes

The physiological features of erythrocytes

The functions of erythrocytes

• Erythropoiesis: the production of RBCs Mature RBC

Erythroid progenitors Intermediate normoblast

BFU-E (burst forming unit–erythroid)

The erythropoiesis and its regulation

The erythropoiesis and its regulation

The erythropoiesis and its regulation

The erythropoiesis and its regulation

Metabolic pathway showing interaction of

The erythropoiesis and its regulation

The erythropoiesis and its regulation

The life span and destruction of erythrocytes

The life span and destruction of erythrocytes

The life span and destruction of erythrocytes

The life span and destruction of erythrocytes

White blood cells (leukocyte/WBC) are colourless nucleated cells

• leucocyte count & its classification

The physiological features of leukocytes

The physiological features of leukocytes

The physiological features of leukocytes

• Neutrophils killed by the toxins released from the bacteria are

The production & regulation of leukocytes

• The production &