Blood

Functions of the blood

1. Transport O
2
and nutrients.
2. Remove CO
2
and waste products.
3. Defence.
4. Carry hormones.
5. Contribute to homeostasis.
6. Prevent blood loss.



What we will learn in this chapter?

1. Blood components
2. Hemostasis and Blood Coagulation
3. Anticoagulation
4. Fibrinolysis





Blood components

1. Total body fluid
Intracellular fluid(ICF) 40%
Interstitial fluid 15%
Extracellular fluid(ECF) 20%
Blood plasma 5%
Other extracellular fluid , such as lymph, CSF.
2. Blood volume

About 7-8% of body weight.




3. Blood components

A. Plasma
B. Formed elements
i. Red blood cells (erythrocytes)
ii. White blood cells (leukocytes)
iii. Platelets (thrombocytes)



Hematocrit
Definition:
The hematocrit is the percentage
of total blood volume occupied by the
erythrocytes.
Normal value:
Male: 45%
Female: 42%

A. Plasma
Components: (Table 3-1)
a. Water (93%)
b. Electrolytes
c. Small organic molecules
d. Plasma proteins:
albumin, globulin and fibrinogen


Osmolarity of the blood plasma
Osmolarity: The osmolarity of a solution
refers to the number of solute particles
per unit volume of solvent.

It depends only on the number of solute
molecules or ions, NOT on their chemical
composition and size.


Osmosis: Net diffusion of the water across a
semipermeable membrane to a region in which
there is a higher concentration of solute.
H
2
0 moves by osmosis into the lower [H
2
0] until
equilibrium is reached.
osmotic pressure
The osmosis of the water molecules can be
opposed by applying a pressure in direction
opposite that of the osmosis.
The precise amount of pressure required to
prevent the osmosis is called the osmotic
pressure.
osmotic pressure
The total plasma osmotic pressure
300 mOsm/L
It consists of two parts.
The plasma crystal osmotic pressure
Generated by all crystal substances, particularly electrolytes.
Important in maintaining fluid balance across cell membrane.
The plasma colloid osmotic pressure
Generated by plasma proteins, especially albumins.
Important in fluid transfer across capillaries.
Iso-osmotic, hypoosmotic,
hyperosmotic solution
A solution whose osmolarity is equal to the
osmolarity of the plasma is called iso-osmotic
solution.
e.g. 0.9%NaCl solution (physiological saline)

hypoosmotic solution
hyperosmotic solution

Isotonic, hypotonic, and hypertonic solution
In isotonic solution, RBCs maintain their
normal shape.



1.9% urea solution is isoosmotic, but not isotonic.
In hypertonic solution,
RBCs are dehydrated and
shrink.
In hypotonic solution,
RBCs swell and hemolysis.
The tonicity of solutions depends on the concentrations
of solutes to which the cell membrane is impermeable.
Cells in normal condition usually begin
to hemolyze at 0.5%NaCl solution and
hemolyze completely at 0.3%NaCl solution.
If red cells are hemolyzed by saline of
concentrations greater than 0.55%NaCl,
they show increased osmotic fragility.
Osmotic fragility is susceptibility of RBC
to hemolysis when exposed to a series of
increasingly dilute saline solutions.
The sooner hemolysis occurs, the greater
the osmotic fragility of the cells.


B. The red blood cells (erythrocytes)
Normal Range:
RBC
Male: 4.5~5.5 10
12
/L (510
12
/L)
Female: 3.8~4.6 10
12
/L (4.210
12
/L)
Hemoglobin
Male: 160g/L
Female: 140g/L

C. The white blood cells (leukocytes)
Normal Range:
4 - 10 10
9
/L
Granulocyte

D. The platelets (thrombocytes)
Normal Range:
150 - 400 10
9
/L
Physiological Hemostasis
Concept: Hemostasis means prevention
of blood loss.
Bleeding time (BT)
When a sharp needle is used to pierce
the tip of the finger or lobe of the ear,
bleeding ordinarily lasts for 1~3 minutes.

Events in hemostasis

Local vasoconstriction
Formation of the platelet
plug
Blood coagulation

vasoconstriction
Injury to a blood vessel elicits a contractile
response of the vascular smooth muscle and
thus a narrowing of the vessel.
It may be mediated by
a. Nervous reflexes
b. Humoral factors (thromboxane A2 and catecholamine)
c. Local myogenic spasm
Formation of the platelet plug
a. Thrombocyte adhesion
Contact of platelets with a damaged
vascular surface leads to the adhesion of
platelets to collagen fibers.
Von willebrands factor (vWF) can
facilitates this interaction.
b. Thrombocyte aggregation
i. Platelets adhering to each other is
called thrombocyte aggregation.
ii. Endogenous ADP is responsible to
irreversible aggregation


C. Release function
Platelets release large amount of ADP,
ATP, 5-hydroxyptamine(5-HT), platelet factor 3
(PF3), and thromboxane A2 which in turn act
on nearby platelets to activate them .
d. Contractile function
Thrombosthenin can contract in the
presence of Mg
2+
, using ATP as its energy
source.


Blood coagulation (clotting)
Blood coagulation or clotting is the
transformation of blood into a solid gel
termed a clot or thrombus.
A cascade of reactions occurs by which
one activated factor activates another.
2. Mechanism of Blood Coagulation

Coagulation factors
Coagulation factors are designated
by Roman numerals, from to XIII, but
no . In addition, prekallikrein (PK),
high molecular weight kininogen (HMW-
K), and PF3 also are coagulation factors.
(Table 3-5)
Many clotting factors are synthesized
in the liver and their manufacture is
dependent upon vitamin K, e.g. , ,
, and .
Many of the factors exist in inactive
forms, which become activated during
the coagulation process, e.g. a.
(FXIII)
General mechanism of blood clotting
a. Formation of prothrombin activator
b. Formation of thrombin
c. Formation of fibrin

What is serum?
Within a few minutes after a clot is
formed, it begins to retract and extrude fluid
that is similar to plasma. This fluid from the
blood clot is serum.

What are the differences between serum and
blood plasma?
Serum lacks fibrinogen and some factors,
such as F and , but it contains some
substances that are produced by endothelial
cells or platelets during blood coagulation.
Initiation of Coagulation :
Formation of Prothrombin Activator
The extrinsic pathway
It is activated by a factor from outside
the blood i.e. tissue factor (factor or
thromboplastin ).
The intrinsic pathway
all of the elements required to activate
it are present in normal blood .
The intrinsic pathway
A. Blood trauma cause activation of F and
release of platelet phospholipids(PF3).
B. Activation of Factor .
C. Activation of Factor .
D. Activation of Factor (Note role of F
antihemophilic factor).
E. Action of Factor a to form prothrombin
activator (Note role of F ).
(HMW kininogenprekallikrein)
(Factor II)
The extrinsic pathway
A. Release of tissue factor.
B. Activation of Factor (Note role of F
and tissue factor).
C. Effect of F a to form prothrombin
activator (Note role of F ).

Prothrombin
Tissue trauma
Tissue factor
VII VIIa
X
Activated X
Ca
2+
Ca
2+
Ca
2+
V
Prothrombin
activator
platelets
phospholipids
Thrombin
Prothrombin
(1)
(2)
(3)
(Factor II)
Positive feedback or vicious
circle of clot formation
A. Thrombin can act on many other clotting
factors (prothrombin , Factor , , ,
, , platelet ) in addition to fibrinogen.
B. Activation of prekallikrein by a will in
turn accelerate activation of factor .
Interaction Between the two Pathways
and Characteristics of two Pathways
a. Both pathways begin after blood vessels
rupture. Factor initiates the extrinsic
pathway. Contact of Factor and platelets
with collagen in the vascular walls initiates
intrinsic pathway.
b. F a-F complex can directly activate F
, therefore participating in the intrinsic
pathway.
c. Differences between the two pathways :
i. The triggers of two pathways differ
F intrinsic pathway
F extrinsic pathway
ii. Activation of F in intrinsic pathway requires
contact of F with collagen or other foreign
substances, whereas, activation of extrinsic
pathway requires the release of F from
damaged tissues.
iii. The extrinsic pathway can be explosive. The
intrinsic pathway relatively is slow.

iv. More clotting factors participate in the
coagulation in intrinsic pathway than those
in extrinsic pathway.

v. All clotting factors participating in blood
coagulation exist in bl ood i n intri nsic
pat hway. But F i s r el eased f r om
damaged tissues in extrinsic pathway.

3.Anticlotting Systems (Anticoagulation)

Antithrombin ( a serine protease inhibitor )
Its arginine residues combine with the
serine residues in the active sites of
serine proteases , such as thrombin , Fa ,
Fa , Fa , and F and inactivate these
enzymes.
Heparin (a highly negatively charged
conjugated polysaccharide ) :
It functions by combining with antithrombin
to increase the effectiveness of antithrombin .
The complex of heparin and antithrombin
inactivates several other activated coagulation
factors in addition to thrombin , such as F , ,
, and .

Protein C ( a vitamin K- dependent protease )
Protein C functions as an anticoagulant
By inactivating Fa and Fa.
By blocking the binding of Fa with platelets
phospholipids.
By stimulating the release of plasminogen activators.

Tissue Factor Pathway Inhibitor (TFPI)
TFPI combines with Fa to form TFPI-Fa complex ,
t her eby i nact i vat i ng Fa and changi ng t he
conformation of TFPI.
Then, TFPI-Fa combines with Fa-TF to form
Fa-TFPI-TF complexes, thus inactivating Fa TF
complex .

4. Fibrinolysis
The process of liquefaction of
fibrin is fibrinolysis.
4. Fibrinolysis
Plasminogen activators
Plasminogen Plasmin
Fibrin
Fibrin degradation
products
(+)
(+)
Inhibitors
(-)
(1)
(2)
Sources of Plasminogen Activators
a. Vessel plasminogen activators
b. Tissue plasminogen activators:
urokinase
c. Activators depending on the activity
of factor : kallikrein
Exogenous activators ,e.g.
streptokinase

Plasmin
Plasmin is able to digest the fibrin
fiber and the fibrinogen as well as F,
F, prothrombin, and F by splitting
peptide linkages involving arginine and
lysine .
Plasminogen inhibitors
a. The plasminogen activator inhibitor type-1
b.
2
-antiplasmin
Summary
1. Defination:
Hematocrit
Hemostasis
Blood coagulation
Fibrinolysis

2. Summarize the three main events in hemostasis.

3. Describe the three stages of blood coagulation
(General mechanism of blood clotting ).