Download THE PHYSIOLOGY OF BLOOD

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THE PHYSIOLOGY
OF BLOOD
Objectives
1. HEMOGLOBN
2. HEMOSTASIS
Practical tasks
Determination of hemoglobin blood content
Blood coagulation time determination (Lee White)
Determination of bleeding time by Duke
Determination of prothrombin time by Quick
HEMOGLOBIN – composed of
4 subunits bound together
each having HEME molecule combined with long POLYPEPTIDE chain
called GLOBIN
HEME is made of pyrrole compound in the centre of which is Fe. The oxygen
and polypeptide are bound to coordination bonds of the iron atom as molecular O2
Hb DERIVATIVES
Depend on gass content or Fe form
OXYHEMOGLOBIN Hb(O2)4
DEOXYHEMOGLOBIN = CARBAMINOHEMOGLOBIN Hb(CO2)4
CARBOXYHEMOGLOBIN Hb(CO)4
METHEMOGLOBIN Fe++ is oxygenized to Fe+++
Hb TYPES
Depend on slight variations in aminoacid
composition of the polypeptide portion
Hb A – ADULT form of Hb
Contains 2alpha and 2 beta chains
Hb A2 – MINOR COMPONENT
Contains 2 alpha and 2 delta chains
Hb F – FETAL Hb
Contains 2 alpha and 2 gamma
Hb loads up with oxygen in lungs and unloads oxygen in the tissue capillaries
In both cases oxygen moves according to its diffusion gradient
Calculation of oxygen capacity of blood
The blood normally contains approximately 15 g of hemoglobin for 100 ml =
15% = 150 g per one liter of blood
1g of Hb can bind with maximum 1,34 ml of oxygen
15 . 1.34 = 20.1 ml of oxygen in 100 ml of blood
BLOOD CLOTTING
INCLUDES THE ROLE OF THREE SUBSYSTEMS
1. PLATELETS ACTIVATION
2. VASOCONSTRICTION
3. PLASMA COAGULATION FACTORS ACTIVATION
In injured vessel collagen of subendothelial connective
tissue is exposed to blood – initiation of 3 separate
hemostatic mechanisms
1. PLATELET ADHESION TO COLLAGEN
mechanical attachment provided by plasma protein
Von Willebrandt factor that circulates as a complex
with f. VIII
2. PLATELET ACTIVATION
(viscous metamorphosis, liberation of ADP, Thromoboxane,
Serotonin, platelet f. 3., from cytoplasmic granules)
3. PLATELET AGGREGATION
4. PLATELET PLUG FORMATION
5. BLOOD CLOT includes contraction of platelets and fibrin
The same time local myogenic spasm occurs in wounded
vessel – vasoconstriction, which helps to close the wound
Platelet factors promote vasoconstriction
Platelets – disc shaped
cells without nuclei,
diameter 2-4 micrometers,
formed in bone marrow
from megacaryocytes,
lifespan 10 days
PLASMA CLOTTING FACTORS
= plasma proteins present in blood activated by intrinsic or extrinsic pathways
Blood in test tube will clot as a result of INTRINSIC PATHWAY
Damaged tissues release f.III. that initiates “shortcut” to the formation of fibrin, and
That is EXTRINSIC PATHWAY
I. FIBRINOGEN
II. PROTHROMBIN
III. TISSUE TROMBOPLASTIN
IV. CALCIUM IONS
V. PROACCELERIN
VI. DOES NOT EXIST
VII. PROCONVERTIN
VIII. ANTIHEMOPHILIC FACTOR
IX. PLASMA THROMBOPLASTIN COMPONENT (PTC) CHRISTMAS FACTOR
X. STUART-PROWER FACTOR
XI. PLASMA THROMBOPLASTIN ANTECEDENT (PTA)
XII. HAGEMAN FACTOR
XIII. FIBRIN STABILIZING FACTOR
Plasma without clotting factors is called serum
a
Bleeding Disorders
A deficiency of a clotting factor can lead to
uncontrolled bleeding.
The deficiency may arise because
•not enough of the factor is produced or
•a mutant version of the factor fails to perform
properly.
Examples:
•von Willebrand disease (the most
common)
•hemophilia A for factor VIII deficiency
•hemophilia B for factor IX deficiency.
•hemophilia C for factor XI deficiency
In some cases of von Willebrand disease,
either a deficient level or a mutant version
of the factor eliminates its protective effect on
factor 8.
SYMPTOMS
•Easy Bruising
•Frequent nosebleeds that are hard to stop
•Bleeding longer than expected following circumcision,
surgery, or having a tooth pulled
•Bleeding into joints and soft tissues
•Women often have heavy bleeding with menstrual periods
(menorrhagia)
Hemophilia A and B
The genes encoding factors 8 and 9 are on the X chromosome.
Thus their inheritance is X - linked
Like other X-linked disorders, hemophilia A and B are found
almost exclusively in males because they inherit just a single
X chromosome, and if the gene for factor 8 (or 9) on it is defective,
they will suffer from the disease.
Queen Victoria (1819-1901) of Great Britain had a defective gene for Clotting
Factor VIII, which caused "royal hemophilia" in her son Leopold as well as many other
of Victoria's numerous royal descendants. Many of Victoria's descendants married
into other royal families, spreading the defective gene widely and greatly affecting
world history.
Today, people with abnormal Factor VIII can use powdered, freeze-dried CF VIII to
help them cope with this disorder. Unfortunately, it was originally derived from
human donor blood and risks blood-borne disease transmission including hepatitis and
HIV. In fact, the HIV epidemic took a huge toll on hemophilia sufferers during the
1980s and 1990s. However, today synthetic (recombinant) sources of CF VIII and
other therapies have made hemophilia treatments safer and more effective.