lecture 11 & 12 clot
TRANSCRIPT
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Lymphocytes
Agranulocyte 20-45% of WBCsSpherical, dark-staining
nucleusThin rim of blue staining
cytoplasmEach lymphocyte
recognizes and acts against a specific antigen
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Lymphocytes
T lymphocytes can attack foreign cells directly
(17.6)
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Lymphocytes B lymphocytes transform into plasma cells and
secrete antibodies
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Hemostasis means prevention of blood loss and this achieved by:
1. Vascular constriction2. Formation of a platelet plug3. Formation of blood clot4. Growth of fibrous tissue into the blood clot
Hemostasis
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After blood vessel has been cut, the smooth muscle wall contract; this immediately reduces the flow of blood from the ruptured vessel
Vascular Constriction
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Platelets or thrombocytesFormed in the bone marrow from
megakaryocytes Do not have nuclei Function in the clotting process.Normal value – 150,000 to 300,000/cubic
millimeter.It has a half life in the blood of 8 – 12 days, its
functional process run out over several weeks
Formation of platelet plug
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Formed by fragmentation from megakaryoctyes
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1. Contractile protein thrombosthenin that can cause the platelet to contract
2. Endoplasmic reticulum that store Calcium ions
3. Mitochondria capable of forming ATP4. Enzymes that can synthesize prostaglandins
which involves in local tissue reactions5. Contain fibrin stabilizing factor6. Growth factors that causes vascular cells to
grow and multiply
Platelet functional characteristics
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Platelet begin to swell and assume irregular forms when comes in contact with collagen fibers
They become sticky so that they adhere to collagen in the tissue
They secrete ADP and form thromboxane which activate nearby platelets
The damaged vascular wall activates increasing numbers of platelets thus forming platelet plug. (In small vessels the platelet plug is all that is necessary to stop the bleeding).
Mechanism of platelet plug
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Platelet Plug Formation
1. Exposed collagen binds and activate platelets
2. Release of platelet factors
3. Attract more platelets
4. Aggregate into platelet plug
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Blood coagulation take place in three steps 1. As result of rupture blood vessels, formation of
prothrombin activator (protein manufacture in the liver)
2. Conversion of prothrombin to thrombin in the presence of calcium
3. The thrombin acts as enzyme to convert fibrinogen (blood protein) into fibrin fibers that enmesh platelet, blood cells and plasma to form clot
Note: vitamin K is required by liver for formation of prothrombin
Blood coagulation in the ruptured vessel
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ProthrombinProthrombin CaActivator
Thrombin
Fibrinogen Fibrinogen monomer
CaFibrin fibers
Activated fibrinStabilizing factor
Cross linked fibrin fibers
Blood Coagulation
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SEM of a clot with platelet, fibrin mesh, rbc’s
The clot composed of meshwork of fibrin fibers entrapping blood cells, platelets and plasma
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Overview of Hemostasis: Clot Formation & Vessel Repair
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Prothrombin activator is generally formed in two ways
1. Extrinsic pathway (begins with trauma to the vascular wall)
2. Intrinsic pathway (begin with the blood)
Initiation of coagulation
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Pathways for initiating clotting
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Preventing blood clotting in vascular system is
1. Smoothness of the endothelial cell surface2. Layer of glycocalyx on the endothelium3. Protein bound with the endothelial
membrane thrombomodulin which binds thrombin
Prevention of blood clotting in the vascular system
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The most important anticoagulant in the blood1. Fibrin fibers2. Antithrombin III or antithrombin-heparin
cofactor Both fibrin fibers and antithrombin acts as
antithrombin About 85-90% of thrombin becomes adsorbed
to the fibrin fibers The thrombin that does not adsorb combines
with antithrombin III which block the effect of thrombin
Antithrombin action of fibrin and antithrombin III
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Heparin is anticoagulant, low concentration in the blood
Effectiveness of antithrombin III increases when it combines with heparin
Heparin is formed by basophilic and mast cell
Heparin
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Plasma protein contain euglobulin called plasminogen when activated becomes plasmin
Plasmin resemble trypsinPlasmin digest fibrin fibers and other protein
coagulantsPlasmin caused lysis of a clot
Fibrinolysis of blood clot - plasmin
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Injured tissue release activator called tissue plasminogen activator (t-PA) which convert plasminogen to plasmin
Activation of plasminogen
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Dissolving the clot
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Red blood cells White blood cells Platelets
1 Site of formation
formed in bone marrow, life-span: 4 months
formed in bone marrow or thymus
formed in blood marrow
2 Shape biconcave discs,no nucleus,red colour
phagocytes: irregular, lobed nucleus & granular cytoplasm
irregular shape,no nucleus,tiny pieces of cell fragments,
A comparison of RBCs, WBCs and Platelets
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Red blood cells White blood cells Platelets
3 Size small in size some large & some small
tiny cell fragments
4 Number 5,000,000 /mm3 7,000 /mm3 250,000/mm3
5 Function
contain haemoglobin to carry oxygen from lungs to all parts of body
phagocytes kill pathogens & digest dead cellslymphocytes produce antibodies for killing pathogens
for blood clotting
A comparison of RBCs, WBCs and Platelets
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AlbuminHelps control osmotic pressureHelps control diffusion of water
Globulin Includes antibodies (Abs)Transport proteins (lipids, iron, copper, etc.)
Fibrinogen Involved in clotting
Plasma proteins
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All the albumin and fibrinogen and 50 – 80% of globulin are formed in the liver
The reminder of the globulin are formed in the lymphoid tissues
Formation of the plasma proteins
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Normal values
Total protein: 4.2 - 5.6 g/dlAlbumin: 2.3 - 3.5 g/dlGlobulin: 1.9 – 2.1 g/dl
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66 kDa
ALBUMIN
·Accounts for ~50% of the total plasma protein and ~ 50% of the total liver protein production
Half-life ~ 20 days
Highly polar
At pH 7.4 it is anionic with 20 negative charges per molecule
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Regulation of colloidal pressure
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Functions of albumin
Maintenance of the osmotic pressure of plasmaTransport of free fatty acids
ALBUMIN
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GlobulinGlobulin is made up of different proteins called alpha, beta, and gamma types.
Some globulins are made by the liver, while others are made by the immune system.
Other globulins transport metals, such as iron, in the blood and help fight infection.