Platelets

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Platelets

• 20 / 4 /10

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Hemostasis

• Definition
• Prevention of blood loss.

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Events Involved In Hemostasis
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• Whenever a vessel is ruptured, hemostasis is
  achieved by
• Vascular constriction
• Formation of a platelet plug
• Formation of a blood clot as a result of blood
  coagulation.
• Eventual growth of fibrous tissue into the blood
  clot to close the hole in the vessel permanently.

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Vascular Constriction
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• In ruptured blood vessel
• 1. Pain impulses from the site of trauma as well
  as from the surrounding nervous tissue originate
  and reach the spinal cord.
• From the spinal cord order signal arise.

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• The order signals pass through the sympathatic
  nerves
• Lead to spasm of the vessel.
• 2. Local muscle also contribute to the vascular
  vasospasm.
• 3. local autacoid factors from the traumatized
  tissues and blood platelets.

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• As the vessel wall is damaged the action
  potential developed along the vessel wall lead to
  vasoconstriction.
• The vasospasm lasts for almost half an hour and
  it is directly proportional to the intensity of
  trauma.

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• Vasoconstriction resulting from local myogenic
  contraction of the blood vessels is initiated by
  direct damage to the vascular wall.
• In the smaller vessels, the platelets are
  responsible for much of the vasoconstriction by
  releasing a vasoconstrictor substance,
  thromboxane A2.

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Formation of the Platelet Plug
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Platelets
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• Platelets or thrombocytes are small colorless,
  non nucleated cells.
• Shape is spherical or rod shaped and become oval
  or disc shaped when inactivated.
• Size 1 to 4 micrometers in diameter.
• Life span 10 - days

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• Development From the pluripotentstem
• cells in the bone marrow.
• CFU-M Colony forming megakaryocytes
• Megakaryoblast
• Promegakaryoctye
• Megakaryocytes
• Platelets

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• Normal concentration
• 150,000 to 300,000 per microliter.
• Structure
• Cell membrane
• Microtubule
• Cytoplasm

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Cell Membrane of Platelet
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• It is 6 nm thick and contain lipids
  (phospholipids, cholesterol and
  glycolipids),Carbohydrates(glycocalyx), Proteins
  and glycoproteins.
• Out of all glycoprotein and phospholipids are
  functionally important.

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Glycopropteins

• Prevents the adherence of platelets to normal
  endothelium.
• Accelerates the adherence of platelets to
  collagen and damaged endothelium in ruptured
  blood vessels.
• Forms a receptor for ADP and thrombin.

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Phospholipids

• Accelerate clotting reactions.
• Form precursors for thromboxane A .
• Microtubules
• The microtubule form a ring around the
  cytoplasm below the cell membrane.

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• The microtubules are made up of polymerized
  protein called tubulin .
• The tubules provide structural support for the
  inactivated platelets to maintain disc shape.

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Platelets-2

• 21 /4 /10

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Cytoplasm

• The cytoplasm of the platelets include
• Golgi apparatus
• Endoplasmic reticulum
• Mitochondria
• Microtubule
• Microvessels
• Microfilaments
• Granules

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• Cytoplasm also contains
• Proteins
• Enzymes
• Hormones.
• Chemical substances

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Proteins

• The major proteins present are contractile
  proteins which are responsible for the
  contraction of platelets
• Actin
• Myosin
• Thrombosthenin

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• Fibrin-stabilizing factor. Clotting factor
• Platelet derived growth factor (PDGF)
  ............. helps repair damaged vascular
  walls.

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Enzymes

• The enzymes present are adenosine triphosphatase
  and the enzymes necessary for the synthesis of
  prostaglandin.
• Hormones
• Adrenaline
• Serotonin vascular and local tissue
  reactions
• Histamine

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Chemical substances

• Calcium ions
• Mg- ions.
• Adenosine triphosphate (ATP)
• Adenosine diphosphate (ADP)

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Function Of Platelets

• Its surface has glycoprotein coat that adhere it
  to injured endothelial cells .preventing
  bleeding.
• Actin, myosin thrombosthenin that are
  contractile proteins. cause clot retraction.

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• Secretes growth factor that promotes growth
  multiplication of vascular endothelial cells,
  vascular smooth cells fibroblasts. repair
  damaged vascular wall.
• Its membrane has phospholipids that activate
  intrinsic system of blood clotting

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• Endoplasmic Reticulum and Golgi apparatus
  synthesize enzymes and store Ca ions.
• Have enzyme system to synthesize prostaglandins.

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Life span O f Platelets

• Platelets are eliminated from the circulation
  mainly by the tissue macrophage system in the
  spleen.

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Mechanism of the Platelet Plug

• When platelets come in contact with a damaged
  vascular surface, platelets attach to the exposed
  collagen fibers in the vascular wall.
• Platelets immediately change their own
  characteristics.

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• Platelets begin to swell and assume irregular
  forms with numerous irradiating pseudopods
  protruding from their surfaces
• Contractile proteins in the platelets contract
  forcefully and cause the release of granules that
  contain multiple active factors

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• Adenosine diphosphate (ADP) is released which
  causes surface of nearby circulating platelets
  to become sticky and it adheres to the first
  layer of aggregated platelets

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• The aggregated platelets adhere to the von
  Willebrand factor that leaks into the traumatized
  tissue from the plasma
• It leads to the release of more ADP , which cause
  more platelets to pile up at the defected site.

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• The aggregating process is reinforced by the
  formation of Thromboxane A2.
• It directly promotes platelet aggregation and
  further enhances it indirectly by triggering the
  release of even more ADP from the platelet
  granules.
• Formation of platelet plug takes place

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• The aggregated platelet plug not only
  physically seal the break in the vessel but, also
  perform three other important roles
• Actin and myosin which were the contractile
  proteins in the platelets contract

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• This compacts and strengthens the the plug which
  was initially, a loose plug.
• Secondly, various chemicals released from the
  platelet plug include several vasoconstrictors
  (serotonin, epinephrine and Thromboxane A2 )
  cause vascular vasospasm

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• Thirdly, the platelet plug release other
  chemical substances that play a role in blood
  clotting.
• Platelet plugging mechanism alone is sufficient
  to seal tears in the capillaries and small
  vessels but, large holes require formation of
  blood clot to stop bleeding.

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Limitation of Platelet Plug

• Normal endothelium of the vessel release
  Prostacyclin which prevents platelet aggregation.
• So, platelet plug is limited to the defected part
  of the vessel and does not spread to the normal
  vascular tissue.

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Formation Of Blood Clot

• If there is a large defect in the vessel then
  blood clot platelet plug are required to stop
  bleeding.
• As clot on the top of platelet plug supports it
  and reinforces the seal over the break in the
  vessel.

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• Onset Of Formation Of Blood Clot
• 15 20 sec in severe trauma.
• 1 2 min in minor trauma.

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• Ultimate step in clot formation is the conversion
  of fibrinogen which is a soluble protein that is
  produced by the liver and is normally always
  present in the plasma to fibrin which is
  insoluble thread like molecule.
• thrombin
• Fibrinogen Fibrin

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• Fibrin molecules adhere to the damaged vessel
  surface forming a loose netlike meshwork that
  traps the cellular elements of blood.
• The clot appears red because of abundance of RBC
  that are trapped in it.

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• The original fibrin web is weak because the
  fibrin threads are loosely interlaced.
• Rapidly, various chemical linkages are formed
  between adjacent strands to strengthen and
  stabilize the clot mesh work.

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• The cross linkage process which is catalyzed by
  a clotting factor known as factor XIII (Fibrin
  stabilizing factor).

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• End Of Todays Lecture!!!

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Hemostasis-1

• 22 /4 /10

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Fibrous Organization or Dissolution of the Blood
Clot
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• Once a blood clot has formed, it can follow
  one of two courses
• It can become invaded by fibroblasts, which
  subsequently form connective tissue all through
  the clot.
• It can dissolve.

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• The usual course for a clot that forms in a small
  hole of a vessel wall is invasion by
  fibroblasts, beginning within a few hours after
  the clot is formed.
• This event is promoted at least partially by
  growth factor secreted by platelets.

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• Complete organization of the clot into fibrous
  tissue takes place within 1 to 2 weeks.
• When excess blood has leaked into the tissues and
  tissue clots have occurred where they are not
  needed.

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• Special substances within the clot itself usually
  become activated. These function as enzymes to
  dissolve the clot.

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Mechanism of BloodCoagulation
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• Procoagulants
• Substances that cause or affect blood coagulation
  that have been found in the blood and in the
  tissues. promote coagulation
• Anticoagulants
• Substances that inhibit coagulation are called
  Anticoagulants.

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• Whether blood will coagulate depends on the
  balance between these two groups of substances.
• In the blood stream, the anticoagulants normally
  predominate, so that the blood does not coagulate
  while it is circulating in the blood vessels.

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• But when a vessel is ruptured, procoagulants from
  the area of tissue damage become activated and
  override the anticoagulants, and then a clot does
  develop.

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Three Essential Steps Involved In Clotting
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• (1) In response to rupture of the vessel or
  damage to the blood itself, a complex cascade of
  chemical reactions occurs in the blood involving
  more than a dozen blood coagulation factors.
• Formation of a complex of activated substances
  collectively called prothrombin activator.

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• (2) The prothrombin activator catalyzes
  conversion of prothrombin into thrombin in the
  presence of sufficient amounts of ionic Ca.
• (3) The thrombin acts as an enzyme to convert
  fibrinogen into fibrin fibers that mesh with
  platelets, blood cells, and plasma to form the
  clot.

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• The clotting cascade may be triggered by the
  intrinsic pathway or the extrinsic pathway
• The intrinsic pathway precipitates clotting
  within damaged vessels as well as clotting of
  blood samples in test tubes.

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• All elements necessary to bring about clotting by
  means of the intrinsic pathway are present in the
  blood.

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• End of todays lecture!!!