Platelets (thrombocytes) correc


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Platelets (thrombocytes) correc

  1. 1. PLATELETS (THROMBOCYTES) Lecture by GK Mbassa
  2. 2. Purpose of knowing structure, biochemistry and functions of platelets <ul><li>Understand qualitative platelet abnormalities </li></ul><ul><li>Gain knowledge on hemostasis for treatment of diseases </li></ul>
  3. 3. <ul><li>Know platelets role in tumor metastases, atherosclerosis and inflammation resulting from cytoplasmic fragments of megakaryocytes, e.g. arachidonic acid. </li></ul>
  4. 4. Morphology of platelets <ul><li>Heterogenous in blood smears; discoid, spheroid, elongated, flat </li></ul><ul><li>Granular organelles distributed in cytoplasm. </li></ul><ul><li>Some organelles in centre (granulomere) </li></ul>
  5. 5. <ul><li>Platelet cytoplasm is hyalomere, which is clear </li></ul><ul><li>Platelet is bounded by thin membrane, smooth or having fine projections </li></ul>
  6. 6. <ul><li>EDTA anticoagulant minimizes platelets clumping </li></ul><ul><li>Platelets may clump to other cells (erythrocytes and neutrophils), called satellitism. </li></ul>
  7. 7. <ul><li>Platelet volume in dog, pig, man is 7.6 – 8.3 fl, in cattle, equine, sheep, rat, guinea pig, mouse it is 3.2. – 5.4 fl, while in the cat it is 15.1 fl, </li></ul><ul><li>Platelet counts vary (1- 10 x 1011/l) </li></ul>
  8. 8. <ul><li>Larger platelets are metabolically and functionally more active than small platelets. </li></ul><ul><li>Scanning electron microscope show platelets to have discoid or lentiform shape, with smooth surfaces, slightly biconcave surface, has shallow indentations at external openings of the open canalicular system </li></ul>
  9. 9. <ul><li>Surface projections represent protractions of platelets granules </li></ul>
  10. 10. <ul><li>Surface features of platelets are similar in most species. </li></ul><ul><li>Platelets diameter length is 1.3 – 4.7 µm in dog, cat, equines, cow, sheep and goat. </li></ul><ul><li>Platelet thickness is 0.5 µm </li></ul>
  11. 11. <ul><li>Transformed platelets acquire pseudopods or projections, found also in normal blood Surface projections occur very fast when blood is taken out of vessel, vary in number and sizes between species </li></ul>
  12. 12. Ultrastructural features of the platelet <ul><li>Unit membrane covered with amorphous material (external or exterior coat) </li></ul><ul><li>Bundles of microtubules in matrix beneath membrane </li></ul>
  13. 13. <ul><li>Internal structure comprises of heterogenous granules (alpha-granules) </li></ul><ul><li>Clycogen particles </li></ul><ul><li>Dense granules </li></ul><ul><li>Mitochondria </li></ul><ul><li>Lysosomes </li></ul><ul><li>Peroxisomes </li></ul>
  14. 14. <ul><li>Poorly developed Golgi complex </li></ul><ul><li>Endoplasmic reticulum (rarely) </li></ul><ul><li>Spongy like channels, called open canalicular system) </li></ul><ul><li>Open canalicular system communicate with substance of platelet, open to surface at invaginations. </li></ul>
  15. 15. <ul><li>Open canalicular system is lined by unit membrane, covered by external coat </li></ul><ul><li>Another system of platelet channels is the dense tubular system. </li></ul><ul><li>Dense tubular system occurs under marginal band of microtubules and appears to open to surface, but does not open on the platelet surface. </li></ul>
  16. 16. <ul><li>Platelets of many animals have similar morphology. </li></ul><ul><li>Platelets have two types of granules, (1) alpha-granules, and (2) dense granules. </li></ul><ul><li>Dense and alpha granules are homogeneously distributed, but vary in electron density, number and size. </li></ul>
  17. 17. Functional organization of the platelet <ul><li>The platelet is divided into four structural regions </li></ul><ul><li>(1) Peripheral zone </li></ul><ul><li>(2) Sol-gel zone </li></ul><ul><li>(3) Organelle zone </li></ul><ul><li>(4) Membrane system </li></ul>
  18. 18. Peripheral zone <ul><li>Composed of external (exterior) coat, unit membrane, sub-membraneous area </li></ul><ul><li>Functions, maintain platelet integrity, receive and transmit stimuli triggering platelet responses (adhesions, aggregations) </li></ul>
  19. 19. <ul><li>Exterior coat has glycoproteins (glycocalyx) contains mucopolysaccharides and Mg2+ dependent AT Pase, plasma proteins (fibrinogen, IgG, IgM), coagulation factors (vitamin K-dependent factors, factors V and VIII) </li></ul>
  20. 20. <ul><li>Glycoproteins have receptors for platelet activation and aggregation. </li></ul><ul><li>Seven glycoproteins recognised, including glycoprotein 1b (reaction site for von Willebrand factor, a component of coagulation factor VIII) necessary platelet adhesion to endothelium on injured blood vessel </li></ul>
  21. 21. <ul><li>Platelet membrane; maintains platelet integrity, rich in phospholipids. </li></ul><ul><li>Platelet phospholipids function in blood coagulation (eg </li></ul>
  22. 22. Sol-gel zone <ul><li>Represented by matrix of platelet cytoplasm, contains microfilaments and microtubules, which function as cytoskeletal elements. </li></ul><ul><li>Microfilaments and microtubules maintain discoid platelet shape, form contractile system for shape change, pseudopod formation, internal contractions and granule secretion. </li></ul><ul><li>Microfilaments also function in clot retraction . </li></ul>
  23. 23. <ul><li>Microfilaments are also associated with thrombosthenin, a contractile protein (has actin-myosin) </li></ul><ul><li>Microtubule tubulin dissolves at 4oC, when exposed to colchicine or vinca alkaloids, leading to platelet shape irregularities. </li></ul>
  24. 24. Organelle zone <ul><li>Composed of all internal platelet components, except microtubules, microfilaments (sol-gel zone) components and membrane system. </li></ul>
  25. 25. <ul><li>Main component of organelle zone are platelet granules, that are morphologically and biochemically heterogeneous, azurophilic granules (alpha-granules under electron microscope) </li></ul>
  26. 26. <ul><li>Alpha-granules are membrane bound, oval, round, electron dense, contain platelet factor 4 (antiheparin), congulation factor V, fibrinogen, beta-thromboglobulin (a thrombin-sensitive protein), fibronection, factor VIII- related antigen, and a mitogenic or growth factor. </li></ul><ul><li>Platelets in von Willebrand disease lack factor VIII related antigen </li></ul>
  27. 27. <ul><li>Electron dense granules, called delta granules, or dense bodies contain non metabolic pool ATP and ADP, Ca2+, mono-amines (serotonin, histamine). </li></ul><ul><li>Dense granules vary with species. </li></ul>
  28. 28. External coat Microfilaments Alpha granule Open canalicular system Dense tubular system Microtubules Golgi complex Lysosome
  29. 29. <ul><li>Lysosomal granules contain acid hydrolases; acid phosphatase, β-glucuromidase, Contraction of microtubules forces all internal organelles towards the centre squeezing or without squeezing their contents to the exterior via open canalicular system. </li></ul><ul><li>Platelet activation triggers secretion of various platelet constituents. </li></ul>
  30. 30. Membrane system <ul><li>Memberane system comprises the </li></ul><ul><li>Open canalicular system </li></ul><ul><li>Dense tubular system </li></ul><ul><li>Open canalicular system provides a passage for externalization of platelet secretory products and internalization of substances from plasma into the platelet. </li></ul>
  31. 31. <ul><li>Dense tubular system provides a site for sequestration of Ca2+ and localization of enzymes needed for prostaglandin synthesis </li></ul><ul><li>Release of Ca2+ from the dense tribular system triggers platelet aggregation </li></ul>
  32. 32. Platelet constituents Platelet location Constituent Function Exterior coat Fibrinogen Platelet aggregation Membrane Arachidonic acid Prostaglandin synthesis Plaletet factor 3 (phospholipid) Enhances Coagulation cAMP Inhibits release reaction
  33. 33. Platelet constituents Microtubules Tubulin Cytoskeleton Contractility Microfilaments Thrombosthenin Shape change, clot reaction, release reaction Alpha-granules Beta-thromboglobulin Impedes prostacylin production from endothelial cells Catalase Enzymic process
  34. 34. Factor VIII-relatedantigen Platelet adhesion to subendothelium Fibrinogen Shape change, clot reaction, release reaction Beta-thromboglobulin Impedes prostacylin production from endothelial cells Fibronectin Adherence to extracellular matrix Promote wound healing