platelets (thrombocytes) correc
TRANSCRIPT
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PLATELETS (THROMBOCYTES)
Lecture by GK Mbassa
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Purpose of knowing structure, biochemistry and functions of
platelets
• Understand qualitative platelet abnormalities
• Gain knowledge on hemostasis for treatment of diseases
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• Know platelets role in tumor metastases, atherosclerosis and inflammation resulting from cytoplasmic fragments of megakaryocytes, e.g. arachidonic acid.
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Morphology of platelets
• Heterogenous in blood smears; discoid, spheroid, elongated, flat
• Granular organelles distributed in cytoplasm.
• Some organelles in centre (granulomere)
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• Platelet cytoplasm is hyalomere, which is clear
• Platelet is bounded by thin membrane, smooth or having fine projections
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• EDTA anticoagulant minimizes platelets clumping
• Platelets may clump to other cells (erythrocytes and neutrophils), called satellitism.
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• 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,
• Platelet counts vary (1- 10 x 1011/l)
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• Larger platelets are metabolically and functionally more active than small platelets.
• 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
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• Surface projections represent protractions of platelets granules
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• Surface features of platelets are similar in most species.
• Platelets diameter length is 1.3 – 4.7 µm in dog, cat, equines, cow, sheep and goat.
• Platelet thickness is 0.5 µm
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• 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
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Ultrastructural features of the platelet
• Unit membrane covered with amorphous material (external or exterior coat)
• Bundles of microtubules in matrix beneath membrane
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• Internal structure comprises of heterogenous granules (alpha-granules)
• Clycogen particles
• Dense granules
• Mitochondria
• Lysosomes
• Peroxisomes
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• Poorly developed Golgi complex
• Endoplasmic reticulum (rarely)
• Spongy like channels, called open canalicular system)
• Open canalicular system communicate with substance of platelet, open to surface at invaginations.
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• Open canalicular system is lined by unit membrane, covered by external coat
• Another system of platelet channels is the dense tubular system.
• Dense tubular system occurs under marginal band of microtubules and appears to open to surface, but does not open on the platelet surface.
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• Platelets of many animals have similar morphology.
• Platelets have two types of granules, (1) alpha-granules, and (2) dense granules.
• Dense and alpha granules are homogeneously distributed, but vary in electron density, number and size.
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Functional organization of the platelet
The platelet is divided into four structural regions
• (1) Peripheral zone
• (2) Sol-gel zone
• (3) Organelle zone
• (4) Membrane system
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Peripheral zone
• Composed of external (exterior) coat, unit membrane, sub-membraneous area
• Functions, maintain platelet integrity, receive and transmit stimuli triggering platelet responses (adhesions, aggregations)
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• 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)
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• Glycoproteins have receptors for platelet activation and aggregation.
• 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
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• Platelet membrane; maintains platelet integrity, rich in phospholipids.
• Platelet phospholipids function in blood coagulation (eg
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Sol-gel zone
• Represented by matrix of platelet cytoplasm, contains microfilaments and microtubules, which function as cytoskeletal elements.
• Microfilaments and microtubules maintain discoid platelet shape, form contractile system for shape change, pseudopod formation, internal contractions and granule secretion.
• Microfilaments also function in clot retraction.
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• Microfilaments are also associated with thrombosthenin, a contractile protein (has actin-myosin)
• Microtubule tubulin dissolves at 4oC, when exposed to colchicine or vinca alkaloids, leading to platelet shape irregularities.
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Organelle zone
• Composed of all internal platelet components, except microtubules, microfilaments (sol-gel zone) components and membrane system.
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• Main component of organelle zone are platelet granules, that are morphologically and biochemically heterogeneous, azurophilic granules (alpha-granules under electron microscope)
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• 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.
• Platelets in von Willebrand disease lack factor VIII related antigen
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• Electron dense granules, called delta granules, or dense bodies contain non metabolic pool ATP and ADP, Ca2+, mono-amines (serotonin, histamine).
• Dense granules vary with species.
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External coat
Microfilaments
Alpha granule
Open canalicular system
Dense tubular system
Microtubules
Golgi complex
Lysosome
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• 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.
• Platelet activation triggers secretion of various platelet constituents.
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Membrane system
Memberane system comprises the
• Open canalicular system
• Dense tubular system
Open canalicular system provides a passage for externalization of platelet secretory products and internalization of substances from plasma into the platelet.
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Dense tubular system provides a site for sequestration of Ca2+ and localization of enzymes needed for prostaglandin synthesis
Release of Ca2+ from the dense tribular system triggers platelet aggregation
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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
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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
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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