Platelets Lecture 3 GU Fall 2024 PDF

Thrombocytes(Platelets) Thrombopoiesis Prof. Manal Shaaban| Professor of Histology Professor of Histology and cell biology Faculty of Medicine, Fall 2024 Galala University gu.edu.eg  1.Describe structure and correlated functions of...

Thrombocytes(Platelets) Thrombopoiesis Prof. Manal Shaaban| Professor of Histology Professor of Histology and cell biology Faculty of Medicine, Fall 2024 Galala University gu.edu.eg  1.Describe structure and correlated functions of the blood platelets. 2. Identify the steps of development of platelets. 3. Describe the structure (LM and TEM) of megakaryocytes. 4. Compare between megakaryoblasts and megakaryocytes.  Platelets (Thrombocytes) Blood platelets :- Small 2-4 μm in diameter, non-nucleated, Megakaryocyte membrane-bound cell fragments. Origin:- Platelets arise as fragmentation of giant polyploid megakaryocyte ( Bone marrow cells). Platelets promote blood clotting and help repair minor tears or leaks in the walls of small blood vessels, so preventing blood loss Number: 150,000- 400,000/mm3. Thrombocytosis = Increase in platelets number (Primary or Secondary due to cancer or inflammatory disorders ). Thrombocytopenia= Decrease in platelets number. Circulating platelets have a life span of about 10 days.  Histological characters of platelets (Thrombocytes) ❖ By L.M: appear in clumps in stained blood films. Shape: ovoid- discoid cell fragments. Size: 2-4 μm in diameter They Have;- ✓ Hyalomere ; a lightly stained peripheral zone. ✓ Granulomere; darker-staining central zone rich in granules. The cell membrane is surrounding by glycocalyx =cell coat formed of glycoproteins and several coagulation factors adsorbed from the plasma, which are involved in adhesion and activation during blood coagulation. The integral membrane proteins form receptors in platelet surface.  Histological characters of platelets ❖ By E.M: ✓ Hyalomere have; 1.A peripheral marginal bundle of microtubules, actin and myosin to form a network supporting the plasma membrane & maintain the platelet’s shape. 2.Two systems of membrane channels:- a. Open canalicular system: is an invagination from the cell membrane, facilitating platelets’ uptake of factors from plasma. b. Dense tubular system: is derived from the ER and stores Ca2+ ions. The two membranous systems help rapid exocytosis of the granules (degranulation) during platelets activation. TEM of platelets  Histological characters of platelets ❖ By E.M: ✓ Granulomere have; 1.Mitochondria, ribosomes, glycogen granules. Three types of granules: ✓ 1.α (alpha) granules (larger & majority) contain fibrinogen , coagulation factors & platelets-derived growth factors(PDGF). ✓ These granules play a role in the initial phase of vessel repair, blood coagulation, and platelet aggregation. ✓ 2.δ (delta) granules (electron dense )contain ADP, ATP and serotonin which facilitate platelet adhesion and vasoconstriction in the area of the injured vessel. PDGF is a potent mitogen for cells of mesenchymal origin, ex fibroblasts & smooth muscle cells. So it promotes wound healing and repair process.  Histological characters of platelets ✓ 3.λ (lambda) granules are actually lysosomes play a role in clot retraction during the later stages of vessel repair. ✓Calcium ions and adenosine diphosphate (ADP) increase the stickiness of the glycocalyx and enhance platelets aggregation  Development of platelets (Thrombopoiesis) Platelets are continuously produced in red bone marrow. Origin:- Platelets arise as fragmentation of giant polyploid megakaryocyte ( Bone marrow cells). Megakaryocyte is derived from Megakaryoblast under the effect of thrombopoietin.  Development of platelets 4.Megakaryoblast ❖ The megakaryoblast:- 25-50 μm in diameter. The nucleus is large ovoid or kidney-shaped with numerous nucleoli. The cytoplasm is homogeneous (Non granular) and highly basophilic. Before differentiating, these cells undergo endomitosis, with repeated rounds of DNA replication not separated by cell divisions, resulting in a nucleus that is highly polyploid (from 8N to 64N).  Development of platelets 5.Megakaryocytes ❖ The megakaryocyte:- is a giant cells, up to 150 μm in diameter (larger than megakaryoblast). They are widely scattered in marrow, near blood sinusoidal. The nucleus: is polyploid, large and irregularly lobulated with coarse chromatin. The cytoplasm: is Basophilic & Granular. It contains numerous mitochondria, a well-developed RER, and Golgi complex to form specific granules of platelets.  Mature megakaryocytes have numerous invaginations of plasma membrane spread throughout the cytoplasm, called demarcation membranes. The importance of demarcation membranes that act a membrane reservoir to facilitates the continuous rapid elongation of pro-platelets. Proplatelets platelets originate by separation from the ends of cytoplasmic processes extending from giant polyploid bone marrow cells called Megakaryocyte  Development of platelets 5.Megakaryocytes To form platelets, megakaryocytes extend several long branching processes called proplatelets. These processes enter between the sinusoidal endothelium and are exposed in the circulating blood in bone marrow to liberate platelets at their tips.  Functions of platelets ❑ 1-Platelets aggregation: When a blood vessel wall is injured, the exposed connective tissue at the damaged site promotes Platelet Plug. (by releasing von Willebrand factor (vWF) from endothelial cells). Platelets that adhere to the vWF are activated. Adhesion of activated platelets at the damaged site triggers their degranulation and release of serotonin (contraction of smooth muscles of small vessels), ADP & thromboxane-A. Platelets aggregation occurs only in regions where the endothelium is damaged???  Functions of platelets ❑ 2. Blood coagulation :The glycocalyx of the platelets provides a reaction surface for the conversion of soluble fibrinogen into fibrin meshwork. This meshwork cause trapping of red blood cells and more platelets to form a blood clot or thrombus.  Functions of platelets ❑ 4-Clot retraction & finally clot removal due to the activity of platelet-derived actin and myosin and by process of plasminogen activation to produce plasmin. Contraction of the clot permits the return of normal blood flow through the vessel. Platelet-derived growth factors released from the granules stimulates smooth muscle cells and fibroblasts to divide and allow tissue repair and wound healing ogen  Some clinical disorders Thrombocytopenia :- A reduction in the number of circulating platelets, result in bleeding disorders. Causes of thrombocytopenia:- 1.Deficiencies of folic acid or vitamin B12. 2. Thrombocytopenic purpura (there are small spots or petechiae in the skin from poorly inhibited bleeding) ✓ Thrombocytosis:- An increase in the number of circulating platelets. ✓ Causes of thrombocytosis: secondary to cancer and autoimmune diseases. ❖ Platelet function is compromised by autoimmune reactions. Textbook guide 20