5. Hemostasis

Hemostasis

  • Hemostasis is the process of stopping bleeding and involves a fast series of reactions.
  • Blood is divided into plasma and formed elements.
    • Plasma contains proteins, including fibrinogen, which is crucial for blood clotting.
    • Fibrinogen is an inactive form of fibrin, essential for clot formation.
    • The suffix "-ogen" indicates an inactive state. It is faster to activate pre-existing inactive proteins than to synthesize them de novo through transcription and translation.
    • Thrombocytes (platelets) are found in the formed elements and are also vital for clotting.

Plasma vs. Serum

  • Plasma is the liquid component of blood containing clotting factors.
  • Serum is plasma without the clotting factors (i.e., plasma minus fibrinogen). Serum occurs after clotting has taken place.
  • To obtain plasma for analytical tests (to measure the clotting factors), anticoagulants must be added to blood collection tubes to prevent clotting.

Components Required for Clotting

  • Plasma proteins (especially fibrinogen).
  • Thrombocytes (platelets).
  • Electrolytes, particularly calcium (Ca^{2+}).

Steps of Hemostasis

  1. Vascular Spasm (Vasoconstriction)

    • Reduces blood flow past the damaged point.
    • Triggered by:
      • Injury itself.
      • Chemicals released by the damaged vessel wall.
      • Activated platelets.
      • Pain reflexes.

  2. Platelet Plug Formation

    • Platelets are activated upon exposure to the extracellular matrix (ECM) outside the blood vessel.
    • Activation causes platelets to:
      • Change shape and swell.
      • Become spiky and sticky.
      • Release chemical signals (positive feedback) to activate more platelets.
    • The plug is a temporary seal over the vessel damage.
    • Nitric oxide (NO) and prostacyclin from the intact vessel wall prevent accidental platelet activation.

  3. Coagulation (Blood Clotting)

    • The platelet plug is reinforced by a fibrin mesh.
    • This process involves two pathways:
      • Tissue Factor Pathway (Extrinsic): Triggered by tissue factor protein in the blood. Starts within the blood itself.
      • Contact Pathway (Intrinsic): Triggered by contact with the extracellular matrix (ECM) outside the blood. Needs a signal from outside the blood.

Clotting Cascade

  • Both pathways converge to activate prothrombin into thrombin.
    • "Pro-" prefix indicates an inactive state.
  • Thrombin converts fibrinogen into fibrin.
  • Fibrin strands create a mesh over the platelet plug, trapping red blood cells and stabilizing the clot.
  • Requires coagulation factors (proteins), calcium (Ca^{2+}), and activated platelets.
  • Inflammation can trigger clotting via the intrinsic pathway (tissue factor), requiring calcium (Ca^{2+}) and liver-derived coagulation factors.

Summary of Coagulation Process

  1. Damaged vessel exposes collagen fibers in the extracellular matrix.
  2. Platelets are activated, releasing chemicals to activate more platelets.
  3. Damaged cells release factors that lead to thrombin formation.
  4. Plasma factors like calcium (Ca^{2+}) and vitamin K are essential.
  5. Prothrombin is converted to thrombin.
  6. Thrombin converts fibrinogen to fibrin.
  7. Fibrin fibers create a mesh trapping platelets and red cells, forming a stable plug.

Clot Retraction and Repair

  • Clot retraction assists with repair by pulling the broken vessel edges closer together.
  • Actin and myosin in platelets cause contraction, reducing the clot's size.
  • Contraction squeezes out serum (plasma without clotting factors), which may be observed as a clear, yellowish liquid.
  • Endothelial cells regenerate to fill the gap in the vessel wall.
  • Platelet-derived growth factor (PDGF) stimulates:
    • Fibroblasts to rebuild the extracellular matrix.
    • Smooth muscle cells to divide and proliferate.
  • Vascular endothelial growth factor (VEGF) stimulates endothelial cells to undergo mitosis and restore the endothelial lining.

Fibrinolysis

  • Once the vessel is repaired, the clot needs to be dissolved.
  • Plasminogen (inactive) is converted to plasmin (active).
  • Plasmin is an enzyme that digests fibrin, breaking down the fibrin strands.
  • This process is called fibrinolysis (fibrin breaking).