Overview
This lecture explains how the body prevents blood loss through blood clotting, focusing on the roles of platelets, fibrin, and the coagulation cascade pathways.
Blood Vessel Injury and Initial Response
- Blood vessels are lined with endothelial cells that seal blood from surrounding tissue.
- Vessel injury breaks this seal, risking blood loss.
- Platelets quickly gather at the injury site to form an initial plug.
Formation of a Stable Clot
- The platelet plug is stabilized by fibrin strands forming a mesh.
- Fibrin strands are polymers of fibrin subunits that naturally stick together.
- Fibrin is not present in circulating blood; instead, blood contains fibrinogen (inactive form).
- Fibrinogen has an extra piece blocking its active site, preventing polymerization.
Conversion of Fibrinogen to Fibrin
- Fibrinogen converts to fibrin only at injury sites.
- Injury exposes new proteins (e.g., tissue factor) that trigger this conversion.
- Thrombin is the key enzyme that converts fibrinogen to fibrin.
- Thrombin itself is generated from prothrombin (inactive precursor).
The Coagulation (Clotting) Cascade
- The cascade amplifies clotting via sequential activation of factors.
- Intrinsic pathway: factors XII → XI → IX (+VIII) → X (+V) → II (thrombin) → I (fibrin).
- Each factor is activated by the previous, not converted into it.
- Extrinsic pathway: tissue factor (III) activates VII → X.
- Extrinsic pathway is the initial spark; intrinsic is the main workhorse for clotting.
- Thrombin provides positive feedback, activating multiple factors (V, VII, VIII, XI, XIII).
Stabilizing and Regulating the Clot
- Factor XIII cross-links fibrin strands for a strong mesh.
- Negative feedback prevents over-clotting; thrombin activates anti-thrombin and plasmin (which dissolves clots).
Hemophilia and Factor Deficiencies
- Hemophilia results from deficiencies in clotting factors, leading to excessive bleeding.
- Hemophilia A: lack of factor VIII (intrinsic pathway).
- Hemophilia B: lack of factor IX.
- Hemophilia C: lack of factor XI.
Key Terms & Definitions
- Endothelial cells — cells lining blood vessel walls.
- Platelets — cell fragments that form plugs at injury sites.
- Fibrin — protein forming a mesh to stabilize blood clots.
- Fibrinogen — inactive precursor of fibrin in blood.
- Thrombin — enzyme converting fibrinogen to fibrin.
- Prothrombin — inactive precursor to thrombin.
- Coagulation cascade — series of steps activating clotting factors.
- Intrinsic pathway — clotting triggered inside vessels.
- Extrinsic pathway — clotting triggered by external tissue damage.
- Anti-thrombin — inhibitor that prevents excessive clot formation.
- Hemophilia — genetic disorder causing impaired blood clotting.
Action Items / Next Steps
- Review the clotting cascade diagram and memorize key factor numbers and their sequence.
- Study differences and roles of intrinsic vs. extrinsic coagulation pathways.