Blood Vessel Injury and Response

Blood Vessel Injury and Clotting

• When a blood vessel gets hurt, its walls break open, and cells no longer seal the vessel, which can lead to blood loss.
• The body has a mechanism to contain the blood and prevent excessive loss.

Initial Plug Formation

• Platelets circulating in the body come to the site of injury and form an initial plug to stop the bleeding.
• The platelet plug is not solid enough, and the body needs a second mechanism to solidify it.

Fibrin Strands and Fibrinogen

• Fibrin strands, composed of fibrin sub-units or proteins, act as a mesh to hold the platelet plug together.
• Fibrin molecules have a natural affinity for each other, forming a polymer when brought together.
• Fibrinogen is the precursor to fibrin, but it cannot circulate in the blood because it would form fibrin strands spontaneously.

Fibrinogen Conversion to Fibrin

• When the endothelium is injured, new proteins are exposed or released, which trigger the conversion of fibrinogen to fibrin.
• Thrombin is the enzyme that converts fibrinogen to fibrin.

Thrombin and Clotting Cascade

• Thrombin is activated from an inactive form called prothrombin.
• Thrombin activates other clotting factors, leading to a cascade of reactions that ultimately form a fibrin mesh.
• The clotting cascade is an amplification sequence, with each step increasing the amount of active clotting factors.

Intrinsic and Extrinsic Pathways

• There are two pathways that lead to the formation of fibrin: the intrinsic pathway and the extrinsic pathway.
• The intrinsic pathway is the "workhorse" that does most of the coagulation, while the extrinsic pathway is the "spark" that initiates the process.
• The extrinsic pathway is activated by tissue factor, which is exposed or released when the endothelium is injured.

Thrombin's Role in Clotting

• Thrombin activates factors V, VII, VIII, XI, and XIII, which are necessary for the intrinsic pathway.
• Thrombin also has a positive feedback loop, which can lead to an overproduction of fibrin if left unchecked.

Negative Feedback Loops

• To prevent excessive clotting, there are negative feedback loops that reduce the amount of thrombin and fibrin produced.
• Examples of negative feedback loops include thrombin stimulating the production of anti-thrombin and plasmin, which break down fibrin meshes.

Hemophilia

• If the clotting system doesn't work, it can lead to excessive bleeding, a condition known as hemophilia.
• There are three types of hemophilia: A, B, and C, which are caused by deficiencies in factors VIII, IX, and XI, respectively.