In medicine, an embolism is the lodging of an embolus, which may be a blood clot, fat globule, gas bubble, in the bloodstream. This can cause a blockage in a blood vessel. Such a blockage (vascular occlusion) may affect a part of the body distanced from the actual site of the embolism. This is in contrast to a thrombus, which causes a blockage at the site of origin.
The endothelium is the thin layer of simple squamous cells that lines the interior surface of blood vessels and lymphatic vessels, forming an interface between circulating blood or lymph in the lumen and the rest of the vessel wall. The cells that form the endothelium are called endothelial cells. Endothelial cells in direct contact with blood are called vascular endothelial cells, whereas those in direct contact with lymph are known as lymphatic endothelial cells.
Vascular endothelial cells line the entire circulatory system, from the heart to the smallest capillaries. These cells have unique functions in vascular biology. These functions include fluid filtration, such as in the glomeruli of the kidney, blood vessel tone, hemostasis, neutrophil recruitment, and hormone trafficking. Endothelium of the interior surfaces of the heart chambers is called endocardium.
Enzymes are macromolecular biological catalysts. They are responsible for thousands of metabolic processes that sustain life. The study of enzymes is called enzymology. Enzymes are highly selective catalysts, greatly accelerating both the rate and the specificity of metabolic chemical reactions: from the digestion of food to the synthesis of DNA. Most enzymes are proteins, although a few are catalytic RNA molecules, such as theribosome. Enzymes fold into a specific three-dimensional structure, and may use organic (e.g. biotin) and inorganic (e.g. magnesium ion) cofactors to aid catalysis.
Enzymes work by converting starting molecules (substrates) into different molecules (products). Almost all chemical reactions in a biological cell need enzymes to happen at rates high enough to sustain life. Because enzymes are selective for their substrates, they speed up only a few reactions from among many possibilities. The set of enzymes made in a cell determines which metabolic pathways occur in that cell.
Like all catalysts, enzymes increase the rate of a reaction by lowering its activation energy. Most enzyme reaction rates are millions of times faster than the un-catalyzed reactions, and some are so fast that they are limited only by how fast substrates can diffuse to the enzyme. As with all catalysts, enzymes are not consumed by the reactions they catalyze, nor do they alter the equilibrium of these reactions. However, enzymes do differ from most other catalysts in that they are highly specific for their substrates. Enzymes are known to catalyze about 4,000 biochemical reactions.
Enzyme activity can be affected by other molecules: decreased by inhibitors or increased by activators. Manydrugs and poisons are enzyme inhibitors. Activity is also affected by temperature, pressure, chemical environment (e.g., pH), and the concentration of substrate. Some enzymes are used commercially, for example, in the synthesis of antibiotics. In addition, some household products use enzymes to speed up biochemical reactions (e.g., enzymes in biological washing powders break down protein or fat stains on clothes; enzymes in meat tenderizers break down proteins into smaller molecules, making the meat easier to chew).
The main role of the tissue factor pathway is to generate a “thrombin burst”, a process by which thrombin, the most important constituent of the coagulation cascade in terms of its feedback activation roles, is released very rapidly. FVIIa circulates in a higher amount than any other activated coagulation factor. The process includes the following steps:
- Following damage to the blood vessel, FVII leaves the circulation and comes into contact with tissue factor (TF) expressed on tissue-factor-bearing cells (stromal fibroblasts and leukocytes), forming an activated complex (TF-FVIIa).
- TF-FVIIa activates FIX and FX.
- FVII is itself activated by thrombin, FXIa, FXII and FXa.
- The activation of FX (to form FXa) by TF-FVIIa is almost immediately inhibited by tissue factor pathway inhibitor (TFPI).
- FXa and its co-factor FVa form the prothrombinase complex, which activates prothrombin to thrombin.
- Thrombin then activates other components of the coagulation cascade, including FV and FVIII (which activates FXI, which, in turn, activates FIX), and activates and releases FVIII from being bound to vWF.
- FVIIIa is the co-factor of FIXa, and together they form the “tenase” complex, which activates FX; and so the cycle continues. (“Tenase” is a contraction of “ten” and the suffix “-ase” used for enzymes.)