BCMB 230 1st Edition Lecture 17 Outline of Last Lecture I.Physics of Blood FlowII.Physics of the HeartIII.Control of Blood FlowOutline of Current Lecture I.PressureII.Coagulation and HemostasisIII.ClottingCurrent LectureI. PressurePressure regulation can happen over the short-term or over the long-term.-short term: vasoconstriction and vasodilation; issue is that we may cause problems with flow (constriction may cause decrease in blood flow)-long term: regulate blood volume; job of the kidneysEndothelial cells-make walls of blood vessels (capillaries); are very flat and thin-use diffusion to get oxygen and other nutrients through blood vessel walls-we want a bulk flow and whatever is dissolved in water to go out of blood, circulate through tissues and then come back inPathway: travel from blood to ultra filtrate to interstitial fluid, then return to bloodUltrafiltrationhappens in most capillariesFiltrationonly in the glomerulus—name of capillaries in the kidneysTwo kinds of pressures:Hydrostatic pressure-due to heart, vasoconstriction, muscle contractions, influenced by blood volume-on artery side (closer to heart, have lots of muscle) has high hydrostatic pressure-forces fluid (water) out into interstitial fluid, leaving high protein concentration inside vessel on artery side (have higher pressure inside vessel, lowest pressure in interstitial fluid)-on vein side, have lower hydrostatic pressure-also forces fluid out, but not as much (leaves low concentration of proteins inside)-lowest hydrostatic pressure is outside of the vesselThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.-need a pressure gradient in order to get flow (go from high to low)Osmotic pressure-due to solute gradients, mostly dissolved proteins-proteins inside pull water in because more protein in capillaries/blood than out in the interstitial fluid-on artery side, lower osmotic pressure-pulls fluid back into vessel-on vein side, higher osmotic pressure-pushes fluid back into vessel-opposing forces of pressure cause blood to go in and outStarvation-fluid fills abominable cavityEdema-swelling; have high hydrostatic pressure—favor movements out of the vessel which buildups in the tissuesIf tissue is damaged, release a lot or proteins into interstitial fluid (allowed to flip the pressure gradient)-most serious problem for a burn victim is maintaining blood pressure-blood volume is dropping because there is less fluidII. Coagulation and HemostasisCoagulation/Hemostasis-stop bleeding from injury if vessel is damaged; largely controlled by positive feedback-damage causes a reduce in flow, which decreases blood lossThree parts of the process:Vascular spasm-vasoconstriction that can help reduce flowPlatelet activation-endothelial cells get damaged and expose inside of vessel to collagen/connective tissue on the outside-aggregration-blood cells or cell fragments get sticky and stick to damaged area and to each other; forms a platelet plug-secretion-secrete chemicals that promote more platelet activation-can still have blood loss because there is space between cellsClotting-take water-soluble protein called fibrinogen and turn it to fibrin which is insoluble-fills in spaces in platelet plug; forms clots-These three parts don’t happen independently of each other; they all influence each other.Von Willibrand factor-component of blood made of endothelial cells that bind to collagen; platelet bonds to Von Willibrand factor which activates platelet—serves as a link between platelet plug and collagen; happens when the cell is damagedThromboxane A2-acts to activate more platelets through positive feedback which causes the platelet plug to grow-have to counteract this before it goes too far or it will block flow in vesselInhibitors of platelet activation:-prostacyclin (PGI2)/prostaglandin (general chemical class)-limit platelet aggregation to place of injury-nitric oxide (NO)-vasodilation; helps maintain flow; shuts down platelet aggregation so it does not spread too much-secreted by endothelial cells-happens in all vessels which are made by endothelial cells—can happen in artery or veinsIII. ClottingTwo ways of starting process:Clotting factors-already present in blood in inactive form, formed by liver-need to activate it in a certain sequence: multi-step pathway (get amplification—go very fast).; get multiple control points.-link into one common pathway; shared by both intrinsic and extrinsic-intrinsic-everything you need is inside the vessel-extrinsic-everything you need is outside the vesselThrombin-key player; activates fibrinogen to fibrin; activate factor 13 which acts on fibrin and stabilizes it-thrombin activates itself indirectly through loops-also activates plateletsIf we don’t have platelet action, clotting can still happen but it is reduced and vice versa becausethey are both linked—independent processes but are connected.Hemophilia-defect in factor 8; blood can still clot but not as quicklyVon Willibrand’s disease-genetic defect in gene for Von Willibrand factor-freely bleeds and has difficulty stopping it-inhibit s platelet activation which inhibits clottingDrug TherapyCoumadin: inhibits GI absorption of Vitamin K which is crucial in clotting-can be administered after heart surgery to allow wounds to heal without clotting-need dietary regulation to make sure patient does not receive too much of it-also called Warfarin which is used in rat