cardiovascular: vasculature Flashcards
layers of an artery (from innermost to outermost layers)
endothelial-> internal elastic lamina-> tunica media (smooth muscle)-> external elastic lamina-> tunica adventitia (fibroblast/Sympathetic nerves/collagen/vasa vasorum)
layers of a capillary (from innermost to outermost layers)
endothelial-> basal lamina (fibrous proteins)-> pericyte (regulate capillary diameter in CNS)
layers of a vein (from innermost to outermost layers)
endothelial-> tunica media-> adventitia (sympathetic nerves)
how is vascular tone controlled? examples
extrinsically: SNS/hormones eg adr/angiotensin II
intrinsically: autocoids/tissue metabolites/blood borne substances/flow/pressure
smooth muscle contraction process
myosin light chain kinase + calmodulin + [ca] increase -> active complex
active complex causes phosphorylation of myosin
phosphorylated myosin + actin -> crossbridge cycle
what is myosin dephosphorylated by? how is this enzyme activated or inhibited
myosin phosphatase;
activated by NO via cGMP
inhibited by agonist via rho kinase-> ca sensitisation (promotes contraction)
what effects does NA or angiotensin 2 have on a smooth muscle cell
bind to receptor-> rho kinase activated-> ca sensitisation
bind to receptor-> phospholipase c activated-> PIP2 cleaved into IP3 + DAG
IP3-> ca release from SR
DAG-> activates receptor gated channels-> influx of na + ca
na influx-> depolarisation-> VGCC activated-> ca influx
what else do endothelial cells release?
prostacyclin which inhibits platelet aggregation
endothelin which is a vasoconstrictor at smooth muscle cell receptors
NO vasodilating mechanism; what enzyme halts this process
NO released by endothelial cell-> diffuses into smooth muscle cell-> activates guanylate cyclase-> GTP converted into cGMP
cGMP -> activated myosin phosphatase-> ca desensitisation
cGMP-> increased uptake by SERCA and plasma membrane ca atpase
cGMP-> activates K channels-> K efflux-> membrane hyperpolarisation-> vgcc closes
how do endothelial cells produce NO? what exactly triggers its release?
bradykinin/ atp/ histamine/H+/ co2/ ach -> GPCR -> increased ca levels -> increased eNOS (an enzyme) -> increased conversion of L-arginine to NO
OR
shear forces (blood flow) -> increased eNOS (an enzyme) -> increased conversion of L-arginine to NO
3 mechanisms of vasodilation
NO-mediated
endothelium-derived hyperpolarisation
PKA pathway: b2 receptors/ prostacyclin receptors/ adenosine receptors-> stimulate adnylate cyclase-> cAMP synthesis-> PKA activation -> vasodilation
mechanism of endothelium-derived hyperpolarisation
bradykinin/ atp/ histamine/H+/ co2/ ach/shear forces to endothelial cell-> increased [ca] in endothelial cell-> increased activation of ca-activated k+ channels-> K efflux-> hyperpolarisation of endothelial cell-> hyperpolarisation of smooth muscle cell via GAP JUNCTION-> decreased [ca] in smooth muscle cell -> relaxation
how is oxidative stress associated with cardiovascular disease? examples of ROS
impairs vasodilation by overproduction of ROS
eg superoxide [o2.-] (reacts with NO to produce peroxynitrite)
eg h2o2
explain myogenic response in autoregulation of blood flow
flow= change in pressure/ R
pressure increase-> immediate increase in flow-> artery balloons up; flow increases, resistance is same-> myogenic response: slows constriction-> resistance increases-> flow is restored
effect of tissue metabolites on vascular tissue
metabolites produced-> vasodilation-> blood flow increases-> washout -> vasoconstriction (actually just reduced vasodilation)-> resistance increases-> flow decreases
what’s metabolic hyperaemia
increased metabolic rate-> increased production of metabolites eg K; H; CO2; lactic acid; adenosine-> vasodilation-> increased blood flow-> increased washout
what is reactive hyperaemia
local blood flow cut off-> metabolites accumulate-> vasodilation
types of endothelium; features; where are they present
continuous: in most tissues; monolayer/joined by tight junctions/least permeable
fenestrated: kidneys/joints/intestines; contain pores/10x more permeable to hydrophilic molecules
sinusoids: liver/spleen; large proteins can diffuse rapidly across capillary wall
routes of transport across capillary wall; what kind of molecules are carried via each route
wide intercellular gap (in acute inflammation): large lipophobic molecules
transendothelial channel: large lipophobic molecules
vesicular transport: large lipophobic molecules
transcellular route: lipophilic molecules
paracellular route: small lipophobic molecules
fenestral route: lipophobic molecules
net volume of plasma filtered by entire microcirculation
4-8 litres
2 types of pressure gradient regulating fluid filtration; how do they regulate it
hydrostatic pressure: in open capillary, pressure at arteriolar end is 40mmHg; venous is 15mmHg; interstitium is 0mmHg-> filtration (out of capillaries)
osmotic pressure gradient: protein concentration within capillaries is higher than interstitium -> absorption (water into capillaries)
why are proteins considered in the osmotic pressure gradient
they are larger-> less permeable -> higher reflection coefficient
starling equation (describes net movement of fluid across capillary) how is it transiently affected by standing up
(Pcapillary-Pinterstitium) - (osmoticcap- osmotic interstitium)
if u stand up, Pcapillary increases transiently-> increased filtration
what happens to movement of fluid when arterial end of capillary constricts
normally when its open, filtration is occurs. hydrostatic pressure gradient present at arteriole and venous end.
but when its closed, hydrostatic pressure gradient at arteriole end is reduced; and at venous end it is 0. filtration still occurs at arteriole end, but at venous end, absorptive forces due to osmotic pressure gradients is dominant
lymphatic system functions
preserves fluid balance (once filtered, lymphatic capillaries return an amount of drain fluid back to circulation)
transports fat from small intestine into circulation
transports foreign materials into lymph nodes
transports lymphocytes into blood
lymphatic capillary/trunk/lymph node features; what is a functional unit of a lymph vessel called
lymphatic capillaries contain intercellular clefts-> one-way entry of fluid into lymphatic trunk, driven by tissue compression
lymphatic trunk runs next to major bv, has smooth muscle that contracts rhythmically due to presence of pacemaker cells, has one-way valve;
lymphangion (lies between two one-way valves)
lymph node: some reasbsorption of lymph occurs here; lymphocytes activated here
