regulation of blood flow Flashcards
why do organs need to regulate their blood flow (4)
to match blood supply to metabolic rate; to allow for efficient delivery of nutrients/removal of waste; increase/decrease heat loss; ensure blood flow to vital organs is maintained in the case of major haemorrhage
how is blood flow controlled (vascular level)
change in vascular tone
structure of non-striated vascular smooth muscle
single nucleus; membrane has Caveolae (similar to t tubules); dense bodies of a-actin (origin of actin + myosin filaments, similar to sarcomere); unorganised
what extrinsic factors affect vascular tone
circulating hormones; autonomic stimulation
what is the ion most important in sm contraction
Ca2+; intracellular levels govern contraction; L-type Ca2+ channels are found on vascular smooth muscle -> CCBs can affect contraction
what needs to occur to vsm myosin in order for it to form cross bridges with actin
phosphorylation of the light chain
light chain phosphorylation pathway
intracellular Ca2+ levels increase -> binds to calmodulin-> Ca2+-calmodulin activates myosin light chain kinase -> MLCK phosphorylates myosin - allows cross bridges to form
what happens to Ca2+ post contraction
binds with Calsequestrin in the sarcoplasmic reticulum and is stored there; or is transported out of the cell via Na+/Ca2+ exchanger etc.
an upregulation of what 2 molecules causes VSM to relax?
c-AMP (inhibits MLCK) and c-GMP (activates myosin phosphatase)
resistance equation (ohms law)
R = flow (V)/pressure (I)
what is autoregulation (blood flow)
intrinsic ability of an organ to maintain constant blood flow changes in perfusion pressure in the absence of external neural/hormonal stimuli i.e. constant flow is maintained despite changes in the perfusion pressure
what is the myogenic theory of autoreg
stretch receptors in the bv walls are activated -> influx of Ca2+ -> sm contraction -> decreased radius -> flow remains the same despite greater transient blood flow; bayliss myogenic response
what is the metabolic theory of autoreg
decrease in blood flow leads to an increase in waste product accumulation -> waste products activate receptors which cause vasodilation (Ca2+ influx etc.) -> blood flow increased back to desired rate
examples of vasodilatory metabolites (9)
↓ PO2; ↓pH; ↑ pCO2; ↑ temp; ↑K+; ↑ lactate; ↑osmolality; ↑histamine; ↑ products of ATP breakdown (adenosine, inorganic phosphate)
what is the effect of vasodilatory (waste) metabolites on the lungs
vasoconstriction
how does adenosine cause muscle relaxation
binds to AT2 receptors -> activates c-AMP -> inhibits MLCK binding -> vasodilation
what does eNOS activation lead to
brachial artery vasodilation
what is endothelin
a powerful vasoconstrictor; there are 3 isoforms coded for by different genes; produced as pro-hormone big endothelians, converted by endothelian converting enzyme
what are prostoglandins synthesised by?
vascular endothelium from arachidonic acid
what types of prostoglandins are vasoconstrictors and which are vasodilators
VC - F series, serotonin;
VD - E, I series, PGE2/4
what can be given to raynauds patients to ease symptoms
prostacyclin (PGI2) - vasodiliator
what hormones are vasodilators (3)
kinins (bradykinin, lysylbradykinin); adrenomedullin; atrial natiuretic peptide (ANP)
kinin precursors
kininogens
how do kinins work
act on B2 receptors on endothelial cells, causing a release of NO in endothelial cells
role of kinins in clotting
plasma kallikrenin acts on HMW kininogen to make bradykinin
action of adrenomedullin
a depressor polypeptide that inhibits alodsterone; releases NO and increases c-AMP in cells; exerts action through calcitonin receptor like recptor and RAMP2/3
action of ANP & BNP (3)
secreted from the heart (ANP from atria and BNP from ventricles); lowers BP by antagonising various vasocontrictors - released when the heart is stretched; inhibits renin secretion;
circulating vasoconstrictors (4)
angiotensin/renin; noradrenaline; urotensin II; vasopressin
pre ganglionic NT (ANS)
Ach
post ganglionic sympathetic NT
NA
post ganglionic parasympathetic NT
Ach
what does NA exist alongside in NT vesicles
ATP; neuropeptide Y
what is the neural mechanism of blood flow regulation
regulation of BF that depends on cardiovascular centres in the medulla oblongata
what does baroreceptor firing cause (neural mech of BF)
reflex via the medullary cardiovascular centre - decreased symp to heart, arterioles, veins; increase parasymp to heart
RAAS pathway
renin –> angiotensin – (liver)–> angiotensin I – (ACE) –> angiotensin II –> vasoconstriction (↓GFR, ↓urine output); adrenal gland stimulaton –> aldosterone –> ↑Na+ retention, ↑ water retention –> ↑ BP
