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lkubin@phl.vet.upenn.edu
circulatory regulation continued:

clarification from before, re: valsalva maneuver.

test consists of asking person to produce forced expiratory effort 
against occluded airway. this generates positive pressure in the thorax, 
pushing on low pressure vessels and impeding venous return. models 
hypotension. what you can observe is that after a brief increase in 
arterial pressure due to mechanical event, arterial pressure rapidly 
drops off to reflect reduced venous return, but then it is restored to 
normal, and when test ends, BP increases tremendously.

arterial blood pressure control mechanisms:
C in handout. p 2/10. 
mechanisms important for restoration of volume:
realize that during shock, there is strong sympathetic outflow, 
peripheral resistance is increased, this raises blood pressure but 
reduces flow to individual organs. (someone has had his hand raised for 
some time, but instructor is staring at floor *sigh*). also, re: 
vasoconstriction, note that it occurs at the smooth muscle regions called 
precapillary sphincters which occlude the metarterioles. so, mostly, when 
you discuss vasoconstriction, it occurs on arteriolar side of capillary 
bed. this leads to reduced pressure in capillaries. this causes increased 
filtration of fluid into capillary lumen from extracellular space. this 
is called autotransfusion or capillary fluid shift and is a helpful 
mechanism.
so, the capillary fluid shiftin addition to redistributing the fluids 
also causes a change in osmolarity of ECF. will increase the osmolarity 
of ECF (because fluid goes into vessels leaving solute.) and so 
osmoreceptors in hypothalamus are stimulated. those cells respond to 
increased osmolarity of ECF by releasing vasopressin.

note p 3 of handout- table of mechanisms 

so. the osmoreceptors cause release of vasopressin. vasopressin has mild 
primary vasoconstrictor effects, and also it will cause thirst, and will 
increase collecting duct permeability, causing water reabsorption. makes 
new channels, requires transcription, takes a few hours and lasts a 
while.

two other mechanisms to discuss....one, originates in low pressure 
receptors within the heart and large thoracic vessels. mechanoreceptors 
which are excited by volume of blood. but they are on low pressure end, 
so more sensitive to blood volume, not pressure. main effects are on 
vasopressin releasing neurons.

also, special atrial natruretic peptide is released by atria under normal 
conditions, and less of it is made under low pressure conditions. 
normally, woud cause excretion of Na+ and H2O and inhibit 
renin/angiotensin, but less is made during low pressure...

see handout.

circulatory effects of angiotensin II: include increased aldosterone 
production.
unfortunately, the instructor is staring at the screen, not looking at 
us, his accent is heavy, and his words are garbled, and i can't see his 
lips, so...

aldosterone something transcription factor, causes production of 
increased sodium channels. relatively slow acting process--see p 8 of 
handout. whole mechanism is slow acting, because of need for 
transcription, making new protein, putting in channels, etc. effect of 
aldosterone is on active transportof Na+; effect of vasopressin is on 
transport of water.

see chart p 7 for chart of circulating vasomotor factors.
note ACH effects tend to be local, but it's controlled by cns and is 
considered humoral? i think that's what he means. also re: NO release is 
mediated by ACH and bradykinin. ACH itself has receptors on precapillary 
vessels but normally ACH is a vasodilator. ACH primarily acts through the 
stimulator pathway causing NO production, and NO vasodilates. ****that 
doesn't make sense. slide showed NO causing vasoconstriction??

circulating NON vasomotor humoral factorsactivated during compensatory 
rxn to shock:

erythropoeitin, causes erythropoiesis in marrow....
aldosterone, causes sodium resorption
plasma protein replacement - proteins made mainly in the liver

going back to original distributed resistance 
diagram...mumblemumblemumblemumblemumblemumblemumblemumble

neural regulation: first, axon reflex. this is a huleyermechay for 
regulation of bloodflow to the skin. requires that sensory neurons that 
has a sensory ending in the skin and one purpose or function of the 
neuron is to transmit excitation from periphery to CNS/cord. but those 
neurons we're talking about have a collateral ramification of central 
axon going to local vessels senseiehgjemsntys. and those neurons generate  
substance P, a peptide vasodilator. has local vasodilatory effects. 
substance p is vasodilator and increases permeability of capillary walls. 
so when you stimulate some sensory endings, for the most part endings 
that are pain sensors, locally within the same area to that ending will 
be the release of substance p. which will cause extravasation of fluid, 
opening of some arterioles (dilation) increasing blood flow locally. may 
be important during injury, crushing, occlusion etc. so if you scratch 
down on your skin, you see it gets white, then red, in part due to this 
mechanism of increased local blood flow.

reactive hyperemia, is what this is called. 
another local method of controlling blood pressure is autoregulation of 
blood flow, see back of handout p.9
some organs have strong autoreg, in others, it is relatively weak. what 
is it? mechanism through which even though blood pressure may increase, 
flow won't increase proportionately to driving force but will rather have 
a range of pressures through which flow is relatively independent (eg 
flow stays same despite pressure change.). how? look at two curves..one 
for normal and one for increased vasoconstriction. at a given flow, 
certain pressure needed. as pressure exceeds minimum, flow increases. 
vessels have some compliance, cross sectional area will increase with 
pressure, so flow increases faster than just directly proportional to 
pressure. with increased sympathetic tone, vessels are less compliant, 
and flow will slow down at a given pressure.
looking at mechanisms of autoreg, in spite of increasing pressure, flow 
may stay the same. now, carbon dioxide in brain is STRONG vasodilator. as 
CO2 levelgoes up, flow increases, washing out CO2, removing vasodilating 
factor
so there is a range over which flow is kept constant despite changes in 
pressure due to metabolic and mechanical factors. mechanical: Bayless 
mechanism:
increased translumenal pressure causes stretching of smooth muscle, 
causing calcium release and contraction eg vasoconstriction, which will 
narrow vessel and decrease the flow.


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