cardiac work, metabolism and CV loads Flashcards
name the layers of blood vessels
tunica intima
tunica media
tunica adventitia
how to calculate blood flow
blood flow (F) is directly proportional to pressure gradient between beginning / end of vessel (change in pressure = P1 - P2)
F is inversely proportional to resistance blood meets in vessel (R)
therefore F = change in pressure/R
R is directly proportional to viscosity of blood + length of vessel
R is inversely proportional to radius of vessel ^4
therefore R = (viscosity x length)/ r^4
what affects blood viscosity
-hematocrit (% of blood by volume of RBC’s in blood)
5x viscosity of water
directly proportional
increased hematocrit, increases viscosity, increases R, decreases F
- conc. of plasma proteins
1.5x viscosity of water
what are the factors affecting blood flow
blood viscosity
diameter of vessel
what are the effects of diameter of blood vessel on blood flow
directly proportional to F
indirectly proportional to R
changes in blood vessel diameter may be physiological (diverting blood to match metabolic needs) or pathological (atherosclerosis)
what are the types of blood flow
streamline (laminar) flow - when all particles in fluid flow parallel to wall of vessel, don’t move at same velocity where particles at center flow fastest and further away from center move slower, helps eliminate energy loss
turbulent flow - any disruptions to laminar flow caused by changes in velocity
mean linear velocity = flow/ cross sectional area
velocity is indirectly proportional to cross sectional area
therefore velocity of blood flows is highest in arteries / lowest in capillaries
what are the aims of changes in blood flow
increasing blood supply to active tissues
controlling heat loss
maintaining blood flow to vital organs
how to achieve changes in blood flow
changing CO (directly proportional)
changing diameter of blood vessels (especially arterioles which control F to tissues locally)
VC = increased R / decreased F
VD = decreased R / increased F
what is the molecular mechanism of vascular SM contraction/ vasoconstrictors
stretch caused by blood pressure opens ion channels which leads to a partial depolarization and partial contraction of SM
bayliss effect- vascular SM responds to stretch by contracting
physiological mediators can cause increased/decreased contraction as appropriate
local regulation of blood flow can be achieved by
secretion of vasoactive agents by endothelial cells/platelets
metabolite control of local blood flow (pre capillary sphincter of arterioles, which are the main site of peripheral resistance, is regulated by local metabolite conc. which controls blood flow)/ auto regulation
local hormones / autocoids
examples of endothelial/ platelet mediated vasodilators
NO / endothelium derived relaxing factor (EDRF)
endothelium derived hyperpolarizing factor (EDHF)
prostacyclin (PGI2)
examples of endothelial/ platelet mediated vasoconstrictors
tromboxane A2 / TxA2
prostaglandin H2 / PGH2
endothelins (1/2/3)
describe the effects of NO on blood vessels
short half life of a few seconds
must be generated continuously (triggered by increased stress on vessel wall by increased blood velocity)
causes short term changes in blood vessel diameter
main site of action is large diameter arterioles
what are the effects of vasodilator drugs (nitrovasodilators) on the heart
on capacitance vessels, decrease VR therefore decreasing preload
on resistance vessels, decrease ABP therefore decreasing afterload
both these effects decrease cardiac metabolism + oxygen demand and may relief coronary spasm
describe the effects endothelins and prostaglandins on blood vessels
ET-1 is the most potent and causes very strong vasoconstriction (mainly in veins)
platelets release tromboxane A2 causing vasoconstriction + increased platelet aggregation
endothelium releases prostacyclin (PGI2) causing vasodilation + decreased platelet aggregation
balance between thromboxane and prostacyclin maintains localized blood clots, preventing excessive extension which maintains blood flow
define auto regulation of local blood flow
adjusting blood flow to tissues based on their metabolic activities so that blood flow remains constant in spite of any changes to ABP
what are the mechanisms of autoregulation of blood flow
myogenic autoregulation - bayliss effect/intrinsic contractile response of vascular SM to stretch, increased ABP increases blood flow initially but also causes stretch of wall of arterioles which results in contraction of SM leading to VC + decreased blood flow back to normal
metabolic autoregulation - increased tissue metabolism results in relaxation of arterioles + precapillary sphincters leading to increased local blood flow + vice versa
what is the mechanism of metabolic autoregulation
increased tissue metabolism leads to
- accumulation of vasodilator metabolites:
- CO2/ H+/ K+/ lactic acid in skeletal muscle/ adenosine in muscle/ histamine in injured tissue
- increased H+ conc. opens ATP-sensitive K+ channels on SM causing hyperpolarisation and relaxation/VD which increases blood flow
- decreased oxygen/ hypoxia + decrease in other nutrients needed to maintain vascular SM contraction
- hypoxia leads to opening of ATP sensitive K+ channels causing VD
- release of vasodilator PGs
- (except in pulmonary circulation where hypoxia causes constriction of pulmonary vessels
what are the mechanisms of systemic regulation of blood flow
occurs mainly in arterioles
hormonal/ humoral regulation
nervous control
what hormones are involved in the hormonal control of regulation of blood flow
local hormones/autocoids (mainly part of pathological events)
- histamine (VD)
- bradykinin (indirect VD)
- serotonin/ 5-HT (VC)
- endothelium derived mediators (NO/ PGI2 - prostacyclin/ endothelins)
systemic hormones
- renin angiotensin system
- ADH (vasopressor)
- adrenal medulla catecholamines
- ANP
what are the effects of the local hormone histamine
synthesized and stored in mast cells/ basophils/ skin/ lung/ gut
action is mediated via receptors H-1/2/3
H1 - mediates vascular actions, inflammatory response to trauma/ allergy
- increases capillary permeability in edema
- in severe conditions, leads to arterioles/ capillary dilation which reduces circulating volume (hypovolemia), causes hypotension and anaphylactic shock
H2 - controls gastric acid secretion
H3 - acts as a neurotransmitter in nervous system
what are the effects of the local hormone bradykinin
generated during inflammatory response
binds to endothelial cell receptors, increases production of NO (VD) therefore lowering BP
increases capillary permeability + attracts leukocytes
dilation of arterioles
increase in venule permeability
increases blood flow to actively secreting glands (sweat/ salivary/ exocrine pancreas)
most potential autocoid/ local hormone in pain responses
*inactivated by angiotensin converting enzyme (ACE)
what are the effects of the local hormone serotonin
contributes to inflammatory response
VC of large arteries/ veins
increased permeability of venules
platelet released 5-HT causes local VC, limits blood loss at site of injury
5-HT released from argentaffin cells in intestine contribute to (local) regulation of blood flow
5-HT in cerebral circulation, induces arterial vasospasm (vessel narrows, blocking blood flow), associated with onset of migraines + response to subarachnoid hemorrhage
what are the effects of the systemic renin-angiotensin system
renin hormone is secreted by the kidney if
- ABP falls/ hypotension
- ECF volume is decreased/ hypovolemia
renin splits plasma angiotensinogen releasing AgI (inert) + AgII, catalyzed by angiotensin-converting enzyme/ ACE
ACE is bound to endothelial cells
angiotensinases rapidly inactivates AgII in blood
AgII, potent VC, released when ABP falls very low, acts on AT1 receptor
actions of AT1 receptor include:
- direct pressor/ VC via receptors on vascular SM
- indirect pressor/ VC effect by promoting formation of endothelial VC’s (ET-1 / TxA2)
- potential ion of sympathetic NS activity
- stimulates aldosterone synthesis in adrenal cortex (increases Na + water reabsorption from kidney which increases blood volume)
- increases ADH secretion from posterior pituitary gland, inducing thirst response/ dispogenic action (drink more, increase blood volume)
what are the effects of the systemic hormone ADH
potent VC, on systemic + peripheral arteries
reduces urine formation by kidney (more water is reabsorbed therefore decreasing volume of urine)
formed in hypothalamus, stored in posterior pituitary gland
released into circulation when:
- osmotic pressure of blood is increased (dehydration/ high salt intake)
- reduced stimulation of atrial B receptors (discharge during atrial diastole) (hypovolemia)
what are the effects of the systemic adrenal medullary hormones
noradrenaline has more significant effect on circulatory function than adrenaline (VC)
stimulation of B1 receptors in heart = +inotropic (force of contraction) / +chronotropic effect (rate of contraction)
stimulation of a1 receptors in blood vessels = VC
stimulation of a2 receptors in peripheral circulation = VC
stimulation of B1/B2 receptors in blood vessels = VD
what are the effects of the systemic hormone ANP
when ECF volume increases, VR increases causing stretch of atrial stretch receptors, ANP gets released
ANP regulates blood volume/ pressure
potent diuretic (increased water in urine) + natriuretic (increased Na in urine) effect on kidney = decreased circulatory volume
dilates resistance (decreases ABP) + capacitance (decreases VR) blood vessels
how does the ANS control peripheral circulation
SNS
- VC mediated by a1 receptors (found mainly in peripheral blood vessels)
- skeletal muscle/ coronary blood vessels have some B1/B2 receptors that can cause VD when stimulated
PNS
- no parasympathetic nerve supply to most of peripheral circulation
- PNS activation = VD + erection in genitalia
- VD in pancreas/ salivary glands, increases secretions (rest and digest)
what are the secondary causes of HT
renal disease (increased activity of RAAS)
pheochromocytoma (increase catecholamines secretion)
conn’s syndrome (increases adrenal cortex aldosterone secretion)
what are the 2 types of atherosclerosis and the differences between them
hyaline atherosclerosis - associated with benign HT, lesion is caused by leakage of plasma components into vessel wall
appearance = homogenous pink material + increased ECM production by SM
hyperplasticity atherosclerosis - associated w/ malignant atherosclerosis, fibrinoid deposits, necrotising arteriolitis
appearance = concentric laminations of SM + reduplicated basement membrane
what are the other vascular disorders associated with HT
aortic dissection
subarachnoid hemorrhage
intracerebral hemorrhage
