Vascular Physiology Flashcards
where in the CV system does BP decrease?
from LV to RV (systemic)
from RV to LV (pulmonary)
what is the equation for mean arterial pressure?
diastolic BP + 1/3 pulse pressure (difference between systolic and diastolic)
how can BP be reduced medically?
modifying TPR
define BP
circulation of fluid contained within a space of definite volume
how do arterioles regulate blood flow?
intrinsic - local conditions surrounding blood vessels
extrinsic - nervous system input
what is the sympathetic regulation of blood vessels?
nerve terminals release neurotransmitters acting on vascular smooth muscle to induce vasoconstriction or vasodilation
name 3 signalling molecules responsible for vasoconstriction
norepinephrine
ATP
neuropeptide Y
name 2 signalling molecules responsible for vasodilation
vasoactive intestinal peptide (VIP)
nitric oxide
name the factors that alter vascular resistance
vascular viscosity
blood vessel length (increased length = increased resistance)
blood vessel radius
what increases after vasodilation in arterioles?
capillary pressure
what are some of the local controls of arterioles?
changes in O2, CO2, cellular metabolites dilate arterioles (active hyperaemia)
blocking blood flow induces reactive hyperaemia
flow autoregulation: flow through vessels releases molecules regulating blood vessel diameter
what is blood flow determined by?
pressure gradient (high -> low)
TPR
what are the controlled variables in the central control of BP?
CO
TPR
local controls
capillary fluid shift
what happens in the brain during BP control? (increase)
baroreceptor input to nucleus tractus solitarius (NTS) at a2 receptors
vagal nucleus activated producing ACl reducing CO
bulbar circulatory centres inhibited reducing noradrenaline, dilating blood vessels
what happens in the brain during BP control? (decrease)
baroreceptor input goes to NTS at b1 receptors
vagal nucleus inhibited reducing ACl production increasing HR
bulbar circulatory centres activated producing noradrenaline constricting veins increasing force/flow
what are the risk factors for hypertension?
age
obesity
salt-heavy diet
sedentary lifestyle
explain the structural changes occuring in vessels with hypertension
loss of elasticity
arteriole - arteriolosclerosis
artery - arteriosclerosis
endothelial lining damage
collagen deposition and calcification
vessel layer overstretching
what are the causes of secondary hypertension?
renal hypertension
pheochromocytoma
what can chronic hypertension lead to?
atherosclerosis
stroke
MI
heart/renal failure
retinopathy
give some examples of beta adrenoreceptor blockers and explain the mechanism
propranolol (b1/b2), atenolol (b1)
competitive reversible antagonists
lower BP by blocking sympathetic tone on heart and reducing renin released from kidney
also lowers HR, SV and CO
what are the side effects of beta adrenoreceptor blockers?
exacerbates asthma (b2 block)
intolerance buildup
hypoglycaemia
vivid dreams
give some examples of alpha adrenoreceptor blockers and explain their mechanism
phentolamine (a1/a2), doxazosin/prazosin (a1)
competitive reversible antagonists lowering BP and PR by decreasing sympathetic tone in arterioles (a1)
what are the side effects of alpha adrenoreceptor blockers?
postural hypotension (loss of sympathetic venoconstriction)
reflex tachycardia (via baroreceptors)
give some examples of ACE (angiotensin converting enzyme) inhibitors and explain their mechanism
capropril/enalapril (-pril suffix)
inhibits renin-angiotensin-aldosterone system (RAAS) which converts angiotensin I into active angiotensin II
explain the actions of angiotensin II
raises BP (vasoconstriction)
reduces blood volume through aldosterone release (reduced renal reabsorption of Na and water)
what are the side effects of ACE inhibitors?
sudden fall in BP on first dose
persistent irritating cough (reduced bradykinin breakdown)
what are the subtypes of angiotensin receptors and what medication can target one of them?
AT1 and AT2
AT1 mediates vasoconstriction and aldosterone release from AT2
AT1 blockers - losartan/candesartan
(side effects better than ACE inhibitors)
name an example of a diuretic and explain their mechanism
bendroflumethiazide (a thiazide)
lowers BP by reducing blood volume (reducing renal reabsorption of Na and water)
small vasodilator action reduces PR
what is the side effect of diuretics?
reduced K+ plasma concentration
what are the 3 types of Ca channel blockers? give an example of each
dihydropyrodines (amlodipine)
phenylalkylamines (verapamil)
benzothiazepines (diltiazem)
how do L-type voltage operated Ca channels work?
open on membrane depolarisation allowing Ca entry into cardiac and vascular smooth muscle
blocked by Ca channel blockers
explain the mechanisms of Ca channel blockers
reduces BP by blocking Ca entry into vascular smooth muscle (induces vasodilation and reduces PR)
reduces CO by blocking Ca entry into cardiac muscle (lowers HR)
what conditions must be met for Ca channel blockers to work?
must have allosteric modulators bound to allosteric site to reduce probability of channel opening at a given voltage
what are the side effects of Ca channel blockers?
headache (cerebral vasodilation)
constipation (relaxed GI smooth muscle)
heart block (low Ca reduces contractility of heart)
cardiac failure
what kind of input does the vasomotor nerve provide and what does it do?
sympathetic input
vasoconstricts blood vessels
what is atherosclerosis?
the hardening of blood vessels involving plaque formation due to endothelial disruption
what are the general risk factors for vascular endothelial damage?
smoking
high shear stress
infection
diabetes
explain the formation of FOAM cells in atherosclerotic plaques
damage to vascular endothelium causes LDLs to diapedeses into cell where they oxidise
this promotes monocyte receptors on t-intima surface
monocytes enter and become macrophages
LDL + macrophage = FOAM cell
what is the action of FOAM cells acting on the tunica media?
FOAM cells release IGF promoting SM cells from t-media to enter t-intima
SM cells produce collagen in the t-intima
what occurs in atherosclerotic plaques to cause inflammation?
FOAM cells release chemokines to recuit more monocytes
when FOAM cells die, their lipid debris recruits lymphocyes and pro-inflammatory factors
T cells adhere to monocytes and produce inferferon gamma to promote inflammation
what occurs in unstable fibrous plaques?
fibrous cap thins due to oxidant and stress and eventually ruptures
thrombus forms which can cause intraplaque haemorrhage, vessel occlusion or MI
what is cholestorol essential for?
cell membrane incorporation
maintaining membrane fluidity and permeability
steroid and fat-soluble vitamin production
what is the role of the liver in terms of cholestorol?
monitors cholestorol levels and regulates them through synthesis, absorption and bile secretion
(drugs to treat hyperlipidaemia target this process)
what is cholestorol carried around the bloodstream in?
lipoproteins
what is contained in a lipoprotein?
lipids - cholestorol, triglycerides, phospholipids
apoproteins - unique metabolic functions (one or more per protein)
name the 5 different lipoproteins?
chylomicrons
VLDL
IDL
LDL
HDL
what is the function of chylomicrons?
carries triglycerides from intestines to liver/muscle/adipose
what is the function of VLDL’s?
carry newly synthesised triglycerides from liver to adipose
what is the function of LDL’s?
cholestorol resevoir
taken up via LDL receptors by endocytosis
what is the function of HDLs?
absorb cholestorol released by dying cells
reverse transport - return cholestorol to liver
explain the exogenous pathway of cholestorol
intestine -> chylomicron -> if liproprotein lipase present: adipose, if not: chylomicron remnant -> remnant receptor on liver -> liver
explain the endogenous pathway of cholestorol transport
liver -> VLDL -> capillary -> if LDL: adipose, if not: IDL -> liver -> hepatic lipase turns IDL into LDL -> peripheral tissue
what occurs in the liver and capillaries in hypercholestorolaemia?
lowered LDL receptors in liver means more VLDL enters capillaries, resulting in higher IDL than LDL in tissues
what are the signs of familial hypercholestorolaemia?
xanthomas (fatty cholestorol deposits in skin)
xanthelasmas (fatty deposits in eyelids)
arcus senilis (white ring around cornea)
what are the common causes of hypercholestorolaemia?
high circulating cholestorol and triglycerides (primary)
diabetes, alcoholism, hypothyroidism, liver disease, drugs, diet (secondary)
give examples of statins and explain their mechanism of action
simvastatin/pravastatin/rosuvastatin
competitive inhibitors of rate limiting step in cholestorol biosynthesis
decreases cholestorol levels and stimulates LDL receptor up-regulation
(most effective at night)
what is the main difference between selective and non-selective alpha adrenoreceptor antagonists?
selective - no effect on HR or CO
explain the main characteristics of lipids and name the main types
soluble in organic solvents and insoluble in water
cholestorol, triglycerides, phospholipids
name 3 things cholestorol produces or is a precursor for
vitamin D
bile acids
steroid hormones
describe the structire of lipoproteins
spherical shaped
centre core of hydrophobic lipids (triglycerides)
surface layer of polar components (phospholipids/proteins)
what are apolipoproteins
amphiphilic compounds with a hydrophobic region interacting with a lipid core to provide structure, and a hydrophilic region acting with aqueous environment
what is the function of apolipoproteins?
form lipoproteins by acting as ligands for lipoprotein receptors
activators/inhibitors of enzymes in lipoprotein metabolism
