Cardiovascular Physiology Flashcards
what is cardiac infarct?
formation of dense wedge-shaped block of dead tissue in heart muscle following interruption to blood supply
what is single circulation?
blood flows through heart once during each trip around body
what is double circulation?
blood flows from heart to lungs for gas exchange then back to heart to be re-pressurised before flowing to rest of body- flows through heart twice
what blood vessels take blood away from heart?
arteries
what blood vessels have highest blood pressures?
arteries
what artery takes blood away from the heart? (systemic circulation)
aorta
what does blood return to the right side of the heart via?
superior and inferior vena cava
what vessel carries blood from heart to lungs?
pulmonary artery
what returns oxygenated pulmonary blood to left atrium?
pulmonary veins
where is the heart located?
within pericardial sac
what is the lower surface of the pericardial sac attached to?
diaphragm
what holds the cardiac valves?
the annulus fibrosus
what forms the AV valves?
thin flaps of tissue joined at the base of the connective ring
what do the AV valve flaps connect to?
the chordae tendinar- collagenous tendons tethered to papillary muscle
what is the role of the chordae tendinae?
prevent AV valves from being pushed back into atrium
what is the mitral valve?
AV valve separating LA from LV
what is the tricuspid valve?
AV valve separating RA from RV
where is the aortic valve?
between left ventricle and aorta
where is the pulmonary valve?
between right ventricle and pulmonary artery
what part of the SL valves stops blood from flowing back into ventricles?
both have 3 cup-like leaflets which snap closed when filled with blood trying to flow backwards
why don’t SL valves have chordae tendinae?
due to their shape they don’t need them
what is the 3 layer general structure of all blood vessels (except capillaries)?
tunica intima, tunica media, tunica adventitia
what form the tunica intima?
thin layer of endothelial cells and elastic connective tissue
what forms the tunica media?
dense population of smooth muscle cells organised concentrically with bands/fibres of elastic tissue
what makes up the tunica adventitia?
collagenous extracellular matrix containing fibroblasts, blood vessels, nerves
function of the tunica adventitia?
add rigidity and form to the blood vessel
why do large elastic arteries have a large tunica media?
to expand and recoil during ventricular contraction and relaxation, smoothing the pressure changes so vessels can temporarily store energy
how close to a capillary are almost all cells in the body?
within at least 10µm
why do venules and veins have valves?
prevent blood flowing backwards
relative thickness of venule/vein walls?
thin
why do venules and veins have a low resistance?
large cross-sectional area
how much of the blood is held in veins?
about 2/3
can veins contract?
only some
what is the function of venoconstriction?
aids venous return thereby helping to maintain cardiac output
what is the supply of oxygenated fetal blood dependent on within the womb?
placenta
why does the fetus need adaptations that allow greater oxygen binding?
limited oxygen delivery to fetus from placenta
what are the adaptations of fetal haemoglobin?
high O2 affinity- can bind greater concentrations of oxygen, relinquishes bound oxygen at lower PO2
what are the adaptations in fetal circulation for oxygen delivery?
has shunts to ensure adequate supply of oxygenated blood to tissues most at risk of hypoxic damage- like brain
what are the fetal shunts?
ductus venosus, foramen ovale, ductus arteriosus
where does the ductus venosus shunt blood?
from placenta to fetal heart bypassing liver circulation
where does oxygenated blood from the placenta travel to?
through umbilical cord to right atrium of fetal heart
what shunts blood from right atrium to left atrium, bypassing the fetal lungs?
foramen ovale
what shunts blood from pulmonary artery to descending aorta, bypassing the fetal lungs?
ductus arteriosus
what is the cardiac cycle?
all of the events associated with blood flow through the heart during 1 complete heartbeat
what takes place in the cardiac cycle?
ventricles (L & R) contract synchronously (systole), whole heart relaxes (diastole) (ventricles refill), atria (L&R) contract together providing ventricles with more blood, ventricles contract again
what happens in atrial systole?
last 20% of filling of ventricles due to atria contracting- opens AV valves, forces additional blood into ventricles- called the atrial kick. small amount of blood forced backwards in venae cavae- can be seen as pulse in jugular vein of normal person lying with head and neck elevated about 30%
what is the atrial kick/boost?
the additional blood forced into the ventricles when the atria contract
what is isovolumetric contraction?
ventricular contraction without any change in ventricular volume- forces AV valves closed, pressure builds up in ventricles without changing ventricular volume
what are the phases of the cardiac cycle?
atrial systole, isovolumetric contraction, ventricular ejection, isovolumetric relaxation, late diastole
what happens in ventricular ejection?
as ventricles contract they generate enough pressure to open the SL valves, blood ejected into arteries, driven by pressure generated by ventricles. high pressure blood forced into arteries pushing low pressure blood that fills them further into the vasculature, ventricular blood enters aorta faster than it can leave so arterial pressure rises, large elastic arteries become distended with blood
what happens in isovolumetric relaxation?
ventricles begin to relax leading to rapid fall in ventricular volume and pressure, as ventricular pressure falls below aortic, small amount of blood flows backward and closes aortic valve- brief rise in arterial pressure (dicrotic notch), final 1/3 of ventricular blood flows away from heart against pressure gradient due to kinetic energy
what is the dicrotic notch?
brief rise in arterial pressure in isometric relaxation as aortic valve closes
what does stroke volume measure?
overall change in ventricular volume during phases 3 and 4 of cardiac cycle
what happens in late diastole?
both sets of chambers relaxed, ventricles begin to fill with blood passively before atrial systole and beginning of new cycle
what is the simplest direct method of assessment of heart function?
auscultation- listening through chest wall
how many audible sounds are there usually in auscultation? what causes them?
2- 1st from closure of AV valves, 2nd from closure of SL valves
what may be heard through auscultation in abnormal conditions?
3rd sound (gallops), clicking caused by abnormal valve movement, murmurs caused by blood leaking through incompletely closed valve- valvular incompetence
what does EMG stand for?
electromyogram
what is an EMG?
recording of electrical activity when muscle contracted - by placing 2 electrodes 2cm apart over biceps
what does EEG stand for?
electroencephalogram
what is an EEG?
recording of electrical activity relating to neuronal activity- by placing 2 electrodes on skull
what is an ERG?
electroretinogram- electrodes placed on eye to detect neuronal activity caused by light flashes
what is an ECG?
electrocardiogram- electrodes placed over heart to record electrical events coupled to mechanical events in cardiac cycle
what are the 2 major components of an ECG?
waves and segments- waves= deflections above and below baseline and segments= sections of baseline between 2 waves
what are the 3 main waves on a normal ECG?
P wave (corresponds to atrial depolarisation), QRS complex (trio of waves representing ventricular depolarisation), T wave (represent ventricular repolarisation)
why is atrial repolarisation not represented in a normal ECG?
it is masked by the QRS complex (ventricular depolarisation)
what interval is an accurate measure of heart rate in an ECG?
R-R interval
what usually causes long Q-T syndromes?
inherited channelopathies- mutations in myocardial Na+ and K+ channels
what is a cardiac pressure-volume loop?
plot of changes in pressure against changes in volume
what is the end diastolic volume?
volume in the ventricles after the atria contract and ventricle has finished relaxing- when maximal filling has occurred
what is the end systolic volume?
amount of blood left in the heart at the end of ventricular contraction
what does the width of the cardiac pressure-volume loop represent?
stroke volume
what does the area within the cardiac pressure-volume loop represent?
the ventricular stroke work
why is left ventricular emptying impaired in aortic stenosis?
high outflow resistance caused by reduction in valve orifice area when it opens, causes large pressure gradient to occur across aortic valve during ejection so peak systolic pressure within ventricle greatly increased
what is contractility of the heart dependent on?
the degree to which myocytes are stretched
what is EDV?
end diastolic volume
what is the end diastolic volume?
the amount of blood left at the end of the cardiac filling phase
what is ESV?
end systolic volume
what is the end systolic volume?
amount of blood left at the end of the ejection phase
what is preload?
the end diastolic pressure in the ventricles- measure of cardiac filling
what is afterload?
peripheral resistance
what happens in peripheral resistance and heart rate are kept constant and preload (cardiac filling) is increased?
CO increases due to increased stroke volume, left ventricular and aortic pressures increase as greater volume of blood being ejected against same resistance, end diastolic volume increased as ventricles stretch, force of contraction increases in response to stretch
what is the Frank-Starling mechanism?
when the heart increases the force of contraction in response to elongation or stretch
what is the Starling Law of the heart?
the energy of contraction is a function of the length of the muscle fibre
what happens in heart rate and filling pressures are kept constant and peripheral resistance (afterload) is increased?
heart finds it harder to force blood through system, aortic and left ventricular pressures increase, initially SV and CO fall, less complete emptying of ventricles in ejection increases ESV, EDV increases- which increases CO so CO recovers
what is the Anrep effect?
an autoregulation method in which myocardial activity increases alongside afterload
what causes the Anrep effect?
sustained myocardial stretch activates tension dependent Na+/H+ exchangers bringing Na+ ions into the sarcolemma. this reduces the Na+ gradient, stops the sodium-calcium exchanger from working effectively so Ca2+ ions accumulate in the sarcolemma and are uptaken by SERCA pumps, CICR from the SR is increased on stimulation of the cardiac myocyte from an AP so increased fore of contraction of cardiac muscle- increases SV and CO
where do the nerves that innervate the heart originate from?
cardiovascular centre in medulla oblongata
sympathetic influences on the heart?
cardiac accelerator nerves from thoracic region of spinal cord -> SAN, AVN and most portions of myocardium; impulses in cardiac accelerator nerves release noradrenaline- binds to beta1 receptors on cardiac muscle fibres, increases frequency of contraction at SAN and contractile fibres in ventricles
parasympathetic influences on the heart?
reach heart via right and left vagus nerves. release ACh which acts on muscarinic receptors at the SA and AV nodes and on atrial myocardium. ACh reduces heart rate, little or no effect on contractility of ventricles in most species
endocrine influences on the heart?
some hormones affect SAN and contractility of ventricles- most common is adrenaline released from medulla of adrenal gland- also acts on cardiac beta1 receptors to increase frequency and force of contraction, maintaining neurally-mediated sympathetic effects
what is the pacemaker potential?
the spontaneous slowly increasing potential of the SA node
how do sympathetic and parasympathetic influences affect pacemaker potential to change heart rate?
sympathetic increases the pacemaker slope- takes less time to reach threshold value- parasympathetic does the opposite
what is Darcy’s law of flow?
flow in steady state is linearly proportional to pressure difference between 2 points and inversely proportional to resistance
what is the perfusion pressure?
pressure difference between the arteries that supply a region and veins that drain it
what is vascular resistance?
resistance in circulation
what is vascular resistance inversely proportional to?
blood flow
what is blood flow equal to in the cardiovascular system?
perfusion pressure/vascular resistance
relationship between CO, BP and vascular resistance?
CO = BP/vascular resistance
what determine cardiac output?
amount of blood pumped out of each ventricle per beat (SV) and how fast it is pumped out (heart rate)
what is relationship between CO, SV and heart rate?
CO = SV x heart rate
what causes vascular resistance?
friction against vessel wall, radius of tube, length of tube, viscosity of fluid
what determines blood viscosity and how can it be calculated?
ratio of RBCs to plasma, can be calculated by haematocrit
what is the Fahraeus-Lindqvist effect?
viscosity of fluid decrease with decrease in diameter of tube it travels through
what causes the Fahraeus-Lindqvist effect?
erythrocytes move to centre of vessel leaving plasma at wall of vessel. so effective viscosity of cell-free layer lower than tat of whole blood, acts to reduce resistance to blood flow
what variable affects vascular resistance the most?
vessel radius
what is vasomotion?
changes in vessel diameter
what is vasoconstriction?
decrease in vessel diameter
what is vasodilation?
increase in vessel diameter
what characterises sympathetic nerves?
short pre-ganglionic fibre and long post-ganglionic fibre
pre-ganglionic neurotransmitter in sympathetic nerves?
ACh
post-ganglionic neurotransmitter in sympathetic nerves?
noradrenaline
effect of sympathetic nervous system on total peripheral resistance?
maintains it by tonically causing vasoconstriction
effect of noradrenaline on blood vessels?
causes vasoconstriction
which is more innervated, arterioles or venules?
arterioles
what is the result of increased arteriole constriction?
increased total peripheral vascular resistance and increased arterial blood pressure
result of increased constriction of venules?
increase in venous return
what is the most efficient method to dilate a blood vessel?
to withdraw/inhibit sympathetic tone
effect of adrenaline on blood vessels?
constricts some circulations and dilates others- mostly vasoconstriction in peripheral circulations to maintain ABP, may cause dilatation in skeletal muscle- need more O2 and nutrients for fight or flight
role of endothelium in promoting changes in peripheral vascular tone?
vasodilator arterial response to ACh changes to vasoconstrictor response if endothelial lining rubbed away- ACh stimulates endothelium to produce nitric oxide- causes vasodilatation rather than ACh causing it directly
how is NO produced by endothelial cells?
cleavage from arginine by NO synthase
what regulates activity of NO synthase, what is the effect of this?
level of intracellular Ca2+-calmodulin complex- agents that promote extracellular Ca2+ entry into endothelial cells increase rate of NO synthesis
what is a sphygmomanometer used for?
to estimate arterial blood pressure
what causes Korotkoff sound?
pressure cuff compresses artery, blood squeezing through causes Korotkoff sound
what is the systolic pressure recorded as when using a sphygmomanometer?
the pressure at which Korotkoff sound first heard
what is the diastolic pressure recorded as using a sphygmomanometer?
the pressure at which Korotkoff sound disappears
how is mean arterial blood pressure calculated?
diastolic plus a third of the difference between systolic and diastolic
what is arterial stiffness?
measure of the rigidity of blood vessels
what causes blood vessels to become rigid?
deposits of calcium and collagen with ageing and disease
what does increased pulsatility signify?
increased vascular resistance
simplest reflex arc model?
sensor sends information to brainstem via afferent pathways, brainstem integrates information and sends commands to effector organs via efferent pathways
what sensors control blood pressure?
baroreceptors and chemoreceptors
what do arterial baroreceptors respond to?
changes in ABP
what are the 2 types of arterial baroreceptors?
carotid and aortic baroreceptors
where is the carotid group of arterial baroreceptors located?
within carotid sinus at bifurcation of internal and external carotid arteries
where is the aortic group of arterial baroreceptors located?
in the aortic arch
what do carotid baroreceptors do when stimulated?
send afferent information to brainstem (medulla) via carotid sinus nerves which join onto the glossopharyngeal nerve
what are the centres within the cardiovascular centre?
cardiac centre, vasomotor centre
what are the regions within the vasomotor centre?
depressor and pressor region
what are the regions within the cardiac centre?
cardioacceleratory region and cardioinhibitory region
what do aortic baroreceptors send information to the brainstem via?
aortic nerve which joins onto vagus
why are baroreceptor reflexes necessary?
fall in blood pressure will reduce perfusion of oxygenated blood to tissue, increase in blood pressure can cause damage to fragile circulations such as in brain, can lead to atherosclerosis
what are the 2 baroreceptor reflexes?
carotid sinus reflex and aortic reflex
function of carotid sinus reflex?
helps maintain normal pressure in circulation perfusing brain
function of aortic reflex?
governs systemic ABP homeostasis
how does baroreceptor cardiac reflex work?
tonically active so send continuous bursts to brainstem in phase with ABP pulse, when individual baroreceptor fibre stretched by increased MAP, frequency of APs increased, stimulates cardiac inhibitory centre, increasing efferent parasympathetic discharge and inhibits acceleratory centre, reducing efferent sympathetic discharge. end result= decrease in heart rate and force of ventricular contraction
how does baroreceptor vasomotor reflex work?
increased rate of APs to vasomotor centre results in reduced sympathetic impulses along sympathetic fibres which cause peripheral vasoconstriction to cause fall in arteriolar and venomotor tone
result of fall in ABP on outflow from carotid and aortic baroreceptors?
decreased frequency of discharge- causes ABP to increase
effect of phenylephrine?
acts on α1-adrenergic receptors to cause peripheral vasoconstriction, and thus an increase in arterial BP- triggers fall in heart rate by cardiac baroreflex
how do vasodilators cause increased heart rate?
cause fall in BP, cardiac baroreflex triggers increase in heart rate
what is central-resetting of the baroreflex?
when rise in arterial BP not accompanied by fall in heart rate because baroreflex reset centrally to operate around higher pressure, stimulation of cardiovascular centre
what is peripheral resetting of the baroreflex?
when pressure raised in sustained manner, stimulus-response curve shifts to right so set point of baroreflex changes
why is peripheral re-setting needed?
allows greater resting BP without sustained increase in baroreceptor discharge (which would use a lot of energy)
what is an example of peripheral resetting?
at birth when ABP is changed from fetal to newborn levels
change in baroreceptor sensitivity with age?
becomes less sensitive with increasing age
types of arterial chemoreceptor?
carotid and aortic
how do carotid arterial chemoreceptors transmit information?
send afferent fibres to brainstem via carotid sinus nerves which join onto glossopharyngeal nerve
how do aortic chemoreceptors transmit information?
send afferent fibres to brainstem via aortic nerve which joins onto vagus nerve
what are glomus cells?
islands of type 1 cells which make up peripheral chemoreceptor tissue, act as oxygen sensors
properties of glomus cells?
lots of mitochondria, dark vesicles containing peptides needed for chemotransduction
what is hypoxaemia?
fall in arterial PO2
effect of hypoxaemia on carotid and aortic chemoreceptors?
output of both increases
what is the chemoreceptor threshold/set point?
PO2 at which peripheral chemoreceptor discharge starts
what is peripheral chemoreceptor re-setting?
a shift of peripheral chemoreceptor discharge curve towards lower or high PO2
what is an example of peripheral chemoreceptor re-setting?
that which occurs during transition from fetal to post-natal life- failure for this to occur can contribute to SIDS
why do fetal chemoreceptors have a lower set point than adult ones?
PO2 of fetal blood is much lower
cardiovascular response to hypoxia?
increased heart rate, increased blood flow to most circulations (including brain, heart, adrenal glands), vasodilation in peripheral circulations
experiment to determine interaction between ventilatory and cardiovascular responses mediated by peripheral chemoreceptors, to hypoxia?
induced hypoxia in dogs with spontaneous breathing and dogs with mechanical ventilation. dogs with spontaneous breathing = increased heart rate and decreased femoral vascular resistance. mechanically ventilated dogs= couldn’t hyperventilate, hypoxia induced fall in heart rate and increase in femoral vascular resistance
what is the interaction between ventilatory and cardiovascular responses mediated by peripheral chemoreceptors, to hypoxia?
hypoxia elicits primary chemoreflex cardiovascular responses (fall in heart rate, increase in peripheral vascular resistance), which are modified by hyperventilation to secondary chemoreflex cardiovascular responses (increase in heart rate and decrease in peripheral vascular resistance
why does hyperventilation cause secondary chemoreflex cardiovascular responses to hypoxia?
stretch receptors in lungs increase afferent discharge to brainstem- influences cardiac and vasomotor centres to inhibit vagal discharge to heart and sympathetic outflow to peripheral circulations
why does fetus make breathing movements in utero?
to practice for after birth and develop intercostal muscles and alveoli- doesn’t uses this for oxygenation as obtains oxygen via placenta
effect of hypoxia on fetus?
ceases to make breathing movements- wasted energy and don’t provide O2, primary chemoreflex cardiovascular response: heart rate reduction, increased vascular resistance
what 2 important concepts were illustrated by placing dog hearts with high output pumps and reducing/increasing pumping capacity?
heart is necessary to maintain CO, heart doesn’t normally limit CO
why can’t the heart increase the arteriovenous pressure gradient beyond a certain point?
at a certain negative pressure in the veins venous collapse limits venous return and hence CO
what is the main determinant of CO?
mean systemic filling pressure
how can MSFP be increased?
by extra filling or by constricting filled volume
what is the unstressed volume of the circulation?
volume of blood that just fills circulation without stretching the vessel walls
why does movement of blood cause a steeper rise in pressure in arteries than veins?
arteries are less compliant
how can CO be quantified?
(ABP-RAP)/TPR
what can often be omitted from the CO equation?
RAP as it is often very small compared to ABP
what is the key point of control of CO?
RAP- increased MSFP would increase RAP which would increase SV and therefore CO to return RAP close to 0
why does blood loss decrease BP?
decreases MSFP so decreases maximum CO
what determines MSFP?
volume of blood and mean tension in blood vessel walls
what is the RAP equivalent to at venous return of 0?
the MSFP
effect of sympathetic venoconstriction on MSFP and venous return curve?
increases MSFP, shifts venous return curve higher at any RAP
how is venous return calculated?
VR= MSFP - RAP
if the heart can’t increase CO, what will the effect of an increase in MSFP be?
increased RAP but no CO increase, increased capillary pressures resulting in oedema
what is circulatory shock?
if the CO is inadequate to supply sufficient metabolic substrates for aerobic respiration to all of the tissues
typical signs of circulatory shock?
hypotension, tachycardia accompanying signs of reduced organ perfusion such as low urine output and loss of consciousness
cause of hypovolaemic circulatory shock?
failure of CO due to severe loss of circulating volume
cause of cardiogenic circulatory shock?
cardiac pathology
cause of distributive circulatory shock?
a severe fall in vascular tone
what is the principle variable controlled by the cardiovascular system?
mean arterial blood pressure
how can blood flow to individual tissue be regulated?
controlling local arteriolar resistance
principle determinants of ABP?
CO and total peripheral resistance
what is pulse pressure?
difference between systolic and diastolic pressures
what can cause increased pulse pressure?
if arterial compliance reduces, if blood can flow aways faster in diastole
what are the 2 separate mechanisms for regulating ABP?
regulating CO and regulating TPR
what are the 3 mechanisms the body uses to monitor blood pressure?
high pressure baroreceptors, low pressure baroreceptors, arterial chemoreceptors
what are the 2 high pressure sites where mechanoreceptors sense ABP?
carotid sinus and aortic arch baroreceptors
mechanism of mechanoreceptor stimulation?
stretch sensitive nerve endings intermeshed with elastic lamellae in regions with relatively little collagen and smooth muscle so stretch triggers increased activity in baroreceptor fibres of glossopharyngeal nerve and vagus.
what nerve do the baroreceptor fibres in the carotid sinus belong to?
glossopharyngeal nerve
what nerve do the baroreceptor fibres in the aortic arch belong to?
vagus nerve
what do the baroreceptor fibres from the carotid sinus and aortic arch stimulate?
neurons in the nucleus tractus solitarius that inhibit the vasomotor centre
experiment to prove different sensitivities of different baroreceptor fibres to BP?
carotid sinus of dog B connected into circulation of dog A, when A injected with noradrenaline triggered almost immediate reflex fall in BP of dog B
effect of denervation of arterial baroreceptors? what does this suggest?
ABP much more variable but mean ABP stays relatively constant- suggests mean ABP is regulated by other mechanisms
where are chemoreceptors found?
carotid and aortic bodies and in medulla
role of arterial chemoreceptors in ABP control?
when BP is very low or PO2 significantly reduced aortic and carotid bodies detect low O2 delivery and medullary chemoreceptors detect high arterial CO2, afferent signals form carotid aortic bodies travel by glossopharyngeal and vagus nerves to the baroreceptors
where are the low pressure/cardiopulmonary baroreceptors?
low pressure areas of circulation: junctions of atria with the corresponding veins, in the atria themselves
role of the low pressure/cardiopulmonary baroreceptors?
long term control of ABP. detect RAP- if RAP is raised it suggests circulation is over-filled so heart can’t maintain low venous pressures, if RAP is low suggests CO is maximal for the current MSFP.
effect of denervation of low pressure baroreceptors and high presssure baroreceptors?
produces rise in mean ABP and increased variability seen with high pressure baroreceptor denervation
how do low pressure baroreceptors signal?
afferent signals travel via vagus nerve to nucleus tractus solitarius (NTS) in medulla and then to hypothalamus, where they influence secretion of ADH, sympathetic activity, thirst, sodium appetite. increased signaling with increase pressure, leading to increased fluid and sodium retention raising circulating volume and MSFP
why don’t common stresses on ABP regulation such as exercise. standing up, mild blood loss, cause detectable ABP drops?
they trigger feed-forward mechanisms to preserve ABP
how is drop in ABP prevented in exercise?
inputs to medulla from cortex, cerebellum and muscle + joint receptors
what pathways does the medulla control ABP via?
sympathetic and parasympathetic divisions of the ANS
what does sympathetic outflow from the medulla act on?
vasculature and the heart
what does parasympathetic outflow from the medulla act on?
only the heart
what is the sympathetic pathway from the medulla?
pathway from medulla to spinal cord (bulbospinal) activates pre-ganglionic pathways which synapse at nicotinic synapses with postganglionic sympathetic neurons within prevertebral and paravertebral sympathetic ganglia. these run with large blood vessels to innervate muscular arteries and arterioles and veins
how does increased sympathetic activity to vasculature cause vasoconstriction?
action of noradrenaline on α1 receptors
effect of arteriolar vasoconstriction?
increases TPR
effect of venoconstriction?
increases MSFP
how does sympathetic activity to blood vessels cause some redistribution of blood flow?
vasculature of some organs receives little sympathetic vasoconstrictor innervation- such as heart and brain which show little vasoconstriction
what does resting sympathetic vasoconstrictor nerve tone allow?
allows inhibition of sympathetic activity when ABP needs to be reduced
effect of spinal cord damage above T1 on BP?
severe and rapid drop in BP as abolishes resting sympathetic outflow
what is the sympathetic innervation of the chromaffin cells of the adrenal medulla?
preganglionic sympathetic fibres in the splanchnic nerves
effect of chromaffin cell activity?
stimulates adrenaline release into the circulation which acts on the heart and vasculature in broadly similar manner to direct sympathetic innervation via α1 receptors
tissues with more β2 than α1 receptors?
coronary blood vessels and skeletal muscle
effect of β2 receptors?
trigger vasodilatation thereby increasing coronary and skeletal muscle blood flow
what receptors does noradrenalin from sympathetic nerves act on primarily?
α1 receptors
what cardiovascular tissues does the vagus nerve innervate?
the SAN, AVN and cardiac conducting system
what is an example of one of the rare parasympathetic pathways with tonic activity?
vagal supply to the heart
effect on heart rate of using atropine?
atropine inhibits the vagus, leads to significant acceleration of heart rate
what is responsible for small adjustments of TPR?
sympathetic vasoconstriction of blood vessels
what is responsible for maintaining ABP in the short term when there is a significant fall in TPR?
sympathetic venoconstriction to increase MSFP along with reduced vagal and increased sympathetic stimulation of the heart to increase heart rate and contractility- increases CO
what is hypertension?
excessively high arterial BP- more than 140/90 mmHg in humans
what problems are caused by hypertension?
overwork of heart and damage to blood vessels (atherosclerosis) -> cardiac failure, cardiac arrhythmia and ischaemic damage to organs (stroke, myocardial infarction)
what is atherosclerosis?
build-up of inflammatory lipid deposits under endothelium of blood vessels
problems caused by atherosclerosis?
narrow blood vessels restricting flow, endothelial damage promoting clotting can cause local block or distant blockage (embolism), weaken blood vessel walls leading to aneurysm + rupture
risk factors for atherosclerosis?
hypertension, diabetes, smoking, obesity
what is angina pectoris?
pain caused by cardiac ischaemia when atherosclerosis is affecting coronary arteries
what is the normal response of muscle to increased workload?
hypertrophy- enlargement of the cells of the heart -> increase in cardiac mass
what does exercise induce in the heart? (long term)
eccentric hypertrophy where ventricular volume increases along with the muscle mass
what is concentric hypertrophy?
induced in heart by hypertension, heart muscle expands inwards reducing ventricular volume
3 major problems caused by concentric hypertrophy?
increased myocardial oxygen demand, diastolic dysfunction (cardiac filling + hence SV impaired), increased risk of cardiac arrhythmias
what can concentric hypertrophy progress to?
ventricular dilatation where the heart is unable to fully empty in addition to filling poorly
what is often measured as a proxy for CO?
VO2
what is used to calculate flow through a capillary bed downstream from a single arteriole?
difference between arterial and venous pressure/sum of the pre-capillary, capillary and post-capillary resistances - simplifies to 1/arteriolar resistance
how is local blood flow matched to local demand in general?
local control of arteriolar resistance- can be metabolic, myogenic or from vasoactive compounds released in paracrine fashion by capillary endothelium
role of central autonomic control of arteriolar resistance?
controls TPR to maintain constant mean ABP- can be neurogenic or endocrine control
what are the 2 broad intracellular control systems that the arteriolar smooth muscle tone control pathways converge on?
regulation of myosin-binding site of actin by caldesmon and regulation of MLC by phosphorylation
why is skeletal muscle the best studied vasculature?
rapid and enormous changes in metabolic rate occur under physiological conditions and are reproducible in experiments
changes that accompany increased metabolism/normal metabolism in reduced local blood flow, in all tissues? what do these changes promote?
reduced PO2, increased PCO2, decreased pH, increased adenosine, increased extracellular K+. promote vasodilatation of systemic arterioles (opposite effect of reduced PO2 and PCO2 in pulmonary circulation)
changes that accompany anaerobic metabolism? what do these changes promote?
decreased pH, increase lactic acid concentration. stimulate vasodilatation- appears to be direct effect of pH on smooth muscle
myogenic control of arteriolar resistance?
some vascular beds (e.g. brain, heart, kidney) respond to pressure changes by changing diameter to reduce change in flow. increased pressure increases resistance so flow increases less than expected. serves to maintain constant capillary pressure
why do brain and heart need constant capillary pressure?
to prevent oedema as have poor lymphatic drainage
why do kidneys need constant capillary pressure>
to regulate filtration pressures
myogenic and metabolic effect of increased arterial pressure?
causes vasoconstriction by myogenic mechanism and vasoconstriction as increased perfusion washes out local metabolites
when was the importance of the endothelium in regulating vascular response first noted?
when realised ACh could only dilate arteries when endothelium intact
what is the sign from endothelium to vascular smooth muscle?
NO
how does ACh (+bradykinin) stimulate the endothelium to stimulate vasodilatation?
stimulate NO production in endothelium by action of NO synthase on L-arginine in endothelium. NO is lipophilic, diffuses quickly, stimulates soluble guanylyl cyclase in vascular smooth muscle. cGMP dependent protein kinase then phosphorylates MLCK, inhibiting it
how does viagra work?
reduces cGMP breakdown enhancing vasodilator pathway
what does endothelium release?
NO and other vasodilator/vasoconstrictor substances, pro-coagulants, anti-coagulants, fibrinolytics, antibacterials, growth factors
net effects of endothelium under physiological conditions?
anticoagulant and vasodilatory
what is endothelial damage/dysfunction associated with?
raised vascular resistance, hypertensions, atherosclerosis, increased risk of clots
what may cause endothelial dysfunction?
diabetes, hypertension, smoking, atherosclerosis, hyperlipidaemias
how do β2 receptors work?
activated by circulating adrenaline. linked to Gαs which activates adenylate cyclase raising cAMP levels so activating protein kinase A (PKA) which phosphorylates MLCK reducing its activity hence reducing phosphorylation of MLC
what are eichosanoids?
arachidonic acid derivatives involved in clotting and inflammatory responses in blood vessels
what synthesises most eicosanoids?
enzyme cyclooxygenase- enzyme inhibited by some non-steroidal anti-inflammatory drugs
what type of molecule are prostaglandins?
eicosanoids
what is the function of PG-F?
vasoconstrictory
what is the function of PGs I, D, and E
vasodilatory
where are prostaglandins produces?
endothelium
effect of PGI2 (prostacyclin)?
causes vasodilatation and inhibits platelet aggregation. involved in inflammatory response and some changes in parturition. opposes action of thromboxane A2
what sort of molecule is thromboxane A2?
an eicosanoid
what is thromboxane A2 produced by?
platelets
effect of thromboxane A2?
vasoconstriction and platelet aggregation. important part of clotting response
effect of endothelial damage on PGI2/thromboxane A2 balance?
shifts balance in favour of thromboxane A2 so can lead to reduced blood flow and clotting
rationale behind using aspirin to prevent myocardial infarction?
aspirin irreversibly blocks COX-1 which is required to synthesis both thromboxane A2 and PGI2. since PGI2 synthesised in endothelial cells which have nuclei these can synthesise more COX-1 to produce more PGI2, whereas thromboxane A2 is produced by platelets without nuclei so production significantly diminished. so vasodilation promoted
primary role of capillaries in lungs, liver and kidneys (renal glomeruli)?
in lungs exchange of O2 and CO2, in liver passage of newly synthesised plasma proteins, in renal glomeruli bulk flow of water
what is the most common type of capillaries?
continuous capillaries
what do continuous capillaries allow relatively free passage of?
water and ions
which tissues have tight junctions between capillary endothelial cells?
brain and testes
what are sinusoidal capillaries, where are they found?
found in liver, have large gaps between cells as well as fenestrae to allow transendothelial passage of proteins
what do the fenestrae in fenestrated capillaries allow?
ion diffusion through as well as between cells
what does flow across capillary membrane depend on?
permeability of solute, surface area, concentration gradient
how does increasing number of capillaries perfused in a tissue increase the flow across the capillary?
increases the area for exchange
how can permeability of a substance across a capillary be changed?
endothelial cells can change shape in response to signaling molecules, widening interendothelial clefts
what does capillary concentration of a substance depend on?
rate of delivery into capillary and rate of extraction from capillary
what does interstitial fluid concentration of a substance depend on?
rate at which substance is used up in local tissue and rate at which it is extracted from capillary
driving forces for water movements across capillary wall?
hydrostatic pressure and osmotic pressure gradient
change in hydrostatic pressure from arteriolar to venous end of capillary?
drops along length of capillary as result of resistance and outward movement of water
what is the interstitial fluid composed of?
complex gel of proteoglycans and water within network of collagen fibres
what determines colloid osmotic pressure of capillary?
osmolarity of the plasma protein which can’t cross the capillary wall - includes albumin, globulins, fibrinogen
what does flow of fluid out of the capillaries depend on?
the net filtration pressure (difference between hydrostatic and colloid osmotic pressure), the colloid reflection coefficient, hydraulic permeability
what is the colloid reflection coefficient?
correction factor between 0 and 1 to account for any leakiness of the capillary to proteins
influences on the balance between hydrostatic and colloid osmotic pressures?
arterial blood pressure, venous pressure, resistance in the upstream arteriole, colloid pressure, leakiness of capillaries to proteins
relationship of capillary pressure to venous and arterial pressure?
closely follows venous pressure (must always be higher than venous pressure) but isn’t closely related to arterial pressure
effect of reduced ABP on capillary pressure?
reduced ABP may reduce capillary pressure- partly a direct result, partly due to increased sympathetic drive and arteriolar vasoconstriction
what is autotransfusion? why does this decrease the haematocrit?
process after blood loss which allows tissue fluid to buffer blood volume as reduced ABP results in reduced capillary pressure. means tissue fluid dilutes the blood
what is haematocrit?
concentration of blood cells
what prevents fluid from moving out of the initial lymphatics back into interstitial fluid?
inter-endothelial junctions between cells that behave as microvalves to allow fluid in but not back out
how much fluid leaves the capillaries and enters the lymphatic system each day?
2-4 litres
what is interstitial oedema? what causes this?
when fluid collects in the interstitium expanding the extracellular space. occurs if the rate of filtration of fluid out of the capillaries exceeds its removal by lymphatics
where is the swelling greatest in generalised oedema?
lower parts of the body due to effect of gravity on venous pressure
problems caused by oedema in systemic circulation?
increases difference between cells and capillaries so interferes with solute exchange, can starve cells of nutrients
problems caused by oedema in pulmonary circulation?
fluid can accumulate in alveoli interfering with gas exchange and decreasing lung compliance
what can cause localised oedema?
lymphatic blockage or increased capillary leakiness to proteins in inflammation, ischaemia reperfusion injury, head injury
what can cause generalised oedema?
most commonly congestive cardiac failure, also loss of colloid proteins in malnutrition or from kidneys in nephrotic syndrome
what constitutes ‘too high’ atrial pressure?
atrial pressure should be close to 0, if any higher impedes venous return and tends to raise capillary pressures
why is it possible to find symptoms of heart failure and hypertension in the same patient?
too low ABP which can’t be raised causes increased sympathetic drive, causes venoconstriction, arteriolar vasoconstriction and retention of fluid (with renal responses)- raises TPR and MSFP, causes atrial pressure to rise as CO can’t increase
causes of the symptoms of heart failure?
inability to adequately increase CO reduces exercise capacity and can induce fatigue, and the increased atrial pressure causes raised venous pressures, raised capillary pressures so oedema
oedema caused by right-sided heart failure?
peripheral oedema
oedema caused by left-sided heart failure?
pulmonary oedema
how can drugs relieve symptoms of heart failure?
lower MSFP and TPR- e.g. angiotensin converting enzyme inhibitors, diuretics, beta adrenergic blockers
what is Van’t Hoff’s equation?
osmotic pressure = osmolarity x gas constant x absolute temperature
what is the cardiovascular response to exercise?
17 fold decrease in local resistance- TPR drops and systemic mechanisms responsible for maintaining ABP and cardiovascular homeostasis by increasing CO (increase in heart rate and SV), also may partially oppose locally mediated vasodilatation in muscle
what is the main cause of increased blood flow to muscles in exercise?
functional hyperaemia
what are the 2 phases of functional hyperaemia?
1= blood flow increases very rapidly after initiation of contractions. 2= slow increase in blood flow to sustained high levels
local changes that cause vasodilatation when muscles active?
system of multiple redundancies. reduced PO2, increased PCO2, decreased pH, increased extracellular K+, lactic acid production, increased extracellular ADP, AMP and adenosine all have same effect
what is the first phase of exercise hyperaemia (the fast phase)?
muscle APs produce immediate fast increases in extracellular K+, hyperpolarises arteriolar smooth muscle which close VGCaCs, relaxes the muscle (vasodilatation)- because enhances Na+/K+-ATPase activity and enhances activation of inwardly rectifying K+ channels. muscle contractions also accelerate venous return enhancing CO and reducing local venous pressure so enhancing pressure gradient through muscle capillaries
evidence for increased extracellular K+ causing arteriolar smooth muscle hyperpolarisation by activating Na+/K+-ATPases and inwardly rectifying K+ channels?
if block Na+/K+-ATPase by ouabain and inwardly rectifying K+ channels by barium then vasodilatation attenuated by approx. 60%
what happens in the maintained phase of exercise hyperaemia?
reduced PO2 alters skeletal muscle metabolism, metabolites produced have further influences. circulating adrenaline activates β2 receptors in vascular smooth muscle, has vasodilatory effect. increased O2 offloading from Hb means more ATP and NO released from RBCs, low O2 stimulates enzymes that produce adenosine from ATP which is vasodilatory. adenosine accumulates around active muscle fibres, acts on A2A receptors to increase cAMP levels in smooth muscle, leads to hyperpolarisation and so vasodilatation
how is increased CO in exercise achieved?
sympathetic venoconstriction to increase MSFP, reduced cardiac vagal stimulation to increase HR, increased cardiac sympathetic stimulation to increase HR and myocardial contractility
how is it possible to separate the central command to exercise from actual occurrence of exercise and what is seen in this case?
using curare to block the NMJ. increase in heart rate still occurs without actual exercise occurring
limiting factors in exercise with normal lungs and reasonable fitness?
O2 uptake not limiting, ability of muscles to perform work not limiting, circulation and CO is the ultimate limiting factor
proof that O2 uptake isn’t limiting factor in exercise with normal lungs?
no significant improvement in performance by raising levels of PO2
what responses does response to haemorrhage usually comprise?
responses to reduced blood volume and pain/emotional state
sequential effects of uncompensated loss of blood?
reduction in blood volume, reduction in MSFP, reduction in venous return/CO, reduction in blood pressure
what detect the changes caused by uncompensated loss of blood? what responses do they cause (within seconds)?
arterial baroreceptors and low pressure baroreceptors. sympathetic nerves increase arteriolar and venous tone and heart rate, vagal tone to heart decreases, catecholamine, AngII and ADH released which have vasoconstrictory effects,
changes within minutes of uncompensated blood loss?
changes to microvasculature- reverse stress relaxation whereby smooth muscle contracts when stretch reduced; mobilisation of tissue fluid as reduced capillary pressures shift the balance of Starling filtration-reabsorption forces towards reabsorption of fluid
changes within 10s of minutes of uncompensated blood loss?
renal conservation of water and salt, thirst and sodium appetite act to restore circulating volume
changes 24-48 hours after uncompensated blood loss?
plasma proteins replaces by synthesis in liver, increased RBC production to restore lost erythrocytes stimulated by release of erythropoietin from kidneys in response to reduced O2 delivery (for 5-7 days)
