cardiac structure, properties, electrical activity and function Flashcards
define incompetent valve
results from failure of valve to close completely, results in regurgitation/backflow of blood
define stenotic valve
results from failure of valve to open completely, obstructs forward flow of blood
what is the cause of heart murmurs
turbulent flow through diseased valves (incompetent/ stenotic) which produces abnormal heart sounds
characteristics of ARF/ heart disease
pancarditis
endocarditis on heart valves results is fibrinoid necrosis + fibrin deposition forming small vegetations along lines of closure
aschoff bodies (associates w/ zones of fibrinoid necrosis, result from inflammation in heart muscle)
characteristics of chronic rheumatoid heart disease
valvular fibrosis
fibrous lesions
permanent retraction + thickening of valve cusps
results in stenosis/ incompetence
effect of chronic rheumatic heart disease on mitral valve
shortening/ thickening/ fusion of chordae tendinae
commissural fusion + calcification (causing fishmouth/ buttonhole stenosis)
leaflet thickening
state which valves are most affected by rheumatic heart disease in order of most to least affected
mitral valve
aortic valve
tricuspid valve
pulmonary valve (almost always escapes injury)
characteristics of tight mitral stenosis (associated with ARF)
LA dilation due to pressure overload
results is atrial fibrillations (Afib) + formation of large mural thrombus
LV is generally normal
clinical features of ARF
ARF more common in children
principle manifestation is carditis
onset of symptoms in all age groups begins 2-4 weeks after initial streptococcal infection and are heralded/preceded by fever + migratory polyarthritis
cultures are negative for streptococci at time of symptom onset however serum tigers for antibodies against streptococci agents are elevated
how is ARF diagnosed
diagnosis of ARF is made based on serologic evidence of previous streptococcus infection (elevated serum tigers of antibodies against streptococci agents such as streptolysin/ DNAse)
+ 2 or more of the jones criteria
(major)
- carditis
- migratory polyarthiritis of large joints
- subcutaneous nodules (rarely noticed)
- erythema marginatum
- syndenham chorea
(minor)
-fever
- arthralgia
- EKG changes
- elevated acute phase reactants
what are the 2 types of infective endocarditis
acute IE:
occurs on previously normal valves
destructive + fatal results
rapid disease
organism is staphylococcus aureus
leads to large, friable vegetations on heart valves that can embolise around blood stream
common in IV drug abusers and affects right side valves
subacute IE:
occurs on top of already diseased valves by rheumatic heart disease/ prosthetic
slow disease
organism is less virulent streptococcus viridan
vegetations are smaller/firmer and embolization is less common than in acute IE
what is infective endocarditis
an inflammatory condition affecting the endocardium, specifically on the heart valves
leads to the development of large, friable vegetations on the heart valve
fragments of these vegetations split from the main mass and embolize around blood stream + impact distant vessels causing infarction and spreading infection
difference in vegetations formed by ARF and IE
ARF vegetations are small, 1-2mm in size
IE vegetations are large, 0.5-1cm in subacute/ 1-2cm in acute
morphology of IE
large vegetations
0.5-1cm in subacute
1-2cm in acute
vegetations may be single or confluent valve-destroying mass (forming a large mass)
in acute IE valve cusps may be perforated/ bacteria may infiltrate myocardium causing abscess formation
vegetations are on the upper/atrial surface of tricuspid and mitral valves
lower/ventricular surface of pulmonary and aortic valves
what are the consequences of IE
embolus formation - may travel along coronary arteries/ systemic circulation, can cause infection which weakens walls of vessel leading to a dilated artery (mycotic aneurysm)
valve perforation/ destruction seen in acute IE - causes infection to spread into myocardium which may lead to heart failure
immune complex tissue injury - may cause glomerulonephritis in kidney/ vascular is in skin/ arthralgia in joints (caused by deposition of immune complexes circulating in bloodstream)
what are the 5 phases of contractile cardiomyocyte action potential in ventricles
phase 0 - initial rapid depolarization (Na influx)
phase 1- rapid, partial, early repolarization (K outflux, opening of L-type voltage gated Ca channels)
phase 2- prolonged period of slow repolarization/ plateau phase (simultaneous K outflux + Ca influx)
phase 3- rapid repolarization (inactivation of L type
Ca channels + continued K outflux)
phase 4- complete repolarization/ RMP
which phase corresponds to absolute and relative refractory periods respectively
ARP = phase 2
RRP = phase 3
what are the 3 phases that make up pacemaker potential
phase 4- diastolic depolarization (influx of Na through h/funny channels + Ca influx through T channels at -55mV for more rapid depolarization)
phase 0- depolarization (Ca influx through L type channels up to +10mV)
phase 3- repolarization (Ca channel inactivation + opening of K channels)
what are the factors affecting myocardial rhythmicity
sympathetic nerve stimulation at SAN, increases rate of phase 4/ depolarization therefore threshold potential is reached faster and heart rate increases
parasympathetic nerve stimulation via the vagus nerve slows heart rate by hyperpolarisation of SAN cells so rate of depolarization at phase 4 is therefore also reduced therefore it takes longer for threshold potential to be reached
hyperkalaemia, a rise in plasma K, consequence of acidosis/ inadequate excretion of K from body, life threatening because it can lead to depolarization of cardiomyocytes (resting potential rises to 0) meaning Na channels stay inactivated (membrane cannot return to -ve potential) which may lead to cardiac arrest
define myocardial excitability
ability of cardiac muscle to respond to a stimulus by generating an action potential followed by contraction
what are the 4 properties of cardiac muscles
automaticity (spontaneous depolarization)
excitability
conductivity
contractility
characteristics of absolute refractory period in cardiomyocytes
no sensitivity to additional stimulation as all Na channels are active
cardiomyocytes cannot respond to restimulation whatever the strength of stimulus may be as Na voltage gated channels are inactive therefore further stimulation cannot produce action potential
corresponds to depolarization + 2/3 of repolarization (phases 0, 1, 2, beginning of phase 3)
mechanically corresponds to whole period of systole and early diastole
duration in ventricles = 0.25-0.3s
duration in atria = 0.15s
characteristics of relative refractory period in cardiomyocytes
reduced sensitivity to additional stimulation as only some Na channels are active
cardiomyocytes can respond to restimulation by a greater than normal stimulus as some Na channels are active, causes premature contraction
corresponds to last 1/3 of repolarization (rest of phase 3)
mechanically corresponds to middle of diastole
duration in ventricles = 0.05s
duration in atria = 0.03s
what is the significance of long refractory period in cardiomyocytes
lasts almost as long as entire systole
prevents sustained tetanic contractions (sustained muscle contraction)
mechanism allowing sufficient time for ventricles to empty + refill prior to next contraction essential for pumping function of heart
factors affecting myocardial excitability
1- innervation
- sympathetic stimulation leads to increased excitability
- parasympathetic stimulation (vagal nerve) decreases excitability
2- ECF ion conc.
- hyperkalemia, increases excitability initially however, if sustained it results in inactivation of Ca and K channels causing loss of excitability leading to cardiac arrest and heart stops in diastole
- hypokalemia decreases excitability
- hypercalcemia decreases excitability
define myocardial conductivity
ability of myocardiocytes to transmit impulse generated in SAN to the rest of the heart
why is the SAN the primary pacemaker/ why do cardiac impulses originate from the SAN
because its the region of the heart w/ the fastest intrinsic spontaneous discharge rate (110-120bpm)
where in the heart are the SAN and AVN found
SAN - right atrium near SVC
AVN - right atrium at posterior part of inter atrial septum close to opening of coronary sinus
which cardiac cells have the longest refractory period
AVN + purkinje fibers
this allows only forward conduction from atria to ventricles preventing re-entry of cardiac impulses from ventricles to atria
conduction speed in AVN
AVN has the slowest conduction velocity (0.05m/s)
long absolute refractory period
leads to 0.1s of AVN delay
this is caused by the small diameter of AVN cells and slow conductive fibers
AVN delay is shortened by sympathetic stimulation/ prolonged by vagal stimulation
what is the significance of slow conduction in AVN
allows atria to empty completely before beginning of ventricular contraction
protects ventricles from abnormal atrial rhythms (Afib)
what are the functions of the AVN
receives impulse originating from SAN and transmits it to ventricles through bundle of his
AV nodal delay (which allows for complete atrial emptying before ventricular contraction + protects ventricles from abnormal atrial rhythms)
can initiate cardiac impulses but at a slower rate (40-60bpm) if SAN gets damaged
functional differences between AVN and SAN
initial resting potential of AVN is -80mV compared to -60mV of SAN
depolarization of AVN doesn’t exceed +5-+10mV
depolarization in phase 4 is slower because of absence of a population of Na channels causing the slower intrinsic rate of firing
what is the significance of purkinje fibers having the fastest conduction rate of all cardiac muscle
ensures simultaneous contraction of all parts of ventricles, essential from pumping function of heart
define WPW/ pre-excitation syndrome
the presence of an electrical leak in the fibrous ring separating atria from ventricles (anulus fibrosis) leading to an alternative direct route for spread of action potential from atria to ventricles resulting in arrhythmia
what are the steps of transmission of a cardiac impulse through the heart
-cardiac impulse originates in the SAN
-impulse spreads across left/right atria
- impulse proceeds across internodal pathway
- impulse reaches AVN and passes to bundle of his
- wave of depolarization spreads on top of ventricular septum to purkinje fibers down each side of the septum before spreading to all parts of the ventricles
what is the force of muscle contraction dependent on
the no. of actomyosin cross bridges formed which in turn is dependent on the conc. of Ca inside the cell
factors affecting force of contraction
sympathetic NS activation
drugs increasing intracellular Ca
how does physiologic stimulation of sympathetic nerves to the heart result in an increased force of contraction
B1-ADR activation leads to rise in intracellular cAMP, a secondary messenger which activates several protein kinases causing phosphorylation of protein phospholamban
protein phospholamban accelerates the transport of Ca into the SR, favoring the retention of Ca in SR at the expense of efflux back across plasma membrane (more Ca gets reabsorbed into SR instead of effluxed back through membrane)
contractility of the heart is therefore increased by raising the amount of Ca stored in the SR (more Ca gets released into myocyte which increases the force of contraction)
rate of relaxation of cardiac muscle is also increased as Ca re-enters the SR more quickly
effects of cAMP can be manipulated by caffeine/ milrinone which as as phosphodiesterase inhibitors therefore prolonging the half life of cAMP
sympathetic stimulation also causes phosphorylation of L-type Ca channels which increases their permeability to Ca allowing more entry of Ca from ECF into the myocyte
what are positive inotropes + examples
agents which increase the force of contraction
examples include
- sympathetic stimulation
- sympathomimetic agents
what are negative inotropes + examples
agents which decrease the force of contraction
examples include
- intracellular acidosis (high H+)
- reduced binding of Ca to troponin which decreases the no. of cross bridges formed
- Ca channel blocking drugs
what are the 2 types of contraction
isometric - fibers contract w/o shortening, tension developed rises very high, most energy is liberated as heat, no work is done, pressure inside heart raises to a high level essential to opening aortic/ pulmonary valves, volume of heart remains constant
isotonic - fibers shorten to contract, tension doesn’t increase/ remains same throughout work, pressure inside heart raises only slightly, volume of heart decreases as it pumps blood into lungs/body by decreasing in size
phases of the cardiac cycle
atrial systole - 0.1s
ventricular systole - 0.3s
isovolumetric contraction
rapid ejection
reduced ejection
diastole - 0.4s
isovolumetric relaxation
maximum filling
reduced filling
what is the effect of heart rate on the duration of the cardiac cycle
when HR increases the duration of each cardiac cycle decreases + duration of action potential decreases
duration of diastole decreases by a greater % than the the duration of systole
meaning that the heart doesn’t remain relaxed long enough to allow complete filling of the cardiac chambers before the next contraction
location + organization of CVC/ vasomotor center
located bilaterally, mainly in medulla oblongata + lower 1/3 of pons
contains vasoconstrictor/ vasodilator/ sensory areas
describe vasoconstrictor area in CVC
located in rostral ventro-lateral medulla (RVLM)
sends fibers to thoraco-lumbar segments of spinal cord
activity is sympathetic postganglionic fibers leads to generalized vasoconstriction elevating ABP (depressor effect)
describe vasodilator area in CVC
located in caudal ventro-lateral medulla (CVLM)
receives impulses from sensory neurons
not connected to any vasodilator fibers
when stimulated it inhibits vasoconstrictor area causing generalized vasodilation lowering BP (depressor effect)
describe sensory area in CVC
located in posterolateral part of medulla oblongata + lower pons (in nucleus tractus solitarius/ NTS)
lateral portion - sends excitatory signals through sympathetic nerves to heart
medial portion - sends signals to adjacent nucleus ambiguous in MO from which preganglionic parasympathetic vagal fibers arise that relay in terminal ganglia in nodal tissue of RA, postganglionic fibers supply atria/ bundle of his/ coronary vessels (right vagus supples SAN/ left vagus supplies AVN) causing inhibition
what is the function of vagal/parasympathetic fibers to heart
negative chronotropic (rate of contraction) effect
negative inotropic (force of contraction) effect
negative dormotropic effect (decreased conduction at AVN)
decreased excitability
decreases release of NA (vasopressor) from nearby sympathetic nerve fibers
what is the vagal/ventricular escape phenomenon
vagal fibers to heart produce a negative dormotropic effect which leads to decreased conduction at AVN, strong vagal activity may lead to complete AV block where ventricles stop beating, they may then regain their function by idioventricular rhythm (a slow regular ventricular rhythm, typically with a rate of less than 50, absence of P waves, and a prolonged QRS interval)
what is the function of sympathetic fibers to heart
positive chronotropic effect (rate of contraction)
positive inotropic effect (force of contraction)
positive dormotropic effect (conductivity)
increased excitability
decreased effects of vagal stimulation
describe vagal tone of the heart
continuous inhibitory impulses transmitted by vagi to check inherently high rhythm of SAN (110-120 bpm) at the basal level of ABP
its reflexly produced through baroreceptors
high ABP, more impulses sent through baroreceptors to CVC (sensory area/ medial portion), more inhibitory impulses sent by vagus to heart, lower HR
factors affecting HR
gender (females > males due to lower ABP w/ a weaker vagal tone)
age (higher in young due to increased BMR and in elderly)
circadian rhythm (lowest in early morning/ highest in evening)
rest
muscular exercise
posture (HR increases by up to 25% when standing)
emotions
metabolic rate
respiration
nervous regulation of the heart
afferent impulses from CVS (baroreceptors/ low pressure baroreceptors/ peripheral chemoreceptors)
afferent impulses from other regions of the body (contracting voluntary muscles/ painful stimuli)
afferent impulses from higher centers (cerebral cortex, lambic system, hypothalamus respond to emotions/ respiratory center/ CNS ischemic response/ cushing’s reflex)
what are the vasosensory areas and their buffer nerves
carotid sinus, supplies by coronary sinus nerve, a branch of glossopharyngeal IX cranial nerve
aortic arch, supplies by aortic depressor nerve, a branch of vagus X cranial nerve
where are the low pressure baroreceptors/ serial stretch receptors found + their function
4 chambers of the heart/ SVC/ IVC pulmonary artery
increase HR by distention caused by increased blood volume/ venous return
mechanisms of increasing HR include direct stretching of SAN/ brain bridge reflex where increased venous return stimulates type B receptors that discharge during atrial diastole to medullary/vasomotor centers via the vagus nerve leading to decreased vagal tone + increased sympathetic tone of heart
what are the baroreceptors reflexes
decreased HR and force of contraction
generalized peripheral vasodilation
decreased ADH secretion (increased urine volume)
where are peripheral chemoreceptors found + their function
carotid and aortic bodies where rate of blood flow is very high
increase respiration/ vasoconstriction in response to decreased oxygen/ increased CO2/ H+
describe the CNS ischemic response
afferent impulse from a higher brain center for nervous regulation of HR
ABP <60 mmHg results in ischemia of vasomotor centers w/ increased CO2 + lactic acid which stimulates them causing activation of sympathetic NS leading to peripheral vasoconstriction especially in skin/kidneys
describe cushings reflex
afferent impulse from a higher brain center for nervous regulation of HR
caused by increased intracranial pressure which leads to compression of cerebral vessels causing a hypoxia state which activates RVLM neurons leading to systemic vasoconstriction increasing ABP which reflexively decreases HR
causes of increased HR
decreased stimulation of baroreceptors (decreased ABP —> increased HR)
stimulation of arterial stretch receptors
during inspiration
muscular exercise
mild/moderate painful stimuli
mild/moderate emotions (stress/anger)
moderate hypoxia (directly stimulates SAN/ RVLM)
catecholamines
thyroxin
increased body temp
causes of decreased HR
increased stimulation of baroreceptors (increased ABP —> decreased HR)
severe emotions (fear/grief)
severe pain/ pain in trigger areas
during expiration
increased intracranial pressure (cushings reflex)
severe pre-mortal hypoxia/ acidosis
hyperkalemia
define cardiac output
vol. of blood pumped out be each ventricle per minute
at rest = 5-6 L/min
in severe exercise = 25L/min in non-athletes / 35L/min in athletes
factors affecting cardiac output
metabolism
exercise
age
size of body
define cardiac index
cardiac output (volume of blood pumped out by each V/min) per m^2 of body surface area
normal value = 3.2L/m^2/min at rest
define stroke volume
vol. of blood pumped by each V per beat
70-90ml in average size, resting, supine position
ventricular end diastolic volume - end systolic volume = stroke volume
EDV = 130ml
ESV = 50ml (increased ABP or decreased cardiac contractility increase ESV which decreases SV)
how to calculate cardiac output (CO)
CO = HR x stroke volume
stroke volume = EDV - ESV
define ejection fraction
% of end diastolic blood volume that’s ejected per beat
index of ventricular function
EF = (SV/EDV) x 100
at rest it ranges from 60-70%
conditions affecting CO
increases during:
- exercise
- excitement
- anxiety
- eating
- in pregnant women
- exposure to high environmental temp
decreases during:
- on standing from lying down in heart disease (postural hypotension)
no change during:
- sleep
- exposure to moderate change in temp
factors affecting CO
CO = HR x SV
changes in HR/ SV/ both produce changes in CO
- venous return (preload)
- cardiac contractility/ systolic performance of ventricle
- ABP (after load)
- HR
- blood volume +viscosity
preload = EDV
after load = resistance against which blood in expelled (ABP/ pressure in aorta)
explain how VR affects CO
factors affecting VR/ peripheral circulation are the primary controllers of CO
VR = vol. of blood flowing from veins into RA/ min
VR determines stroke volume + cardiac output by affecting EDV
during rest, VR is 5-6L/min which is equal to CO (controlled via intrinsic auto-regulatory mechanisms)
what are the intrinsic auto-regulatory mechanisms controlling CO
sympathetic tone of heart can increase CO by up to 15-25L/min (during muscular exercise), known as cardiac permissive level
outputs greater than the cardiac permissive level can still by ejected by:
1. neuro-hormonal mechanisms such as
- increasing sympathetic activity
- secretion of catecholamines from adrenal medulla
2. cardiac hypertrophy which can increase CO by 35L/min in athletes
what are the mechanisms that increase CO when VR is increased
Frank-Starling law - extra blood in ventricles stretches cardiac muscle to grater extent causing muscle to contract w/ increased force causing an increase in SV therefore increasing CO
brain bridge reflex/ atrial stretch receptor reflex - increased VR stretches wall of RA sending more impulses via atrial stretch receptor which increases sympathetic tone causing an increase in HR therefore increasing CO
what are the factors that affect VR
venous pressure gradient - difference between mean pressure in systemic circulation (7-10mmHg) and RA pressure (2mmHg / 0mmHg in standing position), the greater the VPG the greater the VR and vice versa
skeletal muscle pump - contraction compresses capillaries/ venues in skeletal muscles propelling blood towards heart, occurs by muscle tone/ during exercise
valves in veins - prevent back flow of blood in veins
arteriolar diameter - dilation in skin during hot weather/ splanchnic area during digestion decreases resistance to blood flow + increases VR
capillary tone - 90% are partially/totally closed under normal conditions, severe dilation w/ histamine release/ on tissue injury leads to pooling of blood in capillaries which decreases mean circulatory pressure (decreased venous pressure gradient) therefore decreasing VR + CO causing circulatory shock
respiratory pump - during inspiration, thoracic pressure becomes more -ve so thoracic veins dilate + resistance to blood flow is decreased, at the same time intra-abdominal pressure increases as diaphragm descends which compresses/constricts and increases pressure in abdominal veins, the increase in pressure gradient between thoracic and abdominal veins helps VR towards heart (high pressure in abdomen to low pressure in thorax)
sympathetic stimulation - increases venous tone (partial constriction during rest caused by continuous sympathetic discharge creating an upstream pressure which maintains VR against gravity) + cardiac suction forces ( during ventricular diastole V expands increasing inflow from A decreasing atrial pressure resulting in sanction of blood from veins)
blood volume - decrease in blood volume decreases mean circulatory pressure which decreases venous pressure gradient resulting in a reduction in VR + vice versa
gravity - opposes VR from lower limbs, this effect is normally antagonized by thoracic + muscular pumps/ venomotor tone/ cardiac suction forces
what does mean systemic filling pressure/ mean pressure in systemic circulation depend on
blood volume (proportional)
venous compliance (indirectly proportional) (more blood stays in veins instead of returning to heart)
what is the effect of standing on VR
when standing, effect of gravity is greater than venous pressure gradient
this causes blood to pool down in veins of lower limbs
which increases capillary blood pressure
so fluid escapes into interstitial spaces
resulting in a 15% decrease in blood volume in 15mins
VR is decreased
therefore CO is decreases
syncope (fainting)
this is prevented by
contraction of muscles in lower limbs (muscular pump)
venomotor tone (partial constriction during rest caused by continuous sympathetic discharge creating an upstream pressure which maintains VR against gravity)
cardiac suction forces (V diastole)
explain how myocardial contractility affects CO
defined as the force generated by V muscle during systole
determined by the no. of actomyosin cross bridges formed which depends on:
- preload/ frank-sterling law (pre stretch of V muscle at end of diastole/ EDV)
- level of contractility (change in force of contraction)
what affects level of contractility
neural input - sympathetic stimulation of heart increases force of contraction by increasing Ca entry from ECF causing an increase in ejection fraction/ catecholamines increase +ve inotropic effect of NA released from nerve endings
changes in HR - high HR produces small increase in contractility because Ca enters cell more rapidly than it’s reabsorbed by SR resulting in an increase in intracellular Ca, increased contractility compensates for reduced filling time
Ca availability - increase contractility
digitalis/ other inotropic drugs - increase contractility
heart failure/ hypoxia/acidosis - decrease contractility
explain how afterload/ ABP affects CO
increased ABP/ peripheral vascular resistance causes initial decrease in SV + CO for several beats
EDV of next beat increases leading to increase in force of contraction (frank-starling law) therefore CO returns to normal
changes in ABP don’t affect CO as long as VR remains constant
explain how changes in HR affects CO
proportional relationship (if HR increases/decreases within limits)
excessive acceleration/slowing of HR is associated with a decrease in CO (inversely proportional relationship)
if HR increases above limits where it shortens diastolic time during which filling takes place the CO will decrease rather than increase
HR <70bpm, SV increases (enough time for max filling) so CO remains constant
HR <50bpm, increase in SV doesn’t compensate for slowing of heart so CO is decreased
HR from 180-200bpm, SV is decreased because of shortening of diastolic time but CO remains constant/ increases slightly due to heart acceleration
HR >180-200bpm, diastolic times becomes shorter and decreased EDV/ force of contraction/ SV/ CO, decrease in SV is not compensated for by heart acceleration
explain how changes in blood volume/ viscosity affects CO
increased blood vol increases VR
hemorrhage decreased VR + CO
increased blood viscosity increases resistance against blood returning to heart/ decreases VR
decreased blood viscosity (e.g- anemia) increases VR + CO
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