Cardio Week 1 Flashcards
where is SA node (location of excitation)
right atrium
what is phase 4 of SA node excitation
slow depolarisation and upstroke due to slow Na+
what is phase 0 of SA node excitation
upstroke due to Ca2+ channels
what are Ib and If and when are they activated
funny currents - at end of repolarisation by negative potentialsas threshold approached, transient Ca2+ activated
through what junctions is excitation spread
gap junctions
where is AV node located
base of atrium
why is conduction delayed in AV node
allows atrial systole to precede ventricle systole
what is the role of bundle of his and purkinje fibres
rapid spread of action potential to ventricles
what is phase 0 of ventricular muscle action potential
INa
what is phase 1 of ventricular muscle action potential
closure of Na+ channels and transient K+ efflux
what is phase 2 of ventricular muscle action potential
mainly Ca++ influx
what is phase 3 of ventricular muscle action potential
closure of Ca++ channels and K+ efflux
what is phase 4 of ventricular muscle action potential
resting membrane potential
what causes the plateau phase
opening of voltage gated Ca2+ channels whilst Na+ channels still activated - resultant Ca2+ current is sufficient to slow repolarisation
what is a competitive inhibitor of acetyl choline acting on M2 receptors
atropine - used in extreme bradycardia to speed up heart
what does adrenaline acting on a1 receptors cause
vasoconstriction of the blood vessels of splanchnic, renal, cutaneous and skeletal muscle vascular beds
what does adrenaline acting on B2 receptors cause
vasodilation of cardiac and skeletal muscle arterioles - dilates vessels and increases HR
sympathetic coupling through G protein activates what
adenylyl cyclase to increase cAMP and cause increased HR
what causes increased contractility (positive inotropic) as a sympathetic response
increase in phase 2 of cardiac MUSCLE action potential and sensitisation of contractile proteins to Ca2+
what causes increased conduction (positive dromotropic) as sympathetic response
enhancement of If an Ica in SA node potential
what causes decreased duration of systole (positive lusitropic action) as sympathetic response
increased uptake of Ca2+ into SR
parasympathetic coupling through G protein channels does what
reduced adenylate cyclase and thus cAMP opens potassium channels (GIRK) to cause hyperpolarisation of SA node mediated by Gi BY subunits
what causes decreased conduction in AV node (negative dromotropic)
decreased activity of Ca2+ channels and hyperpolariation (dip) via opening of K+ channels
how is pacemaker potential modulated
depolarising the funny current (If) mediated by channels activated by hyper polarisation and cyclic AMP gated (HCN) channels
what is a selective blocker of HCN channels
ivabradine - slows HR and reduces O2 consumption
what is a summary of the mechanism causing contraction in cardiac MUSCLE cells
opening of Ca2+ channels, Ca2+ influx, Ca2+ release from SR caused by Ca2+ activating RyR2, Ca2+ binds to troponin C and shifts tropomyosin out of actin cleft resulting in cross bridge (contraction via sliding filaments)
what is a summary of the mechanism causing relaxation in cardiac MUSCLE cells
repolarisation in phase 3/4, Ca2+ channel close, Ca2+ efflux occurs by NCX1, Ca2+ release from SR ceases and sequestration via Ca2+ ATPase (SECRA) takes place - Ca2+ dissociates from troponin C and cross bridge break
give examples of b-adrenoceptor agonists on the heart
dobutamine, adrenaline and noradrenaline
what do b-adrenoceptor agonists do to heart
increase rate, force (B1), constricts vessels in skin, mucosa etc to redistribute blood flow (a1) and dilation of coronary arteries (b2)also increases O2 consumption
give examples of b-adrenoceptor antagonists on heart
propranolol (non selective), atenolol, bisoprolol, metoprolol - act only on B1 in heart
what are b-adrenoceptor antagonists used to treat
angina, cardiac arrhythmias, MI (carvediol also causes vasodilation) and chronic heart failure no longer hypertension unless co-morbidities present
what are the adverse effects of b-adrenoceptor antagonists
bronchospasm, aggravation of cardiac failure, bradycardia, hypoglycaemia, fatigue, cold extremities
give example of non-selective muscarinic ACh antagonist
atropine
what is the role of non-selective muscarinic ACh antagonist
blocks parasympathetic system, increases HR esp in athletes, no effect on arterial BP/exercise, first line in severe bradycardia (following MI) and in anti cholinesterase poisoning
what is the role of digoxin
increases contractility by blocking sarcolemma ATPase IV in acute HR or orally in acute HF (particularly HF with AF)
how does digoxin work
inhibits Na+ pump which removes Na+ from cells, thus [Na}i increases so reducing Na+ gradient that drives NCX - less ca2+ removed and peak [Ca2+] force increases
what is the unwanted effects of digoxin
excessive depression of AV node (heart block), propensity to cause arrhythmias, nausea, vomiting, diarrhoea and disturbances of colour vision
give examples of 3 other inotropic drugs
levosimendan - calcium sensitisers (acute decompensated HF - binds to troponin C sensitising it to Ca2+)amrinone and milrinone - indicators (use limited to IV in acute HF - inhibit PDE and increase cAMP)
what is the role of desmosomes within the intercalated discs of cardiac myocytes
provide mechanical adhesion between adjacent cells - ensures tension developed by one passed to next
what are myofibrils
contractile units of muscle - contain actin and myosin arranged into sacromeres
what is the refractory period
a period following an action potential in which it is not possible to produce another action potential
how is the long refractory period protective for the heart
prevents generation of tetanic contractions in cardiac muscle
what is the stoke volume
volume ejected by each ventricle per heart beat SV=EDV-ESV
what effects the SV
preload (Inc=inc), myocardial contractility (inc=inc) and after load (inc=dec)
what is end diastolic volume
volume of blood within each ventricle at end of diastole - determined by venous return to heart
what is the starling law
If EDP (so EDV) increased, the force of the following contraction (thus SV) increases
how is stretch involved in force
increases affinity of troponin for Ca++
what is afterload
resistance into which heart is pumping -> heart unable to eject full SV so EDV rises but eventually force of contraction rises by frank starling
a rise in peak ventricular pressure (contractility of heart at given EDV rises) shifts frank Starling curve in what direction
left
what change in pressure (dP/dt) reduces duration of systole
increases
what does vagal stimulation influence in heart
the rate - NOT FORCE
adrenaline and noradrenaline have what effects
inotropic and chronotropic
what is cardiac output
volume of blood pumped by each ventricle per minute CO = SV x HR (5l per min is normal)
what is diastole
heart ventricles relaxed and filled with blood (0.5)
what is systole
heart ventricles contract and pump blood into aorta (LV) and pulmonary artery (RV) - 0.3 sec
what events occur during passive filling
AV valves open and venous return flows into ventricles - ventricles become 80% full (aortic pressure 80mmHg and pulmonary lower)
what events occur during atrial contraction
completes end diastolic volume (130ml) - EDP is few mmHgcontracts between p wave and QRS
what events occur in isometric ventricular contraction
Pressure rise and when it exceeds atrial pressure the AV valves shut (LUB) - QRS
what events occur in ventricular ejection
SL valves open and SV ejected by each ventricle leaving behind ESV - ST segment - then ventricles relax where the SL valves shut (DUB)
what events occur in isometric ventricular relaxation
ventricle again a closed box and tension falls around closed volume - when falls below atrial pressure, AV valves open and start again
when is s1 (first heart sound) heard
closure of mitral and tricuspid valves - LUB - and heralds beginning of systole
when is s2 (second heart sound) heard
closure of aortic and pulmonary valves - DUB - and heralds end of systole and beginning of diastole
JVP has own a, c and v waves - what do these stand for
a - atrial contraction c - bulging of tricuspid valve into atrium during ventricular contraction v - rise of atrial pressure during atrial filling: release as AV valves open
what is korotkoff sounds
blood flow though vessel when blood exceeds cuff pressure 1st sound - peak systolic2nd - no sound (record diastolic when sound disappears)
what is the equation to calculate pressure gradient between aorta and right atrium that drives blood sound systemic circulation
MAP - CVP (central venous - right atrial pressure)
what is SVR
total peripheral resistance - sum of resistance of all vasculature in systemic circulation MAP = CO x SVR
what is the pressure sensors, control centre and effector in the regulation of MAP
sensor - baroreceptors control centre - medulla effector - heart (HR and SV) and blood vessels (SVR)
how do baroreceptor reflexes correct postural hypotension
fall in MAP –>, decreased baroreceptor discharge, HR increases, SV increases, SVR increases
what are the two main components of EXCF what control blood pressure
water and Na+ (retention - increased BP)
what converts angiotensin I (formed by renin) to angiotensin II
ACE - produced by vascular endothelium
angiotensin II stimulates release of aldosterone - what does this do?
systemic vasoconstriction, increases SVR, thirst and ADH release, steroid hormone which increases Na+ and water
RAAS is regulated by mechanisms which stimulates renin releasee from juxtaglomuler apparatus in kidneys: this includes:
renal artery hypotension, stimulation of renal sympathetic nerves, decreased Na+ in renal tubular fluid (sensed by macula dense)
what are natriuretic peptides (NPs)
peptide hormone synthesised by heart and released in response to cardiac distension
what do NPs cause
excretion of salt and water (reduce blood volume and pressure), decrease renin release, vasodilation, counter regulatory system for RAAS
what is the two main types of NPs
Atrial natriuretic peptide (ANP) and brain type natriuretic peptide (BNP_
what is antidiuretic hormone (ADH) - vasopressin
peptide hormone derived by hypothalamus and stored in posterior pituitary - stimulated by reduced EXF volume or increased EXF osmolarity
what does vasopressin do
vasoconstriction, increases reabsorption of water, increases CO and BP
what is the resistance to blood flow and how is it controlled
directly proportional to blood viscosity and length of blood vessel and inversely proportional to radius of blood vessel to power 4controlled by vascular smooth muscles through changes in radius
what factors cause relaxation of arteriolar smooth muscle resulting in vasodilation and metabolic hyperaemia
decreased local PO2, increased local PCO2, increased [H+], increased extracellular K+, increased ECF osmolarity, adenosine release (from ATP)
what is examples of humoral agents (other chemicals) that cause vasodilation
histamine, bradykinin, nitric oxide
how can NO be stimulated and how does it work
stress on endothelium -> calcium release -> activation of NOS, can also be receptor stimulated NO diffuses into adjacent smooth muscle where it forms cGMP (relaxation)
what are examples of humoral agents that cause vasoconstriction
serotonin, thromboxane A2, leukotrienes, endothelin
how can endothelial damage/dysfunction be caused
HBP, high cholesterol and smoking
how can temperature control MAP
cold cause vasoconstriction, warmth causes vasodilation
what is the myogenic response to stretch
MAP rises - vessels constrict to limit flow MAP falls - vessels dilate to increase flow
how does sheer stress influence arterioles
dilation of arterioles cause sheer stress in arteries upstream to make them dilate
what increases venous return
increased venomotor tone, increased skeletal pump, increased blood volume, increased atrial pressure (caused by increased EDV and SV) and increased respiratory pump
what does increased venomotor tone do
increase venous return, SV and MAP
what does increased vasomotor tone do
increase SVR and MAP
what is the acute cardiovascular response to exercise
HR, SV and force increase, vasoconstriction of kidneys and gut, vasodilation of skeletal and cardiac muscle, decrease SVR and DBP (PP increases)rise in peak ventricular pressure (contractility at given EDV) - Stirling curve shifted to left
what is the chronic CVS response to exercise
reduction in sympathetic tone, increased parasympathetic tone, cardiac remodelling, reduction in plasma renin levels, improved endothelial function (increased dilators, decreased constrictors) and decreased arterial stiffening
what does regular aerobic exercise do to blood pressure
reduces it
