2 - cardiovascular Flashcards
formula for cardiac output
what is the minimum cardiac output?
cardiac output = heart rate x stroke volume
CO = HR x SV
minimum is at least 5L per minute
compare cardiac and skeletal muscle
both skeletal and cardiac:
– straited appearnace
– electrically excitable
– similar contractile response
cardiac cells are interlocked by intercalated discs. cardiac cells are both mechanically (desmosome) + electrically (gap junctions) connected
∴ heart cells function together = contract in sequence = “functional syncytium”
cardiac cells generate own AP = autorhythimcity
draw a diagram representing AP and contractile response in a cardiac cell
include flow of ions
include definitions and values for ARP and RRP
what do these values mean for the function of cardiac cells?
ARP = absolute refractory period
= period where second AP cannot be generated
= 0.25 - 0.30 s
RRP = relative refractory period
= interval immediately after ARP where initiation of second AP is inhibited but no impossible
= 0.05 s
summation and tetanus is prevented
describe the flow of electrical conduction in the heart
pacemakers in SA node of right atrium generate AP
spreads through right atrium and into left atrium
conducting pathways spread to AV nodes and through to ventricles
spread to apex of heart
purkinje fibres spread up sides of ventricles
pathway allows rapid propagation of AP
draw a diagram and table representing APs in different areas of the heart:
– autorhythimcity
– conduction speed
– function
what is responsible for these differences
Differences due to ion channel subtypes present in each cell
SA + AV nodes have unstable resting MP due to slow influx of Na+ and entry of calcium from T-tubules
SA NODE: autorhythimcity = yes conduction speed = slow function = pacemaker
ATRIAL MUSCLE: autorhythimcity = no conduction speed = fast function = atrial contraction
AV NODE: autorhythimcity = yes conduction speed = slow function = secondary pacemaker
PURKINJE FIBRES: autorhythimcity = yes conduction speed = very fast function = conduction of electrical signal / tertiary pacemaker
VENTRICULAR MUSCLE: autorhythimcity = no conduction speed = fast function = ventricular contraction
draw a diagram representing a typical ECG wave
P wave = depolarization of the atria
QRS complex = represents depolarization of the ventricles
T wave = repolarization of the ventricles
how is cardiac output regulated?
vagus nerve innervates pacemaker regions of SAN and AVN via ACh
sympathetic nerves innervate whole heart (wide-spread)
• pre-ganglionic neurotransmitter = acetyl choline
• post-ganglionic neurotransmitter = noradrenaline
how does the parasympathetic nervous system effect cardiac output?
In PNS, ACh acts on muscarinic receptors in cardiomyocytes to:
• slow pacemaker depolarisation and weaken contraction
• slow closure of K+ channels
• resting K+ leakage is increased → hyperpolarisation → slower depolarisation
• slows opening of Ca2+ channels → slower depolarisation
- acetylcholine decreases activity of I(f) channel to slow depolarisation
- acetylcholine opens GIRK (G protein inward rectifying K+) channels. potassium conductance increases resulting in hyperpolarisation
- acetylcholine reduces calcium influx to slow depolarisation. this also reduces calcium availability to weaken atrial + ventricular contraction
OVERALL:
SA node = overall slows pacemaker activity = ↓HR
AV node = decreases node excitability = longer AV delay
Atria = weakened contractions
Ventricles = “ “
how does the sympathetic nervous system effect cardiac output?
SNS acts on adrenergic receptors (particularly β1-adrenoreceptors) in cardiomyocytes to:
• innervate SA and AV nodes and non-pacemaker contractile cells
• decrease K+ permeability
• noradrenaline increases inward calcium current
• noradreanline decreases K+ permeability → accelerates inactivation of K channels → rapid drift to threshold → increased depolarisation rate
- adrenaline/noradrenaline oppose ACh by increasing activity of I(f) channel = faster depolarisation
- adrenaline/noradrenaline oppose ACh by increasing activity of I(Ca) channel = faster depolarisation
** adrenaline/noradrenaline do not effect maximum diastolic potential
SA node = overall increases pacemaker activity = ↑HR
AV node = increase node excitability = shorter AV delay
strengthens ventricular and atrial contractions
draw a diagram comparing the parasympathetic and sympathetic regulation on CA by acting on different receptors
PARASYMPATHETIC:
ACh binds to M2 receptor (GPCR)
G-protein inhibits adenylyl cyclase
SYMPATHETIC:
noradrenaline binds to beta-1 receptor (GPCR)
G-protein stimulates adenylyl cyclase
active adenylyl cyclase —> ATP to cAMP —> activates PKA
activation of PKA increases calcium influx to modulate both heart rate and force of contraction
formula for stroke volume
what is stroke volume at rest?
stroke volume = ventricular end-diastole volume - ventricular end-systole volume
SV = EDV ESV
EDV = volume when fully relaxed = 125mL
ESV = volume when fully contracted = 55mL
∴ SV = 125 - 55 = 70mL
how is EDV intrinsically controlled?
FILLING PRESSURE
• ↑ blood flow = ↑ return to atria = ↑ atrial + ventricular pressure
• ↑ pressure causes ventricular walls to expand a greater extent
• ↑ EDV
FILLING TIME
• more time to fill up
• ↑ EDV
VENTRICULAR COMPLIANCE
• state of cardiomyocyte contraction i.e. how easy it can expand
• ventricle can expand and fill more at same pressure
• ↑ EDV
what does the “frank-starling law” state?
amount of blood pumped out of the heart is proportional to the amount pumped in
the larger EDV, the larger SV (less ESV)
how is ESV intrinsically controlled?
PRE-LOAD
• increase of the EDV increases the stretch on the cardiac muscle
• increases contractility (greater stretch = greater ejection)
AFTER-LOAD
• increased pressure at ventricular outlet
• increases the force of the contractility required to pump the same volume
how is contractility extrinsically controlled?
contractility is extrinsically controlled by iontropic agents
POSITIVE CONTROL:
• catecholamines act on β-adrenoreceptors to ↑Ca2+ influx = stronger contraction
• cardiac glycosides block Na-K ATPase
NEGATIVE CONTROL:
• beta blockers block adrenoreceptors
• diltiazem/verapamil blocks calcium channels
• = weaker contraction
list some factors that effect resistance to blood flow?
vessel radius
vessel length
viscosity of blood
type of blood flow / geometry of blood vessel
relationship between flow and resistance
flow inversely proportional to resistance
relationship between flow and pressure
flow directly proportional to pressure
why doesn’t arterial pressure drop to 0 mmHg during diastole (no flow into arteries)?
elastic properties of arterial walls prevent pressure from dropping to 0mmHg
artery walls contract during diastole = provides driving force which continues to project blood forward
how is arteriolar diameter controlled intrinsically (locally)?
METABOLIC FACTORS
• O2 = constriction
• CO2 = dilation
LOCAL SIGNALS • nitric oxide = dilation • histamine = dilation • endothelin = constrict • prostaglandins = both
LOCAL TEMP
• heat = dilate
• cole = constrict
INCREASED STRETCH
• myogenic response (muscle)
TRUE OR FALSE
extrinsic factors override intrinsic factors in the control of arteriolar diameter
FALSE
intrinsic (local) factors override extrinsic factors in the control of arteriolar diameter
how is arteriolar diameter controlled extrinsically?
AUTONOMIC NERVOUS SYSTEM
• SNS releases NA which acts on ⍺1-adrenoreceptors to induce vasoconstriction
• SNS releases A from medulla which acts on β2-adrenoreceptors to induce vasodilation
ENDOCRINE
• angiotensin/vasopressin = vasocontriction
• bradykinn = vasodilation
how is fluid exchange across capillaries facilitated?
exchange achieved by passive diffusion and bulk flow
passive diffusion of solutes down concentration gradient
bulk flow of extracellular fluid between vascular and interstitial compartments
what is an oedema?
abnormal accumulation of interstitial fluid
reduced plasma proteins:
e.g. renal disease or liver cancer
→ favours filtration → oedema
increased permeability of capillary walls
e.g. local inflammation, allergies
→ more plasma protein in ISF → increased osmotic pressure (outward pressure gradient) → favours filtration → oedema
increased venous pressure
e.g. congestive heart failure
→ favours filtration → oedema
blockage of lymph vessel
e.g. surgical removal of lymph nodes in cancer
→ reduced capacity of lymph drainage → accumulation of ISF → oedema
what are the consequences of oedema?
excess interstitial fluid
increased distance between blood and cells
decreased rate of diffusion
inadequate nutrient supply/removal of waste
what type of receptors detect high pressure in order to regulate blood pressure?
baroreceptors are mechanoreceptors which detect changes in pressure
located in carotid sinus (detect pressure of blood entering brain) and aortic arch (detect pressure of blood entering systemic circuit)
baroreceptors involved in moment-to-moment (short-term) regulation of blood pressure
regulate HR, SV and resistance to maintain relatively constant arteriol pressure
where is the “cardiovascular control centre”?
afference and efference?
how does it regulate CO?
cardiovascular control centre located in medulla
afference = baroreceptors efference = both parasympathetic (vagus nerve) + sympathetic neurons change to correct situation
increase in mean arterial pressure = detected by baroreceptors = efferent pathway activated = CO decreased
draw a flow diagram of the baroreceptor reflex
- blood pressure elevates
- ↑ receptor potential in aortic arch and carotid sinus
- ↑ rate of firing in afferent nerves
- cardiovascular centre
- ↓ sympathetic cardiac/vasoconstrictor nerve activity
↑ parasympathetic nerve activity - ↓ HR, ↓ SV
vasodilation - ↓ CO and ↓ resistance
- blood pressure decreased towards normal
briefly describe the brain-bridge reflex and the chemoreceptor reflex
BRAIN-BRIDGE
• low volume/stretch receptors in atria (and vena cava) detect blood flow coming back to heart and increase HR to compensate
• prevents damming of blood in veins, atria & pulmonary
circuit
CHEMORECEPTOR
• occurs in aortic arch and carotid bodies (like baroreceptors), but also centrally in medulla
• detect low O2, high CO2, high H+
• increase respiratory drive + MAP
briefly describe how hormones can regulate blood pressure
noradrenaline/adrenaline: – from adrenal medulla – vasoconstriction – increase HR and CO – increase veinous return
ADH (vasopressin):
– released from posterior pituitary gland
– regulate water retained in kidneys
– ↑ water retension = ↑ blood volume = ↑ CO
angiotensin:
– potent vasoconstrictor
– increase CO
what is hypertension?
describe the causes, symptoms and treatments
high blood pressure > 140/90 mmHg
caused by:
• essential hypertension = genetics, diet, salt intake, obesity, insulin resistance, ageing, stress, sedentary lifestyle
• secondary hypertension = occurs due to a primary problem = renal - vascular – endocrine system disorders, obstructive sleep apnea
treatments include diuretics (thiazides), beta blockers, angiotensin converting enzyme inhibitors or receptor blockers, dietary and weight management
why don’t baroreceptors resolve high blood pressure in hypertension?
baroreceptors operate around a set point
in hypertension, set point becomes higher i.e. baroreceptors maintain a higher MAP
describe the structure, location and function of the cardiac ryanodine receptor (RyR2)
cardiac ryanodine receptor (RyR2) is a large tetrameric protein that forms a channel between the lumen of the SR and the cytosol of the myocyte (skeletal muscle)
RyR2 facilitates muscle contraction:
– at rest, RyR2 won’t let calcium out of SR (some can leak out)
– when it’s time to contract, RyR2 lets calcium out into SR
– phosphorylation of receptor causes it to open
cytosolic + SR proteins sit alongside RyR2 to stabilise it
these proteins don’t attach to every single receptor ∴ some receptors more prone to movement
TRUE OR FALSE
spontaneous calcium release through RyR2 is triggered by the L type calcium channels
FALSE
spontaneous calcium release through RyR2 is NOT triggered by the L type calcium channels
spontaneous calcium release caused by:
– hyperphosphorylation of RyR2
– store overload
how does the RyR2 receptor respond to heart failure?
during heart failure, heart is becoming weaker
weak heart tries to maintain function
brain sees that heart is not meeting demand ∴ gives heart low-level stress response to increase heart function
PKA phosphorylating RyR2 in many places —> destabilising channel
these phosphorylations remove some of the stabilising proteins
RyR2 receptor becomes more open = calcium leaks out of channel = diastolic Ca2+ leak
how does a myocyte respond to calcium store overload?
heart failure = calcium elevated for a long time
how to clear calcium from cytosol?
– 3Na+/Ca2+ exchanger
– CIRCA —> back into SR —> uses energy
3Na+/Ca2+ exchanger limited because it must bring sodium in —> cannot put that much sodium into cell when there are high levels of calcium
CIRCA takes extra calcium and pumps it into SR
SR over-filled with calcium = RyR2 receptor leaks calcium = STORE OVERLOAD INDUCED CALCIUM RELEASE (SOICR)
each RyR2 receptor has different threshold to SOICR due to stabilising proteins
TRUE OF FALSE
action potential propagates uni-directionally
true :P
how does triggered arrhythmia differ from normal electrical conduction?
in triggered arrhythmia, local calcium leak triggers an electrical impulse between normal contractions
the cells ahead of that impulse are in their refractory period HOWEVER the ones behind aren’t
∴ the signal moves backwards and interferes with the next contraction
what is CPVT?
catecholaminergic polymorphic ventricular tachycardia
sudden cardiac death:
– induced by stress response
– underlying cause is a mutation of a protein
– type of arrhythmia
associated with mutations in RyR2
how does defibrillation work?
application of electrical shock ‘resets’ AP of all myocytes
all myocytes depolarise at once to reset and re-coordinate APs
shock must be sufficient to depolarise every cell simultaneously
next stimulated action potential can now propagate normally through the tissue
list and briefly describe the classes of anti-arrythmic drugs
CLASS 1:
alter AP via Na+ channels
CLASS 2:
block β-receptors to reduce phosphorylation
CLASS 3:
alter AP via K+ channels
CLASS 4:
block Ca2+ channels
what is the β-adrenergic signalling cascade?
adrenaline binds to and activates β-adreneroreceptor
G-protein activates
G-protein activates adenylate cyclase
adenylate cyclase increases [cAMP]
cAMP activates protein kinase A
what are the pros and cons of beta-blockers?
give two examples of beta-blockers
PROS
– effective at preventing arrythmias
– e.g. metoprolol and carvedilol (also stabilises RyR2)
CONS
– low compliance
– slow HR does not increase during exercise = reduced quality of life
– people stop taking drug as they “feel better” without it
