Week 1 - Pacemaker and conduction of the heart

Pacemaker and Conduction SDL, preload, afterload and contraction and finally cardiac output

what is the annulus fibrosis

• 4 interconnected rings of fibrous connective tissue b/w atria and ventricles

• acts as an electrical insulator

what does the annulus fibrosis ensure?

• AP from the SAN only reach the ventricles via the AVN

How does conduction of the myocardium work?

1. SAN cells depolarise by themselves = automaticity

2. Myocytes are connected via gap junctions so more depolarise and they take a ‘highway’ which sends this electrical impulse to the left atrium = Bachmann’s bundle

3. atrial systole

4. Wave of depolarisation reaches the AVN

5. travels down bundle of His, through a left and right bundle down the septum

6. fibres branch from the apex of the heart through the Purkinje fibres

Via what tracts does the wave of depolarisation reach the AVN?

• intranodal: 3 of them

What causes the ventricles to contract after the atria and why?

• AVN causes a delay of around 0.1 seconds

• This ensures the atria empty fully and if it wasn’t delayed it would cause the atria and ventricles to push blood against each other

what is function the SAN

• Initiation of the depolarisation of the atria

what is the function of the AVN

• delaying the wave of depolarisation to ensure complete contraction of the atria and that blood flows in the same direction

what is the function of the bundle of His

• where the wave of depolarisation travels down to ensure contraction of the ventricles starts at the apex of the heart

What is the function of the purkinje fibres

• ensure complete contraction of the ventricles from the apex of the heart

How many phases of AP in cardiomyocytes are there?

• 5 (phase 0-4)

What are the stages of AP generation in cardiomyocytes

• 0 = influx of Na+ ions

• 1 = potassium channels first open up, decrease in mV due to outflux

• 2 = Ca2+ influx is balanced with K+ outflux, stays balanced

• 3 = Ca2+ influx stops, only K+ outflux, decrease in mV

• 4 = resting potential, ~-90mV

what kind of cells are in the SAN, AVN, Bundle of His and Purkinje fibres?

• autorhythmic cells

• this means they have automaticity

what can autorhythmic cells do?

• spontaneously generate AP

how do autorhythmic cells generate AP

• undergo slow depolarisations until a threshold potential is reached

• most rapid in the SAN

Outline the 5 stages of AP generation in the SAN

1. ion channels open that are permeable to both Na+ and K+ which causes a small influx of Na+ ions = I_f current

2. Ca2+ channels begin to open

3. further Ca2+ channels open

4. K+ channels activated allowing efflux of K+

5. K+ channels close and I_f channels open

Like a normal AP generation but with more involvement Ca2+ ions

Explain what this diagram represents

• The SAN reaches the threshold before AVN

• arrival of AP from the SAN speed up the cells of the AVN into reaching the threshold

if the SAN wasn’t working, what would happen to AVN?

• would eventually spontaneously depolarise but at a slower rate

Describe the effects of the parasympathetic nervous system on the SAN and AVN

• ACh decreases rate of depolarisation, lengthening the intervals b/w action potentials = parasympathetic NS decreases heart rate

• activates muscarinic cholinergic receptors on the pacemaker cells

• slows ion channel changes

• takes longer for the cells to reach the threshold → longer interval b/w heartbeats

• heart rate is decreased below its intrinsic or spontaneous level

Describe the effects of the sympathetic nervous system on the SAN and AVN

• NE/NA increases the rate of depolarisation and therefore shortens the interval b/w AP = sympathetic nervous system increases HR above intrinsic spontaneous level

• activates Beta-adrenergic receptors

• speeds up ion channel changes

• enables SAN cells to reach threshold more quickly therefore there’s a shorter interval b/w heartbeats

why is it important both nodes have automaticity?

• if one is damaged/doesn’t depolarise to threshold, the other can still propagate

why does the AVN have a longer refractory period?

• helps protect the ventricles from being stimulated to contract at rates that are too rapid for efficient contraction

How are heart rates below the intrinsic rate achieved

• by the parasympathetic neurones

how are heart beats above the intrinsic rate able to occur?

• during exercise or emotional arousal due to the sympathetic nervous system

why does the parasympathetic nervous system not influence the ventricular muscle cells?

• less innervation in the ventricles

how can the parasympathetic nervous system have an effect on the ventricular myocytes

• inhibits NE release from the sympathetic neurone terminals by releasing ACh

what is an ECG used for?

• summarising the depolarisation spread through the heart

what lead type is being used to produce the rest ECG

• lead II

What is stroke volume

• the volume of blood pumped by the heart for each cardiac cycle

what affects the amount of blood delivered to the tissues?

• stroke volume

• heart rate

• vascular tone

what makes up cardiac output

• stroke volume

• heart rate

what affects blood pressure

• vascular tone

what is cardiac output

CO (ml/min) = HR(bpm) x SV (ml/beat)

• the volume of blood pumped by the heart in one minute

Does the CO from the LV and RV differ?

• no they’re matched

• the heart automatically pumps whatever volume of blood is put into it

• stroke volume must be matched, therefore vol entering lungs = vol entering systemic circulation

why can’t we have different SV from each ventricle?

• increase in P in venous side

• leads to oedema (pulmonary or peripheral)

• CO is tightly regulated by a range of mechanisms as a result

how is CO regulated?

Cardiac output: heart rate and stroke volume

• stroke volume is regulated by preload, afterload and contractility

what is preload

• EDV: end diastolic volume (in the ventricles)
  intrinsic regulation

what is contractility

• ESV: end systolic volume

• affected by SNS

• extrinsic regulation of stroke volume

what is afterload

• resistance to ventricular ejection

what is preload dependent on

• dependent on venous return of blood i.e. central venous pressure

what happens if preload is low

• ventricular filling is reduced, thus stroke volume is reduced

• because preload is dependent on venous return of blood

what happens if preload is high

• ventricular filling is increased, hence stroke volume increases

• because preload is dependent on venous return

what is the Frank-starling mechanism

• a linear relationship between preload and stroke volume

• ventricular muscle stretching leads to a stronger contractile force

Outline the process of the length-tension relationship

1. increased preload

2. increased exposure of myosin to actin

3. increased cross-bridge formation

4. increased force of contraction

what are the 2 limits of the Frank-starling mechanism?

1. excessive stretching causes a decrease in cross-bridge formation

2. Laplace’s law: in a large sphere, more wall tension is required to generate the same internal P as it does in a small sphere as governed by:

   • Pressure = tension/radius

What are the clinical consequences of Laplace’s law

• if the heart fills itself with more blood, it’s at an increasing mechanical disadvantage

• chambers become more difficult to empty

• e.g. dilated cardiomyopathy

What are 2 factors that influence preload

1. filling time of the heart:

   • low rates > longer period of ventricular filling → greater distension of the ventricle

2. venous return:

   • P difference b/w venous system and atrium:

     • skeletal muscle pump

     • respiratory pump

     • SNS activity

     • blood volume

how does the skeletal muscle pump work and how does it affect venous return

1. skeletal muscle contracts

2. veins are compressed

3. blood is forced to the heart

4. increased pre-load

   • increases venous return.

how does an increased respiratory pump increase venous return?

• diaphragm moves caudally

• increasing abdominal pressure

• thorax pressure is reduced

  • INCREASED ABDOMINAL RETURN OF BLOOD

  • increases preload

outline the sympathetic control of venous return

• venous system acts as a ‘reservoir’ of blood

• the SNS stimulates the venous system causing:

  • venous vasoconstriction

  • increased venous pressure

  • increased preload (as a result)

Summaries how stroke volume is increased

Increases SNS → increased blood volume

Increased use of skeletal muscle pump → increased respiratory movements

BOTH:

• increase venous pressure

• increase venous return

• increase EDV

what is the extrinsic regulation of stroke volume

The SNS activation → inotropy of the heart → increased contraction at any given preload

• increasing stroke volume

What is inotropy

• increasing contractility of the heart

how does the SNS lead to increased ventricular contractility

1. empty more completely, thus reduced ESV

2. greater pre-load creating a greater filling volume

3. increased stroke volume → reduced ventricular filling time

4. afterload increases (increased aortic P)

what receptors are involved in increasing ventricular contractility caused by sympathetic stimulation

• B1-adenoreceptory

How can contractility be manipulated pharmacologically

Positive inotropes:

• phosphorylation of Ca2+ channels

• faster calcium re-uptake

• sensitisation of troponin C to calcium

• increased contractility

what are some example clinical drugs that manipulate contractility

• cardiac glycoside e.g. digoxin

• Beta 1 - adrenoreceptor agonists e.g. dobutamine

How does the parasympathetic nervous system affect contractility

• decreases force of contraction

• inhibition of noradrenaline released from sympathetic NS

• decreases heart rate

what receptors are involved in the parasympathetic stimulation of ventricular contractility

• M2 muscarinic receptors

what is the effect of afterload on stroke volume

• creates the resistance against which ventricle pumps

• increased stroke volume → increased CO and thus increased afterload

apart from ventricular systole, what else effects afterload on stroke volume

• pressure of blood in circulation

  • principally affected by vasomotor tone

  • primarily arteriolar tone

what is the normal situation of afterload

• ejection pressure is greater than afterload, hence blood is ejected out of the heart

what is the effect of reducing afterload on stroke volume?

• more blood can be ejected

what is the effect of increasing afterload on stroke volume

• reducing stroke volume

• heart has to work harder to maintain CO

summarise stroke volume: 3 points

1. normal heart pumps venous return each cycle = intrinsic control

2. extrinsic mechanisms can overcome limits of intrinsic control → increased contractility at a given period

3. afterload is a limiting factor in stroke volume in diseased animals e.g. hypertensive animals

what does the ANS control of the heart rate enable

1. rapid response (increase of decreased)

2. tightly regulated to maintain blood P

How does Blood P influence heart rate and cardiac output?

Elevated BP (transient):

• PSNS activation → reduced heart rate, reduced cardiac output, BP returns to normal

Low BP:

• SNS activation → increased HR, increased vascular tone, increased CO, restores blood PS

What contributes to blood pressure?

1. vascular resistance

2. cardiac output (influence each other)

   • HR and SV impact CO

how do we calculate BP?

BP = MAP: mean arterial pressure

cardiac output x total peripheral resistance

what is total peripheral resistance (TPR)

• arterial vascular resistance (tone)

what is TPR influenced by?

• SNS (alpha and beta adrenoreceptors) in the vasculature

• Renin-Angiotensin Aldosterone System (RAAS)

• Local endothelial-derived factors

what do cardiac output and TPR affect

• degree of afterload

how do we calculate blood flow

• pressure difference/resistance

what is resistance proportional to?

Length/Radius⁴

How do we maintain blood flow if radius is halved

• need to increase volume x 16

How do we calculate pulse pressure

P_systolic - P_diastolic

how do we calculate mean arterial pressure

Systolic + 2(diastolic) / 3

what is pulse pressure influenced by

1. arterial compliance (aorta)

   • ability to accommodate the increase in pulse pressure

   • decreases with age

2. stroke volume

3. consistent high pulse pressure will ‘‘age’’ heart quicker

what does a greater stroke volume in relation to pressure

• greater difference b//w systolic and diastolic pressure

When considering cardiac function, what is more important for perfusion of peripheral tissues - cardiac output or blood pressure

• blood pressure is more important, as a decrease in BP will lead to lack of nutrients being delivered to tissues = cell death and organ failure. Too high = oedema

• cardiac output is important as it generates blood P but not as important for perfusion

How does contractility of the heart change during physical exercise. How is this brought about?

• EDV = lower

• squeeze more blood out = stroke volume increases

• SNS stimulates heart to contract with NA (conscious decision)

• chemoreceptors haven’t kicked in yet

• adrenaline will kick in ‘fight or flight’

What changes occur in HR, venous return, total peripheral resistance, tissue fluid volume and urine output after a major haemorrhage?

1. HR = increase - want to maintain cardiac output and correct pressure drop

2. venous return decreases

3. total peripheral resistance = decrease, constrict to maintain pressure

4. tissue fluid volume = decrease

5. urine output = decrease, want to conserve water as much as possiblt

what happens to cardiac output in heart failure

• reduced BP

• may have a miss-match in the L/R side of ventricles

• exercise intolerant, particularly under stress

• CO decreases for any given preload