Week 1 - Cardiac Function

Question 1

What are the 4 chambers of the heart + their functions

Answer 1

1. Left atria
   - re-oxygenated blood brought to heart via pulmonary vein
2. Left ventricle
   - pumps oxygenated blood out of aorta (artery → arterioles → capillaries → tissue)
3. Right atria
   - deoxygenated blood returns via vena cava (superior /inferior)
   venues → veins
4. Right ventricle
   - pumps blood out of pulmonary artery (to lung for re-oxygenation)

Question 2

List the valves

Answer 2

AV Valves:
1. Tricupsid Valve - between right atrium + right ventricle
- has 3 cusps
2. Bicuspid / Mitral Valve - left atrium + left ventricle
- has 2 cusps

SL Valves:
1. Aortic valve - between left ventricle + aorta
2. Pulmonary valve - between right ventricle + pulmonary artery

Question 3

How are cardiac conductive tissue arranged

Answer 3

SA node
AV node
- if SA node fails AV node can act as pacemaker
Bundle of His
Purkinjie fibres
Muscle cells

Question 4

How do cardiac conductive tissue drive coordinated contractions of the heart

Answer 4

1. SA node (in atrium) starts each beat (cells depolarise = electrical impulse / action potentials released to atria travel through internal tract)
2. Atria contracts + pressure inside atria ↑ = AV valves open and blood flows through
3. Impulse reaches AV node depolarisation is delayed (100ms)
   - delay slows down conduction of signal = allows atria to contract + fully empty / push blood into ventricle BEFORE ventricles contract
   - AP upstroke is mediated by L-type Ca channels
   - END-DIASTOLIC VOLUME = vol. of blood in ventricles reaches max. point
4. Atria relaxes + atrial pressure ↓
5. Impulse travels down bundle of his, bundle branches to purkinje fibres
6. Impulse reaches ventricle muscles = contraction + ventricular pressure ↑ = AV valves shut and SL valves open
7. Blood flows from ventricles into artery

Question 5

What is a gap junction + its role in cardiac conduction

Answer 5

• A channel formed between cells that connect the cytoplasm of the 2 cells
  
  • the heme-channel on each cell connect the cells + form gap allowing ions to move directly between cells
• Junctions connect cells in heart and muscle
  - connected via intercalated disks with desmosomes

Cardiac Conduction
- AP generated by cell in SA node moves to neighbouring cells via gap junctions
- Conducting pathway in heart is formed by strings of cells connected by gap junctions

Question 6

How does electrical activity of the heart originate

Answer 6

Cells in SA node release electrical impulses / action potentials by depolarising spontaneously

• slow (Ca2+-dependent) AP in a sino-atrial node cell will trigger a fast (Na+-dependent) AP
• when the signal reaches the AV node it activates a slow (Ca2+-dependent) AP = leads to delay

Question 7

How does electrical excitation lead to muscle contraction

Answer 7

• Excitation (AP) at membrane causes L-type Ca2+ channels to open
  
  • influx of Ca2+ triggers SR to release Ca2+
• more Ca2+ enters cytoplasm + triggers muscle contraction

Muscle cells are permeable to K+ = K+ connately leaks through membrane
- Muscle cells are packed with myofibrils
- Dips in plasma membrane form t-tubules
- have L-type Ca2+ channels on tubules
- Sarcoplasmic Reticulum (SR) surrounds t-tubules and myofibrils holding them together
- SR stores Ca2+ (intracellular store)

Question 8

What is the role of the heart in blood pressure control

Answer 8

Heart beat is controlled by muscle contraction / relaxation + opening / closing of valves

1 cardiac cycle = period from end of one heart beat to end of another
Arterial pressure changes during cardiac cycle

Systole - when ventricular muscles contract + pump blood out of heart
Systolic pressure- maximum pressure in the arterial system

Diastole - when ventricular muscles relax
- low pressure in ventricles = SL valves shut = maintain high pressure in arteries to propel blood
- low pressure ventricles = AV valves open = blood flows ion
Diastolic pressure- minimum pressure in the arterial system

Question 9

Define cardiac output

Answer 9

Flow of blood from one ventricle

Question 10

Define stroke volume

Answer 10

Volume of blood ejected with each heart beat

Question 11

What is an ECG

Answer 11

Electrocardiogram

• Monitors activity of heart
• Detects small electrical signals at skin surface caused by the flow of electrical current through heart
• Detects direction of current flow
• Can be used as part of stress test monitor
• Produces graph by measuring difference in voltage (ST etc.)
• Amplitude of the ECG signal is proportional to the mass of cardiac tissue from which it originates = why QRS complex is bigger than P wave (ventricles bigger than atria)

Place 10 electrodes on body (1 on each wrist + ankle then rest around chest) = to get different views on activity within body
Isoelectric line = difference in voltage between each of the pairs of electrodes

Question 12

Describe the features of a typical ECG trace and their origins

Answer 12

P wave - caused by atria depolarisation
- if absent in ECG = problem with atria or SA node
QRS complex - caused by ventricle depolarisation
- if absent = problems with ventricles or conducting tissues to ventricles
T wave - caused by ventricle repolarisation

PR interval = time between start of P wave and start of Q wave
PR segment = time between end of P wave and start of Q wave
QRS complex = event between start of Q wave and end of S wave
QT interval = from peak of Q wave to end of the T-wave
ST segment = time between end of S wave and start of T wave
RR interval - the period between each cardiac cycle
- when measured will give heart rate (bpm)
P-P interval - when measured shows whether heart corresponds with normal sinus rhythm

Question 13

Key Terms in ECG

Answer 13

Tachycardia = rhythm is too fast
Bradycardia = rhythm is too slow
Tornado de Pointes - life-threatening ventricular tachycardia with irregular rhythm
Atrial flutter - electrical activity in atria is regularly irregular
Ventricular fibrillation - electrical activity in ventricles is irregularly irregular

Question 14

Explain the mechanisms of excitation-contraction coupling in the heart

Answer 14

Excitation refers to the generation of an AP within the muscle cell
AP - rapid depolarisation of membrane

1. depolarization of membrane by an AP
2. depolarisation causes L-type Ca2+ channels to open allowing Ca2+ to enter cell
   - that Ca2+ alone isn’t enough to evoke contraction
3. Ca2+ bind to ryanodine receptors on SR
4. This evokes release of more Ca2+ (from SR)
5. Ca2+ released bunds to contractile proteins leading to contraction

Ca2+ binds to tropmysodin pulling it away from myosin-actin biding site
Allows myosin to bind to actin and generate a power stroke (ATP attached to myosin is hydrolysed)
When new ATP binds myosin detaches

Question 15

Explain the refractory period

Answer 15

Period is caused by inactivation of sodium channels
- Na channels open to generate upstroke of action potential (AP) due to influx of Na+, but when depolarisation reaches peak the Na channels become inactivated = unable to mediate second AP
- Membrane potential must repolarise sufficiently for the Na channels to recover + reopen
- depolarisation opens slow activating K+ channels = K+ outflux of cell = repolarisation

• Refractory period is the time immediately following an action potential, when another AP can’t be activated
• Absolute Refractory period - longest duration between stimuli when it is impossible to depolarise the cell despite size of stimulus)
  - Na channels fully inactivated
• If you stimulate cell again before the initial action potential is over, the stimulus will have little effect
  = doesn’t depolarise = cell doesn’t contract
• If you increase the interval a little may generate a depolarisation but not the full action potential
• Longer period = easier to generate depolarisation + activate an action potential

Question 16

Explain the role of refractory period in cardiac conduction

Answer 16

Cardiac Conduction Role:
- Means AP conducted travels in one direction and the tissue cant be re-excited by a second stimulus immediately following another
- cells in damaged branches can become refectory after signal passes through = next signal that arrives is only conducted through healthy branch
- BUT if Na channels in damaged branch recover = signal will pass through to point B BUT it can also re-excite damaged branch = signal travels backwards = area is continuously re-excited

• Essential for co-ordination of heartbeat
• AP travel down network of branches without interruption from point A to B
  
  • once branches are activated (cells in point B) become refractory to 2nd stimuli = only 1 AP will be generated

Question 17

How Fibrosis Affects Conduction in Heart

Answer 17

• In normal conditions AP can flow through muscle from one cell to another, in 1 direction without interruption or re-excitation
• When fibrosis forms in muscle it can break connections between muscle cells + introduce barrier to conduction
  
  • interrupted path can lead to delay / slow signal conduction in the parts of heart affected as AP has to use alternative routes which may be longer
• In damaged branches the AP will travel slower than the AP in healthy branch
  - when first signal reaches point B it will activate next cells + conduction continues
  - in healthy branches the delay between 2 branches is short = if signal arrives after it won’t conduct another AP
  - BUT in damaged branch the conduction is slower = cells at point B recover + no longer refractory when AP arrives = it is re-excited = ectopic AP + contraction

Question 18

Explain the role of refractory period in preventing cardiac arrhythmia

Answer 18

Cause of Arrhythmia
- Brief depolarisations occurs from signal from damaged branch ~ called delayed after depolarisation (DAD)
- DAD evoke ectopic AP and ectopic contraction
- Excess accumulation of Ca2+ in sarcoplasmic reticulum causes overload = ryanodine receptor channels open + Ca2+ released into cytoplasm
- Na-Ca exchanger removes 1 Ca2+ in exchange for 3 Na+ entry, enabled by the Na+ conc. gradient created by sodium pump
- Net flow of +ive charge = membrane depolarisation occurs = ectopic action

Question 19

Define an excitable cell and excitability

Answer 19

• Excitable - cell has ability when stimulated to generate an AP + create electrical current across membrane
• Non-excitable = cell cant be stimulated to fire an AP
• Electrical stimulus causes cell to depolarise from resting potential
• If depolarisation reaches the cell’s threshold it triggers a larger, rapid depolarisation which is followed by repolarisation to the resting potential (i.e. an action potential)

Question 20

Explain the role of transmembrane ion concentration gradients

Answer 20

• Establish conc. gradient across the membrane
• Gradients are maintained by ion pumps + ATPase enzymes (e.g. Na+/K+ or Na+/Ca2+ pump)

Question 21

Explain the role of membrane ion permeability

Answer 21

• Lipid bilayer is impermeable to ions = gradients are created as
• If barrier is destroyed = ions move down own conc. gradient = gradient will deplete

Ion channel permeability

Question 22

Explain how movement of different ions across membrane controls membrane potential

Answer 22

• Na+ into cell causes membrane to depolarise
  - Na channels activated when threshold is reached
• Ca2+ channel opens, Ca flows into the cell, the more negative the membrane potential, the greater the driving force
  infix of Ca causes plateau in graph
• Cl channel opens if Cl- ions move into cell will hyperpolarise it BUT if move out of cell will depolarises it
• K+ will always move out of cell when a K-permeable channel opens
• Movement of ions from one side of membrane to other (through channels) create an ionic current
• The current changes the membrane potential
• Ions and water can flow through when protein channel pores are open
• Ions flow passively, down their conc. gradient
  - as ions flow across membrane a voltage gradient is created
  - as gradient increases the +ive charge repels further movement of cations = opposes conc. gradient = ions stop moving across membrane until they’re equally distributed on both sides

Nernst (equilibrium) potential - membrane potential at which voltage gradient across membrane equals the the conc. gradient of an ion
- conc. gradient driving ion in direction = electrical force pulling ion in opposite direction
- no net movement of ions
- equation is only for a single ion
GHK Equation - takes into account all ions

Question 23

Define automaticity

Answer 23

The ability of a tissue / organ to function without external control

Autonomic nervous system ~ alters the rate + force of the heart beat (but NOT required for heart to function)

Question 24

Explain how different ion channels give rise to different electrical behaviours in different parts of the heart

Answer 24

Can be voltage or ligand gated
Channels are selectively permeable to specific ions

Voltage-gated:
- Activated by depolarisation (membrane more +ive than resting potential)
- sustained depolarisation can lead to inactivated state = channel remains inactive until membrane depolarises
- Hyperpolarisation = membrane becomes more negative than the resting potential
- slow activating K channels haven’t closed yet when cell depolarises = K+ still outflux
- Ion channels recover when the membrane repolarises

Resting state:
- Channels are close at rest = pore is blocked
- When stimulus (AP) applied channel moves from resting state to activated state

Activated State:
- Channel is open + pore is open allowing movement
- Activated by depolarisation

Inactivated State:
- a.k.a. refractory or desensitised state
- Channel is still open but conformational change in channel results in channel becoming blocked = ion flow is prevented