Theme 3: Lecture 9 - The cardiac pressure volume cycle Flashcards
Features of cerebral circulation
- Constant blood flow and pressure (auto regualtion)
- Circle of Willis - This is an anatomical feature of arteries on the brain’s inferior surface arranged in a surface
- If one branch gets blocked, blood can still reach that part of the brain through another artery
Features of renal circulation
- 20-25% of Cardiac Output. Kidneys form only a 0.5 % of body weight so 50-fold over-perfused vol/weight
- Portal system, glomerular capillaries to peritubular capillaries
- Makes both ACE & Renin (Endocrine functions, Controlling blood volume, Responding to renal blood pressure)
Features of skeletal muscle circulation
- Adrenergic Input leads to vasodilatation
- Can use 80% of Cardiac Output during Strenuous Exercise (40% Adult Body Mass)
- Major Site of Peripheral resistance
- Muscle Pump Augments Venous Return
Features of skin circulation
- Perfusion can increase 100X: role in thermo–regulation
- Arterio–Venous anastomoses: primary role in thermoreg. The anastomoses allow rapid cooling
- Sweat Glands: role in thermoreg, produce a plasma ultrafiltrate
- Response to Trauma: red reaction (skin becomes activated and allows for unusual amounts of blood to go to area), flare (capillaries are more permeable), wheal (leakage of fluid which causes a bump)
What are the four events in a cardiac cycle (pressure volume loop)
- Ventricular filling
- Isovolumic* ventricular contraction
- Ejection
- Isovolumic ventricular relaxation
What is isovolumic ventricular contraction
- The heart muscle is generating force but no contraction occurs
- Begins when mitral valve closes and ends when aortic valve opens
What is isovolumic ventricular relaxation
- Ventricle relaxes but cells don’t get any larger
- Begins when aortic valve closes and ends when mitral valve opens
What is the dicrotic notch
- Seen in a cardiac pressure volume loop
- It’s a brief moment just before the aortic valve completely closes
When does the P wave occur in the cardiac cycle
Near the end of ventricular filling
When the QRS complex occur in the cardiac cycle
At the start of isovolumic contraction
What causes a change in shape of the cardiac pressure volume loop in the ejection portion
Change in afterload
What causes a change in shape of the cardiac pressure volume loop in the isovolumic ventricular relaxation portion
Change in afterload
What causes a change in shape of the cardiac pressure volume loop in the isovolumic ventricular contraction
Change in preload
How does mitral stenosis affect preload and afterload
- Decreased preload
- Decreased afterload
How does aortic stenosis affect preload and afterload
- No change in preload
- Increased afterload
How does mitral regurgitation affect preload and afterload
- Increased preload
- Decreased afterload
How does aortic regurgitation affect preload and afterload
- Increased preload
- No change in afterload
Describe the shape of a pressure volume loop in mitral stenosis
- Graph shifted to the left
- Maximum pressure slightly decreased
- Still has neat corners
Describe the shape of the pressure volume loop in aortic stenosis
- Graph squashed to the (maximum volume in the ventricle remains the same but minimum volume is raised)
- Graph elongated (max pressure is raised but minimum volume stays the same )
- Still has neat corners
Describe the shape of the pressure volume loop in mitral regurgitation
- Oval shaped, no neat corners
- Maximum pressure is decreased
- Minimum volume is decreased and maximum volume is raised and minimum volume stays the same
- Maximum pressure raised
Describe the shape of the pressure volume loop in aortic regurgitation
- Oval shaped, no neat corners
- Maximum volume raised and minimum volume stays the same
- Maximum pressure raised
What causes myocytes to contract
myosin pulling actin:
- Sliding filament model
- Thin filaments (actin) & thick filaments (myosin)
- Myosin is a “motor protein”
- consumes ATP
- Trigger is increase in free Ca2+
- Initiated by increase in Voltage
Name two different types of K+ channels
- Delayed rectifier K+ channels
- Inward rectifier K+ channels
Describe the delayed rectifier K+ channels
- Open when membrane depolarises
- But all gating takes place with a delay
Describe the inward rectifier K + channels
- Open when Vm goes below -60 mV (Very unusual! More open when cells are at rest)
- Functions: to clamp membrane firmly at rest
- K+ channel lets K+ out of cell, repolarising it
Which channels are open when the cell is at rest
-Inward rectifier K+ channels are open, K+ flowing out of the cell is the dominant current
What is the cell’s resting potential
-70mV
Describe how an AP causes a cell to depolarise
- The initial depolarisation causes a few of the Na+ channels to open
- Na+ permeability increases, Na+ current flows through channels into cell
- The additional current of Na+ going into the cell leads to more depolarisation
- This acts as a positive feedback loop
- When the voltage goes above the threshold voltage (-50 mV), the cell is committed to an AP
- APs are “all-or-none”.
Describe how a neural cell becomes repolarised
Due to the passage of time, 2 delayed-action events occur:
- Na+ channel inactivation leads to ↓ Na+ current going in
- Delayed rectifier K+ channels open leads to ↑ K+ going out
What is the refractory period
- Period of time during which neuron is incapable of reinitiating an AP,
- The amount of time it takes for neuron’s membrane to be ready for a second stimulus once it returns to its resting state following an excitation
What is after hyperpolarisation
at the end of an AP the voltage inside temporarily goes slightly more negative than at rest, followed by a return to the resting membrane potential
What are the 5 phases of a ventricular myocyte action potential
Phase 0 - Depolarisation: Na+ gates open in response to wave of excitation from pacemaker
Phase 1 - Transient Outward Current: tiny amount of K+ leaves cell
Phase 2 - Plateau phase: Inflow of Ca2+ just about balances outflow of K+
Phase 3 - Rapid repolarisation phase: Vm falls as K+ leaves cell
Phase 4 - Back to resting potential, inward rectifier K+ channels stabilise membrane current
Compare cardiac and neural action potentials
Neural:
- Roughly 1ms
- Always the same size
- AP completed before contraction begins in skeletal muscle
- Short refractory period means that repeated APs lead to tetany
Cardiac:
- Much longer, roughly 500ms
- Vary in duration and size
- Overlap between AP and contraction
- Long refractory period, no tetany
What is happening in the plateau phase (phase 2) of the cardiac AP in ventricular myocytes
Dynamic equilibrium:
- Ca2+ going into cell
- K+ going out of cell
How does the cardiac AP in ventricular myocytes move from the plateau phase to the repolarisation phase
- A lower membrane potential leads to a smaller Ca2+ current going into the cell
- This also affects K+ so that there is less going out of the cell but to a much lesser extent
- A decrease in the amount of Ca2+ going into the cell leads to even less Ca2+ going into the cell (positive feedback)
- There’s a lot more K+ going out of the cell than Ca2+ going into the cell leading to rapid repolarisation
How does the cardiac AP change in different areas of the heart
It varies in timing and shape
What determines the ECG
The timing of the different cardiac APs
What does the QT interval align with
The ventricular AP
What does the QRS complex represent
Ventricular depolarisation
What does the T wave represent
Ventricular repolarisation
What causes the delay to repolarisation in ventricular myocyte APs
- The depolarisation of the cell that causes it to go very positive
- Opening of voltage dependant Ca2+ channels in the Plateau phase
Why do nodal cells spontaneously depolarise
- They aren’t stable at rest because they don’t have inward rectifier channels
- The voltage slowly creeps up until it reaches the threshold at which point the cell rapidly depolarises
What are the phases of a nodal AP
Phase 0 = depolarisation phase Phase 1 = does not exist Phase 2 = does not exist Phase 3 = repolarisation phase Phase 4 = pacemaker potential
Which ion causes the depolarisation of nodal cells
- Due to a transient increase in inward Ca2+
- NOT Na+
What causes repolarisation of nodal cells
- the K conductance increases shortly after depolarization
- Which initiates repolarisation (as in nerve and skeletal muscle)
How long do nodal APs last
roughly 300ms
What allows SA node cells to be autorhythmic
- Their resting potential in unstable
- The resting potential is close to the threshold potential
Why does the SAN normally beat slower than 100bpm when that is the rate that it will beat at when left to its own devices
Due to parasympathetic input
Why are SA nodal cells responsible for initiation of a heart beat in a healthy heart
They have the fastest natural rate
What does the steepness of the slope in the pacemaker potential determine
- The rate of APs firing
- AKA the diastolic potential
What causes the upward slope of nodal APs between the depolarisations
The funny current
Describe the funny current
- Due to the HCN channel
- Increases upon hyperpolarisation (rather than depolarisation)
- Allows Na+ into cell and K+ out of cell
- Leads to a net inward current (lot of Na+ in and tiny amount of K+ out)
- Depolarises cell towards 0mV
During drug therapy, why do you only block a percentage of the ion channels that you target
If you blocked them all you would kill the patient
What does Na+ channel block lead to regarding cardiac APs
- Lowered conduction velocity
- Changes the organisation of firing in different regions of the heart
- This can prevent (or sometimes cause) arrhythmias
- It does NOT prevent depolarisation or affect HR
What does Ca2+ channel block lead to regarding the cardiac APs
- Slower heart rate
- Reduced contractile force
