Introduction To Cardiovascular Physiology

Front 1

Explain the general characteristics and functions of each region of the system

Back 1

Heart:
- pulmonary circulation delivers deoxygenated blood to the lungs and returns oxygenated blood to the heart.
- systemic circulation delivers oxygenated blood to the body and returns deoxygenated blood to the heart.
- the ventricles of the heart give blood the energy it will need to overcome resistance through their systems of circulation
- CNS can influence cardiac output of the heart to alter heart rate and contractility to meet the body's needs.

Arteries:
- convert pulsatile output of the heart into a continuous flow through the body
- hold about 10% of blood volume, serve as high energy reservoir of the blood

Arterioles:
- main control elements determining flow to capillaries downstream
- major resistance of blood flow, most of the blood's energy is used to get through the arterioles and the largest pressure drop occurs across the arterioles.

Capillaries:
- whole point of CV system is to get blood to capillaries where gas/nutrient exchange occurs by diffusion along concentration gradients.
- represent greatest cross-sectional area of all vessels and the blood flows the slowest through them to give time for exchanges

Venules and veins:
- main réservoir for vascular system, contains 60-70 percent of all blood volume in resting person
- mean circulatory pressure is the pressure that would exist at a pressure equilibrium throughout the CV system after the heart stopped beating --> this principle is thought to move the blood back to the heart.

Front 2

Describe the ionic basis of the resting membrane potential in cardiac cells.

Back 2

Using the Nernst equation, we find the following equilibrium potentials:
- K+ = -94 mV
- Na+ = +71 mV
-Ca2+ = +132 mV

GHK equation weights each of the potentials based on their relative permeability for a particular cell type --> contribution of a specific ion to the resting membrane potential depends on the permeability of the membrane to that ion

In non-pacemaker cardiac muscle cells the resting membrane potential is -85mV
- resting potential is largely determined by the Nernst potential of K+ because its permeability is high and Na+ and Ca2+ have low permeability.
- Therefore the resting potential is near the equilibrium potential of K+ because the cell is highly permeable to K+ and not very permeable to Na+ or Ca2+

Front 3

Use the Nernst equation to determine what happens to membrane potential when ion concentrations change.

Back 3

Nernst equation: potential at equilibrium = (61.5/Z) x log(Co/Ci)
- Co = ion concentration outside the cell; Ci = ion concentration inside the cell; Z = charge of ion

K+out = 4mM, K+in = 140mM,
new Em=-70mM

This makes sense because the Nernst equation takes into account both chemical and electrical gradients of each ion, and in this case we decreased the chemical gradient by increasing extracellular K+

Front 4

List the major types of ion channels in cardiac muscle cells, and describe how changes in these channels lead to the generation of the cardiac muscle action potential.

Back 4

Ion channels:
1) K1- major K+ channel at resting Em, closes when Em becomes less negative

2) K: opens when Em is less negative

3) Kto: opens transiently when Em becomes less negative

4) Fast Na: two gates
- activating gate: opens when Em goes above -70mV
- deactivating gate: opens when Em goes above -70mV

5) Slow Ca: two gates
- activating gate: opens slowly above -35mV
- deactivating gate: closes slowly above -35mV

Hint 4

Phases:

1) Phase 4: resting Em, K1 channels open, others closed

2) Phase 0: Cell depolarizes above -70mV, K1 closes, Fast Na+ channels activate then close, Slow Ca2+ channels begin to open above -35mV

3) Phase 2 "plateau phase": Fast Na+ channels close; Slow Ca2+ channels are activated, but are kept steady by the activated K channels

4) Phase 3 "repolarization": Slow Ca2+ channels close; K channels still open; fast Na+ channels still closed but start to open up again

Front 5

Describe the ionic basis of the pacemaker potential in nodal cells.

Back 5

- Pacemaker cells do not have a stable resting potential due to spontaneous depolarization

- No K1 channels, K+ permeability is low --> less negative "resting" potential

- Fast Na+ channels inactive, but If channels (funny sodium channels) allow for Na+ influx to depolarize the cell

- Slow Ca2+ channels open at threshold and K+ channels help repolarize once depolarized

Front 6

Describe the molecular mechanism of E-C coupling

Back 6

1) Ca2+ flows in during AP
2) Ca2+ binds to ryanodine receptor on SR, stimulating release of Ca2+ into cytoplasm
3) Ca2+ binds to troponin C, allowing for the formation of actin-myosin cross bridges --> muscle contraction
4) Ca2+ is pumped out of the cytosol (sequestered into SR)

Front 7

Describe the origin of the contraction signal and how it is conducted through the heart.

Back 7

1) Origin of contraction is from a single cell called the pacemaker cell (necessary to effect coordinated and nearly simultaneous contraction of cardiac muscles.

2) Pacemaker cells that comprise the SA and AV nodes spontaneously depolarize towards the threshold for the Ca2+ channels. However, the pacemaker cell tends to be in the SA node.

3) depolarization begun in the pacemaker cell is propagated to adjacent cells via gap junctions in the intercalated disks. The intrinsic electrical connectivity of the cardiac muscle cells enables the single pacemaker cell to initiate contraction of the whole heart. --> functional synctium: constituent muscle cells perform as if fused into one giant cell

Hint 7

1) depolarizing wave from SA node spreads to the remaining cells of the atrium in a right to left, top to bottom fashion, arriving at the AV node a mere 65 msec post pacemaker transmission.

2) depolarization of atrial cell is manifested in muscular contraction and the pushing of blood into the ventricle.

3) Cells of the AV node -- pacemaker cells like the SA node -- utilize "slow opening" Ca channels, and therefore depolarize slowly relative to the "fast opening" Na channels of atrial and ventricular muscle cells. Combined with its comparatively low number of gap junctions and the small diameter of its cells, the AV node effectively delays the depolarization signal begun in the SA node, allowing the atria to complete their contraction before the ventricles begin their own.

4) AV node will not permit a wave of depolarization to pass if it is still in the refractory period (allows time for ventricle to fill before contracting).

5) In the event the SA node fails or its conduction is blocked between the nodes, one cell of the AV node will function as the pacemaker; however, the slower rate of depolarization will result in a slower HR (40-60bpm).

6) From the AV node, the depolarization signal continues through the non-conducting connective tissue separating atria from ventricles, into the His Bundle. This architecture ensures ventricular contraction begins only after atrial contraction has concluded.

7) His Bundle is the first part of the larger Purkinje network. Depolarization signal conducted through the AV node and His Bundle is distributed to the ventricular muscles via the Purkinje network. The abundant gap junctions, use of fast-opening Na+ channels, and large fiber diameter make electrical conduction throughout the network extremely fast. Thus, ventricular muscle contraction along the endocardial (inner) surface to the periphery of the ventricles is nearly simultaneous.

8) Like the AV node, the Purkinje network functions as a reserve pacemaker, capable of a slow HR (15-40 bpm). The wave of depolarization continues to the endocardial cells, and finally to the epicardial surface of the ventricle.

Front 8

Describe how the ANS controls HR and signal conduction

Back 8

Innervation:
The SA and AV nodes are each innervated by the SNS and PNS nervous systems. The SNS stimulates both depolarization in the SA node and conduction in the AV node. Conversely, the PNS inhibits both depolarization in the SA node and conduction in the AV node.

Neurotransmitters and Receptors:
The SNS works through NRE, while the PNS uses Ach. Both neurotransmitters use G-protein coupled receptors in nodal cells --> beta-1-adrenergic in the SNS, and muscarinic in the PNS.

- SNS: In general, SNS increases the spontaneous rate of AP, thereby elevating HR, and correspondingly increases the rate of conduction throughout the AV node. beta-1-adrenergic receptor activates Gs, which triggers adenyl cyclase which generates cAMP, which activates pKa, which stimulates slow Ca2+ channels. cAMP also stimulates "leaky sodium" channels (If).
Stimulation of the If channel increases the slope of the electrical potential curve between AP, since more Na ions are permitted to leak into the nodal cell and contribute to depolarization. Moreover, stimulation of the slow Ca channels increases the slope of the AP. This is due to the fact that more Ca ions are allowed into the cell, increasing the rate of conduction in the AV node.

PNS:
Overall the PNS slows the spontaneous rate of AP, thereby decreasing HR, and similarly decreases the rate of conduction through the AV node.
ACh works through muscarinic receptors to stimulate Gi, appropriately named for its role in blocking the activation of adenyl cyclase. (reverse of Gs above) resulting in inhibition of If and the slow Ca2+ channel.
ACh binds directly to the Kach channel. This binding increases K permeability, driving the membrane potential more negative and closer to the Nernst potential for the K ion.
Increased K+ permeability drives the max diastolic potential lower, so it takes the nodal cell longer to reach the -35mV threshold for the Ca2+ channels. This increased time interval translates into a lower HR.
Additionally, inhibition of the If channel decreases the slope of the electrical potential curve preceding the AP, effectively increasing the amount of time between firing. Finally, the slope of the AP is reduced, owing to the inhibition of the slow Ca2+ channels by Gi. The presence of fewer Ca ions reduces the rate of conduction from cell to cell.