Phys-Cardiac

Right atrium --> Rt ventricle--> pulmonary artery --> lungs (oxygenation) --> pulm vein --> left atrium --> left vent --> aorta --> systemic circulation (body) --> vena cavae (sup/inf)--> back to rt atrium

• Systole = contraction
• Diastole = relaxation
• *2 atrium are synchronized with each other & 2 ventricles are synchronized w one another

True.

False: Atria are "primer pumps" and the major pumping work is doe by the ventricles.

• Right vent = C-shaped, 25 mmHg
• Left vent = cylindrical, 120 mmHg

• Right heart:
• - inlet: tricuspid
• - outlet: pulmonic

• Left heart:
• - inlet: mitral
• - outlet: aortic

Papillary muscles/chordae tendinae.

Normal heart sounds are vibrations of the walls of the heart and major arteries caused by the abrupt cessation of blood flow when a valve closes.

• 1st sound "lub": AV valves (tricuspid, mitral) close as ventricular systole begins
• 2nd sound "dub": outlet (semilunar) valves close as ventricular systole ends

• - mitral valve prolapse (turning inside out)
• - valvular insufficiency (regurgitation)
• - valvular stenosis (inability to open fully)

note: all these can result in turbulent blood flow and altered heart sounds ("murmurs")

• - Ventricular myocytes: 20 micrometers in diameter and 100 micrometers in length
• - Atrial myocytes: smaller than vent. myocytes

*both are typically mononucleated but can contain 2 nuclei

• - Myocytes are physically interconnected via intercalated disks, allowing transmission of force.
• - Gap junctions connect cells electrically, allowing propagation of APs inter-cellularly. Gap junctions allow for coordinated contraction of each of the atria and each of the ventricles in alternating fashion.

• •Heart rhythm set by the sino-atrial node in right
• atrium.
• •AP quickly propagates to left atrium via conduction system
• •AP spreads through right and left atria
• •AP propagates via conductive system, and is delayed before propagation to ventricles
• •AP spreads through ventricles (from AV node).

Neither. The contraction of cardiac muscle is accomplished by sliding of thin filaments (mainly actin) to thick filaments (mainly myosin). The active force (or stress) that this can produce depends on the overlap between the myosin cross bridges extending towards actin. Thus, for very long muscle lengths (resulting from stretching), force decreases because there's no overlap and for very short muscle lengths, the force also decreases because the thin filaments "bump into" one another.

The total muscle tension is the sum of the active force and passive force (from elastic elements inside and outside the muscle cell).

Aorta -> arteries -> arterioles -> capillaries -> venules -> veins -> vena cava

• - Aorta: muscular, elastic
• - Arteries, arterioles: muscular, elastic, “Resistance vessels” (changing ease of blood flow to different organs)
• - Capillaries: thin walls (single
• endothelial cell), “Exchange vessels”
• - Venules, veins, vena cava: larger,more numerous than resistance vessels, thin walls, valves. At rest contain 2/3 of blood; “Capacitance Vessels” (if you decrease the size, you move more blood to the arteriole side)

• - Delivery (O2 via RBCs and nutrients via plasma)
• - Disposal (CO2 + metabolites)
• - Distribution system for endocrine and immune systems
• - Temp regulation

• Diffuse rapidly across capillary endothelial cells, and even across walls of arterioles and venules.
• Rapidly equilibrate between blood and interstitial fluid.

Diffuse through tight junctions (also called "spaces", "clefts", "pores") between endothelial cells, or are transported into and out of endothelial cells by specific membrane carriers and pumps

False. Tight junctions vary among tissues. Those in brain capillaries are nearly impermeable, creating the Blood Brain Barrier. Those in kidney, intestine, and liver are very leaky, often even quite large proteins can get through. In most tissues, tight junctions are sufficiently leaky to allow small lipid-insoluble molecules to equilibrate, but not proteins.

• *Net movement of water in and out of a capillary is determined by the balance of filtration and absorption. Q = k[(Pc - Pi) - (pi-c - pi-i)]
• - Hydrostatic pressure inside a capillary (Pc = 35 - 15 mmHg) is greater than the interstitial space (Pc = 0 mmHg), causing water to flow out of the capillary (FILTRATION). Pressure difference is high at arterial end and low at venous end
• - Proteins in blood and interstitial fluid create an osmotic force, called the colloidal osmotic pressure or oncotic pressure. The oncotic pressure of blood within the capillary (pi-c) is higher than that in the interstitial space (pi-i). The difference in oncotic pressure (pi-c - pi-i) draws water into the capillary (ABSORPTION). The oncotic pressure difference is constant (25 mmHg) all along the capillary.

• True.
• - At arterial end: (Pc-Pi) > (pi-c - pi-i), causing net filtration.
• - At venous end: (Pc-Pi) < (pi-C - pi-i), causing net absorption.

• “Typical”: Absorption=filtration”
• (Vasomotion can cause alternation btwn filtration and absorption)
• Renal glomerulus: high Pc; Filtration>Absorption
• Lung: low Pc; Absorption>Filtration
• Congestive heart failure causes increased ­Pc in lung vasculature causing net filtration and fluid accumulation in the lungs

Difference in Pressure = flow x resistance (delta P = Q x R)

• Zero reference point is atmospheric pressure at the height of the tricuspid valve.
• - Pressure is measured by the height of a column of mercury that can be supported by that pressure, and is expressed as mmHg (or torr).

• Total Peripheral Resistance.
• - lump similar vessels together, treating systemic circulation as 5 resistors arranged in series (you add the resistance of small arteries, arterioles, capillaries, venules, and veins for TPR).
• - Unit: mmHg x min/liter

Arterioles have the highest resistance, therefore show the largest drop in pressure. This makes arterioles the "policemen" of the circulatory system; changes in resistance of arterioles is crucial for controlling the distribution of cardiac output.

• False. In a parallel network, individual resistors offer a greater resistance to flow than the network as a whole.
• Dilate arterioles: Decrease R -> Increase flow to
• that tissue & Divert FROM other tissues
• Constrict arterioles: Increase ­R -> Decrease flow to that tissue & Divert TO other tissues

• Q = (deltaP x pi x radius^4)/ (8 x viscosity x Length)
• R = (8 x viscosity x Length)/ (pi x radius^4)

*If radius increases 2-fold, then resistance decreases 16-fold... small changes in vessel radius causes large changes in vessel resistance!*

• Laminar flow is smooth, streamlined, no turbulence. It is quiet. Velocity is zero next to wall, fastest in center.
• Turbulent flow has eddies, whirlpools, etc. It is noisy, wastes energy, causes blood clots, and causes lesions of the vessel wall due to shearing force (viscous drag), which damages endothelial cells.
• *low viscosity, high flow rates, large diameter vessels, and irregularities in vessel wall favor turbulent flow.

• Blood is typically 45% cells by volume (= hematocrit). As hematocrit increases, viscosity increases.
• Viscosity decreases as velocity of blood flow increases (shear thinning).
• Viscosity decreases as the diameter of arterioles decreases (from 70 to 10 micrometers).

• Tension = (delta Transmural Pressure = Pin - Pout) x radius)/ (wall thickness)
• As aneurysm grows in size (­r), tension in vessel wall increases (which tends to cause a further growth in the size of the aneurysm). With time the cells are likely to become weaker, the wall bulges further, and the tension increases further until the aneurysm ruptures.

• Systolic: 120 mmHg
• Diastolic: 80 mmHg
• Mean: 94 mmHg
• Pulse: 40 mmHg (difference between systolic & diastolic)
• Mean circulatory filling: 5-10mmHg

Mean pressure falls as the blood is pushed through systemic circulation.

As blood moves through systemic circulation, the pulse is smoothed out by the elasticity (compliance) of the aorta and resistance vessels. There is little or no pulse in capillaries or veins.

This minimizes the increase in pressure during systole and stores energy.

During diastole the vessels recoil elastically, providing energy to continue to push blood through the systemic circulation.

If the compliance of the aorta decreases, systolic pressure increases, diastolic pressure decreases, and so there is a large increase in pulse pressure.

• Myogenic autoregulation
• Endothelial factors
• Metabolic factors

• Maintains constant flow and important in response to change in posture.
• Vascular smooth muscle contracts in response to passive stretch and relaxes in response to passive reduction in stretch

• -Produced & released by endothelial cells
• Endothelial-derived relaxing factors (EDRFs), such as nitric oxide (basis for Viagra and Levitra -> inhibit enzymes that break down cGMP, which makes vasodilation more effective)
• Endothelial-derived contracting factors (EDCFs), such as endothelin
• EDFRs and EDCFs are important for determining peripheral resistance

• Metabolites (adenosine, K+, H+, CO2, lactate) are potent vasodilators for arterioles in heart and skeletal muscles to adjust local flow needs
• Important for adjusting distribution of flow to meet needs

• Sympathetic input to vasculature is widespread, to both resistance and capacitance vessels.
• Most sympathetic axons release NE, which interacts w alpha-adrenergic receptors, causing vasoconstriction. Vasoconstriction increases peripheral resistance and reduces volume of blood in capacitance vessels.

There is little parasympathetic innervation of blood vessels, but, where it occurs, release of ACh causes vasodilation

• Epinephrine: released by sympathetic input of adrenal medulla; interacts w B2-adrenergic receptors on small arteries in striated (skeletal and cardiac) muscle causing vasodilation. Effects depend on vascular bed.
• Other hormones cause vasodilation (ex: ANP) or vasoconstriction (Angiotensin II)

• Phase 0: Depolarization rapidly increases sodium permeability, therefore Vm goes toward Ena. Sodium channels rapidly inactivating.
• Phase 2: There is a prolonged plateau, Vm = 0 mV, during which calcium influx (Ica) through slowly activating L-type calcium channels is approximately equal to potassium efflux (Ik) through slowly activating delayed rectifier potassium channels.
• Phase 3: Eventually, potassium efflux exceeds calcium influx, the cell repolarizes to Ek.

• - Seen in AV and SA node cells
• - These cells don't have a stable Vm, but depolarize spontaneously to threshold and fire an AP
• Phase 0: There are no rapidly activating Na channels, the relatively slow rising phase of the AP is due to an increase in Ca permeability (Ica); depolarizing.
• Phase 3: Ca+ channels inactivate and delayed rectifier K+ channels (Ik) slowly activate, causing the cell to repolarize toward Ek
• Phase 4: pacemaker depolarizaiton; an unusual cation channel, originally called the "funny"channel, opens in response to repolarization. The influx of Na+ through this channel (If), together w Ca+ influx through the slowly inactivating Ca+ channels (ICa) cause depolarization to threshold. This is opposed by efflux of K+ through slowly closing K+ channels (Ik).

A cluster of cells in the SA node (sinoatrial), located at the junction of the superior vena cava and the right atrium, have slow APs and act as pacemaker cells for the rest of the heart.

• From the SA node through Bachmann's Bundle to the left atrium, through the Internodal Bundle to the atrioventricular node (AV node), and through the atrial muscle cells (atrial myocardium), causing atrial contraction.
• The cells in the conducting pathways (Bachmann's and Internodal Bundles) and the atrial myocardial cells have fast APs and the spread of excitation is very rapid.

• The AV node is a cluster of cells lying between the atria and the ventricles. These small cells have slow APs and excitation spreads through the node very slowly. If the oxygen supply to the heart decreases, the spread of excitation through the AV node may fail.
• *In the normal heart, the AV node is the only place at which excitation can spread from the atria to the ventricles.

The AP spreads from the AV node through the Bundle of His, along the left and right bundle branches on either side of the interventricular septum, amd through the Purkinje fiber system to the ventricular myocardial cells, causing ventricular contraction. The cells in the conducting pathways (Bundle of His, bundle branches, and Purkinje fibers) and the ventricular myocardial cells have fast APs, and so the spread of excitation is very rapid.

• The delay between contraction of the atria and contraction of the ventricles is typically 160 milliseconds, which allows time for atrial contraction to push blood into the ventricle before ventricular contraction begins.
• The delay arises from the time it takes for the AP to spread through the AV node (30 ms) plus the time to spread through the AV node to the ventricles (130 ms).

Under certain conditions, cells in regions of the heart other than the SA node can fire spontaneously and become ectopic pacemakers.

• - P-wave: corresponds to spread of depolarization through the atria
• - QRS complex: corresponds to spread of depolarization through the ventricles
• - T-wave: corresponds to spread of repolarization through the ventricles

This signal is probably lost underneath the large QRS complex.

Too few cells are involved here; the currents are too small to generate a signal that can be recorded from the surface of the body.

• The P-R interval, from the beginning of the P wave to the beginning of the QRS complex, represents the time for excitation to spread from the SA node through the Internodal bundle, the AV node, the Bundle of His, and the bundle branches to the ventricular myocardium.
• In the normal heart, the P-R interval is 160ms.
• Anything over 200 ms is considered abnormal, and is called "1st degree AV block"

The Q-T interval corresponds to the time from the beginning of ventricular depolarization to the end of ventricular repolarization. It is a measure of the length of ventricular APs.

• The S-T segment corresponds to the duration of the plateau phase of the APs in ventricular myocardial cells.
• *Elevation or depression of this segment compared to the baseline indicates damage to the ventricular myocardium.

False. The ECG only measures the electrical activity of the heart. It does not provide information about cardiac output (except during ventricular fibrillation).

• Tachycardia - beating too fast (>100 bpm at rest)
• Brachycardia - beating too slowly (<60 bpm at rest)

• Ventricular fibrillation.
• The organized electrical activity of the heart is completely disrupted and myocardial cells fire spontaneously and randomly. No pressure is developed, cardiac output falls to zero, and the patient requires CPR until a normal rhythm can be re-established.

Contraction of cardiac muscle, as of skeletal muscle, is elicited by an increase in the myoplasmic calcium concentration: the binding of calcium to troponin on the thin filaments enables a force-producing interaction between the thin filaments and the myosin heads of the thick filaments.

An intracellular store, the sarcoplasmic reticulum (SR), serves as the chief source of calcium that causes contraction.

In both muscle types, the release of calcium originates at the junctions between the terminal cisternae of the SR (junctional SR) and the plasma membrane, or plasma membrane invaginations termed transverse tubules (t-tubules).

Dihydropyridine receptor or DHPR

False. The junctional SR contains a different category of Ca2+ channel, which binds the poisonour alkaloid ryanodine, termed RyR.

Cardiac muscle ECC REQUIRES entry of external Ca2+; skeletal muscle ECC does NOT REQUIRE entry of external Ca2+.

• AP spreads into t-tubule system
• Ca2+ channel in t-membrane (DHPR) opens and allows entry of extracellular Ca2+
• Influx of Ca2+ activates RyR2 in SR membrane to cause a much larger flux of Ca2+ from SR into myoplasm
• Ca2+ activates contraction by binding to troponin on thin filaments, allowing actin-myosin cross-bridge cycling and contraction
• Ca2+ is removed from myoplasm by: 1) SERCA2 pumps located in longitudinal SR. Ca2+ diffuses within SR to terminal cisternae, where it binds to calsequestrin (low affinity, high capacity) and 2) NCX Na+/Ca2+ exchanger in junctional domains of plasma membrane and t-tubules and 3) PMCA pump in surface membrane (1 Ca2+ per cycle).

SERCA2 pumps are the most important, taking the majority of Ca2+ ions from myoplasm back into SR. These pumps, found in plasma membrane of longitudinal SR, surround each myofibril & require less energy, since V(sr) = 0.

NCX Na+/Ca2+ exchanger in the junctional domains of the plasma membrane and t-tubules.

In steady state, Ca2+ released from SR is recycled back into the SR by SERCA2, and surface extrusion balances L-type Ca2+ current.

True. Ca2+ efflux in exchange for sodium influx or calcium influx in exchange for sodium efflux.

It operates in [this] mode because of the electrochemical gradient for sodium that is established by the Na/K pump.

These agents work by blocking the Na/K pump, leading to an increase in intracellular sodium. Raising intracellular sodium has a secondary consequence of raising cytoplasmic calcium and the amount of calcium stored in the SR.

• 1) SERCA2 (Smooth ER Ca2+ ATPase) pumps 2 Ca2+ back into SR.
• 2) NCX Na+/Ca2+ exchanger: protein that swaps 3 Na into myoplasm for 1 Ca out to extracellular/T-tubule space; does NOT burn ATP directly.
• 3) PMCA: Plasma Membrane Calcium ATPase pumps out 1 Ca2+ from myoplasm into extracellular space.

False. RyR2 is an enormous homo-TETRAmer with 5,000 amino acids per monomer.

Any Ca2+ released from the SR during diastole would cause Na influx via NCX, resulting in depolarization.

• Diastolic Ca2+ release is dysfunctional in atrial and ventricular myocytes and has been suggested to be a trigger for delay after depolarizations that give rise to arrhythmias.
• The above disease is a result of a mutation in RyR2 that causes it to release Ca2+ too easily. Episodes of this arrhythmia are typically precipitated by elevated levels of norephinephrine and epinephrine.

• Positive chronotropy is increased heart rate, by raising the firing rate of pacemaker cells in the SA node.
• Positively inotropy is increased contractile forces.
• Positive lusitropy is an increased rate of relaxation.

• 1. Increase HR (+ chronotropy)
• 2. Increase contractile forces (+ inotropy)
• 3. Increase Rate of Relaxation (+ lusitropy)

• 1) activation of B-adrenergic receptors
• 2) elevation of cytoplasmic cAMP
• 3) activation of PKA

• 1) the L-type Ca2+ channel
• 2) Phospholamban (PLB)

• Phosphorylation of DHPR increases the amplitude of the L-type Ca2+ current, thus increasing the size of the trigger to activation of RyR2.
• The increased Ca2+ entry also helps to increase the quantity of Ca2+ stored in the SR.
• *Contributes to positive inotropy.

• Phosphorylation causes PLB to dissociate from SERCA2, which relaxes the inhibition and thus increases Ca2+ pumping into the SR.
• This speeds relaxation and increases the quantity of Ca2+ stored in the SR.
• *Contributes to BOTH positive inotropy and positive lusitropy.