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145 Cards in this Set
- Front
- Back
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What is the sequence of events that take place in the contraction of a cardiac myocyte?
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1. Action Potential travels down a T-tubule invagination triggers...
2. Minor entry of activator Ca2+ through L(ong lasting)-type Ca channel 3. Ca 2+ mediated Ca 2+ release from Sarcoplasmic reticulum. 4. Elevated [Ca2+]intracellular initiating 5. Myofilament activation (as in skeletal muscle) followed by... 6. Reuptake of most Ca2+ by SR Ca2+ ATPase, as well as removal by plasma membrane 3Na+/Ca2+ exchanger, and plasma membrane Ca2+ pump, together lowering intracellular Ca2+ allowing... 7. Relaxation |
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Describe the T-tubules. What are their functions and how does the their structure assist in these functions?
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The T-tubules are invaginations of the plasma membrane of muscle cells and closely associate with the SR. These invaginations allow a depolarization to be conveyed to the inside of a muscle cell and trigger release of Ca2+ from the SR as a result.
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Describe the energy requirements/ consumption of cardiac myocytes.
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Cardiac myocytes require massive amounts of ATP. Therefore cardiac myocytes have an abundance mitochondria (30% of volume) to regenerate ATP aerobically using oxygen from blood.
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What are the four transport proteins involved in the mobilization and resequestration of Ca+?
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1. L-type Ca2+ channel in the T-tubule membrane (allows initial calcium spike)
2. Ca2+ release channel in the SR membrane (Ca2+ mediated Ca 2+ release) 3. Ca2+ pump (called SERCA) in the SR membrane (Re-sequestration of Ca 2+ into SR) 4. 3Na/Ca exchanger in the plasma membrane (Lowering Ca2+ concentration to baseline) |
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Other than Ca2+, what regulates force of contraction in CARDIAC muscle?
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1. Sympathetic stimulation by norepinephrine. Activation of cardiac B1 receptors allows a greater increase in intracellular Ca2+ concentration in response to depolarization.
2. Cardiac myocytes contract with more force at longer fiber/sarcomere lengths but contract with less force at a shorter length 3. Intracellular acidification (one consequence of ischemia) reduces contractility |
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Chemical effectors of contractility? (Promoting or depressing Ca2+ release)
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1. Promoting Ca2+ release: Norepinephrine, epinephrine, caffeine, and angiotensin II. Also elevation of serum Ca2+ could promote Ca2+ release as well
2. Depressing Ca2+ release: B1 (Beta) blockers, barbituates, intracellular acidification (hypoxia) |
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What is "activator" Ca2+?
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The Ca2+ influx that comes through the L-type Ca2+ channels in the T-tubules as a result of depolarization. The resulting spike in intracellular Ca2+ is called the Ca2+ "spark" . This activator Ca2+ comprises only 15% of Ca2+ that contributes to contraction.
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What is Ca2+ mediated Ca2+ release?
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Release of Ca2+ from SR as a result of the intracellular Ca2+ spike from the L-type Ca2+ channels in the T-tubules as a result of depolarization. This SR release of Ca2+ comprises 85% of the Ca2+ that initiates contraction.
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What mediates the pumping of Ca2+ back into the SR? What regulates it? What % of released Ca2+ is taken back up by this mechanism?
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SERCA (Smooth/Endoplasmic Reticulum Calcium ATPase) pumps Ca2+ back into the SR. This pump is regulated by phospholamban. SERCA mediates the reuptake of 70-90% of released Ca2+ .
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What are the only two ways in which the force at which the heart contracts?
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1. Change initial fiber length: (ie move along the Starling curve). For example stretching the fiber more (by increased ventricular filling (EDV)) increases the sensitivity of fibers to Ca2+, the overlap of thick and thin filaments, the amount of Ca2+ released by the SR
2. Change Contractility: (at the same fiber length, shifting to a new Frank Starling curve) this is known also as inotropism. In Positive inotropism more Ca2+ is delivered to myofilaments faster, so greater force is developed faster, and Ca2+ is re-sequestered into SR faster, faster relaxation. |
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What determines the initial length of fibers in the intact ventricle?
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The end diastolic volume or EDV. This in turn is determined by the preload; which is the summation of the forces that promote ventricular filling.
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What is the functional implication of the Starling Mechanism?
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The heart can match its output to the venous return. Furthermore, by adjusting SV so that CO matches venous return, the heart can regulate its size (if EDV increases but SV does not the heart would swell more with each subsequent beat)... BOOM!
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What factors cause preload to change beat-to beat?
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Breathing, sympathetic venoconstriction, posture/gravity, and skeletal muscle activity. Functional implication is that an increase in preload causes a correspondingly increased SV on the next beat.
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What is afterload and what are its functional implications.
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Afterload is the resistance the ventricle must overcome to eject its stroke volume. When subjected to a greater afterload such as aortic stenosis muscles will contract slower, less , and the duration of the contraction will decrease.
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What are some conditions that raise afterload?
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Aortic stenosis, artherosclerosis, and systemic hypertension
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What are some conditions associated with a decrease in contractility? What do these do to the stroke volume?
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Ischemia, hypoxia, and acidosis. The increase in contractility causes ESV to increase which in turn decreases SV.
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Name on B1 adrenergic agonist. What mediates its positive inotropic response and what are its effects on muscle cells?
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Norepinephrine is a B1 adrenergic agonist which causes positive inotropy by cAMP and PKA. It stimulates L-type Ca2+ channels to increase entering Ca2+ during AP's. It stimulates SERCA allowing more Ca2+ from SR during systole, It also speeds up relaxation.
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What are some negative inotropes? What are their clinical benefits.
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Acidosis decreases contractility (not a good clinical method). Ca2+ channel blockers are used to decrease the workload on the hearts of patients with ischemic heart disease by decreasing contractility and afterload.
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What is the functional benefit that is accomplished through faster relaxation by B agonists.
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Ventricular filling is dependent on ventricular relaxation, therefore faster relaxation is critical to maintaining the increased output. The second function is to coronary ischemia as the coronary blood perfuses the heart during relaxation/diastole
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What is digitalis? How does it work?
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Digitalis is a positive inotropic agent derived from foxglove. It indirectly allows more Ca2+ to be released from the SR by inhibiting the Na/K pump partially which increases intracellular Na+. The 3Na/Ca+ exchanger cusps on equilibrium so the weakening of the Na gradient reduces its function decreasing the amount of Ca2+ it pumps out of the cell. More Ca2+ remains after each beat. SR loads more Ca2+ during diastole and releases more during systole.
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What are the four determinants of End Diastolic Volume? (Essentially preload)
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Filling Time
Filling Pressure Ventricular Compliance Atrial Contraction (kick) |
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What are the determinants of End Systolic Volume?
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Ventricular Contractility
Afterload |
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What are the determinants of Central Venous Pressure?
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Atrial Contraction/Kick
Blood Volume Venous Capacity |
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Where is most blood held at any given time?
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At any given time most (65-75%) of the blood is held in the veins. When fluid is lost or gained, the veins distend to accommodate the volume, but as a result there is a change in pressure.
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What is the effect of sympathetic activation on the veins?
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Venoconstriction which blocks blood flow into the periphery and mobilizes blood back to the thoracic compartment to be made available to the heart.
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What is capacitance? What blood vessel has a large capacitance? What blood vessel has a low capacitance?
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Capacitance=(ΔV)/(ΔP) or the amount of volume that can be held at a given pressure. Veins have very high compliance; that is they can accommodate a large volume with a very small change in pressure.
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How does the heart not deplete the peripheral venous reservoir? (Think Feedback mechanism)
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The heart's CO goes up as venous return increases. Increase in venous return decreases the volume in the peripheral veins which would decrease the pressure (if not for sympathetic venoconstriction), which causes negative feedback to limit CO from increasing more.
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What is the effect of sympathetic stimulation on the CVP?
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Sympathetic stimulation effects the hearts contractility and cause shifts in CVP, (norepinephrine shifts the Starling Curve to the left and up)
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What factors effect venous return?
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Venomotor Tone
Respiration Gravity Venous Valves Skeletal Muscle Activity |
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Venoconstriction is caused by sympathetic stimulation. Explain the effects of venoconstriction on venous capacitance, venous pressure, and ventricular preload.
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Venoconstriction decreases venous capacitance because it increases CVP, and moves blood volume out of veins and toward the heart. This in turn increases ventricular preload.
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What is the effect of venodilation on venous capacitance, venous pressure and ventricular preload?
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Venodilation increases venous capacitance by decreasing venous pressure. Venoconstriction allows blood to stay in the veins and as such venous return to the heart decreases which in turn decreases ventricular preload.
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How does breathing (inspiration vs expiration) effect the venous return?
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Inspiration accelerates venous return while expiration retards venous return.
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How does gravity effect venous return?
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When one lies down, the force of gravity is equal across the surface of the body. However when one is standing upright gravity is pushes down on the extremities. Blood pools in the peripheral veins and does not return to the heart.
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How do venous valves effect the venous return?
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Venous valves are unidirectional valves that only open to allow blood to go toward the heart. This serves to prevent gravity from pooling all the blood in the periphery.
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How skeletal muscles play a role in venous return?
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When the large skeletal muscles in the extremities contract, they compress the veins running through them and when coupled with unidirectional valves they "milk" the blood back up to the thoracic compartment and the heart. Note that this is extremely important in exercise.
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Flow Rate of Blood?
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Q=Flow
P= Pressure R= Resistance Q=(ΔP)/R |
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Laminar vs turbulent flow?
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Laminar flow is flow through a vessel in concentric rings. The outer rings are stationary or approximately so, while the central dot/ring moves the fastest.
Turbulent flow is flow that is fraught with eddies, vortexes, and is dominated by inertial patterns. The energy of the flow is also dissipated as friction (heat), and sound. |
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What is Reynold's number?
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The quantitative measure of the tendency for turbulent flow to occur.
Re=(density x diameter x velocity) / viscosity When Re is greater than 2000, flow takes on turbulent characteristics (in most parts of the body) |
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What is Poiseuille's Law?
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R= (ηL)/(r^4)
Resistance = (viscosity x Length)/ (radius^4) |
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Resistance in series? (Formula and example?)
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Rt=R1+R2+R3
Physiological example; portal vein from intestines to liver. |
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Resistance in parallel? (Formula and example?)
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1/(Rt)= (1/R1)+(1/R2)+(1/R3)
Means that in a parallel circuit the total resistance will be smaller than any of the individual resistances Physiological example: branching from the aorta into multiple systemic arteries. |
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Name the advantages to having a parallel arrangement of organs in the circulatory system.
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1.Large arteries branching off the aorta distribute the blood to each of organ system with minimal resistance and in parallel, enabling all organ systems to receive blood at the same high pressure.
2. Because each organ is fed by a separate artery, each receives fully oxygenated blood, that is, blood that has not been depleted by previously flowing through another organ first. 3. Because blood reaches the organs through parallel paths, blood flow to each organ can be adjusted to match the constantly changing metabolic needs of the organ without affecting flow to the other organs. |
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What is the dicrotic notch?
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A momentary dip seen in the aortic pressure reading that occurs when the atrioventricular valve closes and the artery recoils slightly causing a momentary reversal.
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What is the Pulse Pressure?
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PP= Systolic pressure - diastolic pressure
PP |
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What is the Mean Arterial Pressure?
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MAP= DP + (1/3)(Pulse Pressure)
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What is Systemic Vascular Resistance (SVR)?
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SVR = (MAP)/CO
MAP Drives, SVR impedes. |
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What is the linear velocity of blood flow?
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Velocity (in cm/s)= (Q (ml/sec))/A (cross sectional area; πr^2)
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What does the ventricle impart to the blood?
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Pressure and momentum.
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What is Transmural pressure?
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the pressure difference between the inside and the outside of a chamber or vessel, e.g., the pressure difference between the inside and the outside of the left ventricle, or the pressure difference between the inside and outside of a blood vessel.
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What is Perfusion Pressure?
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the difference in pressure between two different sites in a system of tubes where fluid is flowing. Perfusion pressure is also called the pressure head or the driving pressure.
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What are the 3 factors that contribute to hydrostatic pressure?
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1. Filling pressure of the fluid in the vasculature. Even without the pumping of the heart the vasculature contains a volume of blood within elastic vessels which contribute small but significant pressure.
2. Gravity contributes to transmural pressure (in someone standing up the pressure in the leg veins > than pressure in the neck veins. 3. Pressure generated when the heart pumps against the resistance of the circuit. |
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What are the three things that determine blood viscosity?
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1. Hematocrit
2. Flow rate (slowing of flow increases viscosity; RBC's can form rouleaux) 3. Vessel radius ( viscosity reduced in vessels where flow is single file) |
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What is Hematocrit?
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The % of blood volume occupied by by cells.
Values: Adult Male: 42-50% Adult Female: 39-48% Newborn: 53-68% Infant (3 months): 30-38% Child (10 years): 37-44% |
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Where is the highest amount of resistance found in the vasculature?
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The arterioles. The reason it is not the capillaries is because there are so many capillaries, and they are arranged in parallel, that their summed resistance is less than that of the arterioles.
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Relate Anemia to hematocrit and explain its effect on the heart and blood flow.
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Anemia is low red blood cells; thereby low hematocrit and lowered viscosity of blood. This lowers the systemic vascular resistance, which causes an increase in Cardiac Output. This can culminate is high output heart failure
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Relate Polycythemia to hematocrit and explain its effects on the heart and blood flow.
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Polycythemia is increased red blood cells. This increases the bloods hematocrit and viscosity. In turn, this increases SVR, and causes hypertension and sluggish blood flow.
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What is the Fahraeus-Lindquist effect?
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At low flow rates through very narrow tubes; the viscosity of blood increases. This is likely due to accumulation of blood cells in faster axial stream stacks known as a rouleaux.Due to this the hematocrit, and viscosity near the wall of the vessel decrease greatly.
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How does the Fahraeus-Lindquist effect assist the heart?
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Without the benefit of the Fahraeus-Lindquist effect the heart would have to develop a much higher perfusion pressure.
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What are some factors that play a role in the heart's output?
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1. Output depends mainly on venous return.
2. During each systole the SV depends mainly on the degree to which the ventricle is filled in the preceding diastole (EDV) 3. Output is determined mainly by the capacitance of the veins. |
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From beat to beat what factors vary or match? What is mechanism responsible for this?
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1. Venous return and preload vary beat to beat.
2. CO and venous return are matched (or nearly matched) beat to beat 3. Outputs from left and right ventricles are matched (or nearly matched) from beat to beat. *The main mechanism by which 2 and 3 achieve this is the Frank-Starling Law of the heart |
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Regional blood flow is controlled by a hierarchy of 4 control systems. What are they?
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1. Intrinsic local control: aka metabolic control.Powerful in critical organs like the brain, heart, and skeletal muscle. Includes local metabolic vasodilaters
2. Nervous control: mediated by sympathetic vasoconsticting fibers. Dominant in non-critical organs such as the gut, kidney, and skin. 3. Hormonal control: such as RAA system, ADH, and adrenal catacholamines. Play a role in kidneys, gut, and skin. 4.Long term control; mediated by tissue vascularity by angiogenesis. Takes place over a course of days to weeks. |
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Intrinsic local control works at what level of the circulation? What blood vessels does this entail?
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This mechanism works at the level of the microcirculation; meaning the arterioles, capillaries, and venules. Of these the arterioles are the key players. They regulate flow by dilating/constricting based on contraction/relaxation of smooth muscle.
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Explain perfusion in tissues such as skeletal muscle when compared to the heart or brain.
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In skeletal muscle at rest, only 10% of capillaries are perfused at any given time, this perfusion increases to 90% during exercise. However, in the brain and heart most (70%) of capillaries are perfused at any given time.
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What is the basal tone? What effects it and how?
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Basal tone is the resting level of contraction in blood vessels. Sympathetic augmentation causes vessels to contract further, and sympathetic denervation causes further dilation. Local metabolic factors however usually can cause maximal dilation.
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How is regional blood flow matched to metabolic demand?
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Metabolism generates wast products which need to be removed. Accumulation of these products causes vasodilation to allow blood to supply oxygen to fuel metabolism and wash away the metabolic wastes.Supply matched to demand.
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What are some local vasodilating agents?
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Adenosine, K+, H+, CO2, Lactate, and a decrease in blood oxygen concentration.
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What are the 4 phenomena that local metabolic vasodilation explains?
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1. Intermittent capillary perfusion,
2. Autoregulation 3. Active hyperemia 4. Reactive hyperemia |
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Describe Reactive hyperemia.
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If a tissue's perfusion is blocked for some time then released, the flow will be about 5X normal then return to normal. Explanation is that ischemia forms nutrient debt which the hyperemia pays.
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Describe Active hyperemia.
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In highly active tissues, such as exercising muscles, there is greater buildup of local metabolic waste products which act to vasodilate and increase local blood flow.
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What is autoregulation and what are two local metabolic response explanations for it?
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Autoregulation is how when a tissue bed faces an increasing arterial pressure, the blood flow increases initially but falls to within 10 to 15% of normal in about 30 seconds. this can be explained by myogenic control or local metabolic vasodilation.
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What is the mechanism explaining the myogenic response to increased blood pressure?
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The increase in luminal pressure causes a stretch induced vascular smooth muscle depolarization which opens voltage gated Ca2+ channels and increases intracellular [Ca2+] which leads to the phosphorylation of myosin light chains, which leads to vasoconstriction. In doing so, this lowers blood flow to the tissues perfused by the arteriole in question.
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What is nitroglycerin? What is used for and how is related to local vasodilation?
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Nitroglycerin is an organic nitrate that mimics the effects of NO (vasodilation). Used in patients of ischemic heart disease; dilates coronary arterioles (relieves the ischemia), dilates systemic arterioles (reducing SVR and afterload). It also decreases MAP and the decreasing of LV afterload decreases cardiac work.
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What is the effect of sympathetic activation in the periphery.
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Vasoconstriction takes place in peripheral arteries to limit blood flow to all but heart, brain, and lungs which are not innervated by these sympathetic fibers at all. These sympathetic nervous fibers also produce venoconstriction; which pushes peripheral blood back to the heart where increased CVP is needed to support the higher cardiac output of this fight or flight response.
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Sympathetic fibers can also cause vasodilation. Explain how this can be possible.
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If sympathetic fibers slow their activity/rate of firing below the level of basal tone (resting diameter of vessels as determined by innervation), the blood vessels can dilate.
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Blood pressure/MAP is regulated by several indenpendent systems of feedback control. What do each of these systems have?
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1. Sensor(s) that detect a deviation in blood pressure from a setpoint.
2. Transducer(s) that processes the information, and transmits corrective instructions to… 3. Effectors that act to restore arterial pressure to the setpoint. |
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What are the key players in the regulation of blood pressure?
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The baroreceptors are the pressure sensing neurons, whose impulses are processed by the CV centers of the brainstem which instructs both PANS and SANS to deploy various effectors heart, arterioles, veins, kidneys, thirst, to restore blood pressure.
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What role does the sympathetic nervous system play in controlling arterial pressure?
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Sympathetic stimulation can effect all of the following determinants of arterial pressure; SVR, HR, cardiac contractility, venous tone, and renal urine output.
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What role does parasympathetic/vagal stimulation play in controlling arterial pressure?
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It has a single effect; slowing of the heart rate.
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What are the 4 major inputs of blood pressure regulation.
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1. Baroreceptors
2. Cardiopulmonary receptors 3. Chemoreceptors 4. Muscle metaboreceptors |
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Describe arterial baroreceptors.
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Two arterial baroreceptors; the carotid sinus, and aortic arch stretch receptors. These are located on the output side of the heart and monitor arterial pressure. These receptors monitor blood flow to critical organs; carotid sinus checks the pressure to the brain, aortic arch checks the pressure to the heart.
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The baroreceptors are sensitive to what specifically?
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The baroreceptors are stretch receptors that are sensitive to changes in pressure as opposed to absolute pressures. Furthermore, baroreceptors not only to pressure change, but rate of changing pressure. Rising pressure causes baroreceptors to fire more frequently.
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What information can be transmitted by the firing of baroreceptors?
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Magnitude of pulse pressure (can detect pressure changes), the frequency of the pulse pressure wave (therefore the heart rate), MAP, and possibly respiratory rate because the HR increases on inspiration and decreases on expiration.
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Describe the pressure ranges at which the baroreceptors fire.
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Both carotid and aortic baroreceptors do not fire below 60mmHg (MAP) and fire most rapidly at pressures of 160mmHg or above. Decreases in pressure are almost entirely detected by carotid baroreceptors, while both carotid and aortic baroreceptors detect increases in MAP.
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Why are baroreceptors considered a short term mechanism for correcting blood pressure?
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Over 1-2 baroreceptors adapt to the changed pressure; therefore if their response to the increased changed pressure fails to resolve the change in pressure, the baroreceptors will see the changed pressure as the new normal/steady state. For example chronic hypertension will not be corrected by baroreceptors because they have acclimated to the new higher MAP.
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What is the baroreceptor reflex?
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When a quick drop in in MAP takes place baroreceptor discharge decreases to brain CV centers. This results in withdrawal of vagal tone and increase in sympathetic firing, which increases MAP by increasing HR, cardiac contractility, and SVR. Example; dizziness on standing from recline goes away as baroreceptors correct for peripheral pooling of blood.
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Describe the cardiopulmonary baroreceptors.
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The cardiopulmonary receptors are stretch receptors situated on the walls on the right atrium and large systemic veins which provide the brain with info about how full the veins are and the filling of the ventricles. Due to their detection changes of blood volume these receptors are known as volume sensers.
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When is the firing rate of the cardiopulmonary baroreceptors maximal?
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Atrial systole.
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Describe the cardiopulmonary sequential response to a decrease in CVP which leads to a decrease in ventricular filling (ex dehydration, hemorrhage)
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↓CVP → ↓ Cardiac filling → ↓ frequency of action potentials → ↑ sympathetic drive → ↑ADH
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What is the function of the arterial chemoreceptors? How is this function achieved?
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The arterial chemoreceptors (the aortic and carotid bodies) are stimulated by arterial hypoxia, high blood CO2, and low blood pH. In cases of low BP these receptors interpret this as hypoxia and instruct the brain to vasoconstrict to normalize the blood pressure. Their primary function is regulation of breathing.
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What is the Cushing reflex?
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Increased intracranial pressure due to head truama or a tumor compresses cerebral vasculature causing hypoxia. This leads to a build of hydrogen and CO2 which cause sympathetic augmentation on a massive scale and increases systemic arterial pressure to attempt to perfuse the hypoxic brain.
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What function do the muscle metaboreceptors play and how do they do so?
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These proprioreceptors in skeletal muscle respond to local metabolites in underperfused exercising skeletal muscles. They detect vasoactive metabolites in exercising muscles and instruct the CV centers of the brain to prepare for exercise; ie increased cardiac output.
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What is the Valsalva maneuver?
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A forced expiration against a closed glottis. This occurs normally when one coughs, lifts weights, or defecates. Clinically it is used to test baroreflex competence.
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What are the 4 phases of the Valsalva maneuver?
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1. Forced expiration: ↑ intrathoracic pressure, compresses thoracic aorta, and ↑ MAP.
2. Sustained forced expiration: ↓preload/venous return, sympathetic augementation takes place, ↑HR, vaso and veno constriction. MAP stabilizes. 3. Release: short ↓ in MAP b/c of release of pressure on thoracic aorta, surge in venous return, ↑SV 4. Rebound:↑MAP, baroreceptor activation, and reflex bradycardia |
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What happens during the Valsalva maneuver in patient with orthostatic hypotension due to autonomic dysfunction?
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During phase 2: ↓ Venous return, preload, SV, and MAP. Inadequate sympathetic augmentation, and inadequate ↑ in HR, vaso and veno constriction. Finally MAP fails to stabilize.
Stage 4: no reflex bradycardia. Result: Syncope/fainting |
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What is vasovagal syncope?
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Fainting. Sudden withdrawal of sympathetic vascular tone along with vagally-mediated bradycardia causing hypotension and inadequate perfusion of the brain.
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What are some things that can trigger a vasovagal sympathy and how does the syncope occur?
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Extreme stress, and deep pain (crushing injuries to viscera and limbs) causes a negative influence on CV center. This ↑parasympathetic tone, ↓ decreases sympathetic augmentation. These summate in ↓ in BP.
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What does activation of cutaneous pain receptors do to BP, and what is another physiological event that acts similarly?
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Cutaneous pain or excitement cause a positive influence on the CV center which ↓ parasympathetic tone,↑ sympathetic stimulation and as a result BP↑.
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What does a carotid sinus massage cause? How does this occur sequentially?
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CSM causes vasovagal syncope.
1. External manual stimulation (of carotid sinus) 2. Stimulation perceived as hypertension. 3. ↑ Vagal drive to SA and AV nodes. 4. ↓ Heart rate |
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What are the 4 hormonal mechanisms involved in arterial pressure regulation.
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1. Epinephrine/Norepinephrine (catecholamines)
2. Natriuretic peptides 3. ADH 4. Renin-Angiotensin-Aldosterone system |
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Which one of the following statements is FALSE?
a. As part of the fight-flight-fight response, cardiac output will increase and be diverted from the gut, kidney, and non-working skeletal muscles to the heart and working skeletal muscles. b.The principal mechanism responsible for matching right heart and left heart outputs from beat-to-beat is the Frank-Starling effect. c.When heart muscle cells are stimulated by sympathetic neurons, additional Ca2+ is made available to the myofilaments, and this Ca2+ is then re-sequestered by the SR quicker, at a given end diastolic fiber length. d. On deep inspiration, the resultant surge in venous return results in greater ventricular contractility (positive inotropy). e. In a patient with a hematocrit of 24%, one might expect a high cardiac index and low systemic vascular resistance. |
d. On deep inspiration, the resultant surge in venous return results in greater ventricular contractility (positive inotropy).
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Which one of the following factors would tend to INCREASE arterial pressure?
a. Anemia. b.Administration of a diuretic drug (to increase urine output). c. Postural displacement of venous blood from thorax to periphery. d. Administration of aldosterone. e. Pain associated with dislocation of a shoulder joint. |
D. Administration of aldosterone.
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Which one of the following would NOT predispose (sensitize) an otherwise healthy individual to syncope?
a. drugs (diuretics) or activities (sweating) that reduce central venous volume. b. drugs (like the alpha-1 adrenoceptor antagonist prazosin) or activities (prolonged standing) that promote peripheral venous pooling. c. Laying down in a supine position d. Carotid sinus massage |
C. Laying down in a supine position
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Which ONE of the following, before reflex compensations, would cause the indicated parameter to INCREASE:
a. Tachycardia on central venous pressure. b.Prazosin (α1-adrenoreceptor blocker) on central venous pressure. c. Arterial hypertension on left ventricular end systolic volume. d. A vasodilating drug (e.g., nitroglycerin) on left ventricular afterload. e. A venodilating drug on central venous pressure. |
C. Arterial hypertension on left ventricular end systolic volume.
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Which ONE of the following factors would cause the indicated parameter to DECREASE:
a.Skeletal muscle contractions on central venous pressure. b.Cushing Reflex on arterial pressure. c.Cellular release of adenosine on local arteriolar resistance. d. Valsalva maneuver on heart rate (during maneuver). e. Endothelial generation of nitric oxide on local blood flow. |
C. Cellular release of adenosine on local arteriolar resistance.
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Which ONE of the following factors would cause the indicated parameter to INCREASE:
a. Furosemide (a drug that promotes diuresis) on ventricular preload. b. Furosemide on ventricular afterload. c. Sympathetic augmentation on renal urine output rate. d. Losartan (an angiotensin-2 receptor blocker) on SVR and LV afterload. e. Carotid sinus massage on ventricular filling time. |
E. Carotid sinus massage on ventricular filling time.
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What is stroke Work?
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Stroke Volume x Aortic Pressure
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What is minute work?
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Minute Work = work per minute =
CO x Aortic pressure |
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What is volume work?
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Volume Work = CO (Liters/minute) ≈
External Work |
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What is pressure work?
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Pressure Work ≈ Aortic Pressure ≈ Internal Work
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What are the two forms of metabolism used in the heart? What substrates do these metabolic pathways use. Which of these metabolic pathways is preferred?
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The two types of metabolism used in the heart are
a. Oxidative metabolism (TCA cycle) which uses Free Fatty Acids. b Aerobic glycolysis which uses glucose/and or glycogen Heart muscle prefers to metabolize FFA over glucose and glycogen if FFAs and oxygen are available. |
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What is Myocardial Oxygen Consumption (MVO2)?
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Rate at which the heart consumes O2. MVO2 correlates directly with cardiac minute work. MVO2 varies as needed to match cardiac minute work.
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Name several ways to cause sympathetic stimulation of the adrenal medulla which leads to the secretion of catecholamines.
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Stress, Exercise, Hypovolumia, and Hypoglycemia.
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What percentage of secreted catecholamines are norepinephrine? What does norepinephrine do (receptors and results)?
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20% of the catacholamines secreted by the adrenal medulla are NE. NE acts primarily on α1 adrenergic receptors found mostly in gut and skin, which produce vasoconstriction. NE can also act on the β1 adrenergic receptors of the SA node and myocardium to increase heart rate and increase contractility
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What percentage of secreted catecholamines are epinephrine? What does epinephrine do (receptors and results)?
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80% of the secreted catacholamines are EPI. EPI acts preferentially on β1 and β2 receptors ↑ HR and cardiac contractility. β2 receptors primarily effect metabolism, but in the arterioles in the heart and skeletal muscle they cause vasodilation. β1 receptors in the heart ↑BP and cardiac contractility
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What is atrial natriuretic peptide? Where does it come from and what does it do?
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Atrial natriuretic peptide (ANP) is secreted by atrial myocytes in response to increased blood volume (stretch of the atria), it acts to decrease blood volume and therefore pressure. It accomplishes this by acting on the kidney where it stimulates fluid and Na+ loss by increasing GFR (dilating afferent arteriole and constricting efferent arteriole) , and inhibits reabsorption of Na+ from urine.
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What is another type of ANP (other than that secreted by atrial myocytes)? What does its presence in plasma indicate?
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B type ANP is released by overstretched ventricular myocytes (overstretched means ↑preload; which in turn means ↑EDP and EDP). Therefore plasma levels of B-ANP are now used as a diagnostic method to indicate severity of CHF.
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ADH/vasopressin is released from the posterior pituitary in response to what stimuli?
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The release of ADH from the pituitary is controlled by neural and humoral factors:
a. HYPOTENSION (via signals from the medullary cardiovascular center); b. HYPOVOLUMIA (sensed by atrial volume receptors); c. PLASMA HYPEROSMOLARITY (sensed by hypothalamic osmoreceptors). The strongest signal for ADH release is plasma hyperosmolarity. |
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What does ADH do systemically and locally to the kidneys?
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ADH is also known as vasopressin, and causes veno and vasoconstriction. In the kidneys, ADH promotes decreased urine output by promoting water retention through apical AQP2. Through these mechanisms ADH can correct hypovolumia (water is retained, and venous blood pulled into thoracic compartment by venoconstriction), hypotension (increases SVR by vasoconstriction) and hypoosmolarity (water retention is isoosmotic therefore Na+ is retained as well)
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What does a deficiency in ADH cause?
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Polyuria which is compensated for by excessive thirst and excessive fluid intake (polydipsia).
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Describe the sequence of the RAA system leading up to the activation of Angiotensin II.
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1. Hypotension/Hypovolumia/ or ↑ Sympathetic stimulation is sensed by juxtaglomerular cells in kidney.
2. JG cells release Renin into blood 3. Renin cleaves and activates angiotensin I (from the liver). 4. AT-1 in blood arrives at lungs where it is cleaved again by angiotensin converting enzyme (ACE) into Angiotensin II (AT-II) |
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What does Angiotensin II do?
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Vasoconstiction (corrects hypotension), acts on hypothalamus to promote thirst and release of ADH (restores volume through retention and replenishment), and causes the adrenal cortex to release aldosterone.
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What does aldosterone do?
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Aldosterone is a hormone released into the blood by the adrenal cortex in response to AT-II. It decreases urine output in the kidney by acting on the distal nephron to promote fluid and Na+ retention/reabsorption.
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What are JG(A) cells and what do they do?
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Juxtaglomerular apparatus (JGA) cells are cells that are locaed near the glomerulus and act as renal baroreceptors. These cells are activated by a drop in renal perfusion pressure (lowered renal artery pressure, lowered wall stretch), or sympathetic activation. In response, they secrete renin which sets off the RAA system cascade to restore homeostatsis.
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What are the consequences of renal artery stenosis?
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Decreased perfusion of the kidney persistently. This will cause persistent JGA activation and secretion of renin, which causes a persistent RAA system activation which causes hypertension.
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What is role of ANP with regards to the RAA system?
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ANP is a vasodilator and diuretic; and acts as an antagonist to the RAA system.
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What is the mechanism for long term regulation of blood pressure? Why is this advantageous?
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The kidney regulates the BP for the long term which provides an enormous benefit; the short term methods of regulation of BP can adapt to higher or lower BP as the new steady state over time, but the kidneys do not, therefore the kidneys will attempt to return the BP to normal even if the other mechanisms have failed.
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Show the consequence of ↑BP in terms of compensation (think RAA and GFR).
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↑BP→↑ Renal Blood Flow→ ↑GFR → ↑Urine Excreted (Pressure Diuresis)
AND ↑BP→ ↓Sympathetic activity→ ↓ Renin release→ ↓ Renal Na+ retention→ ↑Urine excretion |
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How much blood loss is sufficient to entail irreversible shock?
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Normal blood volume is about 5.5L. A loss of 30-40% (1.65-2.2L) is sufficient to cause life-threatening/irreversible shock.
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What serves to refill blood volume after a hemorrhage?
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a. Transcapillary refill
b. Fluid (and ion) retention by the kidneys c. Thirst and sodium appetite. |
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In patients of heart transplant the cardiac output increases during exercise (both HR and SV are increased). However the nerve innervating the heart is not transplanted. How does the heart know when to increase its output?
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The adrenal gland is still functioning, and under the control of the transplant patient. The adrenal response to sympathetic stimulation allows secretion of epinephrine and norepinephrine; which innervate the heart. Even though the heart is no longer innervated by the nerves, the chemical mediators of sympathetic activation can act on the heart
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What are the energy costs of the heart in terms of MVO2 and what is the critical implication of this?
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Cellular Maintenance= 20% MVO2
Electrical Properties= 1% MVO2 Volume Work= 15% MVO2 Pressure Work= 64% MVO2 PRESSURE WORK IS ENERGETICALLY EXPENSIVE |
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What is the Law of Laplace? Show both the equation for cylinders and spheres.
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a. Cylinders
T=(Pr)/H b. Spheres (Heart, blood vessels) T=(Pr)/(2H) Where T= wall stress/tension P= internal pressure r= wall radius H= wall thickness |
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How does the Law of Laplace explain how aneurysms once formed tend to get worse?
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T=(Pr)/(2H)
Aorta is thick; which mitigates the high pressure and large radius, which keeps tension manageable. If the wall weakens due to pathology, the pressure forces the aorta to balloon out; which increases the radius, which increases the tension, which causes the artery to balloon out further resetting the cycle |
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How does the Law of Laplace explain how capillaries withstand their relatively high internal pressure despite how fragile they are?
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T=(Pr)/(2H)
Capillaries have tiny radii, offsetting the relatively large pressure. As a result, the relative tension/stress on the capillary wall is manageable. |
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Where does the heart receive O2 from? What mediate this?
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The heart receives O2 from the blood from the coronary arteries.
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What parts of the heart are fed by which coronary arteries?
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The right coronary artery (RCA) feeds the right ventricle and in 90% of people (right-dominant) also feeds the inferior wall and the posterior left ventricle. The left main artery branches off into the Left anterior descending artery (LAD) which feeds the anterior wall and septum, and the Left circumplex artery (LCx) which feeds the lateral wall.
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Capillary density in the endocardium is very high. Relate this to capillary density of skeletal muscle and explain the functional reason for this.
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Capillary density in cardiac muscle can be 10X times greater than skeletal muscle, furthermore, most of (70%) these cardiac capillaries are constantly perfused. This is because during contraction (ventricular systole) the ventricle is compressed and the capillaries cannot feed the endocardium. The high capillary density serves to nourish the heart (reactive hyperemia)
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Why is increasing O2 extraction a viable method to increase O2 delivery in a active heart?
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O2 extraction is already near maximal in a resting heart (≈70%).
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What is the effect of tachycardia on diastolic reactive hyperemia?
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Tachycardia is an increased HR. This increased HR is accomplished by several pathways, but one of which is decreasing the time for diastole to take place. By doing so, the coronary capillaries have less time to perfuse the heart.
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What are the determinates of MVO2?
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Heart Rate
Contractility Preload and Afterload Wall Stress/Tension |
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What drug types can increase MVO2?
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β1 adrenergic receptor agonists such as epinephrine and Vasoconstrictors such as phenylephrine and vasopressin increase the MVO2.
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What drug types can decrease MVO2?
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β1 adrenergic receptor blockers such as propanolol, nitrates such as nitroglycerin, diuretics such furosemide, vasodilators such as ACE inhibitors (ex:captopril) all reduce MVO2.
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What are the greatest determinants of MVO2 increase?
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Pressure work and HR (both have a 1:1 relationship with MVO2) as well as cardiac contractility (.9:1 relationship)
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What determinant of MVO2 causes the least increase in MVO2?
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Volume work (1:12.5 relationship with MVO2)
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What is the Coronary Flow Reserve (CFR)?
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In healthy individuals coronary vessels can increase flow by 3-4 times to meet demands such as exercise. This capacity to increase flow is known as the coronary flow reserve.
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