Final Exam Study Guide CardioPhys
80. What determines the amplitude of active hyperemia
The amplitude of the active hyperemia is closely related to the increase in metabolic activity (oxygen consumption).
74. What are some examples of reactive hyperemia
The application of a tourniquet to a limb, and then its removal. During surgery, arterial vessels are often clamped for a period of time, release of the arterial clamp results in reactive hyperemia. Transient coronary artery occlusion (coronary vasospasm) result in subsequent reactive hyperemia within the myocardium supplied by the coronary vessel.
What is vasodilator reserve?
The difference between basal flow and maximal flow represents the flow capacity or vasodilator reserve for the organ.
75. Define active hyperemia.
The increase in organ blood flow that is associated with increased metabolic activity of an organ or tissue. Active hyperemia is important because it increases oxygen delivery to tissues at a time of increased oxygen demand.
Define autoregulation.
The intrinsic ability of an organ to maintain a constant blood flow despite changes in perfusion pressure.
What organs have a relatively small vasodilator reserve?
The kidneys.
73. How would longer periods of vascular occlusion affect the reactive hyperemia response
The longer the period of occlusion, the greater the metabolic stimulus for vasodilation, leading to increase in peak flow and duration of hyperemia. Maximal vasodilation, as indicated by a maximal peak hyperemic flow, may occur following <1 minute of complete arterial occlusion, or it may require several minutes of occlusion depending on the vascular bed and its metabolic activity.
96. In terms of the mechanical forces influencing coronary flow, how is the left ventricle different from the right ventricle
The mechanical forces affecting coronary flow are greatest within the left ventricle because this chamber develops pressures that are several fold greater than those developed by the right ventricle. The right ventricle and, to a lesser extent, the atria show some effects of contraction and relaxation on blood flow within their musculature, but it is much less apparent than that observed in the left ventricle.
What is meant by the term "autoregulatory range"
The range of pressures over which flow shows little change. Below or above the autoregulatory range, flow changes are approximately proportional to the changes in perfusion pressure. The autoregulatory range as well as the flatness of the autoregulatory response curve varies among organs. Flow changes relatively little despite a large change in perfusion pressure.
The ratio of basal flow to maximal flow is a measure of what?
The ratio of basal flow to maximal flow is a measure of the vascular tone, which is the degree of vascular constriction.
90. What causes these fluctuations in flow during the cardiac cycle
The reason that coronary flow is influenced by the cardiac cycle is that during systole, the contraction of the myocardium compresses the microvasculature within the ventricular wall, thereby increasing resistance and decreasing flow.
Define reactive hyperemia.
The transient increase in organ blood flow that occurs following a brief period of ischemia, usually produced by temporary arterial occlusion.
102.What mechanisms are involved with this response
The vasodilation occurs because sympathetic activation of the heart also increases heart rate and inotropy through β-adrenoceptors, which leads to enhanced production of vasodilator metabolites that inhibit the vasoconstrictor response and cause vasodilation.
83. How is the vasodilatory capacity during active hyperemia different among organs
The vasodilatory capacity during active hyperemia differs considerably among organs. In skeletal muscle, blood flow can increase more than 20 to 50-fold during exercise, depending on the type of muscle, Cerebral blood flow increases no more than 2-fold at maximal metabolic activity.
What explains the plateau in this curve?
The vessels become maximally dilated and flow can no longer increase. At higher levels of metabolic activity (oxygen consumption), the vasculature becomes maximally dilated, resulting in a maximal increase in blood flow.
What are the primary actions of tissue factors?
These substances act on the blood vessel to produce either relaxation or contraction of the smooth muscle, thereby altering resistance and blood flow. In some cases, these substances indirectly act on the vascular smooth muscle by affecting endothelial function or by altering the release of norepinephrine by sympathetic nerves. Some of these vasoactive substances are tissue metabolites that are products of cellular metabolism or activity.
How does this change during exercise?
This relative distribution of cardiac output, changes greatly depending on environmental conditions and the state of physical activity. When a person exercises, the increased cardiac output primarily goes to the active skeletal muscles, heart, and skin, at the same time, blood flow decreases to the gastrointestinal and renal circulations.
What are tissue factors?
Tissue factors are substances produced by the tissue surrounding blood vessels.
What is local regulation?
Tissues and organs have the ability to regulate, to a varying degree, their own blood flow. This intrinsic ability to regulate blood flow is termed "local regulation" and can occur in the complete absence of any extrinsic neurohumoral influences.
Explain the consequences of pharmacologic inhibition of nitric oxide synthase.
Vasoconstriction occurs in most vascular beds. This demonstrates that there normally is a basal release of nitric oxide that inhibits vascular tone, blocking nitric oxide formation leads to an increase in tone.
Does carbon dioxide cause vasoconstriction or vasodilation?
Vasodilation
Does hydrogen ion cause vasoconstriction or vasodilation?
Vasodilation
Does hypoxia cause vasoconstriction or vasodilation?
Vasodilation
Does osmolarity cause vasoconstriction or vasodilation
Vasodilation
Does potassium ion cause vasoconstriction or vasodilation?
Vasodilation
Does inorganic phosphate cause vasoconstriction or vasodilation?
Vasodilatory activity in contracting skeletal muscle, but its importance is far less than that of adenosine, potassium, and nitric oxide in regulating skeletal muscle blood flow.
79. What mechanisms may explain active hyperemia
Within seconds of initiating contraction and the increase in metabolic activity, blood flow increases. The vasodilation is thought to be caused by a combination of tissue hypoxia and the generation of vasodilator metabolites such as potassium, carbon dioxide, nitric oxide, and adenosine. The increased blood flow (hyperemia) is maintained throughout the period of increased metabolic activity and then subsides after contractions cease and normal metabolism is restored.
What percentage of the resting cardiac output is directed to the heart, brain, skeletal muscle, skin splanchnic organs, and kidneys?
~ 80%
What equation explains the relationship between flow, pressure, and resistance
"F = " "PA - PV " /"R"
98. What is mean coronary flow at maximal exercise
400 mL/min per 100g
97. What is mean coronary flow at rest
80 mL/min per 100g of tissue
What equation is used to calculate perfusion pressure
=Arterial - Venous pressure =PA-PV
What perfusion pressure values represent the autoregulatory range
? When the perfusion pressure falls below 60 to 70 mmHg in the cerebral and coronary circulations, the resistance vessels become maximally dilated and their ability to autoregulate is lost. At very high perfusion pressures approximately ~170 mmHg, the upper limit of the autoregulatory range is reached and the vessels undergo no further constriction with increase in perfusion pressure, therefore, flow increases as pressure increases.
105.What neurotransmitter is released by parasympathetic nerves at the coronary arteries
Acetylcholine.
101.What is the vascular effect of activating sympathetic nerves to the heart
Activation of sympathetic nerves to the heart causes only transient coronary vasoconstriction (α-adrenoceptor mediated) followed by vasodilation.
100.What metabolite is important in this process
Adenosine has been shown to be important in dilating the coronary vessels when the myocardium becomes hypoxic or when cardiac metabolism increases during increased cardiac work. Nitric oxide.
What is an autocrine substance?
Affect the same cell from which they are released.
What is flow-dependent vasodilation?
An increase in vessel flow (an increase in shearing forces acting on the vascular endothelium) stimulates endothelial nitric oxide production, which causes vasodilation.
What is the mechanism by which reactive hyperemia occurs
Arterial occlusion (no flow) for 2 minutes followed by reperfusion results in a transient increase in blood flow (reactive hyperemia). The effects of a 2-minute arterial occlusion on blood flow. During the occlusion period, blood flow goes to zero. When the occlusion is released, blood flow rapidly increases above normal levels (hyperemia) that lasts for several minutes.
Does histamine cause vasoconstriction or vasodilation?
Arteriolar vasodilation
Does bradykinin cause vasoconstriction or vasodilation?
Arteriole vasodilator
How does carbon dioxide get to the vascular smooth muscle?
As a gas, CO2 readily diffuses from parenchymal cells to the vascular smooth muscle of blood vessels.
92. At what point is coronary blood flow the highest
As the ventricle begins to relax in early diastole, the compressive forces are removed and blood flow is permitted to increase. Blood flow reaches a peak in early diastole and then falls passively as the aortic pressure falls toward its diastolic value.
What are some potential mechanisms to explain autoregulation
Autoregulation may involve both metabolic and myogenic mechanisms. If the perfusion pressure to an organ is reduced, the initial fall in blood flow leads to a fall in tissue PO2 and the accumulation of vasodilator metabolites. These changes cause the resistance vessels to dilate in an attempt to restore normal flow. A reduction in perfusion pressure may also be sensed by the smooth muscle in resistance vessels, which responds by relaxing (myogenic response), leading to an increase in flow.
91. During systole, where is the greatest reduction in blood flow
Blood flow is reduced to the greatest extent within the innermost regions of the ventricular wall (in the subendocardium) because this is where the compressive forces are greatest.
How does this change after a person eats a meal?
Blood flow to the gastrointestinal circulation increases.
What is an endocrine hormone?
Circulate in the blood to reach distant target cells.
99. What is the primary regulator of coronary blood flow
Coronary blood flow is primarily regulated by changes in tissue metabolism.
Draw a figure that shows the autoregulation of blood flow in which the x-axis is time and the y-axis is resistance, flow, and pressure.
Decreasing perfusion pressure from 100 to 70 mmHg at point A results in a transient decrease in flow. With autoregulation, the initial fall in pressure and flow are followed by a decrease in vascular resistance, which causes flow to increase to a new steady state level despite the reduced perfusion pressure (point B).
What is a paracrine hormone?
Different cell types surrounding blood vessels can release vasoactive substances referred to as local, paracrine hormones (histamine, bradykinin, and prostaglandins). A substance released by one cell that acts on another nearby cell by diffusing through the interstitial fluid.
88. What are thebesian vessels
Drain directly into cardiac chambers.
What are some examples of extravascular compression regulating blood flow
During cardiac systole or skeletal muscle contraction (particularly tetanic contractions), vascular resistance is greatly increased and blood flow is impeded by mechanical compression. Lung inflation and deflation alter pulmonary vascular transmural pressures and thereby have substantial effects on pulmonary vascular resistance. Excessive distention of the gastrointestinal tract, as occurs during intestinal obstruction, can increase vascular resistance in the wall of the intestine to a point where tissues become ischemic. Blood vessels in organs such as the brain or kidneys, which are surrounded by a rigid cranium or capsule, are particularly susceptible to increases in extravascular pressure that occur with edema, vascular hemorrhage (cerebral stroke), or the growth of a tumor.
By what mechanism does endothelin-1 mediate its vasoactive effects
ET-1 binds to ETA receptors on smooth muscle cells, which are coupled to Gq-proteins.
What are some stimulators of endothelin-1 synthesis and release
ET-1 can also bind to a second type of receptor (ETB) located on the vascular endothelium that stimulates nitric oxide and prostacyclin synthesis and release, which acts as negative feedback mechanisms to counteract the ETA-mediated vasoconstrictor effects of ET-1. ET-1 formation and release by endothelial cells is simulated by angiotensin II, vasopressin (antidiuretic hormone, ADH), thrombin, cytokines, reactive oxygen species, and shearing forces acting on the vascular endothelium.
What enzyme catalyzes the reaction that results in endothelin-1 formation
Endothelin-converting enzyme (ECE)
76. What are other terms for active hyperemia
Exercise or functional hyperemia.
Describe the metabolic theory of blood flow regulation.
Extensive evidence shows that the actively metabolizing cells surrounding arterioles release vasoactive substances that cause vasodilation. These vasoactive substances, which are linked to tissue metabolism, ensure that the tissue is adequately supplied with oxygen and that products of metabolism (CO2, H+, and lactic acid) are removed. Several substances have been implicated in metabolic regulation of blood flow.
89. Describe changes in coronary blood flow during a single cardiac cycle.
Flow is found to decrease during cardiac systole and increase during diastole. Most of the blood flow to the myocardium occurs during diastole.
Why is this important for the coronary circulation?
Flow-dependent vasodilation is particularly important as a mechanism for increasing coronary blood flow when cardiac activity and metabolism are increased. Impaired nitric oxide synthesis or decreased bioavailability, as occurs during coronary artery disease, limits the ability of coronary blood flow to increase when cardiac activity and oxygen demand are increased.
How and where is carbon dioxide formed within the cell?
Formation increases during states of increased oxidative metabolism. CO2 concentrations in the tissue and vasculature can also increase when blood flow is reduced, which reduces the washout of CO2.
How and where is prostacyclin formed?
Formed from arachidonic acid and the cyclooxygenase enzyme within endothelial cells. PGI2
What is the mechanism of this action?
Formed from the action of kallikrein (a proteolytic enzyme) acting on alpha2-globulin (kininogen), which is found in blood and tissues. Acts on vascular bradykinin receptors, which stimulate nitric oxide formation by the vascular endothelium. Bradykinin stimulates prostacyclin formation.
How is inorganic phosphate formed within the cell?
Hydrolysis of adenine nucleotides (ATP, AMP, and ADP).
Under what conditions would adenosine formation increase?
Hypoxia Increased oxygen consumption
Draw a figure that shows the response of blood flow when there is NO autoregulation in which the x-axis is time and the y-axis is resistance, flow, and pressure.
If NO autoregulation occurs, resistance remains unchanged and flow remains decreased.
Can a muscle removed from the body regulate fluid flow through its vasculature?
If a muscle is removed from the body, perfused under constant pressure from a reservoir containing oxygenated blood, and then electrically stimulated to induce muscle contractions, the blood flow increases. The increase in blood flow occurs in the absence of neurohumoral influences and therefore is a local or intrinsic mechanism.
95. How could this be exacerbated by coronary artery disease
If the coronaries are diseased and their vasodilator reserve is limited, increases in heart rate can limit coronary flow and lead to myocardial ischemia and anginal pain.
What is the effect of sympathetic stimulation on vascular function when β-adrenoceptors are blocked?
If β-adrenoceptors are blocked experimentally, sympathetic stimulation of the heart causes coronary vasoconstriction.
Under what conditions does autoregulation occur and why is it important
In hypotension caused by blood loss, despite baroreceptor reflexes that lead to constriction of much of the systemic vasculature, blood flow to the brain and myocardium will not decline appreciably (unless the arterial pressure falls below the autoregulatory range). This is because of the strong capacity of these organs to autoregulate and their ability to escape sympathetic vasoconstrictor influences. The auto regulatory response helps to ensure that these critical organs have an adequate blood flow and oxygen delivery even in the presence of systemic hypotension. Particularly important in organs such as the brain and heart that depend on a steady state delivery of oxygen to maintain normal organ function.
86. What is the benefit of the high capillary-to-fiber density in the coronary circulation
In order to supply enough oxygen to support the high oxidative metabolism of the beating heart, there must be an extensive network of vessels that provide blood flow throughout the myocardium. Coronary arteries and veins. Regulatory mechanisms exist to ensure that adequate oxygen is delivered to the myocardium.
77. Under what conditions does active hyperemia occur
Increased cardiac activity, increased mental activity, and increase gastrointestinal activity during food absorption.
94. How does heart rate affect coronary perfusion
Increases in heart rate can reduce coronary perfusion. At high heart rates, the length of diastole is greatly shortened, which reduces the time for coronary perfusion.
How is hydrogen ion formed within the cell?
Increases through the bicarbonate buffer system when CO2 increases. Also increases during states of increased anaerobic metabolism (during ischemia or hypoxia) when acid metabolites such as lactic acid are produced.
If perfusion pressure were decreased from 100 to 70 mmHg, describe the response of blood flow initially and over the next few minutes.
It causes flow to decrease initially by approximately 30%. Over the next few minutes, flow begins to increase back toward control as the organ blood flow is autoregulated.
What is the exception to this?
It causes vasoconstriction in the pulmonary circulation.
By what mechanism does prostacyclin mediate its vasoactive effects?
It causes vasodilation by activating smooth muscle adenylyl cyclase, which increases cAMP.
93. What is the most important force driving coronary blood flow
It is the aortic pressure during diastole that is most crucial for perfusing the coronaries.
What amino acid is the substrate for this enzymatic reaction?
L-arginine
87. What is the coronary sinus
Located on the posterior side of the heart. Drains into the right atrium.
Explain the concept of extravascular compression and how it can affect blood flow
Mechanical compressive forces can affect vascular resistance and blood flow within organs. Sometimes this occurs during normal physiologic conditions, at other times, compressive forces can be the result of pathologic mechanisms. The pressure that distends the wall of a blood vessel is the transmural pressure (inside minus outside pressure). If the pressure outside of the vessel increases, then the transmural pressure decreases. At very high extravascular pressures, a vessel can completely collapse. Veins, which have a relatively low intravascular pressure, are more likely to collapse when extravascular pressure is elevated. Arteries can also become significantly compressed when extravascular pressure is elevated to very high levels.
What organs have a relatively large vasodilator reserve?
Most organs have a relatively large vasodilator reserve.
By what mechanism does it do this?
Muscle contraction is initiated by membrane depolarization, which results from a cellular influx of Na+ and an efflux of K+. The Na+/K+-ATPase pump is able to restore the ionic gradients. however, the pump does not keep up with rapid depolarizations during muscle contractions, and a small amount of K+ accumulates in the extracellular space.
Explain the myogenic mechanisms of vascular control.
Myogenic mechanisms originate within the smooth muscle of blood vessels, particularly in small arteries and arterioles. When the lumen of a blood vessel is suddenly expanded, as occurs when intravascular pressure is suddenly increased, the smooth muscle responds by contracting in order to restore the vessel diameter and resistance. A reduction in intravascular pressure results in smooth muscle relaxation and vasodilation. Vascular smooth muscle cells depolarize when stretched, leading to calcium entry into the cell (primarily through L-type calcium channels), phosphorylation of myosin light chains, and contraction.
What factors could affect the autoregulatory range
Neurohumoral influences and disease states.
List the endothelial factors that have vasoactive properties.
Nitric oxide Prostacyclin
Describe the steps by which nitric oxide induces it vasoactive effects; begin with the enzymatic synthesis of nitric oxide and end with its vasoactive outcome
Nitric oxide is synthesized in the endothelium by the action of a nitric oxide synthase (NOS) enzyme on the amino acid, L-arginine. Nitric oxide diffuses from the endothelial cell to the smooth muscle cells where it binds to and activates intracellular guanylyl cyclase to form cGMP, which leads to smooth muscle relaxation.
What enzyme catalyzes the reaction to form nitric oxide?
Nitric oxide synthase (NOS).
What are some stimulators of prostacyclin synthesis?
PGI2 synthesis is stimulated by adenosine and nitric oxide, as well as by many other substances, and therefore can play a secondary role to the vasodilation produced by other substances.
Does endothelin-1 cause vasoconstriction or vasodilation
Potent vasoconstrictor.
Does adenosine cause vasoconstriction or vasodilation?
Potent vasodilator in most organs (although adenosine constricts renal vessels).
How is adenosine formed and where does it come from?
Potent vasodilator in most organs. Formed by the action of 5'-nucleotidase, an enzyme that dephosphorylates adenosine monophosphate (AMP). The AMP is derived from hydrolysis of intracellular adenosine triphosphate (ATP) and adenosine diphosphate (ADP). Adenosine formation increases during hypoxia and increased oxygen consumption, both of which lead to increased ATP hydrolysis. Small amounts of ATP hydrolysis can lead to large increases in adenosine formation because intracellular concentrations of ATP are about a 1000-fold greater than adenosine concentrations.
Does prostacyclin cause vasoconstriction or vasodilation?
Potent vasodilator.
Explain the vasoactive action of arachidonic acid metabolites.
Prostaglandin E2 (PGE2) are vasodilators.
What is meant by the term "basal flow"?
Refers to the flow that is measured under basal conditions (when a person is in a fasted, resting state and at normal environmental conditions of temperature and humidity).
What is the source of potassium ion that reaches blood vessels?
Released by contracting cardiac and skeletal muscle.
What is the source of histamine in this context?
Released by tissue mast cells in response to injury, inflammation, and allergic responses.
84. What explains this difference
Resting skeletal muscle has a high degree of vascular tone in contrast to the cerebral circulation, which has relatively low degree of vascular tone because of its higher metabolic rate under basal conditions.
What is endothelial-derived hyperpolarizing factor and what are its actions?
Some substances (acetylcholine, bradykinin) that stimulate nitric oxide production stimulate EDHF as well. The identity of this factor is not known for certain, but its release causes smooth muscle hyperpolarization and relaxation.
Draw a figure that shows the relationship between blood flow and perfusion pressure.
Steady state autoregulatory flows plotted against different perfusion pressures. Points A and B represent the control flow and autoregulatory steady state flow.
103.What is functional sympatholysis
Sympathetic activation to the heart results in coronary vasodilation and increased coronary flow due to increased metabolic activity (increased heart rate, contractility) despite direct vasoconstrictor effects of sympathetic activation on the coronaries.