Chapter 6 Flashcards
What sensors are involved with regulating blood pressure, blood volume, blood chemistry, and plasma osmolarity?
Blood pressure- baroreceptors, blood volume-volume receptors , blood chemistry(chemoreceptors), and plasma osmolarity-osmoreceptors
What is the general role of peripheral and central receptors?
Peripheral and central sensors work together with the neurohumoral mechanisms to ensure that arterial blood pressure is adequate for perfusing organs. Peripheral sensors such as baroreceptors have afferent nerve fibers that travel to the CNS where their activity is monitored and compared against a set-point for pressure.
What is a “set point”?
An optimal point which if deviated from requires action by select neurohumoral controls
What are the primary regions of the central nervous system involved in cardiovascular regulation?
Medulla oblongata (within brainstem), hypothalamus and the cortical regions work together to regulate autonomic function
From what region of the brain do the parasympathetic vagal fibers innervating the heart originate
from?
The medulla contains the cell bodies for the parasympathetic (vagal) and sympathetic efferent nerves that control the heart and vasculature.
What is the dorsal vagal nucleus and the nucleus ambiguus?
The parasympathetic vagal fibers innervating the heart originate from cell bodies located within the medulla of the brainstem. These cell bodies are found in collections of neurons located here
What is the effect of increased activity of these nuclei?
Reduces SA nodal firing (neg. chronotropy) and slows AV nodal conduction (neg. dromotropy)
What is meant by the term “vagal tone”?
Tonically active, resulting in the resting heart rates being significantly below the intrinsic firing rate of the SA nodal pacemaker
What is meant by the term “intrinsic firing rate”?
How often the SA node spontaneously fires
Describe the anatomy, innervation, and effects of efferent vagal nerve fibers.
Efferent vagal fibers exit the medulla as the tenth cranial nerve and travel to the heart within the left and right vagus nerves. Branches from these nerves innervate specific regions within the heart such as the SA and AV nodes, conduction pathways, atrial myocytes, and the coronary vasculature. The preganglionic efferent fibers synapse within or near the target tissue and form small ganglia, from which short postganglionic fibers innervate specific tissue sites.
What are postganglionic fibers and what role do they play in tissue innervation?
Postganglionic fibers innervate specific tissue sites.
Which vagal nerve primarily innervates the SA node?
Right vagus
Which vagal nerve primarily innervates the AV node?
Left vagus
How do efferent parasympathetic fibers cause direct vasodilation?
Direct vasodilation by parasympathetic activation in some tissues is achieved through the release of Ach, which binds to muscarinic receptors on the vascular endothelium to cause vasodilation through the subsequent formation of nitric oxide
How do efferent parasympathetic fibers cause indirect vasodilation?
Parasympathetic stimulation causes indirect vasodilation in some organs by stimulating nonvascular tissue to produce vasodilator substances such as bradykinin, which then binds to vascular receptors to cause vasodilation
Do parasympathetic nerves primarily regulate blood flow within specific organs, regulate systemic vascular resistance, or regulate arterial blood pressure?
Any existing parasympathetic nerves primarily serve to regulate blood flow within specific organs and do not play a significant role in the regulation of systemic vascular resistance and arterial blood pressure
Draw a schematic representation of autonomic sympathetic and vagal interconnections within the central nervous system.
A
Where does sympathetic adrenergic control of the heart originate from?
Neurons found within the medulla, the most important of which are located in the rostral ventrolateral medulla (RVLM)
What are the effects of increased stimulation of sympathetic neurons originating from the medulla (and the rostral ventrolateral medulla)?
Produces cardiac stimulation and systemic vasoconstriction. Sympathetic neurons within the RVLM have spontaneous AP activity, which results in tonic stimulation of the heart and vasculature
What would occur with sympathetic denervation of the heart and vasculature?
Acute sympathetic denervation of the heart and systemic blood vessels usual results in cardiac slowing and systemic vasodilation
At lower heart rates, what are the differences in sympathetic tone in the heart versus the vasculature?
At low resting heart rates, the effects of sympathetic denervation on the heart rate are relatively small because the heart is under a high level of vagal tone and relatively weak sympathetic tone. In contrast, sympathetic vascular tone is relatively high in most organ circulations, therefore, sudden removal of sympathetic tone produces significant vasodilation and hypotension.
Describe the anatomical path of sympathetic nerve axons that leave the medulla.
Axons from sympathetic neurons leave the medulla and travel down the spinal cord and synapse within the intermediolateral cell column of the spinal cord, and then exit at specific thoracolumbar levels (T1-L2)
Draw a schematic representation of sympathetic and vagal innervation of the heart and circulation.
A
Are sympathetic preganglionic nerve fibers typically shorter or longer than parasympathetic preganglionic nerve fibers?
Sympathetic preganglionic nerve fibers are short compared to preganglionic parasympathetic fibers
What are paravertebral ganglia and vertebral ganglia?
Paravertebral ganglia (cervical, stellate, and thoracolumbar sympathetic chain) are located on either side of the spinal cord Prevertebral ganglia are located within the abdomen (celiac, superior mesenteric, and inferior mesenteric ganglia)
Are sympathetic postganglionic nerve fibers typically shorter or longer than parasympathetic postganglionic nerve fibers?
Postganglionic sympathetic fibers are long compared to postganglionic parasympathetic fibers
Do postganglionic sympathetic fibers innervate arteries? Veins? Capillaries?
Innervate arteries and veins while capillaries are not innervated
When postganglionic sympathetic fibers innervate vessels, in what tunic of the vessel do they connect with the vessel?
Small branches of these efferent nerves are found in the adventitia layer of the blood vessels
What are varicosities?
Small enlargements along the sympathetic nerve fibers, provide the site of neurotransmitter release
What components of the cardiovascular system do postganglionic sympathetic fibers innervate?
SA and AV nodes, conduction system, cardiac myocytes and coronary vasculature
What will activation of postganglionic sympathetic fibers do to chronotropy, dromotropy, and inotropy?
Sympathetic activation increases chronotropy, dromotropy, and inotropy
Does sympathetic activation cause vasodilation or vasoconstriction in the coronary vasculature?
Why is this a paradox?
Vasoconstriction. It is a paradox because increases cardiac activity produces metabolic coronary vasodilation that overrides that direct sympathetic vasoconstrictor effects on the coronary vesseles
In the body organs, what does sympathetic activation of resistance vessels do to vascular tone?
Contributes to the vascular tone
What happens to blood flow when an α- adrenoceptor drug is administered?
Blood flow increases, the amount of which depends upon the degree of sympathetic tone and the strength of local autoregulatory mechanisms that will attempt to maintain constant blood flow.
Explain how standing up serves as an example of sympathetic and vagal reciprocity.
Baroreceptor reflexes cause the RVLM to increase sympathetic outflow to stimulate the heart (increase HR and inotropy) and to constrict the systemic vasculature
At rest, which division of the central nervous system (vagal or sympathetic) is more dominant in the heart?
Vagal influences are dominant over sympathetic influences in the heart
What is the flight-or-fight response?
Coordinated responses including sympathetic mediated tachycardia, increased inotropy, catecholamine releases and systemic vasoconstriction. Hypothalamic activation of sympathetic neurons within the RVLM and inhibition of vagal nuclei
What are the effects of sudden fear, strong emotion, fear, and anxiety on the cardiovascular system?
Can sometimes cause vagal activation leading to bradycardia, withdrawal of sympathetic vascular tone and fainting
What is vasovagal syncope?
fainting
What neurotransmitter is released from sympathetic efferent nerves to the heart?
Norepinephrine
What postjunctional receptors for this neurotransmitter are located on the heart?
What postjunctional receptors for this neurotransmitter are located on the heart?
List the order of functional importance for the three postjunctional adrenoceptors in the heart.
B1>B2>A1
What are the effects of sympathetic stimulation on cardiac chronotropy, dromotropy, and inotropy?
Increase inotropy, chronotropy, and dromotropy
What prejunctional receptors can bind to this neurotransmitter?
A2-adrenoceptors
What are the effects of this neurotransmitter binding to prejunctional receptors?
inhibit NE release through a negative feedback mechanism
What neurotransmitter is released from parasympathetic (vagal) efferent nerves to the heart?
ACh
What postjunctional receptors for this neurotransmitter are located on the heart?
M2, muscarinic, principally in the nodal tissue and in the atrial myocardium
What are the effects of vagal stimulation on cardiac chronotropy, dromotropy, and inotropy?
Decreased inotropy, chrontropy, and dromotropy
What prejunctional receptors can bind to this neurotransmitter?
M2, muscarinic
What are the effects of this neurotransmitter binding to prejunctional receptors?
Inhibit release of NE
What signal transduction pathways are activated by adrenergic and muscarinic receptor stimulation?
Gi-protein/cAMP
What neurotransmitter is released from sympathetic efferent nerves to the blood vessels?
NE
What postjunctional receptors for this neurotransmitter are located on the blood vessels?
A1
List the order of functional importance for the three postjunctional adrenoceptors in blood vessels.
A1>A2>B2
What are the effects of sympathetic stimulation on vascular tone?
Smooth muscle contraction and vasoconstriction
What neurotransmitter is released from parasympathetic efferent nerves to the blood vessels?
NE
What postjunctional receptors for this neurotransmitter are located on the blood vessels?
B2-adrenoceptors
What are the effects of parasympathetic stimulation on vascular tone?
Vasodilation in the absence of opposing a-adrenoceptor mediated vasoconstriction
Draw a figure that shows the location and innervation of arterial baroreceptors.
A
What causes stretching of the vessel wall?
Increasing arterial blood pressure
How do arterial baroreceptors respond to stretching of the vessel wall?
increases the firing rate of individual receptors and nerves
What is unique about each individual receptor?
Each individual receptor has its own threshold and sensitivity to changes in pressure
What happens to the number of receptors that are activated as pressure increases?
Additional receptors are recruited as pressure increases
In what range of pressures do the carotid sinus baroreceptors respond?
60 – 180 mmHg
What happens to the firing rate of a single receptor during systole?
Receptors fire more rapidly when arterial pressure is rapidly increasing during cardiac systole
What happens to the firing rate of a single receptor during diastole?
Receptor firing rate decreases
Draw a curve depicting the effects of arterial pressure on the integrated carotid sinus firing rate.
A
Baroreceptors are sensitive to two primary stimuli; what are they?
Rate of pressure change and to a steady or mean pressure
At what pressure is the carotid sinus sensitivity the greatest?
~95mmHg
What is meant by “greatest sensitivity”?
The point of greatest slope of the response curve
What happens to the carotid sinus firing rate curve with hypertension, atherosclerosis, and exercise?
Hypertension: The curve shifts to the right, reducing the firing rate at any given MAP
Atherosclerosis: Become less compliant and stretch less in response to changes in arterial blood pressure, decreasing sensitivity
Exercise: Medullary and hypothalamic control centers can modulate autonomic efferent responses at a given level of baroreceptor firing, thereby resetting arterial pressure to a higher level
How are baroreceptors located in the aortic arch different than those located in the carotid sinus?
They have a higher threshold pressure for firing and are less sensitive than the carotid sinus receptors
Draw and explain the baroreceptor feedback loop.
A
What happens to the baroreceptor feedback loop when a person suddenly stands up?
Gravity causes blood pooling below the heart, specifically the legs. This decreases venous return, CVP and Ventricular preload. This leads to a fall in CO and arterial blood pressure. Decreased stretching of baroreceptors results in decreased baroreceptor firing and decreased NTS activity. Activating sympathetic nerves and inhibiting parasympathetic nerves. Decreased vagal outflow from the medulla contributes to the elevation in heart rate
What is carotid sinus massage and what does it do?
Manual activation of the carotid sinus reflex by rubbing the neck over the carotid sinus. This increases their firing rate which leads to decreased sympathetic and increased parasympathetic outflow from the medulla
What is the Valsalva maneuver?
Conduct a maximal, forced expiration against a closed glottis and maintaining this for at least 10 seconds
What are the effects of the Valsalva maneuver on the baroreceptor reflex?
fill this in
Draw a graph that describes the effect of the Valsalva maneuver on aortic pressure and heart rate, and describe the four phases involved with changes in these variables.
A
Explain the Bainbridge reflex.
Increased heart rate due to increased stretch caused by an increase in venous return via medullary activation of sympathetic efferent activity to the SA node
What are the effects of an increase/decrease in blood volume on antidiuretic hormone?
Increased blood volume and venous pressure stimulates receptors to decrease ADH release by posterior pituitary. Decreased circulating ADH causes diuresis, which leads to a fall in blood volume and venous pressure. The opposite would occur if dehydration or hemorrhage occurred.
What is the neurologic response to increased activation of vagal afferents found in the atria and ventricles? Explain this response in the context of heart failure. Explain this response in the context of hemorrhaging.
The neurologic response to increased activation of vagal afferents found in the A and V is an increased firing rate of these receptors is enhanced with increased atrial and ventricular pressures
In context of heart failure: A and V filling pressures are increased, whereas arterial pressure is decreased. Increased firing by the AV receptors opposes the decreased firing by arterial baroreceptors
In context of hemorrhaging: Cardiac chamber pressures and arterial pressures are both reduced causing the AV receptor and arterial baroreceptors to decrease their firing rates and therefore reinforce each other
What are chemoreceptors and where are they located?
Specialized cells located on arteries (peripheral) and within the medulla (central)that monitor blood PO2 (partial pressure of oxygen), PCO2 (partial pressure of CO2), or pH.
Primary function is to regulate respiratory activity to maintain arterial blood PO2, PCO2 and pH within a certain range.
What conditions may increase chemoreceptor activity?
Impaired respiratory gas exchange, hypoxic environments, cerebral ischemia, and circulatory shock increase chemoreceptor activity, leading to enhanced sympathetic outflow to the heart and vasculature by activating neurons in the RVLM
Where are peripheral chemoreceptors located?
Small carotid bodies are associated with the external carotid arteries near their bifurcation with the interal carotids. Afferent nerve fibers from the carotid body receptors join with the sinus nerve before entering the glossopharyngeal nerve to synapse in the RTS in the medulla
What conditions will stimulate peripheral chemoreceptors?
By reduced carotid body perfusion, as occurs during hypotension associated with circulatory shock
What is stagnant hypoxia?
Inadequate oxygen delivery to the carotid bodies
Where are central chemoreceptors located?
Found in medullary regions that control cardiovascular and respiratory activity
What conditions will stimulate central chemoreceptors?
Increased firing in response to hypercapnia and acidosis but not directly in response to hypoxia
Describe how ischemic brain reflexes affect the heart and circulation.
Insufficient blood flow to the brain, which occurs during sever hypotension, or when there is cerebral vascular occlusion, causes intense sympathetic activation and constriction of the systemic circulation.
What is the Cushing reflex?
A strong, sympathetic-mediated pressor response, often accompanied by baroreceptor=mediated bradycardia
Describe how pain reflexes affect the heart and circulation.
Generalized sympathetic activation, leading to elevated arterial pressure, tachycardia, and increased sweating. If CO decreases significantly because of the ischemic injury, arterial pressure may fall despite the enhanced sympathetic activity. Deep pain produced by trauma or visceral distension can produce hypotension caused by enhanced parasympathetic and decreased sympathetic activity
What is the cold pressor response?
If a person’s hand or foot is submerged into ice-cold water, arterial pressure increases as a result of sympathetic activation
Describe how the Bezold-Jarisch reflex affects the heart and circulation.
Dezold-Jarisch reflex is triggered by stimulation of specific types of chemoreceptors within the heart and coronary arteries and produces bradycardia and hypotension mediated by vagus nerve afferents and efferences.
Describe how pulmonary and muscle stretch receptors affect the heart and circulation.
Lung inflation activates stretch receptors located in the airways and respiratory muscles that inhibit medullary sympathetic centers and cause arterial pressure to fall, HR increases reflexively.
Limb muscles and tendons also possess receptors that sense tension and length changes. Passive or active movement of joints can stimulate sympathetic activity to the heart and circulation and help to reinforce cardiovascular responses to exercise
Describe how temperature reflexes affect the heart and circulation.
Changes in environmental temperature sensed by cold and warm thermoreceptors in the skin can lead to reflex changes in cutaneous blood flow and sweating.
Changes in core temperature, sensed by thermoreceptors located in the hypothalamus, produce changes in sympathetic activity to the skin circulation
What are the two sources of circulating catecholamines?
Originate from the adrenal medulla (80% E, 20% NE) when preganglionic sympathetic nerves innervating this tissue are activated
Also originate from sympathetic nerves innervating blood vessels (Principally NE)
When the adrenal medulla releases catecholamines, what percentage of this release is comprised of epinephrine?
80%
When the adrenal medulla releases catecholamines, what percentage of this release is comprised of norepinephrine?
20%
What nerves innervate the adrenal medulla?
Preganglionic sympathetic nerves
When are these nerves activated?
During times of stress
What are the possible fates of norepinephrine released from sympathetic nerves innervating blood vessels?
Normally NE released by sympathetic nerves is taken back up by the nerves and metabolized.
A small amount of released NE diffuses into the blood and circulates throughout the body. At times of high levels of sympathetic nerve activation, the amount of NE spilling over into the blood can increase dramatically
What is the fate of most of the norepinephrine released from sympathetic nerves innervating blood vessels?
Normally NE released by sympathetic nerves is taken back up by the nerves and metabolized.
During times of high levels of sympathetic nerve activation, what happens to blood levels of norepinephrine?
At times of high levels of sympathetic nerve activation, the amount of NE spilling over into the blood can increase dramatically
What adrenoceptors bind epinephrine?
B1, B2 A1 and A2 adrenoreceptors
Does epinephrine have a greater affinity for α- adrenoceptors or β- adrenoceptors?
B-adrenoceptors
At low levels of circulating epinephrine, what are the effects on heart rate, inotropy, and dromotropy?
At low to moderate circulating levels of epinephrine, HR, inotropy and dromotropy are stimulated
Through what receptor are these effects (At low levels of circulating epinephrine, what are the effects on heart rate, inotropy, and dromotropy?) primarily mediated?
Primarily B1 adrenoceptor mediated
At low levels of circulating epinephrine, what are the effects on the vascular system in skeletal muscle?
Binds to B2 adrenoceptors located on small arteries and arterioles (particular in skeletal muscle) and causes vasodilation
Through what receptor are these effects primarily mediated?
B2 adrenoceptors
Describe the response of systemic hemodynamics when a low dose of epinephrine is injected intravenously.
HR will increase, SVR will fall, but MAP will change very little
Explain how this response would be different at high plasma concentration of epinephrine.
At high plasma concentrations, CV actions of E are different because E binds to A-adrenoceptors as well as to B-adrenoceptors. Increasing concentrations of E results in further cardiac stimulation along with A-adrenoceptor mediated activation of vascular smooth muscle leading to vasoconstriction. This increases arterial blood pressure owing to both an increase in CO and increase in SVR
Why is there little or no change in vascular resistance even at high circulating concentrations of epinephrine?
Due to vasoconstrictor actions E acting through the A adrenoceptors is attenuated by the E that is still bound to the B2 adrenoceptors
If β2-adrenoceptors were blocked pharmacologically, what would be the effects of high circulating epinephrine concentrations?
High concentrations of E produce very large increases in systemic vascular resistance because of the removal of the B2 adrenoceptor vasodilator influence
What adrenoceptors bind norepinephrine?
B1, 2 and A1, 2
What adrenoceptors does norepinephrine have a greater affinity for?
B1 and A1
If norepinephrine were injected intravenously, what would the effect be on mean arterial blood pressure, pulse pressure, and heart rate?
Increase MAP (systemic vasoconstriction) and pulse pressure (owing to increased SV) and a paradoxical decrease in HR after an initial transient increase in HR
What is meant by “a paradoxical decrease in heart rate” in the textbook?
Due to NE binding to B1 in the SA node, whereas the secondary bradycardia is due to a baroceptor reflex (vagal mediated), which is in response to the increase in arterial pressure
What is a pheochromocytoma and how does it affect the cardiovascular system?
High levels of circulating catecholamines, caused by a catecholamine-secreting adrenal tumor
What are the primary functions of the renin- angiotensin-aldosterone system?
Plays an important role in regulating blood volume, cardiac and vascular function, and arterial blood pressure
What is the primary organ responsible for renin and angiotensin formation?
kidney
According to the textbook, what are the three ways to stimulate renin release into the circulation?
Sympathetic stimulation of the kidneys (B1), renal artery hypotension and decreased Na delivery to the distal tubules (usually caused by reduced glomerular filtration rate secondary to reduced renal perfusion)
Define and describe the action of renin, angiotensinogen, angiotensin-converting enzyme, and angiotensin II in the context of the angiotensin-aldosterone system.
Renin: Formed within and released from juxtaglomerlar cells. Enzyme that acts upon angiotensinogen
Angiotensinogen: A circulating substrate synthesized and released by the liver which undergoes proteolytic cleavage to form decapeptide angiotensin I Angiotensin-converting enzyme: Vascular endothelium, particularly in the lungs, has an enzyme, ACE, that cleaves off two amino acids to for the octapeptide, angiotensin II
Angiotensin II: has several important functions that are mediated by specific angiotensin receptors.
List the primary actions of angiotensin II.
- Constricts resistance vessels, increasing SVR and arterial pressure
- Enhances sympathetic adrenergic activity by facilitating NE release from sympathetic nerve endings, inhibiting NE reuptake by nerve endings and by binding to AT1 receptors in the RVLM, increasing sympathetic efferent activity
- Acts upon the adrenal cortex to release aldosterone, which acts upon the kidneys to increase Na and fluid retention, increasing blood volume
- Stimulates release of vasopressin from posterior pituitary, which acts upon the kidneys to increase fluid retention and blood volume
- Stimulates thirst centers within brain to increase blood volume
- Stimulates cardiac and vascular hypertrophy
When is angiotensin II produced?
Continuously produced under basal conditions
Under what conditions can angiotensin II production change?
Different physiologic conditions, such as exercise or posture change
What is primary hyperaldosteronism and what are its effects on the cardiovascular system?
It is caused by an adrenal tumor that secretes large amounts of aldosterone, which increases arterial pressure through its effects on renal Na retention
What are the effects of ACE inhibitors and AT1 receptor blockers on the cardiovascular system?
Effectively decrease arterial pressure, ventricular afterload, blood volume, and ventricular preload, and inhibit and reverse cardiac and vascular remodeling that occurs during chronic hypertension and heart failure
Draw a diagram that depicts the formation of angiotensin II and its effects on renal, vascular, and cardiac function.
A
Define and describe the actions of atrial natriuretic peptide.
ANP is a 28 amino acid peptide that is synthesized stored and released by atrial myocytes in response to atrial distension, angiotensin II stimulation, endothelium, and sympathetic stimulation (B adrenoceptor mediated)
Under what conditions would you expect to see elevated levels of atrial natriuretic peptide?
Found during conditions such as hypervolemia and congestive heart failure, both of which cause atrial distension
Atrial natriuretic peptide is a long-term regulator of what cardiovascular variables?
Na and water balance, blood volume, and arterial pressure. Most being the opposite of angiotensin II, therefore ANP is a counterregulatory system for the renin-angiotensin-aldosterone system
Draw a diagram that depicts the formation and cardiovascular/renal actions of atrial natriuretic peptide.
A
What are potential mechanisms to explain how atrial natriuretic peptide causes systemic vasodilation?
Mechanism of systemic vasodilation may involve ANP receptor-mediated elevations in vascular smooth muscle cGMP (ANP activates particulate guanyly cyclase). ANP also attenuates sympathetic vascular tone which may involve ANP acting upon sites within the CNS as well as through inhibition of norepinephrine release by sympathetic nerve terminals
Define and describe the actions of vasopressin.
It is a nonapeptide hormone released from the posterior pituitary. Two principal sites of action: the kidneys and blood vessels. Increases water reabsorption by the kidneys by increasing water permeability in the collecting duct, thereby permitting the formation of concentrated urine
Draw a diagram that depicts the cardiovascular and renal effects of vasopressin.
A
Explain how neurohumoral mechanisms are integrated to control blood volume, cardiac output, and arterial blood pressure.
These adjustments enable the body to adjust to changes in body posture, physical activity, or environmental conditions.
Act through changes in SVR, venous compliance, blood volume, and cardiac function which can regulate arterial blood pressure. Each mechanism has independent cardiovascular actions, as well as complex interactions with other control mechanisms that serve to reinforce or inhibit the actions of the other control system
Ex: Activation of sympathetic nerves either directly or indirectly increases circulating angiotensin II, aldosterone, adrenal catecholamines, and arginine vasopressin, which act together to increase blood volume, co, and arterial pressure. These humoral changes are accompanied by an increase in ANP which acts as a counterregulatory system to limit the effects of other neurohumoral mechanisms
