GMS 6410 Exam 2 - Exam questions and answers
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GMS 6410 Exam 2 - Exam questions and answers
Circulation Of Blood (University of Florida)
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GMS 6410 Exam 2 - Exam questions and answers
Circulation Of Blood (University of Florida)
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Distance Learning GMS 6410 Exam #2
Your name: Rachel Chandler Answer each question using ~2-5 sentences. When finished, upload on the Assignments page in Canvas.
Dr. Scheuer “Baroreflex” You are helping to run a clinical trial for a Rheos device (to chronically stimulate baroreceptor afferents) to determine if it can significantly lower blood pressure in hypertensive patients. You also have control, normotensive participants. You measure arterial baroreceptor function in all study participants.
A.
How could you test baroreflex function in the participants (i.e. what would be your independent and dependent variables)?
B.
What differences would you expect in baroreflex function between the normotensive and hypertensive patients?
C.
If you could measure nerve activity in the Rostral Ventral Lateral Medulla (RVLM) during a rapid increase in arterial pressure in a normotensive participant, what would you expect to observe just before and during the increase in arterial pressure?
D.
How would stimulation of (i.e. activation of the neurons in) the RVLM influence renal control of sodium excretion? State if there would be an increase, decrease or no change in
sodium excretion and describe the mechanism.
E.
How would stimulation of (i.e. activation of the neurons in) the Caudal Ventral Lateral Medulla (CVLM) influence renin secretion? State if there would be an increase, decrease or no change in renin excretion and describe the mechanism.
A.
To test baroreflex function in the participants, your independent variable could be the lowering of blood pressure and the dependent variable, which is measured
and recorded, would be the heart rate of the patient. B.
In the normotensive patients, you would expect normal increases in heart rate as
blood pressure is reduced however in hypertensive patients, there will not be an increase in heart rate as there will be a difficulty lowering blood pressure.
C.
Just before and during the increase in arterial pressure, you would expect to see a stimulation to the medulla and a release of GABA in the RVLM.
D.
Stimulation of neurons in the RVLM would influence renal control of sodium excretion because the RVLM is the final common efferent pathway responsible for acute BP as well as blood flow increases and is largely responsible for sympathetic nervous activity. This area will serve to influence renal control of sodium excretions because there will be an increase in sympathetic nervous system activity and alpha-2 receptors will be stimulated which will serve to produce large increases in blood pressure and blood flow as well as cause an increase in renal sodium excretion. E.
Stimulation in the Caudal Ventral Lateral Medulla would mean that there has been an increase in the blood pressure which causes increased stimulation of the Downloaded by zee (zezejacks@gmail.com)
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CVLM. The increased blood pressure as part of the baroreceptor reflex will now try to be decreased which will result in a decrease of renin release. Renin in the body serves as an enzyme that acts on angiotensinogen which results in the release of angiotensin 1 which serves to increase blood pressure. Dr. Keller-Wood “Baroreflex in Pregnancy” Pregnancy involves adaptations of the cardiovascular system to the new state.
A.
In human pregnancy, what change in the baroreflex occurs? How is this change reflected in the blood pressure and heart rate measured in pregnant women when they are quietly sitting or lying down?
B.
Other than heart rate, what other measures of baroreflex output (ie the efferent limb of the
reflex) are altered?
C.
What consequences does the change in the baroreflex have on the response to standing in a pregnant woman?
D.
What effect on the baroreflex occurs in women with preeclampsia or pregnancy induced hypertension?
E.
Name two factors that investigators have proposed as mechanisms responsible for the change in baroreflex responses in pregnancy.
A.
In pregnancy, the baroreflex changes because of profound cardiovascular changes caused by increased blood flow and decreased arterial pressure. Increased blood flow means an increase in cardiac output during pregnancy resulting in increased resting heart rate as well as blood flow. There is also decreased uterine vascular resistance as more blood flow is needed to the uterus and decreased resistance in renal circulations as well as smaller constrictor responses and larger dilator responses. Regarding standing and lying down, a lower regulated set point of blood pressure is found during pregnancy and studies have found that cardiac output decreases when pregnant women change from standing to laying down. During pregnancy, blood pressure decreases, and heart rate increases in any position which is contrary to what you would believe. B.
Other than heart rate, renal sympathetic nerve activity is an efferent nerve activity that is altered because of baroreflex alteration in pregnancy. Blood volume as well as cardiac output increase by somewhere from 30 to 50% during pregnancy as well. C.
Due to baroreflex dysfunction and the changes caused during pregnancy, is it shown that a consequence for pregnant women is that they have an impaired sympatho-vagal balance and late gestation women have hypotension immediately after standing. It is also shown that standing for pregnant women produces smaller increases in heart rate, plasma epinephrine and sympathetic nerve recording. D.
In women with preeclampsia or pregnancy induced hypertension, pregnancy induced hypertension is associated with a further increase in sympathetic firing. Also, there is evidence that there may also be a further re-set or desensitization of the baroreflex after hypertension is established in pregnant women. In Downloaded by zee (zezejacks@gmail.com)
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pregnancy induced hypertension, blood pressure does increase without the accompanying renal dysfunction that normally comes with preeclampsia. E.
Investigators have proposed that some of the mechanisms responsible for the factors for change in the baroreflex or changes in the parasympathetic and sympathetic nervous system tones is changes in hormones such as angiotensin, insulin, progesterone/ progesterone metabolites, as well as cortisol. Another mechanism that could be responsible is changes in signals from volume mechanoreceptors that interact with the baroreflex. Dr. Raizada “Gene Therapy Tools” A male patient is admitted to the emergency room with a severe chest pain. The physician determines that he is having a heart attack and needs angioplasty immediately. Cardiac surgeon decides to include a gene therapy strategy to the angioplasty procedure by administrating a viral vector at the site of angioplasty. This viral vector contains a gene that would inhibit vascular smooth muscle cells (VSMC) proliferation:
A.
Why did the surgeon choose a gene that would VSMC proliferation?
B.
Would you recommend that the surgeon uses a vector that can integrate into the patient’s genome so that the inhibitory gene can be expressed for a long time (years)? Give the rationale for the choice.
C.
Would you recommend that the surgeon rather uses a vector that would be effective for a short time period (1-6 weeks). If so, why?
A.
The surgeon would choose a gene that would inhibit vascular smooth muscle cell proliferation because this would help to prevent restenosis after angioplasty which will help prevent scar tissue growth that could cause narrowing of an artery again. B.
I would recommend that the surgeon that uses a vector that can integrate into the patient’s genome so that the inhibitory gene can be expressed for long term because we do want the inhibition of vascular smooth muscle cell proliferation to last for years at a time in a patient that has had a heart attack and needed an angioplasty. We want to further inhibit the vascular smooth muscle cells proliferation so that there is no more blockage occurring in blood vessels and arteries causing more blockages in the heart and then making it so the patient will need more stents and surgeries. C.
A vector that would only be effective for a short period of time such as for 1 to 6 weeks would not be the best course of treatment for this patient because then these vascular smooth muscles could proliferate further and build up scar tissue after a short period of time causing blockages again that need to be attended to. Downloaded by zee (zezejacks@gmail.com)
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Dr. Kasahara “Cardiac Development”
A.
List two reasons why studying cardiac development is important.
B.
What are the advantages to utilizing genetically engineered mouse models for understanding cardiac development, which cannot be achieved in humans (list at least two). C.
Describe two components of the atrial septum.
D.
Describe the advantages to having two components of atrial septum during development. E.
Which part(s) of the conduction system maintain characteristics of embryonic/fetal cardiomyocytes? F.
Describe your thoughts why the part(s) of the conduction system maintain embryonic/fetal characteristics from physiological standpoints. A.
Studying cardiac development is important because the heart is the first organ that becomes functional in the vertebrate embryo and nearly 1% of infants born have some form of congenital heart malformation and there is about a 5-10% incidence of fatal congenital heart malformations therefore studying the development could help to prevent these malformations and deaths.
B.
The advantages to utilizing genetically engineered mouse models for understanding cardiac development that cannot be achieved in humans is that in
mouse models, they can be genetically altered in ways that we are able to find the
exact cause of a loss or gain of function in the heart that leads to a particular heart disease or malfunction and also mice are fast and cheap to produce and maintain which means that they are good for experiments because there is no ethical issues and they are cheap and do not require much space. C.
The atrial septum is formed by 2 different layers, the septum primum which is the top layer component and the ostium secondum. D.
Having two components of the atrial septum has advantages during development
because it helps in preventing any backwards flow of blood and maintains the forward flow. This provides a seal which inhibits movement of blood between the
right and left atrium thus maintaining normal blood flow through the heart. E.
The parts of the conduction system that maintain characteristics of embryonic/fetal cardiomyocytes is the bundle of HIS.
F.
From a physiological standpoint, the conduction system maintains embryonic/fetal characteristics because embryonic myocytes need to maintain function as they are responsible for muscle contraction which causes the heart to
beat. There is no specialized conduction system, and each cardiomyocyte needs to be maintained to keep up with cardiac contractility. Downloaded by zee (zezejacks@gmail.com)
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Dr. Baylis “Long term, renal control of BP”
A.
Give the formula which relates heart function and vascular tone to blood pressure (BP), and explain how kidney function impacts on this relationship.
B.
When a normal person ingests a high NaCl content diet, coordinated actions of the peripheral vasculature and the kidneys prevent a long term rise in BP. Describe how a transient rise in BP and transient rise in blood flow due to a high NaCl meal, each release an agent which changes vascular tone and kidney function, to prevent a chronic rise in BP.
C.
Why do people with chronic hyper-aldosteronism develop secondary hypertension? D.
When renal function is chronically and severely impaired, a “volume-dependent” increase in BP occurs when the subject eats a high NaCl diet. Explain how BP remains elevated at 14 days on a high salt diet, despite the fact that blood volume has returned almost to normal. A.
Flow = BP- venous pressure/ Resistance to flow as well as BP+ TPVR X CO and CO= hr x SV. The Bp is also the driving pressure which is the pressure of the blood from the heart. The kidneys and their function impact this relationship because BP regulation is maintained by organ perfusion and therefore if kidney damage is to occur and they are not perfusing as well, as to say they have a lower or higher volume retention, then although slow, there will be an effect on BP and a decreased arterial BP. Kidney function serves to maintain volumes of fluid within the body and
this will directly impact blood flow and pressure if the volume is increased or decreased from normal. Kidneys are directly responsible for blood volume which controls the venous return and effects cardiac output directly influencing BP.
B.
A transient rise in BP as well as transient rise in blood flow due to a high NaCl meal causes a release of vasodilating/ natriuretic signals such as NO and ANP, which are agents which changes vascular tone and kidney function to prevent a chronic rise in BP. These will serve to help prevent vasoconstriction and cause a direct increase in sodium excretion which will help to increase filtration rate and inhibit sodium reabsorption to maintain BP. C.
People with chronic hyper-aldosteronism also develop secondary hypertension because they have an inappropriately high aldosterone release in relation to the sodium content of the body which results in renal sodium retention and high blood pressure leading to secondary hypertension because of the loss of sodium homeostasis.
D.
BP remains elevated after 14 days on a high salt diet even though blood volume has returned almost to normal because at high sodium intake, there is hypernatremia in the body which increases water retention. Although blood volume has returned to normal after 14 days the BP will still be increased due to damage that has been done to the endothelium and blood vessels are now narrower causing increased resistance and less flow thus keeping BP high. Downloaded by zee (zezejacks@gmail.com)
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Dr. Delp “Vascular Function”
In anesthetized rats, topical application of insulin (120 ng/ml) to the brain (via craniotomy) caused an increase (approximately 30%) in cortical blood flow (
Katakam et al., Journal of Cerebral Blood Flow & Metabolism
(2009)
29,
1955–1967). Assessment of the reactivity of isolated rat cerebral arteries showed a biphasic dose-response to insulin, with an initial vasoconstriction at 0.1
ng
/
mL, followed by vasodilation at 1 to 100
ng
/
mL.
A.
What cells in the vascular wall mediate the vasoconstrictor response to insulin?
B.
What cells in the vascular wall contribute to the vasodilatory response to insulin? C.
What pathways are likely to be involved in mediating the vasodilation to insulin?
D.
Could the contribution of these vasodilatory pathways be separated and evaluated experimentally?
E.
What role would insulin receptors play in mediating its biphasic response, i.e., vasoconstriction followed by vasodilation?
A.
The cells in the vascular wall that mediate the vasoconstrictor response to insulin
are the smooth muscle endothelial cells.
B.
The cells in the vascular wall that mediate the vasodilatory response in insulin are endothelial cells.
C.
The pathways likely involved in mediating the vasodilation to insulin is the endothelial NOS. Insulin, in significant amounts, acts as a vasodilator of blood vessels as it stimulates the eNOS. Blood vessels are activated which in turn serve to activate guanyl cyclase which converts GTP into cGMP, which will cause stimulation of the protein kinase responsible for the blocking of calcium channels located on the endothelial smooth muscles which will lead to smooth muscle cell relaxation and therefore they will vasodilate. Another pathway that insulin can be involved in to cause vasodilation is that it can also cause calcium efflux from endothelial muscle cells via the ca2+-ATPase pump which will also lead to vasodilation of vessels. D.
Yes, the contributing vasodilatory pathways could be separated and evaluated experimentally E.
Insulin receptors can play a role in mediating its biphasic response because when
insulin acts to increase NO synthase action which will increase the amount of NO
causing vasodilation, there is a negative feedback system in the body that activates to then in response counteract this effect. The endothelium and insulin Downloaded by zee (zezejacks@gmail.com)
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receptors are involved in regulating the vascular response to insulin. Insulin promotes the release of nitric oxide and in a state of sustained exposure to higher
concentration, the biphasic response of receptors is to instead have a generation of endothelin which serves in the negative feedback to cause vasoconstriction. Endothelin receptor blockade facilitates the maintenance of vasodilation despite high insulin concentrations.
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