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138 Cards in this Set
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What are sympathomimetics?
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"Sympath" : referring to sympathetic nervous system
"Mimetic" : mimicking Symmpathomimetics are agents that mimic the effects of sympathetic stimulation |
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What are some examples of direct acting sympathomimetics?
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Epinephrine, norepinephrine, and any α or β agonists
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What are some examples of indirect sympathomimetics?
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Reuptake inhibitors
MAOI's Phosphodiesterase inhibitors α2-blockers Releasing agents |
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What are some examples of direct acting sympatholytics?
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α1 and β blockers
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What are some examples of indirect acting sympatholytics?
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Sympathetic CNS depressants
Adrenergic neuronal blocking agents |
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The heart has mostly what type of receptor? What does sympathetic in influence on this receptor due to the heart?
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The heart has predominantly β1 receptors. Sympathetic stimulation by sympathomimetics like the catecholamines causes the SA node to fire more quickly (↑HR), and the hearts contractility to ↑.
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What type of adrenergic receptors are found in the blood vessels of the skin, splanchnic, and skeletal muscles and what is their response to (chemical) sympathetic stimulation?
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Predominantly, these blood vessels have α1 adrenergic receptors (which constrict blood vessels) and β2 adrenergic receptors (which dilate blood vessels).
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What adrenergic receptors does Norepinephrine act on dominantly and what does this stimulation entail?
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NE acts first on α and β1 adrenergic receptors (which produce vasoconstriction in blood vessels of the skin, skeletal and splanchnic muscles, and an increase in HR and contractility respectively). At higher concentrations however, NE can act on β2 receptors, causing blood vessel dilation.
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What adrenergic receptors does Epinephrine act on dominantly and what does this stimulation entail?
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EPI can act on both β1 and β2 receptors producing increased HR and contractility, and vasodilation in blood vessels respectively. At higher concentrations however α receptors can be effected, which can produce vasoconstriction of blood vessels.
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What is the immediate response to α1 stimulation? What is the reflex response to this stimulation?
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Immediate response is ↑SVR (aka TPR). The reflexive response to this stimulation is a reflex bradycardia.
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What is the immediate response to β2 stimulation? What is the reflexive response that results?
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β2 stimulation causes vasodilation which amounts to an ↓ in SVR (aka TPR). The reflexive compensatory response is reflex tachycardia.
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What are the major and reflex effects of α1 agonists? What is an example of such an agent?
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The major effect of α1 agonists is vasoconstriction of blood vessels via intracellular ↑[Ca2+]. The reflexive action that takes place to compensate for the increased BP is to decrease HR; reflex bardycardia. Example of agent; phenylephrine.
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A 55-year-old male high school teacher, who has been treated for mild hypertension for the past five years, when on a two-week vacation to Machu Picchu in Peru without bring his blood pressure medications. Prior to leaving on vacation his blood pressure was well controlled at 120/80 mm Hg. On day three of his vacation, his blood pressure rose to 180/110 mm Hg and heart rate increased to 110 BPM while in Cuzco (elevation = 11,000 ft) waiting for the train to Machu Picchu. What is the most likely thing that happened?
a.Without his medication his blood pressure rose to its untreated level. b.His BP and HR rose because he had two cups of the local drink, coca tea (‘mate de coca’), which contains cocaine. c.His BP and HR rose because he had two cups of jimson weed tea, which contains atropine. d.He was taking propranolol to control his blood pressure for his hypertension and his beta receptors were supersensitized. e.He reacted to the high altitude. |
D. He was taking propranolol to control his blood pressure for his hypertension and his beta receptors were supersensitized.
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A 25-year male was found wandering in downtown Riverside in a confused and agitated state and was brought to the emergency room for evaluation. Physical examination showed B.P. = 190/90, H.R. = 180 bpm, mydriasis (dilated pupils), agitation, hallucinations, hyperthermia, little or no bowel sounds (decreased intestinal peristalsis), profuse sweating, and palpable bladder (positive signs of urinary retention).
Ingestion of which of the following drugs is most likely to give these symptoms? Choose the BEST answer a. Atropine b. Amphetamine c. Nicotine d. Neostigmine e. Clonidine |
B.Amphetamine
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A 24 year-old female patient presents in your office complaining of episodes of where her hands and some times feet get very cold and turn white when she gets angry. Which of the following is the most appropriate initial drug therapy?
a. Phentolamine b. Amphetamine c. Propanolol d. Reserpine e. Yohimbine |
a. Phentolamine
(alpha blocker, which thus prevents the vasoconstriction. She likely has Raynaud's Phenomenon) |
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A 25-year-old ‘Hippie-looking’ patient was found in the woods gathering food for his family and was brought to the E.R with tachycardia, hyperpyrexia, dry skin, no bowl sounds, hard bladder, and blurred vision. Ingestion of which of the following alkaloids (chemicals that are made by plants and contain nitrogen) is most likely to have produced this patient’s symptoms?
a. Yohimbine b, Nicotine c. Cocaine d. Tubocurarine e. Atropine |
E. Atropine
Nontestable Info: Atropine is derived from 'Deadly nighshade' or Atropa belladonna and is found in North America and many other places in the world. Although the crux of this question is in the symptoms, it is useful to note that unless the question regards a clinic in South America the chances of finding ACCIDENTAL ingestion of curare or cocaine unlikely. |
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While climbing Mount Kilimanjaro in northeastern Tanzania (elevation 19,340 ft), you encounter another climber near the summit with the following symptoms: lethargy, dyspnea, tachycardia (pulse 128), crackling breath sounds, and bluish discoloration of nail beds and lips. The most likely underlying cause of this condition is:
a. Dehydration b. Metabolic vasodilation c. Pulmonary Vasoconstriction d. Sepsis e. Orthopnea f. Pulmonary Embolism |
C. Pulmonary vasoconstriction
Note: Out of all of the answers 'sepsis' was a non-seqtuitur. Sepsis is known as blood poisoning; meaning a bacterial infection has made it into the blood supply and is attacking multiple organs at once, Widespread systemic shock occurs as a result of TNF-α and other cytokines. |
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All of the following tend to promote vasoconstriction and renal salt & water retention EXCEPT:
a. Renin-angiotensin-aldosterone system b. Sympatho-adrenal axis c. Natriuretic peptide system d. Vasopressin e. Heart failure |
C. Natriuretic peptide system
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Which one of the following is NOT an expected consequence of coronary thrombosis with ventricular ischemia:
a. impaired ventricular relaxation b. local release of metabolic vasodilators like adenosine c. increased ejection fraction d. slowed conduction through the zone of ischemia e. increased risk of re-entrant excitation f. reduced stroke volume g. angina pectoris h. injury currents |
C. Increased Ejection Fraction
Comment: If ischemia increased ejection fraction than why is ischemia a bad thing? |
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The treatment of ventricular ischemia is aimed at restoring a better balance between coronary flow (supply) and myocardial O2 consumption (demand). Which ONE of the following drugs would NOT improve this balance?
a. Atenolol, a beta-1 selective adrenergic blocker. b. A positive inotropic drug. c. An angiotensin converting enzyme inhibitor. d. Nitroglycerin to relax vascular smooth muscle. |
B. A postive inotropic drug
Comment: Atenolol would block sympathetic ↑ in HR and contractility. ACE inhbitors stop AT-II from vasoconstricting blood vessels, decreasing blood pressure and afterload. Nitroglycerin ↑vasodilation and decreases resistance. Positive inotropic drugs however force the heart to contract with more force, which would aggravate the ischemia. |
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Which ONE of the following statements is NOT correct?
a. Just as each coronary artery perfuses a specific region of the heart, so each region of the heart has a group of EKG leads that best records its electrical activity. b. On orthostasis, gravity promotes a shift of ~600 ml blood from the thoracic veins to the leg veins, and favors blood flow to the base (as compared to the apex) of the lungs. c. Postural hypotension is minimized by the baroreflex and skeletal muscle pump activity. d. As we begin to exercise, the initial increase in heart rate from 70 to 100 beats/min is primarily mediated by augmentation of sympathetic tone. |
D. As we begin to exercise, the initial increase in heart rate from 70 to 100 beats/min is primarily mediated by augmentation of sympathetic tone.
Note: The beginning of exercise causes ↑HR by withdrawal of vagal tone. The next jump in heart rate is mediate by ↑sympathetic tone, but that comes later. |
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Which ONE of the following statements is NOT correct?
a. After hemorrhage (15% of blood volume lost), the expected reductions in circulating fluid volume and ventricular preload are mitigated by transcapillary fluid shifts that mobilize fluid from the interstitial space to the plasma. b. In kwashiorkor and glomerulonephritis, tissue edema results from a reduced plasma oncotic pressure. c. In congestive heart failure, venous edema leads to impaired alveolar gas exchange and swollen ankles. d. Arteriolar constriction will favor fluid filtration along the downstream capillary. e. Lymphatic flow within the lymphatic vessels toward the subclavian vein is ensured by one-way valves and is promoted by periodic contractions of their smooth muscle coat and compression by surrounding skeletal muscles. |
D. Arteriolar constriction will favor fluid filtration along the downstream capillary
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Which ONE of the following statements is NOT correct?
a. Heart failure is characterized by signs and symptoms of intravascular and interstitial volume overload and shortness of breath with rales, along with signs inadequate tissue perfusion (fatigue and low cardiac reserve). b. In classic CHF with systolic dysfunction, the impaired left ventricle is unable to eject against the arterial pressure (afterload) unless EDV is increased by elevated preload to take advantage of the Frank-Starling length-tension relation of the heart. c. In the initial phase of failure, the ventricle grows thicker by fiber hypertrophy in an attempt to mitigate wall stresses, but this can eventually result in a stiff ventricle with low capacitance and poor recoil (diastolic dysfunction). d. In the latter stages of CHF, neurohumoral factors (norepinephrine, angiotensin-II) promote a detrimental remodeling of the ventricular wall, making the wall thinner and the ventricular cavity larger. e. The Law of LaPlace predicts that the tension required for fibers in the ventricular wall to contract (wall stress) will be reduced as the ventricle is filled (dilated) to a greater degree. f. In heart failure, low cardiac output stimulates compensatory renal mechanisms that conserve salt and water that improve cardiac output (and renal perfusion) by increasing ventricular preload. |
E. The Law of LaPlace predicts that the tension required for fibers in the ventricular wall to contract (wall stress) will be reduced as the ventricle is filled (dilated) to a greater degree.
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All are true of the fetal circulation EXCEPT:
a. Immediately after birth, there is a dramatic reduction in pulmonary vascular resistance and a progressive increase in systemic arterial pressure. b. Placentally-oxygenated blood can bypass the nonfunctional lungs via the ductus venosus. c. Patent ductus arteriosis should be suspected in an infant that exhibits dyspnea, tachypnea (rapid breathing) and pulmonary rales. d. In the first 3 months of life, there is a characteristic leftward shift in the cardiac (QRS) vector. |
B. Placentally-oxygenated blood can bypass the nonfunctional lungs via the ductus venosus.
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What % of syncopes can have their etiologies diagnosed at an initial clinical evaluation. What is the remaining percentage known as?
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The underlying etiology of syncope can be diagnosed in greater than 30% of cases. The remaining 70 or so % are referred to as unexplained syncope.
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What is the most common type of syncope? What is it a clinical example of?
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The most common kind of diagnosed syncope is a neurocardiogenic syncope (aka vasovagal sycope). This type of syncope is thought to be a clinical example of the Bezold-Jarisch reflex.
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What is the Bezold-Jarisch reflex? (physiologically speaking)
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This consists of hypovolemia caused by peripheral venous pooling (can be due to staying upright for a long time, or can be set off by a Head Up Tilt-table). which ↑HR and ventricular contractility by sympathetic means. However, the venous return is impaired due to the pooling and the heart contracts on a near empty chamber which causes sympathetic withdrawal (ends vasoconstriction) and vagal activation. Vagal stimulation ↓HRm and blood fails to reach the brain causing fainting/syncope.
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What is exertional sycnope? What are some the causes of exertional syncope?
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Exertional syncope, is a event of syncope that is set off by high exertion activities such as exercise. Causes include obstructive legions (ie aortic valve stenosis), coronary artery disease, exercise induced AV block, exercised induced arrhythmia. In rare cases, neurocardiogenic syncope can cause fainting during exertion.
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What are some types of drugs that can cause syncope?
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a. Vasodilaters (eg nitrates)
b. Antihypertensives (eg β-blockers) c. Drugs that prolong QT i. Antiarrhythmics ii. Antibiotics (eg Macrolides) Note: This list is nowhere near exclusive, these are just some examples. |
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What is HUT?
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Head Up Tilt-table. A diagnostic test intending to provoke syncope in patients with abnormal responses. In normal patients the test will mildly ↓BP but ↑HR. A patient with a abnormal response will suffer hypotension, faint, and HR and BP↓.
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What are the treatments for vasovagal syncope?
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a. Elevate legs of fainted person above head to push peripheral blood back to thoracic compartment
b. Avoid depletion of volume and vasodilators (no Viagra for the 'faint of heart' haha) c. In cases of severe bradycardia, pacemakers indicated d. Drugs: β-blockers, negative inotropes, anticholinergics, and serotonin antagonists) |
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What is the best predictor of a poor prognosis in an abnormal heart left untreated?
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Low Left Ventricular Ejection Fraction (LVEF)
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In structurally normal hearts what tends to mediate syncope?
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In most normal hearts, syncope is relatively benign and often vagally mediated.
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What are the major effects of β1 agonists?
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Major effects: ↑ force & rate of contraction of heart (via ↑[cAMP]) (e.g. dobutamine; used for CHF)
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What are the major effects of β2 agonists?
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Major effects: ↓ BP; bronchodilation (via ↑[cAMP]) (e.g. Albuterol; used for asthma)
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What is amphetamine? What are it's physiological effects and what is known as?
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Amphetamine is an indirect acting sympathomimetic agent; it is more specifically a NE releasing agent. It is taken up by the presynaptic nerve terminal and then displaces NE, EPI and dopamine from their storage sites. In short; the effect of amphetamine mimics that of NE and EPI (by effecting their release).
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One class of Indirect acting sympathomimetics are Reuptake inhibitors. Provide examples of them and their overall effect.
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Cocaine is a strong reuptake inhibitor of dopamine.
Tricyclic antidepressants are strong inhibitors of reuptake of NE. In short reuptake inhibitors cause an exaggeration of adrenergic responses by preventing the reuptake of relevant chemical mediators. |
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What are MAOI's? What is their effect?
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Monoamine Oxidase Inhibitors are inhibitors of Monoamine oxodase, which is involved in the breakdown of NE and EPI, thus MAOI's enhance adrenergic effects.
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What do α2 Blockers do? What is their overall physiological effect?
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α2-Blockers presynpatically ↑NE release, They also act on CNS to ↑Sympathetic Tone. Their summed physiological effect is an enhancement of SANS activity. An example of such an agent is yohimbine.
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What are the physiologic effect of amphetamine? In this, think in the terms of observable 'symptoms' of sorts.
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Relaxation of bronchial muscles due to released epinephrine.
Constriction of sphincters of urinary bladder. Sweating due to released epinephrine. Dilated pupils In cases of overdose: ↑BP with tachycardia |
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Describe the effect of tachyphylaxsis. What kind of agent can cause it?
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Tachyphylaxsis can be observed when amphetamine is used repeatedly. The physiologic response such as ↑BP will decrease with continued administration of amphetamine, however a direct α-agonist will have no response deterioration, What this means is that only the response to amphetamine has decreased, but the response to NE is still the same.
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If a nonspecific MAOI is used (MAOI's can block breakdown of NE, DA, EPI, and serotonin) what are some of the risky reactions that can take place?
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Hypertensive crisis
Coma Seizures Respiratory depression |
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Why do patients using MAOI's have to adhere to a strict diet?
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Tyramine is a monoamine found in all fermented foods, as well as preserved/processed meats and certain fruits and vegetables. In normal people tyramine is broken down by monoamine oxidase. Patients taking MAOI's however cannot break down tyramine, which can set off a hypertensive crisis.
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What is yohimbine? What is its mechanism and what are its actions?
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Yohimbine is an α2-blocker, which inhibits the presynaptic inhibitory autoreceptors which enhances the sympathetic effect of NE. This stimulates wakefulness and
vigilance (↑nervous tension & attentiveness). |
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What are the characteristics of the Direct Receptor Blocking Agents class of sympatholytic agents?
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They inhibit the ability of neurotransmitter or other sympathomimetic amines to interact effectively with receptors (orthosterically or allosterically). e.g
α-blocker, phentolamine; β-blocker, propranolol |
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What are the characteristics of the Central Sympathetic Depressant class of sympatholytic agents?
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These agents are α2-agonists. Their mechanism is to ↓CNS sympathetic outflow. An example is clonidine.
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What are the characteristics of the Adrenergic Neuronal Blocking Agents class of sympatholytic agents?
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They interfere with storage and/or release of NE, but do not inhibit the
adrenergic receptors. An example of such an agent is reserpine. |
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What is phentolamine? What is used for?
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Clonidine is a competitive blocker of α1 and α2 adrenergic receptors. It is used in the treatment of Raynaud's Phenomenon, which presents as vasoconstriction of the blood vessels of the extremities mostly the fingers, usually as a result of cold or extreme emotion. Blocking α1 receptors will prevent the vasoconstriction.
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What are the effects and reflex and or side effects of α1 blockers?
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α1-blockers ↓BP by ↓vasoconstriction. The reflex effects of these agents are orthostatic hypotension and reflex tachycardia.
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What are the effects of β-blockers on both the heart and airways?
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β-blockers can act on the β1 receptors of the heart, and ↓ both HR and cardiac contractility. In the lungs, β-blockers ↑ airway resistance.
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What is propanolol? Describe its mechanism, and clinical use.
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Propanolol is a Non-selective β-Blocker. It acts on the β1 receptors in the heart and ↓HR, contractility, and CO. It also ↑airway resistance in the lungs. The major use for propanolol is in patients of hypertension, In these patients it ↓renin, and CO. It possibly also blocks presynaptic excitatory β receptors in the CNS which causes a ↓ in release of NE.
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What is clonidine? Describe its mechanism, and clinical use.
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Clonidine is α2-agonist (Central Sympathetic Depressant). It causes a ↓in CNS sympathetic outflow. It is used to treat hypertension and pheochromocytoma.
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What is reserpine? Describe its mechanism, and clinical use.
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Reserpine is a Adrenergic Neuronal Blocking Agent. It binds very tightly to the adrenergic storage vesicles thereby blocking uptake of NE & DA and rendering vesicles nonfunctional. It is used most commonly as a antihypertensive in the third world.
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What will happen to the heart rate and blood pressure of a patient when the propranolol he/she has been taking for the past 6 months is withdrawn? Why?
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Increase in heart rate. Propanolol is a non-selective beta-blocker. If withdrawn, there is no antagonism of receptors. Without the antagonism, the receptors are flooded with norepinephrine that they can suddenly bind to. The receptors are also possibly hypersensitized, generating a larger response to the same amount of stimulus.
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A 55 year-old male patient with a history of essential hypertension
comes to your office complaining that his wife does not like him to touch her at night in bed because his hands and feet are very cold. He also is frustrated that he has little energy to play tennis or run for extended periods of time. Which of the following drugs is most likely to give him these problems? a. Reserpine b. Propranolol c. Phentolamine d. Tranylcypromine e. Clonidine |
B. Propanolol
Propranolol; common side effects of beta blockers. Blocking the beta response (vasodilation) unmasks the alpha response (vasoconstriction) which can block blood flow to extremities producing cold hands. |
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What are the effects of muscarinic agonists?
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• Bradycardia (direct effect)
• Vasodilation, via muscarinic receptors in blood vessels => reflex tachycardia (indirect effect). • Increased secretions of fluids (salivation, mucous, lungs, digestive system and sweating) => dehydration. • Bronchoconstriction (respiratory distress). • Increase in peristaltic activity => diarrhea. |
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Dysautonmia is a rare, recessively inherited disease that is characterized by small-fiber peripheral neuropathy. One clinical test for the disease involves the application of a 2.5% solution of methacholine into the conjunctival sac. Patients with this disorder become miotic while normal
individual show no effects. Why does low-dose methacholine produce miosis in dysautonmia patients but not in healthy adults? |
The nerve ennervating the eye (peripheral) is damaged so the receptors are never exposed to Ach. Thus the receptors are SUPERSENSITIZED to any Ach stimulation
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What are acetylcholine esterase inhibitors?
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These drugs are known as cholinesterase inhibitors or indirect acting agents. They prolong the response to parasympathetic stimulation by inhibiting the breakdown of acetylcholine.
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What is BuChE?
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Butrylcholinesterase/Plasma
Cholinesterase. A scavenger esterase in the serum and lever. Cleaves ester bonds of several substrates including but not limited to; heroine, cocaine, ester anasthetics, and succinylcholine. |
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What is the pathology associated with atypical plasma cholinesterase?
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Atypical plasma cholinesterase is a 'disease' that is found in 1/3000 patients. There is no associated pathology, however these patients cannot hydrolyze carboxylic ester bonds commonly found in drugs. As such, if such a patient is for example anasthetized with ester anasthetics, they will be unable to metabolize are clear the anesthetic and may as a result fall into a coma.
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What are the classes of cholinesterase inhibitors, and what are their durations?
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a. Reversible competitive (very short durations)
b. Carbamates (short duration) c. Irreversible competitive (long durations) |
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What are some examples of reversible competitive cholinesterase inhibitors? What are their clinical uses?
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Edrophonium is used in the diagnosis of Myasthenia gravis. Another example is dibucaine; which is used in the detection of atypical cholinesterase. This is because in normal patients dibucaine significantly lowers cholinesterase activity, but patients with atypical cholinesterase are completely unaffected by dibucaine.
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Provide an example of a carbamate inhibitor of cholinesterase.
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Neostigmine. Binds covalently to acetylcholine esterase, but the binding is hydrolyzed, allowing only an intermediate duration of action.
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What are examples of irreversible competitive inhibitors? How do they work?
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Phosphonates are an example of irreversible inhibitors. They inhibit acetylcholin esterase by binding irreversibly to it (activated serine).
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What are the autonomic effects of ChEI's?
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• Autonomic ganglia: All ganglia stimulated leading to complex effects
depending upon which system dominates (PANS or SANS). • Muscarinic autonomic effectors: predictable: eye, GI tract, CV (bradycardia & tachycardia) BP effects complicated, urinary tract, secretions which can lead to dehydration and excess secretion into the lungs. Note: Sweat glands and vascular smooth muscle do not have parasympathetic innervation |
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What are the three classes of cholincytic agents?
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• Antimuscarinics (Parasympatholytics/Anticholinergics)
• Ganglionic Nicotinic-Receptor Blocking Agents • Neuromuscular Blocking Agents (direct and indirect acting) |
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What is atropine?
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Atropine is a Antimuscarinic/Anticholinergic agent. More specifically, it is a muscarinic receptor blocking agent.
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What are the side effects to atropine exposure?
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a. Dilation of pupils
b. ↑HR (very little reflex change in BP b/c no parasympathetic innervation of blood vessels). c. ↓sweating (hyperpyrexia), ↓salivation (dry mouth), ↓mucous secretion and ↓tears. d. Cyclopegia (paralysis of accomodation to nearby objects) e. ↓GI and bladder motility (constipation and urinary retention) f. ↓Bronchial mucus secretions and dilation of bronchioles. |
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What is trimethaphan?
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Trimethaphan is a Ganglionic Nicotinic receptor blocking agent. It is a short acting ganglionic blocking
agent infused intravenously during surgery to produce controlled hypotension. It has a permanent charge so it is unable to enter and effect the brain, so its actions are all on the periphery. |
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How does the pulmonary vaculature differ from the sytemic vasculature hemodynamically?
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The pulmonary system is optimized for gas exchange and hemodynamically it is characterized as being low pressure, low resistance.
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What is the relationship between the volume of blood held in the pulmonary capillaries and stroke volume?
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At rest the pulmonary capillaries hold about 75mL of blood, which is approximately = SV. What this equates to is that the entire of the blood in the pulmonary circulation is displaced and replaced from beat to beat.
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What is the significance of CHF to the pulmonary circulation?
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In CHF in progressively weakening LV must operate at ↑filling pressure to eject a SV sufficient to satisfy baroreceptors (ventricle operates on a higher position on Frank-Starling curve). When the LV requires filling pressures > 20-25mmHg, the pressure is transmitted back to the pulmonary circulation causing excess filtration of fluid into interstitial and alveolar spaces. This is known as pulmonary edema; the consequences of which are poor ventilation and difficulty breathing.
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Where is pulmonary hydrostatic pressure the highest, and where is it the lowest? Why is this?
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The pulmonary hydrostatic pressure is highest (~21mmHg) at the base of the lungs, this high hydrostatic pressure dilates the vessels in the lung and reduces their resistance allowing greater flow. The lowest hydrostatic pressure is found at the apex of the lung (~3mmHg) where the reduced pressure causes the vessels to collapse during diastole (the apex of the lungs are only perfused during systole). This pressure gradient exists due to the force of gravity.
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What is the nature of the relationship of the cardiac output and the pulmonary circulation?
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The entirety of the cardiac output must pass through the pulmonary circulation.
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What is critical aspect of local control of blood flow with respect to the lungs?
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While acidosis and hypoxia cause vasodilation in the systemic circulation to supply O2 to starved tissues, in the lungs acidosis and hypoxia both cause vasoconstriction. This serves to prevent blood flow to a region of the lung where the blood cannot saturate itself with oxygen.
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What is HAPE and how does it occur?
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HAPE: High Altitude Pulmonary Edema
At high altitudes there is lower O2 concentration; alveolar hypoxia→ widespread pulmonary vasoconstriction→ pulmonary hypertension→ pulmonary edema→ impaired gas exchange→ worsening alveolar hypoxia LOOP |
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A patient presents with HAPE. What are some symptoms that you would expect?
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a. Dyspnea and exhaustion
b. Rapid pulse and respiratory rate c. Coughing w/ pulmonary rales d. Fever and cyanosis MOST Important: You need to be working in a hospital at very high altitudes. |
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What are three possible causes for pulmonary hypertension?
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1. High Altitudes (HAPE)
2. Pulmonary Embolism (a clot, air bubble or other source of debris from systemic vasculature lodges in a pulmonary capillary). 3. ↑LA pressure due to left heart failure or mitral valve stenosis. (This increases LVEDV which is transmitted to the pulmonary circulation, causing pulmonary edema). |
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A patient with a pulmonary embolism would present with what satellite of symptoms?
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a. Dyspnea
b. Angina on inspiration c. ↓ Blood O2 saturation (compared to normal) d. Tachypnea (rapid breathing) e. Cough f. Hemoptysis (coughing up blood) g. Tachycardia |
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What are the four shunts of fetal circulation and what does each do?
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1. Placenta: replacement for nonfunctional fetal lungs, kidneys, GI tract, and liver.
2. Ductus venosus: shunts blood away from the nonfunctional liver and into the vena cavae 3. Foramen ovale: allows blood to pass from right atrium to left atrium to divert from the lungs. 4. Ductus arteriosus: shunts blood that escaped FO from the pulmonary artery to the aorta. |
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What is Patent Foramen Ovale (PFO)?
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The foramen ovale is a small hole in the atrial septum that, in the fetus, helps oxygenated, nutrient rich blood to bypass the nonfunctional fetal lungs. Normally this shunt closes at birth when the abrupt increase in left atrial pressure forces a thin flap of tissue on the left side of the atrium, which is an embryological remnant of the septum primum, to seal the hole. This is called “functional closure”.
During the first years of life, the foramen ovale seals permanently, but in a significant proportion of infants, it fails to seal properly; this condition is called “patent foramen ovale” (PFO). |
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What circulatory changes take place at birth?
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a. loss of placental blood flow ↑SVR and thus MAP
b. baby coughs out fluid in lungs; massive ↓ in pulmonary vascular resistance. c. Pressure in RA ↓ below pressure in LA causing FO to close. d. Pressure in aorta↑ while pressure in pulmonary artery↓; ductus arteriosus constricts (1-8 days), and later seals (1-4 months) e. Hypertrophy of left ventricular wall, and hearts electrical axis swings to the left. |
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What are the two FORCES that determine blood pressure?
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1. Hemodynamic pressure generated by the heart
2. Hydrostatic pressure due to the weight of blood under the force of gravity. |
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Which blood vessels are most effected by hydrostatic pressure?
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Gravity/hydrostatic pressure causes the dependent vessels to dilate, but because arteries have thicker walls it takes more pressure to distend them. Veins on the other hand are highly effected by hydrostatic pressure; when standing for long periods of time, hydrostatic pressure causes venodilation and peripheral venous pooling.
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What is the connection between orthostasis and postural hypotension?
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With orthostasis (the act of standing up) 600mL of blood is shifted from the thoracic compartment to the periphery. This takes place DESPITE COMPENSATIONS! This shift in blood causes ↓CVP, ↓preload, ↓SV, and ↓CO by about 40%. The last of these can lead to postural/orthostatic hypotension.
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What are the four mechanisms that act to minimize peripheral venous pooling?
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1. Respiratory pump
2. Venous tone 3. Skeletal muscle contractions (pump) 4. One way venous valves |
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What is the physiological meaning of "anticipation of exercise"?
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Anticipation of exercise supresses vagal tone which is what causes the initial increase in HR as exercise begins. Eventually sympathetic discharge increases as well and together these effects cause
a. ↑HR b. ↑ cardiac contractility c. Venoconstriction to mobilize blood back to thoracic compartment d. ↑ peripheral vascular resistance; to all non working systems (skin, kidneys, gi) |
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What determines perfusion/blood flow during moderate exercise?
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Local metabolic factors determine blood flow during moderate exercise. This allows the blood to perfuse only the muscles that need nutritive blood flow as determined by level of local metabolic vasodialtors. These local agents may be seen as ↑CO2 locally, and a decrease in pH (example). Coupled with increased temperature of the vascular bed this optomizes release of O2 from hemoglobin (shifts the oxyhemoglobin curve to the right).
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What is the greatest mediator of increased CO during exercise?
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The increase in HR.
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What is meant by cardiac reserve?
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Cardiac reserve is the maximum % that the CO can increase above normal
. This is larger in athletes but smaller in patients with coronary artery disease and moderate valvular diseases. In severe MI and valvular diseases however, patients have negative cardiac reserves; that is to say their hearts do not even meet the demands of a resting heart. |
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What is meant by "zone of infarction"?
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A zone of infarction is an area in which the cells are all dead. It is often bordered by a zone of injury.
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What is the meaning of a "zone of injury"?
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A zone of injury surrounds a zone of infarction and is often bordered by a zone of ischemia. In this zone, the function of all the cells it encompasses are irreversibly impaired.
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What is the meaning of a zone of ischemia.
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A zone of ischemia is an area of tissue that is in oxygen debt. The function of the cells in this zone are impaired but the damage is still reversible should normal perfusion resume.
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What are the the satellite of symptoms that are known as the hallmarks of ishemia and infarction?
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a. Angina pectoris
b. Dyspnea c. Diaphoresis (cold sweat) d. Nausea e. Signs of dying heart muscle cells (detected in blood) f. Characteristic EKG changes? |
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What are the signs of myocardial infarction which can be detected by assaying of sampled blood?
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Detection of;
-Troponin-I -Creatine-kinase MB -Myoglobin in the blood Note: These compounds can also be found in samples taken from cases of rhabdomyolysis, however the other symptoms would usually differentiate rhabdo from MI. |
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What are some of the EKG changes associated with MI?
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Transmural Infarction:
a. ST segment elevation b. Abnormal Q waves; wide or deep Non-transmural Infarction: a. ST segment depression |
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How are the cells in an ischemic margin impaired?
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These cells suffer from impaired force generation, slower period of relaxation, and a dissipation of the Na+ and K+ gradients.
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What are the metabolic responses to ischemia in cardiac muscle cells?
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1. Store of creatine phosphate depleted
2. Conversion of metabolism to anaerobic glycolysis a. Depletion of ATP b. Increase of ADP c. Increase of H+ and free phosphate d. Decrease in pH |
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What is the sequence of failure that occurs in ischemic muscle tissue?
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1. Impaired rate of relaxation (brought on by impaired resequestration of Ca2+ by SR, and the ↑ratio of ADP/ATP inhibits release of cross bridges), impaired contractility and leak of K+ and gain of Na+
b. Onset of contracture (rigor) c. Na+/K+ ATPase failure |
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Why does the resting membrane potential in ischemic tissue depolarize?
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In ischemic tissue, there is a leakage of K+ out of the cell, and a net entry of Na+. The membrane potential is determined by the conductances of these ions, and their leakage has caused the Em to depolarize toward the resting potential of Na+.
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Why is conduction in ischemic tissue slowed down in some cells, while some cells do not conduct AP's at all?
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Due to the depolarization of the resting potential of cells in ischemic tissue, there will always be a suboptimal conduction due the fact that some Na+ channels will be refractory. If the cell's resting potential depolarizes sufficiently, all the Na+ channels will be inactivated.
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What are some consequences of a cardiac ischemia in the context of CONDUCTION?
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The speed and path of conduction in the heart will be altered due to the ischemic cells. Furthermore, due to the alterations in refraction in the cells the likelihood of re-entrant circuits (arrythmias) increases.
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How does ischemia promote the formation of injury currents (can be seen on EKGs)?
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In a normal ventricle during diastole the ventricle is uniformly polarized meaning there is no currents. In an ischemic heart, part of the ventricle will be depolarized and refractory allowing a current to exist between the ischemic region and the normal polarized tissue. This local ischemic depolarization also disrupts the spread of conduction and creates the opportunity for reentry.
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What are some therapeutic methods of altering ventricular preload?
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Ventricular preload can be rapidly decreased by nitrates. It can also be decreased (much less rapidly) by diuretics. However, ventricular preload can be increased by intravenous infusions.
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What is congestive heart failure?
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CHF is when the heart is unable to pump enough blood to meet the metabolic demands of the body OR when the heart can only meet metabolic demands of the body by having an ↑LV filling pressure (preload).
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What are the manifestations of inadequate tissue perfusion?
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Fatigue, exercise intolerance, tachycardia, pale clammy skin, and weak pulse.
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What are the signs of (LV) volume overload?
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Dyspnea, rales, edema, jugular vein distension, and nocturia (frequently needing to urinate at night)
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Describe the two forms of CHF.
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Systolic Dysfunction
• Impaired ventricular contractility • LVEF reduced Diastolic Dysfunction • Impaired ventricular compliance & filling • LVEF normal |
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How are patients with CHF "living on preload"?
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In CHF, the left ventricle is unable to sufficiently eject blood into the systemic circulation, which in turn ↑ESV, to which the venous return is added to. As such there is an ↑ in stretch of the myocyctes allowing the failing heart to develop higher pressure (Frank-Starling mechanism).
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Why does left heart failure lead to right heart failure over time?
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In left heart failure the left ventricle fails to pump an adequate SV to meet the needs of the systemic tissues. The ↓ volume causes hypotension which the baroreceptors try to compensate for with the RAA system. Also the hypotension causes ↓ renal perfusion which also activates RAA system. These mechanisms cause retention of Na+ and H2O which increases CVP and thus venous return. The increase in venous return will continue and increase the preload on the right atrium causing its eventual failure as well.
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Why are renin and AT-II elevated in CHF?
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The ↓ in LV stroke volume leads to hypotension activating baroreceptors, and the hypotension also causes ↓ renal perfusion. As a result the RAA system is highly activated in patients with CHF.
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What occurs physiologically in heart sound S4? What does S4 indicate?
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S4 indicates atrial contraction into a stiff and hypertrophied ventricular. Presence of S4 can suggest LV ischemia.
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What occurs physiologically in heart sound S3? What does S3 indicate?
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S3 indicates an inrush of blood into an already overfilled ventricle. The presence of S3 suggests either CHF or mitral regurgitation.
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What are the physiological effects of being treated with vasodilators?
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Vasodilators cause by venodilation and arterial vasodilation. The venodilation causes a ↓ pulmonary congestion, ↓ ventricular size which in turn ↓ventricular wall stress and myocardial work and O2 consumption. The arterial vasodilation decreases afterload, and causes coronary vasodilation. These two cause an ↑CO. Also, myocardial perfusion increases which increases contractility.
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What part(s) of the body fluid compartments comprise the vascular or "first" space?
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The vascular or "first" space is solely comprised of the plasma.
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What part(s) of the body fluid compartments comprise the extravascular or "second" space?
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The extravascular or "second" space is comprised by both the interstitial fluid (ISF) and the intracellular fluid (ICF).
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What does the "third space" entail?
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The "third space" is a solely pathological fluid compartment. This is when body fluids collect in an area where a large volume of fluid should not collect, ie the peritoneal cavity, the pleural cavity, or the lumen of the GI tract.
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What are the three types of capillaries?
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Continuous
Fenestrated Discontinuous |
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What are the characteristics of continuous capillaries?
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Continuous capillaries, found in lung, muscle, skin and other organs, are characterized by a an uninterrupted endothelium and a continuous basal lamina. The seam between adjacent endothelial cells forms narrow intercellular clefts with tight junctions that permit free passage in both directions of only small molecules (≤ 10 nanometers) like H2O, Na+, Cl-, urea, and glucose, but exclude macromolecules like proteins (e.g., albumin and globulins). In the brain, the intercellular clefts are so sparse and impermeable that even small molecules like glucose and amino acids must be actively transported across the endothelial cells which form the capillaries; this capillary border is called the "blood-brain barrier", and its relative impermeability excludes many intravenously delivered drugs from access to the brain.
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What are the characteristics of discontinuous capillaries?
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Discontinuous (sinusoidal) capillaries, found in the liver, bone marrow, and spleen, have a discontinuous basal lamina and much larger much larger gaps, as wide as 40 µm, that allow free passage of proteins, and even cells, between the plasma and interstitium.
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What are the characteristics of fenestrated capillaries?
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Fenestrated capillaries (‘fenestra’, Latin for ‘window’), found in the intestinal mucosa, kidney glomeruli, and pancreas, have circular pores (60-80 nm in diameter) that penetrate the endothelium; in some tissues, the pores are spanned by a thin diaphragm of radially-oriented fibrils. These pores allow small molecules and limited amounts of protein to diffuse.
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What are the four characteristics of capillaries that optimize them for diffusional exchange?
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1. Most cells are within 20µm of a capillary.
2. Large (surface/volume) ratio 3. Low flow velocity 4. Thin walls |
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What is the transcellular route of diffusional exchange?
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The transcellular route of diffusion is the method by which lipid-soluble substances such as dissolved gases like O2 and CO2 permeate and diffuse through the membrane of endothelial cells directly.
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How does diffusion take place with regards to water soluble substances?
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Water soluble substances (ie: glucose, amino acids, Na+, K+, Cl-) are limited mainly to diffusion through the water-filled intercellular clefts, in which case their movement is aided by the physical process of filtration (driven by a pressure gradient).
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What is meant by flow-limited transcapillary exchange? What are some flow limited molecules?
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The rate at which some molecules diffuse across the capillary surface is so much faster than the flow of blood along this surface that their rate of exchange is normally flow limited. Important flow-limited molecules include lipid soluble dissolved gases (O2, CO2) and certain anesthetics; soon after these substances have entered the arterial portion of the capillary, their concentration gradients across the capillary wall rapidly dissipate.
Flow limited: limited by rate of blood flow. |
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What is meant by diffusion-limited transcapillary exchange? What are some diffusion limited molecules?
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Larger molecules which diffuse more slowly, like vitamin B12, may not equilibrate along the length of the capillary and their exchange may instead be diffusion limited.
Diffusion limited: limited by rate of diffusion. |
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What is oncotic pressure and what role does it play with regard to fluids in the capillary?
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Our blood has a relatively high concentration of protein which cannot pass through the capillaries. The interstitial fluids have a much lower concentration, and the the osmotic gradient favors water being absorbed into the capillary.
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What is the Starling equation (NOT the Frank-Starling of the Heart)?
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Fluid filtration = Hydraulic Drive - Osmotic suction
or Filtration = k [(Pc + πi) - (Pi + πc)] where k = filtration constant Pc= capillary hydrostatic pressure Pi= interstitial fluid hydrostatic pres. πc= capillary oncotic pressure πi= intersitial fluid oncotic pressure When filtration positive filtration takes place. When negative absorption takes place. |
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Based on the Starling equation what forces favor absorption?
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Pisf and πcap.
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Based on the Starling equation what forces favor filtration?
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Pcap and πisf.
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Capillary hydrostatic pressure (Pcap_ depends on what four factors?
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1. The distance along the capillary
2. Arterial and venous pressures 3. Gravity 4. Sympathetic vasomotor tone |
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How is Pcap effected by the distance across the capillary.
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Pcapillary decreases along the capillary. What this means is that as blood enters the capillary from the arterial end there is a net filtration, but at the venous end Pcap has decreased such that there is net absorption.
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In normal tissues there is slight discrepancy between filtration and absorption, which summates into a whole body discrepancy. What is this discrepancy and how is it resolved?
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In the average capillary bed, slightly more fluid filters out at the arteriolar end than is reabsorbed at the venular end; for the sum of all capillaries in the body, there is normally a net filtration of ~3 liters/day that is returned to the circulatory system via the lymphatic system.
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What are the four types of edema, and what is the defining characteristic of each of them?
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1. Inflammatory edema: characterized by ↑Permeability of the endothelial barrier.
2. Venous edema: characterized by an ↑venous pressure 3. Hypoprotenemic anemia: characterized by ↓plasma [albumin] 4. Lymphatic edema: characterized by a lymphatic obstruction |
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What is Kwashiorkor and how is characterized?
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Kwashiorkor is severe protein malnutrition. As plasma [albumin]↓ (hypoprotenemia) the the plasma oncotic pressure becomes inadequate to counterbalance capillary hydrostatic pressure.
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How do transcapillary fluid shifts compensate for hemorrhage?
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In hemorrhage some blood (whole blood, meaning protein as well) is lost, which decreases capillary hydrostatic pressure. This decrease in pressure promotes absorption along the length of the capillary which ideally would recruit interstitial fluid into the blood to help restore circulating blood volume.
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How do transcapillary fluid shifts compensate for events such as dehydration/diarrhea/sweating/vomitting?
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The aforementioned events all cause fluid loss (but only fluid loss, not protein loss). This fluid loss concentrates plasma protein which effectively ↑plasma oncotic pressure. This favors absorption of fluid from the ISF into capillaries, which dilutes the plasma protein concentration restoring the plasma oncotic pressure.
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What are the four functions of the lymphatic system?
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1. Return of excess ISF to blood (helps keep tissues compact)
2. Return interstitial protein to blood (maintain capillary oncotic gradient) 3. Transportation of immune cells 4. Transportation of large molecules and debris. |
