C. Gene Cayten, MD, FACS, MPH

• Editor-in-Chief
• Professor of Surgery and Senior Associate Dean
• New York Medical College
• Residency Program Director of General Surgery
• Our Lady of Mercy Medical Center
• Bronx, New York

Effects and Clinical Use Actions include both beneficial antianginal effects (decreased heart rate erectile dysfunction first time purchase cialis jelly 20 mg with amex, cardiac force erectile dysfunction medications cost cialis jelly 20 mg with mastercard, blood pressure) and detrimental effects (increased heart size erectile dysfunction patanjali medicine order 20 mg cialis jelly with visa, longer ejection period; Table 12­1) erectile dysfunction va disability buy 20 mg cialis jelly otc. Like nitrates and calcium channel blockers impotence penile rings buy generic cialis jelly 20 mg line, blockers reduce cardiac work, the double product, and oxygen demand. Beta blockers are used only for prophylactic therapy of angina; they are of no value in an acute attack. They are effective in preventing exercise-induced angina but are ineffective against the vasospastic form. The combination of blockers and nitrates is useful because the adverse undesirable compensatory effects evoked by the nitrates (tachycardia and increased cardiac force) are prevented or reduced by blockade Table 12­1). The decrease in intracellular sodium causes an increase in calcium expulsion via the Na/Ca transporter (see Chapter 13) and a reduction in cardiac force and work. Ivabradine, an investigational drug, inhibits the If sodium current in the sinoatrial node. The reduction in this hyperpolarizationinduced inward pacemaker current results in decreased heart rate and consequently decreased cardiac work. If a blocker were to be used for prophylaxis in this patient, what is the most probable mechanism of action in angina A new 60-year-old patient presents to the medical clinic with hypertension and angina. In considering adverse effects of possible drugs for these conditions, you note that an adverse effect that nitroglycerin and prazosin have in common is (A) Bradycardia (B) Impaired sexual function (C) Lupus erythematosus syndrome (D) Orthostatic hypotension (E) Weight gain 6. A man is admitted to the emergency department with a brownish cyanotic appearance, marked shortness of breath, and hypotension. A 45-year-old woman with hyperlipidemia and frequent migraine headaches develops angina of effort. When nitrates are used in combination with other drugs for the treatment of angina, which one of the following combinations results in additive effects on the variable specified These are the only methods capable of consistently increasing coronary flow in atherosclerotic angina and increasing the double product. A 60-year-old man presents to his primary care physician with a complaint of severe chest pain when he walks uphill to his home in cold weather. After evaluation and discussion of treatment options, a decision is made to treat him with nitroglycerin. In advising the patient about the adverse effects he may notice, you point out that nitroglycerin in moderate doses often produces certain symptoms. One year later, the patient returns complaining that his nitroglycerin works well when he takes it for an acute attack but that he is now having more frequent attacks and would like something to prevent them. Nitroglycerin increases heart rate and venous capacitance and decreases afterload and diastolic fiber tension. It increases cardiac contractile force because the decrease in blood pressure evokes a compensatory increase in sympathetic discharge. The nitrates relax many types of smooth muscle, but the effect on motility in the colon is insignificant. Dilation of arteries in the meninges has no effect on central nervous system function but does cause headache. The calcium channel blockers and the blockers are generally effective in reducing the number of attacks of angina of effort, and most have durations of 4­8 h. Amyl nitrite and the sublingual nitrates have short durations of action (a few minutes to 30 min). Esmolol (an intravenous blocker) must be given intravenously and also has a very short duration of action. Only revascularization increases double product; drugs that decrease cardiac work increase exercise time by decreasing double product. Both drugs cause venodilation and reduce venous return sufficiently to cause some degree of postural hypotension. Bradycardia, lupus, weight gain, and urinary retention occur with neither of them, but prazosin has been used to relieve urinary retention in men with prostatic hyperplasia. Methemoglobinemia is delibrately induced in one of the treatments of cyanide poisoning. Isosorbide dinitrate (like all the nitrates) and prazosin can cause reflex tachycardia. Amlodipine, a dihydropyridine calcium channel blocker, causes much more vasodilation than cardiac depression and may also cause reflex tachycardia. In fact, calcium channel blockers and blockers have been used with some success as prophylaxis for migraine. The effects of blockers (or calcium channel blockers) and nitrates on heart size, force, venous tone, and heart rate are opposite. The effects of blockers and calcium channel blockers on the variables specified here are the same. These observations have been explained as follows: Rapid-acting vasodilators-such as nifedipine in its prompt-release formulation-cause significant and sudden reduction in blood pressure. If coronary blood flow does not increase sufficiently to match the increased requirement, ischemia and infarction can result. Contrast the therapeutic and adverse effects of nitrates, blockers, and calcium channel blockers when used for angina. Explain why the combination of a nitrate with a blocker or a calcium channel blocker may be more effective than either alone. The drugs used in heart failure fall into 3 major groups with varying targets and actions. The fundamental physiologic defect in heart failure is a decrease in cardiac output relative to the needs of the body, and the major manifestations are dyspnea and fatigue. In some cases, it can be ascribed to simple loss of functional myocardium, as in myocardial infarction. It is frequently associated with chronic hypertension, valvular disease, coronary artery disease, and a variety of cardiomyopathies. About one third of cases are due to a reduction of cardiac contractile force and ejection fraction (systolic failure). Another third is caused by stiffening or other changes of the ventricles that prevent adequate filling during diastole; ejection fraction may be normal (diastolic failure). The remainder of cases can be attributed to a combination of systolic and diastolic dysfunction. The natural history of heart failure is characterized by a slow deterioration of cardiac function, punctuated by episodes of acute cardiac decompensation that are often associated with pulmonary or peripheral edema or both (congestive heart failure). The changes in the ventricular function curve reflect some compensatory responses of the body and demonstrate some of the responses to drugs. The homeostatic responses to depressed cardiac output are extremely important and are mediated mainly by the sympathetic nervous system and the renin-angiotensin-aldosterone system. Increased blood volume results in edema and pulmonary congestion and contributes to the increased end-diastolic fiber length. The abscissa can be any measure of preload: fiber length, filling pressure, pulmonary capillary wedge pressure, etc. The ordinate is a measure of useful external cardiac work: stroke volume, cardiac output, etc. In heart failure, output is reduced at all fiber lengths, and the heart expands because ejection fraction is decreased or filling pressure is increased (or both). Compensatory sympathetic discharge or effective treatment allows the heart to eject more blood, and the heart moves to point C on the middle curve. Dashed arrows indicate interactions between the sympathetic and the renin-angiotensin systems. Apoptosis is a later response, and results in a reduction in the number of functioning myocytes. Considerable evidence indicates that angiotensin antagonists, certain -adrenoceptor blockers, and the aldosterone antagonists spironolactone and eplerenone also have long-term beneficial effects. Nesiritide, a recombinant form of brain natriuretic peptide, has vasodilating and diuretic properties and has been heavily promoted for use in acute failure. Prototypes and Pharmacokinetics All cardiac glycosides are cardenolides (they include a steroid nucleus and a lactone ring); most also have one or more sugar residues, justifying the glycoside designation. The cardiac glycosides are often called "digitalis" because several come from the digitalis (foxglove) plant. Digoxin is the prototype agent and the only one commonly used in the United States. Digitoxin is a very similar but longer-acting molecule; it also comes from the foxglove plant but is no longer available in the United States. The increased intracellular calcium is stored in the sarcoplasmic reticulum and upon release increases contractile force. Digitalis also modifies autonomic outflow, and this action has effects on the electrical properties of the heart. Mechanical effects-The increase in contractility evoked by digitalis results in increased ventricular ejection, decreased end-systolic and end-diastolic size, increased cardiac output, and increased renal perfusion. These beneficial effects permit a decrease in the compensatory sympathetic and renal responses previously described. However, because they are not discussed elsewhere in this book, we begin our discussion with this group. Electrical effects-Electrical effects include early cardiac parasympathomimetic responses and later arrhythmogenic actions. Toxic responses-Increased automaticity, caused by intracellular calcium overload, is the most important manifestation of digitalis toxicity. Intracellular calcium overload results in delayed afterdepolarizations, which may evoke extrasystoles, tachycardia, or fibrillation in any part of the heart. Congestive heart failure-Digitalis is the traditional positive inotropic agent used in the treatment of chronic heart failure. However, careful clinical studies indicate that while digitalis may improve functional status (reducing symptoms), it does not prolong life. Because the half-lives of cardiac glycosides are long, the drugs accumulate significantly in the body, and dosing regimens must be carefully designed and monitored. The parasympathomimetic action of digitalis often accomplishes this therapeutic objective, although high doses may be required. Alternative drugs for rate control include blockers and calcium channel blockers, but these drugs have negative inotropic effects. Interactions Quinidine causes a well-documented reduction in digoxin clearance and can increase the serum digoxin level if digoxin dosage is not adjusted. Several other drugs have the same effect (amiodarone, verapamil, others), but the interactions with these drugs are not clinically significant. Digitalis toxicity, especially arrhythmogenesis, is increased by hypokalemia, hypomagnesemia, and hypercalcemia. Loop diuretics and thiazides, which are always included in the treatment of heart failure, may significantly reduce serum potassium and thus precipitate digitalis toxicity. Digitalisinduced vomiting may deplete serum magnesium and similarly facilitate toxicity. Digitalis Toxicity the major signs of digitalis toxicity are arrhythmias, nausea, vomiting, and diarrhea. The normal clearance of digoxin is 7 L/h/70 kg; volume of distribution is 500 L/70 kg; and bioavailability is 70%. Chronic intoxication is an extension of the therapeutic effect of the drug and is caused by excessive calcium accumulation in cardiac cells (calcium overload). This overload triggers abnormal automaticity and the arrhythmias noted in Table 13­2. Severe, acute intoxication caused by suicidal or accidental extreme overdose results in cardiac depression leading to cardiac arrest rather than tachycardia or fibrillation. Correction of potassium or magnesium deficiency-Correction of potassium deficiency (caused, eg, by diuretic use) is useful in chronic digitalis intoxication. Mild toxicity may often be managed by omitting 1 or 2 doses of digitalis and giving oral or parenteral K+ supplements. Severe acute intoxication (as in suicidal overdoses) usually causes marked hyperkalemia and should not be treated with supplemental potassium. Antiarrhythmic drugs-Antiarrhythmic drugs may be useful if increased automaticity is prominent and does not respond to normalization of serum potassium. Agents that do not severely impair cardiac contractility (eg, lidocaine or phenytoin) are favored, but drugs such as propranolol have also been used successfully. Severe acute digitalis overdose usually causes marked inhibition of all cardiac pacemakers, and an electronic pacemaker may be required. Digoxin antibodies-Digoxin antibodies (Fab fragments; Digibind) are extremely effective and should always be used if other therapies appear to be failing. They are effective for poisoning with several cardiac glycosides in addition to digoxin and may save patients who would otherwise die. Beta1-Adrenoceptor Agonists Dobutamine and dopamine are often useful in acute failure in which systolic function is markedly depressed (see Chapter 9). However, they are not appropriate for chronic failure because of tolerance, lack of oral efficacy, and significant arrhythmogenic effects. Beta-Adrenoceptor Antagonists Several blockers (carvedilol, labetalol, metoprolol, Chapter 10) have been shown in long-term studies to slow progression of chronic heart failure. This benefit of blockers had long been recognized in patients with hypertrophic cardiomyopathy but has also been shown to occur in patients without cardiomyopathy. Nebivolol, a blocker with vasodilator effects approved for the treatment of hypertension, is investigational in heart failure. Beta blockers are of no value in acute failure and may be detrimental if systolic dysfunction is marked.

Diastolic blood pressure is affected mainly by peripheral vascular resistance and the heart rate erectile dysfunction medication muse generic 20 mg cialis jelly fast delivery. The pulse pressure (the systolic minus the diastolic pressure) is determined mainly by the stroke volume (a function of force of cardiac contraction) erectile dysfunction over 40 20 mg cialis jelly buy overnight delivery, which is influenced by 1 receptors erectile dysfunction 27 cheap cialis jelly 20 mg mastercard. The systolic pressure is the sum of the diastolic and the pulse pressures and is therefore a function of both and effects blood pressure erectile dysfunction causes cialis jelly 20 mg buy without a prescription. They also increase glycogenolysis in the liver and the resulting hyperglycemia is countered by the increased insulin levels impotence prozac 20 mg cialis jelly. Transport of glucose out of the liver is associated initially with hyperkalemia; transport into peripheral organs (especially skeletal muscle) is accompanied by movement of potassium into these cells, resulting in a later hypokalemia. Predict the probable compensatory responses to a chronic increase in blood pressure caused by a tumor releasing large amounts of norepinephrine. Note that the pulse pressure is only slightly increased by norepinephrine but is markedly increased by isoproterenol (see text). The reduction in heart rate caused by norepinephrine is the result of baroreceptor reflex activation of vagal outflow to the heart. Anaphylaxis Epinephrine is the drug of choice for the immediate treatment of anaphylactic shock (hypotension, bronchospasm, angioedema) because it is an effective physiologic antagonist of many of the mediators of anaphylaxis. Antihistamines and corticosteroids may also be used, but these agents are neither as efficacious as epinephrine nor as rapid acting. Legitimate indications include narcolepsy and, with appropriate adjuncts, weight reduction. The anorexiant effect may be helpful in initiating weight loss but is insufficient to maintain the loss unless patients also receive intensive dietary and psychological counseling and support. The drugs are abused or misused for the purpose of deferring sleep and for their mood-elevating, euphoria-producing action. Eye the agonists, especially phenylephrine and tetrahydrozoline, are often used to reduce the conjunctival itching and congestion caused by irritation or allergy. Newer 2 agonists are in current use for glaucoma and include apraclonidine and brimonidine. Bronchi the agonists, especially the 2-selective agonists, are drugs of choice in the treatment of acute asthmatic bronchoconstriction. The short-acting 2-selective agonists (eg, albuterol, metaproterenol, terbutaline) are not recommended for prophylaxis, but they are safe and effective and may be lifesaving in the treatment of acute bronchospasm. Conditions in which an increase in blood flow is desired-In acute heart failure and some types of shock, an increase in cardiac output and blood flow to the tissues is needed. Beta1 agonists may be useful in this situation because they increase cardiac contractility and reduce (to some degree) afterload by decreasing the impedance to ventricular ejection through a small 2 effect. Norepinephrine, in contrast to earlier recommendations, is an effective agent in septic and cardiogenic shock when used properly. Conditions in which a decrease in blood flow or increase in blood pressure is desired-Alpha1 agonists are useful in situations in which vasoconstriction is appropriate. High doses of vasoconstrictors may worsen shock due to septicemia or myocardial infarction because cardiac reserve is marginal. Alpha agonists are often mixed with local anesthetics to reduce the loss of anesthetic from the area of injection into the circulation. Chronic orthostatic hypotension due to inadequate sympathetic tone can be treated with oral ephedrine or a newer orally active 1 agonist, midodrine. Conditions in which acute cardiac stimulation is desired-Epinephrine has been used in cardiac arrest by intravenous and direct intracardiac injection. Genitourinary Tract Beta2 agonists (ritodrine, terbutaline) are sometimes used to suppress premature labor, but the cardiac stimulant effect may be hazardous to both mother and fetus. Nonsteroidal anti-inflammatory drugs, calcium channel blockers, and magnesium are also used for this indication. Long-acting oral sympathomimetics such as ephedrine are sometimes used to improve urinary continence in the elderly and in children with enuresis. This action is mediated by receptors in the trigone of the bladder and, in men, the smooth muscle of the prostate. A 7-year-old boy with a previous history of bee sting allergy is brought to the emergency department after being stung by 3 bees. Which of the following are probable signs of the anaphylactic reaction to bee stings A 65-year-old woman with impaired renal function and a necrotic ulcer in the sole of her right foot is admitted to the ward from the emergency department. She has long-standing type 2 diabetes mellitus and you wish to examine her retinas for possible vascular changes. Which of the following drugs is a good choice when pupillary dilation-but not cycloplegia-is desired A 60-year-old immigrant from Latin America was told she had hypertension and should be taking antihypertensive medication. In the emergency department, her blood pressure is 50/0 mm Hg and heart rate is 40 bpm. A group of volunteers are involved in a phase 1 clinical trial of a new autonomic drug. In the periphery, their adverse effects are extensions of their pharmacologic alpha or beta actions: excessive vasoconstriction, cardiac arrhythmias, myocardial infarction, hemorrhagic stroke, and pulmonary edema or hemorrhage. In moderate doses, they may induce nervousness, anorexia, and insomnia; in higher doses, they may cause anxiety, aggressiveness, or paranoid behavior. Peripherally acting agents have toxicities that are predictable on the basis of the receptors they activate. Thus, 1 agonists cause hypertension, and 1 agonists cause sinus tachycardia and serious arrhythmias. It is important to note that none of these drugs is perfectly selective; at high doses, 1-selective agents have 2 actions and vice versa. Cocaine is of special importance as a drug of abuse: its major toxicities include cardiac arrhythmias or infarction and seizures. A fatal outcome is more common with acute cocaine overdose than with any other sympathomimetic. Your 30-year-old patient has moderately severe new onset asthma, and you prescribe a highly selective 2 agonist inhaler to be used when needed. Several new drugs with autonomic actions were studied in preclinical trials in animals. A new drug was given by subcutaneous injection to 25 normal subjects in a phase 1 clinical trial. They cause bronchospasm and laryngeal edema and marked vasodilation with severe hypotension. The treatment of anaphylaxis requires a powerful physiologic antagonist with the ability to cause rapid bronchodilation (2 effect), and vasoconstriction (effect). Antihistamines and corticosteroids are sometimes used as supplementary agents, but the prompt parenteral use of epinephrine is mandatory. Antimuscarinics (tropicamide) are mydriatic and cycloplegic; -sympathomimetic agonists are only mydriatic in the eye. Norepinephrine penetrates the conjunctiva poorly and would produce intense vasoconstriction. Phenylephrine is well-absorbed from the conjunctival sac and produces useful mydriasis for 10­30 minutes. This patient shows signs of sympathetic autonomic failure: hypotension, inappropriate bradycardia, constricted pupils. These signs are compatible with a large overdose of a drug that causes marked depletion of stored catecholamine transmitter such as reserpine, an obsolete but inexpensive antihypertensive agent. The indirect-acting agents (amphetamines and tyramine) act through catecholamines in (or released from) the nerve terminal and would therefore be ineffective in this patient. Clonidine acts primarily on presynaptic nerve endings although it can activate 2 receptors located elsewhere. Isoproterenol would stimulate the heart but has no -agonist action and might exacerbate the hypotension. Norepinephrine has the necessary combination of direct action and a spectrum that includes 1, 2, and 1 effects. As a result, autonomic nerve endings degenerate, and cardiac transmitter stores are absent for 2 years or longer after surgery. Therefore, indirect-acting sympathomimetics are ineffective in changing heart rate. All the drugs listed are direct-acting, and all but phenylephrine have significant effects on receptors. Phenylephrine usually causes reflex bradycardia, which requires intact vagal innervation. The drug X dose caused a decrease in diastolic blood pressure and little change in systolic pressure. The decrease in diastolic pressure suggests that the drug decreased vascular resistance, that is, it must have significant muscarinic or -agonist effects. The fact that it also markedly increased pulse pressure suggests that it strongly increased stroke volume, a -agonist effect. Drug Y caused a marked increase in diastolic pressure, suggesting strong vasoconstrictor effects. It caused little or no increase in pulse pressure, suggesting negligible -agonist action. The investigational agent caused a marked increase in systolic and diastolic pressures and a moderate increase in pulse pressure (from 40 to 60 mm Hg). These changes suggest a strong alpha effect on vessels and an increase in stroke volume, a -agonist action in the heart. Note that the stroke volume also increased (cardiac output divided by heart rate-from 70. Reduced aldosterone causes more salt and water to be excreted by the kidney, reducing blood volume. If the tumor releases only norepinephrine, a compensatory bradycardia may also be present, but most patients release enough epinephrine to maintain heart rate at a normal or even increased level. Describe the major organ system effects of a pure agonist, a pure agonist, and a mixed and agonist Describe a clinical situation in which the effects of an indirect sympathomimetic would differ from those of a direct agonist. Paranoia, aggression; insomnia; hypertension Ephedrine: displacer like amphetamine plus some direct activity; oral activity; duration 4­6 h. All of these agents are pharmacologic antagonists or partial agonists and most are reversible and competitive in action. Because and blockers differ markedly in their effects and clinical applications, these drugs are considered separately in the following discussion. Classification Subdivisions of the blockers are based on selective affinity for 1 versus 2 receptors or a lack thereof. Other features used to classify the -blocking drugs are their reversibility and duration of action. Irreversible, long-acting-Phenoxybenzamine is the prototypical long-acting blocker; it differs from other adrenoceptor blockers in being irreversible in action. Reversible, shorter-acting-Phentolamine is a competitive, reversible blocking agent that does not distinguish between 1 and 2 receptors. Alpha1-selective-Prazosin is a highly selective, reversible pharmacologic 1 blocker. Alpha2-selective-Yohimbine and rauwolscine are 2-selective competitive pharmacologic antagonists. Pharmacokinetics Alpha-blocking drugs are all active by the oral as well as the parenteral route, although phentolamine is rarely given orally. Phenoxybenzamine has a short elimination half-life but a long duration of action-about 48 h-because it binds covalently to its receptor. Phentolamine has a duration of action of 2­4 h when used orally and 20­40 min when given parenterally. Mechanism of Action Phenoxybenzamine binds covalently to the receptor, thereby producing an irreversible (insurmountable) blockade. This difference may be important in the treatment of pheochromocytoma because a massive release of catecholamines from the tumor may overcome a reversible blockade. Nonselective blockers-These agents cause a predictable blockade of -mediated responses to sympathetic nervous system discharge and exogenous sympathomimetics (ie, the responses listed in Table 9­1). The most important effects of nonselective blockers are those on the cardiovascular system: a reduction in vascular tone with a reduction of both arterial and venous pressures. The term refers to a reversal of the blood pressure effect of large doses of epinephrine, from a pressor response (mediated by receptors) to a depressor response (mediated by 2 receptors). The effect is not observed with phenylephrine or norepinephrine because these drugs lack sufficient 2 effects. Epinephrine reversal, manifested as orthostatic hypotension, is occasionally seen as an unexpected (but predictable) effect of drugs for which blockade is an adverse effect (eg, some phenothiazine antipsychotic agents, antihistamines). Selective blockers-Because prazosin and its analogs block vascular 1 receptors much more effectively than the 2modulatory receptors associated with cardiac sympathetic nerve endings, these drugs reduce blood pressure with much less reflex tachycardia than the nonselective blockers. The best-documented application is in the presurgical management of pheochromocytoma. Such patients may have severe hypertension and reduced blood volume, which should be corrected before subjecting the patient to the stress of surgery. Phenoxybenzamine is usually used during this preparatory phase; phentolamine is sometimes used during surgery. Phenoxybenzamine also has serotonin receptor-blocking effects, which justify its occasional use in carcinoid tumor, as well as H1 antihistaminic effects, which lead to its use in mastocytosis. Accidental local infiltration of potent agonists such as norepinephrine may lead to severe tissue ischemia and necrosis if not promptly reversed; infiltration of the ischemic area with phentolamine is sometimes used to prevent tissue damage.

Buy generic cialis jelly 20 mg. How To Reverse Erectile Dysfunction (Impotence) Naturally.

Baked beans (Bean Pod). Cialis Jelly.

• What is Bean Pod?
• Dosing considerations for Bean Pod.
• Are there any interactions with medications?
• Are there safety concerns?
• How does Bean Pod work?

Source: http://www.rxlist.com/script/main/art.asp?articlekey=96678

Spinning the body and rotational movements create excessive stimulation of the crista ampullaris and semicircular ducts (choices B and E) erectile dysfunction cures cialis jelly 20 mg low price, which also cause vertigo erectile dysfunction treatment bodybuilding cialis jelly 20 mg buy amex. Organ of Corti (choice D) is situated in the cochlear labyrinth (choice A) and is responsible for hearing perception experimental erectile dysfunction drugs buy cialis jelly toronto. Modiolus refers to the central bony core surrounded by the cone-shaped spiral cochlear canal xyzal impotence safe 20 mg cialis jelly. The cochlea of the guinea pig makes three and one-half turns impotence from smoking order cialis jelly on line amex, as shown in this section through the central axis of the cochlea. The modiolus is composed of spongy bone containing blood vessels, as well as spiral ganglion and nerve fibers of the cochlear branch of the eighth cranial nerve. Bony extensions from the modiolus form the osseous spiral laminae (indicated by the arrows), which provide attachment sites to the basilar membrane of the spiral organ of Corti. Cochlear canal (choice A) is the bony space hosting the membranous cochlear duct (choice B). Vestibule (choice E) is the central compartment of the bony labyrinth containing the membranous saccule and utricle. The cochlear duct, the membranous cochlear labyrinth, is suspended in the cochlear canal (bony cochlea, choice A). The cochlear canal is divided into three parallel longitudinal channels (compartments) running from the base to the apex of the cochlea. The cochlear duct itself is the triangular middle compartment (scala media) that contains endolymph. It is bounded superiorly by the vestibular membrane and inferiorly by the basilar membrane with the organ of Corti (indicated by the arrow) resting upon it. Laterally, the scala media is bordered by a special epithelium termed stria vascularis (indicated by the arrowhead). Scala vestibule and scala tympani (choices D and E) are perilymph-containing channels flanking the scala media. The scala vestibule begins at the oval window, and the scala tympani ends at the round window membrane (second tympanic membrane). They communicate with each other at the apex of the cochlea, through a narrow slit (helicotrema). Bordering the lateral aspect of the scala media (shown in the image for Question 46 and indicated by the arrowhead), the periosteal tissue adhering to the inner surface of the bony cochlea is thickened. Its endolymph-facing surface is lined by a specialized secretory epithelium (stria vascularis) that contains a complex capillary network and produces most of the endolymph in the membranous labyrinth. There are three cell types in the stria vascularis, namely (1) marginal cells lining the endolymphatic space of the scala media, (2) pigment-containing cells scattered among the capillaries, and (3) basal cells separating the stria vascularis from the underlying connective tissue of the spiral ligament. Cells of periosteum (choice C) and cells lining the perilymph-facing surface of the membranous labyrinth secrete the perilymph that fills the scala vestibuli and scala tympani. Vestibular membrane (choice E), also termed the Reissner membrane, is a thin membrane composed of two layers of simple squamous epithelium separated by a basal lamina. It serves mainly as a Special Sense Organs diffusion barrier between endolymph in the scala media and perilymph in the scala vestibule. The basilar membrane is a thick basement membrane stretching from the spiral ligament (choice C) laterally to the osseous spiral lamina (choice B, indicated by the arrowhead) medially. It forms the floor of the scala media and separates it from the scala tympani (indicated by the asterisk). The highly specialized epithelium, the spiral organ of Corti, superimposes on the basilar membrane. A layer of cuboidal cells secreting perilymph lines its surface facing the scala tympani. The width and stiffness of the basilar membrane vary as it coils from base to apex of the cochlea. It is widest and least stiff at the apex of the cochlea and narrowest and most stiff at the base. Sound waves transmitted into the inner ear induce movement of fluid in the cochlea that causes displacement of the basilar membrane. Hair cells of the organ of Corti are subsequently stimulated and activated to convert these mechanical signals into electric nerve impulses. The tectorial membrane is a stiff, gelatinous acellular plate that extends from the spiral limbus. The spiral limbus represents a thickened periosteum of the osseous spiral lamina on the medial aspect of the scala media (indicated by the asterisk). The stereocilia of the outer hair cells in the organ of Corti are embedded in the lower surface of the tectorial membrane. None of the other structures exhibit characteristic features of the tectorial membrane. The tunnel of Corti is a small triangular tunnel-like space at the central part of the spiral organ. Two rows of cells, inner and outer pillar cells (indicated by the arrowheads), line the borders of the tunnel of Corti. Their cell bodies are widely separated but come in contact along the apical aspects of the cells, thereby enclosing a triangular space. Pillar cells contain bundles of keratin that make the cells stiff to outline the tunnel of Corti. Sulcus spiralis internus (choice D) represents the concavity created by the inner projection of the spiral limbus (right side of the image). The tectorial membrane hangs over this space to reach the spiral organ, thereby creating a tunnel-like space 285 (referred to as the internal spiral tunnel). The spiral organ of Corti is a highly specialized epithelium resting on the basilar membrane and exposed to the endolymph in the scala media. It is composed of hair cells, phalangeal cells, pillar cells, Hensen cells, and several other cell types whose functions are not fully known. Hair cells are special auditory receptors and sensory transducers that detect the amplitude and frequency of sound waves. There are two types of hair cells in the spiral organ, namely inner and outer hair cells. The inner hair cells (choice B) form a single row of cells along the inner pillar cells. The outer hair cells are organized into three rows at the base of the cochlea (as shown in this specimen) and increase to five rows at the apex. Phalangeal cells (choice D) and pillar cells (choices E, indicated by arrowheads) provide support to the hair cells. The outer phalangeal cells can be distinguished from the outer hair cells by their location in this image (the three well-aligned nuclei immediately below the three outer hair cells). Hensen cells (choice A) are external limiting cells on the lateral aspect of the spiral organ. Keywords: Ears, spiral organ of Corti, hair cells 52 the answer is B: Oval window. The oval window and round window are two openings of the bony labyrinths within the temporal bone. The oval window is situated on the lateral wall of the vestibule of the bony labyrinth. Movement of the stapes induced by the vibration of the tympanic membrane stirs up the mechanical vibration of the perilymph contained in the scala vestibuli, which in turn causes vibration of the endolymph in the scala media and, subsequently, the perilymph in the scala tympani. The round window (choice C) is located at the inferior aspect of the base of the cochlea and is covered by an elastic membrane termed secondary tympanic membrane. Pressure changes of fluid in the cochlea cause movement (bulging out or in) of this membrane. None of the other structures mediate sound wave conduction from the middle ear to the internal ear. Keywords: Sound conduction, ears, oval window 53 the answer is A: Basilar membrane. As sound vibrations are transferred to the internal ear, a pressure pulse of the perilymph of the scala vestibule causes a traveling wave of deformation along the basilar membrane. The traveling wave of sound of a specific frequency reaches its peak amplitude at a particular location along the basilar membrane. As discussed earlier, the basilar membrane is 286 Chapter 19 narrow and relatively stiff at the base of the cochlea but increases in width and decreases in stiffness as it coils toward the apex of the cochlea. High-frequency sounds cause maximal amplitude of the basilar membrane near the base of the cochlea. By contrast, the basilar membrane near the apex of the cochlea undergoes maximal displacement in response to low-frequency sounds. Thus, different sites along the basilar membrane are specific for sounds with particular frequencies (pitch) and provide a structural basis for frequency discrimination. The receptor cells of the organ of Corti resting on a particular site of the basilar membrane respond best to sounds at particular frequency and convert the mechanical tuning of the basilar membrane into nerve pulses. The degree of displacement of the basilar membrane, in another words, the amplitude at any particular frequency, reflects the intensity or loudness of sound. None of the other structures encode acoustic information based on sound frequency or amplitude. Keywords: Ears, basilar membrane 54 the answer is C: Hair cells of the spiral organ of Corti. The receptor hair cells of the organ of Corti are supported and surrounded by phalangeal cells. At their apical surface, stereocilia of the hair cells attach to the tectorial membrane. The basilar membrane stretches from the osseous spiral lamina medially to the lateral spiral ligament, whereas the tectorial membrane hinges from the spiral limbus. Vibrations of the basilar membrane and tectorial membrane create a shearing effect that deflects and activates stereocilia of the hair cells. The activated hair cells generate action potentials that are conveyed by the cochlear nerve to the central nervous system. Hair cells of the crista ampullaris and macula (choices A and B) are receptor cells responsible for balance and equilibrium. Keywords: Sound perception 55 the answer is B: Dilation of the endolymphatic system. Ménière disease is the triad of vertigo, sensorineural hearing loss, and tinnitus. Ménière disease is characterized pathologically by hydropic distention of the endolymphatic channels of the membranous labyrinth. Dilation of the cochlear duct and saccule occurs at the early stage of disease, and eventually, the entire endolymph-containing network of channels is involved. Patients are afflicted with extensive vertigo and tinnitus, accompanied by nausea and vomiting. None of the other mechanisms of disease are associated with the pathogenesis of Ménière disease. Various organs and tissues are examined during the autopsy of a 70-year-old woman. The wound is cleaned and sutured; however, the boy suffers temporary loss of sensation distal to the wound. Which of the images shown above represents an example of a tissue that would be expected to show degenerative changes in the injured finger of this patient The sections shown below represent four different components of the nervous system. The five sections shown below were obtained from cell-rich glandular tissues that are organized into clusters, acini, or cords. Various lymphoid organs are examined at low magnification in the histology laboratory. Various portions of the digestive tract are examined by light microscopy at low magnification. Various endocrine and reproductive organs are examined at low magnification in the histology laboratory. You examine the biopsy and observe several normal structures in a region adjacent to the neoplasm (shown in the image). A transverse section through the posterior aspect of this organ is examined by light microscopy (shown in the image). The instructor asks you to identify the type of epithelium that is shown in the image. Comprehensive Review 69 Name the parenchymal cells of the organ indicated by the arrow (shown in the image). Skeletal muscle cells (image 1) form large-diameter fibers with peripheral nuclei. Transverse striations composed of alternating dark and light bands are visible across the fiber width. However, cardiac myocytes can be distinguished from skeletal muscle fibers by their distinctive cellular branching patterns. The muscularis externa in the wall of the gastrointestinal tract is composed predominantly of smooth muscle (image 2). Smooth muscle fibers are identified as short, spindle-shaped cells with single, centrally located nuclei. Smooth muscle is more cellular than dense connective tissue, and smooth muscle nuclei are located in the center of each fiber (rules out image 4). This section of tendon shows dense, regular connective tissue that is characterized by densely packed, parallel collagen fibers and bundles. The fibroblast nuclei are flat, elongated, and oriented parallel to the collagen fibers. Proper palmar digital nerves travel along the medial and lateral sides of the finger and are subject to injury. In a severed nerve, the axons and myelin sheaths would be expected to undergo degeneration.

What liver enzyme conjugates serum bilirubin impotence quotes 20 mg cialis jelly order with mastercard, making it water soluble erectile dysfunction signs cialis jelly 20 mg buy overnight delivery, for excretion in the bile On physical examination erectile dysfunction causes high blood pressure buy cialis jelly cheap online, the patient has an enlarged and tender liver and swollen legs erectile dysfunction thyroid order cialis jelly canada. The sinusoids within this liver lobule (arrows erectile dysfunction pump implant cialis jelly 20 mg purchase free shipping, shown in the image) receive most of their blood from which of the following sources Secreted proteins such as albumin, clotting factors, and nonimmune globulins enter what microscopic cavity before entering the liver sinusoid You explain that iron overload can occur due to increased breakdown of erythrocytes (hemolysis) or increased intestinal absorption. The parents believe that she recently swallowed a bottle of acetaminophen tablets. Which of the following enzymes metabolized acetaminophen and generated toxic metabolites in the liver of this young patient Which of the following cytologic features best characterizes these squamous epithelial cells Five hours after intravenous injection of India ink, the animal is sacrificed and the liver is processed for light microscopy. The black cells shown in the image represent Kupffer cells (macrophages) that have internalized carbon. In addition to foreign particles, Kupffer cells internalize and degrade which of the following components of portal venous blood As you attempt to confirm this surprising information through independent study, you learn that cholangiocytes continuously monitor the flow of bile. What subcellular organelle is sensitive to the directional flow of bile in the biliary tree The surgical pathologist asks you to comment on the remarkable capacity of the liver to regenerate. Hepatic stem cells that contribute to liver regeneration reside in which of the following locations An ultrasound examination discloses multiple echogenic objects in the gallbladder (gallstones). The gallbladder is removed (cholecystectomy), and the surgical specimen is examined by light microscopy. Identify the normal epithelial structures indicated by the arrows (shown in the image). Which of the following proteins facilitates the passive transport of water across the plasma membrane of epithelial cells lining the gallbladder In contrast to other organs in the gastrointestinal system, the wall of the gallbladder lacks which of the following layers Which of the following terms describes the glandular epithelial cells shown in the image Which of the following enzymes catalyzes the conversion of pancreatic proenzymes to active enzymes within the lumen of the duodenum What portion of the exocrine pancreas secretes most of this bicarbonate- and sodium-rich alkaline fluid These laboratory data indicate that this patient has suffered injury to which of the following internal organs Increased serum levels of alkaline phosphatase are an indicator of injury to which of the following tissues/structures She is currently seeing a psychiatrist because she is irritable and quarreling with her family. Laboratory studies show a serum glucose concentration of 35 mg/dL (normal = 90 mg/dL). These secretory vesicles most likely contain which of the following pancreatic hormones It is located in the upper right quadrant of the abdominal cavity, where it is protected by the ribcage. It receives blood from two sources: (1) hepatic artery and (2) hepatic portal vein. The parenchymal cells of the liver, termed hepatocytes, form plates that are separated by sinusoidal capillaries. Blood filters through the sinusoids and is drained by terminal hepatic venules to the inferior vena cava. The classic liver lobule is described as a six-sided prism, with portal triads (bile duct, hepatic artery, and portal vein) located at the angles of each lobule. The terminal hepatic venule (also referred to as the central vein) is located at the center of each lobule. None of the other structures listed is found at the center of the classic liver lobule. The circle shown in the image identifies a portal triad composed of a portal vein, bile duct, and hepatic artery. The portal vein (choice E) is thin walled, and its diameter is much larger than that of the hepatic artery (choice C). It delivers poorly oxygenated, but nutrient-rich, blood to hepatocytes lining the sinusoids. Hepatic arteries arise from the celiac trunk-an unpaired branch of the abdominal aorta. None of the other choices exhibit histologic features of the hepatic portal triad. This image reveals the central veins (terminal hepatic venules) of two adjoining liver lobules (arrows, shown in the image). They coalesce to form sublobular veins (choice D) that drain to hepatic veins that empty into the inferior vena cava. Keywords: Liver, terminal hepatic venules 4 the answer is E: Glucuronyltransferase. In order to be removed from the circulation, bilirubin must be transported into hepatocytes, conjugated with glucuronic acid (to make it water soluble), and then excreted into the bile for elimination. Approximately 70% of normal newborns exhibit a transient unconjugated hyperbilirubinemia. This "physiological jaundice" is more pronounced in premature infants due to inadequate hepatic clearance of bilirubin related to organ immaturity. High concentrations of unconjugated bilirubin in a neonate can cause irreversible brain injury (referred to as kernicterus). Patients with right-sided heart failure have pitting edema of the lower extremities and an enlarged and tender liver. A generalized increase in venous pressure, typically from chronic right-sided heart failure, results in an increase in the volume of blood in many organs. The liver is particularly vulnerable to chronic passive congestion because the hepatic veins empty into the vena cava immediately inferior to the heart. In patients with chronic passive congestion of the liver, the central veins of the hepatic lobule become dilated. Increased venous pressure leads to dilation of the sinusoids and pressure atrophy of centrilobular hepatocytes. The other choices are less commonly affected by chronic passive congestion of the liver. Keywords: Liver sinusoids, congestive heart failure 6 the answer is D: Portal vein. As mentioned above, the liver has a dual blood supply: the hepatic artery provides oxygen-rich blood, whereas the portal vein provides blood that is nutrient rich, but oxygen poor. Approximately 75% of the blood flowing through the liver is derived from the hepatic portal vein. Hepatic sinusoids are lined by a discontinuous endothelium that facilitates access of hepatocytes to the blood. Moreover, the basal lamina of the endothelium is absent over large areas, and there are gaps between adjacent cells. Hepatic sinusoids are also lined by resident macrophages (referred to as Kupffer cells). Slit-pore diaphragms (choice D) connect podocyte foot processes in the renal glomerulus, but these structures are not found Liver, Biliary System, and Pancreas in the liver. None of the other cytologic features characterize endothelial cells lining hepatic sinusoids. Keywords: Liver sinusoids, fenestrated capillaries 8 the answer is D: Space of Disse. Hepatocytes are separated from vascular endothelial cells and Kupffer cells by a perisinusoidal space (of Disse). This microscopic space provides a location for the exchange of fluid and biomolecules between hepatocytes and blood. Microvilli on the hepatocyte basal membrane fill the space of Disse and increase the surface area available for transport (endocytosis and exocytosis). RokitanskyAschoff sinuses (choice C) are deep invaginations of the mucosa in the wall of the gallbladder. The space of Mall (choice E) is located between hepatocytes and connective tissue of the portal triads. Hemosiderin is a partially denatured form of ferritin that aggregates easily and is recognized microscopically as yellow-brown granules within the cytoplasm. Hereditary hemochromatosis is an abnormality of iron absorption in the small intestine. In this genetic disease, iron is stored mostly in the form of hemosiderin, primarily in the liver. Bilirubin (choice A) is a product of heme catabolism that may accumulate in liver cells-but does not contain iron. Cytochromes are mitochondrial proteins that contain iron, but do not store iron within hepatocytes. The liver is the principal organ involved in detoxification of foreign substances, including industrial chemicals, pharmaceutical drugs, and bacterial toxins. Small doses of acetaminophen (an analgesic) are absorbed from the stomach and small intestine and conjugated in the liver to form nontoxic derivatives. In cases of overdose, the normal pathway of acetaminophen metabolism is saturated. Excess acetaminophen is then metabolized in the liver via the mixed function oxidase (cytochrome P450) system, yielding oxidative metabolites that cause predictable hepatic necrosis. These metabolites initiate lipid peroxidation, which damages the plasma membrane and leads to hepatocyte cell death. The toxic dose of acetaminophen after a single acute ingestion is in the range of 150 mg/kg in children and 7 g in adults. None of the other enzymes metabolizes acetaminophen to generate reactive oxygen species. Keywords: Liver, predictable necrosis 197 11 the answer is A: Blood products from the spleen. The scattered black objects represent Kupffer cells that have picked up carbon particles from the circulation. Their cellular processes span the hepatic sinusoids, searching for necrotic debris and foreign material to ingest. Portal venous blood transports nutrients and toxins from the gastrointestinal tract (choices B, D, and E), as well as endocrine secretions from the pancreas (choice C); however, Kupffer cells do not internalize these blood components. Bile provides a vehicle for the elimination of cholesterol and bilirubin, and bile salts facilitate the digestion and absorption of dietary fat. Hepatocytes excrete bile into small canals (canaliculi) that drain to bile ducts within the portal triads. These cuboidal to columnar epithelial cells continuously monitor the composition and flow of bile. The patient described in this clinical vignette has an autoimmune disease (primary biliary cirrhosis) that leads to chronic destruction of intrahepatic bile ducts. As a result of this destructive inflammatory process, the small bile ducts all but disappear. Keywords: Primary biliary cirrhosis, cholangiocytes 13 the answer is C: Hepatic stellate cells. Vitamin A is essential for vision, healthy skin, and proper functioning of the immune system. These mesenchymal cells are located between hepatocytes and endothelial cells in the perisinusoidal space of Disse. They store vitamin A as retinyl esters and secrete retinol bound to retinol-binding protein. Retinol is taken up by rods and cones in the retina to form the visual pigment, rhodopsin. Another derivative of vitamin A, retinoic acid, helps regulate the differentiation of squamous epithelial cells. In the cornea, it may progress to softening of the tissue (keratomalacia) and corneal ulceration. Collagen synthesis by Ito cells contributes to hepatic cirrhosis in patients with endstage liver disease. Keywords: Night blindness, vitamin A deficiency, hepatic stellate cells 198 Chapter 14 14 the answer is A: Bile duct. This image shows a portal triad consisting of a portal vein, bile duct, and hepatic artery. The arrow points to a bile duct, and the asterisk indicates the lumen of a thin-walled, portal vein (shown in the image). These columnar epithelial cells are characterized by the presence of apical membrane microvilli, tight intercellular junctions, and a complete basal lamina. Their nuclei are located in the basal cytoplasm, suggesting that their apical cytoplasm is specialized for absorption and/or secretion.

References

• Moosmann P, Egli F, Stahel RA, et al. Weekly paclitaxel and carboplatin combination chemotherapy in patients with advanced squamous cell carcinoma of the head and neck. Onkologie 2003;26(6):568-572.
• Kelly MP, Strassberg DS, Turner CM: Behavioral assessment of couplesi communication in female orgasmic disorder, J Sex Marital Ther 32(2):81n95, 2006.
• Kaljot KT, Ling JP, Gold JW, et al. Prevalence of acute enteric viral pathogens in acquired immunodeficiency syndrome patients with diarrhea. Gastroenterology 1989;97:1031.
• Santiago, L., Yamaguchi, R., Kaswick, J., Bellman, G.C. Laparoscopic management of indeterminate renal cysts. Urology 1998;52:379-383.
• Ohashi K, Nakajima Y, Kanehiro H, et al. Ki- ras mutations and p53 protein expressions in intrahepatic cholangiocarcinomas: relation to gross tumor morphology. Gastroenterology. 1995; 109:1612-1617.
• Assimos D, Krambeck A, Miller NL, et al: Surgical management of stones: American Urological Association/Endourological Society guideline, PART I, J Urol 196:1153n1160, 2016.