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A. Achmed, M.A., M.D., M.P.H.

Co-Director, University of Oklahoma School of Community Medicine

Amyloid deposits may be found in the heart secondary to multiple myeloma or as an isolated event, such as in senile cardiac amyloidosis. Grossly the walls of the heart may be thickened, and there may be multiple small nodules on the left atrial endocardial surface. Iron overload can affect the heart as a result of hereditary hemochromatosis or hemosiderosis. Grossly the heart is a rust-brown color and resembles the heart in idiopathic dilated cardiomyopathy. In hypothyroidism the heart is characteristically flabby, enlarged, and dilated, which results in decreased cardiac output. This reduced circulation results in a characteristic symptom of Cardiovascular System Answers 205 hypothyroidism, cold sensitivity. Histologically there is an interstitial mucopolysaccharide edema fluid within the heart. Most of the secondary cardiomyopathies result in a dilated cardiomyopathy that is characterized by congestion and four-chamber dilation with hypertrophy. Examples of the latter include cobalt, which has been used in beer as a foam stabilizer; anthracyclines; cocaine; and iron, the deposition of which is seen in patients with hemochromatosis. The anthracycline Adriamycin, which is used in chemotherapy, causes lipid peroxidation of myofiber membranes. Other forms of cardiomyopathies include a hypertrophic form, a restrictive form, and an obliterative form. These changes produce hypercontractility that predisposes patients to the risk of sudden death. Patients may experience dyspnea, lightheadedness, and chest pain, especially upon physical exertion; however, many patients appear to be asymptomatic, although sudden, unexpected death occurs not infrequently, especially following or during physical exertion. This risk is increased with factors that either increase the contractility of the heart or decrease the volume of the left ventricle (both of which increase the left ventricular outflow obstruction). Treatment for patients 206 Pathology with hypertrophic cardiomyopathy, therefore, is with drugs that decrease contractility. Examples of these types of drugs include -adrenergic blockers and calcium channel blockers. In individuals with hypertrophic cardiomyopathy, agents that increase contractility are contraindicated. Epinephrine and -adrenergic agonists, which increase cardiac output by increasing stroke volume and heart rate, would also be contraindicated. Diuretics would also be dangerous, as they would decrease intravascular volume, and this would accentuate the bad effects of the septal hypertrophy because of the decreased left ventricular volume. In contrast, dilated (congestive) cardiomyopathy results in a flabby, hypocontractile heart. Constrictive (restrictive) cardiomyopathy is associated in the United States with amyloidosis and endocardial fibroelastosis. It is so named because of the infiltration and deposition of material in the endomyocardium and the layering of collagen and elastin over the endocardium. This deposition affects the ability of the ventricles to accommodate blood volume during diastole. Endocardial fibroelastosis, which occurs mainly in infants during the first 2 years of life, is associated with a prominent fibroelastic covering over the endocardium of the left ventricle. There may be associated aortic coarctation, ventricular septal defects, mitral valve defects, and other abnormalities. In contrast, endomyocardial fibrosis is a form of restrictive cardiomyopathy that is found mainly in young adults and children in Southeast Asia and Africa. It differs from endocardial fibroelastosis in the United States in that elastic fibers are not present. It is characterized by a prominent and hypertrophic interventricular septum that is out of proportion to the thickness of the left ventricle. Histologically the myocardial fibers exhibit disarray, caused by wide fibers with unusual orientation, and prominent hyperchromatic nuclei.

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Clinicians who treat patients with influenza should be aware of local public health data, when available, on the type and subtypes of influenza circulating in their area. Chemoprophylaxis Influenza vaccination is the primary tool to prevent influenza and antiviral chemoprophylaxis is not a substitute for influenza vaccination. When influenza viruses are circulating in the community, chemoprophylaxis can be considered for: Page 66 · High-risk persons during the 2 weeks after vaccination before an adequate immune response to inactivated vaccine develops (6 weeks for children who were not previously vaccinated and who require 2 doses of vaccine). Adults and children aged greater than or equal to 1 year who are at high risk of developing complications from influenza for whom influenza vaccination is contraindicated, unavailable, or expected to have low effectiveness. Contraindications to vaccination include anaphylactic hypersensitivity to eggs or other vaccine components, moderate-to-severe febrile illness, and as a precaution, a history of Guillain-Barreґ syndrome within 6 weeks after receipt of a prior influenza vaccination. Adults and children aged greater than or equal to 1 year who are at high risk of developing complications from influenza virus infection and have not yet received influenza vaccine when influenza activity has already been detected in the community. Whenever possible, influenza vaccine should be administered, and vaccination should continue for recommended persons until influenza is no longer in community circulation. Unvaccinated adults, including health care workers, and for children aged greater than or equal to 1 year who are in close contact with persons at high risk of developing influenza complications during periods of influenza activity. Whenever possible, influenza vaccine should be administered; 2 weeks after administration, chemoprophylaxis may be discontinued (6 weeks for children who were not previously vaccinated and who require 2 doses of vaccine). All residents (vaccinated and unvaccinated) in institutions, such as nursing homes and long-term care facilities, that are experiencing influenza outbreaks. The risk of influenza associated complications is not identical among all highrisk persons, and antiviral chemoprophylaxis is likely to have the greatest benefit among those at highest risk of influenza complications and death, such as recipients of hematopoietic stem cell transplants. Persons at high-risk of developing complications from influenza if influenza vaccine is not available due to shortage. High-risk persons in situations in which there is documented low influenza vaccine clinical effectiveness because of the circulation of · · · · · · · Page 67 influenza virus strains that are antigenically distant from the vaccine strains, such that a substantial increase in vaccine failures is anticipated, as determined by federal, state, and local public health authorities. The safety and effectiveness of prophylaxis with Relenza have not been established for longer than 28 days duration. These studies have demonstrated the protective efficacy of Tamiflu and included prophylactic regimens that lasted 7 to 10 days. The prophylaxis studies conducted in healthy unvaccinated adults during a community outbreak and in elderly residents of skilled nursing homes (as described in the Tamiflu prescribing information) lasted for 42 days (6 weeks). Randomized, placebo-controlled studies of inhaled zanamivir in the treatment of influenza A and B: pooled efficacy analysis. Effectiveness of oseltamivir in preventing influenza in household contacts: a randomized controlled trial. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. Management of influenza in households: a prospective, randomized comparison of oseltamivir treatment with or without postexposure prophylaxis. Updated interim recommendations for the use of antiviral medications in the treatment and prevention of influenza for 2009 ­ 2010 season. Seasonal influenza in adults and children diagnosis, treatment, chemoprophylaxis, and institutional outbreak management: clinical practice guidelines of the Infectious Diseases Society of America. Drug Name: Diacomit (stiripentol) Seizures associated with Dravet syndrome Indicated for seizures associated with Dravet syndrome in patients taking clobazam. Drug Name: Sabril (vigabatrin) Refractory complex partial seizures Indicated as adjunctive therapy for refractory complex partial seizures in patients who have inadequately responded to several alternative treatments and for infantile spasms for whom the potential benefits outweigh the risk of vision loss. Page 70 Drug Name: Nayzilam (midazolam) and Valtoco (diazepam) Acute treatment of intermittent, stereotypic episodes of frequent seizure activity Indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity. Criteria Product Name: Banzel Approval Length Therapy Stage Guideline Type 12 month(s) Initial Authorization Prior Authorization Approval Criteria 1 - One of the following: 1. There is some clinical evidence to support the use of clobazam for refractory partial onset seizures. Diacomit (stiripentol) is indicated for seizures associated with Dravet syndrome in patients taking clobazam. Sabril (vigabatrin) is indicated as adjunctive therapy for refractory complex partial seizures in patients who have inadequately responded to several alternative treatments and for infantile spasms for whom the potential benefits outweigh the risk of vision loss. Adjunctive therapy is defined as treatment administered in addition to another therapy. Nayzilam (midazolam) and Valtoco (diazepam) are indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity.

However, in contrast to the well-accepted benefits of blood pressure reduction, the clinical relevance of modest rises in plasma renin activity as a result of sodium reduction is uncertain. While substantial levels of sulfate are found in foods and various sources of drinking water, the major source of inorganic sulfate for humans is from body protein turnover of the sulfur amino acids, methionine and cysteine. For this reason, neither an Estimated Average Requirement (and thus a Recommended Dietary Allowance) nor an Adequate Intake of sulfate is established. The model consists of a systematic series of scientific considerations and judgments (see Chapter 3). The hallmark of the risk assessment model is the requirement to be explicit in all of the evaluations and judgments made. Water Water intoxication can lead to life-threatening hyponatremia, which can result in central nervous system edema, lung congestion, and muscle weakness. Hyponatremia occurs occasionally in psychiatric patients (psychogenic polydipsia). In unusual circumstances, hyponatremia can also occur from excessive fluid intake, underreplacement of sodium, or both during or after prolonged endurance athletic events. The symptomatic hyponatremia of exercise is typically associated with greater than 6 hours of prolonged stressful exercise. Hyponatremia does not occur in healthy populations consuming the average North American diet. Thus, while hazards associated with overconsumption of fluid can be identified, there is no evidence that habitual consumption of a high total water intake results in identifiable hazards in apparently healthy people. Potassium Gastrointestinal discomfort and ulceration of the gastrointestinal tract have been reported with excess consumption of some forms of potassium supplements but not with potassium from the diet. Cardiac arrhythmias from hyperkalemia are the most serious consequence of excessive potassium intake. The typical sequence of findings is hyperkalemia, followed by conduction abnormalities apparent from electroencephalograms, and then cardiac arrhythmias, which can be life-threatening. Such consequences result from either a high plasma concentration of potassium or from rapid and extreme changes in its concentration. However, in otherwise healthy individuals (that is, individuals without impaired urinary potassium excretion from a medical condition or drug therapy), there have been no reports of hyperkalemia resulting from acute or chronic ingestion of potassium naturally occurring in food. In contrast, excess consumption of supplemental potassium can lead to acute toxicity in healthy individuals. Also, chronic consumption of a high level of potassium can lead to hyperkalemia in individuals with impaired urinary potassium excretion. Hence, supplemental potassium should only be provided under medical supervision because of the well-documented potential for toxicity. Clinical settings in which high intakes of potassium could pose a serious risk include type 1 diabetes, chronic renal insufficiency, end-stage renal disease, severe heart failure, and adrenal insufficiency. For these individuals, salt substitutes (potassium chloride) should be used only under medical supervision. Sodium Chloride the main adverse effect of increased sodium chloride in the diet is increased blood pressure, which is a major risk factor for cardiovascular-renal diseases. Results from the most rigorous doseresponse trials have documented a progressive, direct effect of dietary sodium intake on blood pressure in nonhypertensive as well as hypertensive individuals. The dose-dependent rise in blood pressure appears to occur throughout the spectrum of sodium intake. The strongest dose-response evidence comes from those clinical trials that specifically examined the effects of at least three levels of sodium intake on blood pressure. Individuals with hypertension, diabetes, and chronic kidney disease, as well as olderage persons and African Americans, tend to be more sensitive to the blood pressure raising effects of sodium chloride intake than their counterparts. The rise in blood pressure from increased sodium chloride intake is blunted in the setting of a diet high in potassium or a low-fat, mineral-rich diet; nonetheless, a dose-response relationship between sodium intake and blood pressure still persists. In nonhypertensive individuals, a reduced salt intake can decrease the risk of developing hypertension. Among certain groups of individuals who are most sensitive to the blood pressure effects of increased sodium intake. These groups also experience an especially high incidence of blood pressure-related cardiovascular disease. Sulfate While diarrhea can occur from a high sulfate intake, this condition usually results from ingestion of water with high sulfate content. Like all chemical agents, nutrients and other food components can produce adverse effects if intakes are excessive.

Extensive workup reveals the presence of a medullary carcinoma of the thyroid, a pheochromocytoma, and hyperplasia of the parathyroid glands. A 34-year-old female presents with recurrent episodes of severe headaches, palpitations, tachycardia, and sweating. A physical examination reveals her blood pressure to be within normal limits; however, during one of these episodes of headaches, palpitations, and tachycardia, her blood pressure is found to be markedly elevated. Which one of the following is most likely to be increased in the urine of this individual? Workup reveals hypocalcemia and a marked impairment of cell-mediated immunity resulting from an absence of T cells. Considering this diagnosis, the absence of T cells is a direct consequence of failure of which embryonic structure to develop? Third pharyngeal pouch Fourth pharyngeal pouch Fifth pharyngeal pouch Ultimobranchial body Foramen cecum Endocrine System 435 428. Histologic sections of the thymus that reveal reactive follicles with germinal centers are diagnostic of a. Acute inflammation Chronic inflammation Thymic hyperplasia Thymic hypoplasia Thymoma 429. Epithelial cell Lymphocyte Myoid cell Neuroendocrine cell Thymocyte Endocrine System Answers 400. Somatomedins are small peptides that act on the target organs after being synthesized under the influence of growth hormone. In addition to acral-skeletal expansion, patients with hyperpituitarism of the adult-onset variety (occurring after epiphyseal plate closure) have organomegaly, including increased size of the heart, kidneys, liver, and spleen. The pituitary gland normally doubles in size during pregnancy; hypovolemia during delivery decreases blood flow and may result in infarction of the anterior pituitary. The initial sign is cessation of lactation, which may be followed by secondary amenorrhea due to the loss of gonadotropins. Other signs of hypopituitarism include hypothyroidism and decreased functioning of the adrenal gland. Chronic causes of hypopituitarism include nonsecretory chromophobe pituitary adenomas, empty sella syndrome, and suprasellar (hypothalamic) tumors. Nonsecretory chromophobe adenomas present as space-occupying lesions that cause decreased hormone production. The gonadotropins are lost first, which results in signs of 436 Endocrine System Answers 437 hypogonadism. Types of chromophobe adenomas include null cell adenomas (no cytoplasmic granules), chromophobes (sparse granules), and oncocytic adenomas (increased cytoplasmic mitochondria). For example, bitemporal hemianopsia is classically produced by lesions that involve the optic chiasm. Pituitary tumors may easily compress the optic chiasm and result in bilateral loss of peripheral vision. Involvement of the optic nerve produces blindness in one eye (mononuclear anopsia), while involvement of the optic tract on one side results in homonymous hemianopsia (loss of the same side of the visual field in both eyes). A lesion involving the temporal lobe optic radiations produces a homonymous superior field defect, while a lesion involving the parietal lobe optic radiations produces a homonymous inferior field defect. These benign neoplasms are classified according to the hormone or hormones that are produced by the neoplastic cells. Prolactinsecreting tumors (lactotrope adenomas or prolactinomas) produce symptoms of hypogonadism and galactorrhea (milk secretion not associated 438 Pathology with pregnancy). In females this hypogonadism produces amenorrhea and infertility, while in males it produces impotence and decreased libido. The same symptoms that are seen with a prolactin-secreting pituitary adenoma can also be produced by certain drugs, such as methyldopa and reserpine. A somatotropic adenoma that secretes growth hormone may produce gigantism if it occurs in children prior to the closure of the epiphyseal plates or acromegaly if it occurs in adults after the closure of the epiphyseal plates.