300-301. The answers are A and C, respectively. (Chapters 21, 23) The anion gap (AG) is the difference between the measured sodium level and the sum of the measured chloride and CO2 levels. Normal AG = 12 ± 4. The etiologies of this patient's normal AG (hyperchloremic) metabolic acidosis can be remembered by a helpful mnemonic, HARDUP: H for hypoaldosteronism (Addison's disease), A for acetazolamide, R for renal tubular acidosis, D for diarrhea, U for ureterosigmoidostomy, and P for pancreatic fistula. Salicylate toxicity causes an elevated AG with a normal osmolar gap. Serum osmolality is measured directly by determining the freezing point of the serum. It is calculated from the sodium, glucose, and BUN values with the following equation:

The normal serum osmolarity is 275 to 296 mOsm/L. In this case, the calculated serum osmolarity is 296 mOsm/L. A difference between the measured and calculated osmolarity (osmolol gap) of more than 10 mOsm/L indicates the presence of osmotically active substances (such as alcohols) in the blood.

302. The answer is C. (Chapter 23) The diagnosis of SIADH is primarily one of exclusion that should be made in the absence of hypovolemia, hypervolemia, renal failure, and drugs that impair water excretion. The causes of this syndrome are diverse, ranging from central nervous system disorders and tumors (lung cancer, lymphoma, thymoma) to pulmonary and endocrine disorders, including glucocorticoid insufficiency and hypothyroidism. There are miscellaneous causes such as porphyria, pain, and nausea. Opiates, chlorpropamide, nonsteroidal antiinflammatory medications, cyclophosphamide, phenothiazines, mono-amine oxidase inhibitors, tricyclic antidepressants, and thiazide diuretics are among the drugs that have been implicated in this syndrome.

303. The answer is D. (Chapter 23) The severity of signs and symptoms of hypocalcemia depends greatly on the rapidity of the fall of the calcium. Hypocalcemia is uncommon in the ambulatory setting unless the patient recently had surgery and is hypoparathyroid or has chronic renal disease. Symptoms of hypocalcemia include weakness, fatigue, perioral paresthesias, muscle spasms, and impaired memory. Hypocalcemia should be considered in refractory heart failure. Chvostek's and Trousseau's signs are evidence of hypocalcemia. A positive Tinel's sign signals carpal tunnel syndrome.

304. The answer is C. (Chapter 22) The A-a oxygen gradient measures the extent to which lung function is impaired. The A-a gradient in a healthy individual is less than 15 mm Hg. The formula to calculate the alveolar oxygen level at room air is: 150 - (arterial CO2 X 1.2). The gradient is the difference between this number and the PaO2. In this case, 114 mm Hg — 74 mm Hg = 40 mm Hg.

305. The answer is E. (Chapter 21) Isopropanol, also known as isopropyl alcohol, is commonly found in rubbing alcohol. The clinical features of isopropanol intoxication are similar to those of ethanol intoxication. Laboratory studies of patients who have ingested this alcohol show a normal or minimal AG, with an elevated osmolar gap. Patients with an AG greater than 35 usually have ethylene glycol or methanol intoxication, hyper-glycemic hyperosmolar coma, or lactic acidosis. MUDPILES is the mnemonic for the etiologies of an AG acidosis: M for methanol, U for uremia, D for diabetic ketoacidosis, P for paraldehyde, I for iron/isoniazid, L for lactic acidosis, E for ethanol and ethylene gly-col, and S for salycilates.

306. The answer is E. (Chapter 23) Hemolysis, leukocytosis, and thrombocytosis all can produce a pseudohyperkalemia. Effects of hyperkalemia are more pronounced in patients with concomitant hyponatremia and hypocalcemia. There are many different ways to treat hyperkalemia. Kayexalate (sodium polystyrene sulfonate) is an ion-exchange resin that works in the distal colon to extract potassium. High-dose inhaled albuterol is a useful temporizing measure to move potassium into the intracelluar space. Glucose with insulin can also cause a temporary shift of potassium into the intracellular space. Sodium bicarbonate causes an alkalosis that tends to reduce serum potassium levels. Calcium (preferably CaCl because of the higher concentration of calcium) stabilizes the cell membrane. Dialysis should be used to rapidly remove potassium when the hyperkalemia is severe.

307. The answer is D. (Chapters 23, 202) The serum glucose level that causes hypogly-cemic symptoms is variable. Levels of 35 mg/dL and lower are present in asymptomatic individuals, and levels in the "normal" range can cause symptoms of hypoglycemia that resolve with glucose administration. Patients with hypoglycemia experience both neuro-glycopenic and autonomic symptoms. Neuroglycopenic symptoms result from a direct effect on the brain and manifest as dizziness, confusion, tiredness, difficulty speaking, and headache. Autonomic or sympathomimetic symptoms are due to release of the coun-terregulatory hormone epinephrine and include diaphoresis, anxiety, trembling, and nausea. Glucagon is ineffective in alcoholics and the elderly because they have low glycogen stores.

308. The answer is C. (Chapters 23, 202) The counterregulatory hormones glucagon and epinephrine are released in response to hypoglycemia. Within minutes, glycogenolysis is activated and glucose is released into the bloodstream. Simultaneous to this process, there is a notable decrease in insulin secretion. Glucocorticoid and growth hormone are slower-acting mediators.

309. The answer is B. (Chapters 23, 202) Both alcohol use and diabetes are common causes of hypoglycemia. The established diabetic patient who eats inadequately, has inappropriate medication dosing, is on a multiple-drug regimen, or has a complicating medical problem may present with hypoglycemia. New-onset diabetes presents with hyperglycemia. Insulinomas, overdose of oral hypoglycemics, and liver failure are less frequent causes of low blood sugar.

310. The answer is D. (Chapter 204) The laboratory presentation of alcoholic ketoacido-sis is variable but tends to follow the pattern described in answer D. Glucose levels are mildly elevated. The alcohol level is uncharacteristically low given the patient's history of regular alcohol consumption. Ketones are present in large numbers and cause an elevated AG. The three ketones produced are p-hydroxybutyrate, acetoacetate, and acetone. Acetone is nonacidotic and rapidly excreted in the urine.

311. The answer is E. (Chapter 204) Although AKA classically presents in chronic alcoholics, it can also occur in first-time drinkers who consume insufficient food. Standard therapy of AKA consists of administration of glucose, thiamine, and saline solutions. This regimen restores volume, replenishes glucose, and prevents Wernicke's encephalopathy from developing. As acetoacetate increases and p-hydroxybutyrate decreases, the nipride test becomes more positive. Thus, as the patient's clinical condition improves, laboratory values may transiently worsen. Most patients without co-morbid conditions recover fully from AKA.

312. The answer is B. (Chapter 207) Hypothyroidism has a higher prevalence in women and is especially common in individuals older than 60 years. A high suspicion must be maintained in elderly patients because there is often a paucity of classic signs and symptoms. Autoimmune disorders, idiopathic causes, and postablation of thyroid tissue are common etiologies. In primary hypothyroidism, the TSH levels are high; in secondary hypothyroidism, the TSH levels are low. Amiodarone and lithium may induce hypothyroidism by increasing iodine levels, thereby inhibiting thyroxine production.

313. The answer is C. (Chapter 207) The rare patient who develops myxedema because of prolonged and severe hypothyroidism exhibits all of the listed abnormalities except hypernatremia. The hypothyroid patient typically becomes overloaded with water, leading to dilutional hyponatremia. The etiology of this hyponatremia is not clearly understood. The patient in a myxedematous state is usually hypothermic, lethargic, hypo-ventilating, and bradycardic.

314. The answer is C. (Chapter 203) Diabetic ketoacidosis occurs when inadequate insulin is secreted from pancreatic cells. In response, glucagon levels soar. The elevated glucagon levels result in gluconeogenesis and glycogenolysis. This hyperglycemic state produces an osmotic diuresis, leading to cell dehydration, electrolyte abnormalities, and an altered level of consciousness. The catabolic processes of lipolysis and muscle breakdown are also activated.

315. The answer is D. (Chapter 203) Administration of sodium bicarbonate is controversial. It may cause paradoxical spinal fluid acidosis, adversely affecting brain function. In addition, it shifts potassium ions intracellularly and worsens hypokalemia. The acidosis in diabetic states is protective and shifts the oxyhemoglobin curve to the right. Administering bicarbonate solutions may shift the curve back to the left.

316. The answer is D. (Chapter 203) Patients with DKA have an average water deficit of 5 to 10 L secondary to the osmotic diuresis that occurs with high serum glucose levels. Normal saline administration prevents a rapid fall in osmolality that could lead to excessive transfer of water into the central nervous system. Although the initial serum potassium level is elevated, repletion of potassium is necessary to restore low intracellular levels. To prevent hypoglycemia, dextrose should be added to intravenous fluids when the serum glucose falls to a level between 250 and 300 mg/dL. Even with this level of glucose, continued insulin is needed to resolve the acidosis and ketonemia. Phosphate levels only become critical when below 1.0 mg/dL.

317. The answer is E. (Chapter 205) HHNS occurs primarily in diabetics, although most cases are undiagnosed at the time of presentation. The mortality of HHNS is three to seven times greater than that for DKA. HHNS is characterized by severe dehydration (8-12 L deficit), hyperglycemia (greater than in DKA), and hyperosmolality. In patients with HHNS, high levels of glucose occur without the ketone body formation seen in DKA. However, metabolic acidosis may occur in HHNS from other causes (e.g., excessive lactic acid levels or uremia). Neurologic signs can be prominent in HHNS, with about 15 percent of patients manifesting seizures. Although HHNS is frequently referred to as hyperosmolar nonketotic coma, coma occurs in fewer than 10 percent of such patients. HHNS and DKA can be difficult to distinguish clinically.

318. The answer is E. (Chapter 205) Any comorbid disease process can precipitate HHNS in a diabetic patient. In the nondiabetic population, HHNS can occur after dehydration from heat strokes, burns, or dialysis. Drugs, especially diuretics or those that mediate insulin, are common precipitating factors. Ingestion of enormous amounts of sugar-containing fluids is an unusual cause. Aspirin has not been implicated.

319. The answer is A. (Chapter 21) Lactic acidosis is the most common cause of metabolic acidosis. Lactate is produced in the anaerobic glycolysis pathway. Normally, phys iologic levels of lactate are cleared through gluconeogenesis in the kidney and liver. When this system is overwhelmed and NAD is lacking, lactate levels rise. This commonly occurs in hypoxic or hypovolemic states and is referred to as type A lactic acidosis.

320. The answer is B. (Chapter 184) This patient suffers from phenformin-induced lactic acidosis. Phenformin is an oral hypoglycemic agent used in Europe that is no longer used in the United States. Other drugs such as alcohol, methanol, and antiretrovirals are also associated with type B lactic acidosis. The clinical findings of lactic acidosis are nonspecific. At a pH of 7.1 or lower, depressed cardiac function and hypotension may develop. Administration of sodium bicarbonate solution is controversial. Current recommendations suggest withholding alkali therapy if the pH is above 7.1.

321. The answer is D. (Chapter 206) Although most cases of hyperthyroidism are characterized by low levels of free thyroxine (T4), levels are normal in some thyrotoxic patients. T4 is the predominant circulating thyroid hormone. By cleaving an iodine molecule, triiodothyronine (T3) is produced. T3 is more biologically active than T4, but its half-life is only 1 day. Graves' disease is by far the most common cause of hyperthy-roidism, even in pregnancy. In addition to lithium, iodine, and amiodarone, a patient's own thyroid medication can induce a hyperthyroid state. Despite treatment, mortality rates of thyroid storm are high, ranging from 20 to 50 percent.

322. The answer is c. (Chapter 206) Aspirin use is contraindicated in the setting of thyroid storm because salicylates increase free T3 and T4 levels by displacing the molecules from their carrier thyronine-binding globulin hormone. Free T4 and TSH levels should be drawn before, not after, therapy. (3 Blockers such as propranolol are contraindicated in patients with bronchospastic disease or heart block. A selective p1 blocker (e.g., esmolol) can be used in this setting. Administration of PTU before iodide prevents the incorporation of iodide into the new thyroxine hormone. Steroid use is associated with increased survival, especially in cases with the potential for adrenal insufficiency.

323. The answer is c. (Chapter 208) Adrenal insufficiency is a deficiency produced by inadequate hormone production from the adrenal cortex, not the medulla. Adrenal medulla deficiency does not result in clinical disease. The following hormones are released from the adrenal gland: (a) aldosterone: increases sodium resorption and potassium excretion; (b) cortisol: maintains adequate glucose levels by decreasing glucose uptake and facilitating gluconeogenesis; and (c) androgens: important for certain sexual characteristics. Cortisol is released in response to pituitary release of adrenocorticotropic hormone (ACTH). ACTH is stimulated by corticotropin-releasing factor from the hypothalamus. The male gonads are the most important source of androgens; adrenal production is trivial by comparison.

324. The answer is D. (Chapter 208) The Waterhouse-Friderichsen syndrome is a life-threatening disorder resulting from overwhelming septicemia due to infection with N. meningitidis. Only about 10 percent of meningococcemia cases result in this syndrome. Bilateral adrenal hemorrhage is common. Computed tomography (CT) and ultrasound are both helpful in making the diagnosis. Although steroids are controversial, they are usually administered before antibiotic therapy. Risk factors for adrenal hemorrhage include stress, trauma, anticoagulants, pregnancy, surgery, and burns.

325. The answer is D. (Chapter 208) Adrenal insufficiency manifests insidiously. The findings in this patient are explained by deficiencies in androgens, corticosteroids, and mineralocorticoids. Hyperpigmented lesions represent lack of suppression of ACTH and melanocyte-stimulating hormone. Conn's syndrome results from overproduction of adrenal hormones. Isolated nephrogenic diabetes insipidus would not produce low glucose and elevated potassium. Hyperthyroidism has a vastly different clinical presentation, and glucose levels are often elevated. Depression alone would not account for the hyperpigmented skin or the electrolyte changes.

326. The answer is A. (Chapter 208) This patient's initial stabilization should include all of these measures except beginning mineralocorticoid therapy. Hydrocortisone replenishes the patient's inadequate steroid levels and provides some mineralocorticoid effect. Therefore, early administration of mineralocorticoids is not necessary. Correction of hypoglycemia and hypotension are essential. Early antibiotic administration is important to prevent potentially fatal infections leading to adrenal crisis.

327. The answer is B. (Chapter 276) Both pericarditis and myocarditis are common clinical manifestations in SLE patients. Although pericarditis may be accompanied by effusion, it rarely progresses to pericardial tamponade. Chronic steroid therapy may lead to premature atherosclerotic disease. Therefore, angina and myocardial infarctions should be considered. Costochondritis is a component of lupus arthritis. Aortic stenosis may be seen in association with ankylosing spondylitis, but not with SLE.

328. The answer is D. (Chapter 132) This patient has two major Jones' criteria for ARF. To make the diagnosis, evidence of streptococcal antibodies is needed. Major Jones' criteria include carditis, polyarthritis, erythema marginatum, chorea, and subcutaneous nodules. Fever, arthralgia, and previous rheumatic fever are minor criteria. Evidence of antecedent streptococcal infection plus either two major or one major and two minor criteria are necessary to diagnose ARF.

329. The answer is E. (Chapter 219) Temporal arteritis can cause sudden and permanent loss of vision. This sudden loss of vision is due to narrowing of the ophthalmic or posterior ciliary arteries. Permanent visual loss occurs in approximately 10 percent of these patients. Although a surgical biopsy of the artery is recommended, antiinflammatory treatment with steroids can save sight and should be initiated in the ED based on clinical suspicion alone.

330. The answer is D. (Chapter 278) A first-time painful, swollen joint must be tapped to rule out septic arthritis. The synovial fluid of a gouty joint appears like egg-drop soup, with urate crystals and white blood cells visualized under the microscope. Serum urate may be normal during an acute gouty attack. If a patient is taking chronic suppressive therapy, it should be continued to avoid exacerbating crystal precipitation. Initial therapy for the acute attack consists of indomethacin or oral colchicine. Intravenous colchicine should be used with caution if at all because of serious side effects that include bone marrow suppression, neuropathy, myopathy, and death.

331. The answer is E. (Chapter 278) A high index of suspicion must be maintained to diagnose gonococcal arthritis. Urethral or vaginal discharge is not uniformly present. A thorough history and examination should be performed in any sexually active patient complaining of joint pain without antecedent trauma. Because synovial fluid rarely shows the organism, in suspected gonococcal arthritis, cultures obtained from the urethra, cervix, rectum, mouth, and blood may be needed to confirm the diagnosis.

332. The answer is C. (Chapter 278) A thorough examination of all joints should be performed in intravenous drug users with fever and arthralgias. Joints that have a predisposition for infection and are often overlooked include the sternoclavicular, sacroiliac, and intervertebral. If these joints are tender to palpation, additional work-up with bone scan or joint aspiration is indicated.

333. The answer is D. (Chapter 55) Baker's cysts occur when fluid from a chronic inflammatory arthritis dissects into potential space in the popliteal region. When this collection of fluid ruptures, it can produce pain very similar to that of a DVT. Classically, swelling that spares the foot, a bluish discoloration around the ankle ("crescent sign"), and a sudden decrease in popliteal fullness all support the diagnosis of a ruptured Baker's cyst. The gold standard test is the arthrogram or duplex Doppler scan. The rapidity of pain onset when a Baker's cyst ruptures does not help differentiate it from DVT.

334. The answer is A. (Chapter 145) All of the agents are transmitted through ticks. Ticks should be carefully removed from patients by grasping the head with forceps and applying gentle pressure. Ehrlichia chaffeensis causes ehrlichiosis, isolated neurotoxin causes tick paralysis, R. rickettsii causes Rocky Mountain spotted fever, and Babesia species causes babesiosis. Lyme disease is the most frequently transmitted vector-borne infection in the United States. The three stages of this disease culminate in a prolonged and chronic arthritis.

335. The answer is E. (Chapters 131, 132) Kawasaki's syndrome is a generalized vas-culitis of small and medium-sized arteries. The classic presentation includes fever, conjunctivitis, lip and oral mucosal changes, strawberry tongue, extremity edema or erythema, polymorphous rash, and cervical lymphadenopathy. Associated features affect the cardiovascular, central nervous, hematologic, genitourinary, pulmonary, and gastrointestinal systems. Urethritis with a sterile pyuria can be seen. Coronary artery aneurysms develop in about 20 percent of patients who receive no intravenous immunoglobulin therapy but in only 3 to 4 percent of those who are treated within the first 10 days of illness.

336. The answer is A. (Chapter 132) Patients with suspected HSP should be admitted to the hospital for monitoring of renal function, rehydration, severe abdominal pain, lack of a PMD who is available for close follow-up, or when the diagnosis is in doubt. There is no specific age requirement for admission.

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