2001 Self-Assessment Exercise VI.

. Fluid and electrolyte metabolism [Return to Category List] Questions [Print Directions] Question 40. Answer.

A 16-month-old boy has had severe emesis and diarrhea for 3 days. On physical examination, he appears dehydrated. You administer fluids rapidly to correct his volume loss and serum electrolyte abnormalities. On the next day, he appears confused and exhibits quadriparesis and dysarthria. Magnetic resonance imaging reveals demyelination of the central basis pontis. Of the following, the rapid correction of which condition is MOST likely responsible for these findings? A. B. C. D. E. hyperkalemia hypermagnesemia hypocalcemia hyponatremia hypophosphatemia

Question 139. Answer. On the second day of hospitalization, a 5-year-old child who has pneumococcal meningitis develops a serum sodium concentration of 120 mmol/L (120 mEq/L). Physical examination reveals an awake and responsive child whose weight is 20 kg (an increase of 1 kg from admission), temperature is 37.8C (100F), blood pressure is 100/60 mm Hg, and pulse is 100 beats/min. The MOST appropriate management is A. B. C. D. E. administration of demeclocycline infusion of a solution containing 5% glucose and 0.3% saline at a maintenance rate infusion of 80 mL 3% saline over 10 minutes infusion of 0.9% saline at a maintenance rate restriction of fluids

Question 206. Answer.

A 2-year-old child is admitted to the hospital for evaluation of lethargy. On physical examination, temperature is 36.2C (97.2F) and blood pressure is 100/60 mm Hg. A ventriculoperitoneal shunt is palpated in the left temporal area. Results of laboratory evaluation include: sodium, 125 mmol/L (125 mEq/L); potassium, 4 mmol/L (4 mEq/L); chloride, 95 mmol/L (95 mEq/L); bicarbonate, 25 mmol/L (20 mEq/L); blood urea nitrogen, 0.714 mmol/L of urea (2 mg/dL); and creatinine, 17.7 mcmol/L (0.2 mg/dL). Of the following, the MOST likely urine abnormalities are A. B. C. D. E. high osmolality and high sodium concentration high osmolality and low sodium concentration isosthenuria and low sodium concentration low osmolality and high sodium concentration low osmolality and low sodium concentration

Answers Critique 40. Preferred Response: D

[View Question] In susceptible individuals, rapid correction of serum sodium concentrations may lead to osmotic demyelination or the syndrome of central pontine myelinosis, as described for the boy in the vignette. This syndrome occurs in older children and adults. In the presence of decreased serum sodium, intracellular potassium and amino acids shift outside the cells. Rapid exposure to normotonic or hypertonic rehydration causes a shift of free water from the neurons into the extracellular space, resulting in neuronal dehydration and demyelination. The acute development of hyponatremia results in a variety of neurologic symptoms. With serum sodium concentrations of 120 to 130 mmol/L (120 to 130 mEq/L), there may be somnolence, irritability, hypotonia, or apathy. Seizures may occur when concentrations decrease below 120 mmol/L (120 mEq/L). Specific neurologic symptoms have not been described for the rapid correction of abnormal levels of phosphate, magnesium, calcium, or potassium. References: Cheng JC, Zikos D, Peterson DR, Fisher KA. Symptomatic hyponatremia: pathophysiology and management. Acute Care. 1988-1989;14-15:270-292 Kotagal S. Increased intracranial pressure. In: Swainman KF, Ashwal S, eds. Pediatric Neurology: Principles & Practice. 3rd ed. St Louis, Mo: Mosby-Year Book, Inc; 1999:945-953 Critique 139. Preferred Response: E

[View Question] The child described in the vignette most likely is suffering from the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) caused by the meningitis. The consequence of this condition is decreased urine output. If maintenance fluids such as a solution containing 5% glucose and 0.3% saline continues to be administered, both weight and total body water will increase, resulting in hyponatremia and hypo-osmolality. The expanded intravascular volume suppresses the renin-angiotensin-aldosterone system and stimulates the right atrium to form atrial natriuretic peptide, which results in increased urinary excretion of sodium. Management of SIADH involves treating the underlying disorder and restricting fluids. The fluid restriction is designed to reduce intravascular volume, which will result in decreased sodium excretion. A fluid intake of 800 to 1,000 mL/m2 per day generally is sufficient to treat the fluid and electrolyte abnormalities, as long as urinary sodium losses are replaced. Close monitoring of vital signs, weight, urine output, and electrolytes is necessary. Hypertonic (3%) saline infusion should be reserved for patients who have hyponatremia-induced seizures or coma. Although it may increase the serum sodium concentration transiently, it results in further expansion of the intravascular volume and worsening of the manifestations of SIADH. Concomitant use of intravenous furosemide increases free water excretion relative to the sodium infused, thereby decreasing intravascular volume. Some authors have advocated the use of intravenous furosemide while replacing the urinary losses of sodium. This may require the use of normal (0.9%) saline. However, because the urinary sodium losses are being replaced, maintenance infusion rates are not required. In cases of chronic SIADH, demeclocycline has been used to block the action of antidiuretic hormone on the collecting duct. Lithium carbonate has a similar effect. References: Harris HW Jr. Syndrome of inappropriate secretion of antidiuretic hormone. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics. 16th ed. Philadelphia, Pa: WB Saunders Co; 2000:1684 Louis PT, Fortenberry JD. Syndrome of inappropriate secretion of antidiuretic hormone. In: McMillan JA, DeAngelis CD, Feigin RD, Warshaw JB, eds. Oski's Pediatrics: Principles and Practice. 3rd ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1999:2206-2207 Trachtman H. Sodium and water homeostasis. Pediatr Clin North Am. 1995;42:1343-1363 Critique 206. Preferred Response: A

[View Question] The most likely explanation for the electrolyte abnormalities described for the child in the vignette is the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) (Figure

206A). This syndrome is defined by the inappropriate concentration of urine in the presence of hypotonic hyponatremia and normal renal, adrenal, pituitary, and thyroid functions and the absence of dehydration, hypovolemia, and edema. It is encountered most commonly in patients who have central nervous system pathology, especially infections and trauma. Other causes include secretion of arginine-vasopressin-like peptides by tumors such as bronchogenic carcinoma; pulmonary infections such as tuberculosis; use of positive airway ventilation; and medications such as vincristine, clofibrate, cyclophosphamide, and chlorpropamide. Often SIADH is suspected initially when hyponatremia is discovered in a patient who has no vomiting or diarrhea or signs of intravascular volume depletion. Skin turgor and blood pressure are normal. Such central nervous system (CNS) symptoms as seizures, lethargy, hallucinations, irritability, and confusion may be caused by the low concentrations of serum sodium or the possible CNS pathology that is causing the syndrome. Clinically, there is a decrease in urine output with a concomitant increase in urine osmolality. If fluid intake is unrestricted, body weight increases. Although total body water is increased above normal and the plasma osmolality is decreased, antidiuretic hormone continues to be secreted, and cyclic adenosine monophosphate-mediated water absorption continues in the collecting ducts. This results in further increases in total body water, relative hypervolemia, and hyponatremia. Suppression of the renin-angiotensin-aldosterone system results in natriuresis. In addition, the hypervolemia increases right atrial pressure, resulting in increased atrial natriuretic peptide secretion, which further increases the urinary excretion of sodium. Accordingly, the child described in the vignette would be expected to exhibit high urine osmolality and high urine sodium concentrations. Findings of hyponatremia, high urinary osmolality, and low urinary sodium concentrations suggest dehydration in the appropriate clinical setting. Hyponatremia with a low urine osmolality and high urine sodium suggest a salt-wasting condition such as obstructive uropathy or chronic renal failure. Generally, low urine osmolality and urine sodium concentration suggest diabetes insipidus, which causes hypernatremia, not hyponatremia, when the patient does not have access to free water or develops an illness that increases water losses. References: Harris HW Jr. Syndrome of inappropriate secretion of antidiuretic hormone. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics. 16th ed. Philadelphia, Pa: WB Saunders Co; 2000:1684 Louis PT, Fortenberry JD. Syndrome of inappropriate secretion of antidiuretic hormone. In: McMillan JA, DeAngelis CD, Feigin RD, Warshaw JB, eds. Oski's Pediatrics: Principles and Practice. 3rd ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1999:2206-2207 Trachtman H. Sodium and water homeostasis. Pediatr Clin North Am. 1995;42:1343-1463 2000 Self-Assessment Exercise VI. Fluid and electrolyte metabolism

[Return to Category List] Questions [Print Directions] Question 6. Answer.

A 5-year-old girl has had a rash on the neck for 2 weeks. She has no past history of skin or other diseases. Examination of the skin reveals only a erythematous scaling annule on the left neck. The border of the lesion is well-defined and elevated. Of the following, the MOST likely diagnosis is A. B. C. D. E. granuloma annulare herald patch of pityriasis rosea nummular eczema psoriasis tinea corporis Answer.

Question 62.

The renal threshold for bicarbonate is defined as the plasma concentration of bicarbonate. The mean renal threshold for bicarbonate in a term neonate is A. B. C. D. E. 18 mEq/L 21 mEq/L 24 mEq/L 27 mEq/L 30 mEq/L

Question 111. Answer. A 15-month-old child is admitted with acute renal failure and oliguria. Findings on physical examination include: weight, 10 kg; blood pressure, 90/55 mm Hg; pulse, 100 beats/min; and capillary refill, <2 sec. Laboratory evaluation reveals: serum creatinine, 4 mg/dL; blood urea nitrogen, 40 mg/dL; sodium, 138 mEq/L; potassium, 4.0 mEq/L; chloride, 102 mEq/L; and bicarbonate, 20 mEq/L. Of the following, the most appropriate INITIAL fluid order for this child is A. 5% dextrose in water at 14 mL/h

B. 5% dextrose in water at 14 mL/h plus replacement of urinary volume and sodium losses

C. 5% dextrose in water, 0.2 normal saline at 14 mL/h plus replacement of urinary volume D. E. 5% dextrose in water, 0.2 normal saline at 42 mL/h 5% dextrose in water, 0.45 normal saline at 42 mL/h

Question 155. Answer. A 5-year-old child presents to the emergency department with generalized seizures. Results of laboratory evaluation include: creatinine, 0.5 mg/dL; blood urea nitrogen, 10 mg/dL; glucose, 90 mg/dL; sodium, 120 mEq/L; potassium, 4 mEq/L; chloride, 95 mEq/L; bicarbonate 20 mEq/L; urine sodium, 50 mEq/L; urine potassium, 20 mEq/L; and urine osmolality, 500 mOsm/kg H2O. Of the following, the MOST likely explanation for these findings is A. B. C. D. E. acute renal failure Addison disease congestive heart failure hyponatremic dehydration syndrome of inappropriate antidiuretic hormone secretion

Question 193. Answer. A 3-month-old infant has had diarrhea and lethargy for 4 days. Findings include: blood pressure, 80/40 mm Hg; pulse, 150 beats/min; doughy skin and sunken eyeballs; creatinine, 1.0 mg/dL; blood urea nitrogen, 60 mg/dL; sodium, 170 mEq/L; potassium, 6.0 mEq/L; chloride, 132 mEq/L; bicarbonate, 15 mEq/L; and glucose, 190 mg/dL. Fluid therapy is instituted, and 12 hours later, the patient has a generalized seizure. The MOST likely explanation for these findings is A. B. C. D. E. hyperglycemia hyperkalemia idiopathic epilepsy rapid correction of hypernatremia rapid correction of metabolic acidosis

Question 241. Answer. A 5-year-old boy is evaluated for periorbital edema. Physical examination reveals periorbital, presacral, and pretibial edema; blood pressure, 100/60 mm Hg; and pulse, 90 beats/min. Other findings on the examination are normal.

Of the following, the INITIAL diagnostic study to be performed in this child is A. B. C. D. E. chest radiography echocardiography evaluation for allergens measurement of liver enzymes urinalysis

Answers Critique 6 Preferred Response: E

[View Question] Tinea corporis is characterized by one or a few expanding erythematous, scaling annules or thin plaques, such as described in the girl in the vignette. The border of a lesion is welldefined and often more elevated and inflamed than the center. Central clearing is frequently but not always present. A hallmark of tinea corporis is the presence of scale that may be more prevalent at the edge of a lesion. In some children, small pustules are present at the border or throughout the lesion. Although these clinical features generally permit a diagnosis, if there is uncertainty, a potassium hydroxide preparation will demonstrate the branching hyphae. Several conditions may mimic tinea corporis. Granuloma annulare is a disorder of unknown etiology that produces small, firm papules that merge to form one or more circles or semicircles. Individual lesions are skin-colored, erythematous or violaceous, and usually appear on the wrists, hands, ankles, feet, or digits. Although the ring-like appearance may cause some confusion with tinea corporis, a diagnosis of granuloma annulare is suggested by the lack of scale and the firm, nodular border. Occasionally, individual papules or incomplete circles are present. Because it is an annular, erythematous, scaling macule, the herald patch of pityriasis rosea may mimic tinea corporis. However, the border usually is not elevated, and central clearing is uncommon. Nummular eczema is characterized by coin-shaped macules that may be crusted or somewhat scaly. Unlike tinea corporis, however, lesions are chronic, lasting weeks to months, and lack an elevated border and central clearing. Although psoriasis produces erythematous, scaling lesions, its clinical appearance differs greatly from that of tinea corporis. The lesions of psoriasis are elevated papules or plaques that lack central clearing and have thick adherent scale. In contrast to tinea corporis, children who have psoriasis generally present with multiple lesions involving the scalp, ears, elbows, knees, umbilicus, and gluteal cleft. References:

Guzzo L, Rabinowitz LG, Honig PJ. A head-to-toe guide to common fungal infections. Contemporary Pediatrics. 1986;3:53-78 Rasmussen JE. Cutaneous fungus infections in children. Pediatr Rev. 1992;13:152-156 Stein DH. Tineas-superficial dermatophyte infections. Pediatr Rev. 1998;19:368-372 Critique 62 Preferred Response: B

[View Question] The kidneys regulate bicarbonate concentration via urinary acidification, preventing its loss by reclaiming the filtered load of bicarbonate and generating bicarbonate. Approximately 85% of bicarbonate reabsorption occurs in the proximal tubule through a series of steps that begins with the secretion of hydrogen into the tubular lumen. The hydrogen reacts with the filtered bicarbonate to form carbonic acid, which dehydrates rapidly to form carbon dioxide and water in the presence of carbonic anhydrase. The inert carbon dioxide diffuses into the renal tubular cell where it is rehydrated to form bicarbonate. The bicarbonate then is transported across the basolateral membrane into the blood. Excretion of net acid occurs in the distal segments of the nephron. The kidney is capable of acidification in term neonates, but the threshold for bicarbonate reabsorption is lower than in older children and adults. In term neonates, it is set at 20 to 21 mEq/L. References: Hanna JD, Scheinman JI, Chan JC. The kidney in acid-base balance. Pediatr Clin North Am. 1995;42:1365-1395 Guignard JP. Renal function in the newborn infant. Pediatr Clin North Am. 1982;29:777-790 Critique 111 Preferred Response: B

[View Question] Fluid therapy is designed to provide sufficient volume and electrolytes to maintain normal homeostasis. It consists of three categories: maintenance, deficit replacement, and replacement of ongoing losses. Maintenance fluid and electrolyte requirements are related to baseline metabolic functions, including oxidation of fat, carbohydrate, and protein; urinary excretion of sodium and water; heat production; and insensible water losses. In 1957, Holliday and Segar proposed a simplified method to calculate fluid requirements that relates caloric expenditure to body weight.

Body Weight Up to 10 kg 11 to 20 kg

Caloric Expenditure/Day 100 kcal/kg 1,000 kcal + 50 kcal/kg for each kg above 10 kg

Above 20 kg

1,500 kcal + 20 kcal/kg for each kg above 20 kg

Because fecal losses are negligible, fluid requirements of 100 mL per 100 kcal replaces insensible water losses (through the lungs and skin) and urine output. Generally, one third of the fluid provided during maintenance therapy replaces insensible water losses, which for the child described in the vignette is approximately 14 mL/h. Because insensible water losses contain very low concentrations of sodium, dextrosecontaining solutions are appropriate for replacement of these losses. For the child described in the vignette, who has oliguric acute renal failure, urine losses of salt and water also should be replaced using sodium-containing solutions that approximate these losses after measuring the sodium concentrations present in the urine. References: Dabbagh S, Atiyeh B, Fleischmann LE, Gruskin AB. Fluid and electrolyte therapy. In: Burg FD, Ingelfinger JR, Wald ER, Polin RA, eds. Gellis & Kagan's Current Pediatric Therapy. 16th ed. Philadelphia, Pa: WB Saunders Co; 1999:860-869 Feld LG, Cachero S, Springate JE. Fluid needs in acute renal failure. Pediatr Clin North Am. 1990;37:337-350 Hellerstein S. Fluid and electrolytes: clinical aspects. Pediatr Rev. 1993;14:103-115 Watkins SL. The basics of fluid and electrolyte therapy. Pediatr Ann. 1995;24:16-22 Critique 155 Preferred Response: E

[View Question] Hyponatremia, defined as a serum sodium concentration of less than 130 mEq/L, is a commonly diagnosed electrolyte problem in children. Most patients are asymptomatic and require no specific treatment. When the serum sodium concentration drops below 120 mEq/L, however, serious clinical sequelae can ensue, including apathy, lethargy, and seizures. Hyponatremia can be associated with hypovolemia, euvolemia, or hypervolemia and the intravascular volume of each patient must be assessed to guide appropriate therapy (Table). The most common cause of hyponatremia is dehydration due to extrarenal losses of sodium through the gastrointestinal tract. The urinary loss of sodium is low (<10 mEq/L) because the renin-angiotensin-aldosterone system has been activated to enhance sodium reabsorption, and secretion of atrial natriuretic peptide has been decreased by the depleted intravascular volume. Antidiuretic hormone is secreted appropriately to enhance water absorption in the presence of hypovolemia. Hyponatremia also can be caused by increased urinary excretion of sodium. The most likely explanation for the findings described for the child in the vignette is the

syndrome of inappropriate antidiuretic hormone secretion (SIADH). SIADH is defined as an inappropriate concentration of the urine with respect to the serum in the presence of normal renal function and the absence of dehydration, adrenal insufficiency, hypothyroidism, or liver failure. Generally, the intravascular volume is mildly increased, but patients are not edematous. SIADH typically occurs in patients who have central nervous system pathology, such as meningitis, head trauma, or brain tumors. Other causes include Hodgkin lymphoma, decreased left atrial pressure (eg, pneumothorax, asthma), and drugs (eg, chlorpropamide, vincristine) that stimulate the release of vasopressin centrally, potentiate its effect on the kidney, or both. Accordingly, expected biochemical findings in patients who have SIADH include hyponatremia, normokalemia, inappropriately concentrated urine, and urinary sodium concentrations in excess of 20 mEq/L. Because of volume expansion, the renin-angiotensin-aldosterone system is inhibited, while atrial natriuretic hormone secretion is stimulated, which results in increased urinary excretion of sodium. However, because the underlying problem in patients who have SIADH is retention of water and not wasting of sodium, treatment involves aggressive fluid restriction rather than the administration of sodium. Any patient who has acute renal failure with severe oliguria could develop hyponatremia if free water intake exceeds urine volume and insensible water losses. Edema is present in such patients and urine sodium is more than 20 mEq/L, but there also should be evidence of poor renal function (eg, elevated creatinine levels). Addison disease is caused by destruction of the adrenal cortex, with resulting adrenal insufficiency. The most common cause is an autoimmune destruction of the glands, which may occur as a component of two syndromes. Type I autoimmune polyendocrinopathy is associated with mucocutaneous candidiasis, hypoparathyroidism, and Addison disease. Type I diabetes mellitus and hypothyroidism occur in fewer than 10% of affected patients. Gonadal failure, alopecia, vitiligo, keratopathy, enamel hypoplasia, nail dystrophy, intestinal malabsorption, and chronic active hepatitis also have been associated with the disease. Type I autoimmune polyendocrinopathy is inherited as an autosomal recessive disorder, and the gene has been assigned to chromosome 21q22.3. Some components of the disease may not appear until later in life. Type II autoimmune polyendocrinopathy consists of Addison disease, autoimmune thyroid disease, and type I diabetes mellitus and has been associated with human lymphocyte antigen-DR3 (HLA-DR3) and HLA-DR4. Other causes of adrenal insufficiency include tuberculosis, acute adrenal hemorrhage, and congenital adrenal hyperplasia. Adrenal hemorrhage may occur in the neonatal period following a difficult delivery or asphyxia. Rarely, this hemorrhage may be severe enough to cause death from exsanguination or adrenal insufficiency. However, most infants are asymptomatic and are identified after finding adrenal calcifications on radiography while being evaluated for other disorders. Another cause for adrenal hemorrhage is the Waterhouse-Friederichsen syndrome, which develops in association with septic shock.

The characteristic biochemical findings in patients who have Addison disease are hyperkalemia, hyponatremia, and mild metabolic acidosis. Urinary excretion of potassium is decreased because of the absence of aldosterone, and the urinary excretion of sodium is increased. Blood urea nitrogen concentrations are elevated in patients who are dehydrated. Eosinophilia may be present. In patients who have congestive heart failure, hypervolemia and edema are present. The edema is attributed to increased hydrostatic pressure and excessive transudation of fluid into the interstitial space. Hyponatremia and decreased urinary excretion of sodium are frequent. References: Berry PL, Belsha CW. Hyponatremia. Pediatr Clin North Am. 1990;37:351-363 Gerigk M, Bald M, Feth F, Rascher W. Clinical settings and vasopressin function in hyponatraemic children. Eur J Pediatr. 1993;152:301-305 Gross P, Reimann D, Neidel J, et al. The treatment of severe hyponatremia. Kidney Int Suppl. 1998;64:S6-S11 White PC. Disorders of aldosterone biosynthesis and action. N Engl J Med. 1994;331:250-258 Critique 193 Preferred Response: D

[View Question] The infant described in the vignette has clinical and biochemical findings that are most consistent with hypernatremic dehydration. Because of the hypertonicity of the extracellular fluid, the intracellular fluid shifts from the intracellular space, which results in shrinkage of the cells and maintenance of the intravascular volume for a period of time. Thirst is the most important defense mechanism during any period of hypernatremia and hypertonicity. If the patient is awake and alert and has access to water, he or she will compensate with increased water consumption to maintain normal serum osmolality. Infants who cannot obtain water for themselves, patients who are comatose, or patients who have lesions that affect thirst are most prone to developing hypernatremia. Hypernatremic dehydration results from the loss of hypotonic fluid in excess of sodium losses and accounts for 15% of all cases of dehydration. Acute central nervous system (CNS) symptomatology correlates with the severity of the hypernatremia and the hypertonicity. Permanent CNS damage has been reported when serum sodium concentrations were in excess of 160 mEq/L. The mortality rate can be as high as 10%. Intracerebral hemorrhage or thrombosis may occur when the hypertonicity causes cellular dehydration that results in brain shrinkage and tearing of the bridging vessels. If hypernatremia persists, brain cellular dehydration may resolve following the accumulation of idiogenic osmoles in brain cells, a process that generally requires 24 to 72 hours for completion. These idiogenic osmoles restore brain cell volume and persist as long as the hypernatremia exists. Hypernatremia that is corrected too rapidly can cause swelling of the

brain beyond the cell volume restored by the osmoles, resulting in a seizure. Accordingly, the fluid deficit in affected patients should be corrected over a period of 48 to 72 hours at a rate that would not decrease the serum sodium concentration by more than 10 to 12 mEq/L per day. Hyperglycemia is not a common cause of seizures, particularly at the level described in the vignette. Hyperkalemia typically causes arrhythmias, not seizures. The degree of metabolic acidosis in the infant described in the vignette is not severe. Thus, even if the bicarbonate concentration was normalized within 12 hours, it should not cause seizures. Although idiopathic epilepsy may develop at any age, in the setting of hypernatremic dehydration, too rapid a correction of the fluid deficit is a far more likely cause of the seizure. References: Adelman RD, Solhung MJ. Pathophysiology of body fluids and fluid therapy. In: Behrman RE, Kliegman RM, Nelson WE, eds. Nelson Textbook of Pediatrics. 15th ed. Philadelphia, Pa: WB Saunders Co; 1996:185-222 Conley SB. Hypernatremia. Pediatr Clin North Am. 1990; 37:365-372 Dabbagh S, Atiyeh B, Fleischman LE, Gruskin AB. Fluid and electrolyte therapy in children. In: Burg FD, Ingelfinger JR, Wald ER, Polin RA, eds. Gellis & Kagan's Current Pediatric Therapy. 15th ed. Philadelphia, Pa: WB Saunders Co; 1996:424-434 Trachtman H, Barbour R, Sturman JA, Finberg L. Taurine and osmoregulation: taurine is a cerebral osmoprotective molecule in chronic hypernatremic dehydration. Pediatr Res. 1988;23:35-39 Critique 241 Preferred Response: E

[View Question] Edema develops when there are alterations in transcapillary driving forces (Starling forces) that favor the accumulation of interstitial fluid. These forces include: 1) decreased oncotic pressure, 2) increased capillary hydrostatic pressure, 3) increased capillary permeability, and 4) obstruction to lymphatic flow. In conjunction with salt retention, these changes contribute to the development of generalized edema. For example, the hypoalbuminemia observed in patients who have nephrotic syndrome is caused by proteinuria, which results in decreased intravascular oncotic pressure. Fluid then moves from the intravascular space to the interstitial space, decreasing the effective circulating blood volume. The reninangiotensin-aldosterone system is activated and the concentration of antidiuretic hormone is increased. Because aldosterone enhances the renal reabsorption of sodium, the retention of water and salt is increased and general edema develops. The causes of generalized edema include conditions associated with hypoproteinemia (eg, nephrotic syndrome, malnutrition and starvation, protein-losing enteropathy, liver disease, congenital hypoproteinemia), congestive heart failure,

hypothyroidism, mineralocorticoid excess, medications (eg, certain antihypertensives agents, contraceptives), and capillary leak syndrome (eg, septic shock). Findings on physical examination of the child in the vignette are normal except for generalized edema. Accordingly, the least invasive and most accessible initial diagnostic study to perform in this child is a urinalysis. Using a urine dipstick, albumin at concentrations as low as 30 mg/dL can be detected. Once albuminuria is confirmed, a serum protein concentration should be measured. Chest radiography, echocardiography, and evaluation of liver function tests are not indicated at this time because there are no cardiac, hepatic, or pulmonary signs or symptoms. Evaluation for allergens would not be appropriate for the child described in the vignette. Allergic conjunctivitis, which often accompanies allergic rhinitis, causes edema of the eyelids as well as itching, red conjunctivae and watery secretions. References: Baliga R, Lewy JE. Pathogenesis and treatment of edema. Pediatr Clin North Am. 1987;34:639-648 Hisano S, Hahn S, Kuemmerle NB, Chan JC, DeSanto NG. Edema in childhood. Kidney Int Suppl. 1997;59: S100-S104 1999 Self-Assessment Exercise VI. Fluid and electrolyte metabolism [Return to Category List] Questions [Print Directions] Question 29. Answer.

Two hours after new intravenous fluids were begun, a 1.9 kg neonate appears gray and pulseless with muffled heart tones, despite a heart rate of 150 beats/min. Cardiopulmonary resuscitation and intubation make no improvement. The heart rate on ECG is 130 to 155 beats/min, but distinct P waves are not evident, and QRS complexes are widened. The most appropriate INITIAL intervention is A. B. C. D. E. administration of intravenous calcium chloride administration of intravenous lidocaine administration of intravenous sodium bicarbonate DC electrical cardioversion transcutaneous external cardiac pacing Answer.

Question 56.

Of the following, a TRUE statement regarding use of oral rehydration solutions in the management of acute gastroenteritis is that A. B. feedings are initiated following 24 hours of bowel rest and intravenous fluid therapy fermented carbohydrates are resorbed in the colon

C. fluid and electrolytes are replaced via sodium-glucose cotransport in the small intestine D. E. high sodium concentrations allow for replacement of total body sodium deficiency hyperosmolar solutions containing complex carbohydrates are required Answer.

Question 84.

Secretion of hydrogen ion in the kidney occurs in the A. B. C. D. E. ascending limb of the loop of Henle collecting duct descending limb of the loop of Henle distal tubule proximal tubule

Question 115. Answer. A 5-year-old boy who has Hodgkin lymphoma develops seizures. He received vincristine 10 days ago and has gained 1 kg since then. Findings include: sodium, 120 mEq/L; potassium, 4.0 mEq/L; chloride, 90 mEq/L; bicarbonate, 20 mEq/L; glucose, 90 mg/dL; creatinine, 0.5 mg/dL; urine sodium, 30 mEq/L; urine osmolality, 300 mOsm/kg H2O; chest radiography, normal. The MOST likely cause of this hyponatremia is A. B. C. D. E. congestive heart failure increased gastrointestinal loss of sodium increased renal loss of sodium syndrome of inappropriate antidiuretic hormone secretion volume overload

Question 143. Answer. A 10-year-old boy has gastroenteritis and has had no urine output over the past 12 hours. Findings include: lethargy; blood pressure, 80/50 mm Hg; heart rate, 120 beats/min; capillary refill, >3 sec; sodium, 130 mEq/L; potassium, 5.0 mEq/L; chloride, 100 mEq/L; blood

urea nitrogen, 100 mg/dL; creatinine, 10 mg/dL; bicarbonate, 12 mEq/L; and hemoglobin, 12 g/dL. The MOST appropriate parenteral fluid regimen is to A. B. C. D. E. administer a bolus of normal saline and correct intravascular volume depletion administer maintenance fluids administer maintenance fluids plus replace gastrointestinal losses restrict fluids to insensible water losses restrict fluids to insensible water losses plus urine and gastrointestinal losses

Question 172. Answer. Of the following, the recommendation regarding the use of antidiarrheal agents in the management of acute gastroenteritis in children that MOST closely reflects the position of the American Academy of Pediatrics is to A. B. C. D. E. avoid the use of these agents initiate use after vomiting has subsided use as maintenance therapy following correction of dehydration use during the acute phase of rehydration use to reverse prolonged diarrhea if a lactose-free diet proves ineffective

Question 200. Answer. A 13-month-old child presents with a 2-day history of fever, fussiness, and decreased oral intake. Findings include: a pale, irritable child; dry mucous membranes; cool extremities; weak peripheral pulses; capillary refill time, 4 sec; heart rate, 180 beats/min; blood pressure, 100/50 mm Hg; and respiratory rate, 35 breaths/min. Of the following, the most appropriate INITIAL management of this child is to administer A. B. C. D. E. an intravenous bolus of 10 mL/kg of 5% dextrose in water an intravenous bolus of 20 mL/kg of 0.25% normal saline in 5% dextrose an intravenous bolus of 20 mL/kg of 0.9% normal saline intramuscular ceftriaxone intravenous dexamethasone

Question 226. Answer.

You are evaluating a 2-month-old baby for lethargy. Findings include: no signs of dehydration; heart rate, 130 beats/min; blood pressure, 90/60 mm Hg; blood urea nitrogen, 10 mg/dL; creatinine, 0.2 mg/dL; sodium, 170 mEq/L; potassium, 4.5 mEq/L; chloride, 135 mEq/L; and bicarbonate, 20 mEq/L. Salt was added to the formula instead of sugar for the past three feedings. Of the following, the MOST appropriate therapy is to A. administer an intravenous (IV) solution of 5% dextrose

B. administer an IV solution of 5% dextrose and 38 mEq/L sodium (D5 0.2 normal saline) C. administer an IV solution of 5% dextrose and 50 mEq/L sodium (D5 0.3 normal saline) D. administer an IV solution of 5% dextrose and 75 mEq/L sodium (D5 0.45 normal saline) E. begin peritoneal dialysis

Answers Critique 29 Preferred Response: A

[View Question] Prior to appearing gray and pulseless, the infant described in the vignette had received an inappropriately high concentration of potassium chloride in an intravenous fluid solution. Accordingly, administration of a bolus of intravenous calcium chloride (100 mg/kg) is required. This therapy should normalize the electrocardiographic (ECG) changes and resolve the shock and electromechanical dissociation (EMD) caused by severe hyperkalemia (eg, serum potassium level >10 mEq/L). The socalled "classic ECG" finding of peaked T waves associated with hyperkalemia was not present because the serum potassium concentration was substantially higher than the values at which this harbinger sign is seen on the ECG. Typically, tall T waves occur when serum potassium levels are 6 to 7.5 mEq/L. Poor heart tones, absent pulses, and shock as a result of EMD occur at even higher serum concentrations. As described for the infant in the vignette, the QRS morphology becomes widened, the T waves become smaller in amplitude, and the P-wave amplitude becomes small or not visible during EMD. The ECG tracing may be confused with a ventricular tachycardia. QRS widening is due to hypopolarization of the myocardial cell membrane, resulting in slow conduction of each depolarizing systolic electric wavefront. The heart rate is unaffected, but the QRS morphology of each beat widens, often with a right or left bundle branch block morphology. Shock develops because the myocardial contraction is ineffective. DC cardioversion or administration of intravenous lidocaine would be ineffective treatments because the wide complex rhythm is not a ventricular tachycardia. Similarly, there is no role for cardiac pacing.

Identification of the primary cause of the hyperkalemia is crucial in preventing its recurrence. Administration of intravenous sodium bicarbonate can decrease the effects of hyperkalemia and transiently lower the potassium value. In fact, it will lower potassium for a longer period of time than calcium chloride (approximate 1 to 2 hours versus <1 hour). However, no agent will narrow the wide QRS complex and simultaneously completely abolish EMD in severe hyperkalemia (>10 mEq/L) as quickly and effectively as intravenous calcium. The effect is instantaneous and can be lifesaving. Glucose infusion with insulin is a standard recommended treatment, but it will take longer to be effective than calcium. Newer literature supports the use of inhaled aerosolized beta-agonist drugs (eg, albuterol) to lower elevated serum potassium levels, particularly when the hyperkalemia is moderate and has not caused arrest or as an adjunct once calcium has reversed the hyperkalemia. Administration of potassium-binding resins (eg, sodium polystyrene sulfonate) by nasogastric tube or per rectum is the treatment that has the longest duration of action, but the onset of action is slow compared with calcium chloride. The clinical clue that the infant described in the vignette was not in shock from ventricular tachycardia is the heart rate. Sometimes infants or children have the "slow" ventricular tachycardias (with rates of 110 to 150 beats/min) in which the QRS morphology is widened, but the patient displays no symptoms because the rate of ventricular tachycardia is too slow to compromise the child. An older child could report palpitations from the tachycardia, but little else. Thus, the findings of EMD with wide QRS complexes at a heart rate that should not produce shock is highly suggestive of cardiac arrest due to hyperkalemia. Children who have renal failure but are not receiving dialysis or whose dialysis is not effective are at particular risk for hyperkalemic arrest, as are other critically ill children who have anuria. An Addisonian crisis in a child who has primary or secondary adrenal insufficiency also may result in severe hyperkalemia. When wide QRS complexes are seen during cardiopulmonary resuscitation and the heart rate is extremely slow (10 to 30 beats/min), hyperkalemia is unlikely to be the cause. In children, wide QRS complexes are seen in terminal bradycardias just before death occurs from any cause. DC cardioversion and lidocaine will not be of benefit in such situations because the rhythm is neither ventricular tachycardia nor ventricular fibrillation. External pacing or transvenous internal cardiac pacing usually is ineffective because the terminal bradycardia is not the primary cause of death, and the myocardium cannot respond to the pacing stimuli. Finally, a wide QRS complex with a rate greater than 250 beats/min in an infant or 220 beats/min in a child almost certainly is not due to hyperkalemia. It probably is due to a primary arrhythmia, most likely ventricular tachycardia. In this instance, DC cardioversion is indicated if there is shock or serious hemodynamic compromise. Reference: Martin GB, Nowak RM, Cisek JE, Carden DL, Tomlanovich MC. Hyperkalemia during human cardiopulmonary resuscitation: incidence and ramifications. J Emerg Med. 1989;7:109-113

Critique 56

Preferred Response: C

[View Question] Recent evidence has supported the safety and efficacy of oral rehydration therapy and the rapid introduction of an age-specific diet in the management of the majority of children who have acute gastroenteritis. The Provisional Committee on Quality Improvement of the American Academy of Pediatrics (AAP) has published a practice guide on the management of acute gastroenteritis in young children. In summary, their recommendations include oral rehydration using a balanced glucose-electrolyte solution for a limited period of up to 4 to 6 hours in children who exhibit greater than 3% dehydration. Regular feedings should be continued in children who have minimal dehydration. Breastfeeding should be continued if possible. As soon as the rehydration phase is completed, age-appropriate diets should be initiated. There is no provision for the administration of clear fluids or a BRAT (ie, bananarice-applesauce-toast) diet in the AAP's recommendation. Most children who are vomiting can be given oral rehydration solution in small aliquots or via nasogastric tube. Intravenous fluids should be reserved for individuals who are unconscious, have an ileus, or in whom the vomiting precludes adequate fluid retention. The Committee also recommends that pharmacologic agents be avoided in the management of acute gastroenteritis in children. The development of currently used oral rehydration solutions has been based on sound scientific principles of water, electrolyte, carbohydrate, and protein absorption by the small intestine. Water moves into and out of the intestinal lumen in response to osmotic pressure produced by electrolytes and organic solutes. The movements of glucose and sodium chloride are the most important determinants of water movement. Sodium enters the small bowel cell coupled with glucose, amino acids, and di- and tripeptides. It leaves the cell and enters the extracellular space via the sodium-potassium ATPase pump. Water moves passively along the osmotic gradient created by the new solute movement. The administration of isotonic rehydration solutions minimizes the flow of water into the lumen across the bowel wall that is seen with the use of hypertonic solutions. The first oral rehydration solutions developed contained 90 mEq/L of sodium to approximate the electrolyte composition found in stools of children who had cholera. Initial concern about the potential for developing hypernatremia after receiving such sodium concentrations has faded because the cause of this complication has been identified as an excessive carbohydrate content rather than an increased sodium concentration. Oral rehydration solutions currently used in the United States have been modified to reflect the lower sodium concentration in stools of children who have diarrhea caused by rotavirus or enterotoxigenic Escherichia coli (ie, 45 to 75 mEq/L sodium). The newer oral rehydration solutions contain starch and small proteins (eg, rice, wheat) that enhance fluid and electrolyte absorption and reduce stool volume. Most children who have acute gastroenteritis have isotonic dehydration and require sodium intakes that match the composition of their stool losses. Thus, high sodium concentrations are not necessary in oral rehydration solutions. Feeding should be initiated

as soon as the rehydration phase of therapy is completed; a 24-hour period of bowel rest is not required. Carbohydrate malabsorption is unusual in children who have viral gastroenteritis. On rare occasions, lactose intolerance can cause increased stool volume and frequency after oral feedings are started. Determining the stool pH or checking for reducing sugars will identify the child who has lactose malabsorption. Administration of oral rehydration solutions that have excessive carbohydrate concentrations results in hypertonic dehydration because of the osmotic effect of the sugars upon the colon. A carbohydrate content of 2 g/100 mL appears to be optimal for sodium absorption. Although hyperosmolar solutions containing complex carbohydrates may stimulate net sodium and water absorption, such hypertonic solutions also cause water to move from the blood into the intestinal lumen. References: Brown KH, Perez F, Gastanaduy AS. Clinical trial of modified whole milk, lactose hydrolyzed whole milk, or cereal-milk for the dietary management of acute childhood diarrhea. J Pediatr Gastroenterol Nutr. 1991;12:340-350 Provisional Committee on Quality Improvement, Subcommittee on Acute Gastroenteritis. Practice parameter: the management of acute gastroenteritis in young children. Pediatrics. 1996;97:424-435 Reis EC, Goepp JG, Katz S, Santosham M. Barriers to use of oral rehydration therapy. Pediatrics. 1994;93:708-711 Snyder JD. Use and misuse of oral therapy for diarrhea: comparison of US practices with American Academy of Pediatrics recommendations. Pediatrics. 1991;87:28-31 Critique 84 Preferred Response: B

[View Question] The body generates 1 to 3 mEq/kg of hydrogen ion in children and 50 to 75 mEq in adults daily through the metabolism of food and the turnover of muscle and other tissues. The kidney has two roles in regulating acid-base balance. The proximal tubule reclaims approximately 85% of the filtered bicarbonate (HCO3-). In the proximal tubules, regulation of HCO3- recycling is accomplished by a Na+/H+ antiporter that actively transports one molecule of H+ into the urinary space in exchange for one molecule of Na+ that is transported from the urine into the cell. H+ reacts with HCO3- to form H2CO3, which dissociates into H2O and CO2 under the influence of carbonic anhydrase. CO2 diffuses into the proximal tubular cell, is hydrated under the effect of carbonic anhydrase, and dissociates into H+ and HCO3-. The HCO3- is transported into the circulation at the basal lateral side of the renal tubule cell. Consequently, this reclamation process does not involve a net H+ excretion. This process continues to a lesser degree in the loop of Henle and the distal tubule; the primary function of the loop of Henle is to concentrate the urine.

The process of acidification occurs in the intercalated cells in the collecting duct. These cells are capable of generating H+ and excreting it into the urinary space under the influence of H+-ATPase (without requiring an exchange with Na+), while HCO3- is exchanged for chloride (Cl-) at the basolateral membrane of the collecting duct. A steep H+ gradient is created, allowing the urine pH to fall to 4.0 to 4.5. H+ is bound in the urinary space by inorganic phosphate and other organic acids to form titrable acids. The inner medullary collecting duct can acidify the urine because of the prevailing high ammonia (NH3) concentrations. Ammonia is generated by the metabolism of glutamine, which also results in the generation of new HCO3-. NH3 diffuses into the urinary space to form ammonium (NH4+). Because NH4+ is positively charged, it is trapped in the urine. References: Hanna JD, Scheinman JI, Chan JC. The kidney in acid-base balance. Pediatr Clin North Am. 1995;42:1365-1395 Schwartz GJ. General principles of acid-base physiology. In: Holliday MA, Barratt TM, Avner ED, eds. Pediatric Nephrology. 3rd ed. Baltimore, Md: Williams & Wilkins; 1994:222-246 Critique 115 Preferred Response: D

[View Question] The biochemical findings described in the vignette suggest the diagnosis of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). This syndrome is defined as the inappropriate concentration of urine in the presence of serum hypo-osmolality and the absence of renal failure, cortisol deficiency, congestive heart failure, or liver failure. The intravascular volume of affected patients generally is increased. As described in the vignette, they may present with the signs and symptoms of hyponatremia, including lethargy and seizures. Several drugs are known to impair renal concentrating capacity and cause hyponatremia. Vincristine causes SIADH because of its neurotoxic effect on the hypothalamus. Intravenous administration of cyclophosphamide impairs water excretion, which can lead to acute water intoxication. The symptoms appear within 4 to 12 hours following infusion of the drug and persist for approximately 12 hours. Chlorpropamide, an oral hypoglycemic agent, augments both the release of vasopressin from the neurohypophysis and its action on the renal tubule. The latter effect appears to be related to inhibition of vasopressin-related prostaglandin synthesis. Among the diuretics, thiazides and metolazone are important causes of hyponatremia. These agents block the reabsorption of sodium and chloride in the cortical diluting segment, thereby impairing the renal diluting capacity. Because salt reabsorption in the ascending limb of the loop of Henle is unaffected by thiazides, patients are capable of maximally concentrating their urine. Thus, they retain water and lose electrolytes,

particularly sodium, in the urine. Withdrawal of the diuretic results in normonatremia and restores maximal diluting capacity in the kidney. Unlike doxorubicin, vincristine therapy is not associated with any cumulative cardiac toxicity that might be expected to cause congestive heart failure. SIADH is a much more likely explanation for the hyponatremia described in the vignette than the other options of volume overload or sodium loss via the gastrointestinal tract or the kidneys. References: Bressler RB, Huston DP. Water intoxication following moderate-dose intravenous cyclophosphamide. Arch Intern Med. 1985;145:548-549 Haycock GB. Sodium and water. In: Holliday MA, Barratt TM, Avner ED, eds. Pediatric Nephrology. 3rd ed. Baltimore, Md: Williams & Wilkins; 1994:171-214 Robertson GL, Bhoopalam N, Zelkowitz LJ. Vincristine neurotoxicity and abnormal secretion of antidiuretic hormone. Arch Intern Med. 1973;132:717-720 Weissman PN, Shenkman L, Gregerman RI. Chlorpropamide hyponatremia: drug-induced inappropriate antidiuretic-hormone activity. N Engl J Med. 1971;284:65-71 Critique 143 Preferred Response: A

[View Question] Acute renal failure is defined as the sudden loss of renal function associated with decreased effective circulating blood volume (prerenal); renal cell injury due to inflammation, ischemia, or toxin (renal); or obstruction of urinary flow (postrenal). When renal cell injury causes acute tubular necrosis and decreases its reabsorptive capacity, the glomerular filtration rate (GFR) also decreases as an adaptive response to this renal tubular injury. Intravascular volume depletion and decreased renal perfusion have similar effects on the kidney. As long as there is no renal cell injury, the GFR remains normal and the tubular reabsorptive capacity is enhanced. Decreased delivery of fluid to the distal nephron should stimulate the production of renin by the juxtaglomerular apparatus; this results in increased production of aldosterone and subsequent sodium reabsorption. In addition, hypovolemia stimulates the release of antidiuretic hormone, which acts at the collecting duct to increase water reabsorption. However, when renal perfusion is severely reduced below the level that can be compensated for by autoregulation, renal cell injury occurs. The goal of fluid therapy in patients who have acute renal failure is to restore and maintain normal intravascular volume. The child described in the vignette exhibits signs of severe intravascular volume depletion, and results of renal function tests suggest the presence of renal cell injury (ie, the blood urea nitrogen to serum creatinine ratio is 10 to 1). Accordingly, a fluid bolus (20 mL/kg of normal saline or 5% plasmanate) should be administered intravenously over 30 to 60 minutes to this patient regardless of the presence of oliguria or anuria. If hemorrhage has occurred, blood transfusions also are required. Delay in administering such therapy not only jeopardizes full recovery of renal function, but it may

damage other vital organs. Potassium supplementation should be avoided until urine flow is restored and the serum potassium concentration is measured. Central venous pressure monitoring also may be needed to monitor intravascular volume status and guide further management. Once the intravascular fluid volume is corrected, further fluid management will depend on the patient's clinical status. Generally, patients require restriction of fluids to replacement of insensible fluid losses and all other losses (eg, gastrointestinal losses, pleural losses, urine output). To avoid volume overload, fluid intake should be measured daily, including all fluid sources administered to the patient (fluids, catheter flushing, medications). References: Feld LG, Cachero S, Springate JE. Fluid needs in acute renal failure. Pediatr Clin North Am. 1990;37:337-350 Sehic A, Chesney RW. Acute renal failure: diagnosis. Pediatrics in Review. 1995;16:101-106 Siegel NJ, Gaudio KM, VanWhy SK, Boydstun II, Devarajan P. Acute renal failure. In: Holliday MA, Barratt TM, Avner ED, eds. Pediatric Nephrology. 3rd ed. Baltimore, Md: Williams & Wilkins; 1994:1176-1203 Critique 172 Preferred Response: A

[View Question] In 1996, the Provisional Committee on Quality Improvement of the American Academy of Pediatrics published a practice guide on the management of acute gastroenteritis in young children. In summary, their recommendations included endorsement of oral rehydration involving the administration of a balanced glucose-electrolyte solution for a period of up to 6 hours in children who had greater than 3% dehydration. They also recommended that regular feedings or breastfeeding should not be interrupted in children who have minimal dehydration. In children who have more than minimal dehydration, age-appropriate diets should be initiated as soon as the rehydration phase of therapy is completed. There is no provision in their recommendations for the administration of clear fluids, a BRAT (bananasrice-applesauce-toast) diet, or lactose-restricted feedings. The Committee also considered the role of pharmacologic therapy in the management of acute gastroenteritis in children. Such agents are classified according to their specific mechanism of action including: alteration of intestinal motility, alteration of intestinal secretion, adsorption of toxins and water, and alteration of the intestinal microflora. Pharmacotherapy of diarrhea is intended to decrease the loss of water and electrolytes and to relieve discomfort, but formed stools also may contain excessive amounts of water. Further, such agents may prolong the duration of the gastrointestinal infection by inducing an ileus. Most of the available medications are not approved for use in children younger than 2 years of age, and many have toxic side effects in this age group. After review of the limited number of published studies describing the use of these drugs in the management of acute infectious gastroenteritis, the Committee recommended that such

pharmacologic agents generally not be used to treat acute diarrhea in children. Among the agents that should be avoided are loperamide, opiates, and anticholinergic agents that alter motility (eg, kaolin-pectin, fiber, charcoal). Bismuth subsalicylate and Lactobacilluscontaining compounds also have been reported to reduce the duration of acute infectious gastroenteritis in several studies. However, the Committee suggested that until additional evidence supports the use of these agents in the management of acute gastroenteritis, they also should be avoided in children. References: Brown KH. Dietary management of acute childhood diarrhea: optimal timing of feeding and appropriate use of milks and mixed diets. J Pediatr. 1991;118:S92-S98 Isolauri E, Juntunen M, Rautanen T, Sillanaukee P, Koivula T. A human Lactobacillus strain (Lactobacillus casei strain GG) promotes recovery from acute diarrhea in children. Pediatrics. 1991;88:90-97 Meyers A. Modern management of acute diarrhea and dehydration in children. Am Fam Physician. 1995;51:1103-1118 Provisional Committee on Quality Improvement, Subcommittee on Acute Gastroenteritis. The management of acute gastroenteritis in young children. Pediatrics. 1996;97:424-433 Soriano-Brcher H, Avendano P, O'Ryan M, et al. Bismuth subsalicylate in the treatment of acute diarrhea in children: a clinical study. Pediatrics. 1991;87:18-27 Critique 200 Preferred Response: C

[View Question] Shock is an acute pathophysiologic state that is caused by cardiovascular dysfunction that results in an inability to provide oxygen and other nutrients to meet the metabolic needs of the body's tissues. Shock may be caused by many underlying conditions. Hypovolemic shock, the most common type in children, results from intravascular volume depletion and may be the result of trauma or severe dehydration secondary to gastroenteritis, burns, or other forms of water loss. Distributive shock is due to altered vascular tone; it is seen in patients who have anaphylaxis, sepsis, and some neurogenic conditions. Septic shock is caused by a combination of factors associated with severe infection, including peripheral vasodilation, myocardial depression, hypotension, and hypoventilation. Cardiogenic shock or pump failure may be due to myocarditis, arrhythmias, cardiomyopathies, or congenital heart disease. Other less common causes of shock include ingestions (eg, clonidine), endocrine abnormalities (eg, adrenal insufficiency), and obstructive shock due to tension pneumothorax or pericardial tamponade. The three phases of shock include the compensated, uncompensated, and irreversible stages. The phase of compensated shock is characterized by tachycardia, mild tachypnea, slightly delayed capillary refill (>2 sec), cool extremities, and mildly altered mental status (irritability or lethargy). This phase can be difficult to recognize and requires a

careful and thorough evaluation by the examining clinician. In children, hypotension is a late finding in shock. Due to the body's compensatory mechanisms of vasoconstriction, hypotension often is not seen until the child has lost 25% to 30% of his or her blood volume. Blood pressure frequently is normal in children in shock. Accordingly, normotension does not exclude the diagnosis of shock. In the early stages of septic shock, tachycardia and tachypnea are present, but the extremities may be warm, with increased peripheral pulses. As untreated shock progresses, the effects of cellular ischemia and the associated release of vasoactive and inflammatory mediators begin to affect the microcirculation. The child then will show signs of brain, kidney, and cardiovascular compromise, including worsening tachypnea, tachycardia, skin mottling, prolonged capillary refill time, decreased peripheral pulses and skin temperature, and hypotension. Decreased urinary output, altered mental status, and acidosis also occur. If unrecognized and untreated, this constellation will progress to multisystem organ failure and death. Shock must be recognized early so that treatment can begin promptly. Because all types of shock follow a common pathophysiologic pathway, initial management is the same. The first steps are to ascertain that the child has an adequate airway, assess breathing, and optimize oxygenation by providing oxygen (ie, 100% Fio2) via a nonrebreathing oxygen mask. Intravascular access should be established immediately by either an intravenous or an intraosseous route, and aggressive fluid management should begin with a fluid bolus of 20 mL/kg of an isotonic crystalloid solution (eg, 0.9% normal saline solution). Administration of colloids (eg, 5% albumin) also may be helpful, but should be reserved for specific indications, which do not include initial fluid therapy for patients who are in shock. Solutions such as 5% dextrose in water or 0.25% normal saline in 5% dextrose should not be used because this fluid will leave the intravascular space quickly, and the solutions do not increase the circulating intravascular blood volume significantly. Following these initial steps, careful reassessment is necessary, including reevaluation of the child's respiratory and neurologic status and expected response to initial fluid therapy (eg, decreased heart rate, improved color and capillary refill, increased pulse quality and urinary output). If there is minimal response, the fluid bolus should be repeated. The administration of antibiotics (eg, ceftriaxone) that would be effective against the pathogens likely to cause sepsis in that age group should be considered after stabilizing the child's airway, breathing, and circulation. Administration of corticosteroids, such as dexamethasone, has no proven value in the initial management of shock. References: American Academy of Pediatrics, American Heart Association. Pediatric Advanced Life Support. Elk Grove Village, Ill: American Academy of Pediatrics; 1997 Bell LM. Shock. In: Fleisher GR, Ludwig S, eds. Textbook of Pediatric Emergency Medicine. 3rd ed. Baltimore, Md: Williams & Wilkins; 1993:44-54 Tingelstad J. Shock. Pediatrics in Review. 1995;16:347-348 Critique 226 Preferred Response: A

[View Question] The infant described in the vignette represents a classic example of hypernatremia without evidence of dehydration due to salt poisoning. Generally, sodium intoxication is encountered when excess sodium bicarbonate is administered during resuscitative efforts or when sodium chloride is administered accidently, as occurred in the vignette, when salt inadvertently was added to the formula. It also happens following the ingestion of large quantities of sea water. An excessive intake of sodium is accompanied by increases in both total body sodium and extracellular water. Pulmonary edema may occur, particularly in patients who have compromised renal function. Severe acidosis ensues because the organic acids and hydrogen ions shift into the extracellular fluid. As water shifts from brain cells into the cerebral circulation, complications such as subdural, subarachnoid, and intracerebral hemorrhage can occur. Treatment of patients who have salt poisoning is aimed at rapid removal of the excess salt. In contrast to patients who have hypernatremia and dehydration, idiogenic osmoles are not present in the brain, and correction can be undertaken more rapidly. In patients who have hypernatremic dehydration, gradual rehydration over 48 to 72 hours is recommended. Intravenous fluids should consist of 5% dextrose in water with additional potassium acetate and calcium as needed. The intravascular volume of the patient must be monitored carefully to avoid developing hypervolemia. Peritoneal dialysis (using 4.25% glucose-containing solutions) should be instituted in a child who has severe salt intoxication in which the serum sodium concentration is in excess of 200 mEq/L.

References: Adelman RD, Solhung MJ. Isolated disturbances in blood pH and concentrations of electrolytes. In: Behrman RE, Kliegman RM, Nelson WE, eds. Nelson Textbook of Pediatrics. 15th ed. Philadelphia, Pa: WB Saunders Co; 1996:216-219 Conley SB. Hypernatremia. Pediatr Clin North Am. 1990;37:365-372 Hellerstein S. Fluids and electrolytes: clinical aspects. Pediatrics in Review. 1993;14:103-115 1998 Self-Assessment Exercise VI. Fluid and electrolyte metabolism [Return to Category List] Questions [Print Directions] Question 12. Answer.

A 6-week-old boy presents with weight loss and dehydration. He has been vomiting after each feeding for the past 2 weeks. The emesis is forceful and contains only formula. The

infant always appears to be hungry. Physical examination reveals an emaciated infant who has dry mucous membranes. A discrete abdominal mass is palpable in the right upper quadrant. Measurement of serum electrolytes in this infant is MOST likely to reveal A. B. C. D. E. hypochloremic metabolic acidosis hypochloremic metabolic alkalosis normal electrolyte levels respiratory acidosis with metabolic compensation respiratory alkalosis Answer.

Question 17.

A 5-month-old infant who has bronchopulmonary dysplasia is hospitalized with failure to thrive. Current medications include furosemide and spironolactone. Findings include: poor skin turgor and dry mucous membranes; blood urea nitrogen, 40 mg/dL; creatinine, 0.4 mg/dL; sodium, 132 mEq/L; potassium, 2.5 mEq/L; chloride, 80 mEq/L; bicarbonate, 40 mEq/L; arterial pH, 7.52; and PCO2, 50 torr. The MOST likely cause of these findings is A. B. C. D. E. Bartter syndrome primary hyperaldosteronism pseudohyperaldosteronism respiratory acidosis volume depletion Answer.

Question 43.

A 7-day-old infant is hospitalized because of lethargy. Findings include: blood pressure, 80/40 mm Hg; pulse, 140 beats/min; respiratory rate, 60 breaths/min; creatinine, 0.6 mg/dL; sodium,140 mEq/L; potassium, 5.0 mEq/L; chloride, 100 mEq/L; bicarbonate, 10 mEq/L; blood glucose, 90 mg/dL; white blood cell count, 12,000/mm; normal cerebrospinal fluid; and urine pH of 5.5. Of the following, the MOST likely diagnosis is A. B. C. meningitis organic acidemia renal tubular acidosis, type 1

D. E.

renal tubular acidosis, type 2 urea cycle defect Answer.

Question 66.

A 7-year-old boy who has cardiomyopathy and chronic congestive heart failure presents with generalized weakness and an irregular heart beat. He is taking digoxin, furosemide, and captopril. Laboratory evaluation reveals: serum sodium, 130 mEq/L; potassium. 2.5 mEq/L; chloride, 85 mEq/L; CO2, 19 mEq/L; and calcium, 8.0 mg/dL.Of the following, the MOST appropriate treatment is intravenous administration of A. B. C. D. E. calcium gluconate digoxin-specific antibody glucose and insulin potassium chloride sodium bicarbonate Answer.

Question 88.

One week after moving to a mountain city, a 6-year-old child is evaluated for abdominal pain. Physical examination reveals: agitation; respiratory rate, 45 breaths/min; pulse, 120 beats/min; blood pressure, 100/50 mm Hg; and normal abdominal examination. Arterial blood gases reveal pH, 7.48; PCO2, 20 torr; and bicarbonate, 15 mEq/L. Of the following, the MOST likely abnormality to be found in the urine of this child is A. B. C. D. E. fractional excretion of sodium <1% increased excretion of bicarbonate increased excretion of glucose increased excretion of phosphorus increased excretion of titratable acids

Question 112. Answer. A 4-week-old boy is evaluated for projectile vomiting for the past several weeks. Physical examination reveals slightly dry mucous membranes, good capillary refill, and a palpable mass in the midepigastrium. Among the following, the MOST likely laboratory findings in this patient would be

PH

PCO2 (torr)

HCO3 (mEq/L)

A. B. C. D. E.

7.20 7.20 7.55 7.55 7.55

20 55 20 55 55

8 23 17 17 48

Question 133. Answer. A 5-year-old girl is noted to have fever and widespread purpura. Despite appropriate antibiotic therapy, fluid resuscitation, and administration of vasopressor agents, profound shock ensues. Of the following, the most likely results of an INITIAL blood gas analysis in this patient who is breathing spontaneously would be

PH A. B. C. D. E. 7.15 7.20 7.35 7.40 7.55

PCO2 75 25 40 40 25

PO2 90 100 50 90 100

Question 159. Answer. A 2-year-old boy who lives in Arizona has a history of poor weight gain; loose, foul-smelling stools; and a persistent cough. In July, after playing outside for 3 hours, he is noted to be drowsy and dehydrated. Among the following, the MOST likely serum electrolyte concentrations in this boy would be

Sodium Chloride

Carbon dioxide Potassium

(mEq/L) (mEq/L) (mEq/L) (mEq/L) A. B. 120 135 85 105 35 <5 3.1 4.0

C. D. E.

135 140 160

112 105 120

7 25 10

7.0 4.0 5.5

Question 183. Answer. A 2-week-old breastfed infant is admitted to the hospital because of a generalized seizure. Findings include: weight, 2.5 kg (300 g below birthweight); blood pressure, 70/40 mm Hg; pulse, 140 beats/min; respiratory rate, 50 breaths/min; glucose, 120 mg/dL; blood urea nitrogen, 50 mg/dL; sodium, 170 mEq/L; bicarbonate, 12 mEq/L; calcium, 8.5 mg/dL; and magnesium, 1.5 mg/dL. The MOST likely cause of this infant's seizures is A. B. C. D. E. hypocalcemia hypoglycemia hypomagnesemia intracranial hemorrhage meningitis

Question 204. Answer. A 2-month-old infant presents with lethargy. His mother inadvertently added salt rather than sugar to his formula. Findings include: weight, 4.0 kg (unchanged from 1 week ago); blood pressure, 95/60 mm Hg; pulse, 120 beats/min; respiratory rate, 40 breaths/min; doughy skin; hyperreflexia; sodium, 172 mEq/L; potassium, 6.0 mEq/L; chloride, 134 mEq/L; and bicarbonate, 21 mEq/L. The BEST description of this infant's volume status is A. B. C. D. E. decreased extracellular fluid volume decreased intracellular fluid volume unchanged extracellular fluid volume increased intracellular fluid volume unchanged intracellular fluid volume

Question 228. Answer. A 2-year-old child who has congenital heart disease presents with a 1 day history of respiratory distress and edema of the lower extremities. Laboratory findings include: blood

urea nitrogen, 40 mg/dL; creatinine, 1.5 mg/dL; sodium, 125 mEq/L; potassium, 4.0 mEq/L; chloride, 95 mEq/L; and bicarbonate, 20 mEq/L. The MOST appropriate study to determine the cause of the hyponatremia is measurement of A. B. C. D. E. serum osmolality urine fractional excretion of sodium (FENa) urine pH urine specific gravity venous pH

Question 251. Answer. A 2-year-old boy who has a single ventricle and chronic congestive heart failure presents with generalized weakness and abdominal distension. His weight is less than the 5th percentile for age. He is not in respiratory distress. Current medications include digoxin and furosemide. You suspect hypokalemia and obtain an electrocardiogram. Of the following, the electrocardiographic findings MOST consistent with hypokalemia are A. B. C. D. E. delta waves peaked T waves premature ventricular beats prolonged QRS interval shortened QTc interval

Answers Critique 12 Preferred Response: B

[View Question] Hypertrophic pyloric stenosis (HPS) is characterized by nonbilious vomiting that typically begins at approximately 3 weeks of age. Initially, the vomiting may be nonprojectile and occur intermittently after feedings, but it progresses to projectile vomiting. The infant often is hungry immediately following an episode of emesis. As the vomiting progresses, there is an increased loss of fluid, hydrogen ion, and chloride, leading to hypochloremic metabolic alkalosis. Although serum potassium concentrations may be normal, frequently there is a deficit of total body potassium. This depletion of potassium results in an enhanced renal exchange of hydrogen for potassium and causes an aciduria. The electrolyte and fluid imbalances usually can be corrected within 12 hours using intravenous fluid therapy, after which surgical correction can be undertaken safely.

Twenty percent of infants who have HPS will become symptomatic shortly after birth. The incidence of HPS ranges from 1 in 200 to 1 in 750, with males (typically the first born) being affected four to six times more often than females. The children of mothers or fathers who have HPS are more likely to develop the disorder (20% of male children and 10% of female children). Although HPS is rare in Asians, there is controversy over whether African-Americans are more or less likely than Caucasians to be affected. The etiology of HPS is unknown, and pyloric hyperplasia is rarely present at birth. Suggested pathogenic mechanisms for HPS include abnormal muscle innervation, postnatal hypergastrinemia, increased prostaglandin E2 concentrations, and most recently, a deficiency of nitric oxide (a smooth muscle relaxant). The diagnosis of HPS is made by palpation of a mobile pyloric mass (pyloric olive). An experienced examiner can palpate the hypertrophied pylorus in 60% to 80% of cases. Imaging procedures are indicated in cases where the diagnosis cannot be confirmed. Pyloric ultrasonography is successful in diagnosing HPS in 90% of infants and is comparable to contrast radiography. The Ramstedt pyloromyotomy is the preferred surgical procedure for treatment of HPS. It is associated with a mortality rate of less than 0.5% and a recurrence rate of 1%. Postoperative vomiting can occur in 50% of patients, but typically it resolves within 24 hours. Prolonged vomiting is more common in infants who had hematemesis and esophagitis preoperatively. Balloon dilatation of the hypertrophied pylorus and atropine-induced regression of the pyloric muscle also are being evaluated as treatment options. References: Alexander F. Pyloric stenosis and congenital anomalies of the stomach and duodenum. In: Wyllie R, Hyams JS, eds. Pediatric Gastrointestinal Disease: Pathophysiology, Diagnosis, Management. Philadelphia, Pa: WB Saunders Co; 1993:414-428 Blumhagen JD, Noble HG. Muscle thickness in hypertrophic pyloric stenosis: sonographic determination. AJR Am J Roentgenol. 1983;140:221-223 Breaux CW Jr, Georgeson KE, Royal SA, Curnow AJ. Changing patterns in the diagnosis of hypertrophic pyloric stenosis. Pediatrics. 1988;81:213-217 McKeown T, MacMahon B. Infantile hypertrophic pyloric stenosis in parent and child. Arch Dis Child. 1955;30:497-500 Wyllie R. Pyloric stenosis and other congenital anomalies of the stomach. In: Nelson WE, Behrman RE, Kliegman RM, Arvin AM, eds. Nelson Textbook of Pediatrics. 15th ed. Philadelphia, Pa: WB Saunders Co; 1996:1060-1062 Critique 17 Preferred Response: E

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The infant in the vignette has chronic metabolic alkalosis associated with hypochloremia and hypokalemia due to ingestion of loop diuretics (furosemide) as treatment for bronchopulmonary dysplasia. The external response to metabolic alkalosis can be divided into two components. First, there is buffering of excess bicarbonate by titration of nonbicarbonate acid buffers in the plasma and intracellular space. Intracellular buffering occurs by sodium-hydrogen and potassium-hydrogen exchange, with subsequent titration of bicarbonate and formation of CO2 and water in the extracellular space. Plasma proteins contribute significantly to the buffering process by the following reaction: HProtein + HCO3- [becomes] H2O + CO2 + Protein Second, there is a compensatory rise in PCO2 (hypercapnia), which is caused by pulmonary hypoventilation and mediated by inhibition of the chemoreceptors in the medullary respiratory center in the brain. The renal response to metabolic alkalosis is to increase urinary excretion of bicarbonate. Within hours, net acid excretion is decreased to zero but it is very difficult to maintain metabolic alkalosis without associated volume contraction. Findings on physical examination in the infant in the vignette, including dry mucous membranes, poor skin turgor, and tachycardia, suggest intravascular volume depletion. Furosemide is a loop diuretic that acts by inhibiting the sodium-potassium-chloride pump in the ascending thick loop of Henle. The loss of sodium, potassium, and chloride in the urine results in depletion of total body potassium. This causes movement of hydrogen ion into the cell in exchange for potassium ion and promotes the proximal tubular reabsorption of bicarbonate. The loss of sodium and water leads to intravascular volume depletion, decreased glomerular filtration rate, and secondary hyperaldosteronism. Thus, the pathophysiology of metabolic alkalosis involves both a generation phase (ie, pharmacologic action of furosemide) and a maintenance phase (ie, intravascular volume contraction). Metabolic alkalosis is classified into chloride-responsive and chloride-resistant disorders. A spot urine for chloride is helpful in distinguishing between these two classes. Urine chloride concentration is less than 10 mEq/L in chloride-responsive disorders and more than 20 mEq/L in chloride-resistant disorders. Urine chloride concentration may be less than 10 mEq/L in the presence of chronic diuretic therapy. The most common causes of metabolic alkalosis are listed in the table. Bartter syndrome is characterized by hypokalemic metabolic alkalosis associated with secondary hyperaldosteronism, renal wasting of potassium and chloride, hyperplasia of the juxtaglomerular apparatus, and normal blood pressure. Associated findings include increased urinary excretion of prostaglandin E, high plasma levels of atrial natriuretic hormone, defect in platelet aggregation, hypercalciuria, hypomagnesemia, and hyperuricemia. The perinatal course of affected infants typically is complicated by polyhydramnios and preterm delivery. Therapy is directed at replacement of potassium chloride and the use of indomethacin.

Primary hyperaldosteronism (Conn syndrome) results from the autonomous production of aldosterone. It is rare in children and is characterized by hypertension, hypokalemia, and suppression of the renin-angiotensin axis. During the generation phase of the disorder there is an increase in net acid excretion due to the hyperaldosteronism, with consequent reabsorption of sodium chloride and extracellular volume expansion. In addition, there is an increase in renal potassium excretion, which results in potassium depletion. During the maintenance phase, there is increased proximal reabsorption of bicarbonate prompted by potassium depletion. The latter stimulates the formation of ammonia and further enhances net acid excretion in the distal tubule. Pseudohyperaldosteronism (Liddle syndrome) is a rare disorder of tubular transport of potassium and sodium that simulates primary hyperaldosteronism. Patients present in infancy and early childhood with failure to thrive, polydipsia, polyuria, arterial hypertension, and hypokalemic metabolic alkalosis. Plasma concentrations of aldosterone are low. This condition resembles 11 beta-hydroxysteroid dehydrogenase deficiency, in which cortisol is not converted to cortisone. Cortisol binds to the aldosterone receptors, resulting in apparent hyperaldosteronism. In the absence of hypertension, a low plasma aldosterone concentration, and an elevated urine chloride level, this condition can be excluded as a cause of metabolic alkalosis in the infant in the vignette. Respiratory acidosis occurs when PCO2 is retained due to poor respiratory effort caused by neuromuscular disorders (eg, brainstem disorders), airway obstruction (eg, severe bronchospasm), vascular injury (eg, pulmonary embolism), administration of sedatives, pneumothorax, or severe pneumonia. Compensatory mechanisms involve buffering of the PCO2 by nonbicarbonate buffers, increased acid excretion by the kidney, and enhanced reabsorption of bicarbonate by the renal proximal tubule. Thus, the plasma pH returns to near-normal levels and bicarbonate concentration may be increased to above-normal levels in patients who have respiratory acidosis. References: Garella S, Chang BS, Kahn SI. Dilution acidosis and contraction alkalosis: review of a concept. Kidney Int. 1975;8:279-283 Hanna JD, Scheinman JI, Chan JC. The kidney in acid-base balance. Pediatr Clin North Am. 1995;42:1365-1395 Rodriguiz-Soriano J. Tubular disorders of electrolyte regulation. In: Holliday TM, Avner ED, Kogan BA, eds. Pediatric Nephrology. 3rd ed. Baltimore, Md: Williams & Wilkins; 1994:624639 Critique 43 Preferred Response: B

[View Question] The first step in assessing a patient who has suspected acidosis is to calculate the anion gap. The anion gap is estimated from the difference in measured cations and anions, using the formula: serum sodium - (chloride + bicarbonate). The difference is equal to the

concentration of unmeasured ions, such as protein, organic acids, phosphate, and sulfate. The normal anion gap ranges from 8 to 16 mEq/L. The infant in the vignette has a high anion gap metabolic acidosis (140 - [100 + 10] = 30 mEq/L), which can be caused by a number of etiologies, summarized by the mnemonic MUD PILES.These disorders typically are normochloremic, in contrast to the hyperchloremic acidosis associated with a normal anion gap. The latter group is represented by the mnemonic USED CARP. The most likely etiology for the high anion gap acidosis in the infant in the vignette is organic acidemia, such as proprionic or methylmalonic acidemia. The majority of infants who have these conditions appear healthy at birth, but develop poor feeding, lethargy, dehydration, and clinical signs of metabolic acidosis that rapidly progress to coma and death. Seizures occur in about one third of infants. Laboratory evaluation reveals the presence of high anion gap acidosis, ketosis, neutropenia, and thrombocytopenia associated with moderate-to-severe hyperammonemia. The latter is postulated to occur because the enzyme carbamylphosphate synthetase (CPS) is inhibited by the organic acid. Urea cycle defects, which also present in the neonatal period with hyperammonemia, are not associated with metabolic acidosis. They are caused by deficiency of CPS or orthithine transcarbamylase (OTC). CPS deficiency is an autosomal recessive trait that presents in the first few days of life, although late forms have been reported. Infants present with mental retardation and recurrent episodes of vomiting and lethargy. OTC has an X-linked inheritance. Males present in the neonatal period; the heterozygote female may present later in life with episodes of hyperammonemia, vomiting, and lethargy that may be confused with gastrointestinal disorders. Infants who have urea cycle defects often are misdiagnosed as having signs of sepsis unless the serum ammonia concentration is measured and found to be elevated. Renal tubular acidosis, type 1 is caused by the inability of the distal renal tubule to acidify the urine. Thus, urine pH does not decrease below 5.5 in older children and adults and below 6 in newborns. Renal tubular acidosis, type 2 is caused by the inability of the proximal tubule to reclaim bicarbonate because the renal threshold for bicarbonate is set at a lower serum bicarbonate concentration than normal. This results in bicarbonaturia. Because patients who have this disorder can acidify their urine, urine pH can decrease to less than 5.5. Both disorders are characterized by hyperchloremia and normal anion gap acidosis, which eliminates them as potential causes of the findings in the infant in the vignette. The normal cerebrospinal fluid findings for the infant in the vignette makes meningitis unlikely. Although sepsis remains a possibility, measurement of serum levels of ammonia is helpful and may be lifesaving in infants who have inborn errors of metabolism. References: Hanna JD, Scheinman JI, Chan JC. The kidney in acid-base balance. Pediatr Clin North Am. 1995;42:1365-1395

Rezvani I. Urea cycle and hyperammonemia. In: Nelson WE, Behrman RE, Kliegman RM, Arvin AM, eds. Nelson Textbook of Pediatrics. 15th ed. Philadelphia, Pa: WB Saunders Co; 1996:350-355 Rezvani I. Valine, leucine, isoleucine, and related organic acidemias. In: Nelson WE, Behrman RE, Kliegman RM, Arvin AM, eds. Nelson Textbook of Pediatrics. 15th ed. Philadelphia, Pa: WB Saunders Co; 1996:340-345 Critique 66 Preferred Response: D

[View Question] The patient in the vignette has laboratory findings indicative of hypokalemia. Administration of intravenous potassium chloride is the first-line therapy in this condition. In contrast, intravenous calcium, glucose, insulin, and sodium bicarbonate all can be used for emergency treatment of hyperkalemia. Progression of electrocardiographic changes in the presence of hyperkalemia may be rapid. Initial findings of a prolonged QRS interval and peaked T waves may progress to a sinusoidal QRS associated with severe myocardial depression or cardiac arrest. Unless the hyperkalemia is recognized and treated, resuscitation will not be successful. Digoxin-specific antibody is the drug of choice for patients who have digitalis toxicity but would not be administered unless a toxic digoxin level has been confirmed. References: Jospe N, Forbes G. Fluids and electrolytes--clinical aspects.03654 Pediatrics in Review. 1996;17:395-404 Park MK. Electrolyte disturbances. In: Pediatric Cardiology for Practitioners. 3rd ed. St Louis, Mo: Mosby-Year Book, Inc; 1996:362-363 Siegel NJ, Carpenter T, Gaudio KM. The pathophysiology of body fluids. In: Oski FA, DeAngelis CD, Feigin RD, McMillan JA, Warshaw JB, eds. Principles and Practice of Pediatrics. 2nd ed. Philadelphia, Pa: JB Lippincott Co; 1994:60-79 Critique 88 Preferred Response: B

[View Question] The child in the vignette developed respiratory alkalosis due to hypoxemia and hyperventilation after moving to a mountain city. Clinically, patients who are experiencing difficulty with altitude adjustment may present with various degrees of dyspnea, abdominal pain, nausea, lassitude, headaches, insomnia, dizziness, and increased fatigability. The hyperventilation is induced by the hypoxia. Acute hypocapnia due to the hyperventilation results in hypophosphatemia and depletion of red blood cell energy stores, with a decrease in intracellular adenosine triphosphate (ATP). Reduced ATP concentration may contribute

further to peripheral tissue hypoxia by causing a shift to the right in the oxyhemoglobin dissociation curve. These changes are accompanied by a decrease in the fractional excretion of phosphate and blunting of the phosphaturic effect of parathyroid hormone. Hyperchloremia (due to cellular shifts), hypocalcemia, and hypomagnesemia may occur. The kidney adapts by increasing the excretion of bicarbonate and decreasing (rather than increasing) the excretion of titrable acids. In this situation, the fractional excretion of sodium is greater than 1%. There is no effect on the renal handling of glucose. References: Meehan RT, Zavala DC. The pathophysiology of acute high-altitude illness. Am J Med. 1982;73:395-403 Staubli M, Ott P, Waber U, et al. Erythrocyte adenosine triphosphate depletion during voluntary hyperventilation. J Appl Physiol. 1985;59:1196-2000 Critique 112 Preferred Response: E

[View Question] The infant described in the vignette has hypertrophic pyloric stenosis, a diffuse hyperplasmia and hypertrophy of the smooth muscle that narrows the pylorus of the stomach and causes gastric outlet obstruction. This hypertrophic area produces a hard, olive-shaped mass that, in many cases, can be palpated in the epigastrium to the right of the midline. The projectile vomiting associated with pyloric stenosis characteristically results in metabolic alkalosis due to excessive losses of hydrogen and chloride ions. Contraction of extracellular fluid volume (which increases bicarbonate reabsorption in the renal tubule) may accentuate metabolic alkalosis further in affected infants. In general, in interpreting acid-base status, the first result of an arterial blood gas analysis to examine is pH. If pH is less than 7.40, the primary disturbance is an acidosis; if it is greater than 7.40, an alkalosis is present. If a calculation of the serum bicarbonate has been performed, the metabolic state may be determined from that value. A bicarbonate concentration below 25 mEq/L suggests metabolic acidosis and greater than 25 mEq/L suggests metabolic alkalosis. The distinction between acidosis and alkalosis is agedependent. For example, infants have lower concentrations of serum bicarbonate than adults. Both the pH and the plasma bicarbonate concentration are increased in metabolic alkalosis, although the normal body buffer systems function to minimize the change in pH. For example, in a patient who has metabolic alkalosis, hypoventilation and elevation of PCO2 occur as part of the respiratory compensatory mechanism. Typically, these responses are incomplete and do not actually normalize the pH. Thus, the most likely laboratory findings for the infant presented in the vignette are an elevated pH (7.55) and bicarbonate level (48 mEq/L), despite a compensatory increase in PCO2 (55 torr).

The patient would not be expected to have a metabolic acidosis (pH 7.20; HCO3, 8 mEq/L) with a compensatory decrease in PCO2 (20 torr) given the findings of only mild dehydration and normal tissue perfusion. Similarly, the infant should not have respiratory acidosis (pH, 7.25; PCO2, 55 torr; HCO3, 23 mEq/L) or respiratory alkalosis (pH, 7.55; PCO2, 20 torr; HCO3,17 mEq/L). Finally, it is physiologically impossible for an infant who has an elevated Pco2 (55 torr) and a decreased bicarbonate concentration (17 mEq/L) to have an increased pH (7.55) because the changes in Pco2 and bicarbonate concentration independently cause a decrease in pH. Reference: Adelman RD, Solhung MJ. Pathophysiology of body fluid and fluid therapy: Hydrogen ion. In: Nelson WE, Behrman RE, Kliegman RM, Arvin AM, eds. Nelson Textbook of Pediatrics. 15th ed. Philadelphia, Pa: WB Saunders Co; 1996:200-206 Jefferson LS, Bricker JT. Acid-base balance and disorders. In: Fuhrman BP, Zimmerman JJ, eds. Pediatric Critical Care. St Louis, Mo: Mosby Year Book; 1992:689-696 Winters RW. Acid-base disorders. In: Principles of Pediatric Therapy. 2nd ed. Boston, Mass: Little, Brown and Co; 1982:23-55 Critique 133 Preferred Response: B

[View Question] In metabolic acidosis, pH is depressed because of acidosis and tissue hypoxia. The mechanism of this acidosis is not fully understood. It represents either an inability of cells to use oxygen or a failure of oxygen to be delivered to the tissues. When a patient is breathing spontaneously, the central nervous system is stimulated by chemoreceptors that are sensitive to acidosis; thus, metabolic acidosis leads to hyperventilation and serum hypocarbia. Accordingly, results of an initial blood gas for the child in the vignette are most likely to reveal findings consistent with a compensated metabolic acidosis (pH, 7.20) and hypocarbia (PCO2, 25 torr). When hypercarbia (eg, PCO2, 75) causes acidosis (eg, pH, 7.15), respiratory or neuromuscular failure should be suspected; hypermetabolism or central nervous system dysfunction also may be the cause. In contrast, respiratory alkalosis would be expected in patients who have primary hyperpnea (ie, secondary to brain lesions) with hypocarbia. In patients who have lung disease, a ventilation/perfusion mismatch usually causes isolated hypoxemia (pH, 7.35; PCO2, 40 torr; PO2, 50 torr). Reference: Jefferson LS, Bricker JT. Acid-base balance and disorders. In: Fuhrman BP, Zimmerman JJ, eds. Pediatric Critical Care. St Louis, Mo: Mosby Year Book; 1992:689-696 Critique 159 Preferred Response: A

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The child in the vignette has "classic" clinical findings of cystic fibrosis (CF), including the triad of poor weight gain, foul-smelling stools, and persistent cough. Profound hypoelectrolytemia that cannot be explained by gastrointestinal losses is characteristic of CF. Children who have CF produce sweat that contains excessive amounts of sodium, chloride, and potassium. A sweat chloride concentration of more than 60 mEq/L on a sweat test is consistent with the diagnosis of CF. In hot weather, when large amounts of sweat are produced by most people, patients who have CF may lose even greater amounts of salt. Such excessive salt loss in a heat-stressed young child may cause a severe hyponatremic, hypokalemic, and hypochloremic metabolic alkalosis. Thus, in the child in the vignette, a combination of low sodium (120 mEq/L), low chloride (85 mEq/L), low potassium (3.1 mEq/L), and elevated carbon dioxide levels (35 mEq/L) is the most likely serum electrolyte profile. References: Boat TF. Cystic fibrosis. In: Nelson WE, Behrman RE, Kliegman RM, Arvin AM, eds. Nelson Textbook of Pediatrics. 15th ed. Philadelphia, Pa: WB Saunders Co; 1996:1239-1250 Colin AA, Wohl ME. Cystic fibrosis.02304 Pediatrics in Review. 1994;15:192-200 Farrell PM, Koscik RE. Sweat chloride concentrations in infants homozygous or heterozygous for F508 cystic fibrosis. Pediatrics. 1996;97:524-528 Kravath RE. Cystic fibrosis. In: Finberg L, Kravath RE, Hellerstein S, Saenger P, eds. Water and Electrolytes in Pediatrics. 2nd ed. Philadelphia, Pa: WB Saunders Co; 1993:240-244 Rosenstein BJ. Cystic fibrosis. In: Oski FA, DeAngelis CD, Feigin RD, McMillan JA, Warshaw JB, eds. Principles and Practice of Pediatrics. 2nd ed. Philadelphia, Pa: JB Lippincott Co; 1994:1490-1501 Stokes DC. Cystic fibrosis. In: Roberts KB, ed. Manual of Clinical Problems in Pediatrics. 4th ed. Boston, Mass: Little, Brown and Company; 1995:281-287 Critique 183 Preferred Response: D

[View Question] The infant in the vignette exhibits clinical and biochemical findings commonly seen in hypernatremic dehydration. Because the extracellular fluid is hypertonic, fluid shifts from the intracellular space, resulting in shrinkage of the cells and maintenance of the intravascular volume for a period of time. Infants who have hypernatremic dehydration are irritable and lethargic, their skin is doughy, and they have a high-pitched cry. This type of dehydration results from a greater loss of hypotonic fluid than sodium and accounts for 15% of all cases of dehydration. Because the patient has no clear history of gastroenteritis, the hypernatremia may be related to an inadequate supply of human milk that cannot match the obligatory water losses. Alternatively, it may be related to a high concentration of sodium in the human milk. Generally, colostrum contains 12 to 60 mEq/L of

sodium, which decreases to 7 mEq/L by the third or fourth week after delivery (ie, mature milk). However, some mothers continue to excrete high concentrations of sodium in mature milk and may not be able to breastfeed their infants because of the potential for recurrent episodes of hypernatremia. Thus, it is important to test the sodium concentration of human milk and to assess carefully the dietary intake of infants who present with hypernatremic dehydration in the absence of gastrointestinal losses. Acute central nervous system (CNS) symptomatology, including seizures, correlates with the severity of hypernatremia and, hence, the effect of hypertonicity on the CNS. Permanent CNS damage has been reported with serum sodium concentrations in excess of 160 mEq/L; the mortality rate can be as high as 10%. Intracranial hemorrhages or thromboses occur when the hypertonicity causes cellular dehydration; this results in brain shrinkage and tearing of the bridging vessels. This has been reported in neonates following the administration of an acute sodium load. If hypernatremia persists, brain cellular dehydration may resolve as "idiogenic osmoles" accumulate in brain cells, a process that generally requires 24 to 72 hours for completion. Thus, to avoid acute brain swelling with its associated CNS sequelae, the fluid deficit should be corrected over a period of 48 to 72 hours at a rate that would decrease the serum sodium concentration by no more than 10 to 12 mEq/L per day. Although hypocalcemia, hypoglycemia, and hypomagnesemia are metabolic causes of seizures, serum levels of calcium, glucose, and magnesium are normal in the infant in the vignette. In patients who have hypernatremic dehydration, hyperglycemia (caused by overstimulation of glucagon during the episode of hypernatremia) and hypocalcemia are seen commonly. Meningitis and other CNS infections must be considered in any 2-week-old infant who develops a generalized seizure with or without fever. However, the markedly elevated sodium concentration makes this less likely than hypernatremia as an explanation of these findings. References: Adelman RD, Solhung MJ. Pathophysiology of body fluids and fluid therapy. In: Nelson WE, Behrman RE, Kliegman RM, Arvin AM, eds. Nelson Textbook of Pediatrics. 15th ed. Philadelphia, Pa: WB Saunders Co; 1996:185-222 Conley SB. Hypernatremia. Pediatr Clin North Am. 1990;37:365-372 Dabbagh S, Atiyeh B, Fleischmann LE, Gruskin AB. Fluid and electrolyte therapy in children. In: Burg FD, Ingelfinger JR, Wald ER, Polin RA, eds. Gellis & Kagan's Current Pediatric Therapy. 15th ed. Philadelphia, Pa: WB Saunders Co; 1996:424-434 Trachtman H, Barbour R, Sturman JA, Finberg L. Taurine and osmoregulation: taurine is a cerebral osmoprotective molecule in chronic hypernatremic dehydration. Pediatr Res. 1988;23:35-39 Critique 204 Preferred Response: B

[View Question] Hypernatremia may result from sodium excess or from water deficit. Pure sodium excess or salt poisoning is unusual, but it has been reported in infants due to improper mixing of infant formulas, human milk containing high concentrations of sodium, or an iatrogenic addition of salt, instead of sugar, to the formula, as occurred in the vignette. Salt poisoning also has been reported during the administration of large amounts of sodium bicarbonate during resuscitation or following ingestion of sea water. Hypernatremia is accompanied by hypertonicity. Fluid shifts from the intracellular space to the extracellular compartment, resulting in shrinkage of the cells. In the absence of dehydration, there is an increase in the extracellular volume. Patients are at risk of developing pulmonary edema, particularly during fluid administration. In cases of severe salt poisoning, peritoneal dialysis may be needed to correct the hypernatremia. References: Conley SB. Hypernatremia. Pediatr Clin North Am. 1990;37:365-372 Dabbagh S, Atiyeh B, Fleischmann LE, Gruskin AB. Fluid and electrolyte therapy in children. In: Burg FD, Ingelfinger JR, Wald ER, Polin RA, eds. Gellis & Kagan's Current Pediatric Therapy. 15th ed. Philadelphia, Pa: WB Saunders Co; 1996:424-434 Critique 228 Preferred Response: B

[View Question] Hyponatremia, defined as a serum sodium concentration of less than 130 mEq/L, is reported to occur in 1.5% of children hospitalized after the newborn period. Symptoms usually are related to the underlying cause of hyponatremia. Clinical manifestations vary and tend to manifest at sodium concentrations of less than 120 mEq/L. The disorder is classified into three major categories: hypovolemic, euvolemic, and hypervolemic. Measurement of the urinary fractional excretion of sodium (FENa) is helpful to determine the cause of the hyponatremia. The peripheral edema and respiratory distress seen in the child in the vignette likely are related to congestive heart failure. The cause of the hyponatremia is fluid overload. Other clinical features of congestive heart failure include distension of the neck veins, pulmonary rales, and congested liver. Such affected patients avidly retain sodium. Although hypervolemia does occur in congestive heart failure, the effective circulating blood volume is decreased. This stimulates the renin-angiotensin-aldosterone system and increases secretion of antidiuretic hormone. The result is enhanced urinary reabsorption of sodium and water retention. Despite the elevated levels of atrial natriuretic hormone, the kidneys do not respond to the hormone's diuretic and natriuretic actions, probably because of downregulation of its renal receptors. Measurement of serum osmolality is not helpful in determining the cause of hyponatremia because it is expected to be decreased.

Because of the decrease in effective circulating blood volume and its effects on antidiuretic hormone, urine specific gravity should be elevated, which eliminates its usefulness in determining the cause of hyponatremia. Neither urine nor venous pH are helpful in this clinical situation; they are helpful in assessing disorders of acid-base metabolism. References: Berry PL, Belsha CW. Hyponatremia. Pediatr Clin North Am. 1990;37:351-363 Briggs JP, Sawaya BE, Schnermann J. Disorders of salt balance. In: Kokko JP, Tannen RL, eds. Fluids and Electrolytes. 2nd ed. Philadelphia, Pa: WB Saunders Co; 1990:70-138 Dabbagh S, Atiyeh B, Fleischmann LE, Gruskin AB. Fluid and electrolyte therapy in children. In: Burg FD, Ingelfinger JR, Wald ER, Polin RA, eds. Gellis & Kagan's Current Pediatric Therapy. 15th ed. Philadelphia, Pa: WB Saunders Co; 1996:424-434 Critique 251 Preferred Response: C

[View Question] Premature ventricular beats have been shown to occur in the presence of hypokalemia, particularly when the patient is receiving digoxin, such as the boy in the vignette. Delta waves are manifestations of ventricular preexcitation or Wolff-ParkinsonWhite syndrome; they are not related to any electrolyte abnormalities. Peaked T waves, prolonged QRS interval, and prolonged PR interval are indicative of hyperkalemia rather than hypokalemia. The corrected QT interval (QTc) is affected primarily by serum calcium concentrations and not potassium levels; hypercalcemia shortens the QTc interval and hypocalcemia prolongs it. A prolonged QTc interval (>0.455 sec) also can be a marker for an inherited form of ventricular arrhythmias (ie, Romano Ward syndrome) and should be followed up with an appropriate evaluation. References: Jospe N, Forbes G. Fluids and electrolytes--clinical aspects.03654 Pediatrics in Review. 1996;17:395-404 Park MK. Congestive heart failure. In: Pediatric Cardiology for Practitioners. 3rd ed. St Louis, Mo: Mosby-Year Book, Inc; 1996:405-406 Park MK. Electrolyte disturbances. In: Pediatric Cardiology for Practitioners. 3rd ed. St Louis, Mo: Mosby-Year Book, Inc; 1996:362-363 Siegel NJ, Carpenter T, Gaudio KM. The pathophysiology of body fluids. In: Oski FA, DeAngelis CD, Feigin RD, McMillan JA, Warshaw JB, eds. Principles and Practice of Pediatrics. 2nd ed. Philadelphia, Pa: JB Lippincott Co; 1994:60-79