Pediatric Examination and Board Review (214 page)

SELECT THE ONE BEST ANSWER

1.
The serum osmolality in this patient is

(A) 296

(B) 302

(C) 306

(D) 300

(E) none of the above

2.
The most likely cause for this infant’s failure to thrive is

(A) metabolic acidosis because of renal tubular acidosis and urinary concentration defect

(B) nephrogenic diabetes insipidus

(C) Bartter syndrome with polyuria

(D) Gitelman syndrome

(E) Liddle disease

3.
Other laboratory investigations that may be helpful include

(A) spot urine calcium-to-creatinine ratio

(B) serum vasopressin levels

(C) nasal vasopressin (DDAVP) test

(D) B and C

(E) A, B, and C

4.
This disease is most commonly inherited as

(A) an autosomal recessive disorder

(B) an autosomal dominant disorder

(C) an X-linked recessive disorder

(D) an X-linked dominant disorder

(E) none of the above

5.
This condition is most appropriately treated with

(A) low-solute diet

(B) thiazide diuretics with amiloride and prostaglandin-synthesis inhibitors, such as indomethacin

(C) thiazide diuretics and prostaglandin-synthesis inhibitors, such as indomethacin

(D) all of the above

(E) A and C

6.
Urine osmolality
in this patient
is measured to determine

(A) urine osmolal gap

(B) urine anion gap

(C) urine concentration defect

(D) none of the above

(E) A and B

7.
Urine osmolality should be measured in the urine

(A) in all patients routinely

(B) if a urinary concentration defect is suspected

(C) to measure the urine osmolal gap

(D) all of the above

(E) B and C

8.
Normal range of urine osmolality in a child is

(A) 200-1200 mOsm/kg of H
₂
O

(B) 100-1000 mOsm/kg of H
₂
O

(C) 50-1400 mOsm/kg of H
₂
O

(D) 400-800 mOsm/kg of H
₂
O

(E) 300-900 mOsm/kg of H
₂
O

9.
In acquired or secondary nephrogenic diabetes insipidus

(A) aquaporin 5 expression is decreased

(B) aquaporin 2 expression is decreased

(C) aquaporin 6 expression is decreased

(D) aquaporin 1 expression is decreased

(E) aquaporin 4 expression is decreased

10.
Secondary diabetes insipidus can be caused by

(A) analgesic nephropathy

(B) amoxicillin

(C) lithium therapy

(D) all of the above

(E) A and C

11.
Secondary diabetes insipidus occurs with

(A) obstructive uropathy

(B) chronic renal failure

(C) chronic pyelonephritis

(D) all of the above

(E) A and C

12.
Secondary diabetes insipidus can occur in

(A) hypokalemia

(B) hyponatremia

(C) hypercalcemia

(D) A and C

(E) diabetes mellitus

13.
Acquired nephrogenic diabetes insipidus can be caused by all of the following except

(A) sarcoidosis

(B) iron deficiency anemia

(C) renal dysplasia

(D) nephrocalcinosis

(E) sickle cell anemia and trait

14.
Nephrogenic diabetes insipidus can be all of the following except

(A) caused by unresponsiveness of renal tubules to vasopressin

(B) caused by a vasopressin deficiency

(C) a familial disorder

(D) an acquired disorder

(E) caused by decreased aquaporin expression

15.
Infants with nephrogenic diabetes insipidus can present with all of the following except

(A) failure to thrive

(B) seizures

(C) polyphagia

(D) constipation

(E) dilated ureters

16.
Nephrogenic diabetes insipidus in children can cause all of the following except

(A) short stature

(B) mental retardation

(C) hydronephrosis

(D) microcystis

(E) hyperactivity

17.
Children with nephrogenic diabetes insipidus are at risk of developing dehydration with all of the following except

(A) gastroenteritis

(B) low salt intake

(C) hot weather

(D) exercise

(E) fever

ANSWERS

1.
(C)
Sodium is the major cation in extracellular water and accounts for most of the plasma osmolality. However, under pathologic conditions, serum urea nitrogen (as in acute renal failure) and glucose (as in diabetic ketoacidosis) can also contribute significantly to the serum osmolality. Therefore, the serum osmolality is calculated as (2 × serum sodium in mEq/L) + (serum glucose in mg/dL/18) + (BUN in mg/dL/2.8). The serum osmolality in this patient is (2 × 148) + (72/18) + (17/2.8) = 306 (normal range: 285-295).

2.
(B)
This infant does not have renal tubular acidosis and metabolic acidosis because the serum bicarbonate of 20 mEq/L is in the normal range for infants (20-24 mEq/L). This is one of the typical presentations of congenital nephrogenic diabetes insipidus. Urine specific gravity and osmolality are low with borderline high serum sodium. An initial diagnosis of diabetes insipidus can be made with measurement of paired urine and plasma osmolality. A high serum osmolality with low urinary osmolality (< 200 mOsm/kg H
₂
O) provides evidence for a renal urinary concentration defect. This infant was initially breast-fed on demand but changed to fixed intervals while on formula. Had breastfeeding on demand continued, the infant would have received enough free water to continue to gain weight because human breast milk has low salt and protein content, and therefore there is less osmolar load in the glomerular filtrate requiring less obligate water loss in the urine. Demand breastfeeding would have provided adequate fluid intake appropriate to thirst. When switched to formula feeds, however, the baby was on a fixed volume of feeds at 120-150 mL/kg per day. Cow’s milk has a higher solute and protein load that would lead to greater urinary osmolar load and greater free water losses. Weight loss and failure to thrive are the result.

Bartter syndrome is characterized by a defect in the Na-K-2Cl cotransporter in the ascending limb of the loop of Henle, leading to loss of sodium (Na), potassium (K), and chloride (Cl) in the urine and hypokalemic hypochloremic metabolic alkalosis. This infant does not have metabolic alkalosis.

Gitelman syndrome occurs in older children and is a result of a defect in the Na-Cl cotransporter in the distal convoluted tubule, leading to a loss of Na, K, and Cl in the urine and hypokalemic hypochloremic metabolic alkalosis as well as hypomagnesemia, a result of increased urinary magnesium loss.

Liddle syndrome occurs in adolescents and adults and is caused by upregulation of the epithelial sodium channel (ENaC) in the principal cell of the cortical-collecting duct. It leads to excessive sodium absorption with hypokalemia due to increased Na-K exchange and K loss in the urine. Hypertension is a result of volume expansion.

3.
(D)
Nephrogenic diabetes insipidus is characterized by renal tubular insensitivity to antidiuretic hormone (ADH) or arginine vasopressin (AVP); therefore vasopressin levels are normal or may even be slightly increased in these patients. A vasopressin test may be performed and consists of intranasal administration of a single dose of DDAVP (1-desamino-8-D-arginine vasopressin) followed by urine collection over the next 5
¹
/
₂
hours. Patients with nephrogenic diabetes insipidus fail to concentrate their urine and the urine osmolality remains low, usually 200 mOsm/kg H
₂
O or less.

4.
(C)
Congenital nephrogenic diabetes insipidus (NDI) is inherited, most commonly (about 90%) as an X-linked recessive disorder, and therefore unaffected female carriers transmit the disease to their sons. This usually results in episodes of hypernatremic dehydration during infancy. One common presentation is failure to thrive when an infant is switched from breast milk to formula feeds. Rare cases (about 10%) have been described that are a result of mutations in the aquaporin water channel gene as an autosomal recessive or autosomal dominant disorder. Patients with this mutation present with hypokalemia. Associated conditions include renal dysplasia, obstructive uropathy, chronic renal failure, chronic pyelonephritis, sickle cell anemia and trait, analgesic nephropathy, and persons on lithium therapy.

5.
(D)
Free water replacement is the most important part of the treatment of NDI. Because this can be difficult in infants, a low-solute diet to decrease obligate free water losses in the urine by decreasing the urine osmolar load is prudent.

Thiazide diuretics and dietary salt restriction can decrease the urine volume up to 50% but need supplementation of diet with K because they can cause hypokalemia. A combination of a thiazide diuretic with another diuretic like amiloride that acts on ENaCs in the principal cell of the cortical collecting duct is K sparing and effective. Thiazide diuretics have also been used in combination with prostaglandin synthesis inhibitors such as indomethacin as an effective regimen in decreasing the urine output in NDI.

6.
(C)
In this patient, hypernatremia with low urine specific gravity is suggestive of a urinary concentration defect, and therefore a simultaneous plasma and urine osmolality would be necessary to make the diagnosis of diabetes insipidus. Urine osmolality can also be measured to determine the urine osmolal gap. This is the measured urine osmolality minus the calculated urine osmolality (based on the formula: [2 × urine sodium in mEq/L] + [glucose in mg/dL/18] + [urea in mg/dL/2.8]). The difference should be a positive number (because the measured osmolality is higher than the calculated osmolality) and under most circumstances represents the amount of ammonium chloride being excreted in the urine. Thus this calculation measures the amount of ammonium excreted in the urine in patients who are suspected to have renal tubular acidosis. However, in this patient, we are suspecting diabetes insipidus, not renal tubular acidosis.