I. A patient with lymphoma who is known to excrete 1.

5 g urinary protein per day has a negative dipstick evaluation for urinary protein. The reason for the seeming inconsistency is: 1.The size of the excreted protein is too small to be detected by the test strip. 2 The urine is not concentrated enough. 3. Only heavy chain sequences are recognized by the test strip. 4. Tamm-Horsfall protein blocks the reaction between the secreted protein and the test strip. 5. Dipstick preferentially detects albumin compared with immunoglobulin because albumin is negatively charged.*

The explanation for the correct response is: Up to 150 mg/d of protein may be excreted by a normal person. The bulk of normal daily excretion is made up of the Tamm-Horsfall mucoprotein. Urine dipsticks may register a trace result in response to as little as 50 mg protein per liter and are definitively positive once the urine protein exceeds 300 mg/L. A false negative may occur if the proteinuria is due to immunoglobulins, which are positively charged. If proteinuria is suspected or documented, a 24-h urine collection should be undertaken to measure the absolute protein excretion. Urine immunoelectrophoresis also may identify the particular immunoglobulin that is produced in excess.

II. A 75-year-old female nursing home resident is brought to the emergency department because of increasing obtundation. She is found to communicate poorly. Brief physical examination reveals diminished skin turgor. Blood pressure is 100/60, pulse 120, respiratory rate 20, and temperature 37C (98.6F). Blood tests reveal the following serum electrolytes: sodium 160 mmol/L, potassium 5.0 mmol/L, bicarbonate 30 mmol/L, chloride 110 mmol/L. The most appropriate management at this time would include administration of 5% dextrose in 1. Normal saline, 100ml/hour 2. Normal saline solution, 250ml/hour 3. Half normal saline, 100ml/h 4. Half normal saline, 200ml/h 5. Water, 150ml/h

The explanation for the correct response is: Because of the powerful effect of ADH secretion in the setting of hypertonicity, severe persistent hypernatremia is possible only in patients who cannot respond to thirst by ingesting water. A nursing home patient with a fever may lose significant amounts of body fluid, which can result in dangerous levels of hypernatremia. Manifestations of hypernatremia include central nervous system dysfunction such as neuromuscular irritability, seizures, obtundation, or coma. Calculation of water replacement needs is based on total body water, since water loss occurs from both intracellular and extra cellular sites. In this case, a 60-kg woman has a plasma sodium of 160 mmol/L, which one would like to lower to 140 mmol/L. Total body water is roughly 60 percent of weight (36 L). To reduce the plasma sodium, this volume must be increased to 160/140 times 36 L, or about 41 L. Thus, a positive

water balance of 5 L (41-36) is needed. This deficit is best corrected fairly slowly, with the aim being to replace about half the water deficit in the first day. If correction is done in this conservative fashion with close monitoring of electrolytes, progressive central nervous system dysfunction is not likely. If the patient had signs of circulatory collapse indicating an associated sodium deficiency, treatment would begin with normal saline to provide intracellular volume. In certain situations, such as hyperosmolar diabetic coma, the plasma osmolarity is elevated because of hyperglycemia as well as hypernatremia. Therefore, initial treatment should consist of normal saline to ensure circulatory integrity and insulin to lower plasma glucose and partially reduce intracellular osmolarity. Finally, half normal saline could be used to slowly replace the remaining water and salt deficits.

III. Laboratory evaluation of a 19-year-old man being worked up for polyuria and polydipsia yields the following results: Serum electrolytes (mmol/L): Na+ 144; K+ 4.0; Cl- 107; HCO3- 25 BUN: 6.4 mmol/L (18 mg/dL) Blood glucose: 5.7 mmol/L (102 mg/dL) Urine electrolytes (mmol/L): Na+ 28; K+ 32 Urine osmolality: 195 mosmol/kg water After 12 h of fluid deprivation, body weight has fallen by 5 percent. Laboratory testing now reveals the following: Serum electrolytes (mmol/L): Na+ 150; K+ 4.1; Cl- 109; HCO3- 25 BUN: 7.1 mmol/L (20 mg/dL) Blood glucose: 5.4 mmol/L (98 mg/dL) Urine electrolytes (mmol/L): Na+ 24; K+ 35 Urine osmolality: 200 mosmol/kg water One hour after the subcutaneous administration of 5 units of arginine vasopressin, urine values are as follows: Urine electrolytes (mmol/L): Na+ 30; K+ 30 Urine osmolality: 199 mosmol/kg water The likely diagnosis in this case is

1. Nephrogenic diabetes insipidus* 2. Osmotic diuresis 3. Salt loosing nephropathy 4. Psychogenic polydipsia 5. None of the above
The explanation for the correct response is: Failure to concentrate urine despite substantial hypertonic dehydration suggests a diagnosis of diabetes insipidus. A nephrogenic origin will be postulated if there is no increase in urine concentration after exogenous vasopressin. The only useful mode of therapy is a low-salt diet and use of a thiazide or amiloride, a potassium-sparing distal diuretic agent. The resultant volume contraction presumably enhances proximal reabsorption and thereby reduces urine flow.

IV. A 70-year-old man with diabetes mellitus and hypertension has the following
serum chemistries: Electrolytes (mmol/L): Na+ 138; K+ 5.0; Cl- 106; HCO3- 20 Glucose: 11 mmol/L (200 mg/dL) Creatinine: 176 mol/L (2.0 mg/dL)

All the following may contribute to worsening hyperkalemia EXCEPT

1. 2. 3. 4. 5.

propranalol indomethacin captopril digitalis carbenicillin*

The explanation for the correct response is: This man's electrolyte pattern is consistent with the "syndrome of hyporeninemic hypoaldosteronism," or type IV renal tubular acidosis. The defect is believed to be due to an insufficiency of both angiotensin (because of impaired renin release) and adrenal mineralocorticoid secreting capacity. Inhibition of the renin-angiotensin system by nonsteroidal anti-inflammatory agents, converting-enzyme inhibitors, and beta2-adrenergic blockade can contribute to hyperkalemia. Beta blockade also can interfere with intracellular potassium uptake. Potassium can leak out of cells owing to the digitalis-induced poisoning of the Na+, K+-ATPase. Use of carbenicillin can lead to hypokalemia, since this drug acts as an unresorbed anion, promoting the potassium loss associated with distal tubular secretion.

The explanation for the correct response is: This man's electrolyte pattern is consistent with the "syndrome of hyporeninemic hypoaldosteronism," or type IV renal tubular acidosis. The defect is believed to be due to an insufficiency of both angiotensin (because of impaired renin release) and adrenal mineralocorticoid secreting capacity. Inhibition of the renin-angiotensin system by nonsteroidal anti-inflammatory agents, converting-enzyme inhibitors, and beta2-adrenergic blockade can contribute to hyperkalemia. Beta blockade also can interfere with intracellular potassium uptake. Potassium can leak out of cells owing to the digitalis-induced poisoning of the Na+, K+-ATPase. Use of carbenicillin can lead to hypokalemia, since this drug acts as an unresorbed anion, promoting the potassium loss associated with distal tubular secretion.

V. A 40-year-old alcoholic male presents with a 6-day history of binge drinking. Serum chemistry tests reveal the following: Electrolytes (mmol/L): Na+ 145; K+ 5.0; Cl- 105; HCO3- 15 BUN: 7.1 mmol/L (20 mg/dL) Creatinine: 133 g/L (1.5 mg/dL)

Glucose: 9.6 mmol/L (172 mg/dL) The nitroprusside (Acetest) agent gives a minimally positive result. Optimal therapy to ameliorate the patient's acid-base disorder would include 5% dextrose in

1. Water 2. Normal saline* 3. Normal saline, insulin and sodium bicarbonate 4. Half normal saline and insulin 5. Half normal saline, insulin and sodium bicarbonate
The explanation for the correct response is: A reasonable way to approach the diagnosis of metabolic acidosis is to separate patients into those with an increased anion gap and those with a normal anion gap (hyperchloremic acidosis). A calculation of these unmeasured anions consists of the sum of plasma bicarbonate and chloride minus the plasma sodium concentration (the normal value is 8 to 16 mmol/L). Reasons for increased acid production include diabetic ketoacidosis, alcoholic ketoacidosis (as in this patient), starvation, lactic acidosis caused by circulatory failure, certain drugs and toxins, and poisoning resulting from salicylates, ethylene glycol, or methanol. Finally, renal failure increases the anion gap because sulfate, phosphate, and organic acid ions are not excreted normally. Normal anion gap acidosis is due to renal tubular dysfunction or

colonic losses. Since the ratio of beta-hydroxybutyrate to acetoacetate is high in alcoholic ketoacidosis, ketonemia can be missed by the routinely employed nitroprusside (Acetest) reagent, which detects acetoacetate but not betahydroxybutyrate. Patients suffering from alcoholic ketoacidosis do well on infusions of glucose and saline. Neither insulin nor alkali is required in these situations unless the acidosis is extreme (bicarbonate less than 6 to 8 mmol/L).

VI. A 45-year-old woman who has had slowly progressive renal failure begins to
complain of increasing numbness and prickling sensations in her legs. Examination reveals loss of pinprick and vibration sensation below the knees, absent ankle jerks, and impaired pinprick sensation in the hands. Serum creatinine concentration, checked during her most recent clinic visit, is 790 mol/L (8.9 mg/dL). The woman's physician should now recommend 1. 2. 3. 4. 5. a therapeutic trial of phenytoin a therapeutic trial of pyridoxine a therapeutic trial of cyanocobalamine initiation of renal replacement therapy * neurological reference for nerve conduction studies

The explanation for the correct response is: Development of advancing peripheral neuropathy is an indication for dialysis. Delaying dialysis could allow the development of irreversible motor deficits, such as foot drop. Prompt institution of dialysis, by contrast, usually prevents the progression of uremic peripheral neuropathy and may ameliorate early sensory defects. No pharmacologic agent would be of significant benefit in the clinical situation described. VII. In patients with chronic renal failure, all the following are important contributors to bone disease EXCEPT 1. impaired renal production of 1, 25 dihydroxy vit.D3 2. Hyperphosphataemia 3. Aluminium containing antacids 4. Loss of vit.D and calcium via dialysis.* 5. Metabolic acidosis.

The explanation for the correct response is: Impaired renal production of 1, 25-dihydroxyvitamin D3 leads to decreased calcium absorption from the gut. Impaired renal phosphate excretion leads to hyperphosphatemia, which initiates hyperparathyroidism. Hyperparathyroidism is worsened by hypocalcaemia, which is present because of hyperphosphatemia and decreased enzymatic conversion of 25(OH) D to 1, 25(OH) D, leading to decreased gut absorption of calcium. Finally, 1, 25(OH) D deficiency worsens hyperparathyroidism, as 1, 25(OH) D is a direct inhibitor of PTH secretion into bone. The resultant decreased serum calcium concentration leads to secondary hyperparathyroidism. Chronic metabolic acidosis leads to dissolution of bone buffers and decalcification. Aluminum administered in long-term therapy, although useful in controlling hyperphosphatemia and thereby hypocalcaemia, can be taken up by bone

and contribute to altered bone matrix. There is no significant loss of vitamin D or calcium associated with currently employed dialysis techniques. VIII. A 50-year-old man is hospitalized for treatment of enterococcal endocarditis. He has been receiving ampicillin and gentamicin for the past 2 weeks but is persistently febrile. Laboratory results are as follows: Serum electrolytes (mmol/L): Na+ 145; K+ 5.0; Cl- 110; HCO3- 20 BUN: 14.2 mmol/L (40 mg/dL) Serum creatinine: 300 mol/L (3.5 mg/dL)

Urine sodium: 20 mmol/L Urine creatinine: 3000 mmol/L (35 mg/dL) Which of the following is the most likely cause of this patient's acute renal failure? 1. 2. 3. 4. 5. Tubular necrosis * Insensible skin losses. Renal artery embolism Cardiac failure. Nausea and vomiting

The explanation for the correct response is: To offer optimal management to patients with acute renal failure, it is helpful to distinguish prerenal azotemia (generally managed with volume replacement or amelioration of cardiac dysfunction) from intrinsic renal dysfunction. Sodium reabsorption, which is quite avid in prerenal azotemia, is impaired in intrinsic renal disease. However, creatinine is reabsorbed less efficiently than sodium in both conditions. Therefore, the fractional excretion of sodium is very helpful in distinguishing between these two etiologies of renal failure. The fractional excretion of sodium is calculated by multiplying the urine sodium by the plasma creatinine, dividing this by the plasma sodium times the urine creatinine, and multiplying by 100. In this case the result is approximately 1.4, which suggests that impaired reabsorption of sodium is ongoing and that intrinsic renal failure is occurring. Only about 15 percent of patients receiving nephrotoxins such as amino glycosides or radio contrast agents have renal failure associated with a fractional excretion of sodium of less than 1 percent, and so an elevated value in this case points in the direction of nephrotoxic injury. The other causes of acute renal failure listed here are all associated with prerenal azotemia and therefore with a more avid reabsorption of sodium than that described. IX. A 23-year-old man has recurrent episodes of hematuria over the past year. Each of the episodes seems to be associated with an upper respiratory infection. Physical examination currently is normal. Urinalysis reveals a relatively bland sediment; dipstick is positive for both protein and blood. Renal biopsy most likely will reveal

1. 2. 3. 4. 5.

Extensive extra capillary proliferation on light microscopy. Diffuse mesangial proliferation on light microscopy Autosomal dominant polycystic kidney disease. Diffuse mesangial deposition of IgA on immunoflorescence * Deposition of C3 on capillary walls on immunoflorescence.

The explanation for the correct response is: One of the more common forms of asymptomatic urinary abnormalities is Berger's disease, which may be a cause of recurrent hematuria of glomerular origin. Such episodes of macroscopic hematuria may be associated with minor flu like illnesses or vigorous exercise. Skin rash, arthritis, and abdominal pain usually are absent, which tends to distinguish this entity from Henoch-Schnlein purpura. Occasionally patients develop a nephrotic or nephritic syndrome. Serum IgA levels are increased in about 50 percent of all cases, though serum complement is normal. Renal biopsy in these situations may reveal a spectrum of changes, though diffuse mesangial proliferation or focal and segmental proliferative glomerulonephritis is most common. The essential feature of Berger's disease is the finding of diffuse mesangial deposition of IgA on immunoflorescence microscopy. IgG, C3, and properdin, but not C1q or C4, also may be found on this study. Although the disease progresses slowly, about 50 percent of patients develop end-stage renal failure within 25 years of the original presentation. Men with hypertension and proteinuria (>1 g/d) are most likely to progress. Except for a recent report suggesting that omega-3 fatty acids may play a role, specific therapy has not been useful. However, glucocorticoids or antibiotics may reduce the frequency of episodic gross hematuria. IgA deposition in the kidney and recurrent renal failure may occur in about 35 percent of those who receive a renal allograft. Fortunately, such recurrent pathologic findings usually are not associated with loss of renal function.