Renal - BRS

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3. A 45-year-old woman develops severe diarrhea while on vacation. She has the following arterial blood values: pH = 7.25 Pco2 = 24 mm Hg [HCO3-] = 10 mEq/L Venous blood samples show decreased blood [K+] and a normal anion gap. 3. The correct diagnosis for this patient is (A) metabolic acidosis (B) metabolic alkalosis (C) respiratory acidosis (D) respiratory alkalosis (E) normal acid-base status

The answer is A An acid pH, together with decreased HCO3- and decreased Pco2, is consistent with metabolic acidosis with respiratory compensation (hyperventilation). *Diarrhea causes gastrointestinal (GI) loss of HCO3-, creating a metabolic acidosis.*

26. Which of the following causes hyperkalemia? (A) Exercise (B) Alkalosis (C) Insulin injection (D) Decreased serum osmolarity (E) Treatment with β-agonists

The answer is A Exercise causes a shift of K+ from cells into blood. The result is hyperkalemia. Hyposmolarity, insulin, β-agonists, and alkalosis cause a shift of K+ from blood into cells. The result is hypokalemia.

13. Which of the following would produce an increase in the reabsorption of isosmotic fluid in the proximal tubule? (A) Increased filtration fraction (B) Extracellular fluid (ECF) volume expansion (C) Decreased peritubular capillary protein concentration (D) Increased peritubular capillary hydrostatic pressure (E) Oxygen deprivation

The answer is A Increasing filtration fraction means that a larger portion of the renal plasma flow (RPF) is filtered across the glomerular capillaries. This increased flow causes an increase in the protein concentration and oncotic pressure of the blood leaving the glomerular capillaries. This blood becomes the peritubular capillary blood supply. The increased oncotic pressure in the peritubular capillary blood is a driving force favoring reabsorption in the proximal tubule. Extracellular fluid (ECF) volume expansion, decreased peritubular capillary protein concentration, and increased peritubular capillary hydrostatic pressure all inhibit proximal reabsorption. Oxygen deprivation would also inhibit reabsorption by stopping the Na+-K+ pump in the basolateral membranes.

34. Which set of arterial blood values describes a patient with a 5-day history of vomiting? pH HCO3- PCO2 a) 7.65 48 45 b) 7.50 15 20 c) 7.40 24 40 d) 7.32 30 60 e) 7.31 16 33

The answer is A The history of vomiting (in the absence of any other information) indicates loss of gastric H+ and, as a result, metabolic alkalosis (with respiratory compensation).

8. To maintain normal H+ balance, total daily excretion of H+ should equal the daily (A) fixed acid production plus fixed acid ingestion (B) HCO3- excretion (C) HCO3- filtered load (D) titratable acid excretion (E) filtered load of H+

The answer is A Total daily production of fixed H+ from catabolism of proteins and phospholipids (plus any additional fixed H+ that is ingested) must be matched by the sum of excretion of H+ as titratable acid plus NH4+ to maintain acid-base balance.

28. Which of the following is an action of parathyroid hormone (PTH) on the renal tubule? (A) Stimulation of adenylate cyclase (B) Inhibition of distal tubule K+ secretion (C) Inhibition of distal tubule Ca2+ reabsorption (D) Stimulation of proximal tubule phosphate reabsorption (E) Inhibition of production of 1,25 dihydroxycholecalciferol

The answer is A. Parathyroid hormone (PTH) acts on the renal tubule by stimulating adenyl cyclase and generating cyclic adenosine monophosphate (cAMP). The major actions of the hormone are *inhibition of phosphate reabsorption in the proximal tubule, stimulation of Ca2+ reabsorption in the distal tubule, and stimulation of 1,25-dihydroxycholecalciferol production*. PTH does not alter the renal handling of K+.

12. Enormously enlarged kidneys similar to the one shown in the figure are found at autopsy in a 65-year-old woman. Which of the following is a well-known association or characteristic of this disease process? (A) Berry aneurysm of the circle of Willis (B) Nephrotic syndrome (C) Polycystic ovaries (D) Polycythemia vera (E) X-linked inheritance

The answer is A. Berry aneurysm of the circle of Willis sometimes leading to subarachnoid hemorrhage is a well-known association of adult polycystic kidney disease. Inheritance is by an autosomal dominant mode of inheritance. Secondary polycythemia, not polycythe- mia vera, is a complication and is caused by increased secretion of erythropoietin.

7. A 28-year-old woman presents with fever, dysuria, urinary frequency, and flank tenderness. The urine contained numerous neutrophils and many white cell casts. Urine protein was moderately increased. A quantitative urine culture revealed more than 105 bacteria per milliliter. The most likely causative organism is (A) Escherichia coli. (B) Haemophilus influenzae. (C) Neisseria gonorrhoeae. (D) Proteus vulgaris. (E) Pseudomonas aeruginosa.

The answer is A. Organisms involved in urinary tract infections are most often normal flora of the colon, and the most frequent of these is E. coli. The other pathogen that would be likely in this patient is S. saprophyticus, however that was not an answer choice.

31. Which set of arterial blood values describes a patient with partially compensated respiratory alkalosis after 1 month on a mechanical ventilator? pH HCO3- PCO2 a) 7.65 48 45 b) 7.50 15 20 c) 7.40 24 40 d) 7.32 30 60 e) 7.31 16 33

The answer is B The blood values in respiratory alkalosis show decreased Pco2 (the cause) and decreased [H+] and [HCO3-] by mass action. The [HCO3-] is further decreased by renal compensation for chronic respiratory alkalosis (decreased HCO3- reabsorption).

16. Compared with a person who ingests 2 L of distilled water, a person with water deprivation will have a a) higher free-water clearance (CH2O ) b) lower plasma osmolarity c) lower circulating level of antidiuretic hormone (ADH) d) higher tubular fluid/plasma (TF/P) osmolarity in the proximal tubule e) higher rate of H2O reabsorption in the collecting ducts

The answer is E *The person with water deprivation will have a higher plasma osmolarity and higher circulating levels of antidiuretic hormone (ADH)*. These effects will increase the rate of H2O reabsorption in the collecting ducts and create a negative free-water clearance (-CH2O). Tubular fluid/plasma (TF/P) osmolarity in the proximal tubule is not affected by ADH.

32. Which set of arterial blood values describes a patient with chronic renal failure (eating a normal protein diet) and decreased urinary excretion of NH4+? pH HCO3- PCO2 a) 7.65 48 45 b) 7.50 15 20 c) 7.40 24 40 d) 7.32 30 60 e) 7.31 16 33

The answer is E In patients who have chronic renal failure and ingest normal amounts of protein, fixed acids will be produced from the catabolism of protein. Because the failing kidney does not produce enough NH4+ to excrete all of the fixed acid, metabolic acidosis (with respiratory compensation) results.

14. Which of the following substances or combinations of substances could be used to measure interstitial fluid volume? (A) Mannitol (B) D2O alone (C) Evans blue (D) Inulin and D2O (E) Inulin and radioactive albumin

The answer is E Interstitial fluid volume is measured indirectly by determining the difference between extracellular fluid (ECF) volume and plasma volume. *Inulin*, a large fructose polymer that is restricted to the extracellular space, is a marker for ECF volume. *Radioactive albumin* is a marker for plasma volume.

33. Which set of arterial blood values describes a patient with untreated diabetes mellitus and increased urinary excretion of NH4+? pH HCO3- PCO2 a) 7.65 48 45 b) 7.50 15 20 c) 7.40 24 40 d) 7.32 30 60 e) 7.31 16 33

The answer is E Untreated diabetes mellitus results in the production of keto acids, which are fixed acids that cause metabolic acidosis. Urinary excretion of NH4+ is increased in this patient because an adaptive increase in renal NH3 synthesis has occurred in response to the metabolic acidosis.

13. A 4-year-old boy presents with severe proteinuria, hypoalbuminemia, generalized edema, and hyperlipidemia. The patient improves on an empiric trial of corticosteroids, with complete resolution of protein- uria. Which of the following is the most likely diagnosis? (A) Diabetic nephropathy (B) Focal segmental glomerulosclerosis (C) Lupus nephropathy (D) Membranous glomerulonephritis (E) Minimal change disease

The answer is E. Minimal change disease (lipoid nephrosis) is the prototype of the nephrotic syndrome in children, who usually respond well to steroid therapy. Minimal change disease is characterized grossly by lipid-laden renal cortices. Light microscopy reveals normal glomeruli, but electron microscopy demonstrates the fusion of epithelial foot processes.

24. Which of the following substances has the highest renal clearance? (A) Para-aminohippuric acid (PAH) (B) Inulin (C) Glucose (D) Na+ (E) Cl-

The answer is A Para-aminohippuric acid (PAH) has the greatest clearance of all of the substances because it is both filtered and secreted. Inulin is only filtered. The other substances are filtered and subsequently reabsorbed; therefore, they will have clearances that are lower than the inulin clearance.

12. A buffer pair (HA/A-) has a pK of 5.4. At a blood pH of 7.4, the concentration of HA is (A) 1/l00 that of A- (B) 1/10 that of A- (C) equal to that of A- (D) 10 times that of A- (E) 100 times that of A-

The answer is A The Henderson-Hasselbalch equation can be used to calculate the ratio of HA/A-: pH=pK+logA− HA 7.4=5.4+log A− HA 2.0=logA− HA 100=A− HAorHA A− is1100

20. A 25-year-old man presents with hematuria, periorbital edema, hypertension, and hemoptysis. He has also experienced nausea, vomiting, fever, and chills. Serologic testing is positive for antiglomerular basement membrane antibodies. Which of the following is the classic histologic finding in this renal disease? (A) Linear immunofluorescence (B) "Lumpy-bumpy" immunofluorescence (C) "Spike and dome" appearance of the glomerular basement membrane (D) Subendothelial immune complex deposition (E) Tram-track appearance of the glomerular basement membrane on electron microscopy

The answer is A. The clinical description is that of Goodpasture syndrome (antiglomerular basement membrane disease), caused by antibodies directed against antigens in the glomerular and pulmonary alveolar basement membranes. Because antigens are an intrinsic component of the basement membrane, labeled antibodies "paint" the surface of the basement membrane, resulting in the characteristic linear immunofluorescent pattern characteristic of this disorder. "Lumpy-bumpy" immunofluorescence is very coarse, granular immunofluorescence found in poststreptococcal immune complex deposit disease. The tram-track appearance is seen in membranoproliferative glomerulonephritis. The "spike and dome" appearance is seen in membranous glomerulonephritis. Subendothelial immune complex deposition is seen in lupus nephropathy.

7. The following information was obtained in a 20-year-old college student who was participating in a research study in the Clinical Research Unit: Plasma [Inulin] = 1 mg/mL [X] = 2 mg/mL Urine [Inulin] = 150 mg/mL [X] = 100 mg/mL Urine flow rate = 1 mL/min Assuming that X is freely filtered, which of the following statements is most correct? (A) There is net secretion of X (B) There is net reabsorption of X (C) There is both reabsorption and secretion of X (D) The clearance of X could be used to measure the glomerular filtration rate (GFR) (E) The clearance of X is greater than the clearance of inulin

The answer is B To answer this question, calculate the glomerular filtration rate (GFR) and CX. GFR = 150 mg/mL × 1 mL/min ÷ 1 mg/mL = 150 mL/min. CX = 100 mg/mL × 1 mL/min ÷ 2 mg/mL = 50 mL/min. Because the clearance of X is less than the clearance of inulin (or GFR), net reabsorption of X must have occurred. Clearance data alone cannot determine whether there has also been secretion of X. Because GFR cannot be measured with a substance that is reabsorbed, X would not be suitable.

18. A patient has the following arterial blood values: pH = 7.52 Pco2 = 20 mm Hg [HCO3−] = 16 mEq/L Which of the following statements about this patient is most likely to be correct? (A) He is hypoventilating (B) He has decreased ionized [Ca2+] in blood (C) He has almost complete respiratory compensation (D) He has an acid-base disorder caused by overproduction of fixed acid (E) Appropriate renal compensation would cause his arterial [HCO3-] to increase

The answer is B First, the acid-base disorder must be diagnosed. Alkaline pH, low Pco2, and low HCO3- are consistent with respiratory alkalosis. *In respiratory alkalosis, the [H+] is decreased and less H+ is bound to negatively charged sites on plasma proteins. As a result, more Ca2+ is bound to proteins and, therefore, the ionized [Ca2+] decreases*. There is no respiratory compensation for primary respiratory disorders. The patient is hyperventilating, which is the cause of the respiratory alkalosis. Appropriate renal compensation would be decreased reabsorption of HCO3-, which would cause his arterial [HCO3-] to decrease and his blood pH to decrease (become more normal).

22. A woman has a plasma osmolarity of 300 mOsm/L and a urine osmolarity of 1200 mOsm/L. The correct diagnosis is (A) syndrome of inappropriate antidiuretic hormone (SIADH) (B) water deprivation (C) central diabetes insipidus (D) nephrogenic diabetes insipidus (E) drinking large volumes of distilled water

The answer is B This patient's plasma and urine osmolarity, taken together, are consistent with water deprivation. The plasma osmolarity is on the high side of normal, stimulating the posterior pituitary to secrete antidiuretic hormone (ADH). Secretion of ADH, in turn, acts on the collecting ducts to increase water reabsorption and produce hyperosmotic urine. *Syndrome of inappropriate antidiuretic hormone (SIADH) would also produce hyperosmotic urine, but the plasma osmolarity would be lower than normal because of the excessive water retention.* Central and nephrogenic diabetes insipidus and excessive water intake would all result in hyposmotic urine.

15. A 55-year-old man presents with painless hematuria. On cystoscopy, a papillary mass is found in the bladder. Which of the following is a characteristic of this lesion? (A) Hematuria as a late manifestation (B) Marked tendency to recur after resection (C) Much more likely to be benign than malignant (D) Occurrence only in the bladder and nowhere else in the urinary tract (E) Usual presence of distant metastases at the time of diagnosis

The answer is B. *The majority of urinary tract tumors are transitional cell carcinomas.* Following resection, there is a marked tendency to recur. These tumors tend to spread contiguously rather than to distal locations. An early sign is hematuria.

20. Which of the following causes a decrease in renal Ca2+ clearance? (A) Hypoparathyroidism (B) Treatment with chlorothiazide (C) Treatment with furosemide (D) Extracellular fluid (ECF) volume expansion (E) Hypermagnesemia

The answer is B. *Thiazide diuretics have a unique effect on the distal tubule; they increase Ca2+ reabsorption, thereby decreasing Ca2+ excretion and clearance.* Because parathyroid hormone (PTH) increases Ca2+ reabsorption, the lack of PTH will cause an increase in Ca2+ clearance. Furosemide inhibits Na+ reabsorption in the thick ascending limb, and extracellular fluid (ECF) volume expansion inhibits Na+ reabsorption in the proximal tubule. At these sites, Ca2+ reabsorption is linked to Na+ reabsorption, and Ca2+ clearance would be increased. Because Mg2+ competes with Ca2+ for reabsorption in the thick ascending limb, hypermagnesemia will cause increased Ca2+ clearance.

23. A 30-year-old man presents with hypertension, hematuria, palpable renal masses, and flank pain. He states that a kidney disease runs in his family, and his mother and maternal grandfather have it. Laboratory abnormalities confirm renal failure. Which of the following is associated with the disorder described here? (A) Autosomal recessive inheritance (B) Berry aneurysm of the circle of Willis (C) Clinical manifestation most commonly at birth (D) Multiple small medullary cysts in both kidneys (E) Presence of uric acid stones

The answer is B. Adult polycystic kidney disease is the most common inherited disorder of the kidney and is characterized by autosomal dominant inheritance. The disease is characterized by partial replacement of the renal parenchyma with cysts. An important association of adult polycystic kidney disease is berry aneurysm of the circle of Willis

43. A5-year-old boy swallows a bottle of aspirin (salicylic acid) and is treated in the emergency room. The treatment produces a change in urine pH that increases the excretion of salicylic acid. What was the change in urine pH, and what is the mechanism of increased salicylic acid excretion? (A) Acidification, which converts salicylic acid to its HA form (B) Alkalinization, which converts salicylic acid to its A- form (C) Acidification, which converts salicylic acid to its A- form (D) Alkalinization, which converts salicylic acid to its HA form

The answer is B. Alkalinization of the urine converts more salicylic acid to its A- form. The A- form is charged and cannot back-diffuse from urine to blood. Therefore, it is trapped in the urine and excreted.

10. A syndrome that includes the lesion found in the patient in with Wilms tumor has which of the following additional characteristics? (A) Berry aneurysm of the circle of Willis (B) Hemihypertrophy (C) Increased serum uric acid (D) Marked amplification of genes on the short arm of chromosome 11 (E) Spontaneous regression

The answer is B. Associations of Wilms tumor notably include gene deletions localized to the short arm of chromosome 11 (11p13). In some instances, a "two-hit" mechanism of cancer suppressor gene inactivation, similar to that postulated for retinoblastoma, appears to be operative. Other associations of Wilms tumor include congenital aniridia, genitourinary malformations, and mental-motor retardation (the AGR or WAGR com- plex). Another unusual association is *"hemihypertrophy" (gross asymmetry of the body)* as part of the Beckwith-Wiedemann syndrome; yet another is the Denys-Drash syn- drome, which is characterized by intersexual disorders, nephropathy, and Wilms tumor.

1. A 20-year-old woman with the nephrotic syndrome and slowly progressive impairment of renal function marked by azotemia undergoes a renal biopsy. The patient's response to corticosteroid medication has been unimpressive. The appearance of the biopsy is shows diffuse thickening of the alls of the capillary loops. The most likely diagnosis is (A) focal segmental glomerulosclerosis. (B) membranous glomerulonephritis. (C) minimal change disease. (D) poststreptococcal glomerulonephritis. (E) rapidly progressive glomerulonephritis.

The answer is B. The diffuse thickening of the walls of the capillary loops seen in the illustration is characteristic of membranous glomerulonephritis, the most frequent cause of the nephrotic syndrome in young adults. Expected associated findings in this immune complex disease include granular immunofluorescence and a characteristic "spike and dome" appearance that is best visualized with special stains. Intramembranous and epimembranous (subepithelial) electron-dense immune complex deposits are seen by electron microscopy.

30. Which set of arterial blood values describes a heavy smoker with a history of emphysema and chronic bronchitis who is becoming increasingly somnolent? pH HCO3- PCO2 a) 7.65 48 45 b) 7.50 15 20 c) 7.40 24 40 d) 7.32 30 60 e) 7.31 16 33

The answer is D The history strongly suggests chronic obstructive pulmonary disease (COPD) as a cause of respiratory acidosis. Because of the COPD, the ventilation rate is decreased and CO2 is retained. The [H+] and [HCO3-] are increased by mass action. The [HCO3-] is further increased by renal compensation for respiratory acidosis (increased HCO3- reabsorption by the kidney is facilitated by the high Pco2).

14. A 60-year-old woman dies of a tumor that had invaded the renal vein and entered the inferior vena cava. At autopsy, the kidney has the appearance shown in the figure. Which of the following is a characteristic or association of this neoplasm? (A) Adrenal origin (B) Hematuria (C) Hypocalcemia (D) Tumor cells in the urine (E) Typical symmetrical bilateral involvement

The answer is B. The illustration demonstrates a renal cell carcinoma, which most often arises in one of the renal poles, frequently the upper pole. Hematuria is the most frequent presenting sign. The tumor cells often have a clear cell appearance, which led to an earlier erroneous concept that this tumor was of adrenal origin and to the older name "hypernephroma." The tumor is often quite large and may result in a palpable mass. Malignant cells are only rarely detected in the urine in renal cell carcinoma.

3. A 22-year-old woman presents with fever, malaise, generalized arthralgias, and a skin rash over the nose and malar eminences. Which one of the following possible findings has the greatest relative significance in the overall prognosis for the patient? (A) Atypical verrucous vegetations of the mitral valve (B) Glomerular subendothelial immune complex deposition (C) Immune complexes at the dermal- epidermal junction in skin (D) Perivascular fibrosis in the spleen (E) Pleuritis

The answer is B. The overall prognosis in SLE is most closely related to the glomerular lesions in affected patients. These renal lesions are highly variable. In the diffuse proliferative form, almost all of the glomeruli are involved in a marked inflammatory reaction to widespread subendothelial and mesangial immune complex deposition.

24. A 45-year-old man comes to the emergency department in obvious severe pain. He states that he has severe pain in his right flank that extends down to his right groin. The pain is sharp and severe, and it started several minutes earlier. An abdominal radiograph demonstrates the presence of right ureteral urolithiasis. Which of the following is the most likely composition of this patient's stone? (A) Ammonium magnesium phosphate (B) Calcium (C) Cystine (D) Uric acid

The answer is B. Urolithiasis (calculi or stones in the urinary tract) is a very common problem, especially in men. Calcium stones (composed of calcium oxalate or calcium phosphate, or both) account for 80% to 85% of urinary stones. Such stones are associated with hypercalciuria, which in turn is caused by increased intestinal absorption of calcium, increased primary renal excretion of calcium, or hypercalcemia. Ammonium magnesium phosphate stones are associated with ammonia-producing (urease-positive) bacteria, such as Proteus vulgaris or Staphylococcus. Uric acid stones are associated with hyperuricemia in 50% of patients and can occur secondary to gout or increased cell turnover (leukemias or myeloproliferative syndromes). Cystine stones are almost always associated with cystinuria, a genetically determined aminoaciduria.

4. Two weeks after recovery from a severe bout of pharyngitis, an 11-year-old girl is seen because of the acute onset of periorbital edema, hematuria, malaise, nausea, and headache. Which of the following findings is expected? (A) Hypotension (B) Increased antistreptolysin O titer (C) Marked hypoalbuminemia (D) Polyuria (E) Positive urine cultures for β-hemolytic streptococci

The answer is B. The combination of hematuria (with red cell casts), oliguria, azotemia, and hypertension constitutes the nephritic syndrome, the prototype of which is poststreptococcal glomerulonephritis. An indicator of the prior streptococcal infection is an increased titer of antistreptolysin O. Fluid retention is usually minimal, often limited to periorbital edema, and is the result of reduced renal excretion of salt and water, not hypoalbuminemia. Hypertension, not hypotension, is expected. This disorder is an immune complex disorder, and infection of the kidney does not occur.

5. Use the values below to answer the following question. Glomerular capillary hydrostatic pressure = 47 mm Hg Bowman space hydrostatic pressure = 10 mm Hg Bowman space oncotic pressure = 0 mm Hg At what value of glomerular capillary oncotic pressure would glomerular filtration stop? (A) 57 mm Hg (B) 47 mm Hg (C) 37 mm Hg (D) 10 mm Hg (E) 0 mm Hg

The answer is C Glomerular filtration will stop when the net ultrafiltration pressure across the glomerular capillary is zero; that is, when the force that favors filtration (47 mm Hg) exactly equals the forces that oppose filtration (10 mm Hg + 37 mm Hg).

19. Which of the following would best distinguish an otherwise healthy person with severe water deprivation from a person with the syndrome of inappropriate antidiuretic hormone (SIADH)? (A) Free-water clearance (CH2O) (B) Urine osmolarity (C) Plasma osmolarity (D) Circulating levels of antidiuretic hormone (ADH) (E) Corticopapillary osmotic gradient

The answer is C Both individuals will have hyperosmotic urine, a negative free-water clearance (−CH2O), a normal corticopapillary gradient, and high circulating levels of antidiuretic hormone (ADH). *The person with water deprivation will have a high plasma osmolarity, and the person with syndrome of inappropriate antidiuretic hormone (SIADH) will have a low plasma osmolarity (because of dilution by the inappropriate water reabsorption).*

23. A patient is infused with para- aminohippuric acid (PAH) to measure renal blood flow (RBF). She has a urine flow rate of 1 mL/min, a plasma [PAH] of 1 mg/mL, a urine [PAH] of 600 mg/mL, and a hematocrit of 45%. What is her "effective" RBF? (A) 600 mL/min (B) 660 mL/min (C) 1,091 mL/min (D) 1,333 mL/min

The answer is C Effective renal plasma flow (RPF) is calculated from the clearance of para-aminohippuric acid (PAH) [CPAH = UPAH × V/PPAH = 600 mL/min]. Renal blood flow (RBF) = RPF/1 - hematocrit = 1091 mL/min.

29. A man presents with hypertension and hypokalemia. Measurement of his arterial blood gases reveals a pH of 7.5 and a calculated HCO3− of 32 mEq/L. His serum cortisol and urinary vanillylmandelic acid (VMA) are normal, his serum aldosterone is increased, and his plasma renin activity is decreased. Which of the following is the most likely cause of his hypertension? (A) Cushing syndrome (B) Cushing disease (C) Conn syndrome (D) Renal artery stenosis (E) Pheochromocytoma

The answer is C Hypertension, hypokalemia, metabolic alkalosis, elevated serum aldosterone, and decreased plasma renin activity are all consistent with a primary hyperaldosteronism (e.g., Conn syndrome). High levels of aldosterone cause increased Na+ reabsorption (leading to increased blood pressure), increased K+ secretion (leading to hypokalemia), and increased H+ secretion (leading to metabolic alkalosis). In Conn syndrome, the increased blood pressure causes an increase in renal perfusion pressure, which inhibits renin secretion. Neither Cushing syndrome nor Cushing disease is a possible cause of this patient's hypertension because serum cortisol and adrenocorticotropic hormone (ACTH) levels are normal. Renal artery stenosis causes hypertension that is characterized by increased plasma renin activity. Pheochromocytoma is ruled out by the normal urinary excretion of vanillylmandelic acid (VMA).

9. One gram of mannitol was injected into a woman. After equilibration, a plasma sample had a mannitol concentration of 0.08 g/L. During the equilibration period, 20% of the injected mannitol was excreted in the urine. The woman's (A) extracellular fluid (ECF) volume is 1 L (B) intracellular fluid (ICF) volume is 1 L (C) ECF volume is 10 L (D) ICF volume is 10 L (E) interstitial volume is 12.5 L

The answer is C Mannitol is a marker substance for the extracellular fluid (ECF) volume. ECF volume = amount of mannitol/concentration of mannitol = 1 g - 0.2 g/0.08 g/L = 10 L.

17. Which of the following would cause an increase in both glomerular filtration rate (GFR) and renal plasma flow (RPF)? (A) Hyperproteinemia (B) A ureteral stone (C) Dilation of the afferent arteriole (D) Dilation of the efferent arteriole (E) Constriction of the efferent arteriole

The answer is C. Dilation of the afferent arteriole will increase both renal plasma flow (RPF) (because renal vascular resistance is decreased) and glomerular filtration rate (GFR) (because glomerular capillary hydrostatic pressure is increased). Dilation of the efferent arteriole will increase RPF but decrease GFR. Constriction of the efferent arteriole will decrease RPF (due to increased renal vascular resistance) and increase GFR. Both hyperproteinemia (↑ π in the glomerular capillaries) and a ureteral stone (↑ hydrostatic pressure in Bowman space) will oppose filtration and decrease GFR.

2. Jared and Adam both weigh 70 kg. Jared drinks 2 L of distilled water, and Adam drinks 2 L of isotonic NaCl. As a result of these ingestions, Adam will have a (A) greater change in intracellular fluid (ICF) volume (B) higher positive free-water clearance (CH2O ) (C) greater change in plasma osmolarity (D) higher urine osmolarity (E) higher urine flow rate

The answer is D After drinking distilled water, Jared will have an increase in intracellular fluid (ICF) and extracellular fluid (ECF) volumes, a decrease in plasma osmolarity, a suppression of antidiuretic hormone (ADH) secretion, and a positive free-water clearance (CH2O), and will produce dilute urine with a high flow rate. Adam, after drinking the same volume of isotonic NaCl, will have an increase in ECF volume only and no change in plasma osmolarity. *Because Adam's ADH will not be suppressed*, he will have a higher urine osmolarity, a lower urine flow rate, and a lower CH2O than Jared.

17. A 50-year-old woman with a 20-year history of type 2 diabetes mellitus presents with proteinuria, hypoalbuminemia, edema, and hyperlipidemia. She has not monitored her serum glucose levels over the past several years. Diabetic nephropathy is diagnosed. What is the classic morphologic finding in diabetic nephropathy? (A) Crescentic formation in glomeruli on light microscopy (B) Intramembranous and epimembra- nous immune complex deposits in the glomerular basement membrane on electron microscopy (C) Nodular accumulations of mesangial matrix on light microscopy (D) Sclerosis within capillary tufts that involves only some glomeruli and only parts of affected glomeruli on light microscopy (E) Wire-loop abnormalities from immune complex deposits and thickening of the glomerular basement membrane on light microscopy

The answer is C. Diabetic nephropathy manifests clinically as the nephrotic syndrome; however, this syndrome is compounded by renal failure and hypertension. Ultrastructural changes include a marked increase in the thickness of the glomerular basement membrane and mesangial accumulation of glycosylated basement membrane- like material. Light microscopy findings include diffuse glomerulosclerosis (a diffuse increase in mesangial matrix) and nodular glomerulosclerosis (nodular accumulations of mesangial matrix).

21. A 5-year-old boy presents with hematuria. His mother states that he has had a sore throat for the past 2 days and that he has had hematuria a few times in the past, also concomitantly with a sore throat. She states that his urine usually returns to a normal clear yellow color after a few days. Which of the following is the most likely diagnosis? (A) Alport syndrome (B) Goodpasture syndrome (C) IgA nephropathy (D) Membranoproliferative glomerulonephritis (E) Poststreptococcal glomerulonephritis

The answer is C. IgA nephropathy is the most common glomerular disease and is defined by mesangial deposition of IgA. In its most typical form, the clinical manifestations are limited to a few days of hematuria following an infection; however, there are many etio- logic factors, and the condition can vary from one of little import to a severe form of renal disease.

22. An 18-year-old woman presents with suprapubic pain, urinary frequency, dysuria, and hematuria for the past hour. Urine tests show the presence of pyuria but no white cell casts. Physical examination is remarkable only for suprapubic tenderness on palpation. Which of the following is the most likely diagnosis? (A) Acute pyelonephritis (B) Chronic pyelonephritis (C) Cystitis (D) Fanconi syndrome (E) Nephrocalcinosis

The answer is C. The clinical description is that of cystitis, which is characterized by pyuria and hematuria but with no white cell casts in the urine. Patients with acute pyelonephritis present with fever, leukocytosis, flank tenderness, urinary white cells, and white cell casts in the urine. Chronic pyelonephritis is almost always the result of chronic urinary tract obstruction and repeated bouts of acute inflammation in the kidneys.

8. A 78-year-old man with long-standing prostatic nodular hyperplasia dies of a stroke. At autopsy, both kidneys demonstrate coarse asymmetric renal cortico-medullary scarring, deformity of the renal pelvis and calyces, interstitial fibrosis, and atrophic tubules containing eosinophilic proteinaceous casts. These findings are most suggestive of (A) Berger disease. (B) chronic analgesic nephritis. (C) chronic pyelonephritis. (D) membranoproliferative glomerulonephritis. (E) renal papillary necrosis.

The answer is C. The combination of coarse asymmetric corticomedullary scarring, deformity of the renal pelvis and calyces, and tubular atrophy is characteristic of chronic pyelonephritis. When the atrophic tubules contain eosinophilic proteinaceous casts, the resultant similarity in appearance to thyroid follicles is referred to as "thyroidization." Although an infectious etiology is assumed, the infectious agent is often not demonstrable.

2. A 3-year-old girl presents with generalized edema shortly after recovery from an upper respiratory infection. Laboratory studies reveal marked albuminuria, as well as hypoalbuminemia and hyperlipidemia. Prior similar episodes responded to adrenal steroid medication. The most likely diagnosis is (A) focal segmental glomerulosclerosis. (B) membranous glomerulonephritis. (C) minimal change disease. (D) poststreptococcal glomerulonephritis. (E) rapidly progressive glomerulonephritis.

The answer is C. The combination of generalized edema, massive proteinuria, hypoalbuminemia, and hyperlipidemia constitutes the nephrotic syndrome, the prototype of which is minimal change disease (lipoid nephrosis). This disorder characteristically occurs in young children and demonstrates intracytoplasmic lipid in the proximal convoluted tubules, a paucity of glomerular abnormalities by light microscopy, and "fusing" (absence) of the epithelial foot processes by electron microscopy.

6. A 50-year-old man with hypertension and the nephrotic syndrome undergoes a renal biopsy. The appearance of the biopsy is similar to that showing nodular glomerulosclrosis. Of the following possible additional laboratory findings, which one is most characteristically associated with this lesion? (A) Decreased creatinine clearance (B) Fixed specific gravity of urine (C) Hyperglycemia (D) Hypocalcemia (E) Increased blood urea nitrogen

The answer is C. The illustration shows nodular glomerulosclerosis (Kimmelstiel-Wilson nodules), the most characteristic glomerular finding in diabetes mellitus. The nodules are accumulations of mesangial matrix-like material.

10. A 58-year-old man is given a glucose tolerance test. In the test, the plasma glucose concentration is increased and glucose reabsorption and excretion are measured. When the plasma glucose concentration is higher than occurs at transport maximum (Tm), the (A) clearance of glucose is zero (B) excretion rate of glucose equals the filtration rate of glucose (C) reabsorption rate of glucose equals the filtration rate of glucose (D) excretion rate of glucose increases with increasing plasma glucose concentrations (E) renal vein glucose concentration equals the renal artery glucose concentration

The answer is D At concentrations greater than at the transport maximum (Tm) for glucose, the carriers are saturated so that the reabsorption rate no longer matches the filtration rate. The difference is excreted in the urine. As the plasma glucose concentration increases, the excretion of glucose increases. When it is greater than the Tm, the renal vein glucose concentration will be less than the renal artery concentration because some glucose is being excreted in urine and therefore is not returned to the blood. The *clearance of glucose is zero at concentrations lower than at Tm (or lower than threshold)* when all of the filtered glucose is reabsorbed but is greater than zero at concentrations greater than Tm.

15. At plasma para-aminohippuric acid (PAH) concentrations below the transport maximum (Tm), PAH (A) reabsorption is not saturated (B) clearance equals inulin clearance (C) secretion rate equals PAH excretion rate (D) concentration in the renal vein is close to zero (E) concentration in the renal vein equals PAH concentration in the renal artery

The answer is D At plasma concentrations that are lower than at the transport maximum (Tm) for para-aminohippuric acid (PAH) secretion, PAH concentration in the renal vein is nearly zero because the sum of filtration plus secretion removes virtually all PAH from the renal plasma. Thus, the PAH concentration in the renal vein is less than that in the renal artery because most of the PAH entering the kidney is excreted in urine. PAH clearance is greater than inulin clearance because PAH is filtered and secreted; inulin is only filtered.

25. A woman runs a marathon in 90°F weather and replaces all volume lost in sweat by drinking distilled water. After the marathon, she will have (A) decreased total body water (TBW) (B) decreased hematocrit (C) decreased intracellular fluid (ICF) volume (D) decreased plasma osmolarity (E) increased intracellular osmolarity

The answer is D By sweating and then replacing all volume by drinking H2O, the woman has a net loss of NaCl without a net loss of H2O. Therefore, her extracellular and plasma osmolarity will be decreased, and as a result, water will flow from extracellular fluid (ECF) to intracellular fluid (ICF). The intracellular osmolarity will also be decreased after the shift of water. Total body water (TBW) will be unchanged because the woman replaced all volume lost in sweat by drinking water. *Hematocrit will be increased* because of the shift of water from ECF to ICF and the shift of water into the red blood cells (RBCs), which causes their volume to increase.

6. The reabsorption of filtered HCO3- (A) results in reabsorption of less than 50% of the filtered load when the plasma concentration of HCO3- is 24 mEq/L (B) acidifies tubular fluid to a pH of 4.4 (C) is directly linked to excretion of H+ as NH4+ (D) is inhibited by decreases in arterial Pco2 (E) can proceed normally in the presence of a renal carbonic anhydrase inhibitor

The answer is D Decreases in arterial Pco2 cause a decrease in the reabsorption of filtered HCO3- by diminishing the supply of H+ in the cell for secretion into the lumen. Reabsorption of filtered HCO3- is nearly 100% of the filtered load and requires carbonic anhydrase in the brush border to convert filtered HCO3- to CO2 to proceed normally. This process causes little acidification of the urine and is not linked to net excretion of H+ as titratable acid or NH4+.

1. Secretion of K+ by the distal tubule will be decreased by (A) metabolic alkalosis (B) a high-K+ diet (C) hyperaldosteronism (D) spironolactone administration (E) thiazide diuretic administration

The answer is D Distal K+ secretion is decreased by factors that decrease the driving force for passive diffusion of K+ across the luminal membrane. Because spironolactone is an aldosterone antagonist, it reduces K+ secretion. Alkalosis, a diet high in K+, and hyperaldosteronism all increase [K+] in the distal cells and thereby increase K+ secretion. Thiazide diuretics increase flow through the distal tubule and dilute the luminal [K+] so that the driving force for K+ secretion is increased.

11. A negative free-water clearance (−CH2O ) will occur in a person who (A) drinks 2 L of distilled water in 30 minutes (B) begins excreting large volumes of urine with an osmolarity of 100 mOsm/L after a severe head injury (C) is receiving lithium treatment for depression and has polyuria that is unresponsive to the administration of antidiuretic hormone (ADH) (D) has an oat cell carcinoma of the lung, and excretes urine with an osmolarity of 1,000 mOsm/L

The answer is D. A person who produces hyperosmotic urine (1,000 mOsm/L) will have a negative free-water clearance (-CH2O) [CH2O = V - Cosm]. All of the others will have a positive CH2O because they are producing hyposmotic urine as a result of the *suppression of antidiuretic hormone (ADH) by water drinking*, central diabetes insipidus, or nephrogenic diabetes insipidus.

21. A patient arrives at the emergency room with low arterial pressure, reduced tissue turgor, and the following arterial blood values: pH = 7.69 [HCO3-] = 57 mEq/L Pco2 = 48 mm Hg Which of the following responses would also be expected to occur in this patient? (A) Hyperventilation (B) Decreased K+ secretion by the distal tubules (C) Increased ratio of H2PO4 to HPO4 (D) Exchange of intracellular H+ for extracellular K+

The answer is D First, the acid-base disorder must be diagnosed. Alkaline pH, with increased HCO3- and increased Pco2, is consistent with metabolic alkalosis with respiratory compensation. *The low blood pressure and decreased turgor suggest extracellular fluid (ECF) volume contraction*. The reduced [H+] in blood will cause intracellular H+ to leave cells in exchange for extracellular K+. The appropriate respiratory compensation is hypoventilation, which is responsible for the elevated Pco2. H+ excretion in urine will be decreased, so less titratable acid will be excreted. K+ secretion by the distal tubules will be increased because aldosterone levels will be increased secondary to ECF volume contraction.

4. A 45-year-old woman develops severe diarrhea while on vacation. She has the following arterial blood values: pH = 7.25 Pco2 = 24 mm Hg [HCO3-] = 10 mEq/L Venous blood samples show decreased blood [K+] and a normal anion gap. 4. Which of the following statements about this patient is correct? (A) She is hypoventilating (B) The decreased arterial [HCO3-] is a result of buffering of excess H+ by HCO3- (C) The decreased blood [K+] is a result of exchange of intracellular H+ for extracellular K+ (D) The decreased blood [K+] is a result of increased circulating levels of aldosterone (E) The decreased blood [K+] is a result of decreased circulating levels of antidiuretic hormone (ADH)

The answer is D The decreased arterial [HCO3-] is caused by gastrointestinal (GI) loss of HCO3- from diarrhea, not by buffering of excess H+ by HCO3-. The woman is *hyperventilating* as respiratory compensation for metabolic acidosis. Her hypokalemia cannot be the result of the exchange of intracellular H+ for extracellular K+, because she has an increase in extracellular H+, which would drive the exchange in the other direction. Her circulating levels of *aldosterone would be increased as a result of extracellular fluid (ECF) volume contraction,* which leads to increased K+ secretion by the distal tubule and hypokalemia.

5. Expected findings on electron microscopic examination of the glomerulus from the patient in with postreptococcal glomerulonephritis is: (A) marked subendothelial immune complex deposition. (B) marked thickening of the glomerular basement membrane with numerous intramembranous and epimembranous (subepithelial) immune complex deposits. (C) no changes except for fused epithelial foot processes. (D) normal-appearing glomerular basement membrane with electron-dense "humps" in subepithelial location. (E) striking increase in thickness of glomer- ular basement membrane and diffuse increase in mesangial matrix material.

The answer is D. Characteristic electron-dense "humps" on the epithelial side of the basement membrane (subepithelial location) are an extremely important diagnostic feature of poststreptococcal glomerulonephritis. The basement membrane is not thickened in this acute, usually self-limited disorder.

16. A 25-year-old man presents with generalized edema. Blood tests reveal severe proteinuria, hypoalbuminemia, and hyperlipidemia. The patient does not respond well to a course of corticosteroids. A renal biopsy demonstrates findings indicative of focal segmental glomerulosclerosis. Which of the following best describes the histologic find- ings in this disorder? (A) Crescentic formation in glomeruli on light microscopy (B) Intramembranous and epimembranous immune complex deposits in the glomerular basement membrane on electron microscopy (C) Nodular accumulations of mesangial matrix material on light microscopy (D) Sclerosis within capillary tufts that involves only some glomeruli and only parts of affected glomeruli on light microscopy (E) Wire-loop abnormalities from immune complex deposits and thickening of the glomerular basement membrane on light microscopy

The answer is D. Focal segmental glomerulosclerosis has clinical manifestations similar to minimal change disease, but it tends to occur in older patients and does not respond well to steroid treatment. Glomerular hyaline sclerosis occurs in a focal (some, but not all, glomeruli) and segmental (only part of an affected glomerulus) distribution.

11. A glomerular immunofluorescent pattern for IgG similar to that shown in the figure shouldering linear immunofluorescence, would be expected in which of the following patients? (A) A 3-year-old girl with recurrent bouts of the nephrotic syndrome (B) A 9-year-old boy with "smoky" urine 2 weeks after recovery from a streptococcal infection (C) An 18-year-old woman with nephrotic syndrome and progressive chronic renal disease (D) A 25-year-old man with hemoptysis and hematuria (E) A 26-year-old woman with a "butterfly" rash

The answer is D. The illustration demonstrates linear immunofluorescence, which is characteristic of disease caused by antiglomerular basement membrane antibodies. In Goodpasture syndrome, antibodies directed against antigens in the basement membranes of the glomeruli as well as the pulmonary alveoli result in both hemorrhagic pneumonitis with hemoptysis and glomerular disease with hematuria.

19. A 5-year-old boy diagnosed with post- streptococcal glomerulonephritis was admitted to the hospital several weeks ago. Over the last several weeks, his clinical state has not improved. Severe oliguria has developed, his serum creatinine has continued to rise, and his glomerular filtration rate has decreased by 50% since his admission to the hospital. Which of the following is the most likely diagnosis? (A) Alport syndrome (B) Membranoproliferative glomerulonephritis (C) Membranous glomerulonephritis (D) Rapidly progressive glomerulonephritis (E) Renal papillary necrosis

The answer is D. The clinical description is that of RPGN, which is defined as the nephritic syndrome that progresses rapidly to fulminant renal failure within weeks or months. RPGN is classified into three categories: antiglomerular basement membrane (anti-GBM) antibody disease, immune complex deposit disease, and pauciimmune disease (ANCA- positive). Characteristic histologic findings in RPGN include crescents between the Bowman capsule and the glomerular tuft. In approximately 50% of cases of RPGN, the disease is of poststreptococcal etiology. It should be noted, however, that the most common outcome of poststreptococcal glomerulonephritis is complete recovery, and only a small minority of patients progress to RPGN.

27. Which of the following is a cause of metabolic alkalosis? (A) Diarrhea (B) Chronic renal failure (C) Ethylene glycol ingestion (D) Treatment with acetazolamide (E) Hyperaldosteronism (F) Salicylate poisoning

The answer is E *A cause of metabolic alkalosis is hyperaldosteronism; increased aldosterone levels cause increased H+ secretion by the distal tubule and increased reabsorption of "new" HCO3-.* *Diarrhea* causes loss of HCO3- from the gastrointestinal (GI) tract and *acetazolamide* causes loss of HCO3- in the urine, both resulting in *hyperchloremic metabolic acidosis* with *normal anion gap*. Ingestion of *ethylene glycol* and *salicylate poisoning* leads to metabolic acidosis with increased anion gap.

18. A 5-year-old boy presents with "tea- colored urine," oliguria, and periorbital edema. He had a sore throat 2 weeks ago that had resolved before his parents sought medical treatment. The patient is found to be hypertensive. Urea nitrogen and creatinine are elevated. Antistreptolysin O titer and anti-DNAase B titer are also elevated. Urine tests are positive for blood and red cell casts. Which of the following is the most likely mechanism for this patient's condition? (A) Acute bacterial infection of the kidneys (B) Amyloid deposits (C) ANCA-positive vasculitis (D) Antibody against glomerular basement membrane antigens (E) Immune complex deposits

The answer is E. The clinical description is that of poststreptococcal glomerulonephritis, the prototype of the nephritic syndrome. An antecedent infection, usually of the pharynx or skin, with a group A β-hemolytic streptococcus occurs approximately 1 to 2 weeks before the onset of the renal manifestations. *Poststreptococcal glomerulonephritis is an immune complex disease, with antigen-antibody-complement complexes localizing to the outside (subepithelial side) of the glomerular basement membrane.* An intense inflammatory response is elicited, including chemotactic attraction of neutrophils, release of lysosomal enzymes, partial destruction of basement membrane, and bleeding into the Bowman space.

9. A 2-year-old boy with visible abdominal distention is found to have an enormous left-sided flank mass apparently arising from, but dwarfing, the left kidney. The most likely diagnosis is (A) angiomyolipoma. (B) polycystic kidney. (C) renal cell carcinoma. (D) transitional cell carcinoma. (E) Wilms tumor.

The answer is E. Wilms tumor is the most common renal neoplasm of children. The tumors are often huge and frequently cause abdominal distention. Renal cell carcinoma and adult polycystic kidney can also present as a large flank mass, but not in a child.


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