Campbell-Walsh Urology, 11th Edition

PART VII

Renal Physiology and Pathophysiology

44

Renal Physiology and Pathophysiology

Daniel A. Shoskes; Alan W. McMahon

Questions

  1. The AT1 receptor:
  2. has a more pronounced vasoconstriction on the afferent rather than the efferent arteriole.
  3. is the receptor for angiotensin I.
  4. protects against ischemia-reperfusion injury by intrarenal dilation.
  5. mediates increased release of aldosterone.
  6. is not expressed in the kidney.
  7. Which of the following statements about endothelin is FALSE?
  8. Stimulation of endothelin-1 (ET-1) decreases sodium excretion.
  9. Endothelin is the most potent vasoconstrictor yet identified.
  10. ET-1 release is inhibited by nitric oxide.
  11. ET-1 release stimulates aldosterone secretion.
  12. ET-1 release reduces renal blood flow.
  13. Which of the following is a vasodilator of the renal artery?
  14. Endothelin
  15. Carbon monoxide
  16. Atrial natriuretic peptide
  17. Norepinephrine
  18. Angiotensin II
  19. Which of the following statements is FALSE regarding carbon monoxide (CO) and the enzyme hemoxygenase?
  20. Hemoxygenase-2 (HO-2) is a constitutive enzyme.
  21. HO-1 is an inducible enzyme.
  22. Increased CO increases ischemia-reperfusion injury in the kidney.
  23. HO-1 expression helps to maintain renal medullary blood flow.
  24. HO-1 produces CO through the catabolism of heme.
  25. Which of the following statements regarding erythropoiesis is FALSE?
  26. Reduced erythropoiesis and anemia are common in chronic renal disease.
  27. Erythropoiesis is inhibited by low circulating oxygen tension.
  28. During chronic inflammation, erythropoiesis is decreased.
  29. The kidney makes most of the erythropoietin in the body.
  30. There are erythropoietin receptors in many organs of the body.
  31. Which of the following statements is TRUE about sodium and the kidney?
  32. By definition, hypernatremia is always associated with elevated total body sodium content.
  33. Normal compensation for hyponatremia is decreased antidiuretic hormone (ADH) secretion and thirst suppression.
  34. Abnormal elevation of serum lipids can lead to a false, elevated measurement of serum sodium.
  35. If asymptomatic hyponatremia does not improve within 24 hours, intravenous hypertonic saline should be started.
  36. In therapy for symptomatic hyponatremia, the goal should be a normal serum sodium value of 135 mEq/L within 48 hours.
  37. The syndrome of inappropriate antidiuretic hormone secretion (SIADH):
  38. is associated with decreased aquaporin expression in the kidney.
  39. is always seen in patients with hypervolemia.
  40. is associated with high total body sodium.
  41. is triggered by low circulating volume.
  42. may be treated with lithium or demeclocycline.
  43. Which of the following statements regarding therapy for hyponatremia is FALSE?
  44. Fluid overload as a result of hypertonic saline infusion should be treated with a loop diuretic such as furosemide.
  45. Too-rapid correction can lead to a cerebral demyelination syndrome.
  46. Aggressive therapy should be discontinued when the serum sodium concentration is raised 10% or symptoms subside.
  47. Intranasal desmopressin is a useful adjuvant therapy.
  48. For acute severe hyponatremia with symptoms, a typical infusion rate of hypertonic saline would be 1 mL/kg/hr.
  49. Diabetes insipidus:
  50. may be classified as nephrogenic or urogenic.
  51. is associated with inappropriately concentrated urine.
  52. is associated with hypervolemia.
  53. is associated with mutations of the genes producing aldosterone.
  54. results in impairment of maximum concentrating ability of the kidney due to loss of the medullary osmotic gradient.
  55. Which of the following statements regarding potassium is FALSE?
  56. Angiotensin-converting enzyme (ACE) inhibitors may be a cause of hypokalemia.
  57. Potassium is primarily an intracellular ion.
  58. Acidosis drives potassium out of the cell into the circulation.
  59. High-sodium load in the distal tubule promotes potassium excretion.
  60. Upper limit for safe intravenous potassium infusion is 40 mEq/hr.
  61. Which of the following statements regarding hyperkalemia is FALSE?
  62. Hemolysis of the blood sample may falsely elevate the measured potassium.
  63. Hyperkalemia can cause peaked T waves on the electrocardiogram (ECG).
  64. All patients with a serum potassium value greater than 5.5 mEq/L require immediate therapy.
  65. Nebulized albuterol can reduce serum potassium by promoting an intracellular shift of potassium.
  66. Intravenous calcium does not lower serum potassium but is given to protect the heart from the effects of hyperkalemia.
  67. Which of the following statements is TRUE about acid handling?
  68. Normal pH in the blood is 7.56 to 7.60.
  69. Normal body metabolism produces less than 1000 mmol of acid per day.
  70. All acids produced by metabolism can be excreted by the lungs.
  71. Immediate response to an acid load is through buffers in the blood.
  72. Ammonia (NH4) is the most important buffer in the blood.
  73. Which of the following statements regarding renal handling of acid is FALSE?
  74. Most bicarbonate is reabsorbed in the distal collecting tubule.
  75. Lungs can excrete volatile acid, but the kidneys must excrete fixed acid.
  76. Carbonic anhydrase catalyzes the production of H+and  from H2O and CO2.
  77. Chronic respiratory acidosis should lead to increased H+in the kidney.
  78. Ammonium ion (NH+4) is produced from glutamine, primarily by proximal tubular cells.
  79. A patient who has a blood pH of 7.2 has:
  80. pure metabolic acidosis.
  81. pure respiratory acidosis.
  82. acidemia.
  83. a blood buffer system that is not working.
  84. a mixed acid-base disturbance.
  85. In a patient with acidosis:
  86. increasing the blood  level increases the anion gap.
  87. direct bicarbonate loss from the kidney would lead to metabolic acidosis and a normal anion gap.
  88. lactic acidosis usually presents as a nonanion gap metabolic acidosis.
  89. appropriate respiratory compensation for a metabolic acidosis is decreased respiration with an increased PCO2.
  90. It is not possible to have both a respiratory and metabolic acidosis at the same time.
  91. Which of the following statements regarding renal tubular acidosis (RTA) is FALSE?
  92. The hallmark of RTA type I is a hyperchloremic metabolic acidosis with a high urinary pH (> 5.5) in the presence of persistently low serum .
  93. Type I RTA is also called distal RTA.
  94. Type II RTA is more common in children.
  95. The hallmark of type IV RTA is hypokalemia.
  96. The form of RTA most commonly associated with renal calculi is type I.
  97. Which of the following statements regarding metabolic alkalosis is FALSE?
  98. Paradoxical aciduria may occur due to distal tubule injury.
  99. Excessive nasogastric fluid loss can lead to metabolic alkalosis that is chloride responsive.
  100. Appropriate respiratory compensation is decreased respiration and increased PCO2.
  101. Hyperaldosteronism can lead to chloride-resistant metabolic alkalosis.
  102. Therapy for chloride-responsive metabolic alkalosis requires replacement of chloride AND fluid volume.
  103. Which of the following is NOT a function of ADH?
  104. Increased aquaporin-2 insertion into the luminal membrane of the collecting duct
  105. Increased urea transporter insertion into the luminal membrane of the collecting duct
  106. Increased systemic vascular resistance
  107. Increased sodium reabsorption
  108. Increased free water excretion in response to hypernatremia
  109. Which of the following statements is TRUE about vitamin D metabolism?
  110. Vitamin D deficiency is uncommon in chronic renal failure.
  111. Dermally synthesized cholecalciferol is the most potent form of vitamin D.
  112. Dermally synthesized cholecalciferol must be hydroxylated by both the liver and kidney for maximal potency.
  113. Vitamin D activity is mediated through membrane-bound vitamin D receptors.
  114. Vitamin D increases renal excretion of calcium.
  115. Which of the following statements regarding parathyroid hormone (PTH) is FALSE?
  116. PTH secretion is increased by hypocalcemia.
  117. PTH secretion is increased by hyperphosphatemia.
  118. PTH receptors are found mainly in bone and kidney.
  119. PTH increases calcium and phosphorus reabsorption in the distal tubule.
  120. PTH helps regulate 1,25(OH)-vitamin D levels by increasing 1α-hydroxylase activity.
  121. Renal blood flow (RBF):
  122. is equal in all parts of the kidney.
  123. accounts for 5% to 10% of cardiac output.
  124. courses through the glomerulus through the afferent arteriole and exits through the efferent venule.
  125. is similar in men and women.
  126. is one of the determinants of the glomerular filtration rate.
  127. All of the following can increase total glomerular flow rate (GFR) EXCEPT increased:
  128. RBF.
  129. intraglomerular (hydraulic) pressure.
  130. glomerular permeability.
  131. efferent arteriolar resistance.
  132. functioning nephron number.
  133. All of the following are important in GFR regulation EXCEPT:
  134. afferent arteriolar tone.
  135. distal tubule chloride concentrations.
  136. angiotensin II.
  137. nitric oxide.
  138. serum osmolality.
  139. All of the following statements regarding GFR assessment are true EXCEPT:
  140. Plasma creatinine is an accurate marker of early reductions in GFR.
  141. Inulin clearance is an accurate but impractical measurement of GFR.
  142. Twenty-four-hour creatinine clearance overestimates GFR by 10% to 20%.
  143. Use of the four-variable modification of diet in renal disease (MDRD) formula improves the accuracy of the plasma creatinine.
  144. Plasma urea is an unreliable estimate of GFR.
  145. Which of the following statements regarding glucose handling in the kidney is FALSE?
  146. Glucose is freely filtered across the glomerulus.
  147. Glucose reabsorption is facilitated by specific glucose transporters in the proximal convoluted tubule (PCT).
  148. Glucose reabsorption is linked to bicarbonate reabsorption in the PCT.
  149. Glucose reabsorption is 100% up to plasma glucose levels of 400 mg/dL.
  150. Glucose reabsorption is a passive process.
  151. Which of the following statements about the proximal convoluted tubule is FALSE?
  152. It functions as a bulk transporter, rather than a fine-tuner of ultrafiltrate.
  153. It is able to increase or decrease reabsorption rates in response to changes in GFR.
  154. It has a minor role in sodium reabsorption.
  155. It reabsorbs 80% of filtered water, mainly through aquaporin-1 water channels.
  156. It is the major site of bicarbonate reabsorption.
  157. All of the following statements are true regarding the loop of Henle EXCEPT:
  158. It is responsible for the generation of a hypertonic medullary interstitium, which is necessary for urinary concentration.
  159. It is able to increase or decrease reabsorption rates in response to changes in GFR.
  160. The descending limb is highly water permeable.
  161. The thin ascending limb actively reabsorbs sodium, chloride, and urea.
  162. The thick ascending limb is impermeable to water.
  163. Which of the following statements about the thick ascending limb of the loop of Henle is FALSE?
  164. Twenty-five percent of filtered sodium is actively reabsorbed by the furosemide-sensitive NKCC2 cotransporter.
  165. Calcium and magnesium reabsorption is inhibited by furosemide.
  166. Potassium is reabsorbed and returned to the systemic circulation by renal outer medullary potassium (ROMK) channels.
  167. It is the site of uromodulin secretion.
  168. Ten percent to 20% of filtered bicarbonate is reabsorbed in the thick ascending limb of the Henle loop (TALH).
  169. Regarding the distal convoluted tubule (DCT), all of the following statements are true EXCEPT:
  170. The DCT reabsorbs 10% of filtered sodium by the thiazide-sensitive NCC cotransporter.
  171. Sodium reabsorption is dependent solely on luminal sodium concentrations.
  172. Calcium reabsorption is paracellular and influenced by sodium reabsorption.
  173. Magnesium reabsorption is transcellular by luminal magnesium channels.
  174. Loop diuretics increase sodium reabsorption in the DCT.
  175. All of the following statements are TRUE about the collecting tubule EXCEPT:
  176. The collecting tubule is designed for fine tuning, rather than bulk transport, of ultrafiltrate.
  177. Sodium reabsorption is regulated by aldosterone and occurs passively through luminal sodium channels.
  178. Potassium reabsorption is dependent on both aldosterone and luminal flow rates.
  179. The collecting tubule is impermeable to water at all times.
  180. Intercalated cells are largely responsible for acid-base regulation in the collecting tubule.

Pathology

  1. See Figure 44-1. A renal biopsy is depicted in Figure 44-1and is reported as “normal renal biopsy.” The location of this biopsy is from the:

FIGURE 44-1 (From Bostwick DG, Cheng L. Urologic surgical pathology. 2nd ed. Edinburgh: Mosby; 2008.)

  1. cortex.
  2. medulla.
  3. hilum.
  4. papilla.
  5. capsule.

Answers

  1. d. Mediates increased release of aldosterone.AT1, the receptor for angiotensin II, mediates the release of aldosterone. Intrarenal dilatation is mediated through AT2.
  2. a. Stimulation of endothelin-1 (ET-1) decreases sodium excretion.Despite reduction in renal blood flow, stimulation of ET-1 by endothelin increases net sodium excretion.
  3. b. Carbon monoxide.The others are vasoconstrictors.
  4. c. Increased CO increases ischemia-reperfusion injury in the kidney.CO is protective against renal ischemia-reperfusion injury.
  5. b. Erythropoiesis is inhibited by low circulating oxygen tension.Erythropoiesis is increased by low circulating oxygen tension.
  6. b. Normal compensation for hyponatremia is decreased antidiuretic hormone (ADH) secretion and thirst suppression.
  7. e. May be treated with lithium or demeclocycline.Lithium or demeclocycline may be used to treat SIADH.
  8. d. Intranasal desmopressin is a useful adjuvant therapy.Desmopressin is useful to treat hypernatremia caused by diabetes insipidus.
  9. e. Results in impairment of maximum concentrating ability of the kidney due to loss of the medullary osmotic gradient.In both nephrogenic and neurogenic diabetes insipidus, maximum concentrating ability of the kidney is impaired because of loss of the medullary osmotic gradient.
  10. a. Angiotensin-converting enzyme (ACE) inhibitors may be a cause of hypokalemia.
  11. c. All patients with a serum potassium value greater than 5.5 mEq/L require immediate therapy.Patients with mild elevation of potassium, especially when chronic and not associated with ECG changes, do not require emergent therapy.
  12. d. Immediate response to an acid load is through buffers in the blood.
  13. a. Most bicarbonate is reabsorbed in the distal collecting tubule.Most bicarbonate reabsorption in the kidney occurs in the proximal tubule.
  14. c. Acidemia.The only thing that is certain with a low pH is that there is acidemia. This may be caused by metabolic, respiratory, or mixed disorders.
  15. b. Direct bicarbonate loss from the kidney would lead to metabolic acidosis and a normal anion gap.Direct bicarbonate loss is "measured" in the anion gap and therefore leads to metabolic acidosis with a normal anion gap.
  16. d. The hallmark of type IV RTA is hypokalemia.RTA type IV is most commonly associated with hyperkalemia. Aldosterone deficiency or resistance leads to decreased secretion of potassium in the distal tubule.
  17. a. Paradoxical aciduria may occur due to distal tubule injury. Metabolic alkalosis is often associated with hypovolemia and elevated aldosterone. In an attempt to conserve sodium and water, H+may be exchanged with sodium, leading to aciduria, despite the presence of systemic alkalosis.
  18. e. Increased free water excretion in response to hypernatremia.ADH decreases free water excretion in response to hypernatremia in an attempt to return plasma osmolality to normal.
  19. c. Dermally synthesized cholecalciferol must be hydroxylated by both the liver and kidney for maximal potency.Cholecalciferol is minimally active, but potency increases 100 times after it is hydroxylated at the 1- and 25-position to form calcitriol.
  20. d. PTH increases calcium and phosphorus reabsorption in the distal tubule.PTH increases phosphorus excretion in the kidney.
  21. e. Is one of the determinants of the glomerular filtration rate.
  22. c. Glomerular permeability.Glomerular permeability is already maximal under normal conditions for water and small solutes, so GFR will not increase significantly with increased glomerular permeability. Rather, one sees increased filtration of larger substances such as albumin.
  23. e. Serum osmolality.GFR is not affected significantly by serum osmolality.
  24. a. Plasma creatinine is an accurate marker of early reductions in GFR. Plasma creatinine is a very insensitive marker of early reductions in GFR, because increases in tubular secretion of creatinine keep plasma levels from rising until there has been a significant reduction in GFR.
  25. d. Glucose reabsorption is 100% up to plasma glucose levels of 400 mg/dL.The reabsorptive threshold for glucose is about 200 mg/dL. Plasma levels above this result in urinary glucose wasting.
  26. c. It has a minor role in sodium reabsorption.The PCT accounts for 65% of sodium reabsorption, the most of any tubular segment.
  27. d. The thin ascending limb actively reabsorbs sodium, chloride, and urea.Reabsorption of sodium, chloride, and urea occurs passively in the thin ascending limb.
  28. c. Potassium is reabsorbed and returned to the systemic circulation by renal outer medullary potassium (ROMK) channels.Potassium is recycled in the thick ascending limb of the Henle loop (TALH) rather than reclaimed so that luminal potassium concentrations change very little.
  29. c. Calcium reabsorption is paracellular and influenced by sodium reabsorption.Calcium reabsorption is transcellular through ECaC1 channels, and paracellular calcium movement is inhibited by claudin 8.
  30. d. The collecting tubule is impermeable to water at all times.Water permeability is low in the basal state but increases markedly under the influence of ADH.

Pathology

  1. a. Cortex. The photomicrograph reveals a normal renal biopsy from the cortex. Notice the fine-tufted glomeruli with the vessel entering. Also notice the minimal amount of interstitial tissue. The tubules with the smaller lumen and larger cells are proximal tubules; the tubules with the thinner cells and wider lumens are distal tubule cells. Glomeruli and proximal and distal tubules are located in the cortex, not in the medulla.

Chapter review

  1. The determinants of GFR are hydraulic pressure (intra-arterial pressure), which promotes filtration; oncotic pressure, which opposes filtration; permeability of the glomerular basement membrane, which is normally maximal for water and small molecules; and pressure in Bowman space, which opposes filtration.
  2. GFR is regulated through two mechanisms: autoregulation, which is an intrinsic property of arterial smooth muscle, and tubular glomerular feedback, which involves the renin-angiotensin system.
  3. The ideal substance to measure GFR is freely filtered and not metabolized, secreted, or reabsorbed by the kidney. Because creatinine is secreted by the renal tubule, it is not ideal; however, because of the ease of measurement, it is practical. When bowel is placed in the urinary tract, electrolytes, water, and substances used to measure GFR are reabsorbed by the bowel, thus rendering them less than ideal agents for determining GFR in this circumstance. Also, creatinine is a very insensitive marker of early reductions in GFR, because increases in tubular secretion of creatinine keep plasma levels from rising until there has been a significant reduction in GFR.
  4. The Cockcroft-Gault, MDRD, and CKD-EPI formulae calculate GFR from serum creatinine and thus do not require a urine collection. They take into account the patient's age, sex, and race. They are generally good approximations of GFR, and in selected circumstances, one may be preferred over the other.
  5. For each doubling of plasma creatinine there is an approximately 50% reduction in GFR.
  6. Renal blood flow is 20% of cardiac output. Cortical blood flow is approximately 5 times as great as medullary blood flow.
  7. Sixty percent to 65% of filtrate is reabsorbed in the proximal tubule.
  8. The bulk of bicarbonate is reclaimed in the proximal tubule.
  9. The thick ascending limb of Henle reabsorbs sodium in excess of water and is important for maintaining the medullary osmotic gradient. It is here that loop diuretics have their action.
  10. The kidney secretes protons to maintain acid-base balance in the cortical collecting duct. When a proton is secreted as ammonium, its effect on urinary pH is minimal, and therefore it does not generate a significant hydrogen ion gradient, whereas when protons are secreted and coupled with sulfate and/or phosphate (titratable acid), the urine pH is lowered, thus increasing the hydrogen ion gradient and limiting the ability of the kidney to secrete additional protons by this mechanism.
  11. Tamm-Horsfall protein is the matrix of renal tubule casts.
  12. Atrial natriuretic peptide (ANP) is produced in the atrium and promotes natriuresis. It is useful in monitoring myocardial function.
  13. Vasopressin, in addition to increasing water reabsorption, increases sodium reabsorption, promotes potassium secretion, increases adrenocorticotropic hormone (ACTH) production, and releases factor VIII and von Willebrand factor.
  14. Vitamin D becomes biologically active in the kidney and (a) increases intestinal absorption of calcium, (b) regulates osteoblastic activity, (c) increases reabsorption of calcium in the kidney and, (d) suppresses PTH release.
  15. Parathyroid hormone increases bone reabsorption, increases renal reabsorption of calcium and promotes phosphate secretion, and stimulates production of calcitriol, the active form of vitamin D.
  16. Metabolic alkalosis is often associated with hypovolemia and elevated aldosterone. In an attempt to conserve sodium and water, H+may be exchanged with sodium, leading to aciduria, despite the presence of systemic alkalosis.