e.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 44-1 and 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.)

a.cortex.

b.medulla.

c.hilum.

d.papilla.

e.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.

.a. Angiotensin-converting enzyme (ACE) inhibitors may be a cause of hypokalemia.

.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.

. d. Immediate response to an acid load is through buffers in the blood.

.a. Most bicarbonate is reabsorbed in the distal collecting tubule. Most bicarbonate reabsorption in the kidney occurs in the proximal tubule.

.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.

.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.

.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.

.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.

.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.

.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.

. d. PTH increases calcium and phosphorus reabsorption in the distal tubule. PTH increases phosphorus excretion in the kidney.

. e. Is one of the determinants of the glomerular filtration rate.

.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.

. e. Serum osmolality. GFR is not affected significantly by serum osmolality.

.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.

.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.

.c. It has a minor role in sodium reabsorption. The PCT accounts for 65% of sodium reabsorption, the most of any tubular segment.

.d. The thin ascending limb actively reabsorbs sodium, chloride, and urea.

Reabsorption of sodium, chloride, and urea occurs passively in the thin ascending limb.

.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.

.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.

.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.