The pathophysiology and clinical features of UTO are summarized in Table 313-2. Flank pain, the symptom that most commonly leads to medical attention, is due to distention of the collecting system or renal capsule. Pain severity is influenced more by the rate at which distention develops than by the degree of distention. Acute supravesical obstruction, as from a stone lodged in a ureter (Chap. 312), is associated with excruciating, sometimes intermittent, pain, known as renal colic. This pain often radiates to the lower abdomen, testes, or labia. By contrast, more insidious causes of obstruction, such as chronic narrowing of the UPJ, may produce little or no pain and yet result in total destruction of the affected kidney. Flank pain that occurs only with micturition is pathognomonic of vesicoureteral reflux.
TABLE 313-2Pathophysiology of Bilateral Ureteral Obstruction ||Download (.pdf) TABLE 313-2 Pathophysiology of Bilateral Ureteral Obstruction
|Hemodynamic Effects ||Tubule Effects ||Clinical Features |
↑ Renal blood flow
↓ Medullary blood flow
↑ Vasodilator prostaglandins, nitric oxide
↑ Ureteral and tubule pressures
↑ Reabsorption of Na+, urea, water
Pain (capsule distention)
Oliguria or anuria
↓ Renal blood flow
↑ Vasoconstrictor prostaglandins
↑ Renin-angiotensin production
↓ Medullary osmolarity
↓ Concentrating ability
Structural damage; parenchymal atrophy
↓ Transport functions for Na+, K+, H+
Hyperkalemic, hyperchloremic acidosis
|Release of Obstruction |
|Slow ↑ in GFR (variable) || |
↓ Tubule pressure
↑ Solute load per nephron (urea, NaCl)
Natriuretic factors present
Potential for volume depletion and electrolyte imbalance due to losses of Na+, K+, PO42–, Mg2+, and water
Obstruction of urine flow results in an increase in hydrostatic pressures proximal to the site of obstruction. It is this buildup of pressure that leads to the accompanying pain, the distention of the collecting system in the kidney, and elevated intratubular pressures that initiate tubular dysfunction. In the first days of obstruction, the dilatation of the poorly compliant collecting system may be minimal. As the increased hydrostatic pressure is expressed in the urinary space of the glomeruli, further filtration decreases or stops completely.
Azotemia develops when overall excretory function is impaired, often in the setting of bladder outlet obstruction, bilateral renal pelvic or ureteric obstruction, or unilateral disease in a patient with a solitary functioning kidney. Complete bilateral obstruction should be suspected when acute renal failure is accompanied by anuria. Any patient with renal failure otherwise unexplained, or with a history of nephrolithiasis, hematuria, diabetes mellitus, prostatic enlargement, pelvic surgery, trauma, or tumor should be evaluated for UTO.
In the acute setting, partial, bilateral obstruction may mimic prerenal azotemia with a high blood urea nitrogen-to-creatinine ratio, concentrated urine and sodium retention. Renal vascular resistance may be increased. However, with more prolonged obstruction, symptoms of polyuria and nocturia commonly accompany partial UTO and result from loss of medullary hypertonicity with diminished renal concentrating ability. Failure to produce urine free of salt (natriuresis) is due to downregulation of salt reabsorption in the proximal tubule and of transport proteins including the Na+, K+ adenosine triphosphatase (ATPase), NaK2Cl cotransporter (NaK2Cl) in the thick ascending limb, and the epithelial Na+ channel (ENaC) in collecting duct cells. In addition to direct effects on renal transport mechanisms, increased prostaglandin E2 (PGE2) (due to induction of cyclooxygenase-2 [COX-2]), angiotensin II (with its downregulation of Na+ transporters), and atrial or B-type natriuretic peptides (ANP or BNP) (due to volume expansion in the azotemic patient) contribute to decreased salt reabsorption along the nephron.
Dysregulation of aquaporin-2 water channels in the collecting duct contributes to the polyuria. The defect usually does not improve with administration of vasopressin and is therefore a form of acquired nephrogenic diabetes insipidus.
Wide fluctuations in urine output in a patient with azotemia should always raise the possibility of intermittent or partial UTO. If fluid intake is inadequate, severe dehydration and hypernatremia may develop. However, as with other causes of poor renal function, excesses of salt and water intake may result in edema and hyponatremia.
Partial bilateral UTO often results in acquired distal renal tubular acidosis, hyperkalemia, and renal salt wasting. The H+-ATPase, situated on the apical membrane of the intercalated cells of the collecting duct, is critical for distal H+ secretion. The trafficking of intracellular H+ pumps from the cytoplasm to the cell membrane is disrupted in UTO. The decreased function of the ENaC, in the apical membrane of neighboring collecting duct principal cells, contributes to decreased Na+ reabsorption (salt-wasting), and, therefore, decreased K+ secretion via K+ channels. Ammonium (NH4 +) excretion important to the elimination of H+ is impaired. These defects in tubule function are often accompanied by renal tubulointerstitial damage. Azotemia with hyperkalemia and metabolic acidosis should prompt consideration of UTO.
The renal interstitium becomes edematous and infiltrated with mononuclear inflammatory cells early in UTO. Later, interstitial fibrosis and atrophy of the papillae and medulla occur and precede these processes in the cortex. The increase in angiotensin II noted in UTO contributes to the inflammatory response and fibroblast accumulation through mechanisms involving profibrotic cytokines. With time, this process leads to chronic kidney damage.
UTO must always be considered in patients with urinary tract infections or urolithiasis. Urinary stasis encourages the growth of organisms. Urea-splitting bacteria are associated with magnesium ammonium phosphate (struvite) calculi that may take on a staghorn appearance. Hypertension is frequent in acute and subacute unilateral obstruction and is usually a consequence of increased release of renin by the involved kidney. Chronic kidney disease from bilateral UTO, often associated with extracellular volume expansion, may result in significant hypertension. Erythrocytosis, an infrequent complication of obstructive uropathy, is secondary to increased erythropoietin production.