Porth's Pathophysiology, 9e

1114

UNIT X Disorders of Renal Function and Fluids and Electrolytes

­predisposition to hypovolemia and their high prevalence of renal vascular disorders. Some vasoactive mediators, drugs, and diagnostic agents stimulate intense intrarenal vasoconstriction and can induce glomerular hypoperfusion and prerenal failure. Examples include endotoxins, radiocontrast agents such as those used for cardiac catheterization, cyclosporine (an immunosuppressant drug that is used to prevent trans- plant rejection), and nonsteroidal anti-inflammatory drugs (NSAIDs). 2 Many of these drugs also cause acute tubular necrosis (ATN; discussed later). In addition, several com- monly used classes of drugs can impair renal adaptive mech- anisms and can convert compensated renal hypoperfusion into prerenal failure. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) reduce the effects of renin on renal blood flow; when combined with diuretics, they may cause prerenal failure in persons with decreased blood flow due to large-vessel or small-­ vessel kidney disease. Prostaglandins have a vasodilatory effect on renal blood vessels. NSAIDs can reduce renal blood flow through inhibition of prostaglandin synthesis. In some persons with diminished renal perfusion, NSAIDs can precipitate prerenal failure. Normally, the kidneys receive 20% to 25%% of the car- diac output. 5 This large blood supply is required for the glom- eruli to remove metabolic wastes and regulate body fluids and electrolytes. Fortunately, the normal kidney can tolerate relatively large reductions in blood flow before renal damage occurs. As renal blood flow is reduced, the GFR decreases, the amount of sodium and other substances that are filtered by the glomeruli is reduced, and the need for energy-dependent mechanisms to reabsorb these substance is reduced. 5 As the GFR and urine output approach zero, oxygen consumption by the kidney approximates that required to keep renal tubu- lar cells alive. When blood flow falls below this level, which is about 20% to 25% of normal, ischemic changes occur. 5 Because of their high metabolic rate, the tubular epithelial cells are most vulnerable to ischemic injury. Improperly treated, prolonged renal hypoperfusion can lead to ischemic tubular necrosis with significant morbidity and mortality. However, the majority of people who experience the prolonged renal hypoperfusion do not have tubular epithelial necrosis, so the term ATN is being used less frequently and AKI refers to this intrarenal pathology. 6 Prerenal failure is manifested by a sharp decrease in urine output and a disproportionate elevation of blood urea nitrogen (BUN) in relation to serum creatinine levels. The kidney normally responds to a decrease in the GFR with a decrease in urine output. Thus, an early sign of prerenal failure is a sharp decrease in urine output. A low fractional excretion of sodium (<1%) suggests that oliguria is due to decreased renal perfusion and that the nephrons are respond- ing appropriately by decreasing the excretion of filtered sodium in an attempt to preserve vascular volume. 2 BUN levels also depend on the GFR. A low GFR allows more time for small particles such as urea to be reabsorbed into

the blood. Creatinine, which is larger and nondiffusible, remains in the tubular fluid, and the total amount of creati- nine that is ­filtered, although small, is excreted in the urine. Consequently, there also is a disproportionate elevation in the ratio of BUN to serum creatinine, from a normal value of 10:1 to a ratio greater than 15:1 to 20:1. 2 Postrenal Failure Postrenal failure results from obstruction of urine outflow from the kidneys. The obstruction can occur in the ureter ( i.e., calculi and strictures), bladder ( i.e., tumors or neurogenic bladder), or urethra ( i.e., prostatic hyperplasia). Due to the increased urine not being able to be excreted due to the obstruction, retrograde pressure occurs throughout the tubules and nephrons, which ultimately damages the nephrons. 2 Prostatic hyperplasia is the most common underlying problem. Because both ureters must be occluded to produce renal failure, obstruction of the blad- der rarely causes acute renal failure unless one of the kidneys already is damaged or a person has only one kidney. The treat- ment of acute postrenal failure consists of treating the underly- ing cause of obstruction so that urine flow can be reestablished before permanent nephron damage occurs. Intrarenal renal failure or acute kidney injury, as it is now more commonly known, results from conditions that cause damage to structures within the kidney. The most frequent etiology of intrarenal acute renal failure causes damage to the parenchyma in the glomeruli, vessels, tubules, or inter- stitium. 6 The major causes of intrarenal failure are ischemia associated with prerenal failure, toxic insult to the tubu- lar structures of the nephron, and intratubular obstruction. Acute glomerulonephritis and acute pyelonephritis also are intrarenal causes of acute renal failure. The decreased glomerular filtration and epithelial injury are due to many causes such as intrarenal vasoconstriction, decreased hydro- static pressure in the glomeruli, changes in arterial tone by tubuloglomerular feedback, decreased capillary permeabil- ity in the glomeruli, increased tubular hydrostatic pressure secondary to obstruction, and backflow of glomerular filtrate into the interstitium. 6 Injury to the tubular structures of the nephron is the most common cause and often is ischemic or toxic in origin. Acute Tubular Injury or Necrosis.  Acute tubular injury or necrosis is characterized by the destruction of tubular epithe- lial cells with acute suppression of renal function (Fig. 42.2). This acute injury can be caused by a variety of conditions, including acute tubular damage due to ischemia, sepsis, neph- rotoxic effects of drugs, tubular obstruction, and toxins from a massive infection. 2 Tubular epithelial cells are particularly sensitive to ischemia and also are vulnerable to toxins. The tubular injury that occurs frequently is reversible. Ischemic ATN or acute tubular injury occurs most frequently in persons who have extensive surgery, severe Intrarenal Renal Failure or Acute Kidney Injury