Renal Pathophysiology

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RENAL PATHOPHYSIOLOGY: THE ESSENTIALS

 The major causes of acute kidney injury (AKI) and the diagnostic approach used to establish the correct diagnosis, particularly the distinction between prerenal disease and acute tubular necrosis (ATN)  The renal autoregulatory response to decreased renal perfusion and the different disorders in which renal ischemia can lead to a reduction in the GFR  The pathogenesis of postischemic and toxic ATN  An appreciation for high-risk clinical situations that can lead to AKI  Lack of specific therapies once the injury is established Definition of Kidney Injury The term renal or kidney injury is often applied to an impairment in the glo merular filtration rate (GFR), but it is now generally referred to as acute kid ney injury (AKI). Because the GFR is equal to the sum of the filtration rates in all of the functioning nephrons, the total GFR (as estimated from the plasma creatinine concentration or the creatinine clearance) is assumed to be an in dex of the functioning renal mass (see Chapter 1). Thus, a fall in GFR with intrinsic renal disease usually reflects disease progression with a reduction in the number of functioning nephrons. How ever, the GFR can also be suddenly reduced and lead to AKI. This can occur with a decline in renal perfusion ( prerenal disease ) or if there is an obstruc tion to the flow of urine out of the kidney in the renal pelves, ureters, bladder, or urethra ( postrenal disease ). A decline in GFR may also be seen with acute injury to tubules, vessels, or glomeruli ( intrinsic renal disease ); whether neph rons recover from the injury depends on the type and duration of the injury. The GFR is important because many potential toxins are excreted by glomerular filtration. As a result, worsening renal disease is associated with the gradual retention of a number of substances, some of which are routinely measured (such as blood urea nitrogen [BUN] and plasma creatinine). How ever, BUN and creatinine per se are not toxic but rather the elevation in se rum levels of these compounds correlates with accumulation and toxicity of unknown uremic molecules. Retention of these toxic substances accounts for many of the signs and symptoms associated with end-stage kidney disease . Examples of these ure mic symptoms include fatigue, anorexia, nausea and vomiting, itching, and difficulty with mental concentration. Signs of uremia include pericarditis and peripheral neuropathy (see Chapter 12). Inadequate potassium and sodium ex cretion are also commonly seen, leading to hyperkalemia and edema, respec tively. Impaired acid excretion leads to the development of metabolic acidosis (Chapter 6). Although uremic signs and symptoms are not usually seen until the GFR is < 15 mL/min (normal is 90 to 125 mL/min), edema and many of the laboratory abnormalities may become evident when GFR is < 40 mL/min. The loss of functioning nephrons also impairs the hormonal functions of the kidneys. This may be manifested clinically by bone disease (due in part to

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