RENAL TUBULAR NECROSIS
Introduction
Causes of toxic tubular necrosis
Ischemic tubular necrosis
Consequences of tubular necrosis
Papillary necrosis


INTRODUCTION
After studying this section you should be able to answer the following questions:

What is acute renal failure?
What is acute tubular necrosis?
What are the causes of acute tubular necrosis?
How does ischemic tubular necrosis differ from toxic tubular necrosis?
What are the consequences of acute tubular necrosis?
What are the pathogenesis and consequences of papillary necrosis?

What is ACUTE RENAL FAILURE?

Acute renal failure occurs with there is abrupt impairment of 75% or more of the functional renal capacity. It can be due to prerenal (compromised renal perfusion), intrarenal (compromised renal function) or postrenal (obstruction) factors. Acute tubular necrosis is one of the most common causes of acute renal failure.

What is ACUTE TUBULAR NECROSIS (ATN)?

Injury resulting in the death of tubular epithelial cells is termed acute tubular necrosis (nephrosis) and is the result of toxic or ischemic damage.

The lesion is characterized by coagulative necrosis of tubular epithelial cells (arrows), dilated hypocellular tubules (arrowheads), and intratubular debris (D).

What mechanisms are involved in acute renal failure secondary to tubular damage?

Backleak and tubular obstruction are at least two mechanisms.

In both mechanisms, filtrate (urine) is not excreted and azotemia results. With backleak, the filtrate produced by the glomerulus is not contained in injured tubules - it "leaks back" into the interstitium and is subsequently reabsorbed into blood vessels. Thus wastes are not eliminated and the animal dies of renal failure. Second, the tubule may be obstructed (plugged) and prevent passage of the filtrate. If many tubules are obstructed, azotemia results. In addition, because of activation of the renin-angiotensin system due to tubular damage, intrarenal vasoconstriction occurs resulting in decreased glomerular blood flow and filtration.

Are the lesions of ATN different depending upon the cause?

Yes, toxins generally cause epithelial necrosis whereas ischemia causes necrosis AND RUPTURE of the basement membrane (TUBULORRHEXIS). Thus ischemic lesions are more severe since fibrosis rather than regeneration occurs.

Can injury be confined to certain organelles?

Yes, one example is the microvilli ("brush border") which is sensitive to certain toxins and may disappear completely resulting in less absorption and resultant polyuria.

Other organelles (i.e. mitochondria) and enzymes may also be selectively injured with other agents.

Which part of the tubule is most often injured?

The 3 segments of the PROXIMAL TUBULE are most often injured. The agents that injure this area usually do so by toxic or ischemic action.

The convoluted segments, S1 and S2, are most susceptible to toxic injury and S3 most susceptible to ischemic injury. However, the major take home message is that toxic and ischemic damage usually involves the proximal tubules.

Why do Toxic agents often cause damage to the convoluted segments of the proximal tubules?

Proximal tubular epithelium is metabolically active and has specialized features (microvilli) and numerous mitochondria.

Toxins often damage cell membranes or mitochondria in metabolically active cells. Thus proximal tubular cells are at great risk.

Can toxic tubular damage be reversed?

Yes, the damage may be repaired.

However during the injury state, renal function is impaired.

Remember the proximal tubules are responsible for most of the re-absorptive activities of the kidney - thus they contain biochemical units needed for enzymatic and energy production activities. Toxic agents often interfere with energy production and enzymes. Thus cell function is impaired.

What would be the clinical signs that result from this impaired function of the proximal tubules?

Urine volume could be increased or decreased depending upon the type of injury and the type of functional impairment. An animal would be anuric if backleak or obstruction were severe, and it would be polyuric if tubular absorption was impaired. Therefore, tubular injury can result in polyuria, oliguria, anuria, and ultimately renal failure if damage is severe and extensive.


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