Causes of toxic tubular necrosis
Ischemic tubular necrosis
Consequences of tubular necrosis
After studying this section you should be able to answer the following
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
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?
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
Can injury be confined
to certain organelles?
example is the microvilli ("brush border") which is sensitive
to certain toxins and may disappear completely resulting in less
absorption and resultant polyuria.
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.
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?
tubular epithelium is metabolically active and has specialized
features (microvilli) and numerous mitochondria.
damage cell membranes or mitochondria in metabolically active
cells. Thus proximal tubular cells are at great risk.
Can toxic tubular damage be
damage may be repaired.
the injury state, renal function is impaired.
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
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.