Page 495 - Concise Pathology for Exam Preparation ( PDFDrive )

480 SECTION II Diseases of Organ Systems

Pathogenesis

Tubular epithelial cells are particularly sensitive to anoxia and toxins. There are two im-
portant causes of ATI:
1. Direct tubular injury
2. Ischaemia
In ischaemic ATI, ischaemia leads to vasoconstriction induced by renin–angiotensin
system; whereas, in toxic ATI there is direct damage to tubules. Tubular cell injury is
followed by the following sequence of events:
• Desquamation and detachment of tubular epithelial cells
• Tubular obstruction by oedema, desquamated cells and casts
• Increased intratubular pressure and decreased tubular flow
• Tubular rupture and back-leak of tubular fluid into interstium
• Increased interstitial pressure and compression of tubules and blood vessels causing
further ischaemia and reduced GFR leading to oliguria

Morphology
Ischaemic ATI is characterized by necrosis of short segments of tubules.
• Most lesions are seen in the straight portion of proximal tubule and ascending thick
loop of Henle.
• There is blebbing of brush border, vacuolization of cells, detachment of tubular cells
from their basement membrane and sloughing in the urine.
• Proteinaceous casts are present in distal tubules and collecting ducts; these casts consist
of Tamm–Horsfall protein, secreted normally by tubular epithelial cells along with hae-
moglobin and other plasma proteins. In the later stages, disruption of tubular basement
membrane (tubulorrhexis) adjacent to the casts may be seen.
• The interstium shows oedema and inflammatory infiltrate.
Toxic ATI demonstrates a similar morphology, but tubular necrosis is most prominent in
proximal tubules and tubular basement membrane is spared. The appearance varies
depending on the cause of toxic ATI.
Epithelial regeneration is seen in the form of mitotic activity and replacement of tubular
lining by cuboidal cells.

Clinical Course
ATI evolves through three stages:
1. Initial: Lasts for about 36 h; is dominated by the signs and symptoms of the causative
event; there is an increase in BUN due to a transient decrease in renal output.
2. Maintenance: During the maintenance phase, renal tubule injury is established, the
GFR stabilizes at a level well below normal and the urine output is low or absent.
Although oliguria (or anuria) is one of the clinical hallmarks of ATI, it is absent in a
minority of patients (ARF due to nephrotoxins is typically nonoliguric). The second
phase of ATI lasts usually for 1–2 weeks but may extend to a few months.
3. Recovery: The recovery phase of AKI is characterized by polyuria and gradual normal-
ization of GFR; however, when there is multiorgan dysfunction, regeneration of renal
tissue may be severely impaired, and renal function may not return.

Q. Differentiate between ischaemic and nephrotoxic ATI.

Ans. Differences between ischaemic and nephrotoxic ATI are listed in Table 16.8.

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