Page 695 - Textbook of Pathology, 6th Edition

I. Primary tubular diseases that include tubular injury by 679
ischaemic or toxic agents i.e. acute tubular necrosis.
II. Tubulointerstitial diseases that include inflammatory
involvement of the tubules and the interstitium i.e.
tubulointerstitial nephritis.
ACUTE TUBULAR NECROSIS

Acute tubular necrosis (ATN) is the term used for acute renal
failure (ARF) resulting from destruction of tubular epithe-
lial cells. ATN is the most common and most important cause
of ARF characterised by sudden cessation of renal function.
Various other causes of ARF (pre-renal, intra-renal and post-
renal) as well as the clinical syndrome accompanying ATN
(oliguric phase, diuretic phase and phase of recovery) are
described already on page 654. Based on etiology and
morphology, two forms of ATN are distinguished—
ischaemic and toxic; however both forms have a somewhat
common pathogenesis.

Pathogenesis of ATN
The pathogenesis of both types of ATN resulting in ARF is
explained on the basis of the following sequential mechanism
and is illustrated in Fig. 22.26:
i) Renal tubules are highly susceptible to injury by ischaemia
and toxic agents. CHAPTER 22
ii) Tubular damage in ischaemic ATN is initiated by arteriolar
vasoconstriction induced by renin-angiotensin system, while
in toxic ATN by direct damage to tubules by the agent.
iii) Debris of the desquamated epithelium due to necrosis Figure 22.26 Pathogenesis of ATN.
causes tubular obstruction and may block urinary outflow with
consequent reduction of GFR and also produce casts in the 1. Shock (post-traumatic, surgical, burns, dehydration,
urine. obstetrical and septic type).
iv) These events cause increased intratubular pressure resulting 2. Crush injuries.
in damage to tubular basement membrane. 3. Non-traumatic rhabdomyolysis induced by alcohol,
v) Due to increased intratubular pressure, there is tubular coma, muscle disease or extreme muscular exertion
rupture. (myoglobinuric nephrosis).
vi) Damage to tubules is accompanied with leakage of fluid 4. Mismatched blood transfusions, black-water fever The Kidney and Lower Urinary Tract
into the interstitium causing interstitial oedema. (haemoglobinuric nephrosis).
vii)Leakage of tubular fluid into the interstitium increases MORPHOLOGIC FEATURES. Grossly, the kidneys are
interstitial pressure. enlarged and swollen. On cut section, the cortex is often
viii) Leaked fluid incites host inflammatory response. widened and pale, while medulla is dark.
ix) Increased interstitial pressure causes compression of tubules Histologically, predominant changes are seen in the
and blood vessels and setting up a vicious cycle of accentuated tubules, while glomeruli remain unaffected. The
ischaemia and necrosis. interstitium shows oedema and mild chronic
x) Ultimately, it leads to reduced GFR and consequently inflammatory cell infiltrate. Tubular changes are as follows
oliguria. (Fig. 22.27):
1. Dilatation of the proximal and distal convoluted
Ischaemic ATN tubules.
2. Focal tubular necrosis at different points along the
Ischaemic ATN, also called tubulorrhectic ATN, lower nephron.
(distal) nephron nephrosis, anoxic nephrosis, or shock 3. Flattened epithelium lining the tubules suggesting
kidney, occurs due to hypoperfusion of the kidneys resulting epithelial regeneration.
in focal damage to the distal parts of the convoluted tubules. 4. Eosinophilic hyaline casts or pigmented haemoglobin
ETIOLOGY. Ischaemic ATN is more common than toxic and myoglobin casts in the tubular lumina (Fig. 22.28).
ATN and accounts for more than 80% cases of tubular injury. 5. Disruption of tubular basement membrane adjacent
Ischaemia may result from a variety of causes as follows: to the cast may occur (tubulorrhexis).