QPT20504: PATHOPHYSIOLOGY OF GENITO

CHAP 4 TUBULOINTERSTITIAL DISEASES

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TUBULOINTERSTITIAL DISEASES
Acute tubular necrosis
Acute pyelonephritis
Chronic Pyelonephritis
Acute drug-induced interstitial nephritis
Analgesic Nephropathy
ACUTE PYELONEPHRITIS
Common suppurative inflammation of the kidney and the renal pelvis,
Caused by bacterial infection.
Pyelonephritis is almost always associated with infection of the lower urinary
tract.
Most commonly affects females??
Causes
The principal causative organisms are the gram-negative rods.
Escherichia coli is the most common one.
Other important organisms are species of Proteus, Klebsiella, Enterobacter,
and Pseudomonas;
- these are usually associated with recurrent infections, especially in patients
who have congenital or acquired anomalies of the lower urinary tract
2 routes bacteria can reach kidney
a) blood stream (not very common)
b) lower urinary tract (ascending infections)
i) - catheterization
ii) - cystoscopy
Most commonly affect females:
a) shorter urethra
b) close proximity to rectum
c) lack of antibacterial prostatic secretions
Urine sterile, flushing keeps bladder sterile.
Predisposing factors:
a) Obstructive uropathy:
i) Prostate hypertrophy
ii) UT obstructions
b) Incompetence vesicoureteral orifice:
reflux of urine into ureters vesicoureteral reflux (VUR) usually congenital
defect 30-50% of young children with UTI
c) Diabetes have high risk of:
i) septicemia
ii) recurrence of infection
d) Pregnancy: 6% develop pyelonephritis; 40- 60% develop - UTI if not
treated
-high levels of progesterone make bladder musculature flaccid and less able
to expel urine.

QPT20504: PATHOPHYSIOLOGY OF GENITO

CHAP 4 TUBULOINTERSTITIAL DISEASES

Pathology
One or both kidneys may be involved.
The affected kidney may be normal in size or enlarged.
Characteristically, discrete, yellowish, raised abscesses are grossly apparent
on the renal surface
Suppurative necrosis or abscess formation within the renal parenchyma
WBC casts
Necrosis, pus (neutrophils)
Acute pyelonephritis. An extensive infiltrate of
neutrophils
is present in the collecting tubules and interstitial
tissue.

Clinical Feautures
Pain at the costovertebral angle,
fever, chills, malaise
Urine: pyuria, bacteria
Dysuria, frequency, urgency

CHRONIC PYELONEPHRITIS

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Interstitial inflammation and scarring with deformity of the pelvicalyceal system

1. Chronic obstructive pyelonephritis

Obstruction predisposes kidney to infection

Recurrent infections
2. Reflux nephropathy

Vesico-ureteral reflux

infections
Pathology
One or both kidneys
Uneven scarring/inflammation
Papillary blunting and calyceal deformities

QPT20504: PATHOPHYSIOLOGY OF GENITO

CHAP 4 TUBULOINTERSTITIAL DISEASES
Dilation/atrophy of tubules, colloid casts (thyoidization)
Vascular changes

Clinical feautures
Late presentation: renal insufficiency, hypertension
Frequent pyuria and bacteriuria
Tubular dysfunction: polyruia/nocturia

ACUTE DRUG-INDUCED INTERSTITIAL NEPHRITIS

Acute drug-induced interstitial nephritis:
Antibiotics
NSAIDs
Diuretics
Begin 15 days after exposure
Fever, eosinophilia, rash
acute renal failure, hematuria, proteinuria
Pathogenesis
Immune mechanism, hypersensitivity
Drug is trapped in the kidney during secretion
Results in injury

Pathology
Edema
Inflammatory infiltrate: lymphocytes, macrophages, eosinophils
NSAIDs may cause minimal change disease like picture

ANALGESIC NEPHROPATHY

Analgesic Nephropathy:
Chronic users
Chronic interstitial nephritis
Renal papillary necrosis
Aspirin, acetaminophen, caffeine, codeine

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QPT20504: PATHOPHYSIOLOGY OF GENITO

CHAP 4 TUBULOINTERSTITIAL DISEASES

Pathogenesis
Unclear, papillary necrosis, inflammation
Oxidative damage
Aspirin inhibits prostaglandin synthesis (vasoconstriction)
Pathology:
Papillary necrosis and calcification
inflammation
Tubular atrophy
Scarring
Vessels: basement membrane thickening
Clinical
Chronic renal failure
Hypertension
Increase risk of transitional cell carcinoma

ACUTE TUBULAR NECROSIS

The most common cause of acute renal failure

Reversible lesion
Destruction of tubular epithelium
Acute suppression of renal function (urine >400ml/day)
Types of Acute Tubular Necrosis
1. Ischemic
State of hypoperfusion
Eg. Trauma, septicemia, hypotension, shock
2. Nephrotoxic:
Heavy metals: mercury
Antibiotics. Gentamicin
Pathogenesis
1. Tubular injury
Sensitive to ischemia and toxins
Functional defect: increase Na delivery to distal tubules vasoconstriction
Tubular debris block urine outflow increase the pressure
Fluid leak in interstitium collapse of tubules
2. Blood flow disturbance (persistent, severe), (Endothelial cell injury)
Vasoconstriction
Endothelial injury: release of endothelin, decrease in nitric oxide
Others: renin-angiotensin, norepinephrine)

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QPT20504: PATHOPHYSIOLOGY OF GENITO

CHAP 4 TUBULOINTERSTITIAL DISEASES

Pathology
Subtle findings, similar in ischemic and toxic
Interstitium- edema, mild acute inflammation
Proximal tubules
Necrosis
Rupture of basement membrane
Proteinaceous cast in distal and collecting tubules

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