DISEASES OF RENAL

TUBULES AND
INTERSTITIUM
 (1) inflammatory involvement of the
tubules and interstitium (interstitial
nephritis)
 (2) ischemic or toxic tubular injury, leading
to acute tubular necrosis and acute renal
failure.
 Tubulointerstitial Nephritis
Acute Pyelonephritis
 Suppurative inflammation of the kidney and the
renal pelvis, is caused by bacterial infection
 Cause
 Proteus, Klebsiella, Enterobacter, and Pseudomonas,
Staphylococci and Streptococcus faecalis may also
cause pyelonephritis, but they are uncommon
 urinary tract manipulations or have congenital or
acquired anomalies of the lower urinary tract
 Etiology
 Urinary obstruction, congenital or acquired
 Instrumentation of the urinary tract, most commonly
catheterization
 Vesicoureteral reflux.
 Pregnancy.
 Patient's sex and age. After the first year of life (when congenital
anomalies in males commonly become evident) and as far as
around age 40 years, infections are much more frequent in
females. With increasing age, the incidence in males rises as a
result of the development of prostatic hyperplasia and frequent
instrumentation.
 Preexisting renal lesions, causing intrarenal scarring and
obstruction
 Diabetes mellitus, in which acute pyelonephritis is caused by
increased susceptibility to infection and neurogenic bladder
dysfunction
 Immunosuppression and immunodeficiency.
 Pathology
2 routes
 Through the bloodstream (hematogenous)
 septicemia
 infective endocarditis
 From the lower urinary tract (ascending infection
 adhesion to the urothelial lining by bacterial fimbriae
 colonization of the distal urethra
 access to the bladder (urethral instrumentation, including
catheterization and cystoscopy )
 Obstruction at the level of the urinary bladder
 incomplete emptying and increased residual volume
of urine.
 bacteria introduced into the bladder can multiply
undisturbed
 incompetence of the vesicoureteral orifice
 congenital defect
 acquired in individuals with a flaccid bladder resulting from
spinal cord injury and with neurogenic bladder dysfunction
secondary to diabetes
 bacteria ascend the ureter into the pelvis
 Morphology
 normal in size or enlarged
 discrete, yellowish,
raised abscesses are
grossly apparent on the
renal surface
 They may be widely
scattered or limited to one
region of the kidney, or
they may coalesce to form
a single large area of
suppuration.
 Histologic feature of acute pyelonephritis is
suppurative necrosis or abscess formation within
the renal parenchyma. In the early stages the
suppuration is limited to the interstitial tissue, but later
abscesses rupture into tubules. Large masses of
intratubular neutrophils ,white cell casts found in
the urine.
 The glomeruli are not affected
 When obstruction is prominent, the pus may be
unable to drain and thus fills the renal pelvis, calyces,
and ureter, producing pyonephrosis.
A second form of pyelonephritis -papillary necrosis.
 diabetics who develop acute pyelonephritis
 complicate acute pyelonephritis when there is significant
urinary tract obstruction.
 chronic interstitial nephritis associated with analgesic abuse
 ischemic and suppurative necrosis of the tips of the renal
pyramids (renal papillae).
 The pathognomonic gross feature- sharply defined gray-white
to yellow necrosis of the apical two-thirds of the pyramids.
One papilla or several or all papillae may be affected.
 Microscopically
 The papillary tips show characteristic coagulative necrosis,
with surrounding neutrophilic infiltrate
 When the bladder is involved acute or chronic
cystitis results.
 In long-standing cases, the bladder may be grossly
hypertrophic, with trabeculation of its walls, or it may
be thinned and markedly distended from retention of
urine
 Course
 Sudden onset
 pain at the costovertebral angle
 chills, fever, and malaise.
 pyuria and bacteriuria.
 dysuria, frequency, urgency
 benign and self-limited.
 no longer than a week
 bacteriuria may persist much longer
 usually unilateral and thus the patient dosent develop
renal failure
 The development of papillary necrosis is associated
with a much poorer prognosis. Sepsis and, often,
renal failure.
 Diagnosis
 Leukocytes ("pus cells") by urinalysis and urine
culture.
 Chronic Pyelonephritis and Reflux
Nephropathy
 Interstitial inflammation and scarring of the renal
parenchyma is associated with grossly visible
scarring and deformity of the pelvicalyceal
system
 Two forms:
 chronic obstructive pyelonephritis
 Recurrent infections superimposed on diffuse or localized
obstructive lesions lead to recurrent bouts of renal
inflammation and scarring, which eventually cause chronic
pyelonephritis.
 Bilateral, congenital anomalies of the urethra (posterior urethral
valves)
 unilateral, calculi and unilateral obstructive lesions of the ureter.
 Chronic reflux-associated pyelonephritis.
 more common form of chronic pyelonephritic scarring
 superimposition of a UTI on congenital vesicoureteral reflux
and intrarenal reflux.
 Reflux may be unilateral or bilateral; thus, the resultant renal
damage either may cause scarring and atrophy of one
kidney or may involve both and lead to chronic renal
insufficiency
 Morphology
 One or both kidneys
 diffusely or in patches.
 Even when involvement is bilateral, the kidneys are not equally
damaged and therefore are not equally contracted. This uneven
scarring is useful in differentiating chronic pyelonephritis from
vascular sclerosis and chronic GN
 The hallmark of chronic pyelonephritis is scarring involving the
pelvis or calyces, or both, leading to papillary blunting and
marked calyceal deformities
 The microscopic changes are largely nonspecific
 Uneven interstitial fibrosis and an inflammatory infiltrate of
lymphocytes, plasma cells
 Dilation or contraction of tubules, with atrophy of the lining
epithelium. Many of the dilated tubules contain pink to blue,
glassy-appearing PAS-positive casts known as colloid casts that
suggest the appearance of thyroid tissue, hence the descriptive
term thyroidization.
 Often, neutrophils are seen within tubules.
 Chronic inflammatory infiltration and fibrosis involving the
calyceal mucosa and wall.Vascular changes similar to those of
benign arteriolosclerosis caused by the frequently associated
hypertension
 .Although glomeruli may be normal, in most cases,
glomerulosclerosis is seen in areas of better preserved renal
parenchyma. Such changes represent secondary sclerosis
caused by maladaptive changes secondary to nephron loss.
 Course
 come to medical attention relatively late
 hypertension
 Pyelograms show the affected kidney to be
asymmetrically contracted blunting and deformity of
the calyceal system
 If the disease is bilateral and progressive, tubular
dysfunction occurs with loss of concentrating ability,
manifested by polyuria and nocturia
 Drug-Induced Interstitial Nephritis
 Acute Drug-Induced Interstitial Nephritis
 This is an adverse reaction to any of an increasing number of drugs
 Occurs with synthetic penicillins (methicillin, ampicillin ), other
synthetic antibiotics (rifampin ), diuretics (thiazides), nonsteroidal
anti-inflammatory agents, and numerous other drugs (phenindione,
cimetidine).
 Pathogenesis
 immune mechanism as
 latent period
 eosinophilia and rash
 onset of nephropathy is not dose related
 recurrence of hypersensitivity after re-exposure
  Serum IgE levels are increased
 Mononuclear or granulomatous infiltrate, together with
positive skin tests to drugs
 Pathogenesis
 drugs act as haptens
 during secretion by tubules, covalently bind to some
cytoplasmic or extracellular component of tubular
cells and become immunogenic.
 The resultant tubulointerstitial injury is then caused by
IgE- and cell-mediated immune reactions to tubular
cells or their basement membranes
 Morphology
 Interstitium, shows pronounced edema and infiltration by
mononuclear cells, principally lymphocytes and macrophages
 Eosinophils and neutrophils may be present, often in large
numbers
 Methicillin, thiazides, rifampin, interstitial non-necrotizing
granulomas with giant cells may be seen.
 The glomeruli are normal except in some cases caused by
nonsteroidal anti-inflammatory agents when the hypersensitivity
reaction also leads to podocyte foot process effacement (MCD-
like lesion), and the nephrotic syndrome develops concurrently
 Course
 Disease begins about 15 days after exposure to the
drug
 Fever, eosinophilia, a rash, renal abnormalities.
 hematuria, minimal or no proteinuria, and leukocyturia
(sometimes including eosinophils).
 A rising serum creatinine or acute renal failure with
oliguria in about 50% of cases, particularly in older
patients
 Analgesic Nephropathy
 consume large quantities of analgesics or mixtures containing some
combination
 associated with renal papillary necrosis
 Papillary necrosis is the initial event, and the interstitial nephritis in
the overlying renal parenchyma is a secondary phenomenon
 Acetaminophen , a phenacetin metabolite, injures cells by both
covalent binding and oxidative damage.
 The ability of aspirin to inhibit prostaglandin synthesis suggests that
this drug may induce its potentiating effect by inhibiting the
vasodilatory effects of prostaglandin and predisposing the papilla to
ischemia
 Thus, the papillary damage may be caused by a combination of two
 Morphology
 necrotic papillae appear yellowish brown, as a
result of the accumulation of breakdown products of
phenacetin and other lipofuscin-like pigments
 Later on, the papillae may shrivel, be sloughed off,
and drop into the pelvis.
 Microscopically, the papillae show coagulative
necrosis
 dystrophic calcification may occur
 cortex drained by the necrotic papillae shows tubular
atrophy, interstitial scarring, and inflammation.
 The small vessels in the papillae and urinary tract
submucosa exhibit characteristic PAS-positive
basement membrane thickening
 Clinical Course
 chronic renal failure, hypertension, and anemia.
 The anemia results in part from damage to red cells
by phenacetin metabolites.
 Cessation of analgesic intake may stabilize or even
improve renal function.
 Complication -increased incidence of transitional-
cell carcinoma of the renal pelvis or bladder
 Acute Tubular Necrosis
 Reversible renal lesion that arises in a variety of
clinical settings characterized morphologically by
damaged tubular epithelial cells and clinically by
acute suppression of renal function
 It is the most common cause of acute renal
failure.
 Causes
 Nephrotoxic ATN
 heavy metals (e.g., mercury); organic solvents (e.g., carbon
tetrachloride); and a multitude of drugs such as gentamicin
and other antibiotics, and radiographic contrast agents

.
 periodof inadequate blood flow to the peripheral
organs like (inischemic ATN)
 severe trauma
 acute pancreatitis
 Septicemia
 hypotension and shock. The pattern of ATN associated with
shock is called Mismatched blood transfusions
 hemolytic crises
 Myoglobinuria
 Other causes of acute renal failure (urine flow
falls within 24 hours to less than 400 mL per
day) include
 (1) severe glomerular diseases manifesting as RPGN,
 (2) diffuse renal vascular diseases such as
microscopic polyangiitis and thrombotic
microangiopathies,
 (3) acute papillary necrosis associated with acute
pyelonephritis,
 (4) acute drug-induced interstitial nephritis, and
 (5) diffuse cortical necrosis.
 Pathogenesis
 1) tubular injury and
 2) persistent and severe disturbances in blood flow
resulting in diminished oxygen and substrate delivery
to tubular cells
 factors predispose the tubules to toxic injury,
 vast electrically charged surface for fluid reabsorption
 active transport systems for ions and organic acids
 the capability for effective concentration
Pathogenesis of ATN due to structral
alterations
Pathogenesis due to hemodynamic changes
 Effect of intra renal vasoconstriction
 reduced glomerular plasma flow
 reduced oxygen delivery to the functionally important
tubules in the outer medulla (thick ascending limb and
straight segment of the proximal tubule)
 Intrarenal vasoconstriction caused by
 Renin-angiotensin, thromboxane A2
 sympathetic nerve activity), some triggered by the
increased distal sodium delivery
 the current opinion is that vasoconstriction is
mediated by sublethal endothelial injury, leading to
increased release of the endothelial vasoconstrictor
endothelin and decreased production of vasodilatory
nitric oxide and prostaglandins
 Morphology
 Necrosis of short segments of the tubules. Most of
the lesions in the straight portions of the proximal
tubule and the ascending thick limbs
 widespread overt necrosis of tubular cells is
uncommonly seen in renal biopsy
 often a variety of tubular injuries,
 attenuation of proximal tubular brush borders,
 blebbing and sloughing of brush borders
 vacuolization of cells, and detachment of tubular cells from
their underlying basement membranes with sloughing of cells
into the urine.
 proteinaceous casts in the distal tubules and
collecting ducts. (consist of Tamm-Horsfall protein
(secreted normally by tubular epithelium) along with
hemoglobin and other plasma proteins). When crush
injuries have produced ATN, the casts are composed
of myoglobin.
 interstitium usually shows generalized edema along
with a mild inflammatory infiltrate consisting of
polymorphonuclear leukocytes, lymphocytes, and
plasma cells
 In toxic ATN necrosis is most prominent in the
proximal tubule, and the tubular basement
membranes are generally spared.
 If the patient survives for a week, epithelial
regeneration becomes apparent in the form of a low
cuboidal epithelial covering and mitotic activity in the
persisting tubular epithelial cells.
 Except where the basement membrane is destroyed,
regeneration is total and complete.
 Course
 Initiation phase
 lasting about 36 hours
 dominated by the inciting medical, surgical, or obstetric event
causing ATN.
 renal involvement is a slight decline in urine output with a rise
in serum creatinine.
 oliguria explained on the basis of a transient decrease in
blood flow to the kidneys.
 Maintenance phase
 second to the sixth day
 Urine output falls markedly, usually to between 50 and 400
mL per day (oliguria)
  complete anuria is rare.
 Oliguria may last a few days or persist as long as 3 weeks.
 uremia and fluid overload
 With good care, survival is the rule
 Recovery phase
 Steady increase in urine volume, reaching as much as about
3 L/day over the course of a few days.
 As tubular function is still deranged, serious electrolyte
imbalances may occur
 increased vulnerability to infection.
 25% of deaths from ATN occur during this phase.