Debre Markos University

School of Medicine
Renal Pathology for PC2
By: Zelalem Tadesse(MD)
July, 2018

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 Diseases affecting Tubules and
Interstitium
1, Acute tubular necrosis ( ATN)
2, Tubulointerstitial nephritis ( TIN)
Acute Tubular Necrosis ( ATN)
• Clinicopathologic entity characterized
morphologically by destruction of tubular epithelial
cells and clinically by acute suppression of renal
function with granular casts and tubular cells
observed in the urine.
• It is the most common cause of ARF ( suppression of
renal function and urine flow < 400 ml in 24hrs).
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 Cont’d…
• ATN accounts for ~50% hospitalized pts of ARF
• The principal causes of acute tubular necrosis are
– ischemia
– toxins
Ischemic ATN
• Follow a variety of clinical situations like trauma, burns
and infections which cause hypotension and shock.
• Profound hypotension causes hypoperfusion of the
peritubular circulation
• Tubule cell injury
• Hemodynamic alterations

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 Cont’d…
Histology
• Epithelial cell injury along the entire length of the
tubules
• Rupture of basement membrane (tubulorrhexis)
• Casts composed of cellular debris and protein (Tamm-
Horsfall protein)
Toxic ATN
• Result from exposure to a wide variety of substances
• Heavy metals (lead, mercury..)
• Organic solvents ( CCl4… )
• Iodinated radiographic contract medium

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 Cont’d…
• The kidneys appear swollen and red
• Histologicaly there is marked vacuolation of
the tubular epithelial cytoplasm
• The damage is characteristically restricted to
the proximal tubular cells those of the distal
tubule being spared

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 Clinical course
• Classic case has three phases:
Initiating phase
• lasts for about 36hrs , is dominated by the inciting agent
Maintenance stage
• decreased urine output ,rising BUN, hyperkalemia
metabolic acidosis and other manifestations of uremia
Recovery phase
• steady increase in urine output up to 3L/day
• tubular damage -sodium and potassium loss
• tubular function is restored eventually BUN and
creatinine begins to return to normal
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 Cont’d…
Prognosis depends on clinical setting
• In ATN caused by toxins recovery is possible in
up to 95% of cases -in those related to sepsis or
intensive burn mortality rate may rise to more
than 50%.
• Up to 50% of patients may not have oligouria
(non-oliguric ATN) –occurs particularly with
nephrotoxins.

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 Tubulo-interstitial Nephritis
• A group of renal diseases characterized by histologic and
functional alterations that involve the tubules and
interstitium.
• The glomeruli may be spared
altogether or affected only late in the course
• can be acute or chronic.
• acute – acute clinical onset, interstitial edema, leukocytic
infiltration focal tubular necrosis.
• chronic- infiltration of mononuclear cells, prominent
interstitial fibrosis ,widespread tubular atrophy.
• The most common forms are those caused by infections
(pylonephritis) and drugs.
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 Pyelonephritis and Urinary tract
infection
• Pyelonephritis – one of the most common
diseases of the kidney affecting tubules,
interstitium and renal pelvis
• Acute pyelonephritis – caused by bacterial
infection and is associated with urinary tract
infection
• Chronic pyelonephritis – bacterial infection
plays a role but other factors like
vesicoureteral reflux, obstruction are involved

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 Etiology and pathogenesis
• In > 85% of the cases of UTI -Gram negative bacilli
that are normal inhabitants of intestine are
etiologies
• Leading cause is E. coli followed by Proteus ,
Klebsiella, Enterobacter
• In most patients organisms are derived from the
patients fecal flora.
• Two routes by which bacteria can reach the kidney:
1. Hematogeneous
2. Ascending infection from lower UT
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 Cont’d….
Hematogeneous:
• Less common route
• In the course of septicemia or infective endocarditis
• In debilitated patients, immunosuppressive therapy with
non-enteric org. E.g. staph.
Ascending infection
Steps
• Colonization of the distal urethra and interoitus
• From urethra to the bladder
-Catheterization (long term)
-UTI much more common in females (shorter urethra)

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Cont’d…

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 Cont’d…
• Multiplication in the bladder.
- out flow obstruction or bladder dysfunction.
• Vesicoureteral reflux
-Incompetence of the vesicoureteral valve which
allows reflux of bladder urine into ureter
- can be congenital or acquired
• Intrarenal reflux
- Leads to urine propulsion to the renal pelvis and
deep into the renal parenchyma

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Cont’d…

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 Acute pyelonephritis
• Acute suppurative inflammation of the kidney
caused by bacterial infection.
• It is an important manifestation of urinary tract
infection (UTI), which implies involvement of the
lower (cystitis, prostatitis, urethritis) or upper
(pyelonephritis) urinary tract, or both.

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 Predisposing conditions
• Urinary obstruction
• Instrumentation of urinary tract- catheterization
• Vesicoureteral reflux
• Pregnancy
• Sex and age
• Preexisting renal lesions
• DM
• Immunosuppression and immunodeficiency

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 Morphology
• Characteristically, discrete, yellowish, raised
abscesses are grossly apparent on the renal
surface .
• Hallmarks are patchy interstitial suppurative
inflammation and tubular necrosis
• Complications include
-Papillary necrosis-common in diabetics.
-Pyonephrosis
-Perinephric abscess

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18
 Clinical Course
• The onset of uncomplicated acute pyelorephritis
is usually sudden, with pain at the costovertebral
angle and systemic evidence of infection, such as
chills, fever, and malaise.
• Urinary findings include pyuria and bacteriuria.
• In addition, there are usually indications of
bladder and urethral irritation (dysuria,
frequency, urgency).
 Cont’d....
• The symptomatic phase of the disease usually
lasts no longer than a week, although bacteriuria
may persist much longer.
• The development of papillary necrosis is
associated with a much poorer prognosis.
• These persons have evidence of overwhelming
sepsis and, often, renal failure.
• The diagnosis of acute pyelonephritis is
established by finding leukocytes ("pus cells") by
urinalysis and urine culture
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 Chronic Pylonephritis
Characterized by:
- Chronic tubulointerstitial inflammation
- Renal scarring
- Pathologic involvement of the calyces and pelvis
• Is an important cause of end stage kidney disease
• 10-20% of patients in renal transplant or dialysis
Two forms:
• Chronic obstructive pylonephritis
• Reflux nephropathy

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 Cont’d…
Morphology
• Grossly the kidneys are irregularly scarred
cortico-medullary scarring overlying dilated
blunted or deformed calyx.
• Microscopically the tubules show atrophy, in
some areas hypertrophy and dilation.
• Dilated tubules may be filled with colloid casts (
thyroidization)
• Chronic interstitial inflammation and fibrosis

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 Clinical feature
- Can present acutely or insidiously
- Acute symptoms include back pain, fever,
pyuria, bacteruria

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 Diseases Involving Blood Vessels

• Nearly all diseases of the kidney involve the

renal blood vessels secondarily.
• Systemic diseases(diabetes, hypertension,
immunologic diseases) also involve renal vessels
• The kidney is intimately involved in the
pathogenesis of both essential and secondary
hypertension.
• Renal vascular diseases → ↓renal blood flow →
↑renin → ↑blood pressure

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 Benign Nephrosclerosis
The term used for the renal changes in benign
hypertension, is always associated with
hyaline arteriolosclerosis.
Morphologically shows:
 atrophic kidneys
 hyaline arteriolosclerosis
The frequency and severity of the lesions are
increased at any age when hypertension or
diabetes mellitus are present.
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 Clinical course
All patients with this lesion usually show:
• Some functional impairment, such as loss of
concentrating ability or a variably diminished
GFR.
• A mild degree of proteinuria is a frequent
finding.

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27
Malignant Hypertension and Malignant
Nephrosclerosis
• Malignant hypertension is far less common in
the United States than benign hypertension
and occurs in only about 5% of persons with
elevated blood pressure.
• It may arise de novo (i.e., without preexisting
hypertension), or it may appear suddenly in a
person who had mild hypertension.
• In less developed countries, it occurs more
commonly.

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 Pathogenesis
- Long-standing benign hypertension, with
eventual injury to the arteriolar walls
- The result is increased permeability of the small
vessels to fibrinogen and other plasma
proteins, endothelial injury, and platelet
deposition.

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 Morphology
• Fibrinoid necrosis of arterioles and small
arteries and intravascular thrombosis
• Hyperplastic arteriolosclerosis
• Small, pinpoint petechial hemorrhages may
appear on the cortical surface from rupture of
arterioles or glomerular capillaries, giving the
kidney a peculiar, “flea-bitten appearance”.

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Cont’d…

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 Clinical Course
The full blown malignant HTN presents with:
papilledema, encephalopathy, cardiovascular
abnormalities, and renal failure
The early symptoms are due to increased ICP like
headache, nausea, vomiting, and visual impairment
90%of deaths are caused by uremia and the other
10% by cerebral hemorrhage or cardiac failure.

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 Thrombotic Microangiopathies
This term describes lesions seen in various clinical
syndromes, characterized morphologically by
widespread thrombosis in the microcirculation
and clinically by microangiopathic hemolytic
anemia, thrombocytopenia, and, in certain
instances, renal failure.

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 Childhood Hemolytic uremic
Syndrome (HUS)
Common cause of acute renal failure in children
75% of cases follow intestinal infection by Shiga
toxin-producing E. coli
The toxin which is carried to the circulation by
neutrophils has multiple effects on the
endothelium.

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 Effects of Shiga toxin
Increased adhesion of leukocytes, increased
endothelin production, and loss of endothelial
nitric oxide (both favoring vasoconstriction), and
endothelial damage and direct cell death.
The resultant endothelial damage leads to
thrombosis, which is most prominent in
glomerular capillaries, afferent arterioles, and
interlobular arteries, as well as vasoconstriction,
resulting in the characteristic thrombotic
microangiopathy.
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 Clinical Course
Typically, childhood HUS is characterized by the
sudden onset, usually after a gastrointestinal or
flulike prodromal episode, of bleeding
manifestations (especially hematemesis and
melena), severe oliguria, hematuria,
microangiopathic hemolytic anemia, and (in
some persons) prominent neurologic changes.

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 References
1.Robbins Basic Pathology 9th edition
2.General and systemic pathology, 4th edition

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THANK YOU

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