PATHOLOGY OF KIDNEY AND URINARY TRACT
CONGENITAL RENAL MALFORMATIONS
-renal agenesis -is a failure of development of kidneys
- bilateral - rare, results in death in utero or soon after delivery- affected infants
have characteristic features- called Potter face- wide-set eyes, prominent inner
canthi, broad flattened nose, large and low-set ears, and receding chin
- unilateral -more common, it is asymptomatic
-renal hypoplasia - rare, usually unilateral
kidney small in size (less than 50 g in an adult) but of normal structure,
-ectopic kidney - ectopic position of one or both kidneys is not unusual
the most common location is the pelvis, renal ectopia is usually asymptomatic, but
infections are more common
-horseshoe kidney-abnormal fusion of both kidneys, with the lower poles
fused across the midline by broad band of renal tissue,
-relatively common abnormality, most patients are asymptomatic
-two ureters, which may be narrowed- higher incidence of urinary infections
-renal dysgenesis- renal dysplasia
-dysplasia refers to dysgenesis, to abnormal development, may be total or
segmental, characterized by the presence of multiple cysts,
- depending upon the severity of dysgenesis, renal failure may develop
CYSTIC DISEASES OF THE KIDNEY
- many causes of multiple cysts within kidneys
-adult polycystic disease
- inherited disorder- accounts for 5-10% cases of chronic renal failure- dialysis
and transplantation
grossly- both kidneys are enlarged, replaced by multicystic mass - cysts involve
both cortex and medulla
microscopically- the cysts are lined by renal epithelium, glomeruli are
progressively destroyed
-patients with adult polycystic disease have increased tendency to infections
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-many patients have also cyst in the liver, pancreas, spleen etc.
-infantile polycystic disease
-is a rare autosomal recessive disorder that manifests by severe renal failure in
infancy
microscopically- no normal renal parenchyma, kidney is replaced by multiple small
merging cysts lined by renal epithelium
-many patients have associated bile duct dilatations (microhamartomas) or
congenital hepatic fibrosis
-medullary cystic disease
-affects medulla selectively-two distinctive diseases
-medullary sponge kidney- relatively common, may be unilateral or bilateral,
presents in older patients- 40-60 years-usually asymptomatic
-increased frequency of urinary stones
-uremic medullary cystic disease- is a rare disease of children- characterized by
presence of multiple cysts in the medulla, cortical atrophy, interstitial fibrosis
-chronic renal failure progresses to death at about 5-10 years of age
-simple renal cysts
-are very common, they may be multiple and large, they are of no clinical
significance
TUBULOINTERSTITIAL DISEASES.
- group of diseases characterized by primary abnormalities in the renal tubules
or/and interstitium
-morphologic changes in tubulointerstitial diseases include:
-acute tubular necrosis- results in acute renal failure
-atrophy of tubules with fibrosis of interstitium, associated with loss of
glomerular function-results in chronic renal failure
-interstitial inflammation - either acute with numerous leukocytes (acute
interstitial nephritis) or chronic- with lymphocytes, plasma cells and
macrophages- (chronic interstitial nephritis)
-tubular basement membrane thickening- in DM, systemic amyloidosis, renal
transplant rejection
-deposits of abnormal substances, such as amyloid, myeloma protein,
calcium, etc.
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INFECTIOUS DISEASES
1. Acute pyelonephritis -is bacterial infection, ascending from the lower urinary
tract- occurs at all ages
-etiologic factors include -stasis of urine from any cause
-structural abnormalities in the urinary tract associated either with
obstruction or abnormal communication between the urinary tract and intestine,
skin or vagina
-vesicoureteral reflux of urine -half of cases of acute pyelonephritis in
infants and children are associated with reflux
-cathetrization of the bladder- often associated with ascending infection
-diabetes mellitus
pathology:
grossly: acute pyelonephritis may be unilateral or bilateral
-kidney is enlarged-shows areas of suppuration in the cortex-multiple small yellow
foci and the renal pelvis is erythematous, frequently is covered by exudate
-perinephritic abscess- is an extension of suppurative inflammation into the
perirenal soft tissue
microscopically: acute suppurative inflammation- hyperemia and leukocytic
infiltration- abscess formation, liquefactive necroses of the tubules with
suppuration- involvement is typically patchy
clinically: onset is with high fever, chills, pain and dysuria
-the urine shows proteinuria with neutrophils, bacterias in sediment- treatment
with antibiotics is effective -prognosis is excellent
complications:
-gram-negative bacterial sepsis with shock
-renal papillary necrosis-extreme suppurative inflammation of the renal papillaepatients with diabetes mellitus
-emphysematous pyelonephritis - acute inflammation characterized by anaerobic
bacterial fermentation with gas formation in renal parenchyma-occurs rarely in
diabetic patients
2. Chronic pyelonephritis
chronic pyelonephritis may be associated with several different etiologic factors,
such as
1. chronic obstructive pyelonephritis
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-is common, at all ages, obstruction may be mechanical-calculi, tumors, congenital
malformations, retroperitoneal fibrosis, prostatic hyperplasia
or paralytic- neuropathic bladder
2. chronic pyelonephritis associated with vesico-ureteral reflux
approximately 50% of children with V-U reflux develop chronic
pyelonephritis-surgery can prevent development of chronic renal infections
pathology:
-grossly the kidney in chronic pyelonephritis show asymmetric involvement with
fibrosis and scarring, hydronephrosis and suppuration may be present, larger
scars and asymmetry of involvement distinguish from chronic glomerulonephritis
-microscopically -marked patchy inflammation and fibrosis of the interstitial
tissue -plasma cells and lymphocytes, with scattered neutrophils, atrophy of
tubules with hyaline change of glomeruli, thyroidization - dilated tubuli filled with
hyaline casts superficially resemble thyroid follicles
-xantogranulomatous pyelonephritis- inflammatory infiltrate composed of
lymphocytes, plasma cell and numerous lipid-laden foamy histiocytes
clinically- presents with hypertension or chronic renal failure
TOXIC AND METABOLIC NEPHROPATHIES
1. Analgesic nephropathy
-abuse of analgetic may be complicated by chronic nephropathy
pathologically-necrosis of the apices of the renal papillae, called renal papillary
necrosis
-interstitial medullary fibrosis, calcification
clinically-hematuria, progressive renal failure, hypertension
2. Drug-induced nephrotoxicity
-several drugs can cause acute interstitial nephritis- sulfonamides, diuretics,
penicilin derivates, etc.
pathologically- tubular regressive changes and necrosis, inflammatory infiltration
(lymphocytes, plasma cells, eosinophils)
clinically, patients develop renal symptoms about 2 weeks after administrations of
the drugs-fever, hematuria, proteinuria, acute renal failure
3. Urate nephropathy - gout
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-acute urate nephropathy- urate crystals deposited in the tubules-may
cause acute obstruction
-chronic urate nephropathy-occurs in protracted hyperurikemia- chronic
inflammatory cells and fibrosis in the interstitium
4. Myeloma kidney
-in multiple myeloma- may result in chronic interstitial disease
pathology- deposits of light chains of IgG = Bence-Jones protein in the distal
convoluted and collecting ducts - homogenous eosinophilic casts- blockage of renal
tubules -in some cases results in renal failure
- interstitial granulomatous inflammatory reaction
GLOMERULAR DISEASES
=this group of diseases is characterized by primary disorder of glomerulus morphologically (edema, inflammatory infiltration, cellular proliferation,
basement mebrane thickening) and functionally (increased permeability of
glomerular membranes resulting in proteinuria)
glomerular diseases- are acute and chronic
pathological changes in glomerular diseases:
-focal- some glomeruli are involved
-diffuse-all glomeruli are involved
-segmental glomerular involvement- only a portion of individual glomerulus is
affected
-global change- involves the whole glomerulus
1.-proliferation of cells in the glomeruliendothelial cel proliferation-may cause obliteration of capillaries,
mesangial cell proliferation- is recognized as increased
number of nuclei in central part of glomerular lobule,
epithelial cell proliferation-if excessive it leads to formation of
crescents- these are crescent-shaped masses composed of cellular and
collagenous tissue that obliterates the Bowman space
2.-infiltration of glomeruli by inflammatory cells-neutrophilic, lymphocytes,
macrophages-glomerular hypercellularity, fluid exudation and edema in acute
glomerulonephritis
3.-capillary basement membrane thickening-increased amounts of BM
material -thickening of BMs is associated with depositions of immune complexes,
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immunoglobulins and complement components in glomerular BMs-typically causes
an increase of the permeability to proteins leading to nephrotic syndrome
-such deposits may be subepithelial, intramembranous, and subendothelial
4.-increase in amount of mesangial matrix material-caused by depositions
of immunoglobulins and in mesangial matrix
5. -epithelial foot process fusion- nonspecific feature that is believed to
result from lekage of proteins from glomerular capillaries
6.-fibrosis- can affect a portion of glomerulus (mesangium or Bowmans
capsule) or an entire glomerulus- global sclerosis may follow all the above
mentioned changes
Pathogenesis of glomerular diseases:
most cases of glomerular disease are caused by one of two major mechanisms:
1- immune complex disease-is the most common cause of glomerular injury
-immune complexes are deposited
mesangium-IgG deposits are patchy
in
basement
membranes
or
in the
2-anti-glomerular basement membrane antibody -linear deposits of IgG
and complement (antibodies against BM-associated antigens) in glomerular
basement mebranes
CLASSIFICATION OF GLOMERULAR DISEASES:
1.-minimal change glomerular disease
-occurs more commonly in children, rare in adults
-associated with different allergic diseases- suggests a possibility of humoral
immune mechanism
-light microscopy does not show any changes, elmi- fusion of foot processes of
epithelial cell
clinically-one of the most common causes of nephrotic syndrome in the youngproteinuria
-corticosteroid therapy
2. -postinfectious (poststreptococcal) glomerulonephritis
-acute diffuse glomerulonephritis
-is one of the most common renal diseases in childhood, rare in adults
-in most cases- infection by group A-beta-hemolytic streptoccocus of the skin or
throat:1-3 week after infection glomerular disease develops,
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-organisms other than streptococci may also cause glomerulonephritisStaphylococcus aureus, pneumococcus, meningococcus, and even viruses were
shown to associate with acute glomerulonephritis
-immune complexes composed of antigens of infective agents and host antibodies
are deposited in BMs of glomeruli, fix the complement and lead to inflammation
pathology:
-grossly- the kidney is enlarged, smooth surface, scattered petechial
hemorrhages
-microscopy-glomeruli are enlarged, edematous and hypercellular- the increased
cellularity is due to mesothelial and endothelial cell proliferation and to
inflammatory infiltration, epithelial cell proliferation-formation of crescents may
be present in some glomeruli
-rapidly progressive renal failure- if formation of crescents is excessive
clinically-the patients with postinfective glomerulonephritis usually present with
acute onset of renal symptoms, such as hypertension, proteinuria and elevated
serum urea and creatinine
-short term prognosis is good- most patients return to norma renal functions- in
some cases progression to renal failure
3. - crescentic
glomerulonephritis
glomerulonephritis-
rapidly
progressive
subacute
is a rare disease defined by the presence of epithelial crescents in more than 80%
of glomerulicrescents appear in severe glomerular damage- caused by epithelial cell
proliferation in Bowmans spaces
pathogenetically- unclear, only in some patients- the anti-BM antibodies are found
-prognosis is poor
4. -anti-glomerular basement membrane disease
=Goodpasture
hemorrhage
syndrome-
proliferative
glomerulonephritis
with
pulmonary
-is rare disease, it occurs in young adults, males are more often affected
- serum contains antibodies of IgG type to glomerular basement membranesthese antibodies bind both to BM antigens of lungs and kidneys
pathology- initially- focal proliferative glomerulonephritis, later diffuse
glomerular involvement- necrosis and epithelial crescent formation- sclerosis
becomes prominent in later stages
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-IgG and complement depositions in linear fashion
-the lungs show extensive alveolar damage-alveolar hemorrhages
clinically-Goodpasture syndrome presents with hematuria, proteinuria and
progressive renal failure, patients have recurrent hemoptysis, dyspnea cough,
-chronic blood loss in the urine and lungs results in severe iron deficiency anemia
-prognosis is poor
5. -IgA Nephropathy-Bergers
glomerulonephritis)
disease
(mesangial
proliferative
-accounts for 2-5% of all cases of primary glomerulonephritis
-is most common in the age group from 10 to 30 years of age
pathology: on light microscopy-mesangial hypercellularity and increased mesangial
matrix due to heavy IgA depositions
clinically: the patients present with hematuria and proteinuria
-the progression of disease is slow, but the ultimate prognosis is poor- chronic
renal failure within 5-6 years
6. -membranous nephropathy (membranous glomerulonephritis)
-is an important and common cause of nephrotic syndrome in adults, rare in
children
-results from accumulation of circulating immune complexes in the glomerular
capillaries
-most cases are idiopathic
-few cases are associated with systemic infections, such as hepatitis B, malaria,
syphilis or with toxic influences, such as drugs, or with neoplasms, such as Hodgkin
lymphoma, malignant lymphoma, carcinomas etc
pathology- subepithelial electron-dense deposits, epithelial foot process fusion,
later the stage II is characterized by spikes of basement membrane material
protruding outward toward the epithelial side between deposits, finally-basement
membrane thickening is apparent even on light microscopy
clinically, the patients present with proteinuria or with nephrotic syndrome
most patients show slow progression to chronic renal failure, prognosis is better in
children
7. -membranoproliferative glomerulonephritis
-is characterized by the presence of combination of thickening of the capillary
wall and proliferation of mesangial cells
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-most commonly = type I- it is characterized by depositions of subendothelial
immune complexes in the glomerular capilllaries
-most cases are idiopathic
microscopy: diffuse thickening of capillary walls and proliferation of mesangial
cells
-basement membrane appears split-" tram-track appearance"
-relatively common in children and young people
-overall prognosis is poor
-second type is characterized by dense intramembranous deposits on light
microscopy-thickened basement membranes, less prominent mesangial
proliferation ( dense-deposit disease)
-most common in children
-prognosis is poor
8. -focal glomerulosclerosis
-is uncommon disease that affects children, the cause is unknown
pathology- focal segmental hyaline change of glomeruli
clinically- associated with nephrotic syndrome or proteinuria
-prognosis is poor
9. -secondary acquired glomerulonephritis
renal involvement is common manifestation of numerous collagen disorders, such
as systemic lupus erythematodes, scleroderma, polyarteriitis nodosa and
Wegeners granulomatosis
10. -chronic glomerulonephritis
-is common pathologic lesion of kidney that represents end-stage of many
different entities affecting the glomeruli
grossly- the kidneys are greatly reduced in size, they show finely granular
surface- granular contracted kidney
microscopically- great reduction of the number of nephrons, glomeruli show
sclerosis, there is atrophy of tubules and lymphocytic infiltration in the
interstitium -thyroidization
-electron microscopically-variable changes including dense deposits of IgGs
clinically-chronic renal failure, arterial hypertension, microscopic hematuria,
proteinuria and sometimes nephrotic syndrome
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11. -diabetic nephropathy
-ten percent of patients with adult type of diabetes mellitus- show diabetic
nephropathy - even more common in type I-juvenile diabetes
-results from diabetic microangiopathygrossly- kidney shows little abnormality-fine granularity or scarring
light microscopy- focal nodular and diffuse glomerulosclerosis
clinically-proteinuruia, in some cases nephrotic syndrome, renal lesion is
progressive to renal failure
12.-renal amyloidosis
-kidneys are almost always affected in systemic amyloidosis AA type and in about
30% of primary amyloidosis AL type
-amyloid deposits occur in glomerular capillaries, in basement membranes of
tubules and blood vessels
clinically-deposition of amyloid increases the permeability of glomerular
capillary-nephrotic syndrome
-amyloidosis is progressive disease- renal failure is common cause of death in
systemic amyloidosis
VASCULAR DISEASES
1. Benign nephrosclerosis
-common finding, often asymptomatic
- occurs in most patients with essential hypertension
- similar changes seen in elderly patients with advanced arteriosclerosis
pathology: grossly- bilateral symmetric reduction in size
-renal surface has a fine granularity- uniform thinning of the renal cortex
histologically- hyaline thickening of the walls of small arteries, global sclerosis of
glomeruli, atrophy with interstitial fibrosis
-renal failure does not occur
2. Malignant nephrosclerosis
occurs with malignant hypertension
-kidneys are normal in size- smooth surface with numerous petechial hemorrhages
-histologically: numerous fibrinoid necroses of arterioles and glomerular
capillaries
clinically it manifests by proteinuria, hematuria followed by acute renal failure
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treatment: antihypertensive therapy
3. Renal artery stenosis
causes: atherosclerosis- most common, fibromuscular dysplasia-rare condition of
unknown cause
pathogenesis -narrowing of the renal artery- results in diffuse ischemia of the
kidney-increased renin secretion by the juxtaglomerular apparatus-aldosteron
secretion-sodium retention-hypertension (Goldblatt type- renal hypertension)
treatment- surgical removal of the stenotic segment, prognosis- dependent on the
duration of the disease
NEOPLASMS OF THE KIDNEY
BENIGN TUMORS
1. -renal cortical adenoma
-common benign tumor derived tubular epithelium, incidental finding at autopsy,
occurs in about 20% of adult kidneys
-grossly-well circumscribed yellowish nodule in the cortex
-microscopically-solid or papillary tumor without cytologic polymorphism
2. -renal oncocytoma
-is a special type of renal cortical adenoma composed of oncocytes-uniform
eosinophilic cells with abundant pink granular cytoplasm
grossly- distinction from renal cell carcinoma may be difficult, homogenous brown
colour without necroses or hemorrhages, central stellate scar is often present
3. -angiomyolipoma
-is rare renal tumour composed of an intimate mixture of fat, blood vessels, and
smooth muscle.
Grossly: this tumor may show striking resemblance to malignant renal cell
carcinoma, because of its yellow colour, intratumoral hemorhages and frequent
extrarenal growth
-May occurs as solitary or multiple- multiple tumors are found in about one
third of cases (component of tuberous sclerosis- cutaneous and brain
mesenchymal tumors)
prognosis: benign tumor, sometimes may cause massive bleeding, capsular invasion
may be present, occassionally- recurrences, but no reports of distant metastases
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MALIGNANT TUMORS
1. -Renal cell carcinoma (clear cell carcinoma)- Grawitz tumor
-is the most common malignant tumour of the kidney- accounts for 1-2% of all
cancers in adults
-occurs most frequently in the 6th-7th decades
pathology- renal cell carcinoma varies in size-grossly: it is solid, cystic
hemorrhagic, partly necrotic
-cut surface may be hemorrhagic, yellowish in colour, with focal necroses, and
calcifications
-infiltrative growth pattern, invasion of the renal veins is a characteristic feature
- tumor may extend via blood vessels into cava vein and to the right heart atrium
and the ventricle
microscopically- composed of mixture of clear cells with water-clear empty
looking cytoplasm (content of glycogen and fat), and pink cells with oncocytic
features
-in well-differentiated tumors- solid, tubular and papillary structures
-in less well-differentiated carcinomas, tumor cell are large, more
polymorphic, wwith high mitotic rate, necroses and hemorrhages
clinically- hematuria, palpable renal mass, early metastases- lungs, bone marrow,
brain, liver
-extension to renal vein and the inferior vena cava-edema of the lower extremity
-treatment and prognosis- surgical removal- prognosis correlates with the
stage-unpredictable clinical behavior
2. -nephroblastoma- Wilms tumor
-constitues about 25 to 30% of malignant tumors in childhood
-second most common tumor in childhood (first are lymphomas and
leukemias)
-arises from primitive blastema cells that may persist in the outer part of kidney
-all bilateral and about 30 % of unilateral cases are hereditary-homozygous
recessive genes responsible- chromosomal abnormalities- deletion of part of the
short arm of chromosome 11
pathology- grossly- large firm tumour, sometimes undergoes a cystic change
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microscopically- composed of small round and spindle-shaped primitive tumour
cells with large polymorphic basophilic nuclei and scant cytoplasm, anaplasia,
mitoses, necroses are common
clinically- most patients present with large mass, treatment is a combination of
surgery and chemotherapy and radiation
-5-year survival is higher than 50 %
PATHOLOGY OF URINARY TRACT
1. Urolithiasis-common clinical problem, occurs in about 1-2 % of population, more often in men,
most of the patients are elderly
-urinary calculi may be formed at any site of the urinary tract, most commonly in
the urinary bladder and renal pelvis
clinically- calculi typically present with acute ureteral obstruction- ureteral colic,
and hematuria- due to mucosal trauma
-urinary tract obstruction- occurs when the stone becomes impacted in the
ureter- hydronephrosis, urinary stasis, urinary tract infection, and acute
pyelonephritis commonly follow
treatment- removal of the stones by cystosomy, mechanical cysto-lithotripsy
2. Idiopathic hydronephrosis
-represents a functional obstruction at the ureteropelvic junction leading to
massive hydronephrosis
-there is no mechanical obstruction- it has been suggested tha congenital
abnormalities of innervation or arrangement of muscle fibers result in failure of
peristalsis at the ureteropelvic junction
3. Urothelial tumors-transitional cell carcinoma
-urothelial neoplasms may occur through the whole urinary tract, but fairly
common- in urinary bladder
bladder cancer- up to 2 % of cancer-related deaths
- bladder tumors are more common in industrial countries
-positive correlation with cigarette-smoking habits, men are affected more
often than women, more common in older patients-over 50 years of age
pathology- well-differentiated tumors- grossly reveal papillary configuration,
poorly differentiated- usually ulcerated solid lesions with diffuse infiltration of
the bladder wall and adjacent tissues
histologically-most are transitional cell carcinomas- composed of papillary fronds
lined by atypical transitional urothelial cell epithelium
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-grading of urothelial carcinoma-varies histologically from well-differentiated grade I carcinoma to poorly differentiated anaplastic - grade IV-very important
for prognosis
-clinical staging- depends on the degree of invasion by the neoplasm and the
presence of metastases
treatment- the therapy has to be individual- taking into account the age of the
patient, surgical risk, the extent of the tumor, stage, and microscopic gradesurgery- cystectomy, intravesical chemotherapy
prognosis of the bladder carcinoma is related to many parameters, such as
clinical stage- by far the most important prognostic indicator
microscopic grade- the recurrence rate for grade I and II following local
excision-about 50%
-age of patients- young in 1st-3rd decades of age- usually excellent
prognosis
-vascular invasion-associated with much higher recurrence rate
-cell proliferation- correlates with the grade
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