Pathology 5.

01B
School of Medicine
P a th o lo g y o f th e U rin a ry T ra c t (H a n d o u t)
Batch 2023
January 21, 2021
KIDNEY STRUCTURE AND FUNCTION INTERDEPENDENT (Robbins)
 A structurally complex organ wherein every cell is highly  Damage to one usually secondarily affects the others
specialized in maintaining essential body functions for human  Whatever the origin, all forms of chronic kidney disease ultimately
survival since its embryonic development. damage all 4 components → end-stage kidneys

MAINTENANCE OF HOMEOSTASIS 2 TYPES OF NEPHRONS

1. Waste products elimination Superficial glomeruli located near the cortical surface and
2. Fluid volume and electrolyte balance regulation Nephrons short loops of Henle
 (Robbins) Precisely regulates the body’s concentration of: Juxtamedullary glomeruli located near the cortico-medullary
 Water Nephrons junction and long loops of Henle descending
 Salt
 Calcium deeper into the renal medulla
 Phosphorus
 Other anions and cations GLOMERULUS
3. Acid-base balance control  Responsible for filtration of urine retaining proteins and other
4. Hormone production large molecules in the blood
Serves as an endocrine organ  Complex tuft of capillaries contained within the Bowman’s space
Prostaglandin influences vascular tone and affects salt and  Capillary wall serves as the filtration barrier and composed of:
water regulation Endothelial fenestrated allowing the plasma direct contact with the
Erythropoietin stimulates RBC production cells underlying basement membrane
Renin increases vascular tone (thru the angiotensin confers size selectivity through fenestrae with
pathway) and aldosterone diameters between 70 to 100 nm.
production. Plays a role in the charge-dependent filtration
 Each kidney consists of approximately 1 million nephrons Synthesize, release, and bind coagulation factors
Convert more than 1700L of blood per day into about 1L of a highly concentrated fluid Participate in antigen presentation by expressing Class
called urine. (Robbins)
II MHC
 Urine formation begins in the glomeruli
 Filters about 800 liters of plasma daily resulting in 180
Basement composed of a network of Type IV collagen fibrils to
liters of filtrates, most reabsorbed in tubules.
membrane which other glycoproteins are attached
 Kidneys receive 20 to 25% of the cardiac output
 Approximately 1,200 ml/min of renal blood flow. Layer confers charge selectivity to the filtered particles.
Podocytes – visceral epithelium of specialized cells that
NEPHRON STRUCTURE AND FUNCTION lines the glomerular basement membrane and forms
 Basic unit composed of a glomerulus connected to a tubule the outermost layer of the filtration barrier
 Renal pathologies can be categorized depending on the affected a) Possess foot processes enveloping the
segment of the nephron. capillary loops forming a slit diaphragm
through interdigitating long and thin foot
processes and sustaining integrity of the
capillary loops
b) Largely responsible for the synthesize of
basement membrane
c) Important in the charge-dependent
filtration.
Mesangial cells
a) supports the capillary tuft
b) can contract, phagocytose, proliferate and
lay down both matrix and collagen
c) secretes several mediators

FILTRATION BARRIER

achieved Charge-dependent – normally retaining proteins in the

thru: plasma due to:
1) Polyanionic glycoprotein in the cell membranes of
4 BASIC MORPHOLOGICAL COMPONENTS (Robbins) the endothelial and epithelial cells
GLOMERULUS Most glomerular diseases are immunologically mediated 2) Polyanionic proteoglycans in the glomerular
TUBULES Tubular and interstitial disorders - frequently caused by basement membrane
INTERSTITIUM toxic or infectious agents Size-dependent due to:
BLOOD VESSELS Primary d/o of the blood vessels affect all structures 1) Network of collagen IV in basement membrane
supplied by these vessels. 2) Slit diaphragm of epithelial cells.

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 BLOOD CIRCULATION d) Descending limb permeable to water and small solutes while the
 Glomerular capillaries flanked by two resistance vessels ascending limb impervious to water but permeable to solutes.
1) afferent arterioles
2) efferent arterioles JUXTAGLOMERULAR APPARATUS (JGA)
 Regulates intraglomerular pressure thus maintaining a high  Located near the glomerular vascular pole; regulates glomerular
pressure in the glomerular capillaries despite a fall in filtration rate through the tubulo-glomerular feedback
pressure towards the venous end.  Composed of the macula densa cells of the cortical
ascending limb and the granular smooth muscle cells of the
JUXTAGLOMERULAR APPARATUS afferent arteriole of the glomerulus
 Cluster of specialized cells at the vascular pole of the glomerulus  Functionally and structurally connected by glomerular
 Secrete renin acting as a precursor molecule to form angiotensin mesangial cells.
II and secreted in response to:
a) Reduced blood volume DISTAL CONVOLUTED TUBULES (DCT)
b) Low sodium concentration in the distal tubular fluid  DCT comprises the nephron segment between the macula densa
c) Sympathetic stimulation and the cortical collecting tubule (CCT)
d) Renal ischemia  Arises from the ascending limb and gets transformed as
the DCT after returning to the renal cortex near its
TUBULES STRUCTURE AND FUNCTION glomerulus of origin
 Ultrafiltrate from the glomeruli flow into the Bowman’s spaces  Consists of tall cells containing the largest number of
then into the proximal convoluted tubules mitochondria among the other segments of the nephron
 Responsible for fine-tuning the urine
PROXIMAL CONVOLUTED TUBULES (PCT)  Contributes 10% in the reabsorption of filtered sodium
 Lined by simple cuboidal epithelium characterized by a brush and chloride, as well as with K+ secretion.
border of microvilli thus increasing the surface contact of the  Water-impermeable causing further dilution of the urine.
glomerular ultrafiltrate with the abundant long, thin
mitochondria lining the basal pole of the cell and numerous  JGA AND DCT: Plays important role in acid-base balance
vesicles  Macula densa – specialized arrangement of closely packed
a) Involved in transcellular transport of 60 to 80% of the cells; final adjustment to the sodium concentration made
ultrafiltrate from the tubular lumen into the blood of the  Sodium exchanged for potassium and hydrogen ions under
peritubular capillaries the influence of aldosterone
b) Dedicated to the absorption and transport of water, electrolytes,  De-aminate amino acids producing ammonia and
and other particles combining with hydrogen ions producing ammonium salts
c) Vulnerable to injury caused by ischemia or toxins due to its high
metabolic activity. CONNECTING AND COLLECTING TUBULES
d) Peritubular capillaries surround the PCT  Last part of the nephron where fine-tuning of the urine occurs
 Responsible for the blood supply of the tubules and the  Receives modified filtrate from the distal convoluted
recovery of the reabsorbed free water, ions, and other tubules and pass thru the medulla
plasma constituents like amino acids and glucose  Epithelial cells selectively permeable to water under the
e) Only 1.5 to 2 L of urine is excreted from the 160 to 180 L of influence of antiduretic hormone
ultrafiltrate produced per day  Regulate hydrogen and bicarbonate secretion
 Reabsorption of 60 to 65% of free water and NaCl occurs in  Filtrate passing thru the hypertonic medulla allows water
the PCT to be osmotically reabsorbed under the influence of
 Most of the potassium, phosphate, HCO3, and nearly all antidiuretic hormone released from the pituitary.
nutrients, such as glucose and amino acids reabsorbed in
this segment. CONGENITAL DISEASES
 Also responsible for active solute secretion, hormone  Congenital anomalies of the kidney and urinary tract include a
production, and renal gluconeogenesis. wide spectrum of anomalies, with a reported incidence of up to
f) Solute and water reabsorption is isotonic with minimal change in 2% of births.
luminal osmolarity.  Genetics play a major role in the etiology
 family history identified in 10%-50% of affected
LOOP OF HENLE children
 Causes the development of high osmotic pressure within the Bilateral Failure of ureteric bud to develop; incompatible with
medulla thru the process of countercurrent system. agenesis life
a) Descending loop – extension of the PCT as it penetrates the a) Occurs in 0.04% of pregnancies
renal medulla b) Associated with severe reduction of amniotic fluid
 Tubule becomes narrower and the cells become smaller (oligohydramnios) caused by absence of fetal urine
with fewer mitochondria and shorter microvilli. c) Majority of cases are stillborn
b) Tubule then makes a turn upward towards into the cortex d) Associated with other developmental anomalies.
becoming the thick ascending limb. Unilateral Affects up to 0.1% of the population
 Lining cells become larger with more numerous microvilli agenesis a) Opposite kidney markedly hypertrophied
and mitochondria to engage in the active transport of b) Children do not survive long due to associated
sodium to dilute the urine congenital anomalies.
c) Reabsorption of 30 to 40% of sodium occurs in this segment with Hypoplasia Abnormally small kidneys; prone to infections and
important changes in urine osmolarity. stone formation.

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Multicystic Most common cause of a congenital solitary kidney
dysplastic a) May be unilateral (most common cause of solitary
kidney) or bilateral
b) Associated with abnormalities of the lower urinary
tract
c) Kidneys enlarged and multicystic
d) Characterized by islands of undifferentiated
mesenchyme or cartilage within therenal parenchyma.
Ectopic Abnormal location usually in the pelvis; may be
kidneys associated with malrotation of intestines
Horseshoe Due to fusion of the two nephrogenic blastemas during
kidney fetal life; usually fused at the lower pole; renal function
usually normal.
CYSTIC DISEASE
 Heterogeneous group of conditions
 May be congenital or acquired
 Some may cause renal failure
SIMPLE RENAL CYST
 Smooth inner lining containing clear fluid
 Common finding increases with age
 Single or multiple and of varying sizes from few millimeters
to several centimeters
 Renal function not affected
AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE
 Always bilateral
1) Kidneys enlarged usually weighing 1 kilo or more; distorted by
many cysts with thin bands of renal tissue in-between the cysts
2) Renal function usually maintained until the enlarging cysts
compress the adjacent parenchyma causing ischemia to
hypertension to renal failure.
3) May be associated with berry aneurysm of the circle of Willis.
AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY DISEASE
– several subgroups depending on degree of renal involvement
Perinatal 10% of patients; 90% of nephrons involved
Kidneys enlarged; cortex and medulla replaced
by cysts extending to the capsular surface
Neonatal, infantile Less involvement with longer survival
and juvenile Associated with liver abnormalities i.e., bile duct
proliferation and cysts to hepatic fibrosis.
ACUTE RENAL FAILURE
 Characterized by sudden loss of the kidneys’ ability to excrete
wastes, concentrate urine, conserve electrolytes, and maintain
fluid balance
 Caused by acute kidney injury (AKI) that abruptly or rapidly
causes a decline in renal filtration function
 Majority of nephrons suddenly ceases to function.
 AKI may be classified as follows:
Prerenal Usually an adaptive response to severe volume depletion
and hypotension with structurally intact nephrons
Represents the most common form of kidney injury
Intrinsic In response to cytotoxic, ischemic, or inflammatory insults
to the kidney with structural and functional damage
Structural injury in the kidney is the hallmark
Postrenal Commonly due to mechanical obstruction of the urinary
collecting system
a) Renal pelvis
b) Ureters
c) Bladder
d) Urethra
TRANSCRIBED BY: PEREZ, RAZEL NEFERTTI G.
Clinically characterized by:
1 Fluid and electrolyte imbalance
2 Hyperkalemia
3 Metabolic acidosis
4 Elevation of urea (retention of nitrogen) and creatinine.
 Often reversible when cause is immediately removed; if damage,
recovery may not occur.
ETIOPATHOGENESIS
Central perfusion Leads to inadequate perfusion of kidneys
failure Epithelial cells of proximal and distal
convoluted tubules are most sensitive
component of the nephron to poor
perfusion leading to acute tubular necrosis;
(e.g., hypovolemic shock, heart failure).
Glomerular disease Damage to majority of glomeruli causing
occlusion of glomerular capillaries thus
preventing blood flow into the efferent
arterioles and adequate perfusion of the
peritubular capillaries, (e.g., immune
mediated glomerulopathies)
Tubular and interstitial Caused by hypoxia, toxic or infectious
disease injury.
PATHOLOGY
– frank necrosis is not prominent in most human cases of acute
tubular necrosis and tends to be patchy; characterized by:
1 Loss of brush borders
2 Flattening of the epithelium
3 Detachment and excretion of cells in the urine
4 Formation of intratubular casts
5 Dilatation of the lumen.
 Pathologic changes observed predominantly in proximal tubules,
although injury to the distal nephron can occur
 Distal nephron may become obstructed by desquamated cells
and cellular debris.
CHRONIC RENAL FAILURE
– term encompassing all degrees of decreased kidney function from
mild, moderate, and severe failure.
 Caused by progressive destruction of nephrons over a prolonged
period progressively impairing renal function; in contrast to
acute renal failure opportunity for metabolic compensation can
occur
 Associated with an increased risk of cardiovascular disease and
end-stage renal disease
PATHOPHYSIOLOGIC EFFECTS
1. Normal kidney contains approximately 1 million nephrons, each
of which contributes to the total glomerular filtration rate
2. In the face of renal injury (regardless of the etiology), the kidney
has an innate ability to maintain GFR, despite progressive
destruction of nephrons, as the remaining healthy nephrons
manifest hyperfiltration and compensatory hypertrophy.
3. Nephron adaptability allows for continued normal clearance of
plasma solutes.
 Plasma levels of substances (e.g., urea and creatinine) start
to show measurable increases only after total GFR has
decreased 50%.
 With a 50% reduction in GFR plasma creatinine value
approximately double.
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4. Hyperfiltration and hypertrophy of residual nephrons, although
initially beneficial has been hypothesized to represent a major
cause of progressive renal dysfunction.
 Increased glomerular capillary pressure may damage the
capillaries, leading progressively to glomerulosclerosis.
CLINICAL MANIFESTATIONS
1 HYPERKALEMIA
– ability to maintain potassium excretion at near-normal levels
generally maintained in chronic kidney disease if aldosterone secretion
and distal blood flow to the nephron are maintained.
 Another defense against potassium retention in patients with
chronic kidney disease (CKD) is increased potassium excretion in
the gastrointestinal tract which is also regulated by aldosterone.
2 METABOLIC ACIDOSIS
– mixture of normal anion gap and increased anion gap; the latter
is observed generally with stage 5 (severe chronic renal failure)
chronic kidney disease but with the anion gap generally not higher
than 20 mEq/L.
 In CKD, the kidneys are unable to produce enough ammonia in
the proximal tubules to excrete the endogenous acid into the
urine in the form of ammonium.
 In stage 5 CKD, accumulation of phosphates, sulfates, and other
organic anions are the cause of the increase in anion gap.
 Anion gap – difference between primary measured cations
(sodium Na+ and potassium K+) and the primary measured
anions (chloride Cland bicarbonate HCO3- ) in the blood serum
 Causes deleterious effects on protein balance. (e.g., negative
nitrogen balance, increased protein degradation, increased
essential amino acid oxidation.
3 ALTERED SALT AND WATER HANDLING
– extracellular volume expansion and total-body volume overload
results from failure of sodium and free-water excretion.
 Lead to peripheral edema and, not uncommonly, pulmonary
edema and hypertension
 Sodium and fluid retention lead to hypertension
4 ANEMIA
 Normochromic normocytic anemia develops from decreased
renal synthesis of erythropoietin responsible for bone marrow
stimulation for red blood cell production.
 Anemia starts early during the disease becoming more
severe as viable renal mass and GFR progressively
decreases.
Erythropoietin Glycoprotein cytokine produced by the interstitial
fibroblasts closely association with the peritubular
capillary and proximal convoluted tubule
Also produced by the hepatic perisinusoidal cells.
5 UREMIA
– clinical syndrome marked by elevated concentrations of urea in the
blood and associated with fluid, electrolyte, and hormone imbalances
and metabolic abnormalities
 Literally means urine in the blood; first used by Piorry to
describe the clinical condition associated with renal failure
 Commonly develops in the later stages of CKD; may occur
with acute kidney injury (AKI) if loss of renal function is
rapid.
 Causes direct and indirect toxic effects on tissues that may
cause seizure, coma, cardiac arrest, spontaneous bleeding
and death. can occur with severe uremia and may include
gastrointestinal (GI) bleeding.
TRANSCRIBED BY: PEREZ, RAZEL NEFERTTI G.
GLOMERULAR DISEASES
– many different criteria exist for classifying glomerular diseases,
including those within the broad term of glomerulonephritis.
GLOMERULONEPHRITIS
– nominally indicates an inflammation of glomeruli.
 Not all the glomerular diseases necessarily show an
inflammatory component at histologic examination.
 Term used to broadly characterize kidney diseases that occur as
a result of immunologic and inflammatory injury to the glomeruli.
 Term GN used by some investigators to indicate all the diseases
that mainly affect the glomeruli of both kidneys.
 Although the terms GN and glomerulopathy are interchangeable,
GN frequently used more from a traditional and historical
perspective, rather than for accuracy.
ETIOLOGY
Most classification based on possible etiology and subdivided into:
1 Primary
caused by factors intrinsic to the kidney
2 Secondary
associated with systemic diseases (e.g., diabetes mellitus, systemic
autoimmune diseases).
MECHANISMS OF GLOMERULAR INJURY
– usually mediated by the actions of both the innate and adaptive
immune systems or non-immunologic mechanisms, resulting in
diverse clinical and pathologic manifestations.
IMMUNE GLOMERULAR INJURY
– most common cause of glomerular injury
Two mechanisms:
1 Nephrotoxic antibodies
– anti-GBM disease occurs when IgG antibodies against an
antigenic glycoprotein within the GBM are formed
 Uncommon cause of glomerulonephritis (e.g., Goodpasture’s
syndrome)
2 Immune complex deposition
– immune complexes cleared by kidney;
glomeruli vulnerable to the deposition of immune complexes due to
large amount of blood filtered by kidney; deposition may occur thru:
 Passive entrapment leading to mesangial and subendothelial
deposits
 Binding to a native component of the glomerular wall leading to
subepithelial deposits by in-situ formation
 Binding to non-glomerular antigen previously planted and
subsequent in-situ formation; planted antigen involves an
extrinsic antigen non-immunologically bound to the BM.
ROLE OF COMPLEMENT
– immune complexes normally eliminated by glomeruli and
systematically by attaching to circulating RBCs and other cells by a
receptor for C3b (complement receptor) which are further modified
and eliminated by the monocyte- macrophage system
 Patients with complement deficiencies tend to develop
glomerulonephritis.
CELL-MEDIATED GLOMERULAR DAMAGE
– sensitized T-cells can cause glomerular damage and involved in the
progression of some glomerulonephritis initiated by antibody-
mediated mechanisms.
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 ROLE OF GLOMERULAR CELLS IN GLOMERULAR DAMAGE 3 Hyalinosis and sclerosis
– indigenous glomerular cells produce a variety of inflammatory – may obliterate the glomerular capillary lumina; end result of
cytokines some of which may: different types of glomerular injury
1. Stimulate the production of extracellular matrix material  Hyaline accumulation of homogenous and eosinophilic material
2. Inhibition of mesangial proteases impairing remodeling of excess into the glomerular structure; when extensive may obliterate the
ECM and contributing to glomerulosclerosis. glomerular capillary lumina; result ofdifferent types of
glomerular injury
MEDIATORS OF GLOMERULAR DAMAGE  Sclerosis – deposition of extracellular collagenous matrix;
– localization of immune complexes within the GBM activate the may be confined to the mesangium.
complement cascade and the release of vasoactive substances which
are mediators of acute inflammation; inflammation damages the BM PRIMARY GLOMERULAR DISEASES
and alters its properties; not all mediators involved in every case. – group of disorders characterized by pathologic alterations in the
Complement – plays a major role in the inflammatory process glomerular structure and function, independent of systemic disease
 Classical pathway activated by immune complex and fixed within processes.
the glomeruli  Caused by disorders of the adaptive immunity triggered by the
 Attracts the neutrophils, increases vascular permeability, and activation of the innate immunity with consequent production of
damages BM. an inflammatory microenvironment.
 Frequently used contemporary classification of glomerular
NEPHRITIC FACTORS diseases is a pathological one, mainly based on the results of
– immunoglobulin binding and inactivating inhibitors of the converting optical microscopy, supplemented by immunofluorescence and
enzymes of the complement cascade electron microscopy.
 Consequently, the breakdown of C3 continues unchecked  An etiopathogenetic classification based on current knowledge:
resulting in depletion of C3 from the plasma. 1) Acute post-infectious glomerulonephritis
2) Anti-glomerular basement membrane glomerulopathy
POLYMORPHONUCLEAR CELLS 3) Focal segmental glomerulosclerosis
– attracted by C5a; neutrophils bind to the complexes by their C3 4) IgA nephropathy
and Fc receptors 5) Membranous nephropathy’
 However, neutrophils unable to phagocytose the fixed 6) Membrano-proliferative glomerulonephritis
complexes thus releasing their lysosomal enzymes in the vicinity 7) Crescentric glomerulonephritis
of the complexes aggravating damage to the GBM. 8) Monoclonal immunoglobulin GN
9) Minimal change disease.
REACTIVE OXYGEN SPECIES
– derived from recruited leukocytes and native glomerular cells DIFFUSE PROLIFERATIVE GLOMERULONEPHRITIS
1) Enhance degradation of BM – results in a variety of reactions and lesions depend on the nature of
2) Enhance neutrophilic binding by endothelial cells the immune complexes deposited.
3) Promote thrombus formation by influencing arachidonic acid  Usually associated with a post-infective etiology with acute
metabolism. lesion following a transient infection.
 Deposition of immune complexes from antibodies against
CLOTTING FACTORS organisms elicits an acute inflammatory response
– mediate glomerular damage; fibrin found in glomerulonephritis Post-streptococcal – often due to nephritogenic strains of
 Fibrin entraps platelets forming microthrombi, their glomerulonephritis Streptococcus pyogenes
degranulation and release of vasoactive peptides thus increasing  Primary infection usually causes pharyngitis or a middle ear
vascular permeability. or skin infection
 Children more commonly affected 7-14 days after the onset
HISTOPATHOLOGIC FEATURES OF GLOMERULAR INJURY of sore throat
 Clinical manifestations
1 Hypercellularity a. Oliguria
– characterized by increase number of cells in glomerular tuft; may be b. Hematuria
due to increase in the number of: c. facial edema
a. Endothelial or mesangial cells d. mild hypertension
b. Leukocytic infiltration – includes monocytes and  Grossly – kidneys may be enlarged with a “flea-bitten”
neutrophils appearance
c. Crescent formation – due to the proliferation of  Histologically – glomeruli diffusely enlarged and
predominantly parietal cells and leukocytes hypercellular due to neutrophils and macrophages and
 Occurs after immune/inflammatory injury to the capillary wall proliferation of mesangial and endothelial cells.
and the leakage of plasma protein where the coagulation factors  Immunofluorescence – granular deposits of IgG and C3 at
are activated leading to fibrin deposition. the peripheral basement membrane and within the
2 Basement membrane thickening mesangium
may be caused by:  Electron microscopy – electron-dense deposits at the
a. Deposition of immune complex on the endothelial or outer aspect of basement membrane beneath the
epithelial side of or within the BM epithelial cells; referred to as “humps.”
b. Increased synthesis of the protein components of the BM
e.g., diabetes mellitus  Prognosis – good in children; only 60% of adults fully recover.
c. Formation of additional layers of BM.

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 ANTI-GLOMERULAR BASEMENT DISEASE
(GOODPASTURE SYNDROME)
– uncommon aggressive form of autoimmune disorder occurring
predominantly in young men.
 Characterized by the presence of circulating autoantibodies
directed against proteins in the glomerular and alveolar
basement membranes
 Due to an autoimmune response against type IV collagen
 Antibody may cross-react with collagen in the pulmonary
alveolar capillary membrane and cause intra-alveolar
hemorrhage and hemoptysis (Goodpasture syndrome).
 In Goodpasture syndrome, pulmonary hemorrhage
accompanies the glomerulonephritis due to anti-
glomerular basement antibodies cross-reacting on the
alveolar basement membrane.
 Histology – alveolar walls show focal necrosis, septal
fibrous thickening with mild hyperplasia of alveolar lining
cells; linear deposits of immunoglobulin along basement
membrane and hemosiderin laden macrophages.
 In the kidneys, autoantibodies bind with the glomerular
basement membrane that activate the complement cascade and
can lead to rapidly progressive glomerulonephritis
 Causes rapidly progressive renal failure
 Histology – early or mild disease: segmental proliferative
change or fibrinoid change with neutrophilic and
lymphocytic infiltrates (focal or segmental
glomerulonephritis).
 Severe disease – crecentric glomerulonephritis may occur.
 Poor prognosis.
FOCAL SEGMENTAL PROLIFERATIVE GLOMERULOSCLEROSIS
– term used to describe both a disease characterized by primary
podocyte injury, and a lesion that occurs secondarily in any type of
chronic kidney disease leading to obliteration of the capillary lumina
by matrix.
 Heterogeneous disease that may be caused by circulating factors
and various injuries.
 Characterized by endothelial or mesangial cell proliferation
affecting the glomeruli in a focal and segmental pattern
a. Focal implies involvement of some but not all glomeruli
b. Segmental implies involvement of only a portion of the
glomerular tuft.
PATHOGENESIS
– can occur due to many causes (e.g., circulating factors, underlying
mutations in podocyte genes, infections, drug use)
 Inherent injury within or directed to the podocytes resulting in
diffuse foot process fusion and proliferation of the mesangial,
endothelial and epithelial cells then followed by scarring of
glomeruli (glomerulosclerosis).
 Podocyte limited ability to proliferate, and podocyte loss is
tightly linked to development of glomerulosclerosis.
 Proposed mechanisms – viral- or toxin-mediated damage
or intrarenal hemodynamic changes such as glomerular
hyperperfusion and high intraglomerular capillary pressure.
a. May be immunologically mediated and reflects an
overloading of the mesangium’s capacity to clear
immune complexes
b. Complexes not removed from some of the
glomerular tuft accumulate and activate the
complement cascade causing localized inflammation
TRANSCRIBED BY: PEREZ, RAZEL NEFERTTI G.
c. Degeneration and focal disruption of visceral
epithelial cells (podocytes) with effacement of foot
processes.
 Histology – wide range of morphological appearances
often characterized by:
a. Collapse of capillary loops
b. Increase in matrix and segmental deposition of plasma
proteins along the capillary wall
c. Capillary lumina occlusion and segmental sclerosis of the
glomerular tuft.
 Immunofluorescence – IgM and C3 deposits in mesangium
and/or sclerotic segments.
 Prognosis - 25-30% of patients develops end-stage renal
disease by 5 years; 30-40% of these patients by 10 years.
IgA NEPHROPATHY
– most common type of glomerulonephritis worldwide.
 Slowly progressive disease; major cause of chronic renal failure
affecting children and young adults
 Characterized by predominant glomerular mesangial IgA
deposition
 Clinically, episodic hematuria coinciding with upper respiratory
tract infection, proteinuria, nephritic syndrome, hypertension,
raised serum IgA levels
PATHOGENESIS
– may be caused by disturbance in mucosal immunity promoting the
excess production of aberrant form of IgA1 which may be triggered by
viruses or food proteins.
 Histologically, wide spectrum of changes from mild focal
mesangial proliferation (good prognosis) to markedly
hypercellular glomeruli (mesangiocapillary pattern) with
segmental necrosis (poor prognosis)
 Immunofluorescence – IgA and C3 in the mesangium of all
glomeruli
 Usually follows a benign course, although 20-30% develops end-
stage renal disease over a 10-20-year period.
MEMBRANOUS NEPHROPATHY
– a common form of nephrotic syndrome in the adult population
which can either be idiopathic or secondary in 30%
 Chronic immune-complex-mediated disorder with a distinct
histologic pattern
 Renal lesions may subside when cause is removed
 Pathogenesis: uncertain
 Clinically, affects all ages; more common in adult males;
proteinuria or nephrotic syndrome, hypertension
 Prognosis in children better than in adults
 Histologically, immune complexes deposit in the
subepithelial space.
a) Capillary wall thickening with characteristic spikes
seen with silver-impregnation stain
b) No proliferation or inflammation.
 Immunofluorescence – granular deposits of IgG and C3 in
the thickened capillary wall
 Electron microscopy – immune complexes deposited on
the outer aspect of the BM beneath the epithelial cells
 May be caused by:
1) Infections e.g., malaria, hepatitis B
2) Drugs
3) Tumors e.g., lymphomas.
PATHO PAGE 6 OF 12
 MEMBRANO-PROLIFERATIVE GLOMERULONEPHRITIS (MPGN)
– represents a pattern of injury seen by light microscopy caused by a
variety of diseases; not a diagnosis.
 Characterized by cell proliferation and membranous thickening
with accentuation of lobular architecture
PATHOGENESIS
 May occur when there is an increased level of circulating
immune complexes
 May occur due to the dysregulation of the alternative pathway
of complement.
Type I MPGN Mesangiocapillary glomerulonephritis
– immune complex mediated lesion characterized by subendothelial
deposits and reduplication of basement membrane
 Occurs in a variety of diseases
 In most cases, cause is not apparent
 Majority of cases present with nephrotic syndrome
 Low serum C3 (hypocomplementemia) seen in 2/3 of cases.
Type II MPGN
– characterized by markedly thickened capillary walls expanded by
discontinuous linear deposits of C3
 Due to abnormality in the synthesis or degradation of BM
resulting in the activation of complement via the alternative
pathway
 Electron microscopy – large electron dense ribbon-like
deposits.
CRESCENTRIC GLOMERULONEPHRITIS
– also called rapidly progressive glomerulonephritis (RPGN)
 Clinically, manifestation of severe glomerular injury
characterized by a rapid decline in the glomerular filtration rate
(GFR) of at least 50% within a short time period.
 Classified pathologically into 3 categories based on the presence
or absence of antineutrophil cytoplasmic antibodies (ANCA)
Anti-GBM antibody disease Goodpasture syndrome with lung and
(about 3%) kidney involvement
Immune complex disease postinfectious (staphylococci/
(about 45%) streptococci)
Pauci-immune disease granulomatosis with polyangiitis
(about 50%) (Wegener granulomatosis)
PATHOGENESIS
 Pathogenesis of ANCA-associated disease is believed to be
caused by ANCAs inducing a premature activation and
degranulation of marginating neutrophils leading to the release
of lytic enzymes and toxic oxygen metabolites at the site of
injury.
 Histologically – characterized by the presence of crescents
in the Bowman’s space which compresses the glomeruli
causing rapid decline of renal function within weeks;
crescents consist of:
 Mixture of epithelial cells, macrophages, blood and
fibrin gain access into the Bowman’s space
 Most common cause of death in patients presenting with ANCA-
associated disease is due to massive pulmonary hemorrhage.
MINIMAL CHANGE DISEASE
– aka lipoid nephrosis or nil disease due to the presence of fat in the
tubular epithelial cells; relatively benign disorder
 Most common cause of nephrotic syndrome in children; less
common in adults
 Characterized by massive proteinuria, edema and
intravascular volume depletion
TRANSCRIBED BY: PEREZ, RAZEL NEFERTTI G.
PATHOGENESIS
 Pathogenesis unclear; primary visceral epithelial cell injury
current leading hypothesis
 Dysfunction of T-cells resulting in the elaboration of a
cytokine (permeability factor) that damages the epithelial
foot processes
 Decreased synthesis of polyanions from the glomerular
basement membrane
 Polyanions constitute the normal charge barrier to
the filtration of macromolecules, such as albumin.
 Histologically, glomerular change absent or minimal by
light microscopy
 Proximal tubular epithelial cells laden with lipid and
protein due to reabsorption of lipoproteins
 Electron microscopy – diffuse loss of visceral epithelial foot
processes (podocytes) due to flattening, retraction, and
swelling of podocytes.
 Prognosis: good in children with no permanent renal
damage.
CHRONIC GLOMERULONEPHRITIS
– end-stage glomerular disease.
 Most forms of acute glomerulonephritis, if disease progression
not halted with therapy, tend to progress to chronic kidney
disease
 May have no antecedent history of acute
glomerulonephritis
 May result from a specific type of glomerulonephritis e.g.,
membranous glomerulonephritis, IgA nephropathy,
crescentric glomerulonephritis
 Characterized by progressive glomerular and tubulointerstitial
fibrosis leading to irreversible reduction in the glomerular
filtration rate (GFR), retention of uremic toxins and
cardiovascular disease.
 Clinically, chronic kidney disease is classified into 5 stages
depending on the glomerular filtration rate and characterized by:
Stage 1 kidney damage with a normal GFR (≥ 90 mL/min)
Stage 2 kidney damage with a mild decrease in the GFR (60-90
mL/min)
Stage 3 moderately decreased GFR (to 30-59 mL/min)
Stage 4 severe decrease in the GFR (to 15-29 mL/min)
Stage 5 kidney failure
PATHOGENESIS
– initial injury reduces nephron mass and glomerular filtration rate
 Reduction in GFR leads to hypertrophy and hyperfiltration of the
remaining nephrons thus increasing intraglomerular pressure
(hypertension) and GFR of the remaining nephrons.
 Ultimately, increased intraglomerular pressure, ultimately, leads
to glomerulosclerosis and further nephron loss.
PATHOLOGY
– kidneys grossly symmetrically contracted with granular cortical
surfaces
 Histologically – glomeruli obliterated and transformed into
an acellular eosinophilic mass caused by trapped plasma
proteins, increased mesangial matrix, basement
membrane-like material, and collagen.
 Prognosis – most cases chronic glomerulonephritis
develops gradually and progresses slowly into renal
insufficiency or death due to uremia.
PATHO PAGE 7 OF 12
 NEPHROTIC SYNDROME  Nephritic syndrome differs from nephrotic syndrome i.e.,
– clinical syndrome caused by an abnormality of glomerular in the latter mediated by damage to the podocyte and the
permeability. glomerular basement membrane.
Classified into:
Primary a disease specific to the kidneys (e.g., minimal  Clinically characterized by:
change, membranous glomerulopathy) 1. Hematuria – presence of dysmorphic RBCs or RBC casts always
May be congenital resulting from mutations of genes indicates glomerular hematuria and hallmark of the syndrome.
encoding the podocyte proteins  May relate to problems in the tubular and collecting duct
Secondary renal manifestation of a systemic disease, (e.g., system.
diabetes mellitus, systemic lupus erythematosus) 2. Pyuria – presence of WBCs or WBC casts indicative of
inflammation.
Clinically characterized by: 3. Proteinuria and edema – typically present but less compared to
1 Massive proteinuria – loss of 3.5 gm of protein daily nephrotic syndrome.
2 Hypoalbuminemia – plasma albumin levels less than 30 g/dL 4. Renal dysfunction – typically present and characterized by
3 Generalized edema increased serum creatinine and oliguria.
4 Hyperlipidemia and lipiduria 5. Hypertension – due to sodium retention.

PATHOPHYSIOLOGY Examples of diseases presenting with nephritic syndrome

– the chart hereunder illustrates the pathophysiology of nephrotic a) Acute postinfectious glomerulonephritis
syndrome b) Membranoproliferative glomerulonephritis
c) Crecentric glomerulonephritis
d) IgA nephropathy
e) Anti-glomerular basement membrane glomerulonephritis.

 Prognosis - nephritic syndrome is a syndrome and not a disease

and, therefore, prognosis depends on the underlying cause.
 Generally, prognosis better in children compared to that of
adults.

TUBULO-INTERSTITIAL NEPHRITIS
– indicates damage and inflammation of the renal tubules and
surrounding (interstitial) tissue and sparing the glomeruli.
 Accounts for a significant number of cases presenting with
impaired renal function
 Most cases result from exposure to drugs or other nephrotoxic
agents such as heavy metals
 Hypersensitivity reaction to medications (allergic
interstitial nephritis) most common form.

PATHOPHYSIOLOGY
 Principal mechanism is hypersensitivity reaction to drugs
a) Penicillin
 Multiple diseases present with the nephrotic syndrome; diseases b) nonsteroidal anti-inflammatory drugs (NSAIDs)
in this category generally demonstrate normal glomerular c) sulfa drugs.
cellularity and lack of immune deposits; examples:
1. Minimal change disease  Another mechanism caused by infection, viral or bacterial
2. Focal segmental glomerulosclerosis associated with tubular obstruction or reflux
3. Membranous glomerulopathy  Sublethal or lethal injury to tubular and interstitial cells
4. Diabetic glomerulosclerosis. activates proinflammatory and chemoattractant cytokines
which leads to expression of new local antigens
 Prognosis  Cytokines produced by inflammatory cells (ie,
Primary Depends on its cause. macrophages, lymphocytes) and by the kidney cells (i.e.,
Congenital nephrotic syndrome – dismal prognosis: proximal tubule, vascular endothelial cells, interstitial cells,
survival beyond several months possible only with fibroblasts).
dialysis and kidney transplantation  Outcome can be acute or chronic nephritis.
Secondary – morbidity and mortality related to the primary disease  Kidneys remarkably resistant to structural damage in bacterial
infections
NEPHRITIC SYNDROME  In the absence of obstruction, damage from bacterial
– occurs due to inflammatory damage to the renal endothelium. infection extremely unlikely to occur.
 Characterized by glomerular proliferative changes and leukocytic
infiltration associated with antibody-mediated damage, and Prognosis – may progress to end-stage renal disease.
immune complex deposition.  Most patients with allergic interstitial nephritis recover upon
cessation of the causative agent.

TRANSCRIBED BY: PEREZ, RAZEL NEFERTTI G. PATHO PAGE 8 OF 12

 ACUTE TUBULAR NECROSIS LESIONS ASSOCIATED WITH METABOLIC DISORDERS
– clinico-pathologic entity; most common cause of acute renal injury. 1 Hypokalemic nephropathy – may be caused by chronic diarrhea,
 Clinically divided into: hyperaldosteronism, and chronic abuse of diuretics or laxatives;
a. Initiation characterized by coarse vacuolar degeneration of proximal
b. Maintenance tubules.
c. recovery phase 2 Gouty nephropathy – due to elevated uric acid in the blood
 Clinical phases relate to cellular events that occur during (gout); uric acid crystallizes in an acid environment
these phases. 3 Hypercalemic nephropathy – due to hypercalcemia causing
ACUTE ISCHEMIC TUBULAR NECROSIS “metastatic” calcification.
Causes:
1) Hypovolemic states (e.g., hemorrhage, burns) PYELONEPHRITIS
2) Low cardiac output states (e.g., heart failure, cardiac – most common kidney disease caused by infection of the renal
arrhythmia) parenchyma thru the hematogenous or retrograde ureteric routes
3) Systemic vasodilation (e.g., sepsis, anaphylaxis) from the lower urinary tract.
4) Disseminated intravascular coagulation. ACUTE PYELONEPHRITIS
s – bacterial infection caused by pyogenic organisms; usually
NEPHROTOXIC ACUTE TUBULAR NECROSIS associated with lower urinary tract infection; commonly thru the
– kidney vulnerable target for toxins, exogenous and endogenous. retrograde route (ascending infection).
Exogenous a) Aminoglycoside-related toxicity occurs in 10-  Potentially organ and/or life-threatening infection that
nephrotoxins 30% of patients characteristically causes significant renal damage and scarring.
b) Sulfa drugs  Often preceded by bladder infection
c) Anti-cancer drugs  Common organisms – about 80% caused by gram-negative bacilli
Endogenous  Myoglobinuria caused by rhabdomyolysis (e.g., E. coli, Proteus spp., Klebsiella pneumoniae, Enterobacter)
nephrotoxins resulting from traumatic or nontraumatic  More common in young women due to shorter urethra,
injuries. pregnancy, and urethral trauma during sexual intercourse.
 Most cases of rhabdomyolysis are  Pathology – interstitial edema and neutrophilic infiltrates in the
nontraumatic (e.g., alcohol abuse, statins) or interstitium and tubular lumina in cortex and medullar; may be
drug-induced muscle toxicity (eg, statins alone associated with abscess formation
or in combination with fibrates)  Inflammation may extend into the mucosa of the
 Hemoglobinuria rare complication of calyxes and pelvis.
hemolysis associated with transfusion  Complications
reactions. Renal papillary inflammation of the interstitium compromises
necrosis theblood supply to the medulla
PATHOPHYSIOLOGY Pyonephrosis stagnant fluid pelvis and calyxes suppurates
 Usually presents clinically with severe oliguria (<100 cc of and obstructs urine outflow
urine/24 hours) Perinephric abscess extension of infection beyond the renal
 Hyperkalemia triggering cardiac arrhythmia a serious treat capsule.
 Mortality – probably related more to the severity of the  Prognosis – causes considerable morbidity
underlying disease than to ATN itself.  Mortality higher in patients older than 65 years and those
 5% mortality if no damage to other organs, 50% if associated associated with septic shock, bedridden status, and
with shock/sepsis immunosuppression.
Initiation (oliguric phase)
– acute marked decrease in GFR associated with CHRONIC PYELONEPHRITIS
sudden increase in serum creatinine and BUN – caused by recurrent or persistent bacterial infection secondary to
concentrations urinary tract obstruction or vesico-ureteric reflux.
Blockage of renal tubules by necrotic tubular epithelial cells leading to  Characterized by renal inflammation and scarring
reduction in glomerular blood flow (caused by arteriolar  Occurs almost exclusively in patients with major anatomic
vasoconstriction) leading to reduced glomerular filtration anomalies, most commonly young children with vesicoureteral
Maintenance – sustained marked reduction in GFR persisting reflux
commonly about 1-2 weeks; creatinine and BUN  Vesico-ureteric reflux due to the 90% angle of the terminal
levels continue to rise. portion of ureter to the bladder mucosa which allows reflux of
Cells undergo repair, migration, apoptosis and proliferation to urine during micturition.
reestablish and maintain cellular and tubule integrity  Pathogenesis – reflux of urine increases the intrapelvic and
Recovery – tubular function restored; increase urine volume intracalyceal pressure causing intra-parenchyma reflux, most
and gradual decrease in BUN and serum creatinine to important factor in causing chronic pyelonephritis
their preinjury levels.  Pathology – grossly, broad, depressed irregular cortical scars
 Removal of necrotic material by phagocytic cells from the  Histology – interstitial fibrosis with dilated and atrophic tubules
tubular lumina and regeneration of tubular epithelial cells plus containing eosinophilic casts so called “thyroidization”
increase blood flow leads to polyuria (resembling thyroid); lymphocytic infiltrates.
 Polyuria initially occurs due to regenerating tubular cells are Xanthogranulomatous a form of chronic pyelonephritis resulting
undifferentiated and not differentiated yet to reabsorb pyelonephritis in a yellowish nodular appearance of the
electrolytes and water kidney due to the presence of lipid-laden
 Differentiation of tubular epithelial cells restoring renal function foamy macrophages; often caused by
homeostasis. Proteus specie.

TRANSCRIBED BY: PEREZ, RAZEL NEFERTTI G. PATHO PAGE 9 OF 12

 NEPHROSCLEROSIS
– almost always secondary to systemic hypertension
 Prognosis - poor prognostic factors included poor or no control
of arterial blood pressure by anti-hypertensive drugs
HYPERTENSIVE NEPHROSCLEROSIS (BENIGN NEPHROSCLEROSIS)
– caused by a sustained systolic pressure of > 140 mm Hg and a
diastolic pressure > 90 mm Hg.
 Clinical syndrome characterized by:
1) Long-term essential hypertension
2) Hypertensive retinopathy
3) Left ventricular hypertrophy
4) Minimal proteinuria
5) Progressive renal insufficiency
 Pathogenesis – arterial response to hemodynamic changes
coupled with changes due to aging and genetic defect
 Endothelial cell injury causes extravasation of plasma
proteins and increase deposition of basement membrane
matrix
 Pathology – grossly, atrophy of both kidneys with fine
granularity of thinning of the cortex
 Histology – some glomeruli appear normal, other acellular,
densely eosinophilic and solid due to ischemic changes;
tubular atrophy, interstitial fibrosis and chronic
inflammation
 Large arteries – intimal fibrotic thickening and
multilayering of the internal elastic lamina
 Arterioles – concentric hyaline thickening of wall; loss of
smooth muscle cells (hyaline arteriolosclerosis).
MALIGNANT HYPERTENSIVE NEPHROSCLEROSIS
– relatively uncommon condition characterized by accelerated
(malignant) hypertension with a diastolic pressure >130 mmHg;
associated with retinal vascular changes, papilledema, and renal
functional changes
 Frequently in men with a history of benign hypertension;
associated with headache, dizziness, and visual disturbances;
hematuria and proteinuria frequent findings.
 Pathogenesis – essentially caused by vascular injury resulting
from various disorders e.g., arteritis, coagulopathy, hypertension
 Injury leads to increase permeability of small vessels to
fibrinogen and other plasma proteins and vascular wall cell
death
 Fibrinoid necrosis of arterioles and small arteries with
activation of platelets and coagulation factors leads to
intravascular thrombosis
 Marked ischemia triggers the renin-angiotensin system.
 Pathology – grossly, kidney size varies; surface pin-point
petechial hemorrhages with cortical infarcts ("Flea bitten"
appearance)
 Microscopically – changes of benign nephrosclerosis plus
arterioles demonstrating:
a) Fibrinoid necrosis
b) “Onion skinning” caused by the elongation and concentric
arrangement of smooth muscle cells and collagen; and
deposition of proteoglycans and plasma protein seen as
pale-staining material.
TRANSCRIBED BY: PEREZ, RAZEL NEFERTTI G.
RENOVASCULAR HYPERTENSION
– caused by stenosis or complete occlusion of a main renal artery;
 Atherosclerosis most frequent cause in older adults
 Fibromuscular dysplasia of renal artery frequent cause in young
adults and children; more common on women
 Characterized by fibromuscular thickening of the intima,
media or adventitia.
RENAL INFARCT
– commonly caused by embolization of atheromatous debris into the
renal vasculature in patients with severe aortic atherosclerosis; may
be spontaneous or caused by catheterization procedures.
 Large renal infarction commonly from cardiac mural thrombus or
vulvular vegetations.
NEPHROLITHIASIS
– specifically refers to calculi forming in the kidneys, and/or ureter
(ureterolithiasis)
 Ureteral calculi almost always originate in the kidneys
Calcium oxalate 75-80% of all calculi; often mixed with calcium
phosphate
 Calculi may continue to grow once lodge in the ureter.
 Commonly in men; may vary in size <1 mm to large enough to
lodge within the renal calyces, pelvis and/or urinary tract and
obstruct urinary outflow
 Erodes the mucosa causing hematuria
 Pain generated by renal colic primarily due to acute
ureteral obstruction causing dilation, stretching, and spasm.
 May vary in size <1 mm to large enough to lodge within the renal
calyces, pelvis and/or urinary tract and obstruct urinary outflow.
 Appears to be related to the socioeconomic status of the patient
population.
 Lower the economic status, less likely for renal stones to
develop.
ETIOPATHOGENESIS
– may be caused by the following:
1. Supersaturation of the urine by stone-forming constituents
(e.g., uric acid, calcium, oxalate, cysteine)
 Crystals or foreign bodies can act as nidi on which ions
from the supersaturated urine form microscopic crystalline
structures
 Supersaturation of the urine commonly the underlying
cause of uric and cystine stones
2. Decreased urine volume – low fluid intake, with a subsequent
low volume of urine production, produces high concentrations of
stone-forming solutes in the urine.
3. Infections – urea splitting bacteria leads to precipitation of
magnesium ammonium sulfate
4. Changes in urine pH
5. Deficiencies of urinary crystal inhibitors e.g., pyrophosphate,
diphosphonate, citrate.
 Complications
Obstructive uropathy impedance of urinary outflow causing renal
dysfunction
Hydronephrosis dilatation of the collecting system
progressing from distal to proximal tubules;
glomeruli spared
PATHO PAGE 10 OF 12
 RENAL TRANSPLANTATION  Clinical presentation:
– increasingly performed for end-stage renal disease 1) Hematuria
 Therapy of choice for end-stage renal disease. 2) flank pain
 First organ transplant procedures to develop because of live 3) palpable abdominal mass
donor availability and the crucial backup of dialysis. 4) occasionally ectopic hormone production leading to:
 Complications include: a. Hypertension
1) transplant rejection b. Hypercalcemia
2) recurrence of disease in transplanted kidney c. Polycythemia
3) thrombosis of surgical vascular anastomosis. d. Gynecomastia

 Two most common groups of tissue antigen inciting rejection: PATHOLOGY

a. ABO blood group antigens – expressed on endothelial cells and
RBCs; mismatch between donor and recipient incite preformed
antibodies against foreign blood group binding to endothelial
cells in the transplanted kidney and causing hyperacute rejection.
b. Major histocompatibility complex – expressed on most cell
membranes may induce acute or chronic rejection mediated by
humoral and cell-mediated mechanisms.
PATHOPHYSIOLOGY OF RENAL REJECTION
– T cells sensitized and react against donor antigens expressed on
antigen presenting cells and donor cells
 Delayed type hypersensitivity
 Macrophages and granulocytes frequently recruited and mediate
tissue injury.
TRANSPLANT REJECTION & HISTOPATHOLOGY
Three Patterns
1 Hyperacute
– occurs within a very short time after the transplanted kidney is
perfused by the host’s blood; characterized by:
 Widespread intravascular thrombosis, necrosis, and
neutrophilic infiltrates often resulting from host’s
preformed antibodies reacting immediately to graft’s
antigens.
2 Acute rejection
– occurs within weeks after transplantation or after cessation of
immunosuppressive therapy; termed acute due to its rapid
progression
 Interstitial edema and inflammatory infiltrate
 Presence of tubulitis: inflammatory cells within and among
tubular epithelium.
3 Chronic rejection
– leading cause of late graft rejection; occurs slowly and
progressively resulting from slow breakdown of the host’s tolerance to
the graft; may be due to inadequate suppression
 Arterial intimal fibrosis leading to ischemic changes
 Tubular atrophy and interstitial fibrosis with mononuclear
inflammatory infiltrate
 Glomeruli – segmental and global sclerosis.
– Grossly, large bossellated tumor usually in upper pole with a
yellowish-gray cut surface
 Histology – composed of either clear or granular cells
containing glycogen and fat
 Various pathologic subtypes predominantly papillary
or tubulopapillaryarchitecture
 Prognosis – difficult to predict
 5-year survival may be as high as 70% if no evidence
of metastasis at presentation
 15-20% when renal vein involved.
UROTHELIAL (TRANSITIONAL CELL) CARCINOMA
– 5-10% of primary renal tumors in adults; arises from urothelium of
renal pelvis
 Up to 50% associated with lower tract disease
 Associated with analgesic abuse and exposure to aniline dyes
used in plastic, dye, rubber, and gas industries.
 Poor prognostic features:
1) TNM stage
2) vascular invasion
3) older patient age
4) high tumor grade
5) nodal metastases.
WILMS TUMOR (NEPHROBLASTOMA)
– an embryonal malignant tumor which originates from the
nephrogenic blastema and imitating the appearance of the developing
kidney
 Most common intra-abdominal tumor in children less than 10
years of age
 Peak incidence 1- 4 years of age; involves both sexes
equally
 Majority of cases (90%) – sporadic and unilateral; subset
inherited and frequently bilateral
 Due to genetic alterations of embryological development of the
genitourinary tract
 Mutation in the Wilms tumor gene (WTI), a tumor
suppressor gene regulating transcription of growth factors,
occurs in a subset of sporadic and inherited lesions.

RENAL CELL CARCINOMA PATHOLOGY

– arises from the proximal tubular epithelium – grossly, large, spherical, solitary mass, sharply demarcated from the
 90% of all renal malignant tumors; commonly in male adults renal parenchyma.
usually >50 years of age.  Histologically, mixture of 3 components:
 Risk factors: 1) blastemal (small ovoid cells)
a. Obesity 2) stromal (spindle cells)
b. Smoking 3) epithelial (small tubular structures)
c. Hypertension  Prognosis – approximately 80-90% of children survive with
d. acquired cystic kidney disease due to end stage renal current modes of treatment.
disease
e. occupational exposure (e.g., trichloroethylene)
 Genetic susceptibilities accounts for 2 - 4% of cases.

TRANSCRIBED BY: PEREZ, RAZEL NEFERTTI G. PATHO PAGE 11 OF 12

 URETERS  Urothelial (transitional cell) carcinoma is the predominant
 Double or bifid ureters may occur in association with structural histologic 90% of all bladder malignancy.
abnormalities of pelvi-calyceal system  Strongly associated with certain industrial chemicals
1. Hydroureter – dilated and often tortuous; most frequent cause  Usually preceded by dysplasia and carcinoma-in-situ
low urinary obstruction and pregnancy.  Frequently multifocal indicating that the entire urothelium
2. Inflammation – may be part of a urinary tract infection unstable due to carcinogen exposure
3. Obstruction – frequent cause of intense pain called renal colic  Prognosis depends on grade and stage.
commonly due to calculus.
 Squamous cell carcinoma – arises from metaplastic squamous
URINARY BLADDER epithelium; metaplasia often in association with calculi;
prognosis poor.
1 Diverticula  Adenocarcinomas – uncommon
– outpouching of the bladder mucosa; congenital or acquired  Sarcomas – rare
 Urinary stasis within the diverticula predisposes to infections and
calculus formation. 6 Secondary tumors
– usually due to direct extension from the cervix, prostate or rectum
2 Acute cystitis  Metastasis from distant sites may occur, e.g., lungs.
– clinical diagnosis manifesting as:
1. frequency of urination TRANSCRIBER’S MESAGE
2. Lower abdominal pain
3. dysuria (pain or burning during urination)
 Common in young women of reproductive age, older men and
women
 Commonly occurs as part of a urinary tract infection
 Causal organism usually derived from patient’s fecal flora
a. E. coli (most common)
b. Proteus
c. Klebsiella
d. Enterobacter
 Predisposes to pyelonephritis
 Inflammation associated with neutrophilic infiltration,
hemorrhage, fibrinousexudates.

3 Chronic cystitis
– commonly in women (90%) between 30-50 years of age; probably
due to shorter urethra.
 Many factors contribute to its development, recurrence and REFERENCE
chronicity including antibiotic resistance  Dr. Emmanuel Dela Fuente’s Lecture Handout
Anatomic or physiologic factors may trigger and prolong UTI  Robbins and Cotran Pathologic Basis of Disease (10th ed.)
Physiologic factors – prolonged/repeated bouts of UTI by bacterial
pathogens (commonly gram negative), radiation
for neoplasm
Anatomic factors – bladder outlet obstruction (e.g., prostatic
enlargement), neurogenic or muscular
dysfunction of the bladder (e.g., paralysis due to
spinal cord injury), congenital anomalies (e.g.,
vesicoureteral reflux in childhood).
 Mononuclear cells (lymphocytes and macrophages) infiltrate the
lamina propria.

4 Obstruction
– usually occurs at the base of the bladder
 Bladder stones and bladder cancer more commonly seen in men
than women.
 Prostatic disease in elderly men
 Prolapsed in elderly women
 Urethral strictures
 Neurological damage
 Tumor.

5 Primary tumors
 Bladder cancer is the most common malignancy involving the
urinary system.

TRANSCRIBED BY: PEREZ, RAZEL NEFERTTI G. PATHO PAGE 12 OF 12