CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 1 CONGENITAL ANOMALIES NAME Agenesis CHARCTERISTICS Total bilateral agenesis

s is incompatible with life Unilateral agenesis is uncommon but compatible. Remaining kidney usually hypertrophic to compensate and pt later develops progressive glomerular sclerosis chronic renal failure. Failure for kidney to grow to normal size A truly hypoplastic kidney shows no scars and has a reduced number of renal lobes and pyramids. Lie just above the pelvic brim or within the pelvis. Kinking or tortuosity of the ureters may cause some obstruction to urinary flow bacterial infections Fusion of the upper or lower (90%) of the kidneys Most common congenital kidney disorder goes undetected. ed incidence in Turners syndrome

Hypoplasia Ectopic Horseshoe

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 2 CYSTIC DISEASES OF THE KIDNEY NAME Cystic Renal Dysplasia PICTURE GENETICS/EPIDEM No inheritance pattern. Most common cystic disease in children PATHOLOGY (GROSS and HISTOLOGICAL) Abnormality in metanephric differentiation with abnormal structures and lobar organization in the kidney Gross Usually enlarged, extremely irregular, multicystic Histological Presence of islands of undifferentiated mesenchyme, often with cartilage, and immature collecting ducts. Multiple expanding cysts of both kidneys that ultimately destroys the renal parenchyma and cause renal failure Mechanisms uncertain (See below) Gross Bilateral enlargement, external surface mass of cysts!!! Histologically functional nephrons dispersed among cysts, cysts filled with serous, but usually red-brown hemorrhagic, fluid CLINICAL COURSE Discovery by appearance of flank mass surgical exploration OUTCOME Excellent prognosis after surgical removal of the affected kidney

AD (adult) Polycystic Kidney Disease

AD with high penetrance Mutations on Ch 16 involving PKD1 (85%, more severe, suppressor fxn) and PKD2 genes.

Cysts initially involve only portions of the nephrons, so renal function is retained until 4-5 decade. Asymptomatic until renal insufficiency Larger masses on palpation Insidious onset of hematuria proteinuria, polyuria, and HTN Enlargement of cysts and interstitial fibrosis progressing PKD Associated with 1. Polycystic liver disease 2. Berry aneurysms 3. Mitral valve prolapsed

CRF by 40-60 Pts may survive many yrs with azotemia slowly progressing to uremia. Dialysis prolongs life COD in pts 1. Heart or HTN dx 2. Infection 3. Rupture berry aneurysm

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 3 NAME AR (child) Polycystic Kidney Disease PICTURE GENETICS/EPIDEM AR Association with PKHD1 gene encodes fibrocystin PATHOLOGY (GROSS and HISTOLOGICAL) Gross enlarged w/ smooth external appearance, cut-section shows numerous small cysts in cortex and medulla spongelike appearance. Histological Cylindrical dilation of all collecting tubules. Cysts have uniform lining of cuboidal cells (from collecting ducts) Multiple cystic dilations of the collecting ducts in the medulla Gross Papillary ducts in medulla are dilated and may contain small cysts, Swiss cheese striations Histological Cysts lined with cuboidal cells, occasionally transitional cells. Complex of diseases that have variable number of cysts in the medulla, usually concentrated at the corticomedullary junction The tubulointerstitial damage is the cause of the eventual renal insufficiency Gross Cysts in medulla, most prominently at corticomedullary junction, small cysts also seen in cortex Histological Cysts lined by cub or flattened cells, surrounded by inflammation or fibrous tissue. CLINICAL COURSE Pts who survive infancy may develop a peculiar type of hepatic fibrosis portal HTN with splenomegaly OUTCOME Perinatal, neonatal form incompatible with life. Infants and children that survive usually die in childhood.

Kidney Diseases of Renal Medulla Medullary Sponge Kidney

No inheritance Occurs in adults

Nephronoph thisisMedullay Cystic Disease Complex

AR NPH1, NPH2, NPH3 gene mutation (nephrocystin) is child form. AD MCKD1, MCKD2 gene mutation is adult Sporadic forms. Child form thought to be most common genetic cause of end stage renal disease in children and young adults.

Discovered by urography incidentally. Complications include calcifications w/i dilated ducts, hematuria, infection, and urinary calculi Renal function usually normal. Affected children first present with polyuria and polydipsia Marked defect in concentrating ability Sodium wasting and tubular acidosis

Benign

Terminal renal failure 5-10 years

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 4 NAME Acquired (DialysisAssociated ) Cystic Disease PICTURE GENETICS/EPIDEM No inheritance 50% of long term dialyzed pts PATHOLOGY (GROSS and HISTOLOGICAL) Numerous cysts in cortex and medulla due to prolonged dialysis Contain clear fluid, often with calcium oxalate crystals (form due to obstruction of tubules by interstitial fibrosis or oxalate crystals) Single or multiple, usually cortical, cystic spaces Translucent Lined by a gray, glistening, smooth membrane Radiography smooth contours, almost always avascular, give fluid rather than solid signals on US (opposite of tumors) CLINICAL COURSE Asymptomatic but sometimes the cysts bleed causing hematuria. Complication is development of renal cell cancer in walls of cysts Hemorrhage into them may cause sudden distention and pain No clinical significance though really. OUTCOME End stage renal failure already so not so good.

Simple Cysts

No inheritance Most common adult renal cyst

Benign

Adult Polycystic Kidney Disease Mechanism

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 5 NEPHRITIC SYNDROMES GLOMERULAR PATHOLOGY LM IMMUNO FLO EM Diffuse Diffuse proliferative Influx of leukocytes

NAME Nephritic Syndrome General

PATHOGENESIS Lesions caused by immune complexes

Post-streptococcal (strep pyogenes) glomerulonephritis

Other nonstrep include staph endocarditis, pneumococcal pneumonia, meningococcemia, hepB/C, mumps, HIV, varicella, mono, malaria, toxoplasmosis

Ab mediated (circulating or planted Ag) 1-4 wks after strep skin or pharynx infection Swelling of endothelial cells and leukocyte infiltration obliterates the capillary lumens

Diffuse proliferative Leukocytic infiltration Severe cases have crescents

Granular IgG, IgM, and C3 in GBM and mesangium

CLINICAL Hematuria Azotemia Variable proteinuria Oliguria Edema HTN Electrodense Interstitial edema deposits on Red cell casts subepithelial Oliguria, fever, malaise, humps hematuria 1-2 wks after sore throat Periorbital edema Mild proteinuria Mild-moderate HTN Elevated ASO titer in serum complement (b/c its being used up) Children better prognosis than adults (90% : 60% recovery) Recurrent microscopic/gross hematuria Acute nephritis Can progress to nephrotic syndrome CRF HTN

SLE Mesangial Lupus GN

Mesangial cell proliferation and lack of involvement of glomerular capillary walls.

Granular

Mesangial deposits of Ig & complement

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 6 Focal Proliferative GN Only affects 50% of glomeruli Lesions are associated with hematuria and proteinuria. Most serious renal lesions in SLE Produce crescents in Bowmans capsule Fibronoid necrosis, prominent infiltration by leukocytes, cell death, and hyaline thrombi Widespread thickening of capillary walls. Subendothelial deposits See above

Diffuse Proliferative GN

Wire loops homogenous thickening of the capillary wall created by subendotheli al deposits

Subendothelial deposits

See above

Membranous GN

Subepithelium deposits

See above

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 7 RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS NAME ALL FORMS PATHOGENESIS Severe glomerular injury Kidneys are enlarged, pale often with petechial hemorrhages on cortical surfaces Formation of distinctive crescents (formed by proliferation of parietal cells and migration of macrophages and monocytes into the urinary spaces.) Eventually obliterated Bowman space and compressed glomerular tuft. Fibrin strands are prominent. GLOMERULAR PATHOLOGY EM: Distinct ruptures of GBM, allowing leukocytes, proteins, and inflammatory mediators into the urinary space where they trigger crescent formation CLINICAL Hematuria with red cell casts Moderate proteinuria occasionally reaching nephritic range Variable HTN and edema

Type 1 Anti-GBM Antibody Induced disease Idiopathic RPGN

Anti-GCM Ab

Goodpasture Syndrome

Antibodies against collagen type IV Ag (Anti-GBM COL4-A3 Ag) that is a fixed intrinsic Ag normally found on the basement membrane of glomerulus and lung alveoli (due to cross rxn with antiGBM antibodies) Severe crescentic glomerulonephritis Exposure to virus and hydrocarbon solvents (paints and dyes) have been associated High prevalence in HLA-DRB1 subtype

LM: Proliferation, Focal necrosis, Crescents IF: Linear IgG and C3 in GBM EM: No deposits LM: Proliferation, Crescents IF: Diffuse linear pattern of IgG and C3 staining all along the BM, Fibrin in crescents EM: No deposits, GBM disruptions, Fibrin

Acute nephritis Proteinuria Acute renal failure If not txed, death from renal failure w/i weeks or months Plasmapheresis is part of tx to remove the pathogenic antibodies Steroids help too Recurrent hemoptysis or life-threatening pulmonary hemorrhage

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 8 NAME Type II Immune complex-mediated disease Idiopathic Post-Infectious SLE CAUSES PATHOGENESIS MORPHOLOGY IF: Granular CLINICAL Cannot be treated with plasmapheresis, require tx for underlying disease.

IgA nephropathy

Type III Pauci-Immune Type ANCA associated Idiopathic Wegener granulomatosis Microscopic polyarteritis nodosa

Most common type of glomerulonephritis worldwide Secondary IgA nephropathy occurs in pts with - liver disease: defective hepatobiliary clearance of IgA - intestinal disease: intestinal mucosa defects A genetic or acquired abnormality of immune regulation leading to ed mucosal IgA synthesis in response to respiratory or GI exposure to environmental agents The lack of anti-GBM antibodies or immune complexes by IF and EM Antineutrophil cytoplasmic antibodies (ANCA)

IgA1-containing immune complexes are trapped in the mesangium, where they activate the alternative complement pathway and initiate glomerular injury.

LM: Lesions vary; associated with focal proliferative GN in which healing may cause focal segmental sclerosis; may be normal IF: prominent IgA deposits often with C3 in the mesangial regions EM: Electron dense deposits in the mesangium

Recurrent gross or microscopic hematuria after a respiratory, GI, or UT infection Mild proteinuria Many maintain normal renal function for decades Nephrotic syndrome may develop

EM: No deposits

Related to systemic vasculitis

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 9 NEPHROTIC SYNDROMES NAME Nephrotic Syndrome General PATHOGENESIS Initial event is a derangement in glomerular capillary walls ed permeability to plasma proteins massive proteinuria. Children younger than 17 in US, the nephrotic syndrome is almost always caused by a lesion primary to the kidney. Among adults, it may be associated with a systemic disease such as diabetes, SLE, and amyloidosis (see below) CLINICAL >3.5g/day proteinuria liver cant compensate. Hypoalbuminemia Edema made worse by the activation of RAAS, stimulation of sympathetic system, reduction in secretion of natriuretic factors such as ANP. Hyperlipidemia and lipiduria liver es synthesis of protein and cholesterol. Vulnerable to infections like staph and strep pneumo b/c of loss of Ig or complement in the urine. Thrombotic and thromboembolic complications due to loss of anticoagulant factors.

NAME Membranous Glomerulonephropathy

PRIMARY GLOMERULAR LESIONS THAT CAUSE NEPHROTIC SYNDROME CAUSES PATHOGENESIS MORPHOLOGY Most common form in adults Autoimmune disease LM: Diffuse thickening of GBM or normal in early Idiopathic C5-C9 causes activation stages. of glomerular epithelial Secondary MGP can be and mesangial cells, IF: Granular deposits of associated with another inducing them to Ig and complement disease liberate proteases and 1. Drugs peniciilamine, oxidants capillary wall EM: Electron-dense Ig captopril, gold, NSAIDs injury and protein 2. Underlying malignant deposits in leakage. tumors of lungs, colon, subepithelium, BM and melanoma material is laid down 3. SLE 15% of GN is this btwn deposits type irregular spike look. 4. Infections Spikes thicken dome 5. Other autoimmune like protusions that close disease over Ig deposits and bury them in the membrane.

CLINICAL Course is variable but indolent. Proteinuria is nonselective and does not respond to corticosteroid therapy Progression is associated with increasing sclerosis of glomeruli with rising BUN and development of HTN Must rule out secondary cause because tx of underlying problem can resolve this.

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 10 PRIMARY GLOMERULAR LESIONS THAT CAUSE NEPHROTIC SYNDROME CAUSES PATHOGENESIS MORPHOLOGY Most frequent cause of Involves some immune LM: Glomeruli are nephrotic syndrome in dysfunction, eventually normal children (2-6 y/o) resulting in the elaboration of a cytokine IF: No deposits Sometimes follows a that damages visceral respiratory infection or epithelial cells and routine prophylactic EM: Visceral epithelial causes proteinuria immunization cells show a uniform and Autoimmune related diffuse effacement of foot processes. Mutation in the nephrin gene causes hereditary form

NAME Minimal Change Disease

Membranoproliferative Glomerulonephritis

Primary (idiopathic) - Type I (see rest of chart) - Type II (densedeposit disease, see study guide) Secondary MPGN due to other systemic disorder and etiologic agents. 1. Chronic immune complex disordersSLE, hep B/C, endocarditis, HIV, schistosomiasis 2. Alpha-antitrypsin deficiency 3. Malignant diseasesCLL and lymphoma

Evidence of immune complexes in the glomerulus and activation of both classical and alternative complement pathways

LM: Glomeruli are large and hypercellular due to proliferation of mesangial cells and leukocyte infiltration; GBM is thickened, often focally. IF:, C3, IgG present in granular pattern EM: Subendothelial electron-dense deposits

CLINICAL Renal function remains good No HTN or hematuria Proteinuria is highly selective, most is albumin Dramatic response to corticosteroid therapy (completely reverses damage) Associated with Hodgkins disease Good prognosis Presents as a nephrotic syndrome in older children and young adults usually with a nephritic component (hematuria or mild proteinuria) Slow progression but unremitting 50% CRF w/i 10 years Tx with steroids, antiplatelet drugs, and immunosuppresants not very effective.

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 11 PRIMARY GLOMERULAR LESIONS THAT CAUSE NEPHROTIC SYNDROME CAUSES PATHOGENESIS MORPHOLOGY With association of HIV, Endothelial & epithelial LM: Lesions tend to heroin addiction, sickle injury ed involve some, not all, cell anemia, and massive glomerular permeability juxtomedullary glomeruli obesity to proteins and only sections of the accumulation of proteins affected ones; hyalinosis; As a secondary event, in the mesangial matrix lipid droplets; foam cells reflecting glomerular proliferation of scarring, in cases of focal mesangial cells glomerulonephritis (IgA IF: May show nonspecific infiltration of nephropathy) deposition trapping of macrophages ed IgM and C2 in the As a component of the accumulation of ECM sclerotic segment. adaptive response to segmental and global loss of renal tissue in sclerosis and hyalinosis advanced stages of other EM: Diffuse effacement of glomeruli renal disorders (renal of foot processes (both Compensatory ablation) sclerotic & nonsclerotic) hypertrophy of As a hereditary disease remaining glomeruli but linked to mutations in soon es in nephron genes encoding nephrin mass. (key component of slit Contributing to the diaphragm and may progressive injury is the control glomerular inability of mature permeability) and podocytes to proliferate podocin (localized to slit after injury. diaphragm) Idiopathic SYSTEMIC CAUSES OF NEPHROTIC SYDNROME PATHOGENESIS MORPHOLOGY SEE BELOW FOR DETAILS

NAME Focal segmental glomerulosclerosis

CLINICAL Proteinuria is nonselective Microscopic hematuria Hemodynamic changes such as ed GFR, capillary HTN, systemic HTN Poor response to corticosteroids Poor prognosis CRF

NAME Diabetes SLE Amyloidosis

CAUSES

CLINICAL

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 12 GLOMERULAR DISEASES ASSOCIATED WITH SYSTEMIC DISEASES NAME SLE CAUSES Autobodies against self-constituents Most common in 3-8 y/o but can occur in adults where the renal problems are more severe. Onset often follows an upper respiratory infection PATHOGENESIS Immune complexes to deposit in skin, joints, kidney, and serosal membranes Consists of purpuric skin lesions involving extensor surfaces of arms and legs as well as buttocks; abdominal manifestations including pain, vomiting, and intestinal bleeding; nonmigratory arthralgia, and renal abnormalities. IgA deposited in the glomerular mesangium in a distribution similar to that of IgA nephropathy. Glomerular lesions represent immune complex nephritis Also affects the arterioles, causing hyalinizing arteriolar sclerosis High glucose is responsible for biochemical alterations in diabetic GBM, including ed amount and synthesis of collagen IV and fibronectin and ed synthesis of heparin sulfate proteoglycan Nonenzymatic glycosylation of proteins Hemodynamic changes (early stage of diabetic nephropathy has ed GFR and glomerular hypertrophy) Kidney suffers from ischemia, develops tubular atrphy and intersitital fibrosis, undergoes overall contraction in size MORPHOLOGY Granular Depends on type (see SLE above) Vary from mild focal mesangial proliferation diffuse mesangial proliferation crescentic GN IF: deposition of IgA, sometimes with IgG and C3, in the mesangial region. CLINICAL See above

Henoch-Schonlein Purpura

Gross and microscopic hematuria Proteinuria Nephrotic syndrome Course is variable but recurrence s of hematuria for years may occur.

Bacterial Endocarditis Diabetic Glomerulosclerosis

Caused by the metabolic defect of insulin deficiency and hyperglycemia. Lesions involving the glomeruli include nonnephrotic, nephrotic, and chronic renal failure

Capillary basement membrane thickening Diffuse mesangial sclerosis

Nodular glomerulosclerosis Kimmelstiel-Wilson disease. Nodules will enlarge with disease progression and obliterate the glomerular tuft.

Hematuria Proteinuria Microalbuminuria + ed GFR + glomerular hypertrophy HTN may occur Followed by more overt proteinuria + ed GFR end-stage renal failure. Most pts with end stage are on dialysis or renal transplant Glucose control and ACE inhibitors greatly delay progression. ed suspectibility to development of pyelonephritis, particulary papillary necrosis.

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 13 NAME Amyloidosis CAUSES Pts with long term hemodialysis for renal failure develop amyloidosis owing to the deposition of 2microglobulin (it cannot be filtered) Similar to amyloid deposits PATHOGENESIS Deposits of amyloid within the glomeruli, most commonly AL or AA type. In time the mesangial and GBM depositions cause capillary narrowing and distortion of the glomerular vascular tuft. MORPHOLOGY Typical congo red amyloid-positive fibrillary deposits in mesangium and capillary walls. CLINICAL May present with nephrotic syndrome and die of uremia. Kidney size normal or ed.

Fibrillary and Immunotactoid Glomerulonephritis

Associated with characteristic fibrillar deposits in the mesangium and glomerular capillary walls.

Fibrils larger than amyloid Do not stain in Congo red Lesions exhibit membranoproliferative or mesangioproliferative patterns by LM IF: selective for IgG with C3

Nephrotic syndrome Hematuria Progressive renal insufficiency

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 14 CHRONIC GLOMERULONEPHRITIS NAME Chronic GN CAUSES PATHOGENESIS Kidneys on long-term dialysis: 1. Arterial intimal thinning caused by accumulation of smooth muscle-like cells and a loose, proteoglycanrich stroma 2. Focal calcification 3. Extensive deposition of calcium oxalate crystals in tubules and interstitium 4. Acquired cystic disease 5. ed numbers of renal adenomas and adenocarcinomas MORPHOLOGY Kidneys are symmetrically contracted Diffusely granular, cortical surfaces Cortex thin with peripelvic fat Hyaline obliteration of glomeruli acellular eosinophilic masses CLINICAL Presents with nonspecific complaints such as loss of appetite, anemia, vomiting, and weakness. May lead to HTN Dialysis changes (see pathogenesis) Pts dying of uremia 1. Uremic pericarditis 2. Uremic gastroenteritis 3. Secondary hyperparathyroidism 4. Renal osteodystrophy 5. Left ventricular hypertrophy due to HTN 6. Uremic pneumonitis

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 15 DISORDERS AFFECTING TUBULES AND INTERSTITIUM NAME Acute Tubular Necrosis CAUSES Ischemia due to or interrupted blood flow, accompanied by marked hypotension and shock. Nephrogenic 1. Direct toxic injury to the tubules by drugs, radiocontrast dyes, myoglobin, hemoglobin, radiation 2. Acute tubulointerstitial nephritis hypersensitivity rxn to drugs DIC Urinary obstructiontumors, BPH, blood clots PATHOGENESIS It is the most common cause of acute renal failure resulting in renal fxn and urine flow Tubular injury tubular epi cells vulnerable to ischemia and toxins. Ischemia ATP intracellular Ca2+ activation of proteases, phospholipases, generation of ROS, activation of capsases cytoskeletal disruptions, damaged membranes, and apoptotic cell death!! Injured cells detach and obstruct lumen intratubular pressure and GFR. Fluid from the damaged tubules can leak into the interstitum edema, ed pressure, and further damage. Persistent and severe disturbances in blood flow Intrarenal vasoconstriction ed glomerular plasma flow and ed oxygen delivery to functionally important tubules in the outer medulla MORPHOLOGY Destruction of tubular epithelial cells CLINICAL Acute diminution or loss of renal function Reversible lesion 3 stages 1. Initiation phase Some event causing ischemic ATN. Slight in urine output with a BUN. 2. Maintenance phase Sustained oliguria, with salt and water overload, BUN, hyperkalemia, metabolic acidosis, uremia. 3. Recovery phase urine volume up to 3L/day, tubules still damaged so lots of loss of water, Na, and K, hypokalemia, eventually tubular fxn is restored with improved concentrating ability.

Ischemic ATN eosinophilic hyaline casts and pigmented granular casts are common particularly in DCT and collecting ducts. Those casts consist mainly of TammHorsfall protein, a urinary glycoprotein normally secreted by cells of TAL and DCT. There is epi regeneration by flattened cells which repopulates tubules in the event on survival, leaving no evidence of damage! Toxic ATN- necrosis mostly in PCT.

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 16 NAME Tubulointerstitial Fibrosis CAUSES Infections Toxins Metabolic Diseases Physical Factors Neoplasms Immunologic rxns Vascular diseases Miscellaneous PATHOGENESIS Ischemia of tubule segments downstream from sclerotic glomeruli Acute and chronic inflammation in the adjacent interstitium Damage or loss of the peritubular capillary blood supply Proteinuria causes direct injury to and activation of tubular cells adhesion molecules, cytokines, chemokines, growth factors that contribute to interstitial fibrosis. MORPHOLOGY CLINICAL Interstitial edema Impaired ability to concentrate urine, evidenced clinically by polyruia or nocturia. Salt wasting Diminished ability to excrete acids (metabolic acidosis) Isolated defects in tubular reabsorption or secretion.

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 17 CAUSES OF TUBULOINTERSTITIAL FIBROSIS NAME Pyelonephritis and UTI TYPE Infections PATHOGENESIS
Acute bacterial infection affecting the tubules, interstitium, and renal pelvis. Chronic complex, bacteria play role but other factors like vescicoureteral reflex and obstruction involved. 85% caused by gram bacilli (E. coli > Proteus > Klebsiella > Enterobacter) In IC pts, viruses can cause infection. (Polyoma virus in kidney allografts) Two routes bacteria can take to reach the kidney 1. Bloodstream (hematogenous infection) 2. Lower urinary tract (ascending infection) which is more common. (A) Bacterial must colonize in distal urethra and introitus and adhere to cells; (B)they must then gain entry to the bladder from the urethra by catheterization or in women, shorter urethral, trauma during intercourse, and absence of antibacterials found in prostatic fluids; (C) multiply in bladder, especially with stasis; (D) vesicourethral reflux; (E) Intrarenal reflux Early stages, the neutrophilic infiltration is limited to the interstitial tissue. With progression, involves tubules and produces a characteristic abscess with destruction of the engulfed tubules. Neutrophils can extend into the collecting tubules but glomerulus is resistant. Three complications of acute pyelonephritis 1. Papillary necrosis diabetics and urinary tract obstructions. Tips or distal 2/3 of pyramids have gray-white yellow areas of coagulation necrosis with preservation of outlines of tubules. Could lead to acute renal failure. 2. Pyonephrosis total or almost complete obstruction. Suppurative exudate is unable to drain and fills the renal pelvis, calyces, and ureter. 3. Perinephric abscess extension of suppurative inflammation though the renal capsule into the perinephric tissue. Healing occurs with PMN infiltrate replaced by M and lymphocytes. Inflammatory foci replaced by scars seen as fibrous depressions. Patchy interstitial suppurative inflammation Intratubular aggregates of neutrophils Tubular necrosis May occur as discrete focal abscesses involving one or both kidneys large wedge shaped areas of suppuration Onset is usually sudden Pain at costovertebral angle Systemic evidence of infection fever and malaise Leukocyte casts

MORPHOLOGY

CLINICAL

Acute Pyelonephritis

Infections

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 18 NAME Chronic Pyelonephritis and Reflux Nephropathy TYPE Infections PATHOGENESIS Chronic tubulointerstitial inflammation and renal scarring pathology in calyces and pelvis Important cause of end-stage kidney disease and kidney destruction in children with severe lower urinary tract abnormalities. Divided into two forms: 1. Reflux-associated more common form of scarring. Occurs early in childhood when superimposition of UTI on congenital vesicourethral reflux and intrarenal reflux. Damage may cause scarring and atrophy of one or both kidney chronic renal insufficiency. 2. Chronic obstructive - Recurrent infections superimposed on diffuse or localized obstructive lesions recurrent bouts of renal inflammation and scarring chronic pyelonephritis. Effects of obstruction parenchymal atrophy. Glomerulosclerosis may be attributable to the adaptive glomerular alterations secondary to loss of renal mass caused by pyelonephritic scarring (renal ablation nephropathy) Immune mech is idiosyncratic, not dose related. Drugs include sulfonamides such as synthetic penicillins (methicillin, ampicillin), other synthetic antibiotics like rifampin, diuretics (thiazides), NSAIDs, allopurinol, cimetidine. Drugs act as haptens, which during secretion by tubules, covalently bind to some cytoplasmic or extracellular component of tubular cells and become immunogenic injury due to IgE and/or cell-mediated immune rxn to tubular cells or their BM. MORPHOLOGY CLINICAL Gross kidneys are irregularly May be insidious scarred which is distinguished onset or present with from chronic GN which the clinical manifestations kidneys are diffusely and of acute recurrent symmetrically scarred. pyelonphritis with Hallmark is a coarse, discrete, back pain, fever, corticomedullary scar frequent pyuria, and overlying a dilated, blunted, or bacteriuria. deformed calyx Loss of tubular fxn concentrating ability Microscopic Involve tubules and interstitum. Some tubules polyuria and show atrophy, other show nocturia. hypertrophy and dialation Some pts develop which can have colloid casts. focal segmental Arcuate and interlobular glomerulosclerosis vessels demonstrate with significant obliterative intimal sclerosis in proteinuria which is a the scarred areas. In presence poor prognostic sign of HTN, hyaline chronic renal arteriosclerosis is seen in failure. entire kidney. May be periglomerular fibrosis Abnormalities in the Begins about 15 days interstitium with edema after administration of and infiltration of the drug lymphocytes and M Fever, eosinophilia, rash Tubulitis is common in 25% of pts, renal abnormalities (hematuria, Variable degrees of mild proteinuria, tubular necrosis and leukocyturia, serum regeneration are present. [creatinine] or ARF with oliguria in 50% of cases.

Acute Drug Induced Interstitial Nephritis (ADN)

Toxins

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 19 NAME Analgesic Nephropathy TYPE Toxins PATHOGENESIS Form of chronic renal disease caused by excessive intake of analgesic mixtures. Chronic tubulointerstitial nephritis with renal papillary necrosis. Papillary necrosis starts first and then cortical tubulointerstitial nephritis. Phenacetin metabolite acetaminophen injures cells by both covalent binding and oxidative damage. Aspirin inhibits vasodilatory effects of prostaglandins, predisposing the papillae to ischemia. Hemodynamically induced acute renal failure Due to inhibitionof vasodilatory prostaglandin synthesis by NSAIDs Acute hypersensitivity interstitial nephritis causes acute renal failure Acute interstitial nephritis and minimal change disease Membranous GN, with nephrotic syndrome Chronic tubulointerstitial nephritis caused by aristolochic acid Acute urate nephropathy Pts who are on chemotherapy drugs (which death of tumor cells and release uric acid as the nuclei disintegrate) have uric acid precipitate in renal tubules (mainly collecting ducts) obstruction and acute renal failure. Crystal formation is enhanced by an acidic pH in collecting ducts. MORPHOLOGY Kidneys are normal or slightly ed. Depressed areas are cortical atrophy overlying necrotic papillae. Papillae show various stages of necrosis, calcification, fragmentation, and sloughing. CLINICAL More common in women than men Early findings include inability to concentrate urine Renal stones develop because of distal renal tubular acidosis acquired. Headache, anemia, GI symptoms, and HTN Without drug withdrawal chronic renal failure

Nephropathy Associated with NSAIDs

Toxins

Chinese Herb Nephropathy Urate Nephropathy

Toxins

Metabolic Diseases

Interstitial fibrosis with a relative paucity of infiltrating interstitial leukocytes Chronic urate nephropathy (gouty nephropathy) Deposition of monosodium urate crystals in the acidic milieu of the distal tubules and collecting ducts as well as in the interstitium. May form birefringent needle-like crystals in tubule or interstitium.

ed incidence of carcinoma in the kidney and urinary tract Nephrolithiasis urate stones present in 22% of pts with gout and 42% of pts with secondary hyperuricemia

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 20 NAME Hypercalcemia & Nephrocalcinosis TYPE Metabolic Diseases PATHOGENESIS Caused by hyperparathyroidism, multiple myeloma, vitamin D intoxication, metastatic bone disease, or excess calcium stones in kidney. Calcinosis chronic tubulointerstitial disease and renal insufficiency. Calcified cellular debris contributes to obstruction of tubular lumens and causes obstructive atrophy of nephrons with interstitial fibrosis and nonspecific chronic inflammation. Bence Jones proteinuria and cast nephropathy some light chains are directly toxic to epithelial cells. Bence Jones proteins combine with the urinary glycoprotein (Tamm-Horsfall protein) under acidic conditions to form large, tubular casts that obstruct the tubular lumina and induce an inflammatory rxn around the casts. Amyloidosis formed by accumulation of light chains with a predisposition to form amyloid fibrils. Light-chain deposition disease Light chains deposit in GBM and mesangium in nonfibrillar forms glomerulopathy OR in tubular BM tubulointerstitial nephritis Hypercalcemia and hyperuricemia MORPHOLOGY Tubular acidosis and salt-losing nephritis CLINICAL Inability to elaborate a concentrated urine is first defect. Further damage slowly progressive renal insufficiency develops

Multiple Myeloma

Neoplasms

Bence Jones tubular casts appear as pink to blue amorphous masses, filling and distending the tubular lumens. Some of the casts are surrounding by multinucleate giant cells that are derived from mononuclear phagocytes. Adjacent interstitial tissue usually shows a nonspecific inflammatory response and fibrosis.

Overt renal insufficiency occurs in half the pts with this disease. Hypercalcemia Hyperuricemia Chronic renal failure occurs insidiously with slow progression Acute renal failure occurs suddenly with oliguria. Precipitating factors include dehydration, hypercalcemia, acute infection, tx with nephrotoxic antibiotics

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 21

HEREDITARY SYNDROMES OF ISOLATED HEMATURIA NAME Alport Syndrome CAUSES X- linked recessive Mutations in gene encoding the alpha5 chain of collagen type IV, a component of the GBM. PATHOGENESIS Defective GBM synthesis because of the production of abnormal collagen type IV underlies the renal lesions. Pts will also synthesize lesser amounts of other components such as alpha 3 (the antigen in Goodpasture Syndrome) MORPHOLOGY LM: Glomeruli almost always involved IF: Absence or borderline BM lesions antibodies to alpha3,4,5 collagen fail to stain both glomerular and tubular BM in classic disease. Absence of alpha 5 staining in skin biopsy. EM: allows for early detection; diffuse GBM thinning; foam cells in interstitum due to fat accumulation; BM looks like basket weaving Diffuse thinning of GBM CLINICAL Nephritis CRF Nerve deafness Various eye disorders (lens dislocation, posterior cataracts, and corneal dystrophy) Gross or microscopic hematuria Red cell casts Symptoms appear ages 5-20 and renal failure develops 20-50 in men.

Thin Basement Membrane Disease (Benign Familial Hematuria)

Traced to genes encoding alpha 3 and 4 chains in type IV collagen Most patients are heterozygous with this defect, those who are homozygous resemble autosomal recessive Alport disease instead/

Asymptomatic hematuria (found in urinalysis) Mild-moderate proteinuria may be present. Renal function normal Excellent prognosis

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 22 DISEASES OF BLOOD VESSELS NAME Benign nephrosclerosis PATHOGENESIS Sclerosis of renal arterioles and small arteries Results in focal ischemia of parenchyma supplied by vessels with thickened walls and consequent narrowed lumens. 2 main changes 1. Medial and intimal thickening response to hemodynamic changes, aging, genetic defects, or some combo. 2. Hyaline deposition in arterioles caused by extravasation of plasma proteins through injured endothelium and by ed deposition of BM matrix. Initial insult is some form of vascular damage to the kidneys (some form of HTN) permeability of small vessels to fibrinogen and other plasma proteins, endothelial injury, focal death of cells of the vascular wall, and plt deposition. Leads to the appearance of fibroid necrosis of arterioles and small arteries, swelling of the vascular intima, and intravascular thrombosis. Hyperplasia of intimal smooth muscle of vessels hyperplastic arteriolosclerosis typical of malignant hypertension and further narrowing of lumens. Kidneys become markedly ischemic and with severe involvement of the renal afferent arterioles, the RAAS receives a powerful stimulus vicious cycle. Constriction of renal artery. Hypertensive effect due to stimulation of renin secretion by JG cells and production of AII Renal renin hypersecretion can be normalized after renal revascularization BP. Sodium retention, endothelin, loss of NO MORPHOLOGY Gross normal or moderately ed size. Cortex have fine, even granularity. Loss of mass mainly due to cortical scarring and shrinking Histologically Hyaline arteriosclerosis; fibroelastic hyperplasia, characteristic lesion of arcuate and interlobular arteries; Vascular narrowing patchy ischemic atrophy of tubules and glomerulus Gross Petechial hemorrhages may appear on the cortical surface from rupture of arterioles or glomerular capillaries (flea-bitten appearance) Histologically Fibroid necrosis of arterioles and Onion-skinning (hyperplastic arteriolitis) vs. in diabetes nodules. Glomeruli become necrotic and infiltrated with neutrophils. Ischemic atrophy and infarction distal to the abnormal vessels may occur. CLINICAL Moderate in renal plasma flow, but the GFR is normal or only slightly . Mild proteinuria 3 groups of HTNsives at ed risk for renal failure 1. Blacks 2. Pts with more severe BP elevations 3. Pts with a 2nd underlying disease, like DM. Malignant HTN which is diastolic >130, papilledema retinopathy, encephalopathy, cardio abnormalities, and renal failure. Hypertensive crisis episodes of loss of consciousness and even convulsions.

Accelerated nephrosclerosis/ Malignant HTN

Renal Artery Stenosis

Most common cause is occlusion by an atheromatous plaque at origin of renal artery. Second most common is fibromuscular dysplasia of the renal artery.

Occasionally a bruit can be heard. Elevated plasma or renal vein renin, response to ACEI, renal scans, and IVP may aid in diagnosis.

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 23 NAME Thrombotic Microangiopathies PATHOGENESIS MORPHOLOGY CLINICAL Endothelial cell injury and activation with Thrombosis in capillaries and Microangiopathic hemolytic subsequent intravascular thrombosis vascular arterioles throughout the body anemia obstruction and vasoconstriction distal ischemia Thrombocytopenia Endothelial denudation exposes subendothelial Some cases of renal failure tissue ed production of PGI2 and NO which due to plt and plt-fibrin enchances plt aggregation and vasoconstriction thrombi in interlobular renal distal ischemia. arteries, arterioles, and glomeruli, together with Factors causing initial injury are bacterial endotoxins and cytotoxins, cytokines, viruses, necrosis and thickening of drugs, abnormal von Willebrands factor multimers. vessel walls. 75% of cases occur after intestinal infection with verocytoxin-producing E. coli (O157:H7). One of the main cause of renal failure in kids. Sudden onset Bleeding manifestations (hematemesis and melena) Severe oliguria, hemturia, a mciroangiopathic hemolytic anemia, and some prominent neurologic changes. Mechanisms unclear. See notes for details if you want. Inherited deficiency in protein factor H, which breaks down the alternative pathway C3 convertase and protects cells from damage by uncontrolled complement activation Manifested by fever, neurologic symptoms, hemolytic anemia, thrombocytopenic purpura, presence of thrombi in glomerulus and afferent arterioles. Acquired or genetic defect in ADAMTS-13 protease which cleaves those big von Willebrand factors down to smaller multimers. Large multimers promote plt aggregation. Atherosclerotic Ischemic Renal Disease Atheroembolic Renal Disease Sickle Cell Disease Nephropathy hematuria and inability to concentrate. Patchy papillary necrosis may occur cortical scarring. Diffuse Cortical Necrosis Renal infarcts

Classic (Childhood) HUS

Adult HUS Familial HUS Idiopathic TTP

Other Vascular Disorders

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 24 URINARY TRACT OBSTRUCTION MOST COMMON CAUSES Congenital abnormalities Posterior urethral valves Bladder neck obstruction Ureteropelvic junction narrowing or obstruction Severe vesicoureteral reflux See below Carcinoma of the prostate Bladder Continuous malignant disease Carcinoma of the cervix or uterus Prostatitis Ureteritis Urethritis Retroperitoneal fibrosis

Hydronephrosis
Dilation of the renal pelvis and calyces associated with progressive atrophy of the kidney due to obstruction to the outflow of urine. Dilation happens because GFR does not decrease initially, even with complete obstruction. Also leads to interstitial inflammatory interstitial fibrosis. With bilateral, partial obstruction, see an ability to concentrate urine as seen with polyuria and nocturia. Some pts will develop distal tubular acidosis, renal salt wasting, secondary renal calculi, and typical tubulointerstitial nephritis with scarring and atrophy of the papilla and medulla. With complete bilateral obstruction, oliguria or anuria is incompatible with long survival unless the obstruction is relieved.

Urinary Calculi BPH Tumors

Inflammation

Sloughed papillae or blood clots Normal pregnancy Uterine prolapsed and cystocele Functional disorders

Neurogenic spinal cord damage or diabetic neuropathy Others dysfunctional obstruction

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 25 UROLITHIASIS Calcium oxalate (70%) Caused by hyperPTH, diffuse bone disease, sarcodosis, other hypercalcemic states 5% have hypercalicemia and hypercalciuria. 55% have hypercalciuria w/o hypercalcemia caused by absorption of Ca in the intestine or intrinsic defect in renal tubular reabsorption of calcium. Hypocitraturia associated with acidosis and chronic diarrhea of unknown cause may produce calcium stones. Formed largely after infections by urea-splitting bacteria (proteus and some staph) which convert urea ammonia Alkaline urine causes the precipitation of these salts. Staghorn calculi are almost always a consequence of infection Common in pts with hyperuricemia and diseases involving rapid cell turnover such as the leukemias. Unexplained tendency to excrete urine of pH below 5.5 may predispose to uric acid stones. Uric acid is insoluble in relatively acidic urine. They are radiolucent Caused by genetic defects in the renal reabsorption of amino acids leading to cystinuria. Form at low urinary pH.

Magnesium ammonium phosphate (15%) Uric Acid (5-10%)

Cystine (1-2%)

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 26 NEOPLASMS OF THE KIDNEY NAME Wilms Tumor MECHANISM/DESCRIPTION The most common 1* renal tumor in kids, 4th most common kid cancer. ed risk with 3 congenital malformations 1. WAGR syndrome aniridia, gential anomalies, and mental retardation 33% risk. 2. Denys-Drash syndrome gonadal dysgenesis and early-onset nephropathy 90% risk. Lesion is diffuse mesangial sclerosis 3. Beckwith-Wiedemann syndrome organomegaly omphalocele, hemi-hypertrophy and abnormal large cells in adrenal cortex See examples below Most common sites of metastasis are lungs, bones, regional lymph nodes, liver, adrenals, and brain. 5 year survival rate is 45-70% without metastasis. 15-20% with. Nephrectomy has been the tx of choice partial preserves renal function with similar outcome. GENETICS Associated with ch 11 WT1 gene which encodes a tx factor in kidney crucial for development (mutations associated with WAGR and DD syn) WT2 gene associated with BW syn Usually de novo though CLINICAL Present with large ab mass Hematuria Pain in ab after trauma, Intestinal obstruction HTN KEY WORDS/OTHER Children 2-5 years old 90% 2 year survival which implies cure. Classic triphasic combination of blastemal, stromal, and epithelial cell types.

Renal Cell Carcinoma General

2/3 of pts with VonHippel Lindau syndrome will get this Hereditary papillary carcinoma

3 classic diagnostic features but only in 10% Costovertebral pain Palpable mass Hematuria (most reliable) Tumor will give rise to constitutional symptoms Number of paraneoplastic syndromes due to abnormal hormone production

Occurs in older individuals 6-7th decade of life. Tobacco is most significant risk factor Obesity, HTN, unopposed estrogen therapy, and environmental exposures also risk factors. ed incidence in pts with CRF, cystic disease, and tuberous sclerosis

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 27 Types of Renal Cell Carcinomas MECHANISM/DESCRIPTION GENETICS 70-80% of renal cell cancers Most cases are sporadic Made up of cells with clear or granular Almost all have loss of cytoplasm and are nonpapillary sequences in short arm of chromosome 3 (3p12 3p26) VHL gene (see above) is on 3p25.3. It acts as a tumor suppressor gene 10-15% of renal cancers Not associated with 3p deletions Most common type of renal cell carcinoma in dialysis patient who have Most common cytogenic cystic disease abnormalities are trisomies 7, 16, and 17. PRCC gene (papillary renal cell carcinoma) on chromosome 1 in sporadic forms mostly in children 5% of renal cell cancer Exhibit multiple chromosome losses and extreme Thought to grow from intercalated cells hypodiploidy of collecting ducts and have an excellent prognosis compared with that of clear cell and papillary cancers. 1% or less Arise from collecting duct cells in medulla. Characterized by nests of malignant cells enmeshed within a prominent fibrotic stroma, typically in medullary location

NAME Clear cell carcinoma

MORPHOLOGY Arise from proximal tubular epithelium Occur as solitary unilateral lesions Margins usually sharply defined and confined w/i the capsule.

Papillary carcinoma

Arise from distal convulted tubules. Can be multifocal and bilateral Typically hemorrhagic and cystic Tendency to invade renal vein and grow as a solid column of cells wi the vessels. Psammoma bodies are present

Chromophobe renal carcinoma

Composed of cells with prominent cell membranes and pale eosinophilic cytoplasm, usually with a halo around the nucleus.

Collecting duct carcinoma

Irregular channels lined by highly atypical epithelium with a hobnail pattern

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 28 PROSTATE/BLADDER CHANGES/NEOPLASMS NAME Prostatitis PATHOGENESIS/EPI Acute bacterial prostatitis Caused by the same bugs that would cause a urinary tract infections --which are E. coli, other gram rods, enterococci, and staphylococci. Sometimes follows some surgical manipulation on the urethra or prostate gland itself, such as catheterization, cystoscopy, urethral dilation, or resection procedures on the prostate. Chronic bacterial prostatitis- One thing that is noticeable, however, is recurrent urinary tract infections caused by the same organism. Chronic abacterial prostatitisMost common form today. There is no hx of recurrent urinary tract infections though. Granulomatous prostatitis- Most common cause in the US is related to instillation within the bladder of Bacillus CalmetteCuerin (BCG) for tx of superficial bladder cancer. MORPHOLOGY On examination, prostate is exquisitely tender and boggy CLINCIAL Clinically associated with fever, chills, and dysuria. Diagnosis by urine culture and clinical features. TREATMENT Antiboitics

May present with lower back pain, dysuria, and perineal and suprapubic discomfort or may be asymptomatic.

Difficult to diagnosis and treat.

Clinically it is indistinguishable from chronic bacterial prostatitis.

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 29 NAME Benign Prostatic Hyperplasia (Nodular Hyperplasia) PATHOGENESIS/EPI Most hyperplasias occur in the transitional zone. 20% of men 40 years, 70% of men by 60, 90% of men by 70. 30% of white American males over 50 have moderate to severe symptoms. Stromal cells in the prostate are the main site of dihydrotestosterone synthesis, which is the main trophic factor mediating BPH. MORPHOLOGY CLINCIAL Clinical symptoms of lower urinary tract obstruction are also due to smooth musclemediated contraction of the prostate, which is mediated by the 1adrenoreceptor localized to the prostatic stroma. Compression of the urethra with difficulty in urination Retention of urine in the bladder with subsequent distention and hypertrophy of the bladder, infection of the urine, and development of cystitis and renal infections. Frequency, nocturia, hestitancy, overflow dribbling, and dysuria. TREATMENT -adrenergic receptor antagonists for the relief of urinary obstruction in pts with BPH. Since 5-reductase is the enzyme that converts testosterone DTH, inhibitors of this enzyme have decreased prostatic volume and urinary obstruction due to the in DTH. Mild cases can be treated with ing fluid intake, especially prior to bedtime, moderating the intake of alcohol and caffeine-containing products, and following timed voiding schedules. Transurethral resection of the prostate (TURP) is effective in reducing symptoms, improving flow rates, and decreasing postvoid residual urine. It is the first line of therapy in certain situations such as with recurrent urinary retention.

Hyperplasia of prostatic stromal and epithelial cells, resulting in the formation of large, fairly discrete nodules in the periurethral region of the prostate. If large enough, can compress the urethra to the point of obstruction. Microscopically, the hallmark of BPH is nodularity due to glandular proliferation or dilation and to fibrous or muscular proliferation of the stroma.

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 30 NAME PATHOGENESIS/EPI MORPHOLOGY Glands lined by a single uniform layer of cuboidal or low columnar epithelium. More crowded and no papillary infoldings. High-grade prostatic intraepithelial neoplasia (PIN) are benign glands that demonstrate nuclear anaplasia. es risk of prostate cancer. CLINCIAL Most prostatic cancers arise peripherally, away from the urethra, therefore, urinary symptoms occur late, which are hestitancy, dysuria, frequency, and hematuria. Can locally extend into the seminal vesicles and the base of the urinary bladder urethral obstruction Hematogenous spread to bone (osteoblastic) Gleason grading: Grade 1 (well-differentiated) Grade 5 (no glandular differentiation and tumor cells infiltrate the stroma) Top two patterns are added together to get the score (2-10) Classically produce painless hematuria Frequency, urgency, and dysuria sometimes When urethral orfice is involved, pyelonephritis or hydronephrosis may follow. TREATMENT Surgery, radiotherapy, and hormonal manipulations Most common tx for localized prostate cancer is radical prostatectomy External beam radiotherapy used to tx prostate cancer that is too locally advanced to be cured by surgery. Endocrine therapy is the mainstay for tx of advanced, metastatic carcinoma. Main aim is to deprive the tumor cells of testosterone (achieved by orchiectomy)

Prostate Adenocarcinoma

Most carcinomas occur in the peripheral zone. Most common form of cancer in men, second most common cause of death in men. Androgens play a role, but dont know how. Their role is essentially permissible b/c androgens are required for the maintenance of the prostatic epithelium. Strong family history correlates with diease at an earlier age. Most common genetic alteration is hypermethylation of glutathione S-transferase (GSTP1) gene promoter located on ch 11q13.

Bladder Cancer

Urothelial tumors represent 90% of all bladder tumors. Any of these lesions can be seen where there is urothelium (renal pelvis distal urethra) Nonivasive papillary tumors arise from papillary urothelial hyperplasia more common than Carcinoma in situ is flat urothelial

95% are of epithelial origin. Most are composed of urothelial (transitional) type cells. Overall papillary tumors are low grade. Papillomas mostly seen in younger pts.

Treatment depends on grade, stage, and whether the lesion is flat or papillary Small, localized papillary tumors that are not high grade initial diagnostic transurethral resection is all that is done.

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 31 carcinoma 50% of pts at presentation the tumor has already invaded the bladder wall. Major in survival when it invades musclaris propria (detrusor muscle) Squamous cell carcinomas make up 3-7% of bladder carcinomas. Nearly always associated with chronic bladder irritation and infection. Risk factors smoking, industrial exposure to arylamines, schistosoma haematobium infections, long term use of analgesics, heavy long term exposure to cyclophosphamide, prior exposure of the bladder to radiation. Two pathway model for carcinogensis 1) initiated by deletions of tumor-suppressor genes on 9p and 9q papillary tumors 2) initiated by p53 mutations CIS with loss of ch 9 invasion. Usually arise singly as small, delicate structures superficially attached to the mucosa by a stalk. Covered by transitional epithelium. Inverted papillomas benign lesions that are interanastomosing cords of bland urothelium extending down into the lamina propria. High grade papillary cancerdyscohesive and large hyperchromatic nuclei Carcinoma in situ presence of malignant cells within a flat urothelium. Lack of cohesiveness shedding of cells into the urine give rise to denuded urothelium with only a few CIS cells clinging to the BM. Invasive urothelial cancercan be associated with high grade papillary or CIS. Multifocal bladder tumors topical chemotherapy into the bladder, in the immediate postoperative period. Pts at high risk of recurrence receive topical immunotherapy of intravesical installation of BCG. Tumor invading the muscualris propria radical cystectomy

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 32 URETERS CONGENTIAL ANOMALIES DOUBLE URETERS derived from a double or split ureteral bud. The two commonly are joined within the bladder wall and drain though a single ureteral orifice. The majority are unilateral and of no clinical significance. URETEROPELVIC JUNCTION OBSTRUCTION results in hydronephrosis and is the most common cause of that in infants and children. There is an agenesis of the kidney on the opposite side, probably resulting from obstructive lesions in utero . DIVERTICULA are saccular outpouchings of the ureteral wall. They are rare but important as pockets of stasis and secondary infections.

INFLAMMATION TUMORS AND TUMOR-LIKE LESIONS OBSTRUCTIVE LESIONS

HYDROURETER- dilation of the ureters that may reflect some neurogenic defect in the innervation of the ureteral musculature hydronephrosis URETERITIS may develop as one component of UTIs. Persistence of infection or repeated acute exacerbations may give rise to chronic inflammatory changes within the ureters. BENIGN TUMORS most common are MALIGNANT TUMORS majority are transitional cell fibroepithelial polyps and leiomyomas. carcinomas. Patterns similar to those arising in renal pelvis, calyces, and bladder INTRINSIC EXTRINSIC SCLEROSING RETROPERITONEAL 1. Calculi - of renal origin. Impact 1. Pregnancy FIBROSIS at loci of ureteral narrowing 2. Periureteral inflammation Uncommon cause of ureteral which are ureteropelvic junction, salpingitis, diverticulitis, narrowing or obstruction where ureters x iliac vessels, and peritonitis, sclerosing characterized by a fibrous where they enter bladder. retroperitoneal fibrosis proliferative inflammatory 2. Strictures 3. Endometriosis process encasing the 3. Tumors see above. Usually 4. Tumors of the rectum, retroperitoneal structures and transitional cell carcinomas bladder, prostate, ovaries, uterus, causing hydronephrosis. Causes 4. Blood clots cervix, lymphomas, sarcomas. include drugs, adajacent Neurogenic interruption of the inflammatory conditions, or neural pathways to the bladder. malignant disease.

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 33 URINARY BLADDER CONGENTIAL ANOMALIES DIVERTICULA - A pouchlike eversion or evagination of the bladder EXSTROPHY VESICOURETERAL wall. Congenital may be due to focal failure of development of Developmental failure in the REFLUX most normal muscle or to some urinary tract obstruction during fetal anterior wall of the common and serious development. Acquired are often seen with prostatic enlargement, abdomen and in the anomaly. Major producing obstruction to urine outflow, and marked muscle bladder, so that the bladder contributor to renal thickening of the bladder wall. The increased intravesical pressure either communicates infection and scarring. causes outpouching of the bladder wall and formation of diverticula. directly through a large Signifant because its a site of urinary stasis and predispose to defect with the surface of infection and the formation of bladder calculi. Predisposes to the body or lies as an vesicoureteral reflux as a result of impingement on the ureter. opened sac. ACUTE AND CHRONIC CYSTITIS INTERSTITIAL CYSTITIS MALACOPLAKIA Peculiar pattern POLYPOID CYSTITIS Bacterial pyelonephritis is (HUNNER ULCER) A of vesical inflammatory reaction Inflammatory frequently preceded by infection persistent, painful form of characterized macroscopically by condition resulting of the urinary bladder, with chronic cystitis occurring soft, yellow, slightly raised mucosal from irritation to the retrograde spread into the in women and associated plaques 3-4 cm in diameter and bladder mucosa. kidneys and their collecting with inflammation and histologically by infiltration with Indwelling catheters ducts. Organisms include E. coli, fibrosis of all layers of the large, foamy M with occasional are common to cause Proteus, Klebsiella, and bladder wall. Clinical this but any injurious multinucleated giant cells and Enterobacter along with Candida features include severe, agent may give rise to interspersed lymphocytes. Related albicans and Schistosoma subrapubic pain, the lesion. to chronic bacterial infections haematobium, viruses, frequency, urgency, particularly E. coli. ed frequency Chlamydia, and Mycoplasma. hematuria, and dysuria with tranplant recipients. Usually Clincial features include without bacterial M points to defects in phagocytic frequency, low ab pain, dysuria. infection. Mast cells are or degradation of undigested prominent. bacteria in phagosomes. SEE ABOVE In males, the most common lesion is enlargement of the prostate gland due either to nodular hyperplasia or to carcinoma. In females, outlet obstruction is more often caused by cystocele of the bladder.

INFLAMMATION

NEOPLASMAS OBSTRUCTIVE LESIONS

CHARTS OF KIDNEY AND LOWER URINARY TRACT PATHOLOGY 34 URETHRA INFLAMMATIONS URETHRITIS Classically divided into gonococcal and non-gonococcal urethritis (E. coli and other enterics) Often accompanied by cystitis in women and prostatitis in men. Various strains of Chlamydia are the cause of 25-60% of nongonococcal urethritis in men and about 20% in women. Urethritis is one of the components of Reiter syndrome, which comprises the clinical triad of arthritis, conjunctivitis, and urethritis. URETHRAL CARUNCLE inflammatory lesion PRIMARY CARCINOMA OF THE URETHRA uncommon presenting as a small, red, painful mass about lesion. It tends to occur in advanced age in women. the external urethral meatus in the female Proximal urerthra tumors tend to show urothelial patient. Histologically it is composed of highly differentiation and are analogous to those occurring vascularized, young, fibroblastic connective within the bladder. Those lesions found within the tissue, usually heavily infiltrated with leukocytes. distal urethra are more typically squamous carcinomas.

TUMORS AND TUMOR-LIKE LESIONS