Pathology of the Urinary System

Professor Peivand Pirouzi, Ph.D., M.B.A., C.C.P.E.School of Health Sciences Seneca College of Applied Arts and TechnologyToronto, Canada

Normal Urinary Tract

Normal Nephron

Overview of Major Kidney Diseases

• Immunologic disorders (e.g., glomerulonephritis)

• Metabolic disorders (e.g., diabetic nephropathy)

• Circulatory disturbances (e.g., prerenal renal failure)

• Bacterial infections (e.g., pyelonephritis – urinary tract infection)

• Tumors

• Urinary Tract Infection movie 4’

Developmental Disorders

• Renal agenesis: bilateral or unilateral

• Horseshoe kidney (renal fusion or super kidney)

• Polycystic kidney disease (inherited, progressive failure)

• Multicystic renal dysplasia (unilateral, dysfunctional kidneys)

Autosomal Polycystic Kidney Disease

Glomerulopathies

DIS- -Disseminated intravascular coagulation

GN: Glomerulonephritis

SLE: systemic lupus erythematosus

Glomerular Diseases

• Immunologic diseases: glomerulonephritis

•Metabolic diseases: diabetes, amyloidosis*

•Circulatory disturbances: hypertension, atherosclerosis, disseminated intravascular coagulation (DIS)

* buildup of misfolded proteins known as amyloids

Immune-Mediated GlomerularDiseases: Clinical Presentation

• Acute renal failure (RPGN): crescentic glomerulonephritis (GN)

• Nephritic syndrome: acute GN, systemic lupus erythematosus (SLE)

• Nephrotic syndrome: lipoid nephrosis, membranous nephropathy*, focal segmental glomerulosclerosis**

• Isolated hematuria/proteinuria: Berger’s (IgA) disease, SLE

• Chronic renal failure: chronic GN

*deposition of immune complexes on the glomerular basement membrane

(GBM) with GBM thickening

**scar tissue in the filtering unit of the kidney

Nephritic Syndrome: Clinical Features

• Hematuria

• Red blood cell (RBC) casts, dysmorphic/fragmented RBCs in urinary sediment

• Oliguria (the production of abnormally small amounts of

urine.)

• Proteinuria

• Hypoalbuminemia

• Edema, generalized

• Hypertension

Normal Glomerulus byElectron Microscopy (EM)

Poststreptococcal AcuteGlomerulonephritis by Electron Microscopy

Acute Glomerulonephritis: Microscopy

Crescentic Glomerulonephritis

Membranous Nephropathy: Light Microscopy

Membranous Nephropathy: Immunofluorescence Microscopy

Membranous Nephropathy: Electron Microscopy

Nephrotic Syndrome: Electron Microscopy

End-Stage Glomerulopathy: Macroscopic Features

End-Stage Glomerulopathy: Microscopic Features

Diabetic Glomerulosclerosis

Urinary Stones

• Calcium stones: calcium phosphate or calcium oxalate stones (75%)

• Struvite stones (15%)

• Uric acid stones (5%)

• Cystine stones (1%)

Struvite Stone

Urinary Infections

• Pyelonephritis: invasion of kidney

• Acute

• Chronic

Symptoms: Fever, Chills, high WBC

• Cystitis: superficial infection

• Acute

• Chronic

Symptoms: Dysurea (Difficult or painful urination) , urgency

Routes of Renal Infection

Chronic Pyelonephritis

Acute Cystitis

Chronic Cystitis

Circulatory Disturbances

• Acute tubular necrosis*

• Nephroangiosclerosis

• Hypertension

• ATN: death of tubular epithelial cells that form the renal tubules of

the kidneys

• ** associated with hypertension; sclerosis of the renalarterioles redu

ces blood flow that can lead to kidney failure and heart failure

• *** also called renovascular hypertension, is elevated blood

pressure caused by kidney disease. It can usually be controlled by

blood pressure drugs.

Neoplasms of Urinary Tract

• More often malignant than benign

• Wilms’ tumor: only neoplasm found in children; all others occur in older adults

• Originate from epithelial cells of kidney or urothelium (transitional cell lining of pelvis, ureter, urinary bladder, posterior urethra)

Urinary Tract Tumors• Most important:

• Wilms’ tumor

• Transitional cell carcinoma

• Renal cell carcinoma:

Urinary Tract Tumors (Cont’d)

Renal Cell Carcinoma

• Common: 27,000 new cases; 11,000 cancer-related deaths per year in U.S.

• No strong risk factors identified

• Found in 5% of chronic end-stage kidney disease patients

• Occurs in older adults (>50 years)

• Prognosis guarded: 50% survive 5 years

Renal Cell Carcinoma: Macroscopic Features

Renal Cell Carcinoma: Microscopic Features

Renal Cell Carcinoma: Clinical Features

• Hematuria: most common finding (50%)

• Typical triad (hematuria, flank pain, palpable abdominal mass) found only in 10%

• Nonspecific symptoms common, often found accidentally (“internist’s tumor”)

• Paraneoplastic syndromes: hypercalcemia, erythrocytosis, or amyloidosis (20%)

Wilms’ Tumor

• Tumor of infancy, childhood

• Composed of immature cells resembling renal blastemal (mass of undifferentiated cells)

• Related, in some cases, to deletion or mutation of tumor suppressor gene WT1

• May be familial or bilateral in 10% cases

• Good prognosis: surgery + chemotherapy

Carcinoma of Urinary Bladder

• Most common cancer of urinary tract: 52,000 new cases per year in the U.S.; 10,000 cancer-related deaths

• Most tumors are transitional carcinomas, but may be squamous or adenocarcinomas

• Variable prognosis: depends on grade/stage of tumor

Urinary Bladder Carcinoma

Urinary Bladder Carcinoma: Microscopic Features

Urinary Bladder Carcinoma:Clinical Features

• Hematuria

• Dysuria

• Lower abdominal pain

• Diagnosis made on urine cytology and cystoscopic biopsy

• Grade I tumors localized to mucosa: 98% 5-year survival, but tend to recur

• Grade III tumors with metastases: 15% 5-year survival

Bladder Cancer