The Urinary System

KIDNEY

1. Gross Anatomy

Kidneys are bean-shaped paired organs.
Weight: ~150 gm in adult males, ~135 gm in adult females.
Located on either side of the vertebral column.
Hilum (on medial side): Entry/exit for renal artery, vein, lymphatics, and ureter.
Surrounded by a thin fibrous capsule (especially adherent at the hilum).

2. Gross Internal Structure

Cut surface reveals three main parts:

Cortex (outer):
- ~1 cm thick.
- Contains all glomeruli and ~85% of nephron tubules.
- Columns of cortex between pyramids: Renal columns of Bertin (contain interlobar arteries).
- Medullary rays: Striated structures in cortex made of straight tubules headed to the medulla.
Medulla (inner):
- Contains 8–18 renal pyramids (cone-shaped).
- Base of pyramid: Cortico-medullary junction.
- Apex (renal papilla): Opens into minor calyces for urine drainage.
Renal Pelvis (innermost):

Funnel-shaped collecting area.
Minor calyces (8–18): Collect urine from papillae.
Join into 2–3 major calyces, which drain into the renal pelvis → ureter.

🔹 Histology of the Kidney

Each kidney contains ~1 million nephrons, which are the functional units of urine formation.

Parts of a nephron:

Glomerulus + Bowman’s capsule
Proximal convoluted tubule (PCT)
Loop of Henle
Distal convoluted tubule (DCT)
Collecting duct

🔹 Important Functional Components

1. Renal Vasculature

Renal artery (from aorta) → divides into anterior & posterior divisions.
Branches:

Segmental arteries → Interlobar arteries → Arcuate arteries → Interlobular arteries
Afferent arterioles from interlobular arteries supply individual glomeruli.
Efferent arterioles leave glomeruli:

Form peritubular capillaries (around cortical nephrons)
Form vasa recta (in juxtamedullary nephrons) → supply medulla.

🧠 Clinical Concepts:

Cortex gets ~90% of blood; thus, more prone to hypertension-related damage.
Medulla has low perfusion, making it vulnerable to ischemia/necrosis.
Arteries are end-arteries (no collateral circulation): Occlusion = infarction.

2. Glomerulus

Formed by capillary tuft inside Bowman’s capsule.
Blood supply: Afferent arteriole in → Efferent arteriole out
Covered by podocytes (visceral epithelial cells).
Bowman’s space: Where filtrate collects before entering proximal convoluted tubule (PCT).

Glomerular Filtration Barrier:

Fenestrated endothelium
Glomerular basement membrane (GBM): 3 layers – lamina rara interna, lamina densa, lamina rara externa
Slit pores between podocyte foot processes

✅ GFR (Glomerular Filtration Rate) ≈ 125 ml/min
✅ No proteins or cells in filtrate under normal conditions

3. Juxtaglomerular Apparatus (JGA)

A specialized structure at the vascular pole of the renal corpuscle, where the distal convoluted tubule (DCT) comes into close contact with the afferent arteriole (and partly efferent arteriole) of the same nephron.

It plays a key role in autoregulation of GFR and systemic blood pressure control through the renin–angiotensin–aldosterone system (RAAS).

Components of JGA

Juxtaglomerular (JG) cells
- Modified smooth muscle cells in the wall of the afferent arteriole.
- Contain renin granules → secrete renin in response to:
  - ↓ Renal perfusion pressure (stretch receptors).
  - Signals from macula densa (low NaCl).
Macula densa
- Specialized epithelial cells of the distal convoluted tubule (DCT).
- Located where DCT touches the afferent arteriole.
- Function: Sense NaCl concentration in tubular fluid.
  - Low NaCl → signals JG cells → ↑ renin release.
  - High NaCl → signals afferent arteriole → vasoconstriction → ↓ GFR.
Extraglomerular mesangial cells (Lacis cells)
- Transmit signals between macula densa & JG cells. Provide structural support and phagocytosis.

Functions of JGA

Regulation of Blood Pressure & GFR via RAAS:

↓ BP or ↓ NaCl → JG cells release renin.
Renin → converts angiotensinogen → angiotensin I → angiotensin II.
Angiotensin II → vasoconstriction + aldosterone release → ↑ BP & Na⁺ retention.

4. Tubules

i) Proximal Convoluted Tubule (PCT):

First part of nephron after Bowman’s capsule.
Lined by cuboidal cells with brush border (microvilli).
Function: Reabsorbs ~80% of water and electrolytes like Na⁺, K⁺, glucose, amino acids, etc.

ii) Loop of Henle:

Parts: Descending limb → Thin ascending → Thick ascending
Descending: Simple epithelium
Ascending: Columnar epithelium
Function: Concentrates urine via:
- Active transport of ions
- Passive reabsorption of water

iii) Distal Convoluted Tubule (DCT):

Continuation from thick ascending limb.
Lined by cuboidal cells.
Macula densa (part of JGA).
Functions:
- Sodium balance
- Urinary concentration

iv) Collecting Ducts:

Final part where filtrate becomes urine.
Lined by cuboidal cells (no brush border).
Reabsorbs water under ADH influence, and secretes H⁺ & K⁺ ions.

RENAL FUNCTION TESTS

Functions of the Kidneys

The kidneys perform the following vital roles:

Excretion of waste products from protein metabolism (e.g., urea, creatinine).
Acid-base balance by excreting H⁺ and bicarbonate ions.
Water and salt regulation through hormones.
Hormone production:
- Renin → regulates blood pressure.
- Erythropoietin → stimulates RBC production.

Parameters Evaluated in Renal Function Tests

Renal function is assessed via:

Renal blood flow
Glomerular filtration rate (GFR)
Tubular function
Urinary outflow (to detect obstruction)

Main Groups of Renal Function Tests

Urine Analysis
Concentration and Dilution Tests
Blood Chemistry
Renal Clearance Tests

1. Urine Analysis

i. Physical Examination

24-hour output: Normal = 700–2500 mL/day (average = 1200 mL)
Colour: Clear, pale or straw-colored (due to urochrome pigment)
Specific Gravity: Measures concentration (Normal = 1.003–1.030)
pH also assessed

ii. Chemical Tests

Detect protein, glucose, blood (RBCs/hemoglobin)
Dipstick tests: Paper strips with reagents give instant results

iii. Bacteriological Examination

Requires a midstream urine sample, collected aseptically

iv. Microscopy

Fresh, unstained sample examined for:
- RBCs, WBCs, epithelial cells, crystals, and casts
Casts: Protein-based cylindrical structures formed in tubules
- Types of casts:

Hyaline (non-inflammatory)
Leukocyte (inflammatory)
Red cell (haematuria)

2. Concentration and Dilution Tests

Evaluate the tubular function of nephrons:

i. Concentration Test (Water Deprivation Test)

Patient is deprived of fluids
Normal: High solute urine (Specific gravity ≥ 1.025)
Abnormal: Fixed specific gravity (~1.010)

ii. Dilution Test (Excess Water Intake)

Normal: Diluted urine (Specific gravity ≤ 1.003)
Diseased tubules: Fixed specific gravity, fails to dilute urine

3. Blood Chemistry Tests

Assesses retention of waste products:

Urea: Normal = 20–40 mg/dL
Blood Urea Nitrogen (BUN): 10–20 mg/dL
Creatinine: 0.6–1.2 mg/dL
β2-Microglobulin: Increases in glomerular/tubular diseases

Azotaemia: ↑ BUN and creatinine
Uraemia: Azotaemia + clinical symptoms

4. Renal Clearance Tests

Measure glomerular filtration rate (GFR) and renal blood flow

Formula:

C = (U × V) / P
Where:

C = Clearance (ml/min)
U = Urine concentration
V = Urine volume/min
P = Plasma concentration

i. Inulin/Mannitol Clearance

Most accurate for GFR
Requires IV infusion and timed urine samples

ii. Creatinine Clearance

Easy and widely used
Uses 24-hour urine + blood sample

iii. Urea Clearance

Less sensitive
Affected by diet, hydration, infection, etc.

Renal Biopsy

Used for diagnosing kidney disease:

Fixed in alcoholic Bouin’s solution
Examined with:

PAS stain (for basement membrane)
Silver stain (for glomerular/tubular outlines)
Immunofluorescence (for antigens, Ig, complement)
Electron microscopy (ultrastructural changes)

RENAL FAILURE

Types of Renal Diseases

Glomerular diseases – Usually immunologic
Tubular diseases – Often toxic/infectious, acute
Interstitial diseases – Involve tubules + interstitium
Vascular diseases – Due to hypertension or ischemia

Other conditions: Congenital anomalies, obstructions, tumors

Major Renal Syndromes

Acute Renal Failure (ARF)
Chronic Renal Failure (CRF)

ACUTE RENAL FAILURE (ARF)

Definition

Sudden onset of kidney dysfunction
↓ Urine output (oliguria (abnormally low urine output) or anuria)
↑ Waste products in blood (urea, creatinine) → uraemia

Causes of ARF

Pre-renal (↓ Blood supply):
- Hypovolemia, low cardiac output, vascular disease
Intra-renal (Damage inside kidney):
- Glomerular diseases
- Acute tubular necrosis (from toxins or ischemia) aminoglycosides, amphotericin B, cisplatin, radiocontrast, hemoglobin/myoglobin from hemolysis or rhabdomyolysis
- Tubulointerstitial nephritis
- Pyelonephritis (A bacterial infection of the kidney, mainly involving the renal pelvis and renal parenchyma (tubules and interstitium)
Post-renal (Urine flow blocked):
- Obstruction in ureter, bladder, or urethra

Note: Pre- and post-renal causes may lead to intra-renal disease if untreated.

Clinical Patterns of ARF

Acute Nephritic Syndrome (A clinical syndrome resulting from acute inflammation of the glomeruli (glomerulonephritis))
- Often from post-streptococcal glomerulonephritis
- Features:
  - Mild proteinuria
  - Haematuria
  - Oedema
  - Mild hypertension
Tubular Pathology (Acute Tubular Necrosis)
- Three stages:
  - Oliguric Phase (7–10 days): ↓ Urine (<400 ml/day), azotemia, acidosis, hyperkalemia, pulmonary edema
  - Diuretic Phase: ↑ Urine output (dilute), tubules healing
  - Recovery Phase: Full recovery in some; others may die or progress to chronic failure
Pre-renal Syndrome
- No damage to nephron structures
- From ischemia or heart failure
- ↓ GFR → oliguria, fluid retention, but tubular concentration ability remains intact

Chronic Renal Failure (CRF)

Definition

Chronic Renal Failure is a progressive, irreversible decline in kidney function due to slow destruction of the renal parenchyma (The functional tissue of the kidney that performs filtration, reabsorption, and secretion. Composed of renal cortex and renal medulla), ultimately resulting in death when most nephrons are damaged.

Major complication: Metabolic acidosis (↓ Bicarbonate (HCO₃⁻) in blood)
Biochemical hallmark: Azotemia (high nitrogenous waste in blood)
Clinical syndrome: Uremia

Etiopathogenesis

CRF can result from all types of chronic kidney diseases, primarily categorized into:

1. Glomerular Pathology

Glomerular diseases often have an immune basis, leading to nephrotic syndrome (proteinuria, hypoalbuminaemia, edema).

i. Primary Glomerular Causes:

Chronic glomerulonephritis from:
- Membranous glomerulonephritis (Characterized by subepithelial immune complex deposits and thickened GBM)
- Membranoproliferative glomerulonephritis (Pattern with GBM thickening + mesangial proliferation)
- Minimal change disease (Characterized by podocyte foot process effacement)
- Anti-GBM nephritis (Caused by autoantibodies against GBM)

ii. Systemic Glomerular Causes:

Systemic lupus erythematosus (SLE);

Autoimmune disease → formation of antinuclear antibodies (ANA), anti-dsDNA
Immune complex deposition in glomeruli → complement activation → glomerular injury.

Diabetic nephropathy (Persistent hyperglycemia → non-enzymatic glycosylation of proteins → thickened GBM).
Serum sickness nephritis

Occurs after exposure to foreign proteins (e.g., antiserum, certain drugs, infections).
Type III hypersensitivity → circulating antigen-antibody complexes deposit in glomeruli.

2. Tubulointerstitial Pathology

Affects tubular reabsorption and secretion → leads to polyuria and loss of concentration ability.

Categories:

Vascular: Nephrosclerosis ((thickening and hardening) of small renal arteries and arterioles from long-standing hypertension
Infectious: Chronic pyelonephritis
Toxic: Chronic analgesic nephritis (phenacetin, aspirin), heavy metals (lead, cadmium)
Obstructive: Urinary obstruction due to stones, tumors, enlarged prostate

Stages of CRF

Decreased Renal Reserve:
- ~50% nephron function remains
- Normal BUN/Creatinine
- Asymptomatic except during stress
Renal Insufficiency:
- ~75% nephron loss
- GFR ~25%
- Elevated BUN/Creatinine
- Symptoms: Polyuria, nocturia (wake up at night one or more times to pass urine)
Renal Failure:
- ~90% nephron loss
- GFR ~10%
- Loss of sodium and water regulation → Oedema, acidosis, hypocalcemia, uremia
End-Stage Kidney:
- GFR <5%
- Full-blown uraemic syndrome with multi-organ involvement

Clinical Features of CRF

A. Primary (Renal) Uraemic Manifestations

Metabolic Acidosis:
- ↓ Bicarbonate, ↑ H⁺
- hyperkalaemia
Hyperkalaemia:
- Cardiac arrhythmias
- Nausea, muscle weakness, flaccid paralysis
Sodium & Water Imbalance:
- Hypervolaemia, hypertension
Hyperuricemia:
- Can cause gout (uric acid crystals in joints)
Azotemia:
- Accumulation of urea, creatinine → toxicity

B. Secondary (Systemic) Uraemic Manifestations

Anaemia:
- ↓ Erythropoietin
- GI bleeding may worsen anaemia
Skin:
- yellow skin due to urochrome
- Uraemic frost (white powdery deposits on skin)
Cardiovascular:
- Hypertension
Respiratory:
- Pulmonary oedema
Digestive System:
- Mucosal ulceration → GI bleeding
- Nausea, vomiting, diarrhoea
Skeletal System (Renal Osteodystrophy):
- Osteomalacia (due to ↓ active Vitamin D)
- Osteitis fibrosa (due to ↑ PTH → bone resorption)

Congenital Malformations of the Kidney

Prevalence

~10% of individuals
May be isolated or associated with other organ malformations

Types

I. Amount of Renal Tissue

Hypoplasia: One or both kidneys underdeveloped
Supernumerary kidney: Extra kidney present

II. Position/Form/Orientation

Ectopic kidney (e.g., pelvic kidney)
Horseshoe kidney (fusion of kidneys)

III. Differentiation Abnormalities

Cystic diseases of the kidney

Cystic Diseases of the Kidney

Classification

A. Non-Neoplastic Cystic Lesions

Multicystic Renal Dysplasia (Potter Type II)
Polycystic Kidney Disease (PKD)
- ADPKD (Adult, autosomal dominant)
- ARPKD (Infantile, autosomal recessive)
Medullary Cystic Disease
- Medullary sponge kidney
- Nephronophthisis
Simple renal cysts
Acquired cysts
Para-renal cysts

B. Neoplastic Cystic Lesions

Cystic nephroma
Cystic partially differentiated nephroblastoma
Cystic Wilms’ tumor

Multicystic Renal Dysplasia (Potter Type II)

Definition:

Abnormal kidney development with disorganized structure and non-functional cysts
Most common congenital cystic renal disease in infants

Associated Anomalies:

PUJ obstruction
Urethral atresia
Congenital syndromes (e.g., Down syndrome)

Morphology:

Unilateral or bilateral
Gross: Enlarged, cystic kidney (grape-like)

Clinical Features:

Flank mass in infants
Unilateral cases: Good prognosis after nephrectomy
Bilateral cases: Fatal unless transplanted early

2. Polycystic Kidney Disease (PKD)

Divided into:

A. Autosomal Dominant (Adult Type) – ADPKD
B. Autosomal Recessive (Infantile Type) – ARPKD

A. ADPKD

Inheritance: Autosomal dominant.
Genetics:
- PKD1 (chromosome 16) – 85%
- PKD2 (chromosome 4) – 15%
Onset: Adulthood (30–50 years).
Morphology:
- Bilateral kidney enlargement (up to 4 kg).
- Gross: Numerous large cysts (up to 5 cm), clear or brownish fluid; pelvis distorted but cysts do not communicate with it.
- Microscopy: Cysts from all parts of nephron (Bowman’s capsule, tubules, collecting ducts), interstitial fibrosis, inflammation.
Clinical Features:
- Lumbar pain, haematuria, hypertension, polyuria, UTI, progressive CRF.
- Associated Conditions:
  - Liver cysts (~30%)
  - Cysts in pancreas, spleen, lungs

B. ARPKD

Inheritance: Autosomal recessive.
Genetics: PKHD1 gene on chromosome 6 (6p21).
Onset: Neonatal or infantile period.
Morphology:
- Gross: Bilateral smooth kidneys; medullary cysts radiate to cortex—sponge-like appearance.
- Microscopy: Cysts from dilated collecting ducts, cuboidal/columnar epithelium.
Clinical Features:
- Severe forms cause neonatal death.
- May lead to congenital hepatic fibrosis and portal hypertension.

3. Medullary Cystic Diseases

A. Medullary Sponge Kidney

Inheritance: Autosomal dominant.
Features:
- Cystic dilatation of papillary ducts in medulla.
- Usually asymptomatic or mild symptoms: flank pain, haematuria, dysuria.
Morphology:
- Multiple small medullary cysts (<0.5 cm), may contain calculi.
- Cysts lined by various epithelium (columnar to squamous).
- Renal cortex: usually unaffected or shows pyelonephritis.

B. Nephronophthisis-Medullary Cystic Disease Complex

Inheritance: Autosomal recessive.
Types: Infantile, juvenile (most common), adolescent.
Clinical Features:
- Polyuria, polydipsia, enuresis
- Growth retardation, anaemia
- Progressive renal failure → uraemia
Morphology:
- Gross: Small kidneys with granular surface, cortico-medullary cysts.
- Microscopy: Tubular atrophy, interstitial fibrosis, cysts lined by flattened epithelium.

4. Simple Renal Cysts

Common: Seen in >50% people >50 yrs.
Usually asymptomatic.
May cause symptoms if rupture, bleeding, or infection occurs.
Gross: Solitary or multiple cortical cysts, yellow-white wall, clear or rust-coloured fluid.
Microscopy: Flattened epithelium, fibrous cyst wall ± haemosiderin/calcium.

5. Acquired Renal Cysts

Causes:

Dialysis-associated cystic disease
Hydatid cyst (echinococcus)
Tuberculosis
Carcinoma-related cystic degeneration
Traumatic haematoma
Drug-induced (experimental)

6. Pararenal Cysts

Location: Outside the kidney but adjacent.
Types:
- Pyelocalyceal cysts
- Hilar lymphangiectatic cysts
- Retroperitoneal cysts
- Perinephric pseudocysts (trauma)

GLOMERULAR DISEASES

Definition:

Group of diseases primarily affecting renal glomeruli.

Classification:

I. Primary Glomerulonephritis

Glomeruli are the main site of disease.
Types include:
- Acute GN (post-streptococcal/non-strep): Sudden-onset immune-mediated inflammation of glomeruli, often following infections.
- Rapidly Progressive GN (RPGN): (proliferation of parietal epithelial cells (They line the outer (parietal) layer of Bowman’s capsule) + macrophages).
- Minimal Change Disease (MCD): Podocyte injury leading to selective proteinuria.
- Membranous GN: Immune complex–mediated thickening of the glomerular basement membrane (GBM).
- IgA Nephropathy

II. Secondary Glomerular Diseases

Systemic diseases secondarily affect glomeruli:
- SLE (lupus nephritis): Autoimmune disease → production of anti-dsDNA and other autoantibodies → immune complex deposition in glomeruli → complement activation and inflammation.
- Diabetes mellitus: Chronic hyperglycemia → nonenzymatic glycosylation of proteins → basement membrane thickening and mesangial expansion
- Amyloidosis: Deposition of abnormal fibrillary proteins in glomeruli, vessels, and interstitium.
- Vasculitis (e.g., PAN, Wegener’s)
- Infections: HBV, HCV, HIV, malaria

Clinical Manifestations of Glomerular Disease

Four major signs (varying degrees):
1. Proteinuria
2. Haematuria
3. Hypertension
4. Impaired excretory function
Confirmed by renal biopsy (light, EM, IF microscopy)

MAJOR GLOMERULAR SYNDROMES

Glomerular diseases don’t all behave the same way. They cluster into a few classic syndromes based on how the glomerulus is injured and how the kidney responds:

1. Nephritic Syndrome

Pathophysiology: Inflammatory injury to glomeruli → capillary wall damage → blood and mild protein leak.
Key features:
- Hematuria (often microscopic or cola-colored urine)
- Mild-to-moderate proteinuria (<3.5 g/day)
- Oliguria and azotemia
- Hypertension (due to fluid retention)
- Edema (usually mild)
Typical causes:
- Post-streptococcal GN
- Rapidly progressive GN
- IgA nephropathy

2. Nephrotic Syndrome

Pathophysiology: Podocyte injury → massive protein leak without much inflammation.
Key features:
- Heavy proteinuria (>3.5 g/day)
- Hypoalbuminemia
- Generalized edema (including periorbital, ascites)
Typical causes:
- Minimal change disease
- Membranous nephropathy
- Diabetic nephropathy
- Amyloidosis

Pathogenesis of Glomerular Injury

Immunologic reactions — especially involving antigen-antibody (Ag-Ab) complexes — play a key role in most glomerular diseases.

A. Antibody-Mediated Glomerular Injury

1. Immune Complex Disease

👉 Most common mechanism of glomerular injury.

Involves deposits of immune complexes (Ag-Ab) in glomeruli.
Immune complexes contain immunoglobulins (IgG, IgA, IgM) and complement (mainly C3).

Mechanisms of Immune Complex Formation

i. In Situ Formation (Local Formation)

Immune complexes form directly in the glomerulus.
Antibodies bind to:
- Intrinsic antigens (from glomerulus itself)
- Planted antigens (streptococcal proteins, drugs)

ii. Circulating Immune Complexes

Form outside the kidney → get trapped in glomeruli.
Cause injury only when:
- In high amounts
- Have glomerulus-binding properties
- Body fails to clear them

Sources of antigens:

Endogenous: e.g., SLE
Exogenous: e.g., Hepatitis B, syphilis, malaria, tumors

Examples of Immune Complex GN

Membranous GN, membranoproliferative GN, IgA nephropathy, SLE, malaria, syphilis, hepatitis

B. Cell-Mediated Glomerular Injury

Cell-mediated immunity plays a role in some types of glomerular injury, especially when antibody involvement is minimal.

Key Mechanisms:

T cells (CD4+ and CD8+) get activated and release cytokines, which:
- Recruit more immune cells (especially macrophages). Cause cytotoxic injury to glomerular cells.

C. Secondary Pathogenic Mechanisms (Mediators of Immunologic Injury)

These mediators contribute to glomerular injury once immune responses are activated.

1. Neutrophils:

Present in acute proliferative GN.
Cause injury via:
- Complement activation.
- Release of proteases, and reactive oxygen species (ROS).

2. Mononuclear Phagocytes (Monocytes/Macrophages):

Present in many GN forms.
Cause hypercellularity by releasing inflammatory substances.

3. Complement System:

Classical and alternative pathways contribute to injury.
Membrane Attack Complex (MAC: C5b–C9) damages the glomerular basement membrane (GBM) directly.

4. Platelets:

Aggregate and release mediators.
Increased intrarenal platelet consumption observed in some GN types.

5. Mesangial Cells:

Can produce inflammatory mediators and contribute to glomerular damage.

6. Coagulation System:

Fibrin in Bowman’s space stimulates crescent formation and scarring.
Fibronectin promotes transformation into scar tissue.

II. Non-Immunologic Mechanisms of Glomerular Injury

Although immune mechanisms dominate, other causes include:

A. Metabolic Disorders:

Diabetic nephropathy (due to high glucose).
Fabry’s disease (lipid storage disorder).

B. Hemodynamic Injury:

Systemic or intraglomerular hypertension.

C. Deposition Disorders:

Amyloidosis leads to abnormal protein deposition.

D. Infectious Causes:

HBV, HCV, HIV, and bacterial toxins.

E. Drugs:

NSAIDs may cause Minimal Change Disease.

SPECIFIC TYPES OF GLOMERULAR DISEASES

I. PRIMARY GLOMERULONEPHRITIS

Acute Glomerulonephritis

1. Acute Post-Streptococcal GN (APSGN)

Common in children (2–14 years), more rare in adults.
Follows streptococcal throat or skin infection.
Appears 1–2 weeks after infection.

Etiopathogenesis:

Caused by immune complex deposition in glomeruli.
Streptococcal antigens trigger immune response.
Common serotypes: Type 12, 4, 1 of group A β-haemolytic streptococci.
Serologic evidence: ↑ ASO.
↓ Complement levels (C3) due to consumption.

Morphology:

Kidney: Enlarged.

LM:
- Diffuse glomerular hypercellularity.
- Neutrophil & monocyte infiltration.
- Fibrin in capillaries.
IF microscopy: IgG and C3.

Clinical Features:

Abrupt onset in children.
Hematuria, red cell casts, mild proteinuria, hypertension, periorbital edema, oliguria.
Prognosis: Excellent in children; complications more in adults.

2. Acute Non-Streptococcal GN

Caused by:
- Bacteria: Staphylococci, pneumococci, Salmonella, etc.
- Viruses: Hepatitis B, mumps
- Parasites: Malaria
- Syphilis
Similar morphology to APSGN. Prognosis poorer than APSGN.

3. Rapidly Progressive GN (RPGN)

Characterized by rapid decline in renal function (weeks–months).

Goodpasture’s Syndrome (Type I RPGN)

Affects kidney + lungs (causes hemoptysis).
Anti-GBM antibodies target type IV collagen in GBM & alveoli.
IF shows deposits of IgG and C3.

Type II RPGN (Immune Complex)

Seen in post-streptococcal, non-streptococcal GN, and SLE.
Shows granular deposits and low complement.

Type III RPGN (Pauci-immune)

Seen in ANCA (Anti-Neutrophil Cytoplasmic Antibodies)-positive vasculitis.
No immune complexes; normal complement.

Morphology of RPGN:

Gross: Enlarged pale kidneys (white kidney).
LM:

Crescents (proliferations of cells in Bowman’s space) compress glomerular tuft. ↑ Mesangial and endothelial cells.

Fibrin in glomeruli and Bowman’s space.

Tubules: Casts, RBCs, fibrin.
Interstitium: Edema, fibrosis, lymphocytes.
Vessels: May show hypertensive damage.

Clinical Features:

Rapid renal failure in all types.
Prognosis: Poor overall, but better in post-infectious type.

4. Minimal Change Disease (MCD)

Key Points:

Most common cause of nephrotic syndrome in children.
No visible change in glomeruli under light microscope.
Called foot process disease due to podocyte (epithelial cell) flattening.

Etiopathogenesis:

Mostly idiopathic.
Associated with:
- HIV infection, NSAIDs, Rifampicin, Interferon-α
Probable immunologic basis:
- ↑ Suppressor T-cell activity → cytokines (IL-8, TNF) damage podocytes
- Loss of heparan sulfate → ↓ GBM charge (↓ Negative charge → ↓ protein repulsion → Increased leakage of albumin into urine (selective proteinuria)
- Nephrin gene mutation in congenital cases (Defective nephrin → Disrupted slit diaphragm integrity → Loss of size-selective barrier → Severe protein loss in urine from birth)

Morphology:

Gross: Kidneys normal in size and appearance.
Light Microscopy:

Glomeruli: Normal (minimal change)
Tubules: Lipid droplets
Interstitium: May show edema
Vessels: No changes

Electron Microscopy:
- Flattened/fused podocyte foot processes
- Normal GBM
Immunofluorescence: No immune deposits (Nil deposit disease)

5. Membranous Glomerulonephritis (GN)

Characterized by thickened capillary walls in glomeruli

Etiopathogenesis:

Idiopathic (85%) or secondary to:
- SLE, Hepatitis B/C, Syphilis, Malaria
- Drugs: Penicillamine
Immune complex deposition → complement-mediated podocyte damage (via MAC complex C5b-C9)

Morphology:

Gross: Kidneys enlarged, pale, smooth
Light Microscopy:
- Glomeruli: Diffuse GBM thickening
- Tubules: Early lipid vacuolation
- Interstitium: Mild fibrosis, chronic inflammation
- Vessels: Late arteriolar thickening
Immunofluorescence: Granular deposits of IgG + C3

Clinical Features:

Non-selective proteinuria, microscopic Haematuria
Risk of renal vein thrombosis

6. Membranoproliferative GN (MPGN)

Features:
- Mesangial proliferation
- GBM thickening

Morphology:

Gross: Pale, firm kidneys
Light Microscopy:

Glomeruli: mesangial hypercellularity, thickened GBM
Tubules: Vacuolated, hyaline droplets
Interstitium: Chronic inflammation, foam cells
Vessels: May show hypertensive changes

7. Focal Proliferative GN

Key Points:

Focal (only some glomeruli) + Segmental (only some lobules)

Etiopathogenesis:

SLE, IgA nephropathy
Idiopathic

May involve immune complex deposition in mesangium (IgA ± IgG ± C3)

Morphology:

Light Microscopy:
- Some glomeruli show mesangial ± endothelial proliferation
Immunofluorescence: IgA, C3, and fibrin in mesangium

Clinical Features:

Haematuria (most common)
Mild to moderate proteinuria
Hypertension is uncommon

8. Focal Segmental Glomerulosclerosis (FSGS)

Key Points:

Sclerosis and hyalinosis in <50% glomeruli; (Focal: only some glomeruli are affected. Segmental: only a portion of the affected glomerulus shows sclerosis).
Common in adults; ~1/3 of adult nephrotic syndrome cases

Morphology:

Light Microscopy:
- Segmental sclerosis in some glomeruli
- Hyalinosis (eosinophilic material in tissue. In the kidney, it refers specifically to plasma proteins and other macromolecules that accumulate in parts of the glomerular tuft due to capillary wall injury.) = PAS-positive material in capillary loops
- Mesangial hypercellularity
- Tubular atrophy, interstitial fibrosis, mononuclear infiltrates
Electron Microscopy:
- Podocyte foot process flattening, fusion, or loss of the normal interdigitating structure
- Electron-dense deposits at sclerotic sites
Immunofluorescence: IgM + C3 deposits

Clinical Features:

All ages; more in males
Presents with nephrotic syndrome, haematuria, hypertension
May have renal failure at presentation

9. IgA Nephropathy

Key Points:

Most common glomerulopathy worldwide
IgA deposits in mesangium
Often seen in young males

Etiopathogenesis:

Idiopathic (most cases)
Associated with mucosal infections (e.g., respiratory, GI, urinary tract)
Increased IgA synthesis + defective clearance

Morphology:

Immunofluorescence: IgA (± IgG, C3, properdin) in mesangium

Clinical Features:

Common in children/young adults
Recurrent haematuria, often after infections
Mild proteinuria; rarely nephrotic syndrome

Chronic Glomerulonephritis (Chronic GN)

Chronic GN is the final stage of various glomerular diseases leading to irreversible renal damage and chronic renal failure.

Common Causes (in descending order of frequency):

Cause	Approximate % Cases
Rapidly progressive GN	90%
Membranous GN	50%
Membranoproliferative GN	50%
Focal Segmental Glomerulosclerosis (FSGS)	50%
IgA Nephropathy	40%
Acute Post-streptococcal GN	1%
Idiopathic cases (unknown cause)	~20%

Morphologic Features:

Gross Appearance:

Kidneys are small, shrunken and contracted (as low as 50g each).
Capsule is firmly adherent to cortex.
Cortical surface is granular.
Cortex is atrophic; medulla usually unaffected.

Microscopic Features:

Glomeruli:
- Reduced in number.
- Many are completely hyalinised—appear as acellular eosinophilic PAS-positive masses.
Tubules:
- Many are atrophic or completely disappear.
- Tubular degeneration and hyaline casts often seen.
Interstitial Tissue:
- Shows fibrosis.
- Infiltrated by chronic inflammatory cells.
Blood Vessels:
- Show arteriolar and arterial sclerosis, especially in patients with hypertension.

Clinical Features:

Seen in adults.
Presents with:
- Hypertension
- Uraemia
- Progressive renal failure
Death inevitable without renal transplant.
Multiple systemic complications of uraemia may develop.

Secondary Glomerular Diseases

1. Lupus Nephritis (from Systemic Lupus Erythematosus - SLE)

A form of glomerulonephritis caused by Systemic Lupus Erythematosus (SLE), an autoimmune disease.

Frequency: Renal involvement occurs in 40–75% of patients with SLE.
It is one of the most serious complications and a major determinant of prognosis.

Clinical Features / Signs

Patients with lupus nephritis may present with:

Proteinuria (can be mild or nephrotic range)
Haematuria (microscopic or gross)
Hypertension (due to renal involvement and fluid retention)
Urinary casts:
- RBC casts → indicate glomerular bleeding
- WBC casts → indicate inflammation within the tubules/interstitium

Pathogenesis

Autoimmune mechanisms are central:

Genetic susceptibility
- Associated with MHC genes (HLA-DR2, DR3)
- Abnormalities in B-cell signaling (e.g., via TNF and other immune pathways) lead to loss of tolerance.
Immune complex deposition
- Autoantibodies (anti-dsDNA, anti-Sm) form immune complexes.
- These deposit in the glomeruli (mesangium, subendothelial, subepithelial regions).
- Leads to complement activation, inflammation, and glomerular injury.
Inflammatory mediators
- Cytokines, chemokines, and complement split products drive further damage and sclerosis.

2. Diabetic Nephropathy

A major microvascular complication of diabetes mellitus, and the leading cause of end-stage renal disease (ESRD) worldwide.

Type 1 diabetes: affects 30–40% of patients
Type 2 diabetes: affects ~20% of patients

Clinical Presentation

Proteinuria (initially microalbuminuria → overt proteinuria)
Nephrotic syndrome (edema, hypoalbuminemia, hyperlipidemia)
Renal failure (progressive chronic kidney disease)
Hypertension (worsens progression)

Pathogenesis

Chronic hyperglycemia
- Causes non-enzymatic glycation of proteins → advanced glycation end products (AGEs).
- Alters glomerular basement membrane (GBM) and mesangial matrix.
Glomerular hypertension
- Increased intraglomerular pressure → mechanical injury to glomerular cells.
Mesangial protein deposition
- Leads to mesangial expansion and glomerulosclerosis.
TGF-β activation
- Stimulates production of extracellular matrix → fibrosis.
Progression
- Glomerulosclerosis → ↓ filtration surface → chronic renal failure.

Morphologic Types of Lesions

1. Diabetic Glomerulosclerosis

a. Diffuse Type
- GBM thickening (earliest change, detectable by EM)
- Diffuse mesangial expansion
- Fibrin caps (accumulated plasma proteins)
- Capsular drops (hyaline in Bowman’s capsule)
b. Nodular Type (Kimmelstiel–Wilson lesions)
- PAS-positive, spherical hyaline nodules
- Located in mesangium, surrounded by thickened capillaries
- Cause ischemia → glomerular tuft destruction
- Diagnostic of advanced diabetic nephropathy

2. Vascular Lesions

Atherosclerosis (large- and medium-sized renal arteries)
Hyaline arteriolosclerosis
- Involves both afferent and efferent arterioles (unique for diabetes)
- Causes renal ischemia, tubular atrophy, interstitial fibrosis

3. Diabetic Pyelonephritis

An inflammation of the kidney, specifically the renal parenchyma, usually due to bacterial infection.
More common in poorly controlled diabetes
May present as:
- Acute or chronic pyelonephritis
- Papillary necrosis (a severe form, often bilateral)

4. Tubular Lesions (Armanni–Ebstein change)

Glycogen accumulation in proximal tubule cells
Seen in severe hyperglycemia
Reversible with good glycemic control

Primary Glomerular Diseases

Type	Clinical	Pathogenesis	LM	EM	IF
Acute GN	Nephritic	Immune complex	Diffuse prolif.	Subepithelial deposits	IgG, C3
RPGN	Renal failure	Type I: anti-GBM Type II: IC, Type III: pauci-immune	Crescents	Subepithelial or none	Linear/granular/negative
Minimal Change	Nephrotic	T-cell mediated	Normal	Foot process effacement	Negative
Membranous GN	Nephrotic	IC	Capillary wall thickening	Subepithelial	Granular IgG, C3
MPGN	Nephrotic	Type I: IC, Type II: dense deposits	Lobular prolif.	Subendothelial or dense	C3 ± IgG
Focal GN	Variable	IC	Segmental prolif.	Mesangial	IgA ± IgG, C3
FSGS	Nephrotic	Idiopathic/secondary	Segmental sclerosis	Foot process loss	IgM, C3
IgA Nephropathy	Recurrent hematuria	Unknown	Mesangial prolif.	Electron-dense deposits	IgA ± C3
Chronic GN	Renal failure	End-stage of any GN	Hyalinised glomeruli	Variable	Variable

Hereditary Nephritis (Alport Syndrome)

Definition:

Hereditary nephritis, commonly known as Alport Syndrome, is a group of inherited disorders primarily affecting the glomerular basement membrane (GBM), leading to progressive renal failure, hearing loss, and sometimes eye abnormalities.

Genetics and Inheritance:

Most common form: X-linked (85% of cases)
- Mutation in COL4A5 gene on X chromosome, encoding type IV collagen α5 chain.
Less common: Autosomal recessive or autosomal dominant inheritance
- Mutations in COL4A3 or COL4A4 genes (α3 and α4 chains of type IV collagen).

Pathogenesis:

Type IV collagen is a critical component of the GBM.
Mutations in collagen genes cause:
- Abnormal GBM structure
- Progressive thinning, splitting, and lamellation (layering) of GBM.
Over time, this leads to:
- Proteinuria
- Hematuria
- Chronic renal failure

Clinical Features:

Renal Involvement:

Microscopic hematuria (earliest sign; often asymptomatic)
Progressive proteinuria
Chronic renal failure (usually manifests in adolescence or early adulthood)
Hypertension may develop in advanced stages.

Extrarenal Manifestations:

Sensorineural Hearing Loss
- Typically bilateral
- Involves high-frequency hearing
- Begins in late childhood or adolescence
Eye Abnormalities
- Retinopathy
- Corneal dystrophy in some cases

Morphologic Changes:

Light Microscopy (LM):

Initially: Non-specific changes
Later: Segmental sclerosis, interstitial fibrosis, and tubular atrophy

Electron Microscopy (EM):

Key diagnostic tool
Shows characteristic GBM changes:
- Irregular thickening
- Splitting and lamellation of lamina densa (known as “basket-weave” appearance)

Diagnosis:

Urinalysis: Persistent microscopic hematuria, proteinuria
Family history: X-linked inheritance pattern
Renal biopsy: Electron microscopy to detect GBM abnormalities
Genetic testing: Identification of mutations in COL4A3, COL4A4, or COL4A5 genes

Prognosis:

Progressive renal failure in males with X-linked form
Females (carriers) may have milder disease or remain asymptomatic
Early diagnosis and supportive therapy can slow progression

Treatment:

No specific cure; management is supportive:
- ACE inhibitors or ARBs to reduce proteinuria and slow renal damage
- Hearing aids for auditory defects
- Renal transplantation in end-stage renal disease
  - Rare cases may develop anti-GBM nephritis post-transplant (due to immune response against normal GBM)

Renal Vascular Diseases

Affected due to:

High blood pressure
Hemodynamic (Hyperemia (An increased blood flow to a tissue or organ due to dilated arterioles.), Edema, Hemorrhage etc.) or hormonal disturbances

Major Types:

Hypertensive vascular diseases
Thrombotic microangiopathy
Renal cortical necrosis
Renal infarcts

Hypertension and Kidney

➤ Definition:

Stage 1 Hypertension: 140–159/90–99 mmHg
Stage 2 Hypertension: ≥160/≥100 mmHg
Prehypertension: 120–139/80–89 mmHg

➤ Types:

Essential (Primary) Hypertension (90–95%)
- Cause unknown
Secondary Hypertension (5–10%)
- Due to renal, endocrine, vascular, or nervous system disease (renin–angiotensin–aldosterone system (RAAS).

➤ Based on Course:

Benign Hypertension: Gradual progression
Malignant Hypertension: Sudden onset; BP ≥200/140 mmHg

Essential Hypertension: Causes & Mechanisms

➤ Etiologic Factors:

Genetic: Family history, angiotensinogen gene (M235T associated with higher plasma angiotensinogen levels)
Racial/Environmental: More common in African Americans; high salt intake, stress
Other risk modifiers: Age, sex, smoking, diabetes, cholesterol

➤ Pathogenesis:

High catecholamines (↑ Heart rate, contractility, Vasoconstriction. (Dopamine, Norepinephrine, noradrenaline)
Increased blood volume or cardiac output
Renin abnormalities (low or high renin)

Secondary Hypertension

➤ 1. Renal Hypertension:

Renovascular: e.g. renal artery stenosis, polyarteritis nodosa (A systemic necrotizing vasculitis affecting medium-sized muscular arteries, typically sparing arterioles, capillaries, and venules. Characterized by segmental, transmural inflammation → fibrinoid necrosis → aneurysms, thrombosis, and organ ischemia.)
Renal parenchymal: e.g. GN, pyelonephritis, diabetic nephropathy

▶ Mechanism:

Activation of renin-angiotensin-aldosterone system (RAAS); Low renal perfusion or low Na⁺ trigger JG cells to release renin, which converts liver-derived angiotensinogen → angiotensin I, then ACE converts it → angiotensin II. Angiotensin II raises blood pressure by vasoconstriction, stimulating aldosterone and ADH release, and increasing Na⁺/water retention → ↑ blood volume and pressure.

6. Effects of Hypertension on Kidney

➤ Early Marker:

Albuminuria or microalbuminuria indicates renal damage

Nephrolithiasis (Urinary Stones)

➤ Definition:

Formation of calculi anywhere in urinary tract

➤ Epidemiology:

Common in US, India, South Asia
Peak: 2nd–3rd decade
M:F ratio = 2:1

➤ Clinical Features:

Renal colic
Hematuria
May cause obstruction and infection

URINARY CALCULI (Kidney Stones)

Definition:

Solid masses formed from crystals in the urine that may obstruct urinary flow and cause renal colic and hematuria.

Types of Urinary Calculi:

Calcium Stones (75%)

Composition:

Pure calcium oxalate (50%)

Calcium phosphate (5%)
Mixed (45%)

Causes:
- Idiopathic hypercalciuria (no high serum calcium)
- Hypercalcemia due to:
  - Hyperparathyroidism
  - Vitamin D excess
- Hyperuricosuria
Pathogenesis:
- Crystals form due to urine supersaturation
- Alkaline pH, low urine volume, high oxalate/uric acid are risk factors
Morphology:
- Small, hard, ovoid
- Rough surface
- Dark brown due to old blood pigments

Struvite (Mixed) Stones (15%)

Composition: Magnesium-ammonium-calcium phosphate
Also called: Infection or triple phosphate stones

Causes: Infection with urea-splitting bacteria (e.g. Proteus, Klebsiella)
- E. coli does not cause these
Morphology:
- Yellow-white
- Irregular shape

Uric Acid Stones (6%)

Causes:
- Hyperuricemia and hyperuricosuria (e.g. gout, leukemia)
- Acidic urine (pH < 6)
- Low urine volume
Pathogenesis:
- Acidic pH reduces uric acid solubility → stone formation
Morphology:

Smooth, yellow-brown, hard

Often multiple

Cystine Stones (<2%)
- Cause: Genetic defect → cystinuria (defective cystine transport)
- Pathogenesis:
  - Excess cystine (least soluble AA) → crystal/stones
- Morphology:
  - Small, smooth, round
  - Yellow, waxy
  - Often multiple
Other Rare Types (<2%)
- E.g., Xanthine stones from hereditary xanthinuria

HYDRONEPHROSIS

Definition:

Dilatation of the renal pelvis and calyces due to partial or complete obstruction of urine outflow.

Types:

Unilateral Hydronephrosis
- Causes:
  - Intraluminal: Stones
  - Intramural: PUJ obstruction (Pelvi-Ureteric Junction), inflammation, neoplasm
  - Extramural: Tumor compression (prostate, cervix)
Bilateral Hydronephrosis

Causes:

Congenital: Posterior urethral valve, urethral atresia (urethral lumen fails to canalize)
Acquired: Prostatic enlargement, bladder tumors, strictures (A stricture is an abnormal narrowing of the urethra (or sometimes ureter) due to scarring, inflammation, or trauma, leading to obstruction of urinary flow.)

Pathology:

Early stage: Extrarenal sac-like dilatation of pelvis
Advanced:
- Intrarenal hydronephrosis
- Thin renal cortex covering dilated calyces
Microscopy:
- Tubular and glomerular atrophy
- Fibrosis
- Chronic inflammation
- Risk of pyonephrosis (pus in the kidney)

RENAL TUMORS

A. Benign Tumors

Cortical Adenoma
- Tiny, multiple, white or yellow nodules (a usually spherical lesion.)
- Composed of uniform cuboidal tubular cells
- Tumors >3 cm may behave malignantly
Oncocytoma
- From collecting ducts
- Brown mahogany color, granular cytoplasm (rich in mitochondria)
Juxtaglomerular Tumor (Reninoma)
- Produces renin → hypertension
- Epithelioid cells (activated macrophages that have undergone a transformation in chronic inflammation) with rich vasculature

B. Malignant Tumors

1. Renal Cell Carcinoma (RCC)

Also known as: Adenocarcinoma, Hypernephroma
Age: 50–70 years, M > F
Most common primary renal cancer (70–80%)

Risk Factors:

Smoking (main risk)
Genetic syndromes (e.g., VHL disease) (A rare, autosomal dominant hereditary cancer syndrome caused by mutations in the VHL tumor suppressor gene (chromosome 3p)
Polycystic kidney, dialysis cysts (Chronic renal failure → tubular obstruction & ischemia → tubular epithelial proliferation (abnormal repair responses) → cyst formation.)
Obesity, estrogen, asbestos, analgesics

Gross Features:

Yellow, solid, upper pole mass
Necrosis, hemorrhage
May invade renal vein → vena cava

Clinical Features:

Classic triad: Hematuria, flank pain, abdominal mass
Paraneoplastic syndromes:
- Polycythemia (↑EPO)
- Hypercalcemia (PTH-like peptide)
- Hypertension (renin)
Common metastases: Lungs, brain, bones

Prognosis:

5-year survival: ~70%
Poor prognosis: High grade, metastasis, vein invasion

Secondary (Metastatic) Tumors

Kidney is a common site for:
- Leukemia infiltration
- Metastasis from lung, breast, stomach

Lower Urinary Tract: Normal Structure

1. Components

Ureters
Urinary bladder
Urethra

Ureters

Structure: Tubular, ~30 cm long, 0.5 cm wide.
Pathway: From renal pelvis (pelvi-ureteric junction) to bladder (vesico-ureteric junction).
Entry into Bladder: Oblique, preventing vesicoureteric reflux during urination.
Location: Lies retroperitoneally.

Histology

Inner lining: Transitional epithelium (urothelium)
Muscular layer: Thick smooth muscle
Outer layer: Fibrous connective tissue

3. Urinary Bladder

Position: Lies extraperitoneally (Situated outside this peritoneal lining); only dome is covered by peritoneum.
Capacity: 400–500 ml (normal without over-distension).
Micturition (The physiological process of urinating): Controlled reflexively and voluntarily via sympathetic & parasympathetic nerves.

Histology

Muscular Layer: Detrusor muscle (3 layers: inner, middle, outer)
Trigone Muscle: From longitudinal muscle of ureters.
Inner Lining: Transitional epithelium (6–7 layers)
- Umbrella cells: Superficial large eosinophilic cells.

4. Urethra

Male Urethra

Parts: Prostatic, membranous, penile
Lining:
- Prostatic: Transitional epithelium
- Others: Stratified columnar → squamous at orifice
Glands: Mucous glands in mucosa

Female Urethra

Shorter; runs parallel to vaginal anterior wall
Epithelium:
- Columnar epithelium throughout
- Transitional near bladder

Congenital Anomalies

1. Vesicoureteric Reflux

Most common; backward flow of urine from bladder into ureters.

2. Double Ureter

Entire or partial duplication.
Often associated with double renal pelvis.
Two ureteric orifices or joined before entering bladder.

3. Ureterocele

Cystic dilatation of terminal ureter.
Located beneath bladder mucosa.
Visualized by cystoscopy.

Inflammations

1. Ureteritis

Usually secondary to pyelitis (above) or cystitis (below).
May become chronic if infection persists.

2. Cystitis (Urinary Bladder Inflammation)

Causes

Infection: E. coli (most common), Klebsiella, Pseudomonas, Proteus, Candida, Schistosoma.
Others: Radiation, chemicals, trauma, catheters.

Risk Factors

Females: Short urethra, sexual activity
Males: Prostatic obstruction

Symptoms (Triad)

Frequency (frequent urination)
Dysuria (burning pain)
Lower abdominal pain

Types

Acute Cystitis
- Red, swollen bladder mucosa with ulcers/exudate
- Neutrophilic infiltrate, oedema, congestion
Chronic Cystitis
- Red, thickened mucosa, polypoid masses (resembling a polyp)
- Fibrosis, lymphocyte infiltration

3. Urethritis

Types

Gonococcal: Neisseria gonorrhoeae → suppurative, strictures
Non-gonococcal: E. coli (common), accompanies cystitis/prostatitis
Reiter’s Syndrome: Arthritis + Conjunctivitis + Urethritis (Chlamydia trachomatis, Shigella, Salmonella, Yersinia, Campylobacter, Clostridioides difficile)

Tumours

A. Bladder Tumours

Epithelial Tumours (90%)

Arise from urothelium
Types:
1. Transitional Cell Papilloma: Benign, branching papillae
2. Carcinoma in situ (CIS): Pre-cancerous, confined to mucosa
3. Transitional Cell Carcinoma (TCC):
  - Grade I: Mild atypia, non-invasive
  - Grade II: Nuclear hyperchromatism, mitosis, +/- invasion
  - Grade III: Anaplastic, invasive, pleomorphic

Etiological Factors

Industrial exposure (aniline dyes)
Schistosomiasis (S. haematobium)
Smoking
Drugs (cyclophosphamide (Cytotoxic immunosuppressive and chemotherapeutic drug), analgesics)
Chronic inflammation
Genetic mutations: p53, RB, p21

Staging of Bladder Cancer

Stage 0: Confined to mucosa
Stage A: Invades lamina propria; (A layer of loose connective tissue found beneath the epithelium of mucous membranes in many organ systems (e.g., respiratory, gastrointestinal, genitourinary tracts). Together with the epithelium, it forms the mucosa.
Stage B1: Invades superficial muscle
Stage B2: Invades deep muscle
Stage C: Invades perivesical tissue
Stage D1: Regional lymph node metastasis
Stage D2: Distant metastasis