# KIDNEY & URINARY TRACT DISORDERS (Renal Pathology)

## 1. NORMAL ANATOMY & HISTOLOGY
### Anatomy
- Bean-shaped paired organs
- Thin fibrous capsule
- Hilum (medial aspect) → artery, vein, lymphatics, ureter
### Nephron (~1 million per kidney)
- Glomerular capsule (glomerulus + Bowman's capsule)
- Proximal convoluted tubule (PCT)
- Loop of Henle
- Distal convoluted tubule (DCT)
- Collecting ducts
### Glomerulus
- Invagination of blind end of PCT
- Capillary tuft → afferent arteriole in, efferent arteriole out
### Filtration Barrier (3 layers)
- Fenestrated endothelial cells
- GBM (3 sub-layers)
  - Lamina densa (central)
  - Lamina rara interna (endothelial side)
  - Lamina rara externa (visceral epithelial side)
- Podocytes (visceral epithelial cells) with filtration slit pores

## 2. NEPHRITIC vs NEPHROTIC SYNDROME
### Nephritic Syndrome
#### Features
- Haematuria (RBC casts → classical)
- Mild proteinuria (<3 g/24 hr, non-selective)
- Sodium & water retention
- Hypertension
- Mild oedema
- Oliguria
#### Examples – Primary GN
- Post-streptococcal GN
- Rapidly progressive GN (most common cause)
- Membranoproliferative GN
- Focal & diffuse proliferative GN
- IgA nephropathy
#### Examples – Systemic
- SLE
- Polyarteritis nodosa
- Wegener's granulomatosis
- Henoch-Schönlein purpura
- Cryoglobulinaemia
### Nephrotic Syndrome
#### Features
- Heavy proteinuria (>3 g/24 hr, selective)
- Hypoalbuminaemia (albumin 1–3 g/dL)
- Oedema (↓ oncotic pressure)
- Hyperlipidaemia (↑ hepatic lipoprotein synthesis)
- Lipiduria
- Hypercoagulability (↑ renal vein thrombosis risk)
#### Consequences of protein loss
- ↓ Immunoglobulins → infections (pneumococcus, E. coli)
- ↓ Antithrombin III → thrombosis
- ↓ Transferrin → microcytic hypochromic anaemia
- ↓ Cholecalciferol-binding protein → hypocalcaemia
- ↓ Thyroxine-binding globulin → ↓ thyroxine
- ↑ Fibrinogen (hepatic synthesis)
#### Examples – Primary GN
- Minimal change disease (most common in children)
- FSGS (most common in adults)
- Membranoproliferative GN
- Membranous GN
- Focal & diffuse proliferative GN
- IgA nephropathy
#### Examples – Systemic
- Diabetes mellitus
- Amyloidosis
- SLE
### Azotaemia & Uraemia
- Azotaemia = ↑ blood urea nitrogen (BUN)
- Uraemia = symptomatic azotaemia with systemic effects

## 3. GLOMERULONEPHRITIS (GN)
### Pathogenesis Mechanisms
#### 1. Immune-complex Mediated
- In situ – Fixed Ag (e.g., anti-GBM → Goodpasture syndrome; Ag = α3 chain of collagen IV)
- In situ – Planted Ag (bacterial/viral/parasitic/drugs)
- Circulating immune complex (endogenous e.g. SLE; exogenous e.g. Hep B, malaria, tumour Ag)
#### 2. Cell-mediated (Delayed Hypersensitivity)
- CD4 & CD8 T cells → cytokines → cytotoxicity
- Pauci-immune mechanism (no immune complex)
#### 3. Alternative Complement Pathway
- C3 & properdin deposited without Ig
### Deposit Locations (EM)
- Subepithelial
- Epimembranous
- Subendothelial
- Mesangial
### Classification
#### Primary GN
- Acute / Post-streptococcal GN
- Rapidly progressive GN
- Minimal change disease
- Membranous GN
- Membranoproliferative GN
- Focal & diffuse proliferative GN
- FSGS
- IgA nephropathy
- Chronic GN
#### Secondary (Systemic)
- Lupus nephritis (SLE)
- Diabetic nephropathy
- Amyloidosis
- Polyarteritis nodosa
- Wegener's granulomatosis
- Goodpasture's syndrome
- Henoch-Schönlein purpura
#### Hereditary
- Alport syndrome

## 4. INDIVIDUAL GLOMERULAR DISEASES
### 1) Acute / Post-streptococcal GN
- Age: Children (6–10 yrs), M > F
- Follows Group A β-haemolytic Streptococcus (throat/skin)
- Gross: Enlarged, pale cortex → flea-bitten (petechiae)
- LM: Diffuse hypercellularity (endothelial + mesangial), neutrophil infiltration
- EM: Subepithelial humps (immune deposits)
- IF: Granular IgG + C3
- Clinical: Nephritic syndrome; self-limiting; good prognosis

### 2) Rapidly Progressive GN (RPGN)
- Most common cause of nephritic syndrome
- 3 Types
  - Type I: Linear IF (IgG + C3) → Goodpasture syndrome
  - Type II: Granular IF (IgG + C3) → Subepithelial deposits
  - Type III: No deposits → Pauci-immune
- LM: Crescents (parietal epithelial cell proliferation + monocytes)
- Clinical: Nephritic syndrome, rapid deterioration

### 3) Minimal Change Disease (MCD)
- Aliases: Foot process disease, Nil deposit disease
- Age: Children <16 yrs; most common nephrotic syndrome in children (80%)
- Pathogenesis: Cell-mediated
- Gross: Normal size & shape
- LM: No apparent abnormality; slight ↑ mesangial matrix
- EM: Diffuse effacement/fusion of foot processes; no deposits
- IF: No deposits
- Clinical: Massive, highly selective proteinuria; responds to steroids

### 4) Membranous GN
- Antigen: gp330 (podocyte component) → in situ fixed Ag deposition
- Gross: Enlarged, pale, smooth kidneys
- LM: Diffuse thickening + duplication of GBM; no cellular proliferation
- EM: Subepithelial deposits → spikes
- IF: IgG + C3
- Clinical: Nephrotic syndrome in adults

### 5) Membranoproliferative GN (MPGN)
- Also: Mesangiocapillary GN
- Type I (classic, 70%): Subendothelial deposits
- Type II (dense deposit disease, 30%): Along GBM; alternate pathway
- Type III (rare): Features of Type I + membranous nephropathy
- LM: Lobular appearance; tram-track (double contour) GBM
- Clinical: Nephrotic > nephritic

### 6) Focal Segmental Glomerulosclerosis (FSGS)
- Most common nephrotic syndrome in adults
- Focal (some glomeruli) + segmental (part of glomerulus)
- LM: Sclerosis + hyalinosis in segments
- EM: Foot process fusion
- Clinical: Heavy proteinuria; poor steroid response

### 7) IgA Nephropathy (Berger's disease)
- Most common primary GN worldwide
- Pathogenesis: Mesangial IgA deposits (often after mucosal infection)
- IF: IgA + C3 in mesangium
- Clinical: Recurrent haematuria (after URTI); mild proteinuria

### 8) Chronic GN
- End-stage of multiple GN types
- Gross: Small, shrunken, granular kidneys (secondary contracted kidney)
- LM: Global glomerulosclerosis, tubular atrophy, interstitial fibrosis

## 5. DIABETIC NEPHROPATHY
### Glomerular Lesions
#### a) Diffuse glomerulosclerosis
- Thickening of GBM (earliest change)
- ↑ Mesangial matrix + mild mesangial proliferation
- Capsular drop (eosinophilic hyaline, parietal Bowman's capsule)
- Fibrin cap (eosinophilic material on peripheral capillary wall)
#### b) Nodular glomerulosclerosis
- Kimmelstiel-Wilson (KW) lesions → PATHOGNOMONIC
- Ovoid/spherical, laminated, hyaline, acellular, PAS-positive
- Located within glomerular lobule
### Vascular Lesions
- Hyaline arteriolosclerosis
### Tubular Lesions
- Armanni-Ebstein lesions → glycogen vacuoles in PCT epithelial cells

## 6. PYELONEPHRITIS
### Definition
- Inflammatory process affecting renal interstitial tissue & tubules
### Types
#### 1) Acute Pyelonephritis
- Acute suppurative inflammation by pyogenic bacteria
- Organisms: E. coli (90%) > Enterobacter > Klebsiella > Pseudomonas > Proteus
- Post-transplant: Polyomavirus BK (BKV)
- Routes
  - Ascending (most common): Faecal contamination → urethra → upward
    - More common in females (shorter urethra, no prostatic secretions, honeymoon pyelitis)
  - Haematogenous: Blood-borne spread
- Gross: Enlarged, swollen kidney; yellow abscesses; cortical surface abscesses
- Microscopy: Neutrophilic infiltration of interstitium & tubules; abscess formation
- Complications
  - Perinephric abscess
  - Pyonephrosis
  - Papillary necrosis (especially in diabetes)
  - Septicaemia
#### 2) Chronic Pyelonephritis
- Repeated or persistent bacterial infections
- Causes: Vesicoureteral reflux (most common), obstruction
- Gross: Irregular scarring, coarse cortical scars; blunted calyces; asymmetric involvement
- Microscopy
  - Thyroidisation of tubules (dilated tubules with colloid casts → resemble thyroid follicles)
  - Periglomerular fibrosis
  - Interstitial chronic inflammation
- Clinical: Hypertension, CKD, renal failure
### Xanthogranulomatous Pyelonephritis (XPN)
- Rare variant
- Proteus mirabilis most common organism
- Gross: Yellow mass replacing renal parenchyma
- Microscopy: Lipid-laden macrophages (xanthoma cells/foam cells)

## 7. UROLITHIASIS (RENAL CALCULI)
### Types & Features
| Type | Incidence | Aetiology | Notes |
|---|---|---|---|
| Calcium stones | 75% | Hypercalciuria ± hypercalcaemia | Alkaline pH, oxaluria |
| Struvite (mixed) | 15% | Urease-splitting organisms (Proteus) | Alkaline urine |
| Uric acid stones | 6% | Hyperuricosuria (gout) | Acidic urine (pH <6) |
| Cystine stones | 2% | Genetic defect in cystine transport | Yellowish, waxy, rounded |
### Cystine Stones
- Excessive cystine excretion → least soluble amino acid → crystals

## 8. HYDRONEPHROSIS
### Definition
- Dilatation of renal pelvis & calyces due to partial/intermittent obstruction
- Hydroureter always accompanies
- Unilateral or bilateral
### Causes
- Ureteric obstruction (calculi, stricture, tumour)
- Bladder outlet obstruction (BPH, carcinoma)
- External compression
### Gross
- Enlarged kidneys → extrarenal sac → intrarenal thin cortical rim
- Progressive dilatation → pressure atrophy of parenchyma
- Lobulated appearance
### Stages
- Early: Dilatation of renal pelvis
- Late: Thin rim of cortex stretched over dilated calyces
### Microscopy
- Fibrous scarring of wall, chronic inflammatory infiltrate
- Glomerulosclerosis
- Tubular atrophy
- Interstitial fibrosis

## 9. NEPHROSCLEROSIS (Renal Changes in Hypertension)
### Hypertension Classification
- Normal: <120/<80 mmHg
- Prehypertension: 120–139/80–89
- Benign HTN: 140–159/90–99
- Malignant HTN: >180/>120
### 1) Benign Nephrosclerosis
- Associated with benign essential hypertension
- Gross: Small, shrunken kidneys; fine granular surface (granular contracted kidney); capsule strips with difficulty
- Microscopy
  - Hyaline arteriolosclerosis (most characteristic) → pink, homogeneous thickening of arteriolar wall
  - Hyperplastic arteriolosclerosis (in malignant phase)
  - Ischaemic glomerular changes
  - Tubular atrophy
  - Interstitial fibrosis
### 2) Malignant Nephrosclerosis
- Associated with malignant hypertension (diastolic >120 mmHg)
- Gross: Petechial haemorrhages on surface → flea-bitten appearance
- Microscopy
  - Fibrinoid necrosis of arterioles
  - Hyperplastic arteriolosclerosis → onion-skin appearance
  - Necrotising glomerulitis
  - Thrombotic microangiopathy
- Clinical: Renal failure, papilloedema, hypertensive encephalopathy

## 10. RENAL TUMOURS
### A) Benign Tumours
#### Renal Papillary Adenoma
- Most common benign tumour
- Small, cortical, encapsulated
- Papillary pattern
#### Angiomyolipoma (AML)
- Hamartoma → vascular channels + smooth muscle + fat
- Associated with tuberous sclerosis
#### Oncocytoma
- Large eosinophilic cells; mahogany brown cut surface; central stellate scar

### B) Renal Cell Carcinoma (RCC)
- Also: Hypernephroma, Grawitz tumour, clear cell carcinoma
- Most common malignant renal tumour in adults
- 6th most common cancer in men
- Age: >50 yrs; M:F = 2:1
- Risk factors: Smoking (most important), obesity, hypertension, von Hippel-Lindau disease, cadmium exposure
#### Origin
- Arises from renal tubular epithelium
#### Gross
- Usually upper pole
- Large, golden yellow, circumscribed
- May extend into renal vein (cannon-ball thrombus) → IVC → right atrium
#### Classification
| Type | Incidence | Origin | Genetics |
|---|---|---|---|
| Clear cell | 70–80% | PCT | VHL gene (Ch 3) |
| Papillary | 2nd most common | DCT | Trisomy 7,16,17; loss of Y |
| Chromophobe | 3rd | Cortical collecting ducts | Hypodiploidy/monosomy (1,2,6,10,13,17,21,Y) |
| Collecting duct (Bellini) | Least common | Medullary collecting duct | Fibrotic stroma |
#### Microscopy
- Clear cell: Clear cytoplasm (glycogen removed in processing)
- Papillary: Papillary pattern on fibrovascular stalks; psammoma bodies
- Chromophobe: Prominent cell membranes, pale eosinophilic cytoplasm, perinuclear halo
#### Clinical Features (Classic Triad)
- Gross haematuria (most common)
- Flank pain
- Palpable abdominal mass
#### Spread
- Haematogenous → lungs (most common), brain, bone
- Local → liver, perirenal lymph nodes
#### Prognosis
- 5-year survival: 70%
- Poor prognosis: metastases, renal vein invasion, higher nuclear grade
#### Paraneoplastic Syndromes
- Polycythaemia (↑ EPO)
- Hypercalcaemia (PTHrP)
- Hypertension (↑ renin)
- Cushing's syndrome (↑ ACTH/cortisol)
- Feminisation/masculinisation

### C) Wilms' Tumour (Nephroblastoma)
- Most common abdominal malignant tumour in young children
- Age: 1–6 years; M = F
- Mutation: WT1 gene (chromosome 11p13)
- Arises from primitive renal epithelial & mesenchymal components
- Gross: Large, solitary, unilateral; variegated cut surface
- Microscopy (Triphasic)
  - Blastemal cells (small, blue, primitive)
  - Stromal cells (mesenchymal)
  - Epithelial cells (tubular/glomeruloid structures)
- Associated syndromes: WAGR (Wilms', Aniridia, GU anomalies, mental Retardation), Beckwith-Wiedemann, Denys-Drash
- Clinical: Abdominal mass (most common presentation); haematuria; hypertension
- Prognosis: Good (>90% cure with surgery + chemo ± radiotherapy)

### D) Transitional Cell Carcinoma (TCC) of Renal Pelvis
- Arises from urothelium of renal pelvis
- Risk factors: Smoking, analgesic abuse (phenacetin), cyclophosphamide
- Clinical: Painless haematuria
- Often multicentric; may extend to ureter/bladder

## 11. URINARY BLADDER TUMOURS
### Types
#### Transitional Cell Carcinoma (TCC) – Most Common
- Grade I (papillary, non-invasive) → Grade III (high-grade, invasive)
- Risk factors: Smoking, aniline dyes (β-naphthylamine), rubber/chemical workers, schistosomiasis
- Haematuria (painless) → most common presentation
#### Squamous Cell Carcinoma
- Associated with chronic irritation (stones, catheters, schistosomiasis)
#### Adenocarcinoma
- Rare; associated with urachal remnant or bladder exstrophy