9.3 Renal, Urogenital & Reproductive Pathology
Key Takeaways
Nephrotic syndrome (proteinuria above 3.5 g/day, hypoalbuminemia, edema, hyperlipidemia) includes minimal change disease, FSGS, membranous nephropathy and diabetic nephropathy; nephritic syndrome (hematuria, red cell casts, hypertension) includes post-streptococcal and IgA nephropathy.
Acute tubular necrosis shows muddy brown granular casts and can follow rhabdomyolysis, aminoglycosides, vancomycin or contrast; prerenal azotemia shows a BUN-to-creatinine ratio above 20 and a fractional excretion of sodium below 1%.
Chronic kidney disease causes secondary hyperparathyroidism, renal osteodystrophy, anemia from low erythropoietin and calciphylaxis, which presents as painful necrotic skin ulcers on the legs.
Uric acid stones are radiolucent and linked to gout; struvite stones form in alkaline urine from urease-producing Proteus; calcium oxalate stones are the most common.
Disseminated gonococcal infection causes tenosynovitis, dermatitis and migratory polyarthritis, often involving the ankle; prostate cancer typically produces osteoblastic bone metastases.
9.3 Renal, Urogenital & Reproductive Pathology
The Part I pathology outline names renal, urogenital and reproductive systems as disorder categories. Kidney disease shapes drug dosing, wound healing, vascular calcification and bone health, and several sexually transmitted infections present in the foot and ankle.
Glomerular Disease
| Syndrome | Defining features | Main causes and pathology |
|---|---|---|
| Nephrotic | Proteinuria above 3.5 g/day, hypoalbuminemia, generalized and pedal edema, hyperlipidemia, hypercoagulability (antithrombin loss) | Minimal change disease (children; podocyte effacement); FSGS; membranous nephropathy (anti-PLA2R antibodies); diabetic nephropathy (mesangial expansion, Kimmelstiel-Wilson nodules); amyloidosis |
| Nephritic | Hematuria with red cell casts, hypertension, oliguria, modest proteinuria | Post-streptococcal glomerulonephritis (after pharyngitis or impetigo; subepithelial humps); IgA nephropathy (hematuria days after a respiratory infection); rapidly progressive (crescentic) glomerulonephritis, including Goodpasture syndrome and ANCA vasculitis; Alport syndrome |
Nephrotic edema arises because albumin loss lowers capillary oncotic pressure (Starling forces in 15.4), so swelling is soft, pitting and dependent. Diabetic kidney disease is screened with the urine albumin-to-creatinine ratio and eGFR.
Acute Kidney Injury
| Type | Mechanism | Clues |
|---|---|---|
| Prerenal | Reduced renal perfusion (dehydration, heart failure, NSAIDs plus ACE inhibitors and diuretics) | BUN/creatinine ratio above 20; fractional excretion of sodium below 1% |
| Intrinsic: acute tubular necrosis | Ischemia or toxins: myoglobin from rhabdomyolysis (crush injury, compartment syndrome), aminoglycosides, vancomycin (especially combined with piperacillin-tazobactam), iodinated contrast | Muddy brown granular casts; FENa above 2% |
| Intrinsic: acute interstitial nephritis | Hypersensitivity to drugs (beta-lactams, NSAIDs, proton pump inhibitors, sulfonamides) | Fever, rash, eosinophilia, white cell casts |
| Postrenal | Obstruction (prostatic enlargement, stones, tumors) | Hydronephrosis on imaging |
Rhabdomyolysis after crush injury, prolonged immobilization, compartment syndrome or statin-drug interactions (10.4) causes very high creatine kinase and myoglobinuria. Urine dipstick testing is positive for blood but microscopy shows few red cells.
Chronic Kidney Disease (CKD)
CKD is staged by eGFR and albuminuria. Its systemic effects reach the foot:
- CKD-mineral and bone disorder: phosphate retention and low calcitriol drive secondary hyperparathyroidism and renal osteodystrophy (osteitis fibrosa cystica, osteomalacia, adynamic bone). This raises fracture risk and slows fusion after arthrodesis.
- Vascular calcification: medial calcification (Mönckeberg, 8.1) makes the ankle-brachial index unreliable.
- Calciphylaxis (calcific uremic arteriolopathy): small-vessel calcification and thrombosis cause extremely painful livedo, then necrotic ulcers, usually on the thighs, legs or abdomen. Mortality is high, and debridement and wound care must be coordinated with nephrology.
- Anemia from reduced erythropoietin; uremic pruritus; platelet dysfunction with bleeding risk; accumulation of renally cleared drugs (gabapentin, enoxaparin, aminoglycosides, metformin).
Stones, Infection & Cystic Disease
| Stone | Setting | Key point |
|---|---|---|
| Calcium oxalate | Most common; hypercalciuria, enteric hyperoxaluria | Radiopaque; envelope-shaped crystals |
| Uric acid | Gout, high cell turnover, acidic urine | Radiolucent on plain films; alkalinize urine |
| Struvite (magnesium ammonium phosphate) | Urease-producing Proteus infection | Staghorn calculi in alkaline urine (5.2) |
| Cystine | Autosomal recessive cystinuria | Hexagonal crystals |
Urinary tract infection is usually caused by Escherichia coli. Pyelonephritis adds fever, flank pain and white cell casts. Autosomal dominant polycystic kidney disease (PKD1/PKD2) causes enlarged cystic kidneys, hypertension and intracranial berry aneurysms.
Renal & Urothelial Tumors
- Renal cell carcinoma: clear cell type linked to VHL loss and smoking. It may present with hematuria, flank pain and a mass, or with paraneoplastic polycythemia. It spreads hematogenously and can produce lytic bone metastases, including rare acral metastases to the foot.
- Urothelial (transitional cell) carcinoma: painless hematuria in a smoker or a worker exposed to aromatic amines.
- Wilms tumor: the most common renal tumor of childhood.
Reproductive Pathology
Male
- Benign prostatic hyperplasia: transition zone, driven by dihydrotestosterone. Treated with alpha-1 blockers and 5-alpha-reductase inhibitors.
- Prostate cancer: peripheral zone. PSA is used in shared-decision screening. Bone metastases are typically osteoblastic (sclerotic).
- Testicular germ cell tumors: seminoma and nonseminomatous tumors in young men; markers include AFP and beta-hCG.
Female
- Cervical cancer: high-risk HPV 16/18 (E6 and E7 oncoproteins, 6.2); prevented by HPV vaccination and screening.
- Endometrial carcinoma: unopposed estrogen (obesity, anovulation, tamoxifen).
- Ovarian cancer: BRCA1/2; CA-125 is used for monitoring.
- Breast cancer: the most common cancer in women. Hormone-receptor and HER2 status guide therapy, and it often spreads to bone.
- Pregnancy-related conditions: preeclampsia (hypertension, proteinuria, edema; HELLP syndrome), gestational diabetes and a hypercoagulable state that raises the risk of venous thromboembolism after lower extremity surgery.
Sexually Transmitted Infections with Musculoskeletal Findings
| Infection | Lower extremity presentation |
|---|---|
| Disseminated gonococcal infection (Neisseria gonorrhoeae) | Triad of tenosynovitis, pustular dermatitis and migratory polyarthritis; can involve the ankle, or a purulent monoarthritis of the knee or ankle |
| Chlamydia trachomatis | Reactive arthritis with enthesitis and keratoderma blennorrhagica (6.4) |
| Syphilis | Palmoplantar rash in secondary syphilis; tabes dorsalis with Charcot joints (5.5) |
| HIV | Opportunistic foot infections and neoplasms (6.2) |
A construction worker is freed after six hours pinned under a collapsed wall. Twenty-four hours later his urine is dark, the dipstick is strongly positive for blood, microscopy shows almost no red cells, creatine kinase is markedly elevated and creatinine is rising. Which renal lesion is developing?
Acute interstitial nephritis from a hypersensitivity reaction
Acute tubular necrosis from myoglobin toxicity, with muddy brown granular casts
Post-streptococcal glomerulonephritis with subepithelial immune deposits
Minimal change disease with podocyte foot-process effacement
A patient on hemodialysis develops exquisitely painful violaceous livedo of both lateral thighs that progresses to black necrotic ulcers. Biopsy shows calcification and thrombosis of small dermal and subcutaneous arterioles. What is the diagnosis?
Calciphylaxis (calcific uremic arteriolopathy)
Warfarin-induced skin necrosis (protein C drop)
Pyoderma gangrenosum (neutrophilic dermatosis)
Necrobiosis lipoidica
A 22-year-old has fever, pustules on the dorsal foot and wrist, and painful swelling along the extensor tendon sheaths of the ankle that migrated from the knee. Which organism and next diagnostic step are most appropriate?
Neisseria gonorrhoeae; NAAT of genital, rectal and pharyngeal sites plus blood and synovial cultures
Staphylococcus aureus; immediate open debridement of the tendon sheath without obtaining any cultures
Chlamydia trachomatis; HLA-B27 testing alone
Borrelia burgdorferi; serology for erythema migrans
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