Ultimate Urology & Nephrology Exam Guide

Lec 1: Urolithiasis (Renal Calculi)

Epidemiology & Risk Factors

• Prevalence: 1% to 15%. Peaks in the 4th to 6th decades of life.
• Gender: Men > Women (2 to 3 times more). Women catch up after age 50 due to lower urinary calcium prior to menopause.
• Race/Ethnicity: Highest in Whites > Hispanics > Asians > African-Americans.
• Climate/Occupation: Hot, arid climates. High incidence in summer (July-Sept). Steel workers (heat exposure) have higher incidence due to low urine volume and hypocitraturia.
• Body Mass Index (BMI): Direct correlation. Obese patients excrete more oxalate, uric acid, sodium, and phosphorus, lowering pH.
• Fluid intake: Inversely related to stone formation.

Physicochemistry & Inhibitors

• Supersaturation is required. Normal urine calcium oxalate concentration is 4x higher than water solubility, but inhibitors prevent crystallization.
• Inhibitors:
  • Citrate: Complexes with calcium (reduces ionic calcium availability), directly inhibits spontaneous precipitation, prevents heterogeneous nucleation by monosodium urate.
  • Nephrocalcin & Tamm-Horsfall Glycoprotein: Potent inhibitors of calcium oxalate monohydrate aggregation.

Stone Types & Classifications

• Calcium-Containing (75%): Calcium Oxalate (60%), Hydroxyapatite (20%), Brushite (2%).
• Non-Calcium Containing: Uric acid (10%), Struvite (Magnesium Ammonium Phosphate) (10%), Cystine (1%).
• Medication Stones (Rare): Indinavir, Triamterene, Guaifenesin, Ephedrine, Ciprofloxacin.

Pathophysiology of Specific Stones

• Absorptive Hypercalciuria: High GI calcium absorption -> transient high serum Ca -> suppressed Parathyroid Hormone (PTH) -> high renal filtration. Result: Normal serum Ca, High urine Ca.
• Renal Hypercalciuria: Impaired renal tubular reabsorption -> secondary hyperparathyroidism. Diagnosis: High fasting urine Ca + High PTH + Normal serum Ca. Use Thiazide challenge to diagnose.
• Resorptive Hypercalciuria: Most commonly due to Primary Hyperparathyroidism (excess PTH from adenoma). High serum Ca, low serum Phos. Suspect if serum Ca > 10.1 mg/dL.
• Hyperoxaluria (>40 mg/day): Primary (biosynthetic), Enteric (malabsorption, Inflammatory Bowel Disease, short bowel), Dietary (excess Vitamin C).
• Hyperuricosuria (>600 mg/day): Due to high purine intake. Causes heterologous nucleation of calcium oxalate stones.
• Uric Acid Stones: Low urine pH (< 5.5) is the most critical factor! Radiolucent stones. Associated with chronic diarrhea, high animal protein, gouty diathesis.
• Cystine Stones: Autosomal recessive defect in dibasic amino acid transport (COLA: Cystine, Ornithine, Lysine, Arginine). Forms due to poor solubility.
• Infection Stones (Struvite): Magnesium Ammonium Phosphate Hexahydrate. Requires Alkaline urine and urease-producing bacteria (Proteus mirabilis/vulgaris, Ureaplasma urealyticum).
• Xanthine Stones: Radiolucent (often confused with uric acid). Inherited Xanthine Dehydrogenase defect.
• Ammonium Acid Urate: Associated with laxative abuse and inflammatory bowel disease.

🔥 Exam Hints (High-Yield)

• Uric Acid stones are the classic Radiolucent stones and depend almost entirely on low pH (< 5.5).
• Struvite (Infection) stones strictly require an Alkaline pH and bacteria that produce urease (like Proteus).
• To distinguish Renal vs Absorptive Hypercalciuria, use the Thiazide challenge (it corrects renal calcium leak but exacerbates absorptive/resorptive hypercalcemia).
• Primary Hyperparathyroidism should be your #1 suspicion if a stone-former has serum Calcium > 10.1 mg/dL.
• Cystinuria defect involves four amino acids (COLA), but ONLY Cystine forms stones due to poor solubility.

Lec 2: Ureteric, Vesical Stones & Lithotripsy

Management of Renal Calculi

• Stone Burden (Size & Number) is the most critical factor for treatment choice.
• Size Guidelines:
  • < 10 mm: Extracorporeal Shockwave Lithotripsy (SWL) has high success.
  • 10 - 20 mm: SWL is first-line. *Exception*: Lower pole stones have poor clearance with SWL (55%) vs upper/middle pole (>71%).
  • > 20 mm: Primary treatment is Percutaneous Nephrolithotomy (PNL).
• Staghorn Calculi: Fills the renal collecting system. Untreated leads to renal destruction and sepsis. Primary treatment: PNL first (+/- SWL as adjunct). Must be removed completely (especially struvite to stop bacteria).

Extracorporeal Shockwave Lithotripsy (SWL)

• Generators:
  • Electrohydraulic (Spark Gap): High voltage underwater spark. Good fragmentation, but short electrode life & pressure fluctuations.
  • Electromagnetic: Uses acoustic lens. More reproducible, less pain, long life. High rate of subcapsular hematoma.
  • Piezoelectric: Ceramic elements (barium titanate). Highly focused, anesthetic-free, but insufficient power for hard stones.
• Contraindications/Risks: Coagulopathy, Thrombocytopenia, Obesity, Pregnancy.
• Extra-renal Damage: Can injure liver, muscle, spleen, colon (elevated LDH, AST, CPK within 24h).

Ureteral Stones

• Spontaneous Passage: Stones ≤ 5 mm usually pass. Distal ureter (71%) > Proximal ureter (22%).
• Medical Expulsive Therapy (MET): Alpha-adrenergic blockers (superior to nifedipine).
• Impaction sites: Ureteropelvic Junction (UPJ), crossing Iliac vessels, Ureterovesical Junction (UVJ).
• Indications for Urgent Intervention: Obstructive pyelonephritis (sepsis/fever) -> requires urgent drainage (percutaneous nephrostomy or double-J stent); Solitary kidney obstruction; Intractable pain. *Do not perform lithotripsy until culture is negative!*
• Renal damage timing: Complete obstruction causes irreversible loss starting between 2 to 6 weeks.

Bladder Stones

• Endemic (Primary): Common in children in developing countries due to low animal protein/high cereal diet + dehydration. Stones = Ammonium acid urate / Calcium. Symptoms: boy pulling/manipulating penis, interrupted flow.
• Secondary: Most common cause is Urinary Stasis (75%) (e.g., Benign Prostatic Hyperplasia, neurogenic bladder). Spinal cord injury + catheter increases risk 9-fold. Stones = Uric acid, Calcium Oxalate, Struvite.
• Diagnosis: Ultrasound (echogenic mass + posterior acoustic shadowing, moves with gravity). Non-contrast CT is highly accurate. Cystoscopy is definitive and helps plan surgery.
• Treatment: Endoscopic (Transurethral Cystolitholapaxy), Percutaneous, or Open.

🔥 Exam Hints (High-Yield)

• Stone Size rules: < 10mm = SWL. > 20mm = PNL. For 10-20mm in the lower pole, SWL has poor success (55%), prefer alternative.
• Staghorn = PNL. Untreated staghorn (usually struvite) causes renal destruction and sepsis; complete removal is absolutely required.
• Fever + Obstruction = Emergency. If pyelonephritis is present behind a stone, NEVER do lithotripsy. You must do urgent drainage first (stent or nephrostomy).
• Irreversible renal damage from complete obstruction starts at 2 weeks and progresses fully by 6 weeks.
• Endemic pediatric bladder stones are caused by diet (low animal protein/high cereal), not stasis.

Lec 3: Prostatic Diseases (BPH)

Anatomy of the Prostate

• Peripheral Zone (70%): Origin of 60-70% of Prostate Carcinomas (CaP).
• Transition Zone (5%): Origin of Benign Prostatic Hyperplasia (BPH).
• Central Zone (25%).
• Blood supply: Inferior vesical and middle rectal arteries.

Benign Prostatic Hyperplasia (BPH) - Pathophysiology

• Most common benign tumor in men. Age-dependent (>90% by age 80).
• Composed of Stroma (smooth muscle + collagen) and Epithelium.
• Obstruction Types:
  • Mechanical: Intrusion into urethral lumen/bladder neck. *Prostate size on DRE does NOT correlate with symptom severity!*
  • Dynamic: Adrenergic tone of smooth muscle in stroma.
• Bladder Response: Detrusor hypertrophy -> decreased compliance -> trabeculation -> False diverticula (mucosa & serosa only).

Diagnosis & Symptoms

• Obstructive: Hesitancy, weak stream, incomplete emptying, straining, terminal dribbling.
• Irritative: Urgency, frequency, nocturia (due to bladder response).
• AUA Symptom Score: 0-7 (Mild), 8-19 (Moderate), 20-35 (Severe).
• Evaluation: Digital Rectal Examination (DRE) (smooth, firm, elastic), Urinalysis, Serum Creatinine (renal failure in 10%). PSA is optional but standard.

Treatment of BPH

• Watchful Waiting: For AUA score 0-7 (Mild).
• Medical Therapy:
  • Alpha-Blockers (Tamsulosin, Doxazosin, Alfuzosin): Targets smooth muscle (dynamic obstruction). Side effects: Orthostatic hypotension, retrograde ejaculation, rhinitis.
  • 5-Alpha-Reductase Inhibitors (Finasteride, Dutasteride): Blocks Testosterone -> Dihydrotestosterone (DHT). Shrinks epithelium. Takes 6 months for max effect. Reduces PSA by ~50%. Side effects: decreased libido, gynecomastia.
  • Phytotherapy: Saw Palmetto (Serenoa repens), Pygeum africanum.
• Surgical Therapy:
  • Absolute Indications: Refractory retention, recurrent UTI, recurrent gross hematuria, bladder stones, renal insufficiency, large diverticula.
  • Transurethral Resection of the Prostate (TURP): Gold standard (95% done this way). Risks: Retrograde ejaculation (75%), impotence (5-10%), TUR Syndrome (hypervolemic, hyponatremic state due to hypotonic irrigation -> N/V, confusion, bradycardia. Treat with diuresis/hypertonic saline. High risk if >90 mins).
  • TUIP: Transurethral Incision, for small prostates with elevated bladder neck.
  • Open Prostatectomy: For massive glands, or concomitant bladder stones/diverticula.

🔥 Exam Hints (High-Yield)

• Zones: BPH always happens in the Transition Zone. Cancer (CaP) mostly in the Peripheral Zone.
• Prostate Size =/=> Symptoms: Never assume a larger prostate on DRE means worse symptoms. They correlate poorly.
• Alpha vs 5-ARIs: Alpha blockers work FAST on smooth muscle (dynamic). 5-ARIs work SLOW (6 months) on epithelium (mechanical) and reduce PSA by 50%.
• TUR Syndrome is a Hyponatremic, Hypervolemic crisis caused by hypotonic fluid absorption, risk shoots up if surgery is >90 minutes.
• False Diverticula: Formed by the bladder working against BPH obstruction; they contain mucosa and serosa ONLY (no muscle).

Lec 4: Carcinoma of the Prostate (CaP)

Epidemiology & Pathology

• Most common cancer in American men. Risk increases rapidly with age.
• Genetics/Race: African Americans > Whites. 1st-degree relative at age 50 increases risk 7-fold.
• Diet: High animal fat/red meat = High risk. Protective = Lycopene, Selenium, Vitamin E, Omega-3. Harmful = Vitamin D & Calcium.
• Pathology: >95% are Adenocarcinomas. Cytology: Hyperchromatic nuclei, prominent nucleoli, abundant cytoplasm (N:C ratio not helpful).

Gleason Score & Staging

• Gleason Score: Primary pattern (most common) + Secondary pattern (2nd most common). Range 2 to 10.
• Well differentiated = 2-4; Moderate = 5-6; Poorly differentiated = 8-10.
• Metastasis: Most commonly to Bones (osteoblastic/sclerotic lesions), elevating Alkaline Phosphatase. Spinal cord compression (weakness, hyper-reflexia) is a major emergency.

Diagnosis & Tumor Markers

• Prostate-Specific Antigen (PSA): Normal ≤ 4 ng/mL. Produced by benign and malignant tissue (serine protease).
• PSA Kinetics:
  • PSA Velocity: > 0.75 ng/mL/year is highly suspicious for cancer.
  • PSA Density (PSA/Volume): Normal is 0.1 - 0.15.
  • Free PSA: Higher bound PSA = Cancer. > 25% free PSA is reassuring (benign).
• Biopsy: Transrectal Ultrasound (TRUS) guided. ≥ 10 cores directed laterally in the peripheral zone improves detection by 14-20% over traditional 6 sextant biopsies.
• TRUS findings: Hypoechoic areas, bulging capsule, asymmetric seminal vesicles. Better for local staging than DRE.

Treatment Options

• Localized (T1/T2):
  • Active Surveillance: Regular exams, PSA, repeat biopsies for very low-grade disease.
  • Radical Prostatectomy: Complications include erectile dysfunction, incontinence, DVT, pulmonary embolism, lymphocele.
  • Radiotherapy: External beam (6500-7000 cGy) or Brachytherapy (permanent seeds I-125/Pd-103, or temporary Ir-192).
• Metastatic Disease: Androgen Deprivation Therapy (ADT) (70-80% respond).
  • Surgical: Bilateral Orchiectomy.
  • Medical: LHRH agonists + Antiandrogens (e.g., Flutamide, blocks DHT receptors) -> Complete Androgen Blockade.

🔥 Exam Hints (High-Yield)

• Bone Mets: CaP metastasis to bone is characteristically Osteoblastic (sclerotic), causing an elevated Alkaline Phosphatase.
• Gleason Score: Always ranges from 2 to 10 (sum of two most common patterns). 8-10 is poorly differentiated.
• PSA Red Flags: PSA velocity jumping by > 0.75 ng/mL/yr or having low Free PSA (< 25%) points strongly to cancer.
• Biopsy Standard: Minimum of 10 cores (laterally directed) in the peripheral zone gives the best yield.
• Diet: Red meat/animal fat increases risk; Lycopene, Selenium, Vitamin E, Omega-3 are protective.

Lec 5: Renal Failure (AKI & CKD)

Acute Kidney Injury (AKI)

• Abrupt decline in Glomerular Filtration Rate (GFR), causing progressive azotemia.
• Categories:
  • Pre-renal: Volume depletion (hemorrhage, GI loss), Cardiac (low output/MI), Redistribution (hypoalbuminemia, sepsis, bilateral renal artery stenosis).
  • Intra-renal: Glomerulopathies (SLE, Goodpasture, IgA), Infections (Post-strep, Endocarditis), Toxins/Drugs (Allopurinol, Rifampin, Penicillamine).
  • Post-renal: Obstruction. *Must be bilateral* (or involve a solitary functioning kidney) to cause AKI.
• Complications: Fluid overload, Hyperkalemia, Metabolic acidosis, Uremic encephalopathy/pericarditis.
• Management: Correct prerenal factors, eliminate nephrotoxins, correct obstruction. Keep Bicarbonate > 15 mEq/L, protein intake 1-1.8 g/kg/day, carbs >100g/day to prevent catabolism.

Chronic Kidney Disease (CKD)

• Sustained kidney injury > 3 months with GFR < 60 mL/min.
• Top Etiologies: Diabetes Mellitus (44%) > Hypertension (26%) > Glomerulonephritis (7%).
• Stages: Stage 1 (≥90), Stage 2 (60-89), Stage 3 (30-59), Stage 4 (15-29), Stage 5 (<15 = End-Stage Renal Disease/ESRD).
• Refer to Nephrologist when SCr > 1.5 (females) or > 2.0 (males).
• Indications for Dialysis: Anuria/severe oliguria (<50mL/12h), Hyperkalemia (>6.5), Severe acidemia (pH < 7.1), Azotemia (urea >30), Pulmonary edema, Uremic encephalopathy/pericarditis, severe dysnatremia (>160 or <115).

🔥 Exam Hints (High-Yield)

• Post-renal AKI Rule: An obstruction must be Bilateral (or on a solitary kidney) to cause acute kidney injury.
• CKD Timeframe: Must be sustained for > 3 months.
• Most Common Cause of CKD: Diabetes Mellitus (~44%), followed by Hypertension.
• Absolute Dialysis Triggers: Hyperkalemia > 6.5, severe acidosis pH < 7.1, or uremic encephalopathy/pericarditis.
• Nutritional Management of AKI: Give carbs >100g/day to prevent endogenous protein catabolism.

Lec 6: Renal Transplantation

ESRD Treatment & Evaluation

• Median age of new ESRD patients is 64. Incidence higher in men, African-Americans.
• Hemodialysis (HD): Accounts for 2/3 of adults. Peritoneal Dialysis (PD) (~10%) is suited for distant living, diabetics, small stature, heart disease. *Contraindications for PD*: Obesity, hernias, obliterated peritoneal space, Inflammatory Bowel Disease.
• Transplant: Best survival, predominant care for <20 years old.
• Recipient Contraindications: Active infection, noncompliance, active malignancy (Must wait 2 to 5 cancer-free years).
• Diseases that can recur in graft: Focal Segmental Glomerulosclerosis (FSGS), Hemolytic-Uremic Syndrome (HUS), Primary Oxalosis.

Donors & Preservation

• Deceased Donor: Brain death. Ideal criteria: Normal function, no diabetes, no malignancy (except primary brain tumor/superficial skin CA), negative for HIV/Syphilis/Hep. Age 6-50.
• Preservation: University of Wisconsin (UW) solution minimizes cellular swelling (contains lactobionate, raffinose, hydroxyethyl starch). Machine perfusion reliably preserves up to 72 hours.

Rejection Types

• Hyperacute: Immediate (minutes). Preformed cytotoxic antibodies (ABO/HLA). Irreversible thrombosis. Rare now due to cross-matching.
• Accelerated: Days to weeks. Humoral + Cellular. Often unresponsive to therapy.
• Acute: Weeks to months. "Flu-like" symptoms, pain over graft, hypertension, oliguria. Treatable with immunosuppressants.
• Chronic: Gradual decline. Interstitial fibrosis, vascular changes. Positive B-cell crossmatch is predictive.

Immunosuppression & Complications

• Standard Regimen: Glucocorticoids + Calcineurin inhibitor (Tacrolimus/Cyclosporine) + Purine antagonist (Mycophenolate Mofetil / Azathioprine).
• Cardiovascular: MI and Stroke are leading causes of death. Steroids/Cyclosporine cause hyperlipidemia.
• New-Onset Diabetes: High risk due to steroids and calcineurin inhibitors (Tacrolimus is highly diabetogenic).
• Cancer Risk: High incidence of Kaposi sarcoma, Non-Hodgkin lymphoma, skin cancers, and kidney cancer. *Note: NO increase in Prostate Cancer incidence!*
• Vascular Complications: Renal artery stenosis (causes refractory hypertension), Thrombosis (hyperacute rejection).

🔥 Exam Hints (High-Yield)

• Cancer Wait-time: You must wait 2 to 5 years post-cancer treatment before a patient is eligible for transplant.
• Organ Preservation: UW solution relies on impermeant solutes (lactobionate/raffinose) to stop cellular swelling. Machine limits are 72 hours.
• Hyperacute Rejection: Happens in the OR (minutes) due to Preformed antibodies; completely irreversible.
• Post-Transplant Mortality: The #1 cause of death is cardiovascular disease (MI/Stroke).
• Tacrolimus Effect: Very potent calcineurin inhibitor but highly Diabetogenic (leads to new-onset diabetes).

⚖️ Key Comparisons (High-Yield Tables)

1. Types of Hypercalciuria

Type	Pathophysiology	Serum Calcium	PTH Level	Diagnosis / Test
Absorptive	High GI absorption → transient ↑ serum Ca → suppressed PTH → high renal filtration.	Normal	Low/Suppressed	Increased urine Ca after oral Ca load
Renal	Impaired renal tubular reabsorption → Ca leak → Secondary Hyperparathyroidism.	Normal	High	Thiazide Challenge
Resorptive	Excess bone resorption (Usually Primary Hyperparathyroidism / Adenoma).	High (>10.1)	High	Elevated Ca and PTH simultaneously

2. SWL Generators

Generator	Mechanism	Advantages	Disadvantages
Electrohydraulic (Spark Gap)	Underwater spark discharge	Effective in breaking kidney stones	Pressure fluctuations, Short electrode life
Electromagnetic	Acoustic lens focusing	Controllable, long life, less pain	High rate of subcapsular hematoma
Piezoelectric	Ceramic elements (Barium titanate)	Highly focused, Anesthetic-free	Insufficient power for hard stones

3. Prostate Zones Pathology

Zone	% of Young Adult Vol.	Associated Pathology
Peripheral Zone	70%	Origin of 60-70% of Prostate Cancer (CaP)
Transition Zone	5%	Exclusive origin of BPH
Central Zone	25%	Origin of 5-10% of Prostate Cancer

4. Medical Therapy for BPH

Class	Examples	Target / Mechanism	Onset & Effect on PSA	Side Effects
Alpha-Blockers	Tamsulosin, Doxazosin, Alfuzosin	Smooth muscle (Dynamic obstruction)	Fast acting. No effect on PSA.	Orthostatic hypotension, retrograde ejaculation
5-Alpha-Reductase Inhibitors	Finasteride, Dutasteride	Epithelium (Mechanical) - Blocks T to DHT	Takes 6 months. Reduces PSA by ~50%.	Decreased libido, impotence, gynecomastia

5. Renal Graft Rejection Types

Type	Onset Time	Mechanism	Features / Reversibility
Hyperacute	Minutes	Preformed cytotoxic antibodies (ABO/HLA)	Irreversible thrombosis. Rare due to cross-matching.
Accelerated	Days to weeks	Humoral + Cellular	Often unresponsive to therapy.
Acute	Weeks to months	Cellular	"Flu-like", graft pain, oliguria. Treatable with immunosuppressants.
Chronic	Months to years	Interstitial fibrosis, vascular changes	Gradual decline. Positive B-cell crossmatch is predictive.

6. Key Renal Stones Characteristics

Stone Type	Frequency	Urine pH Requirement	Radiopacity	Key Association / Cause
Calcium Oxalate	60% (Most Common)	Variable	Radiopaque	Hypercalciuria, Hypocitraturia, Obesity
Uric Acid	10%	Low (< 5.5)	Radiolucent	High purine diet, Gout, Chronic diarrhea
Struvite	10%	Alkaline	Radiopaque	Urease-producing bacteria (Proteus). Forms Staghorn.
Cystine	1%	Variable	Faintly Opaque	Autosomal recessive transport defect (COLA)