Urolithiasis - Comprehensive Review

1. PATHOLOGY

Definition

Epidemiology

• Lifetime prevalence: 1-20%; rising steadily over four decades in Western populations
• By age 70: ~11% of men and 5.6% of women in the US will develop a symptomatic kidney stone
• Recurrence is high: ~50% within the first decade
• Men are 2x more likely to form stones; peak incidence in the 4th-6th decades; women have a bimodal peak (3rd decade and postmenopause)
• White individuals have higher risk; family history confers 2.5x risk
• Estimated economic burden in the United States approaching $4.7 billion by 2030
• Robbins & Kumar Basic Pathology, p. 527; Bailey & Love's Surgery 28th ed., p. 1496; Brenner & Rector's The Kidney, p. 1277

Pathogenesis

1. Supersaturation - When urinary concentrations of lithogenic solutes exceed their solubility product, crystallization begins
2. Inhibitor failure - Normal urine contains crystal-growth inhibitors: citrate, potassium, magnesium, Tamm-Horsfall mucoprotein. When these are depleted or overwhelmed, nucleation proceeds
3. Crystal nucleation and anchoring - Crystals either pass with urine or anchor onto renal papillae as Randall's plaques (subepithelial calcium phosphate deposits), which serve as a fixed nidus
4. pH effects - Acidic urine (pH <5.5) favors uric acid and cystine precipitation; alkaline urine favors calcium phosphate and struvite formation
5. Urinary stasis - Promotes crystal aggregation; stasis stones are typically multiple, round, smooth ("milk of calcium stones")
6. Organic matrix - All stone types contain ~2.5% mucoprotein matrix by weight

• Bailey & Love's Surgery 28th ed., p. 1496; Robbins & Kumar Basic Pathology, p. 527

Stone Types

• Robbins & Kumar Basic Pathology, Table 12.5, p. 527-528

Calcium Stones - Causes

• Idiopathic hypercalciuria (50% of calcium stone formers): subdivided into absorptive (excessive gut calcium absorption) and renal (tubular reabsorption defect)
• Primary hyperparathyroidism: most common hypercalcemic cause; PTH drives bone resorption and 1,25-dihydroxyvitamin D3 synthesis, increasing intestinal calcium absorption
• Hyperoxaluria: enteric (ileal disease/resection increases colonic oxalate absorption) or primary (rare enzymatic defect)
• Hypocitraturia: distal RTA is the classic cause; citrate normally chelates urinary calcium
• Hyperuricosuria: uric acid crystals act as heterogeneous nidi for calcium oxalate crystallization
• No identified metabolic abnormality in 15-20% of calcium stone formers

Struvite Stones

• Form only in the presence of urease-producing bacteria: Proteus, Klebsiella, Serratia, Enterobacter
• Urease hydrolyzes urea to CO2 and ammonium, raising urine pH and precipitating magnesium-ammonium-phosphate
• Staghorn calculi - branch through the entire pelvicalyceal system; cause progressive renal destruction through chronic infection and obstructive uropathy; complete clearance is mandatory since residual fragments cause rapid recurrence and persistent bacteriuria

Uric Acid Stones

• Radiolucent on plain radiograph (but visible on CT - important diagnostic point)
• 50% of uric acid stone formers have neither hyperuricemia nor increased urinary urate; they simply excrete persistently acidic urine (pH <5.5) - unexplained
• Conditions causing hyperuricosuria: gout, myeloproliferative disorders post-cytotoxic therapy
• Highest geographic prevalence in the Middle East

Cystine Stones

• Autosomal recessive defect in renal proximal tubular and intestinal transport of cystine, ornithine, lysine, arginine (COLA)
• Cystine insoluble even at physiologic pH; worsens with acidic urine
• Very hard due to disulfide bonds - essentially resistant to ESWL

Morphology

• Unilateral in ~80% of patients
• Most common sites: renal pelvis, calyces, bladder
• Typically 2-3 mm; may be smooth or jagged
• Staghorn calculi: massive branching structures creating a cast of the pelvicalyceal system - almost always struvite
• Stones cause mucosal ulceration, hemorrhage, and obstruction; the latter leads to hydronephrosis and, if chronic, loss of renal function
• Robbins & Kumar Basic Pathology, p. 528

2. MEDICINE

Clinical Presentation

• Asymptomatic: increasingly diagnosed incidentally on imaging, especially large pelvic stones
• Ureteric colic: sudden-onset excruciating flank pain radiating to groin, scrotum/labia; caused by hyperperistalsis of ureteric musculature against an obstructing stone
  • Small (3-5 mm) calculi most commonly lodge at the ureterovesical junction (UVJ)
  • Lower ureteric/UVJ stones cause additional urgency, frequency, dysuria
• Hematuria: gross or microscopic in most cases
• Calculuria: passage of sand or gravel
• Nausea and vomiting: from shared celiac innervation
• Fever and rigors: indicates concurrent UTI/urosepsis - a urological emergency
• Malaise and weight loss: with longstanding infection stones or renal failure

Differential Diagnosis of Ureteric Colic

• Clot colic (anticoagulation, haemophilia), papillary necrosis
• Acute appendicitis, bowel obstruction, abdominal aortic aneurysm
• Ectopic pregnancy, ovarian torsion
• Malingering

Investigations

• Urinalysis: hematuria, pyuria (sterile or infected), pH
• Urine culture: if infection suspected or intervention planned
• Bloods: FBC, serum creatinine, electrolytes, calcium, uric acid; pregnancy test (women)
• Plain KUB: detects radiopaque stones; misses uric acid and most cystine stones
• Ultrasound: first-line in children, pregnant women; detects hydronephrosis and stones at kidney/UVJ
• Non-contrast CT (NCCT): gold standard - detects all stone types except indinavir; best for size, location, and degree of obstruction

• 24-hour urine: calcium, oxalate, uric acid, citrate, sodium, creatinine, volume
• Serum: PTH (if hypercalcemic), uric acid
• Stone analysis: analyze all passed or retrieved stones
• Stratify into low-risk (single stone, no metabolic abnormality) vs. high-risk formers

Medical Management

• NSAIDs (diclofenac, ketorolac) - first-line analgesic; antispasmodics are not necessary
• Opioids for refractory pain
• IV hydration if unable to tolerate orally or sepsis is present

• Alpha-1 blockers (tamsulosin): relaxes smooth muscle of the distal ureter; used for distal ureteric stones >5 mm and post-ESWL fragment passage
• Calcium channel blockers: also reduce dysmotive ureteric contractions while preserving expulsive peristalsis
• Spontaneous passage rates: ~95-100% for stones <4 mm; ~50% for 5-10 mm; rarely for >10 mm

• Fluid intake >2.5 L/day (target urine output >2 L/day)
• Do NOT restrict dietary calcium (paradoxically increases oxalate absorption - intestinal calcium binds oxalate in the gut and prevents its absorption)
• Supplemental calcium should be taken at mealtimes
• Reduce animal protein and sodium intake
• Bailey & Love's Surgery 28th ed., p. 1498-1499; Brenner & Rector's The Kidney, p. 1319

3. SURGERY

Indications for Surgical Intervention

• Failure of medical/conservative management
• Impaired or deteriorating renal function
• Complete ureteric obstruction
• Chronic or recurrent infection (staghorn calculi, matrix calculi)
• Urosepsis with obstruction (emergency)
• High-risk occupation (pilots, sailors, long-distance locomotive drivers) or remote geographical location
• Patient preference

Emergency Urinary Decompression

• JJ ureteric stent (retrograde; cystoscopy-guided): provides internal drainage
• Percutaneous nephrostomy (PCN) (antegrade): for failed retrograde approach or anatomical difficulty
• In selected stable patients without sepsis, ureteroscopy with stone removal can be performed primarily

Extracorporeal Shock Wave Lithotripsy (ESWL)

• Non-invasive, outpatient procedure; introduced by Christian Chaussy (1980)
• Mechanism: focused acoustic pulse waves (localized by fluoroscopy ± ultrasound) cause stone fragmentation through direct mechanical stress and cavitation (bubble collapse)
• Indications: renal and ureteric stones <2 cm; first-line for most renal stones <2 cm with favorable anatomy
• Absolute contraindications: pregnancy, uncorrected coagulopathy, active UTI, distal obstruction, aortic/renal artery aneurysm
• Relative contraindications: pacemaker, morbid obesity, musculoskeletal deformities, renal anomalies (horseshoe kidney, pelvic kidney)
• Complications:
  • Steinstrasse ("street of stones"): row of stone fragments lining the distal ureter; usually pass spontaneously but may obstruct
  • "Clinically insignificant residual fragments" (CIRFs, ≤4 mm): 20-40% fail to clear and form a nidus for recurrence

Ureteroscopy (URS) / Retrograde Intrarenal Surgery (RIRS)

• Rigid URS: ureteric stones from proximal ureter to UVJ
• Flexible URS / RIRS: intrarenal stones; access to all calyces
• Energy sources: holmium:YAG laser (gold standard - works on all stone compositions); pneumatic, electrohydraulic, ultrasonic also used
• Indications: ureteric stones at any level; renal stones <2 cm; failed ESWL
• Avoided in children <5 years due to ureteric caliber
• Day-case procedure; no skin incision required

Percutaneous Nephrolithotomy (PCNL)

• Removal of renal stones via a dilated percutaneous track (standard >28 Fr) between skin and pelvicalyceal system
• Position: typically prone; posterolateral calyx used as entry point
• Guidance: fluoroscopy or ultrasound
• Energy sources: ultrasound + pneumatic ± laser

• Renal stones >2 cm
• Lower-pole renal stones with anatomy unfavorable for ESWL
• Failed ESWL or RIRS
• Staghorn calculi (first-line; complete clearance mandatory)

• Hemorrhage (can require selective angioembolization)
• Sepsis/infection
• Pleural violation (supracostal puncture): pneumothorax, hydrothorax
• Injury to adjacent organs (bowel, spleen, liver)

Open/Laparoscopic Surgery

• Reserved for complex/infected stones with anatomical abnormalities preventing endourological access
• Procedures: pyelolithotomy (pelvic stones), anatrophic nephrolithotomy (complex staghorn)
• Rarely performed in the modern era

Special Situation: Pregnancy

• Renal colic = the most common cause of non-obstetric hospital admission in pregnancy
• Physiological changes: increased GFR, progesterone-mediated ureteric dilation, uterine compression
• Imaging: ultrasound first-line; MRI if needed; CT avoided where possible
• Treatment: conservative (most stones pass spontaneously); ureteric stent or PCN for obstruction; ESWL contraindicated; URS can be done if necessary
• Bailey & Love's Surgery 28th ed., p. 1499-1500

Quick Reference Summary

• Robbins & Kumar Basic Pathology, 10th ed., Table 12.5, p. 527-528
• Robbins, Cotran & Kumar Pathologic Basis of Disease, 10th ed.
• Bailey & Love's Short Practice of Surgery, 28th ed., Chapter 82, p. 1496-1500
• Brenner & Rector's The Kidney, 2-Vol Set, Chapter 38, p. 1277-1319
• Campbell-Walsh-Wein Urology, 12th ed.