Urolithiasis Go Go Go Go

Afflictions of the Urinary Tract 1.Urinary Tract Infections 2.Pathologic conditions of the prostate 3.URINARY CALCULI

Urinary Stones Polycrystalline aggregates composed of varying amounts of crystalloid and organic matrix Supersaturated urine – Urinary pH, ionic strength, solute concentration, complexation

Urinary pH Uric acid and cysteine less soluble in acid urine Struvite and calcium phosphate loss soluble in alkaline urine As ionic strength increases, the activity coefficient decreases Ionic Strength

Solute Concentration The higher the concentration of 2 ions, the more likely they are to precipitate lower concentration, undersaturation, higher solubility Solubility product (Ksp) – initiation of crystal growth and heterogenous nucleation Formation product (Kfp) – Unstable, spontaneous homogenous nucleation

Complexation Influences availability of specific ions Decrease free ionic form – Sodium and oxalate Crystal formation inhibitors – Act in active crystal growth sites – Magnesium, citrate, pyrophosphate, trace metals

Mechanisms of Stone Formation 1.presence or abundance of substances that promote crystal and stone formation 2.lack of substances to inhibit crystal formation (e.g.magnesium, citrate) 3.excessive excretion or concentration of salts in the urine leading to supersaturation of the crystallizing salt

Stasis or Anatomic Factors Ureteropelvic junction obstruction Horseshoe or ectopic kidney Autosomal dominant polycystic kidney disease Vesicoureteral reflux Calyceal diverticula

Theories Nucleation theory Crystal inhibitor theory

Stone Components Crystal component – Nucleation – Growth – Aggregation Matrix component – 2-10% of stone by weight – Predominantly protein, with hexose and hexosamine – May serve as a nidus for crystal aggregation – Naturally ocurring “glue” – May have an inhibitory role

Urinary Ions A.Calcium B.Oxalate C.Phosphate D.Uric Acid E.Sodium F.Citrate G.Magnesium H.Sulfate I.Other urinary stone inhibitors

Calcium Major ion present in urinary crystals Factors affecting Ca concentration: – Diuretic medications – Complexation with citrate, phosphate, and sulfate – Monosodium urates and decreased pH

Oxalate Insoluble waste product of metabolism 10-15% from the diet Undergo bacterial decomposition in large bowel Hyperoxaluria – Bowel disorders (i.e. Inflammatory bowel disease, small bowel resection, bowel bypass) Renal calculi in 5-10% of patients – Chronic diarrhea with fatty stools – Ingestion of ethylene glycol

Phosphate Buffer: complexe with calcium in urine Key component in calcium phosphate and magnesium ammonium phosphate stones From diet In hyperparathyroidism – predominant crystal in the form of hydroxyapatite, amorphous calcium phosphate, and calcium apatite

Uric Acid By-product of urine metabolism pKa 5.75 Elevaed pH values increase urate Defect in xanthine oxidase results in incresed xanthine, precipitating in urine Pure stones are radiolucent and not identified on plain abdominal films Some are partially radiopaque because of associated calcium deposits

Urinary Ions Sodium – Increases urinary Ca excretion Citrate – Key factor affecting development of calcium urinary stones – Excretion influenced by estrogen Magnesium – Component of struvite calculi – Mg deficiency associated with increased incidence of urinary stone disease Sulfate – Prevent urinary calculi by complexing with calcium

Other Urinary Stone Inhibitors Glycosaminoglycans Pyrophosphates Uropontin – N terminal AA sequence, acidic AA content, aspartic acid content play inhibitory roles