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- 1. urinary lithiasis module: men’s health
- 2. Objectives • to be able to enumerate the different causes of urinary stones • to be able to discuss the pathogenesis of stone formation • to be able to explain the different Physicochemical phases of stone formation • to be enumerate the different inhibitors of crystal formation • To be able to discuss the classification of renal stones
- 3. References: • Campbell-Walsh Urology 10th ed • https://scialert.net/fulltext/?doi=ajdd.2017.54.62#424020_ja • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410535/ • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5250668/
- 4. epidemiology of renal calculi • Global annual prevalence rate: 3% - 5% • Life time prevalence: 15%-25% • rate of recurrence after 1st time: • 1st year: 14% • 5th year: 35% • 10th year: 52%
- 5. epidemiology of renal calculi • Gender • Race/Ethnicity • Age • Geography • Climate • Occupation • BMI & Weight • Water • typically affects adult males than adult women • however, according to a study “..resource utilization for urinary stone disease rose 22% for men and 52% for women, reflecting an increasing resource use in women compared to men.” --
- 6. epidemiology of renal calculi • Gender • Race/Ethnicity • Age • Geography • Climate • Occupation • BMI & Weight • Water • prevalence by Race is highest among white males> Hispanics> Asians> African-Americans
- 7. epidemiology of renal calculi • Gender • Race/Ethnicity • Age • Geography • Climate • Occupation • BMI & Weight • Water • uncommon < 20 years old • peak incidence: 4th to 6th decade of life • in women, bimodal distribution of stone disease occurs • a 2nd peak occurs on the 6th decade corresponding to the onset of menopause
- 8. epidemiology of renal calculi • Gender • Race/Ethnicity • Age • Geography • Climate • Occupation • BMI & Weight • Water • roughly follows environmental risk factors • higher prevalence in: • hot • arid • dry climates
- 9. epidemiology of renal calculi • Gender • Race/Ethnicity • Age • Geography • Climate • Occupation • BMI & Weight • Water • seasonal variation in stone disease is likely related to temperature by way of fluid losses from perspiration & sunlight induced increases in vitamin D
- 10. epidemiology of renal calculi • Gender • Race/Ethnicity • Age • Geography • Climate • Occupation • BMI & Weight • Water • occupational risk factors: • heat exposure • dehydration • occupations associated with increase risk: • cooks • engineering personnel • steel workers
- 11. epidemiology of renal calculi • Gender • Race/Ethnicity • Age • Geography • Climate • Occupation • BMI & Weight • Water • prevalence & incident risk are directly correlated with weight and BMI in both sexes • higher BMI associated w/ increase excretion of: • Urinary oxalate • Uric Acid • Sodium • Phosphorus
- 12. epidemiology of renal calculi • Gender • Race/Ethnicity • Age • Geography • Climate • Occupation • BMI & Weight • Water • urinary supersaturation of uric acid increases with increasing BMI • association of obesity w/ calcium oxalate stone formation is primarily due to increased excretion of promoters of stone formation • association of obesity and uric acid stone is primarily influenced by urinary pH
- 13. epidemiology of renal calculi • Gender • Race/Ethnicity • Age • Geography • Climate • Occupation • BMI & Weight • Water • water intake is inversely related to kidney stone formation • geographical differences on incidence of stone disease have been associated to the difference in the mineral & electrolyte content of water
- 14. physicochemistry • stone formation is a cascade of events that occurs as the glomerular filtrate traverses the nephron • starts w/ urine becoming supersaturated w/ respect to stone forming salts • crystals that are formed may flow with the urine • however, some crystals become retained in the kidney thru anchoring sites that promote growth and aggregation of crystal leading to stone formation
- 15. physicochemistry state of saturation • concentration product: a solution containing ions/ molecules of a sparingly soluble salt • Saturated solution: a state when a pure aqueous solution of a salt reaches the point at which no further added salt crystals will dissolve • addition of crystals to a saturated solution will cause crystals to precipitate • precipitation is influenced by: • urine pH • temperature
- 16. physicochemistry state of saturation • in urine however, crystallization does not necessarily occur because of the presence of inhibitors and other molecules that may allow higher concentration of salts without precipitation • urine is considered to be metastable with respect to the salt • Formation product: the point where the metastable state of urine can no longer be held in solution so that crystal would already form
- 17. physicochemistry state of saturation • Three major states of saturation in urine: • undersaturated • metastable • unstable • crystals would not form • dissolution of crystals theoretically can be done
- 18. physicochemistry state of saturation • Three major states of saturation in urine: • undersaturated • metastable • unstable • state were most common stone components reside • precipitation does not occur • modulation of factors controlling stone formation may be done • therapeutic intervention is performed at this state
- 19. physicochemistry state of saturation • Three major states of saturation in urine: • undersaturated • metastable • unstable • nucleation will occur • inhibitors not generally effective
- 20. physicochemistry metastable urine state • crystal growth can occur on existing crystal, but de novo formation of crystals cannot occur in the length of time it normally takes for the filtered urine to reach the bladder • BUT crystal formation may occur on certain conditions
- 21. physicochemistry metastable urine state: circumstances when crystals may grow 1. parts of the nephron where local concentration products may exceed the formation product for long enough time periods to allow nucleation to occur 2. local areas of obstruction/ stasis in the upper urinary tract may prolong urinary transit time and allow crystals to form 3. microscopic impurities/ other constituents in the urine can facilitate the nucleation process by absorption of the crystal components in a geometric way that ensemble the native crystals
- 22. physicochemistry Nucleation & Crystal growth, aggregation and retention • Homogenous nucleation is the process by which nuclei form in pure solution • Nuclei are the earliest crystal structure that does not dissolve • Small nuclei is unstable favoring dissolution of the crystal over crystal growth • Nuclei would persist if: • supersaturation level is reached • size of the crystal is adequate • urine transit time is longer that the lag time to nucleation
- 23. physicochemistry Nucleation & Crystal growth, aggregation and retention • crystal growth occurs when: • promoters stabilize the nuclei thus providing a surface with a binding site that accommodates the crystal structure of the nucleus • crystal nuclei usually form through heterogeneous nucleation by adsorption onto existing surfaces of epithelial cells, cell debris or other crystals • Inhibitors of crystal growth • Magnesium • Citrate • Nephrocalcin • Tamm-Horsfall mucoprotein • Uropontin • Bikunin
- 24. physicochemistry two views on formation & growth of crystals • Free-particle mechanism, tubular plugs • Fixed-particle mechanism, papillary plaques • starts with formation of crystals inside the nephron • if the crystals are removed it becomes harmless crystalluria • if not, retention of crystals leads either to: • particles too large to pass • particles adhere to damaged cells
- 25. physicochemistry two views on formation & growth of crystals • Free-particle mechanism, tubular plugs • Fixed-particle mechanism, papillary plaques • retained crystals can: • enter the interstitium • form plugs inside tubules/ ducts of Bellini • crystal plugs were seen in patients w/: • primary hyperoxaluria • primary hyperparathyroidism • enteric hyperoxaluria • distal renal tubular acidosis
- 26. physicochemistry two views on formation & growth of crystals • Free-particle mechanism, tubular plugs • Fixed-particle mechanism, papillary plaques • these conditions have increase serum and renal load of Calcium, Oxalate & Cystine: • primary hyperoxaluria • primary hyperparathyroidism • enteric hyperoxaluria • high renal load leads to increased intratubular concentrations further increasing crystallization
- 27. physicochemistry two views on formation & growth of crystals • Free-particle mechanism, tubular plugs • Fixed-particle mechanism, papillary plaques • overall, plugs consist of random aggregates formed due to an acute high supersaturation of stone components
- 28. physicochemistry two views on formation & growth of crystals • Free-particle mechanism, tubular plugs • Fixed-particle mechanism, papillary plaques • initial step in papillary plaque formation is precipitation of calcium phosphate in the interstitium around the bends of the longest loops of Henle • with alternating accumulation of crystal components and organic material these deposits increase in size • the growing plaque gets exposed to the urine space outside the papilla
- 29. physicochemistry two views on formation & growth of crystals • Free-particle mechanism, tubular plugs • Fixed-particle mechanism, papillary plaques • Plaque formation in the interstitium may form during periods of increased reabsorption of calcium & phosphate • this leads to a supersaturation in the interstitial space • since water in the interstitium is static this allows the salts to crystalize
- 30. physicochemistry two views on formation & growth of crystals • Free-particle mechanism, tubular plugs • Fixed-particle mechanism, papillary plaques • overall, this mechanism contains an initial period of deposition outside the dynamics of urine flow • this is followed by growth and eventual exposure to urine
- 31. physicochemistry inhibitors & promoters of crystal formation • presence of molecules that raises the supersaturation needed to initiate crystal nucleation/ reduce rate of crystal growth to prevent stone formation have been identified • Known Inhibitors of crystal formation: • Citrate • Magnesium • Pyrophosphate
- 32. physicochemistry inhibitors & promoters of crystal formation • Known Inhibitors of crystal formation: • Citrate • Magnesium • Pyrophosphate • acts as an inhibitor of calcium oxalate and calcium phosphate stone formation by: • complexes with calcium to decrease available ionic calcium for binding with oxalate or phosphate • inhibits spontaneous precipitation of calcium oxalate
- 33. physicochemistry inhibitors & promoters of crystal formation • Known Inhibitors of crystal formation: • Citrate • Magnesium • Pyrophosphate • acts as an inhibitor of calcium oxalate and calcium phosphate stone formation by: cont.. • prevents agglomeration of calcium oxalate • reduced calcium phosphate growth • prevents heterogeneous nucleation of calcium oxalate by monosodium urate
- 34. physicochemistry inhibitors & promoters of crystal formation • Known Inhibitors of crystal formation: • Citrate • Magnesium • Pyrophosphate • it’s action is derived from its complex with oxalate • this complex reduces available ionic oxalate concentrations and decrease calcium oxalate supersaturation • it also reduces the rate of calcium oxalate crystal growth
- 35. physicochemistry inhibitors & promoters of crystal formation • Known Inhibitors of crystal formation: • Citrate • Magnesium • Pyrophosphate • inorganic pyrophosphate is responsible for 25% - 50% of the inhibitory activity of whole urine against calcium phosphate crystallization
- 36. physicochemistry inhibitors & promoters of crystal formation • Known Inhibitors of calcium oxalate monohydrate crystal aggregation: • Nephrocalcin glycoprotein • Tamm-Horsfall glycoprotein • Osteopontin/ Uropontin • is an acidic glycoprotein that is synthesized in the proximal convoluted tubules and the thick ascending limb • inhibits growth of calcium oxalate monohydrate crystals
- 37. physicochemistry inhibitors & promoters of crystal formation • Known Inhibitors of calcium oxalate monohydrate crystal aggregation: • Nephrocalcin glycoprotein • Tamm-Horsfall glycoprotein • Osteopontin/ Uropontin • expressed by renal epithelial cells in the thick ascending limb and distal convoluted tubule as a membrane- anchored protein that is released into the urine after the anchoring site is cleaved by phospholipase or proteases • most abundant protein in the urine • potent inhibitor of calcium oxalate crystal aggregation
- 38. physicochemistry inhibitors & promoters of crystal formation • Known Inhibitors of calcium oxalate monohydrate crystal aggregation: • Nephrocalcin • Tamm-Horsfall glycoprotein • Osteopontin/ Uropontin • expressed in bone matrix and renal epithelial cells of the ascending limb of the loop of Henle and distal tubule • inhibits nucleation, growth and aggregation of calcium oxalate crystal • also reduces binding of crystals to renal epithelial cells
- 39. mineral metabolism • Calcium absorption primarily occurs in the small intestines at a rate that is dependent on calcium intake • 1,25-Dihydroxyvitamin D, is the most potent stimulator of intestinal calcium absorption • PTH stimulate 1α-hydroxylase in the proximal tubule of the kidney to convert 25-dihydroxyvitamin D3 to 1,25(OH)2D3 • PTH enhances proximal tubular reabsorption of calcium and renal phosphate excretion • Intestinal oxalate absorption is influenced by luminal calcium, magnesium and oxalate-degrading bacteria
- 40. pathogenesis of upper urinary tract calculi classification of nephrolithiasis • Calcium Stones • Uric Acid Stones • Cystine Stones • Infection Stones • Miscellaneous Stones
- 41. pathogenesis of upper urinary tract calculi classification of nephrolithiasis • Calcium Stones • Uric Acid Stones • Cystine Stones • Infection Stones • Miscellaneous Stones • nearly 75% of all urinary calculi contain calcium • Hypercalciuria • most common abnormality identified • but not all persons w/ hypercalciuria develop stones
- 42. pathogenesis of upper urinary tract calculi classification of nephrolithiasis • Calcium Stones • Uric Acid Stones • Cystine Stones • Infection Stones • Miscellaneous Stones • Hypercalciuria • stone formation may occur with: • increase urinary saturation of calcium salts • decrease inhibitory activity of citrate & chondroitin sulfate
- 43. pathogenesis of upper urinary tract calculi classification of nephrolithiasis • Calcium Stones • Uric Acid Stones • Cystine Stones • Infection Stones • Miscellaneous Stones • Hypercalciuria • definitions: • > 200 mg urinary calcium/day, after adherence to a 400 mg calcium, 100 mg sodium diet x 1 week (Menon, 1986) • excretion of greater than 4 mg/kg/day or greater than 7 mmol/day in men and 6 mmol/day in women (Parks and Coe, 1986)
- 44. pathogenesis of upper urinary tract calculi classification of nephrolithiasis • Calcium Stones • Uric Acid Stones • Cystine Stones • Infection Stones • Miscellaneous Stones • Hyperoxaluria • definitions: urinary oxalate >40 mg/day • leads to urinary saturation of calcium oxalate that leads to calcium oxalate stones formation • it is also involve in crystal growth and retention by means of renal tubular cell injury by lipid peroxidation and generation of oxygen free radicals
- 45. pathogenesis of upper urinary tract calculi classification of nephrolithiasis • Calcium Stones • Uric Acid Stones • Cystine Stones • Infection Stones • Miscellaneous Stones • Hyperoxaluria may be due to: • primary hyperoxaluria • derangement in biosynthesis • enteric hyperoxaluria (malabsorption conditions) • inflammatory bowel disease • celiac sprue • intestinal resection • Dietary hyperoxaluria • excessive dietary intake of vitamin C
- 46. pathogenesis of upper urinary tract calculi classification of nephrolithiasis • Calcium Stones • Uric Acid Stones • Cystine Stones • Infection Stones • Miscellaneous Stones • Hyperuricosuria • urinary uric acid > 600mg/day • 10% of calcium stone formers have hyperuricosuria as the only abnormality • most common cause is increase dietary intake of purine
- 47. pathogenesis of upper urinary tract calculi classification of nephrolithiasis • Calcium Stones • Uric Acid Stones • Cystine Stones • Infection Stones • Miscellaneous Stones • Hypocitraturia • urinary citrate level of: • < 320 mg/day (Park, 1987) • < 0.6 mmol (men), 1.03 mmol (women)/day (Menon and Mahle, 1983) • cause by: • metabolic acidosis due to enhanced renal tubular reabsorption • decrease synthesis of citrate in peritubular cells
- 48. pathogenesis of upper urinary tract calculi classification of nephrolithiasis • Calcium Stones • Uric Acid Stones • Cystine Stones • Infection Stones • Miscellaneous Stones • Low Urine pH • defined as: < 5.5 • may be due to: • high amount of dissociated uric acid • chronic metabolic acidosis • gouty diathesis- formation of urinary stones in persons w/ 1o gout
- 49. pathogenesis of upper urinary tract calculi classification of nephrolithiasis • Calcium Stones • Uric Acid Stones • Cystine Stones • Infection Stones • Miscellaneous Stones • Renal Tubular Acidosis • characterized by metabolic acidosis resulting from defects in renal tubular hydrogen ion secretion/ bicarbonate reabsorption • Types of RTA: • Type 1 • Type II • Type III
- 50. Renal Tubular Acidosis • Normal: kidney must reabsorb filtered bicarbonate to maintain buffering action • Excess acid must likewise be excreted • failure of the two mechanism lead to metabolic acidosis: • decrease buffer (bicarbonate) • increase acid (decrease acid secretion in the tubules) • RTA occurs due to an impairment of • net acid excretion (Type1) • reabsorption of bicarbonate (Type 2)
- 51. types of renal tubular acidosis • Type 1 (Distal) • Type 2 (Proximal) • Type 4 (Distal) • characterized by an abnormal collecting duct function w/c is the inability to acidify the urine in the presence of systemic acidosis • classic findings: • hypokalemia • hypercholerimia • non-anion gap metabolic acidosis • nephrocalcinosis • elevated urine (>6.0)
- 52. types of renal tubular acidosis • Type 1 (Distal) • Type 2 (Proximal) • Type 4 (Distal) • most common associated stone is Calcium Phosphate because of: • hypercalciuria • hypocitraturia: most important factor in stone formation for type 1 • increased urinary pH • Metabolic acidosis promote: • bone demineralization • which lead to hyperparathyroidism • Hypercalceuria
- 53. types of renal tubular acidosis • Type 1 (Distal) • Type 2 (Proximal) • Type 4 (Distal) • characterized by a defect in bicarbonate reabsorption associated with: • initial high urine pH that normalizes as plasma HCO3 - decreases • decrease in amount of filtered HCO3 - • nephrolithiasis is uncommon due to a normal citrate excretion • affects the proximal tubule function • Stone is not common due to a normal citrate excretion
- 54. types of renal tubular acidosis • Type 1 (Distal) • Type 2 (Proximal) • Type 4 (Distal) • associated w/ chronic renal damage seen in patients w/ • interstitial renal disease • diabetic nephropathy • stone formation is not common due to a reduced excretion of stone-forming substances such as calcium and uric acid
- 55. pathogenesis of upper urinary tract calculi classification of nephrolithiasis • Calcium Stones • Uric Acid Stones • Cystine Stones • Infection Stones • Miscellaneous Stones • Hypomagnesuria • rare cause of nephrolithiasis • magnesium binds with oxalate and calcium thus reducing Mg inhibitory activity • Low urinary Mg level associated with decreased urinary citrate levels, w/c. further contributes to stone formation
- 56. pathogenesis of upper urinary tract calculi classification of nephrolithiasis • Calcium Stones • Uric Acid Stones • Cystine Stones • Infection Stones • Miscellaneous Stones • determinants of uric acid stone formation • low pH • most important pathogenic factor • low urine volume • hyperuricosuria • stone formation may be due to: • congenital causes • acquired causes • idiopathic causes
- 57. uric acid stone formation causes • Congenital disorders • Acquired • Idiopathic • associated with: • Defects in renal tubular urate reabsorption • Lesch-Nyhan syndrome • 1o a defect in purine metabolism • deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) • leads to build up of uric acid in all body fluids
- 58. uric acid stone formation causes • Congenital disorders • Acquired • Idiopathic • associated with: • Familial Juvenile Gouty Nephropathy • characterized by elevated serum uric acid concentrations • due to abnormal reabsorption of uric acid
- 59. uric acid stone formation causes • Congenital disorders • Acquired • Idiopathic • chronic diarrhea • volume depletion • myeloproliferative disorders • high animal protein intake • intake of uricosuric drugs (ex. colchicine, allopurinol)
- 60. uric acid stone formation causes • Congenital disorders • Acquired • Idiopathic • gouty diathesis/ idiopathic low urine pH • manifest with: • normal uric acid levels (does not have gout) • acidic urine • Hyperuricosuric calcium nephrolithiasis • manifest with: • hyperuricosuria • normal urine pH
- 61. pathogenesis of upper urinary tract calculi classification of nephrolithiasis • Calcium Stones • Uric Acid Stones • Cystine Stones • Infection Stones • Miscellaneous Stones • main component is cystine • due to crystallization of cystine in urine • Factors determining crystallization of cystine in urine: • urinary cystine concentration • urine pH • ionic strength • urinary macromolecules
- 62. Factors determining crystallization of cystine in urine • urinary cystine concentration • urine pH • ionic strength • urinary macromolecules • supersaturation of cystine in the urine is the main contributor • due to: • no specific inhibitor for cystine crystallization • poor solubility of cystine in urine
- 63. Factors determining crystallization of cystine in urine • urinary cystine concentration • urine pH • ionic strength • urinary macromolecules • cystine solubility is pH dependent • Solubility of cystine at particular pH: • 300 mg/L : pH 5 • 400 mg/L: pH 7 • 1000 mg/L: pH 9 • Average urine pH: 6
- 64. Factors determining crystallization of cystine in urine • urinary cystine concentration • urine pH • ionic strength • urinary macromolecules • Ionic strength influences the solubility of cystine • so that an increase in ionic strength of urine from 0.005 to 0.3 will allow an addition of 70 mg of cystine to be dissolved
- 65. Factors determining crystallization of cystine in urine • urinary cystine concentration • urine pH • ionic strength • urinary macromolecules • colloids can also increase cystine solubility • but the mechanism is still unclear
- 66. pathogenesis of upper urinary tract calculi classification of nephrolithiasis • Calcium Stones • Uric Acid Stones • Cystine Stones • Infection Stones • Miscellaneous Stones • primarily composed of Magnesium Ammonium Phosphate Hexahydrate called struvite • prerequisite in its formation is infection with a urease-producing bacteria • urinary urea is hydrolyzed to ammonia + CO2 (produces alkaline urine, pH 7.2 - 8.0)
- 67. pathogenesis of upper urinary tract calculi classification of nephrolithiasis • Calcium Stones • Uric Acid Stones • Cystine Stones • Infection Stones • Miscellaneous Stones • but alkaline pH favors the formation of ammonia • however in the presence of urease, ammonia continues to be produced despite the alkaline pH • this further increases the pH of urine
- 68. pathogenesis of upper urinary tract calculi classification of nephrolithiasis • Calcium Stones • Uric Acid Stones • Cystine Stones • Infection Stones • Miscellaneous Stones • Alkaline pH also promotes hydration of CO2 to Carbonic acid • Carbonic acid dissociates into bicarbonate + 2 Hydrogen ions
- 69. pathogenesis of upper urinary tract calculi classification of nephrolithiasis • Calcium Stones • Uric Acid Stones • Cystine Stones • Infection Stones • Miscellaneous Stones • Dihydrogen phosphate in the alkaline urine promotes dissociation to produce phosphate ions • Add Magnesium into the mixture you would have: • Ammonium + Phosphate + Magnesium = Magnesium Ammonium Phosphate • Infection stones may also be exacerbated with: • urinary obstruction • urine stasis
- 70. pathogenesis of upper urinary tract calculi classification of nephrolithiasis • Calcium Stones • Uric Acid Stones • Cystine Stones • Infection Stones • Miscellaneous Stones • Common pathogens associated: • Proteus • P. mirabilis: most common organism causing struvite stones • Klebsiella • Pseudomonas • Staphylococcus • incidence is higher in women than in men (2:1)
- 71. pathogenesis of upper urinary tract calculi classification of nephrolithiasis • Miscellaneous Stones • Xanthine & Dihydroxyadenine Stones • Ammonium Acid Urate Stones • Matrix Stones • Medication-Related Stones • radiolucent stone formed due to: • congenital deficiency of xanthine oxidase • results into plasma accumulation and excess urinary excretion of xanthine • xanthine is poorly soluble in urine leading to supersaturation with the subsequent development of xanthine stones
- 72. pathogenesis of upper urinary tract calculi classification of nephrolithiasis • Miscellaneous Stones • Xanthine & Dihydroxyadenine Stones • Ammonium Acid Urate Stones • Matrix Stones • Medication-Related Stones • radiolucent stone formed due to: • congenital deficiency of adenine phosphoribosyltransferase (APRT) • leads to formation and hyperexcretion of dihydroxyadenine (DHA) • low solubility of DHA leads to precipitation and formation of urinary crystals that may grow and form urinary stones
- 73. pathogenesis of upper urinary tract calculi classification of nephrolithiasis • Miscellaneous Stones • Xanthine & Dihydroxyadenine Stones • Ammonium Acid Urate Stones • Matrix Stones • Medication-Related Stones • rare cause of urinary stones, seen in <1% of all stone formers • conditions associated include: • laxative abuse • recurrent UTI • recurrent uric acid stone formation • inflammatory bowel disease
- 74. pathogenesis of upper urinary tract calculi classification of nephrolithiasis • Miscellaneous Stones • Xanthine & Dihydroxyadenine Stones • Ammonium Acid Urate Stones • Matrix Stones • Medication-Related Stones • Pathophysiology has been postulated to be due to: • dehydration 2o GI losses (from abuse of laxatives) causing: • intracellullar acidosis • enhanced ammonia excretion • Urinary sodium is low because of dehydration • urate complexes with ammonia leading to urinary supersaturation of ammonium acid urate
- 75. pathogenesis of upper urinary tract calculi classification of nephrolithiasis • Miscellaneous Stones • Xanthine & Dihydroxyadenine Stones • Ammonium Acid Urate Stones • Matrix Stones • Medication-Related Stones • also known as fibromas/ colloid calculi/ albumin calculi • such stones are made of mucopolysaccharide (1/3) + protein (2/3)
- 76. pathogenesis of upper urinary tract calculi classification of nephrolithiasis • Miscellaneous Stones • Xanthine & Dihydroxyadenine Stones • Ammonium Acid Urate Stones • Matrix Stones • Medication-Related Stones • most common amino acids found were: • threonine • leucine • serine • tyrosine • arginine • lysine
- 77. pathogenesis of upper urinary tract calculi classification of nephrolithiasis • Miscellaneous Stones • Xanthine & Dihydroxyadenine Stones • Ammonium Acid Urate Stones • Matrix Stones • Medication-Related Stones • formation may be due to: • direct precipitation and crystallization of a drug or its metabolite • indirectly by altering the urinary environment favorable for metabolic stone formation
- 78. pathogenesis of upper urinary tract calculi classification of nephrolithiasis • Miscellaneous Stones • Xanthine & Dihydroxyadenine Stones • Ammonium Acid Urate Stones • Matrix Stones • Medication-Related Stones • Drugs associated with calcium stone formation • loop diuretics (furosemide) • acetazolamide: a carbonic anhydrase inhibitor • topiramate: use for seizure disorders and migraine • zonisamide: sulfonamide anticonvulsant and carbonic anhydrase inhibitor
- 79. anatomic predisposition to stone formation • Ureteropelvic Junction Obstruction • Horseshoe kidneys • Caliceal Diverticula • Medullary sponge kidney
- 80. anatomic predisposition to stone formation • Ureteropelvic Junction Obstruction • Horseshoe kidneys • Caliceal Diverticula • Medullary sponge kidney • incidence of renal stones in this abnormality is about 20% • however studies show that metabolic abnormalities play a big role in the development of urinary stones among these patients
- 81. anatomic predisposition to stone formation • Ureteropelvic Junction Obstruction • Horseshoe kidneys • Caliceal Diverticula • Medullary sponge kidney • evidence on the role of metabolic predisposition: • high rate of recurrence of stone formation after correction • metabolic evaluation demonstrated an underlying metabolic abnormality • type and distribution of metabolic abnormality identified in UJO patients where similar to the general population
- 82. anatomic predisposition to stone formation • Ureteropelvic Junction Obstruction • Horseshoe kidneys • Caliceal Diverticula • Medullary sponge kidney • therefore: correction of UPJ obstruction does not prevent stone formation from recurring
- 83. anatomic predisposition to stone formation • Ureteropelvic Junction Obstruction • Horseshoe kidneys • Caliceal Diverticula • Medullary sponge kidney • occurs in 0.25% of the population and renal stone incidence among them is 20% • because of the high insertion of the ureter into the renal pelvis there is impairment of urine drainage
- 84. anatomic predisposition to stone formation • Ureteropelvic Junction Obstruction • Horseshoe kidneys • Caliceal Diverticula • Medullary sponge kidney • Although, risk of stone formation has been related to urinary stasis • underlying metabolic abnormalities are still needed for the formation of stones
- 85. anatomic predisposition to stone formation • Ureteropelvic Junction Obstruction • Horseshoe kidneys • Caliceal Diverticula • Medullary sponge kidney • associated in 40% of patients w/ stones • unclear if the stone formation is caused by local obstruction or because of metabolic factors
- 86. anatomic predisposition to stone formation • Ureteropelvic Junction Obstruction • Horseshoe kidneys • Caliceal Diverticula • Medullary sponge kidney • characterized by ectasia of the renal collecting ducts • associated with: • recurrent infection • urinary stasis • hypercalciuria • impaired renal concentrating ability • defective urinary acidification
- 87. anatomic predisposition to stone formation • Ureteropelvic Junction Obstruction • Horseshoe kidneys • Caliceal Diverticula • Medullary sponge kidney • possible contributing factor for stone formation: • defective renal acidification • Hypercalciuria • Hypocitraturia
- 88. stones in pregnancy • physiologic changes during pregnancy may enhance stone formation • physiologic hydronephrosis brought about by: • high levels of progesterone • compression of the ureters by the gravid uterus • Hydronephrosis may persist up to 4 to 6 weeks postpartum • physiologic dilatation may: • promote crystallization due to urinary stasis • increase renal pelvic pressure
- 89. stones in pregnancy • Other physiologic changes that may modulate risk factors for the development of urinary stone • increase renal blood flow • increase GFR • increase filtered loads of: • calcium • sodium • uric acid
- 90. thank you • supplementary online material: • https://scialert.net/fulltext/?doi=ajdd.2017.54.62#424020_ja • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410535/ • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5250668/