urinary lithiasis etiology , pathogenesis, types of urinary lithiasis .pptx

etiology , pathogenesis, types of urinary lithiasis

1. Urinary Lithiasis Presenter : Dr.Martin Emerald.P 2 nd year PG General surgery Moderator : Dr.Y.Mutheeswariah Professor and HOD General Surgery 8/7/2024 1 Epidemiology , Etiology ,Pathogenesis and Types

2. Introduction Urinary Lithiasis is most common condition in the urological surgery. Historically Theories, diagnosis, and treatment proposed by Hippocrates, Aristotle and Galen. U nderstanding the mechanisms of form ation and the methods of prevention are necessary for the proper management. 8/7/2024 2

3. Epidemiology Prevalence is rising. National estimates from the United States suggest that stones affect 1 in 11 at some point in their lifetime. R ecent estimates of gender distribution of stones between men and women have reported ratios between 1.2 and 1.45 : 1 . 8/7/2024 3 Scales CD Jr , Smith AC, Hanley JM, et al; Urologic Diseases in America Project: Prevalence of kidney stones in the United States, Eur Urol 62(1):160–165, 2012.

4. Epidemiology In adults the incidence of the kidney stones peaks in the fourth to sixth decade of life . Women show a bi modal distribution of stone disease. Second peak seen in sixth decade corresponding to the onset of menopause and fall of estrogen. 8/7/2024 4 Johnson CM, Wilson DM, O’Fallon WM, et al: Renal stone epidemiology: a 25-year study in Rochester, Minnesota, Kidney Int 16:624–631, 1979. Marshall V, White RH, Chaput de Saintonge M, et al: The natural history of renal and ureteric calculi, Br J Urol 47:117–124, 1975

5. Epidemiology Highest prevalence found in the hot, arid, or dry climates such as mountains , deserts or tropical areas. Seasonal variations is related to the temperature by way of the fluid losses from perspiration and sunlight induced increase in the Vitamin D, highest incidence seen in the summer months. 8/7/2024 Prince CL, Scardino PL, Wolan CT: The effect of temperature, humidity and dehydration on the formation of renal calculi, J Urol 75:209–215, 1956 5

6. Epidemiology The increased incidence of stones related to temperature is that more people are exposed to urban heat islands as a result of progressive urbanization. The effects of urban architecture and infrastructure coupled with reduced vegetation result in cities that are warmer than more rural areas. 8/7/2024 Goldfarb DS, Hirsch J: Hypothesis: urbanization and exposure to urban heat islands contribute to increasing prevalence of kidney stones, Med Hypotheses 85(6):953–957, 2015 6

7. Epidemiology Heat exposure and dehydration constitute occupational risk factors for stone disease. Occupations that limit wash room access , such as taxi drivers, operating room personnel are at increased risk of stone formation. 8/7/2024 Linder BJ, Rangel LJ, Krambeck AE: The effect of work location on urolithiasis in health care professionals, Urolithiasis 41(4):327–331, 2013 7

8. Epidemiology Obesity , Diabetes and Metabolic syndrome The prevalence and incident risk of stone directly correlated with weight and body mass index ( BMI) in both sexes, although the magnitude of the association was greater in women than in men. Metabolic syndrome is associated with increased risk of kidney stones. 8/7/2024 Semins MJ, Shore AD, Makary MA, et al: The association of increasing body mass index and kidney stone disease, J Urol 183:571–575, 2010 8

9. Morbidity Morbidity attributed to severe colic, emergency medical care, missed work and surgical treatment. Long term impact of stone disease on quality of life particularly recurrence is common. First time stone formers have propensity to form a stone by 50 % in 10 years. Males had both a higher incidence of calculi overall and a higher recurrence rate. 8/7/2024 9

10. Pathogenesis 8/7/2024 10

11. Saturation state The concentration product at the point of saturation is called the thermodynamic solubility product ( Ksp ), which is the point at which the dissolved and crystalline components are in equilibrium for a specific set of conditions . At this point, addition of further crystals to the saturated solution will cause the crystals to precipitate unless the conditions of the solution, such as pH or temperature, are changed. 8/7/2024 11

12. As concentrations of the salt increase further, the point at which it can no longer be held in solution is reached and crystals form. The concentration product at this point is called the formation product ( Kf ). 8/7/2024 12

13. 8/7/2024 13 soluble crystallization Meta stable

14. Pathogenesis 8/7/2024 14 State of saturation

15. 8/7/2024 15 URINE SATURATION SUPERSATURATION NUCLEATION AGGREGATION RETENTION AND GROWTH

16. Nucleation Nuclei are the earliest crystal structures that will not dissolve. Within the transit time of urine 5 to 7 minutes crystal cannot grow to reach a size sufficient to occlude the tubular lumen. If enough nuclei form , they aggregate to form crystals to occlude the tubular lumen. 8/7/2024 16

17. Nucleation If the driving force ( supersaturation level) and the stability of the nuclei are favorable and the lag time to nucleation is sufficiently short compared with the transit time of urine through the nephron , the nuclei will persist. Inhibitors, such as citrate, destabilize nuclei, whereas promoters stabilize nuclei by providing a surface with a binding site that accommodates the crystal structure of the nucleus. 8/7/2024 17

18. Nucleation Homogenous nucleation : spontaneous formation of crystals. Heterogeneous nucleation: forming crystals on preexisting surfaces. Metastable solutions form crystals by heterogeneous nucleation. Urine is a metastable solution , heterogeneous nucleation frequently occur. 8/7/2024 18

19. Theories Free-particle stone formation is defined as intratubular precipitation followed by intratubular plug formation and eventually stone formation. The fixed-particle mechanism is defined as the formation of a papillary plaque followed by outgrowth into a stone. 8/7/2024 Kok DJ, Khan SR. Calcium oxalate nephrolithiasis , a free or fixed particle disease. Kidney Int. 1994;46:847–854. doi : 10.1038/ki.1994.341 19

20. Randall plaque Randall plaque is microscopically a plaque of calcium deposited in the interstitial tissues of renal papilla. These form nidus for stone formation. 8/7/2024 20

21. 8/7/2024 21 Endoscopic (A) and histologic (B) images of Randall plaques in calcium oxalate patients

22. Evan et al. validated this theory for pathogenesis of stone formation based on analysis of papillary plaques derived from biopsies obtained during percutaneous nephrolithotomy in idiopathic calcium oxalate stone formers. They localized the origin of the plaque to the basement membrane of the thin limbs of the loops of Henle and demonstrated that plaque subsequently extends through the medullary interstitium to a subepithelial location. Once the plaque erodes through the urothelium , it is thought to constitute a stable, anchored surface on which calcium oxalate crystals can nucleate and grow as attached stones. 8/7/2024 Evan AP, Lingeman JE, Coe FL, et al: Randall’s plaque of patients with nephrolithiasis begins in basement membranes of thin loops of Henle , J Clin Invest 111:607–616, 2003. 22

23. Components of stone Crystal component (90-98%) Matrix component (2-10%) 8/7/2024 23

24. Matrix component 2-10 % Non crystalline Matrix, is composed of a combination of mucoproteins , proteins, carbohydrates, and urinary inhibitors. 8/7/2024 24

25. C hemical analysis of matrix: 65% protein, 9% nonamino sugars, 5% glucosamine, 10% bound water, and 12% organic ash. 8/7/2024 25

26. Among the proteins incorporated into the matrix substance are: Tamm- Horsfall protein N ephrocalcin γ- carboxyglutamic acid–rich protein R enal lithostathine Albumin G lycosaminoglycans , F ree carbohydrates, M atrix substance A. 8/7/2024 26

27. Crystalline component 8/7/2024 27

28. 8/7/2024 28

29. Types of stones Calcium Oxalate This is the most common type of stone, constituting 60–85% of all stones. Hypercalciuria , hypercalcaemia , hyperoxaluria,hyperuricosuria and hypocitraturia are known metabolic abnormalities that can predispose to its formation. 8/7/2024 29

30. Types of stones Calcium phosphate Pure calcium phosphate stones are rare. Common forms seen are apatite and B rushite stones . Apatite is seen with infection and B rushite stones are usually seen with distal RTA. 8/7/2024 32

31. Types of stones Uric acid Hyperuricosuria promotes the formation of both calcium oxalate and uric acid stones. Uric acid precipitates into crystals in acidic urine and remains soluble in alkaline urine. Conditions that can cause hyperuricosuria are gout and myeloproliferative disorders after cytotoxic treatment . 8/7/2024 33

32. Types of stones Infection stones These are struvite and apatite stones. They form as a result of urease -producing bacterial infections, such as those caused by Proteus, Klebsiella , Serratia or Enterobacter . Alkalinisation of urine takes place as urease hydrolyses urea to carbon dioxide and ammonium. 8/7/2024 36

33. Types of stones Staghorn calculi grow in a branching pattern, taking the form of the pelvicalyceal system. They can grow large before clinical detection and cause significant morbidity , loss of renal function owing to chronic infection and obstructive uropathy . 8/7/2024 37

34. 8/7/2024 38

35. Types of stones Cystine stones Cystine stones constitute approximately 1% of stones. Cystinuria is an autosomal recessive inherited disease that causes decreased reabsorption of cystine from the intestine and the proximal tubule of the kidney. 8/7/2024 Feliubadaló L, Font M, Purroy J, et al: International Cystinuria Consortium. Non-type I cystinuria caused by mutations in SLC7A9, encoding a subunit ( bo,+AT ) of rBAT , Nat Genet 23:52–57, 1999 40

36. Types of stones Cystine is insoluble even at physiological pH and worsens with increasing acidity. Cystine stones are very hard stones as a result of disulphide bonds and do not fragment with SWL. 8/7/2024 41

37. Calcium stones Hypercalcuria Hyperoxaluria Hyperuricosuria Hypocitruria Low urine pH Renal tubular acidosis Hypomagnesiuria 8/7/2024 44

38. HYPERCALCURIA > 4mg/kg/day . >200 mg urinary calcium after 1 week of 400 mg calcium 100 mg sodium diet for 1 week. 8/7/2024 45

39. Hypercalcuria Absorptive hypercalciuric nephrolithiasis ↑ intestinal absorption 2.Resorptive hypercalciuric nephrolithiasis ↑ bone demineralisation 3.Renal hypercalciuric nephrolithiasis primary renal loss

40. Absorptive hypercalcuria > 0.2mg/kg creatinine urinary calcium excretion after an oral calcium load. ↑ serum calcium ↓ ↓ serum PTH ↓ ↑ renal filtration of calcium ↓ Calcuria Serum calcium levels are normal.

41. Resorptive hypercalcuria Infrequent Associated with primary hyperparathyroidism. ↑PTH ↓ ↑BONE RESORPTION ↓ ↑CALCITRIOL ↓ ↑ INTESTINAL CALCIUM ABSORPTION ↓ ↑ SERUM AND URINE CALCIUM

42. Renal hypercalciuria Hypercalciuria of renal origin is due to an intrinsic renal tubular defect in calcium excretion. Kidney filters about 270 mmol of calcium and reabsorbs 98 % . ( 70 in Proximal Tubule ). ↓absorption of calcium ↓ ↑ urinary calcium levels ↓ Secondary hyperparathyroidism High fasting urinary calcium levels ; normal serum calcium levels.

43. Hyperoxaluria Urinary oxalate > 40 mg /day. Implicated in crystal growth and retention. Membrane injury facilitates fixation of calcium oxalate crystals and subsequent crystal growth. 8/7/2024 50

44. Hyperoxaluria 1. Primary hyperoxaluria Disorders in biosynthetic pathway. 2. Enteric Hyperoxaluria intestinal malabsorption , IBD , celiac sprue , intestinal resection. 3. Dietary hyperoxaluria Increased dietary intake 4. Idiopathic hyperoxaluria

45. 8/7/2024 52 PRIMARY HYPEROXALURIA

46. 8/7/2024 53 ENTERIC HYPEROXALURIA

47. DIETARY HYPEROXALURIA By taking foods rich in oxalates Nuts Chocolates Spinach Potato Beet Brewed tea 8/7/2024 Holmes RP, Assimos DG: The impact of dietary oxalate on kidney stone formation, Urol Res 32:311–316, 2004. 54

48. In all three types vitamin B, appears to be important and as such is used as an adjunct to therapy. Oxalate crystal deposits develop rapidly in transplanted kidneys. Thus, combined liver and renal transplantation has cured this previously fatal rare disease. 8/7/2024 55

49. Hyperuricosuria Urinary uric acid > 600 mg /day Caused by : ↑ dietary purine intake Acquired/ heredietary diseases( gout, thalassemia ) Cameron MA, Maalouf NM, Adams- Huet B, et al: Urine composition and predisposition to uric acid nephrolithiasis , J Am Soc Nephrol 17:1422–1428, 2006

50. 8/7/2024 “salting out,” whereby the solubility of calcium oxalate in solution is decreased by the addition of another salt 57

51. Hypocitraturia Citrate It forms complexes with calcium and decreases saturation of calcium salts. ii. Prevents nucleation of calcium oxalate. iii. Inhibits agglomeration and sedimentation of calcium oxalate. iv. Enhances inhibitory activities of Tamm- horsfall protein. 8/7/2024 Hamm LL, Hering -Smith KS: Pathophysiology of hypocitraturic nephrolithiasis , Endocrinol Metab Clin North Am 31:885–893, viii, 2002. 58

52. Hypocitraturia Hypocitraturia is defined as urinary citrate levels < 320 mg/day. Primary determinant of urinary citrate excretion is acid – base state. Causes : Distal RTA Chronic diarrheal disease Diuretics ACE I Increased animal protein intake Strenuous exercises 8/7/2024 59

53. Low urine pH Urine pH < 5.5 ↓ ↑ undisassociated form of uric acid ↓ ↑formation of uric acid and calcium stones 8/7/2024 60

54. 8/7/2024 NHE3 – sodium hydrogen exchanger 61

55. Renal tubular acidosis Metabolic acidosis resulting from defects in renal tubular hydrogen ion secretion or bicarbonate resorption . Type 1 RTA ( distal ), Most common. Classic findings include hypokalemic , hyperchloremic , non–anion gap metabolic acidosis along with nephrolithiasis , nephrocalcinosis , and elevated urine pH (>6.0) Type 2 RTA ( proximal) Type 4 RTA ( distal) Davidman M, Schmitz P: Renal tubular acidosis: a pathophysiologic approach, Hosp Pract (Off Ed) 23(1A):77–81, 84–88, 93–96, 1988.

56. 8/7/2024 63

57. 8/7/2024 64

58. Uric acid stones Uricase catalyses conversion of uric acid to allantoin . Lacking in humans results in uric acid. ↑ free uric acid - ↑ risk of stone formation. ↓ pH risk factor for uric acid, calcium oxalate, and mixed stones. 8/7/2024 65

59. 8/7/2024 66

60. Infection stones Infection stones are composed primarily of magnesium ammonium phosphate hexahydrate (MgNH4PO4 • 6H2O ). Enterobacteriaceae makes up the majority of urease -producing pathogens . 8/7/2024 67

61. s 8/7/2024 68

62. 8/7/2024 69

63. Infection stones Most common component of stag horn calculi. Most common in women. Also seen in elderly , premature infants , congenital urinary tract malformation , diabetic patients, urinary stasis, spinal cord injuries. 8/7/2024 Griffith DP, Musher DM: Prevention of infected urinary stones by urease inhibition, Invest Urol 11:228–233, 1973. 70

64. Medications Drug-induced stones form either directly as a result of precipitation and crystallization of a drug or its metabolite or indirectly by altering the urinary environment, making it favorable for metabolic stone formation. 8/7/2024 Matlaga BR, Shah OD, Assimos DG: Drug-induced urinary calculi, Rev Urol 5:227–231, 2003 71

65. Directly promoting stone formation Indirectly promoting stone formation Indinavir sulfate Triamterine Guiafenesin and ephedrine Corticosteroids , vitamin D , phosphate binding antacids. Thiazides Loop diuretics Carbonic anhydrase inhibitors Topiramate Laxatives Cytotoxic agents 8/7/2024 72

66. Inhibitors Inhibitors are defined as molecules that increase the supersaturation required to initiate nucleation, decrease crystal growth rate and aggregation. 8/7/2024 73

67. Inhibitors Citrate Magnesium Pyrophosphate Glycosaminoglycans ( chondroitin,heparin,hyaluonic acid) Tamm- Horsfall protein Osteopontin Prothrombin F1 fragment Renal lithostatine Bikunin Calgranulin 8/7/2024 74

68. 8/7/2024 75

69. Anatomic predisposition Uretero pelvic junction obstruction 8/7/2024 76

70. Anatomic predisposition Horse shoe kidneys 8/7/2024 77

71. Anatomic predisposistion Caliceal diverticula 8/7/2024 78

72. Anatomic predisposition Medullary sponge kidney Characterized by ectasia of the renal collecting ducts . 8/7/2024 79

73. Stones in pregnancy 1 in 250 – 1 in 3000 Majority in 2 nd and 3 rd trimester Physiological hydronephrosis due to progesterone and compression by the gravid uterus resulting in urinary stasis. 8/7/2024 80

74. Physiological changes Increased renal blood flow , increased filtered load of calcium, sodium and uric acid. Placental production of calcitriol , increased calcium absorption from intestine , decrease in PTH. Increased excretion of inhibitors ( citrate , mg, glycoproteins ). 8/7/2024 81

75. THANK YOU 8/7/2024 82