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S TONE DISEASE PART 1 Although stone disease is one of the most common afflictions of modern society, it has been described since antiquity. With Westernization.

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Presentation on theme: "S TONE DISEASE PART 1 Although stone disease is one of the most common afflictions of modern society, it has been described since antiquity. With Westernization."— Presentation transcript:

1 S TONE DISEASE PART 1 Although stone disease is one of the most common afflictions of modern society, it has been described since antiquity. With Westernization of global culture, however, the site of stone formation has migrated from the lower to the upper urinary tract, and the disease once limited to men is increasingly gender blind. 1

2 Revolutionary advances in the minimally invasive and noninvasive management of stone disease over the past 2 decades have greatly facilitated the ease with which stones are Removed. Given the frequency with which stones recur, the development of a medical prophylactic program to prevent stone recurrences is desirable. To this end, a thorough understanding of the etiology, epidemiology, and pathogenesis of urinary tract stone disease is necessary. 2

3 EPIDEMIOLOGY OF RENAL CALCULI The lifetime prevalence of kidney stone disease is estimated at 1% to 15%, with the probability of having a stone varying according to age, gender, race, and geographic location. an increase in the prevalence of stone disease has been.observed Gender Stone disease typically affects adult men more commonly than adult women. 3

4 men are affected two to three times more often than women.the difference in incidence between men and women is narrowing. Race/Ethnicity the highest prevalence of stone disease is in whites, followed by Hispanics, Asians, and African-Americans who had prevalences of 70%, 63%, and 44% of whites, Respectively. Age Stone occurrence is relatively uncommon before age 20 but peaks in incidence in the fourth to sixth decades of life. 4

5 women demonstrating a second peak in incidence in the sixth decade of life, corresponding to the onset of menopause. This finding and the lower incidence of stone disease in women compared with men have been attributed to the protective effect of estrogen against stone formation in premenopausal women, owing to enhanced renal calcium.absorption and reduced bone resorption 5

6 Geography a higher prevalence of stone disease is found in hot, arid, or dry climates such as the mountains, desert, or tropical areas. However, genetic factors and dietary influences may outweigh the effects of geography. Climate Seasonal variation in stone disease is likely related to temperature by way of fluid losses from perspiration and perhaps by sunlightinduced increases in vitamin D. 6

7 the highest incidence of stone disease is in the summer months, with the peak occurring within1.to 2 months of maximal mean temperature Occupation Heat exposure and dehydration constitute occupational risk factors for stone disease Those exposed to high temperatures, were.found to have the highest rates of stone formation 7

8 Individuals with sedentary occupations such as those in managerial or professional positions have been found to carry an increased risk of stone formation for unclear reasons. This finding is consistent with an increased risk of stone disease in affluent individuals, countries, and societies, which may be reflective of a more indulgent diet and lifestyle. 8

9 Body Mass Index and Weight the prevalence and incident risk of stone disease were directly correlated with weight and body mass index (BMI) in both sexes, although the magnitude of association was greater.in women than men a reduced risk of incident stone formation with high fluid (men and women) and low protein.intake (men) obesiry and weight gain were independent risk factors for incidentstone formation and could not be accounted for by diet alone. 9

10 Water The beneficial effect of a high fluid intake on stone prevention has long been recognized. Although several investigators reported a lower incidence of stone disease in geographic regions with a “hard” water supply compared with a“soft” water supply, where water “hardness” is determined by content of calcium carbonate others found no difference. 10

11 PHYSICOCHEMISTRY In urine, despite concentration products of stoneforming salt components such as calcium oxalate that exceed the solubility product, crystallization does not necessarily occur because of the presence of inhibitors and other moleculesthat allow higher concentrations of calcium oxalate to be held in solution before.precipitation or crystallization occurs 11

12 the presence of molecules that raise the supersaturation needed to initiate crystal nucleation or reduce the rate of crystal growth or aggregation prevents stone formation from occurring on a routine basis. Citrate acts as an inhibitor of calcium oxalate and.calcium phosphate stone formation 12

13 l Urine must be supersaturated for stones to form. l Supersaturation alone is not sufficient for crystallization to occur in urine, owing to the presence of urinary inhibitors. l Nephrocalcin, uropontin, and Tamm-Horsfall protein are important inhibitors of crystal nucleation, growth, or aggregation. l Urinary calcium and oxalate are equal contributors to urinary saturation of calcium oxalate. l The noncrystalline component of stones is matrix, which is composed of a combination of mucoproteins, proteins, carbohydrates and urinary inhibitors. 13

14 MINERAL METABOLISM Calcium Thirty to 40 percent of dietary calcium is absorbed from the intestine,with most being absorbed in the small intestine and only approximately 10% absorbed in the colon. By a process of intestinal adaptation, absorption of calcium varies with calcium intake. At times of low calcium intake, fractional calcium absorption is enhanced; during high calcium intake, fractional calcium absorption is reduced. 14

15 Because of the saturable component of calcium transport, a larger portion of calcium is absorbed when it is divided into several doses taken hours compared with a large single dose Calcium is absorbed in the ionic state, and incomplete calcium absorption is due in part to formation of soluble calcium complexes in the intestinal lumen. As such, substances that complex calcium such as phosphate, citrate, oxalate,sulfate, and fatty acids reduce the.availability of ionic calcium for absorption 15

16 an oxalate-rich diet reduces calcium absorption. Transcellular calcium absorption is mediated by 1,25(OH) 2 D 3 (calcitriol) The active form of vitamin D, 1,25(OH) 2 D 3, is the most potent stimulator of intestinal calcium absorption. After conversion of 7-dehydrocholesterol in the skin to previtamin D 3 promoted by sunlight, previtamin D 3 is hydroxylated in the liver to 25-hydroxyvitamin D 3, which is further hydroxylated in the proximal renal tubule to 1,25(OH) 2 D 3. The conversion of 25-hydroxyvitamin D 3 to 1,25(OH) 2 D 3 is stimulated by parathyroid (PTH). 16

17 Calcitriol also acts on the bone and kidney in addition to its action in increasing calcium absorption from the intestine. In the bone, 1,25(OH) 2 D 3, along with PTH, promotes the recruitment and differentiation of osteoclasts that subsequently mobilize calcium from the bone. PTH increases renal calcium reabsorption and enhances phosphate excretion, leading to a net increase in serum calcium. It also stimulates synthesis of 1,25(OH) 2 D 3, which leads to enhanced intestinal calcium and phosphate absorption. PTH has no direct effect on intestinal calcium absorption. 17

18 Oxalate only 6% to 14% of ingested oxalate is absorbed Oxalate absorption occurs throughout the intestinal tract, with about half or more occurring in the small.intestine and half in the colon 18


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