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Urinary stone disease

Urinary stone disease. By Dr.Aiman AL Solumany (R2) King Fahd General Hospital. In General. Urinary calculi are the third most common problem of the urinary tract, exceeded only by urinary tract Infections and pathologic conditions of the prostate. 1-Renal calculi

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Urinary stone disease

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  1. Urinary stone disease By Dr.Aiman AL Solumany (R2) King Fahd General Hospital

  2. In General • Urinary calculi are the third most common problem of the urinary tract, exceeded only by urinary tract Infections and pathologic conditions of the prostate. • 1-Renal calculi • 2- medical evaluation

  3. EPIDEMIOLOGY OF RENAL CALCULI • Incidence • 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 • Recurrence rate – with out ttt 10% at 1 yr, 50% at 10 yrs. • Factors :. 1- intrinsic factor. 2- extrinsic factors

  4. EPIDEMIOLOGY OF RENAL CALCULI • Intrinsic Factors • genetics: FHx and race • rare in Natives, blacks • common in Asians and whites • about 25% of patients with kidney stones have a family history of kidney stones. • Age and Sex Peak - 20-40 years old M : F - 3:1 F > M - stones 2nd to infections or abN

  5. EPIDEMIOLOGY OF RENAL CALCULI • Extrinsic Factors: 1. Geography • The prevalence of urinary calculi is higher in those who live in mountainous, desert, or tropical areas. • increased incidence: US, UK, Scandanavia, Mediterranean, northern India/Pakistan, northern Australia, central Europe, and China.

  6. EPIDEMIOLOGY OF RENAL CALCULI 2-climate and seasonal factors : • incidence highest in July, Aug, Sep: 1-2 months after maximal mean annual temperature  dehydration, increased exposure to sunlight and increased vitamin D production w/ increased urinary Ca excretion. 3-water intake: • decreases average time of residence of free crystal particles in urine and dilutes components.

  7. EPIDEMIOLOGY OF RENAL CALCULI 4-Diet:. .high protein and Na ca stones .high purine pH hyperuricosuria .low Vit B12 formation and excretion of oxalate. The risk of stone disease correlates with weight and body mass index.

  8. EPIDEMIOLOGY OF RENAL CALCULI 5-occupation: • stones more likely to be found in pts w/ sedentary lifestyles • professional and managerial groups, affluent countries/regions/societies 6-stress: • lower family income, mortgage problems, emotional life events associated w/ stone disease

  9. PHYSICOCHEMISTRY • State of Saturation: • The physical process of stone formation is a complex cascade of events. • It begins with urine that becomes supersaturated with respect to stone-forming salts, such that dissolved ions or molecules precipitate out of solution and form crystals or nuclei. Once formed, crystals may flow out with the urine or become retained in the kidney at anchoring sites that promote growth and aggregation, ultimately leading to stone formation.

  10. PHYSICOCHEMISTRY • A solution containing ions or molecules of a soluble salt is described by the concentration product, which is a mathematical expression of the product of the concentrations of the pure chemical components (ions or molecules) of the salt. • A pure aqueous solution of a salt is considered saturated when it reaches the point at which no further added salt crystals will dissolve.

  11. PHYSICOCHEMISTRY • The concentration product at the point of saturation is called the thermodynamic solubility product, Ksp, • 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.

  12. PHYSICOCHEMISTRY • In urine, despite concentration products of stone-forming salt components, such as calcium oxalate, that exceed the solubility product, crystallization does not necessarily occur because of the presence of inhibitors and other molecules . • In this state of saturation, urine is considered to be metastable with respect to the salt.

  13. PHYSICOCHEMISTRY • As concentrations of the salt increase further, the point at which it can no longer be held in solution is reached and crystals form. this point is called the formation product, Kf. • KspandKfdifferentiate the three major states of saturation in urine: undersaturated, metastable, and unstable.

  14. PHYSICOCHEMISTRY • Below the solubility product, crystals will not form under any circumstances. • above the formation product, the solution is unstable and crystals will form. • In metastable range,in which the concentration products of most common stone components reside, spontaneous nucleation or precipitation does not occur despite urine that is supersaturated. in this area that modulation of factors controlling stone formation can take place and therapeutic intervention is directed.

  15. PHYSICOCHEMISTRY • Nucleation and Crystal Growth, Aggregation, and Retention: • In normal urine, the concentration of calcium oxalate is four times higher than its solubility in water • calcium oxalate precipitation in urine occurs only when its supersaturation is 7 to 11 times its solubility. • Precip occurs due to the following factors :. 1-Low urinary volumes. 2-High rates of calcium, oxalate, phosphate, or urate excretion. 3- Low citrate and magnesium excretion .

  16. PHYSICOCHEMISTRY • Nuclei are the earliest crystal structure that will not dissolve. • Homogenous nucleation - process of nuclei formation in pure solution • Heterogenous nucleation - nuclei form on existing surfaces - eg epithelial cells, cell debris, urinary casts, crystals - Lower concentration needed • Most of CaOx is heterogenous

  17. PHYSICOCHEMISTRY • Another concept necessary for understanding the genesis of urinary calculi is that of aggregation. • Crystal nuclei cannot grow large enough to attach to and occlude renal tubular lumens within the 5 to 7 minutes that it takes for them to pass through tubules and enter the renal pelvis. They can, aggregate into large clumps within a minute

  18. PHYSICOCHEMISTRY • Inhibitors:. • Whole urine, when added to a solution of calcium phosphate, raises the supersaturation level required to initiate calcium phosphate crystallization. • Citrate, Magnesium, and pyrophosphate together were account for 20% of the inhibitory activity of whole urine, with citrate comprising the most important factor of the three. • no specific inhibitors are known that affect uric acid crystallization.

  19. PHYSICOCHEMISTRY • Citrate acts as an inhibitor of calcium oxalate and calcium phosphate stone formation by a variety of actions: 1- it complexes with calcium, reducing the availability of ionic calcium to interact with oxalate or phosphate

  20. PHYSICOCHEMISTRY 2- It directly inhibits the spontaneous precipitation of calcium oxalate and prevents the agglomeration of calcium oxalate crystals. it has limited inhibitory effect on calcium oxalate crystal growth , more potent activity in reducing calcium phosphate growth. 3- citrate prevents heterogeneous nucleation of calcium oxalate by monosodium urate .

  21. PHYSICOCHEMISTRY Magnesium:. Its complexe with oxalate, which reduces ionic oxalate concentration and calcium oxalate supersaturation. In addition, magnesium reduces the rate of calcium oxalate crystal growth in vitro. Inorganic pyrophosphate:. responsible for 25% to 50% of the inhibitory activity of whole urine against calcium phosphate crystallization.

  22. PHYSICOCHEMISTRY • Two urinary glycoproteins, nephrocalcin and Tamm-Horsfall glycoprotein, are potent inhibitors of calcium oxalate monohydrate crystal aggregation . 1-Nephrocalcin is an acidic glycoprotein containing predominantly acidic amino acids that is synthesized in the proximal renal tubules and the thick ascending limb. In simple solution, nephrocalcin strongly inhibits the growth of calcium oxalate monohydrate crystals .

  23. PHYSICOCHEMISTRY 2. Tamm-Horsfall glycoprotein: .syn - thick ascending limb & distal tubule . inhibits aggregation CaOx- most potent . Under specific condition, THP can promote aggregation (high ionic strength, high calcium and low pH) . Citrate can increase THP and its inhibitory effect

  24. PHYSICOCHEMISTRY • 3. Osteopontin (uropontin): • Osteopontin has been shown to inhibit nucleation, growth, and aggregation of calcium oxalate crystals as well as to reduce binding of crystals to renal epithelial cells in vitro

  25. PHYSICOCHEMISTRY Matrix: • Renal calculi consist of both crystalline and noncrystalline components. • The noncrystalline component is termed matrix, which typically accounts for about 2.5% of the weight of the stone In some cases reached up to 65%.

  26. PHYSICOCHEMISTRY • chemical analysis reveals a heterogeneous mixture consisting of 65% protein, 9% non-amino sugars, 5% glucosamine, 10% bound water, and 12% organic ash . • Non–urease-producing bacteria such as E. coli may play a role in stone formation by increasing the production of urinary matrix substances, thereby increasing crystal adherence to the renal epithelium.

  27. MINERAL METABOLISM Calcium:. 30% to 40 % of dietary calcium is absorbed from small intestine (the jejunum and the proximal portion of the ileum) and only approximately 10% absorbed in the colon. absorption of calcium varies with calcium intake. with low calcium intake, calcium absorption is enhanced; during high calcium intake absorption is reduced.

  28. MINERAL METABOLISM (Calcium) Calcium in Plasma in three form : 1) combined with plasma proteins (40%) 2) combined with other substances but diffusible through capillaries (10%) 3) Ca++ (50%) active

  29. MINERAL METABOLISM (Calcium) • the net absorption of calcium 100 to 300 mg/Day. • Calcium is absorbed in the ionic state; therefore, substances that complex calcium, such as phosphate, citrate, sulfate, oxalate, and fatty acids, reduce the availability of ionic calcium for absorption. • The most important factor that mediates active or transcellular calcium absorption is 1,25-dihydroxyvitamin D3, or calcitriol.

  30. MINERAL METABOLISM (Calcium) • The active form of vitamin D, 1,25(OH)2D3, is the most potent stimulator of intestinal calcium absorption. • After conversion of 7-dehydrocholesterol in the skin to previtamin D3 promoted by sunlight, • previtamin D3 is hydroxylated in the liver to 25-hydroxyvitamin D3, which is further hydroxylated in the proximal renal tubule to 1,25(OH)2D3. • The conversion of 25-hydroxyvitamin D3 to 1,25(OH)2D3 is stimulated by parathyroid hormone (PTH) and by hypophosphatemia.

  31. MINERAL METABOLISM (Calcium) • A decrease in serum calcium increases secretion of PTH, which in turn directly stimulates the enzyme 1α-hydroxylase, which is located in the mitochondria of the proximal renal tubule. • After transport via the bloodstream to the intestine, 1,25(OH)2D3, binds to the vitamin D receptor in the brush border membrane epithelial cells to enhance calcium absorption.

  32. MINERAL METABOLISM (Calcium) • Calcitriol also acts on the bone and kidney in addition to its action in increasing calcium absorption from the intestine. • PTH increases renal calcium reabsorption and enhances phosphate excretion, leading to a net increase in serum calcium, which ultimately suppresses further PTH secretion and synthesis of 1,25(OH)2D3. • Only mature PTH is secreted from the parathyroid gland, and the most potent stimulus for its secretion is a decrease in serum calcium.

  33. MINERAL METABOLISM (phosphorus) • Phosphorus: is transported across the intestine through active and passive mechanisms. Approximately 60% of the phosphate in the diet is absorbed by the intestine. • 1,25-Dihydroxyvitamin D3 stimulates phosphorus absorption in the duodenum and jejunum through a sodium-dependent active transport process . • The transport of phosphate is pH dependent: A decrease in luminal pH inhibits phosphate transport, and an increase in pH stimulates phosphate transport.

  34. MINERAL METABOLISM (phosphorus) • phosphorus is secreted by the ileum and colon. • About 65% of the absorbed phosphate is excreted by the kidney and the remainder by the intestine. • Under normal conditions, approximately 20% of the filtered load is excreted, the other 80% being absorbed by the proximal tubule.

  35. MINERAL METABOLISM (phosphorus) • PTH is the major hormonal regulator of renal phosphate reabsorption. • Daily, about 150 to 200 mmol of calcium and about 100 mmol of phosphorus are filtered: Only 5 mmol of calcium and 10 mmol of phosphorus are excreted in the urine. So, 97% to 99% of calcium and 85% to 90% of phosphorus are reabsorbed by the kidney.

  36. MINERAL METABOLISM (Magnesium) • Magnesiumis also absorbed via active and passive mechanisms by the intestine. • About 35% to 40% of ingested magnesium is absorbed. • Although magnesium is absorbed mostly in the small intestine, some is absorbed by the large bowel also. • Both vitamin D and PTH increase magnesium absorption.

  37. MINERAL METABOLISM (Oxalate) • Oxalic acid is present in many foods and beverages. • poorly absorbed in N pts,  with  Ca in diet. • Oxalate absorption is markedly increased in patients with small bowel resection and an intact colon or inflammatory bowel disease . • stomach and distal bowel may be the primary sites for oxalate absorption.

  38. MINERAL METABOLISM (Oxalate) • Oxalobacterformigenes, utilize oxalate as an energy source and consequently reduce intestinal oxalate absorption. • Recent studies have demonstrated that stone formers have reduced levels or absent colonization with Oxalobacter compared with non—stone-forming. • those individuals lacking the bacteria have higher urinary oxalate levels.

  39. MINERAL METABOLISM (Oxalate) • Intestinal oxalate absorption is influenced by luminal calcium, magnesium, and oxalate-degrading bacteria. • Eighty percent of the oxalate found in urine comes from endogenous production in the liver (40% from ascorbic acid, 40% from glycine), and 10% comes from dietary sources.

  40. Pathopysiology of Stone Formation

  41.   Stone Composition and Relative Occurrence

  42. Pathopysiology of Stone Formation (calcium stone ) • Hypercalciuria is the most common abnormality identified in calcium stone formers. • Between 35% and 65% of all patients with calcium oxalate kidney stones have increased urinary calcium excretion in the absence of raised serum calcium levels. • Pak (1987), who defined it as the excretion of greater than 200 mg of calcium per 24 hours after 1 week's adherence to a 400-mg calcium, 100-mEq sodium diet.

  43. Pathopysiology of Stone Formation (calcium stone ) • Parks and Coe (1986) defined hypercalciuria as excretion of calcium of greater than 4 mg/kg/day or greater than 7 mmol/day (men) or 6 mmol/day (women). • Calcium transport is regulated at three sites: intestine, bone, and kidney. Dysregulation at any of these sites can lead to hypercalciuria.

  44. Pathopysiology of Stone Formation (calcium stone ) • hypercalciuriadivided into three subtypes: 1- Absorptive hypercalciuria due to increased intestinal absorption of calcium. 2- Renal hypercalciuria due to primary renal leak of calcium. 3- Resorptivehypercalciuria due to increased bone demineralization.

  45. Pathopysiology of Stone Formation (calcium stone ) • Absorptive hypercalciuria:. • AH is increased intestinal absorption of calcium, which occurs in approximately 55% of stone formers ( Menon, 1986 ). • AH is classified as :. type I when urinary calcium remains high despite a low calcium diet (400 mg dietary calcium daily). type II when urinary calcium normalizes with a restricted calcium intake.

  46. Pathopysiology of Stone Formation (calcium stone ) • 1,25-dihydroxyvitamin D3levels are elevated in up to 50% of patients with absorptive hypercalciuria, suggesting that, at least in some individuals, this condition is secondary to increased production of or increased sensitivity to vitamin D metabolites. • Another etiology of AH is renal phosphate wasting leading to a subsequent increase in active vitamin D.

  47. Pathopysiology of Stone Formation (calcium stone ) • Mechanisms of absorptive hypercalciuria :

  48. Pathopysiology of Stone Formation (calcium stone ) • Renal hypercalciuria:. • The kidney filters approximately 270 mmol of calcium and must reabsorb more than 98% of it to maintain calcium homeostasis. • Approximately 70% of calcium reabsorption occurs in the proximal tubule. • In renal hypercalciuria, impaired renal tubular reabsorption of calcium results in elevated urinary calcium levels leading to secondary hyperparathyroidism.

  49. Pathopysiology of Stone Formation (calcium stone ) the underlying abnormality is primary renal wasting of calcium. The consequent reduction in circulating serum calcium stimulates PTH production

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