Urinary lithiasis

urolithiasis

1. Urinary lithiasis Dr. Hussein Iman- presenter Dr. Marvin supervisor

2. Epidemiology of Renal Calculi Physicochemistry and Pathogenesis Mineral Metabolism Pathophysiology of Upper Urinary Tract Calculi

3. EPIDEMIOLOGY OF RENAL CALCULI The lifetime prevalence: 1% to 15% varying according to age, gender, race, and geographic location. Gender: men > women. Age. uncommon before age 20 but peaks in incidence in the fourth to sixth decades of life (60 to 69 years) in men. women show a bimodal distribution (1st peak 30-39 years), a second peak in the sixth decade of life corresponding to the onset of menopause and a fall in estrogen levels.

4. ??? protective effect of estrogen against stone formation in premenopausal women, owing to enhanced renal calcium absorption and reduced bone resorption .

5. 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. Occupation Heat exposure and dehydration constitute occupational risk factors for stone disease as well. Cooks and engineering room personnel.

6. Those exposed to high temperatures: exhibited lower urine volumes and pH, higher uric acid levels higher urine specific gravity, All the above lead to higher urinary saturation of uric acid.

7. Obesity, Diabetes, and Metabolic Syndrome Diet. Vegeterians -decreased incindence High sodium intake-increased urinary sodium, urinary pH and calcium with a decreased excretion of citrate. Fluid intake Urinary output- average urinary output in stone formers is 1.6 l/day.

8. Family history .

9. PHYSICOCHEMISTRY AND PATHOGENESIS The physical process of stone formation comprises a complex cascade of events that occurs as the glomerular filtrate traverses the nephron. 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. Stone formation requires supersaturated urine. Supersaturation depends on urinary PH, ionic strength, solute concentration, and complexation

11. Role of solute concentration. A solution containing ions or molecules of a sparingly soluble salt is described by the concentration product, which is a mathematic 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. 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.

12. In urine even when the concentration products of ions are greater than the established solubility product crystals may not form. Other factors play major role in renal calculi formation including complexation . Complexation influences availability of specific ions. For instance sodium complexes with oxalate reducing its free ionic form while sulfates can complex with calcium. Other inhibitors of aggregration .

13. 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 ).

14. The solubility product and the formation product differentiate the three major states of saturation in urine: undersaturated , metastable, and unstable . Below the solubility product, crystals will not form under any circumstances and dissolution of crystals is theoretically possible. At concentrations above the formation product, the solution is unstable and crystals will form.

15. In the metastable range of concentration products, although crystal growth can occur on existing crystals and heterogenous nucleation., de novo formation of crystals cannot occur in the length of time it normally takes for the filtered urine to reach the bladder. However, crystal formation can occur in this range under certain circumstances. -local areas of obstruction or stasis in the upper urinary tract may prolong urinary transit time and allow crystal formation to occur in metastable urine. - microscopic impurities or other constituents in the urine can facilitate the nucleation process by adsorption of the crystal components ( “heterogeneous nucleation”)

16. Nucleation and Crystal Growth, Aggregation, and Retention In normal human urine, the concentration of calcium oxalate is four times higher than its solubility in water. Urinary factors favoring stone formation include low volume and citrate, while increased calcium, oxalate, phosphate, and uric acid all increase calcium oxalate supersaturation . Nucleation initiates the stone process and may be induced by a variety of substances including proteinecious matrix, crystals , foreign bodies and other particulate particles.

17. Heterogenous nucleation ( epitaxy ) which requires less energy and may occur in less saturated urine is a common theme in stone formation. Homogeneous nucleation is the process by which nuclei form in pure solution. Nuclei are the earliest crystal structures that will not dissolve. Small nuclei are unstable; below a critical size threshold, dissolution of the crystal is favored over crystal growth.

18. If the driving force ( supersaturation level) and the stability of the nuclei are adequate 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. In urine, crystal nuclei usually form through heterogeneous nucleation by adsorption onto existing surfaces of epithelial cells.

19. Within the timeframe of transit of urine through the nephron, estimated at 5 to 7 minutes, crystals cannot grow to reach a size sufficient to occlude the tubular lumen. However, if enough nuclei form and grow, aggregation of the crystals will form larger particles within minutes that can occlude the tubular lumen.

20. Fixed particle growth theory presupposes an anchoring site to which crystals bind, thereby prolonging the time the crystals are exposed to supersaturated urine and facilitating crystal growth and aggregation. A number of mechanisms have been proposed to account for crystal fixation. One favored theory proposes that oxalate-induced injury to renal tubular epithelial cells promotes adherence of calcium oxalate crystals

21. Inhibitors and Promoters of Crystal Formation 1.Citrate. 2. Magnesium 3. Polyanion macromolecules, including glycosaminoglycans , acid mucopolysaccharides A. glycosaminoglycan - chondrotin sulfate B. glycoproteins - nephrocalcin -Tamm- Horsfall glycoprotein - osteopontin or uropontin -inter- α- trypsin

22. 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, matrix comprises the majority of the stone (up to 65%), usually in association with chronic urinary tract infection. The exact composition of matrix is difficult to ascertain because only 25% of it is soluble; however, chemical analysis reveals a heterogeneous mixture consisting of approximately 65% protein, 9% nonamino sugars, 5% glucosamine, 10% bound water, and 12% organic ash. The exact role of matrix in stone formation, whether as promoter, inhibitor, orpassive bystander, has yet to be elucidated.

23. Risk factors for people who form stones of calcium oxalate Male sex Low urinary volume Hyperoxaluria Increased urinary pH Hypercalciuria Hyperuricosuria Hypocitraturia Hypomagnesuria

24. Calcium Stones Read about the physiology of calcium absorption Hypercalciuria Hypercalciuria is the most common abnormality identified in calcium stone formers Hypercalciuria (>200 mg/day)

25. Absorptive Hypercalciuria . involves an increase in the amount of calcium absorbed by the intestinal tract. normal serum calcium and a normal or reduced level of circulating intact parathyroid hormone ( iPTH ). Type 1. occurs independent of the diet. Excessive urinary calcium level >150-200mg/24 hours even during calcuim restricted diet

26. Rx of type 1 Cellulose phosphate. Non absorbable exchange resin. May cause seconday hyperoxaluria . Thiazide duiretics

27. Type II. Diet dependent. Is the commonest cause of urinary stone disease. Calcuim excretion returns to normal on calcium restricted diet. No specific medical therapy. Type III. Phosphate renal leak. Decreased serum phosphate---increased 1,25 vit D—increased phosphate and calcium absorption. Renal phosphate leak, however, is a rare cause of nephrolithiasis, affecting at most 2% to 4% of patients Rx. Replace phosphate. Orthophosphate .

28. Renal Hypercalciuria (renal leak hypercalciuria ) is thought to be due to a wasting of calcium by the functioning nephron. Intrinsic renal tubular defect in calcium excretion. As a result of constant loss of calcium from the distal tubules, these patients will demonstrate hypercalciuria during all phases of fasting, loading, or restricting of dietary calcium. Elevated fasting urinary calcium, a normal serum calcium, and a mild elevation of iPTH as the regulatory systems attempt to keep up with the constant loss of calcium. Rx. Thiazide diuretics.

29. Resorptive Hypercalciuria (Primary Hyperparathyroidism). overproduction of parathyroid hormone The hallmark of this disorder is the persistence of increased urinary calcium hypercalcemia and elevations of the parathyroid hormone.

30. Differentiating primary and secondary hyperparathyroidism in patient with urinary stone disease. Administer hydrochlorothiazide challenge 50mg for 10 days. Primary- normal parathyroid hormone. Seconday - elevated parathyroid hormone.

31. Hyperoxaluria Hyperoxaluria , defined as urinary oxalate greater than 40 mg/day, leads to increased urinary saturation of calcium oxalate and subsequent promotion of calcium oxalate stones. Additionally, oxalate has been implicated in crystal growth and retention by means of renal tubular cell injury mediated by lipid peroxidation and the generation of oxygen free radicals. Membrane injury facilitates the fixation of calcium oxalate crystals and subsequent crystal growth. Antioxidant therapy has been shown to prevent calcium oxalate

32. Causes of hyperoxaluria include disorders in biosynthetic pathways (primary hyperoxaluria); intestinal malabsorptive states associated with inflammatory bowel disease, celiac sprue, or intestinal resection (enteric hyperoxaluria); and excessive dietary intake or high substrate levels (vitamin C) (dietary hyperoxaluria).

33. Primary Hyperoxaluria. The primary hyperoxalurias (PHs) are the result of rare autosomal recessive inherited disorders in glyoxylate metabolism by which the normal conversion of glyoxylate to glycine is prevented, leading to preferential oxidative conversion of glyoxylate to oxalate, an end product of metabolism (Fig. 51-6). The markedly high levels of urinary oxalate that ensue (>100 mg/day) lead to increased saturation of calcium oxalate and formation of calcium oxalate complexes and crystals in the renal tubular lumen. Some crystals attach to the surface of renal tubular epithelial cells and further aggregate into stones, whereas others are internalized into tubular cells and then extruded into the renal interstitium , leading to marked nephrocalcinosis

34. Three forms of PH have been identified (types 1, 2, and 3) that differ in the enzyme and intracellular organelle affected. The primary enzyme catalyzing glyoxylate conversion to glycine is the pyridoxal phosphate–dependent alanine- glyoxylate aminotransferase (AGT), which is synthesized in the liver peroxisome. Mutations in this gene (AGXT) result in primary hyperoxaluria type 1 (PH1), and patients with this disorder have elevated levels of oxalate and frequently glycolate . End-stage renal disease (ESRD) occurs during the second to third decade of life in most patients with PH1, making it the most aggressive form of the disease

35. Primary hyperoxaluria type 2 (PH2) is associated with a defect in glyoxylate reductase/ hydroxypyruvate reductase (GRHPR) in the liver, resulting in hyperoxaluric nephrolithiasis, but with a less aggressive course with regard to renal failure than PH1

36. A third type of primary hyperoxaluria has recently been recognized. Primary hyperoxaluria type 3 (PH3) is caused by a defective mitochondrial enzyme, 4-hydroxy-2-oxoglutarate aldolase (HOGA), which is thought to play a role in hydroxyproline metabolism ( Belostotsky et al, 2010). 4-Hydroxy-2-oxoglutarate derived from hydroxyproline is converted to pyruvate and glyoxylate in a reaction catalyzed by HOGA. However, the mechanism by which this defect leads to hyperoxaluria has not been established. Although PH3 is associated with hyperoxaluria and severe hypercalciuria , the recurrent calcium oxalate stone formation seen in early childhood may become clinically silent later in life, and there are no reports to date of progression to ESRD in these patients

37. Enteric Hyperoxaluria . The most common cause of acquired hyperoxaluria is enteric hyperoxaluria . This abnormality is associated with chronic diarrheal states, by which fat malabsorption results in saponification of fatty acids with divalent cations such as calcium and magnesium, thereby reducing calcium oxalate complexation and increasing the pool of available oxalate for reabsorption (Earnest et al, 1975). The poorly absorbed fatty acids and bile salts may increase colonic permeability to oxalate, further enhancing intestinal oxalate absorption

38. Dehydration, hypokalemia, hypomagnesiuria , hypocitraturia, and low urine pH also increase the risk of calcium oxalate stone formation in patients with chronic diarrheal syndrome. Malabsorption of any cause can lead to increased intestinal absorption of oxalate. Therefore small bowel resection, intrinsic disease, and jejunoileal bypass (Cryer et al, 1975) have all been associated with hyperoxaluria.

39. Dietary Hyperoxaluria . Overindulgence in oxalate-rich foods such as nuts, chocolate, brewed tea, spinach, potatoes, beets, and rhubarb can result in hyperoxaluria in otherwise normal individuals. The contribution of dietary oxalate to urinary oxalate excretion can range from 24% to 42% (Holmes et al, 2001). In addition, severe calcium restriction may result in reduced intestinal binding of oxalate and increased intestinal oxalate absorption. Ascorbic acid supplementation has been shown to increase urinary oxalate levels by in vivo conversion to oxalate ( Traxer et al, 2003), although increased clinical rates of stone formation have not been unequivocally linked to ascorbic acid use

40. Recent studies have also implicated O. formigenes , an oxalatedegrading intestinal bacterium, as a potential modulator of intestinal oxalate levels (Duncan et al, 2002). Stone formers were found to have reduced levels or absent colonization of O. formigenes compared with non–stone-forming control subjects, and individuals lacking the bacteria have been shown to have higher urinary oxalate levels

41. Cystic fibrosis patients , many of whom are exposed to prolonged antibiotic use, have also been shown to have absence of O. formigenes from the intestinal tract and corresponding elevated urinary oxalate levels

42. Idiopathic Hyperoxaluria . Several studies have suggested that mild hyperoxaluria is as important a factor as hypercalciuria in the pathogenesis of idiopathic calcium oxalate stones

43. Hypocitraturia Hypocitraturia is an important and correctable abnormality associated with nephrolithiasis that exists as an isolated abnormality in up to 10% of calcium stones. Citrate is an important inhibitor that can reduce calcium stone formation by several mechanisms. Reduces urinary saturation of calcium salts by complexing with calcium. Directly prevents spontaneous nucleation of calcium oxalate. Inhibits agglomeration and sedimentation of calcium oxalate crystals. Enhance the inhibitory effect of Tamm- Horsfall glycoprotein

44. Hypocitraturia is defined as a urinary citrate level less than 320 mg/day. Acid-base state is the primary determinant of urinary citrate excretion. Metabolic acidosis reduces urinary citrate levels secondary to enhanced renal tubular reabsorption and decreased synthesis of citrate in peritubular cells. Estrogen increases citrate excretion thus preventing against stone formation.

45. Low urinary citrate results from a variety of pathologic states associated with acidosis. Distal RTA. Chronic diarrheal states cause intestinal alkali loss in the stool with subsequent systemic acidosis and hypocitraturia . Excessive animal protein can provide an acid load, reducing citrate levels. Drugs. Diuretics such as thiazides induce hypokalemia and intracellular acidosis. Angiotensin-converting enzymes. strenuous exercise may induce lactic acidosis.

46. Low Urine pH At low urine pH (<5.5), the undissociated form of uric acid predominates, leading to uric acid and/or calcium stone formation. Calcium oxalate stones form as a result of heterogeneous nucleation with uric acid crystals (Coe and Kavalach , 1974; Pak et al, 1976). Any disorder leading to low urine pH may predispose to stone formation. Chronic metabolic acidosis can lead to low urine pH, hypercalciuria , and hypocitraturia . Acidosis increases bone resorption and produces renal calcium leak ( Lemann , 1999; Lemann et al, 2003). “Gouty diathesis,” or idiopathic low urine pH, refers to a stone-forming propensity characterized by low urine pH of unknown etiology with or without associated gouty arthritis

47. Renal Tubular Acidosis RTA is a clinical syndrome characterized by metabolic acidosis resulting from defects in renal tubular hydrogen ion secretion or bicarbonate reabsorption. There are three types of RTA: 1, 2, and 4. Type 1 (distal) RTA is of particular significance to urologists not only because it is the most common form of RTA but also because it is the form of RTA most frequently associated with stone formation, which occurs in up to 70% of affected individuals (Van den Berg et al, 1983).

48. Distal and proximal RTA occur as a result of impairment of net excretion of acid into the urine (distal or type 1) or of reabsorption of bicarbonate (proximal or type 2). Type 1 (Distal) Renal Tubular Acidosis. Type 1 RTA comprises a syndrome of abnormal collecting duct function characterized by inability to acidify the urine in the presence of systemic acidosis. The classic findings include hypokalemic, hyperchloremic non–anion gap metabolic acidosis along with nephrolithiasis, nephrocalcinosis , and elevated urine pH (>6.0).

49. Patients with distal RTA commonly present as adults with symptoms of nephrolithiasis (Caruana and Buckalew , 1988). However, children comprise a third of affected individuals, and they often present with vomiting or diarrhea, failure to thrive, or growth retardation. The most common stone composition associated with distal RTA is calcium phosphate as a result of hypercalciuria, hypocitraturia, and increased urinary pH (Van den Berg et al, 1983; Pohlman et al, 1984). The metabolic acidosis promotes bone demineralization, which leads to secondary hyperparathyroidism and hypercalciuria. Profound hypocitraturia, perhaps the most important factor in stone formation in this setting, is due to impaired citrate excretion as a result of metabolic acidosis but may also be related to abnormal renal tubular citrate transport or migration of citrate into the mitochondria as a result of intracellular acidosis

50. Distal RTA occurs as a consequence of dysfunction of the α- type intercalated cells, which secrete protons into the urine via an apical H+-ATPase that is coupled to an anion exchanger (AE1) located at the basolateral membrane

51. Type 2 (Proximal) Renal Tubular Acidosis. Proximal RTA is characterized by a defect in HCO3 − reabsorption associated with initial high urine pH that normalizes as plasma HCO3 − decreases and the amount of filtered HCO3 − falls (Laing et al, 2005). With reduced capacity of the proximal tubule to reclaim filtered HCO3 −, more HCO3 − is delivered to the distal tubule, which has a limited capacity for bicarbonate reabsorption. Consequently, bicarbonaturia ensues, resulting in reduced net acid excretion and metabolic acidosis. As the filtered HCO3 − load declines with progressive metabolic acidosis, less bicarbonate reaches the distal tubule until eventually the capacity of the distal tubule is sufficient to handle the load and no further bicarbonate is lost. At steady state, serum HCO3 − is low (15 to 18 mEq /L) and urine pH is acidic (<5.5).

52. This syndrome is usually associated with generalized defects in proximal tubule function similar to Fanconi syndrome, with loss of glycogen, protein, uric acid, and phosphate (Rocher and Tannen, 1986). Nephrolithiasis is uncommon in this disorder owing to relatively normal urinary citrate excretion (Laing et al, 2005). The clinical manifestations of proximal RTA include growth retardation and hypokalemia in children resulting from metabolic acidosis. Metabolic bone disease is seen more frequently with proximal RTA because of associated abnormalities in vitamin D metabolism and hypophosphatemia ( Kinkead and Menon, 1995).

53. Hypomagnesiuria Hypomagnesiuria is a rare cause of nephrolithiasis, affecting less than 1% of stone formers as an isolated abnormality, although it can be found in conjunction with other abnormalities in 6% to 11% of cases (Levy et al, 1995; Schwartz et al, 2001). Magnesium complexes with oxalate and calcium salts, and therefore low magnesium levels result in reduced inhibitory activity. Low urinary magnesium is also associated with decreased urinary citrate levels, which may further contribute to stone formation.

54. Non calcium calculi Struvite stones. Contain magnesium, ammonia and phosphate. Found commonly in women and may recur rapidly. Are infection stones associated with urea-splitting organisms including proteus,pseudomonas , klebseilla , providencia , staphylococci and mycoplasma. A history of a foreign body (e.g., forgotten stent, suture material, staple) or neurogenic bladder may be noted.

55. Struvite calculi can be quite large and often fill multiple calyces or even the entire collecting system. Present frequently as renal starghorn calculi and rarely present as ureteral stones Urine cultures often will reveal a bacterial pathogen, although the presence of a sterile urine culture does not preclude the sequestration of bacteria within the calculus itself.

56. High ammonium concentration---alkaline urinary pH (> 7.2). Its only at this pH that MAP crystals ppt. MAP crystals are soluble in the normal urinary pH range (5-7). Massive duiresis does not prevent struvite calculi. Long term mgt - removal of all FBs including catheters. A short ileal loop helps decrease the risk of stones in patients with supravesical urine diversion.

57. Acetohydroxamic acid inhibits action of bacterial urease thereby reducing urinary pH and decreasing likelihood of ppt. Most patients have a difficult time tolerating this medicaion .

58. Staghorn Calculi Staghorn calculi are large renal stones that occupy most or all of the renal collecting system. The name arises from the fact that these stones look like the antlers of a deer or stag on imaging. The stones frequently involve the renal pelvis and branch into the surrounding infundibula and calyces. Struvite composes the majority of staghorn stones, although this configuration of collecting system involvement can include any type of stone

59. Untreated, staghorn stones are associated with recurrent UTIs, urosepsis events, renal functional deterioration, and a higher likelihood of death. Complete renal function loss in 50% of affected kidneys can occur after 2 years without treatment.

60. Bilateral staghorn calculi

61. Uric acid stones Compose <5% of renal calculi Found usually in men. Hyperuricosuria is defined as urinary uric acid exceeding 600 mg/ day. Most patients with uric acid stones do not have hyperuricemia . Elevated urine uric acid levels are due to dehydration and purine intake. Patient with urate stones have a pH of <5.5. As urinary pH increases above the dissociation constant pKa of 5.75, it dissociates into a relatively soluble urate ion.

62. The most common cause of hyperuricosuria is increased dietary purine intake. However, acquired and hereditary diseases may also be accompanied by hyperuricosuria, including gout, myeloproliferative and lymphoproliferative disorders, multiple myeloma, secondary polycythemia, pernicious anemia, hemolytic disorders, hemoglobinopathies and thalassemia, complete or partial HGPRT deficiency, overactivity of phosphoribosylpyrophosphate synthetase, and hereditary renal hypouricemia

63. As urinary pH increases above the dissociation Pka 5.75, it dissociates into a relatively soluble urate iron. Treatment is centered on maintaining urine volume >2l/day and urine pH>6. Reducing dietary purines and administration of allopurinol also help reduce uric acid excretion. Alkalinization of urine ( NaHCO3,KHCO3,Potassium citrate or sodium lactate) may dissolve calculi.

64. Xanthine stones Occurs in congenital deficiency of xanthine oxidase. Stones are radiolucent and are tannish yellow in color. High fluid intake recommended.

65. Cysteine stones Secondary to inborn errors of metabolism resulting in abnormal intestinal (small bowel) mucosal absorption and renal tubular absorption of dibasic acids including cysteine, ornithine, lysine and arginine. 1-2% of renal calculi. Peak incidence: second or third decade. Solubility of cysteine is PH dependent with a Pk of 8.1 Are frequently associated with calcium calculi.

66. May present as single, multiple or starghorn stones. Medical therapy: high fluid intake (>3l/day) and alkalinization of urine. A low methionine ( precursor of cysteine) has a limited impact as most of the cysteine is endogenous. Glutamine, ascorbic acid and captopril are effective in some patients. Penicillamine can reduce urinary cystein levels. It complexes with the amino acid and this pdt is more soluble.

67. Many patients poorly tolerate this treatment. It may inhibit pyrodoxine which should be supplemented during treatment (50mg/day). Mercaptopropionylglycine ( Thiola )- forms a soluble complex with cysteine and reduce stone formation.

68. drug-induced stones. Antiretroviral Agents. Indinavir sulfate. Triamterene. Guaifenesin and Ephedrine. Thiazides cause intracellular acidosis and subsequent hypocitraturia Carbonic anhydrase inhibitors such as acetazolamide, Topiramate .

69. Anatomic Predisposition to Stones Patients with anatomic anomalies associated with urinary obstruction and/or stasis have been noted to have a high incidence of associated stones. Ureteropelvic Junction Obstruction The incidence of renal calculi is nearly 20% Horseshoe Kidneys Horseshoe kidneys occur with a prevalence of 0.25% but have an associated rate of renal calculi of 20% Caliceal Diverticula Caliceal diverticula are associated with stones in up to 40% of Patients

70. Medullary Sponge Kidney Medullary sponge kidney (MSK) is a disorder characterized by ectasia of the renal collecting ducts. Nephrocalcinosis and renal calculi are frequent complications of MSK

71. Stones in Pregnancy Symptomatic stones during pregnancy occur at a rate of 1 in 250 to 1 in 3000 pregnant women. The majority of symptomatic stones occur in the second and third trimesters of pregnancy, heralded by symptoms of flank pain or hematuria. The diagnosis can be difficult in this patient population; up to 28% of women are misdiagnosed with appendicitis, diverticulitis, or placental abruption

72. Important physiologic changes in the kidney occur during pregnancy and modulate urinary stone risk factors. Renal blood flow increases, leading to a 30% to 50% rise in glomerular filtration rate, which subsequently increases the filtered loads of calcium, sodium, and uric acid. Hypercalciuria is further enhanced by placental production of 1,25(OH)2D3, which increases intestinal calcium absorption and secondarily suppresses PTH. Hyperuricosuria has also been reported as a result of increased filtered load of uric acid

73. Despite increases in a number of stone-inducing analytes , pregnant women have been shown to excrete increased amounts of inhibitors such as citrate, magnesium, and glycoproteins. Therefore the overall risk of stone formation has been reported to be similar in gravid and nongravid women.

74. Plain x-ray and intravenous pyelogram

75. Clinical features. Upper urinary tract stones usually cause pain. The character of the pain depends on the location. Calculi small enough to venture down the ureters usually have difficulty passing throuh the ureteropelvic junction or entering the bladder at the ureterovesical junction.

76. A. pain. Renal colic- stretching of the collecting system or the ureter. Urinary obstruction is the main mechanism. Non colicky renal pain- distension of the renal capsule. Severity and location of the pain can vary from patient to patient due to stone size, stone location, degree of obstruction, and anatomic variation ( eg intrarenal versus extrarenal pelvis)

77. The stone burden does not correlate with the severity of the symptoms. Small ureteral stones frequently present with severe pain while large starghorn calculi will present with a dull ache or flank discomfort. The pain frequently abrupt in onset and severe and may awaken a patient from sleep. Patients move constantly in an attempt to relieve pain.

78. The symptoms of renal colic depend on the location of the calculi. 1. Renal calyx . Deep dull ache in the flank or back. Caliceal calculi occasionally result in spontaneous perforation with urinoma, fistula or abscess formation. 2 . renal pelvis. Stones >1 cm obstruct UPJ. Severe pain in costovertebral angle just lateral to sacrospinalis muscle and just below the 12 th rib.

79. 3. Upper and mid-ureter. Severe back ( costovertebral ) or flank pain. 4. Distal ureter. Pain that radiates to the groin or testicles in men or labia majora in female. Pain in the distribution of the ilioinguinal nerve or genital branch of the genitofemoral nerve .

80. B. haematuria . Intermittent gross haematuria or occasional tea colored urine (old blood). Microhaematuria . C. infection. - struvite stones -phosphate stones D. obstruction pyonephrosis . Pus in the obstructed collecting system. Xanthogranulomatous pyelonephritis. Fever. Nausea and vomiting. Costovertebral tenderness in acute upper urinary tract obstruction.

81. DIAGNOSTIC EVALUATION OF NEPHROLITHIASIS Any evaluation should be able to identify associated metabolic disorders responsible for recurrent stone disease. These metabolic problems include distal renal tubular acidosis (RTA), primary hyperparathyroidism, enteric hyperoxaluria, cystinuria, and gouty diathesis. In many of these relatively uncommon conditions, it is generally agreed that selective medical therapy is indicated not only to prevent further stone formation but also to correct underlying physiologic disturbances that may lead to nonrenal complications

82. History Underlying predisposing conditions (as per Box 52-1) Medications (calcium, vitamin C, vitamin D, acetazolamide, steroids) Dietary excesses, inadequate fluid intake, excessive fluid loss Surgical history: bowel resection. Multichannel blood screen Basic metabolic panel (sodium, potassium, chloride, carbon dioxide, blood urea nitrogen, creatinine) Calcium Intact parathyroid hormone Uric acid

83. Urine Urinalysis pH > 7.5: infection lithiasis or RTA pH < 5.5: uric acid lithiasis Sediment for crystalluria Urine culture Urea-splitting organisms: suggestive of infection lithiasis Qualitative cystine

84. The urine sediment should be examined for crystalluria, because particular crystal types may give a clue as to the composition of stones the patient is forming. Tetrahedral “envelopes” are seen in calcium oxalate lithiasis (Fig. 52-1), and rectangular, “ coffinlid ” crystals are often seen in patients with struvite calculi (see Fig. 52-1). Hexagonal crystals confirm cystinuria (see Fig. 52-1); uric acid crystals may be seen as amorphous fibers or as irregular plates. The microscopic appearances of common calculi are summarized in Table 52-1.

85. Urine cultures are performed if there is a suspicion of infection-related calculi or if there are signs or symptoms of a UTI. A culture that is positive for urea-splitting organisms such as Proteus, Pseudomonas, Klebsiella, Staphylococcus aureus, and Staphylococcus epidermidis would help explain the formation of a struvite calculus. A positive culture also will warrant therapy with appropriate antibiotics before initiation of any surgical procedure to remove the stone. The surgical management of a calculus during an active infection will place the patient in great risk for bacteremia or sepsis. Unfortunately, many infected calculi will harbor bacteria even after treatment with broad-spectrum antibiotics.

86. Radiography Radiopaque stones: calcium oxalate, calcium phosphate, magnesium ammonium phosphate ( struvite ), cystine . Radiolucent stones: uric acid, xanthine, triamterene Intravenous pyelogram : radiolucent stones, anatomic abnormalities

87. Abdominal x-ray films (kidney-ureter-bladder [KUB]) should be obtained to document the existence of any current stones within the urinary tract. The radiopacity of any existing stones may suggest the type of stones present. Although magnesium ammonium phosphate and cystine stones are often radiopaque, they are not as dense as calcium oxalate or calcium phosphate stones. A plain abdominal film is also useful in identifying nephrocalcinosis (suggestive of RTA). A noncontrast computed tomography (NCCT) scan may be obtained to confirm the presence of radiolucent stones and also identify any anatomic abnormalities that may predispose the patient to stone formation.

88. CT scan.( non contrast). Is the investigationof choice in patients with renal colic. Images other peritoneal and retroperitoneal structures and helps when diagnosis is uncertain. Distal ureteral calculi may be confused with phleboliths . Does not give anatomic details as seen in IVP ( a bifid collecting syatem ) that may be important in planning intervention. Urate stones are visualised the same as oxalate stones.

89. Intravenous pyelogram ( IVP). Can document both stones and upper tract anatomy. Extraosseous calcifications on radiographs may be erroneously assumed to be urinary calculi. Oblique views easily differentiate gall stones from right renal calculi.

90. Tomography. -renal tomography is useful to identify renal calculi when oblique views are not helpful May help identify poorly opacified calculi especially when interfering abdominal gas or morbid obesity make KUB films suboptimal. KUB films and directed ultrasonography.

91. Retrograde pyelography. -delineate the upper tract anatomy - localise small or radiolucent calculi. MRI -Is apoor study to document renal stone disease. Nuclear scintigraphy . -can identify small stones -can not delineate upper tract anatomy in sufficient detail to help direct a therapeutic plan.

92. Stone analysis. Finally, available stones should be analyzed to determine their crystalline composition. The presence of uric acid or cystine would suggest the presence of a gouty diathesis or cystinuria, respectively. The finding of struvite, carbonate apatite, and magnesium ammonium phosphate would suggest infection lithiasis. A predominance of a hydroxyapatite component suggests the presence of RTA or primary hyperparathyroidism and warrants an assessment of basic electrolytes. Stones composed of pure calcium oxalate or mixed calcium oxalate and hydroxyapatite are less useful diagnostically because they may occur in several entities, including absorptive and renal hypercalciuria, hyperuricosuric calcium nephrolithiasis, enteric hyperoxaluria, hypocitraturic calcium nephrolithiasis, and low urine volume

93. Treatment modalities Conservative observation Medical therapy. -dissolution agents. -oral therapy.

94. intervention 1 . conservative observation. most ureteral calculi pass and do not require intervention spontaneous passage depends on stone size, shape,location and associaed ureteral oedema . -ureteral calculi 4-5mm have a 40-50% chance of spontaneous passage. calculi >6mm have <5% chance of passage.

95. The vast majority of stones that pass do so within a 6 weeks period after onset of symptoms. Calculi at the distal ureter-50% chance of spontaneous passage, mid ureter (25%) and proximal ureter( 10%)

96. CONSERVATIVE MANAGEMENT Fluid Recommendations Volume One mainstay of conservative management is the forced increase in fluid intake to achieve a daily urine output of at least 2 liters ( Borghi et al, 1999). Increased urine output may have two effects. First, the mechanical diuresis that ensues may prevent urinary stagnation and the formation of symptomatic calculi. It is more likely that the creation of dilute urine alters the supersaturation of stonemcomponents .

97. KEY POINTS: FLUID RECOMMENDATIONS Patients should be strongly encouraged to consume enough fluids to produce 2 L/day. Water hardness is unlikely to play a significant role in recurrence risk. Carbonated water may confer some protective benefit. Soda flavored with phosphoric acid may increase stone risk, whereas those with citric acid may decrease risk. Citrus juices (particularly lemon and orange juices) may be a useful adjunct to stone prevention.

98. Dietary Recommendations Randomized studies have confirmed the advantage of a diet with reduced animal protein (meat) intake. A diet high in fruits and vegetables imparts a reduced risk for stone formation over diets high in animal protein. Randomized trials have demonstrated a benefit of dietary sodium restriction in both normal volunteers and stone formers.

99. Protein intake increases urinary calcium, oxalate, and uric acid excretion and the mathematically calculated probability of stone formation even in normal subjects

100. They noted that a high sodium intake not only increased calcium excretion but also increased urinary pH and decreased citrate excretion. The net effect of a high-sodium diet was an increased propensity for the crystallization of calcium salts in urine

101. Dietary calcium restriction actually increases stone recurrence risk. Calcium supplementation is likely safest when taken with meals. Calcium citrate appears to be a more stone-friendly calcium supplement because of the additional inhibitory action of citrate. Vitamin D repletion is likely safe for stone formers; however, 24-hour urine calcium should be monitored during vitamin D therapy. Bisphosphonates combined with thiazide diuretics appear to reduce hypercalciuria while protecting the bone.

102. 2. MEDICAL THERAPY OF NEPHROLITHIASIS Improved elucidation of the pathophysiology and the formulation of diagnostic criteria for different causes of nephrolithiasis have made feasible the adoption of selective treatment programs (Pak et al, 1981; Preminger and Pak, 1985). Such programs should (1) reverse the underlying physicochemical and physiologic derangements,(2) inhibit new stone formation, (3) overcome nonrenal complications of the disease process, and (4) be free of serious side effects.

103. Dissolution agents effectiveness depends on stone surface area, stone type, volume of the irrigant and mode of delivery A) oral alkalinising agents -sodium or potassium bicarbonate -potassium citrate 60meq in 3-4 divided doses per day. Indicated in those with calcium oxalate stones secondary to hypocitraturia . It may also treat uric acid lithiasis . Intravenous sodium lactate. Orange juice alkalinises urine.

104. B). Thiols for dissolution of cysteine stones - penicillamine 0.5% solution -n- acetylcysteine 2-5% solution Alpha- mercaptopropionylglycine 5% solution. C) struvite stone dissolution requires acidifiction . - subys G solution. - hemiacidrin ( Renacidin )- not approved FDA

105. MISCELLANEOUS SCENARIOS Medical Management of Bladder Calculi bladder calculi usually occur in men older than 50 years of age and are usually associated with bladder outlet obstruction. The diagnosis of a bladder stone should result in a complete urologic evaluation for factors that cause urinary stasis, such as urethral stricture, benign prostatic hyperplasia, bladder diverticulum, and/or a neurogenic bladder. Occasionally, bladder stones may result as a consequence of a retained foreign body catheter, forgotten double j ureteral stents.

106. bladder stones are usually composed of uric acid (in noninfected urine) or struvite (in infected urine). The occurrence of calcium oxalate or cystine stones in the bladder suggests the presence of calculi in the kidney with subsequent ureteral passage and entrapment in the bladder.

107. Bladder calculi are usually solitary, but may develop in large numbers in the presence of urinary stasis. The typical symptoms of a vesical stone are intermittent, painful voiding and terminal hematuria. Discomfort may be dull, aching, or sharp suprapubic pain, which is aggravated by exercise and sudden movement. Severe pain usually occurs near the end of micturition, when the stone becomes impacted at the bladder neck. Relief may be afforded by assuming a recumbent position. The pain may be referred to the tip of the penis, the scrotum, or the perineum and on occasion to the back or the hip. Besides pain, there may be an interruption of the urinary stream from impaction of the stone at the bladder neck or urethra.

108. Bladder calculi are frequently missed on plain film because of a high component of uric acid and because of overlying prostatic tissue. Such stones form negative shadows in the cystogram phase of intravenous urography. Ultrasonography is useful for detecting radiolucent calculi. Cystoscopic examination is the surest method for detecting vesical calculi.

109. The vast majority of bladder calculi can be removed via endoscopic techniques. Various lithotripters have been used, including ultrasonic handpieces, lasers, pneumatic devices, and electrohydraulic probes. Transurethral and percutaneous approaches have been described with good success ( Dhabalia et al, 2011; Philippou et al, 2011). Renacidin may prove beneficial in irrigating indwelling suprapubic or urethral catheters to decrease and prevent encrustation and occlusion (Kennedy et al, 1992; Getliffe et al, 2000). Twice-daily or thrice-daily irrigation with 0.25% or 0.5% acetic acid solution also serve as beneficial prophylaxis against recurrent struvite calculi when catheters must be left indwelling for long periods. Uric acid calculi may be dissolved by irrigation with alkaline solutions

110. The mainstay of therapy for the prevention of recurrent bladder calculi involves relief of the bladder outlet obstruction. This treatment may include the performance of a transurethral resection of the prostate or an open prostatectomy if the gland is quite large.

111. Neonatal Nephrolithiasis Neonates with furosemide-induced nephrolithiasis present with hematuria, worsening renal function, and calcific densities on ultrasonography or plain film radiography. Nephrocalcinosis is often present on imaging studies. This same process has been seen in other infants with severe low birth weight and/or prematurity and no history of loop diuretic usage.

112. Management of neonatal nephrolithiasis entails the obvious optimization of the infant’s overall health. Cessation of furosemide diuresis is considered helpful and standard therapy. There has been previous suggestion that treatment with thiazide diuretics may actually promote the resolution of this process and reverse the likely parenchymal injury

113. Children and Adolescents the appearance of urinary calculi during childhood should raise the distinct possibility of an inherited genetic disorder, such as cystinuria, distal RTA, or primary hyperoxaluria.

114. Medical Management of Calculi during Pregnancy. Radiation exposure to the fetus should be avidly avoided. Therefore ultrasonography has become the first-line imaging study to search for calculi during pregnancy. Although this modality provides adequate images of the kidneys, it can be difficult to fully discern the ureters and their contents. Additionally, hydronephrosis of pregnancy may be confused for hydronephrosis from an obstructing calculus. A limited intravenous pyelogram (IVP) may be obtained that consists of one scout image followed by one plate taken approximately 30 minutes after the injection of contrast. Each plain film exposes the fetus to 0.1 to 0.2 rads , well below the threshold of 1.2 rads , at which the risk begins to increase. Radiation exposure should be particularly avoided durinthe first trimester during the time of organogenesis and the greatest fetal risk.

115. Approximately 66% to 85% of pregnant women with ureteral colic spontaneously pass the calculi when treated conservatively with hydration, analgesics, and, if infected, antibiotics (Jones et al, 1979; Stothers and Lee 1992). The goal of therapy for the remaining patients is to do the least required to keep the kidney functioning, the patient free from symptoms, and the urine uninfected. Stents should be placed cystoscopically with minimal radiographic or sonographic monitoring

116. Strategies for Nonmedical Management of Upper Urinary Tract Calculi Endoscopic. ureterorenoscopy (URS), percutaneous nephrolithotomy (PCNL), and extracorporeal shock wave lithotripsy (SWL). Ureterolithotomy Nephrolithotomy Retrograde renoscopy —A laser fibre can be introduced through a flexible fibre optic ureterorenoscope , which is introduced through the urethra and bladder, and up the ureter to the renal collecting system. Stones 1 cm in diameter can be disintegrated. Open surgery—This is needed infrequently. Staghorn stones, in which the bulk of the stone lies within calices rather than within the renal pelvis, are treated best by open surgery. Kidneys that contribute 10% of overall renal function should usually be removed. Extensive perirenal fibrosis is usually encountered, which makes such a nephrectomy impossible laparoscopically .

117. Ureteral sones Conservative management —Most stones 5 mm in maximum diameter are likely to pass spontaneously and should be allowed to do so. Stones will pass down the ureter when the ureter peristalses. In the presence of an obstruction, diuresis will provoke ureteric dilatation and reduce peristalsis. Anticholinergic drugs, such as hyosine , similarly will be ineffective. Extracorporeal shockwave lithotripsy—This has been advocated for ureteric stones, when imaging is possible radiographically or by ultrasound. This approach is less successful for ureteric stones than renal stones and is possible only at urological centres that have a static rather than mobile lithotripter. Endoscopic ureterolithotomy — With or without stone disintegration, this is a safe and effective method of managing ureteric stones that need intervention.

118. Open surgery—This is indicated very rarely for ureteric stones. If associated ureteric pathology, such as stricture, is present, open surgery may be the only solution.

119. Treatment Decision by Stone Burden The total kidney stone burden, or total volume of stone(s) requiring treatment, is arguably the most important factor influencing treatment decisions.

120. Kidney Stone Burden up to 1 cm. The majority (50% to 60%) of solitary kidney stones are 1 cm or less in diameter, and many of them are asymptomatic (Cass, 1995; Renner and Rassweiler , 1999; Logarakis et al, 2000). Given enough time, however, many will enlarge or become associated with clinical factors that warrant treatment. Almost all renal stones 1 cm or smaller may be treated with SWL, URS, or PCNL. Laparoscopic or open stone removal is necessary in exceedingly rare cases, most often when there is underlying aberrant anatomy.

121. SWL has been considered first-line treatment for these smaller kidney stones without complicating clinical or renal anatomic considerations because it is the least invasive modality, achieves reasonably high stone-free rates, and requires the least technical skill. For kidney stones 1 cm or less in diameter, SWL achievesstone -free rates of approximately 50% to 90%

122. Over the last decade, technologic advances in flexible endoscope design and instrumentation have facilitated the use of URS, also referred to as retrograde intrarenal surgery, for the treatment of kidney stones. Multiple reports have now clearly established URS as a reasonable alternative for the treatment of most kidney stones, especially those smaller than 1 cm. Contemporary URS for renal stones 1 cm or smaller offers stone-free rates of approximately 80% to 90%,

123. PCNL is reserved for failures of SWL and URS or for patients with anatomic considerations making PCNL vastly superior, such as lower pole stones with acute infundibulopelvic angles or calyceal diverticula.

124. Kidney Stone Burden between 1 and 2 cm. For renal stones between 1 cm and 2 cm, SWL, URS, and PCNL are the most frequently used treatments, with laparoscopic and open stone removal seldom necessary. Stone location, composition, and density and patient anatomic factors become increasingly relevant as stone burden enlarges and have an important impact on treatment outcomes. Larger stone burdens located in lower pole calyces, increasing skin-to-stone distance, and unfavorable lower renal pole anatomy all decrease the success rates of SWL and URS but have limited influence on PCNL outcomes. Thus, for renal calculi between 1 cm and 2 cm, stone-specific and anatomic factors must be carefully considered when weighing the relative outcomes and invasiveness of each procedure

125. For stones between 1 cm and 2 cm that are not located in the lower pole, SWL has traditionally been recommended as first-line therapy, and remains so in the most updated urolithiasis guidelines from the EAU (Turk et al, 2013). In general, SWL is favored when stones are not located in the lower pole, stone attenuation is less than approximately 900 HU, skin-to-stone distance is less than 10 cm, and the patient has no history of SWL-resistant minerals (cysteine, calcium oxalate monohydrate, brushite).

126. Kidney Stone Burden Greater than 2 cm . PCNL should be considered first-line therapy for kidney stone burdens 2 cm and greater. Unlike URS and SWL, the success of PCNL is relatively independent of stone location and stone composition.

127. Staghorn Stones . PCNL is the method of choice for treating partial and complete staghorn kidney stones, with the caveat that poorly or nonfunctioning kidneys and those associated with xanthogranulomatous pyelonephritis may be best managed with nephrectomy.

128. Treatment Decision by Stone Localization Stones situated in the lower pole prove more difficult to clear with URS or SWL, and therefore stones 1 cm or larger within the lower pole may be most efficiently treated with PCNL. Stones in a non–lower pole location tend to respond more readily to SWL and URS, making those techniques more competitive with PCNL.

129. Treatment by Stone Composition Stone composition has significant implications with respect to treatment outcomes primarily with SWL, whereas URS, PCNL, and laparoscopic and open stone surgery appear to be only minimally affected.

130. In general, cystine, calcium phosphate (specifically “brushite”), and calcium oxalate monohydrate stones are the most resistant to SWL. The remainder of the common stone types by order of increasing fragility are struvite, calcium oxalate dihydrate, and finally uric acid stones

131. PCNL is the preferred treatment approach for most matrix renal stones owing to its high success rates and low recurrence rates.

132. ENDOSCOPIC. Ureteroscopic stone extraction. -effective for lower ureteral stones -complication rate 5-30% Ureteral strictures-<5% Postoperative vesicoureteric reflux extremely rare.

133. 1 . percutaneous nephrolithotomy . -removal of renal and proximal ureteral stones -is treatment of choice for large (>2.5cm) calculi, those resistant to ESWL,lower pole calyceal stones and in evidence of obstruction. 2. endoscopic ureterolithotomy .

134. Open surgery - pyelolithotomy - especially with extrarenal pelvis. -radial nephrotomy .- Partial nephrectomy- large stone burden in a renal pole with marked parenchymal thinning. Ureterolithotomy . Stones inaccessible to endoscopy and resistant to ESWL.

135. Other unusual procedures Ileal ureter substitution Autotransplantation with pyelocystostomy .

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