The highest prevalence of stone disease in both men and
women occurs in ___. In men the lowest prevalence occurs in
__, whereas Asian women have been found to
have the lowest prevalence in one series.
Most common type of urinary stone:
Most common type of calcium based urianry stone
Most common type in young females with alkaline urinary ph
type of calcium phosphate stone associated wth recurrence and rapid growth
Calcium based stones
According to hospital discharge rates among U.S. veterans, calcium oxalate stone disease is most prevalent in the___
Southeast. According to hospital discharge rates among U.S. veterans, calcium oxalate stone disease is most prevalent in the southeast.
___ is characterized by obesity, hypertension, dyslipidemia, and insulin resistance, and is associated with an ____ stone formation.
impaired ammoniagenesis accounts for an increased risk of ____ stones due to ___ urine pH. None of the other conditions has been associated with stone disease.
Metabolic syndrome is characterized by obesity, hypertension, dyslipidemia, and insulin resistance, and is associated with an increased risk of kidney stone formation. Although impaired ammoniagenesis accounts for an increased risk of uric acid stones due to low urine pH, association with stone disease in general has been demonstrated. None of the other conditions has been associated with stone disease.
Which of the following occurs when the concentration product of urine is in the metastable range?
URINE IS SUPER SATURATED
The process by which nuclei form in pure solutions is called ___.
Depending on their type, kidney stones contain between 2.5% and 65% of __x. Extensive investigations have characterized matrix as a derivative of several of the __
noncrystalline material or matrix
mucoproteins of urine and serum.
Hyperoxaluria has been described in both stoneforming and non-stone-forming patients who have undergone ___ , with urinary oxalate levels in some patients ___. A mild decrease in ___ compared with stone-forming control subjects has been described by some investigators but is a less consistent and severe finding.
Roux-en-Y gastric bypass surgery
exceeding 100 mg/day
It is generally accepted that ___ is the vitamin D metabolite that is the most potent stimulator of intestinal calcium absorption.D3
1,25- dihydroxyvitamin D3
the setting of a high calcium intake, ___, and during calcium restriction, oxalate absorption ___ because of reduced formation of a soluble calcium oxalate complex and increased availability of oxalate for absorption. H. pylori, which can colonize the stomach, has/has no effect on intestinal oxalate absorption
. O. formigenes, an ___, uses oxalate as a substrate in the intestinal lumen, thereby reducing oxalate absorption. Irritable bowel syndrome, unless it is associated with chronic diarrhea, does/does not affect intestinal oxalate absorption.
oxalate absorption decreases,
oxalate absorption increases
has no effect
an oxalate-degrading bacterium
does not affect/AFFECT
Citric acid intake has a great/limited effect on urinary citrate excretion The majority of absorbed citrate is metabolized to bicarbonate, which is neutralized by the free proton from citric acid, thereby providing no ___ that would increase urinary citrate excretion.
Citric acid intake has a limited effect on urinary citrate excretion because only a small portion of dietary citrate is excreted into the urine unmetabolized. The majority of absorbed citrate is metabolized to bicarbonate, which is neutralized by the free proton from citric acid, thereby providing no net alkali load that would increase urinary citrate excretion.
renal hypercalciuria -? ___ wasting of calcium. In this condition, the underlying abnormality is a primary renal leak of calcium due to impaired: _____
Primary renal wasting of calcium
IMPAIRED renal tubular calcium reabsorption.
T/F : Malabsorption from any cause, including small bowel resection, intrinsic disease, or jejunoileal bypass, increases luminal fatty acids and bile salts. In addition, poorly absorbed bile salts increase colonic permeability to oxalate, further increasing oxalate absorption.
Any bowel surgery, decrease in fat absorption--> increase permeability to oxalate --> Oxalate absorption -- > increase in oxlate exretion --> Oxalate stones :(
LOW URINARY PH FOR T2DM pxs with uric acid stones: ___
Defective ammoniagenesis. Patients with type 2 diabetes mellitus typically exhibit characteristics of the metabolic syndrome, including insulin resistance. Although peripherally, insulin resistance leads to typical symptoms of diabetes, insulin resistance at the level of the kidney leads to impaired ammoniagenesis, by way of reduced production of ammonia from glutamine and reduced activity of the Na+ /H+ exchanger in the proximal tubule that is responsible for either the direct transport or trapping of ammonium in the urine. The result is reduced urinary ammonium and low urine pH.
In idiopathic calcium oxalate stone formers, Randall plaques have been found to originate in the __of the thin loops of Henle. From there, they extend through the ___ where they serve as an anchoring site for calcium oxalate stone formation.
In idiopathic calcium oxalate stone formers, Randall plaques have been found to originate in the basement membrane of the thin loops of Henle. From there, they extend through the medullary interstitium to a subepithelial location, where they serve as an anchoring site for calcium oxalate stone formation.
Urinary saturation of calcium oxalate is strongly, positively correlated with __ and __ . Both contribute equally to urinary saturation of calcium oxalate.
urinary calcium and oxalate concentrations
Randall plaques are invariably composed of calcium ___, which serve as an anchoring site onto which calcium ___ crystals can adhere and grow.
Randall plaques are invariably composed of calcium apatite, which serve as an anchoring site onto which calcium oxalate crystals can adhere and grow.
O. formigenes is an oxalatedegrading bacterium found in the intestinal lumen that uses____ , thereby reducing/increasing luminal oxalate and intestinal oxalate absorption. Oxalobacter is not found in urine.
OXALATE AS AN ENERGY SOURCE
luminal oxalate and intestinal oxalate absorption.
Proteus species are most commonly associated with struvite stones, but more than __ of S. aureus organisms produce urease and are therefore associated with struvite stone formation.
90% of S. aureus organisms
___ in the distal tubule that is unable to excrete excess acid. A defective H+ -ATPase in the distal tubule has been implicated in the inability to excrete excess acid in the presence of an oral acid load among patients with ___
Defective H + -ATPase in the distal tubule that is unable to excrete excess acid. A defective H+ -ATPase in the distal tubule has been implicated in the inability to excrete excess acid in the presence of an oral acid load among patients with distal RTA.
Patients with Lesch-Nyhan syndrome suffer from an inherited deficiency of the purine salvage enzyme ___, which leads to the accumulation of hypoxanthine, which is ultimately converted to uric acid.
___ inhibits xanthine oxidase, which is responsible for converting hypoxanthine to xanthine and xanthine to uric acid. High doses of allopurinol in these patients lead to the accumulation of hypoxanthine and xanthine, but because xanthine is more/less soluble in urine than is hypoxanthine, xanthine stones form.
22. e. Chronic dehydration, intracellular acidosis, and low urinary sodium. Subjects who abuse laxatives are chronically dehydrated, resulting in intracellular acidosis. In addition, urinary sodium is low from sodium loss as a result of the laxatives. In this environment, urate preferentially complexes with the abundant ammonium rather than sodium and produces ammonium acid urate stones. 23. c. Complexing calcium in urine. The primary mechanism of action of citrate is as a complexing agent for calcium, thereby reducing ionic calcium and urinary saturation of calcium oxalate. 24. e. Hypokalemia. 25. b. Proximal tubule. The primary defect in type 2 or proximal RTA is a failure of bicarbonate reabsorption in the proximal tubule, leading to excessive urinary bicarbonate excretion and metabolic acidosis. 26. a. Acidic urine. Patients with uric acid stones often have prolonged periods of acidity in the urine. 27. b. Calcium phosphate. Carbonic anhydrase inhibitors such as acetazolamide and topiramate block reabsorption of bicarbonate in the renal proximal and distal tubules, thereby preventing urinary acidification and inducing a metabolic acidosis. Similar to RTA, carbonic anhydrase inhibition results in the formation of calcium phosphate stones because of the high urine pH, hypercalciuria, and hypocitraturia. 28. c. Increased calcium excretion. Placental production of 1,25- dihydroxyvitamin D3 increases intestinal calcium absorption, further increasing urinary calcium. 29. e. Uric acid. Uric acid is thought to promote calcium oxalate stone formation by removing urinary inhibitors, by “salting out” calcium oxalate in solution and by heterogeneous nucleation, or epitaxy. The other substances are all natural inhibitors of stone formation. 30. a. Arginine. Renal reabsorption of the four dibasic amino acids— cystine, ornithine, lysine, and arginine—is affected by dysfunction of the heteromeric amino acid transporter located in the renal proximal tubule. Because of the poor solubility of cystine in urine, only cystine stones occur in this condition. Chapter Review 1. Renal calculi are two to three times more common in men than women, and in this country whites have the highest prevalence. They are uncommon before the age of 20 years, and the peak incidence occurs in the fourth to sixth decades of life. 2. The prevalence and incidence of stone disease is directly correlated with body mass index; patients with high body mass index excrete increased levels of oxalate, uric acid, sodium, and phosphorus, and are more likely to have urinary supersaturation for uric acid. The incidence and prevalence of stone disease has been increasing around the world. 3. Concentration product is the product of the concentrations of the chemical components. 4. Solubility product is the concentration at which precipitation of the components occurs. 5. A solution is saturated when the solubility product is exceeded. 6. When the solubility product is exceeded and precipitation does not occur, the solution is said to be metastable. When precipitation occurs, the concentration at that point is called formation product. 7. Magnesium and citrate inhibit crystal aggregation (the former complexes with oxalate and the latter with calcium); nephrocalcin inhibits nucleation, growth, and aggregation; Tamm-Horsfall glycoprotein inhibits aggregation; and osteopontin inhibits crystal growth, nucleation, and aggregation of calcium oxalate crystals. 8. Nanobacteria have been implicated in calcifying nanoparticles and serving as a nidus for stone formation. 9. Most stone-forming salts are found in the urine in a supersaturated state. Inhibitors keep them in solution. 10. The noncrystalline component of stones is called matrix and generally accounts for about 2.5% of the weight of the stone. It is composed of mucoproteins, carbohydrates, and urinary inhibitors. 11. Parathyroid hormone increases renal calcium reabsorption and enhances phosphate excretion. 12. Patients with small bowel disease or a history of intestinal resection and an intact colon have an increased oxalate absorption. 13. Calcium absorption occurs primarily in the small intestine at a rate that is dependent on calcium intake. 14. Calcium oxalate accounts for 60% of stones; mixed calcium oxalate and hydroxyapatite, 20%; brushite, 2%; uric acid, 10%; struvite, 10%; and cystine, 1%. 15. Hypercalciuria is the most common abnormality identified in calcium stone formation. Hypercalciuria is defined as a urinary excretion greater than 4 mg/kg/day. 16. Absorptive hypercalciuria is defined as an increased urinary calcium excretion after an oral calcium load and is due to increased intestinal absorption of calcium. Alteration of vitamin D receptors and/or sensitivity has been suggested as the etiology. Renal hypercalciuria is due to impaired renal tubular reabsorption of calcium and leads to secondary hyperparathyroidism. 17. Reabsorptive hypercalciuria is due to hyperparathyroidism. The administration of thiazides to patients with primary hyperparathyroidism exacerbates hypercalcemia. Parathormone-like hormone resulting in hypercalcemia is produced by lung, breast, renal, penile, and head and neck tumors; lymphoma; and myeloma. 18. Hyperoxaluria is defined as greater than 40 mg/day excreted in the urine. Foods that are oxalate rich include nuts, chocolate, brewed tea, spinach, broccoli, strawberries, and rhubarb. 19. Hyperuricosuria is defined as urinary uric acid excretion exceeding 600 mg/day. 20. Hyperuricosuria promotes sodium urate formation, which promotes calcium oxalate stone formation through heterogenous nucleation. 21. Citrate inhibits stone formation by complexing with calcium and thereby preventing spontaneous nucleation of calcium oxalate; it inhibits agglomeration and growth of the crystal, and it enhances the inhibitory effect of Tamm-Horsfall glycoprotein. It prevents heterogeneous nucleation of calcium oxalate by monosodium urate. 22. Hypocitraturia is defined as urinary citrate excretion of less than 320 mg/day. 23. Renal tubular acidosis, type 1 (distal tubular RTA) is characterized by calcium phosphate stone formation, hypercalciuria, hypocitraturia, and an increased urinary pH. 24. Low magnesium levels result in reduced inhibitory activity and are often associated with decreased urinary citrate levels. 25. Cystine stones form due to a defect in the transport of four amino acids: cystine, lysine, ornithine, and arginine. It is inherited as an autosomal recessive and accounts for up to 10% of stones in children. There are two genes involved in the inheritance of the disease. There are three types based on urine excretion amounts: types A, B, and AB. 26. Stones of infection (struvite stones) are composed of magnesium ammonium phosphate and may contain carbonate apatite; they occur in association with urea-splitting bacteria. Urease-producing pathogens include Proteus, Klebsiella, Pseudomonas, and Staphylococcus. 27. The cause of stones associated with horseshoe kidneys and ureteropelvic junction obstructions is due to both the anatomic abnormality resulting in stasis and an underlying metabolic abnormality. 28. Medullary sponge kidney is characterized by ectasia of the renal collecting ducts and leads to stones through renal acidifying defects, hypercalciuria, and hypocitraturia. 29. Most stones in pregnancy pass spontaneously. 30. The most important determinate of uric acid stone formation is low urinary pH. Low urinary pH in uric acid stone formers is likely due to impaired ammoniagenesis associated with insulin resistance. 31. Medications that may precipitate as stones include triamterene, silica, indinavir, ephedrine, and ciprofloxacin. 32. Heterogeneous nucleation occurs when microscopic impurities or other constituents in the urine promote nucleation by providing a surface on which the crystal components can grow. 33. Intestinal oxalate absorption is modulated by dietary oxalate and calcium intake and by the presence or absence of O. formigenes. 34. Acid–base status determines urinary citrate excretion. Metabolic acidosis reduces citrate excretion. 35. The sarcoid granuloma produces 1,25-dihydroxyvitamin D3 , causing increased intestinal calcium absorption, hypercalcemia, and hypercalciuria. 36. Malabsorption from any cause, including small bowel resection, intrinsic disease, or jejunoileal bypass, increases luminal fatty acids and bile salts. Calcium, which normally complexes with oxalate, forming a soluble complex that is lost in the stool, instead binds to fatty acids, thereby increasing luminal oxalate available for absorption. In addition, poorly absorbed bile salts increase colonic permeability to oxalate, further increasing oxalate absorption. 37. Type 1 or distal tubule RTA is characterized by an impairment in hydrogen ion secretion. Type 2, or proximal RTA, is characterized by impaired bicarbonate reabsorption in the proximal tubule. Type 4 RTA is common in diabetics with chronic renal damage who demonstrate aldosterone resistance.
less soluble in urine
etiology of ammonium acid urate stone formation in patients abusing laxatives is. (3)
Chronic dehydration, intracellular acidosis, and low urinary sodium.
The primary mechanism of action of citrate in preventing stone formation is:
COMPLEXING CALCIUM IN THE URINE --> thereby reducing ionic calcium and urinary saturation of calcium oxalate.
Type 1 (distal) RTA is characterized by which abnormality?
it is also associated with impaired NH4 secretion, and urinary ph >5,5 even with acid load
The primary defect in type 2 (proximal) RTA
failure of bicarbonate reabsorption in the proximal tubule
Carbonic anhydrase inhibitors such as acetazolamide and topiramate block __ in the renal proximal and distal tubules, thereby preventin __ and inducing a __. Similar to RTA, carbonic anhydrase inhibition results in the formation of ___ because of the high urine pH, hypercalciuria, and hypocitraturia.
reabsorption of bicarbonate
CALCIUM PHOSPHATE STONES
Physiologic change of pregnancy favoring stone formation:
Increased calcium excretion. Placental production of 1,25- dihydroxyvitamin D3 increases intestinal calcium absorption, further increasing urinary calcium.
Uric acid is thought to promote calcium oxalate stone formation by removing urinary inhibitors, by ___ calcium oxalate in solution and by (2)
a. Matrix-Gla protein b. Bikunin c. Citrate d. Pyrophosphates are all natural __ of stone formation.
Renal reabsorption of the four dibasic amino acids— cystine, ornithine, lysine, and arginine—is affected by dysfunction of the heteromeric amino acid transporter located in the renal proximal tubule. Because of the poor solubility of ___ in urine, only ___stones occur in this condition.
affected in impaired renal reabsorbption in cystinuria --> __
M___ and c__ inhibit crystal aggregation (the former complexes with oxalate and the latter with calcium);
n__ inhibits nucleation, growth, and aggregation;
___ glycoprotein inhibits aggregation;
o___ inhibits crystal growth, nucleation, and aggregation of calcium oxalate crystals
Magnesium and citrate