Stones: Epidemiology and Pathogenesis: Difference between revisions
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*# '''<span style="color:#ff0000">Calcium oxalate (60%)</span>''' | *# '''<span style="color:#ff0000">Calcium oxalate (60%)</span>''' | ||
*# '''<span style="color:#ff0000">Hydroxyapatite</span> (20%)''' | *# '''<span style="color:#ff0000">Hydroxyapatite</span> (20%)''' | ||
*# '''<span style="color:#ff0000">Brushite</span> (2%)''' | *# '''<span style="color:#ff0000">Calcium Phosphate/Brushite</span> (2%)''' | ||
* '''<span style="color:#ff0000">Non-calcium containing stones</span>''' | * '''<span style="color:#ff0000">Non-calcium containing stones</span>''' | ||
*# '''<span style="color:#ff0000">Uric acid</span> (7%)''' | *# '''<span style="color:#ff0000">Uric acid</span> (7%)''' | ||
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*# '''<span style="color:#ff0000">Type 1 (distal) RTA</span>''' | *# '''<span style="color:#ff0000">Type 1 (distal) RTA</span>''' | ||
*#* '''<span style="color:#ff0000">Most common form of RTA and most commonly associated with kidney stones</span>''' (up to 70% of adults with type 1 RTA have kidney stones) | *#* '''<span style="color:#ff0000">Most common form of RTA and most commonly associated with kidney stones</span>''' (up to 70% of adults with type 1 RTA have kidney stones) | ||
*#* '''Characterized by (5):''' | *#* '''<span style="color:#ff0000">Characterized by (5):</span>''' | ||
*#*# ''' | *#*# '''<span style="color:#ff0000">Increased urinary pH''' (>6.0) | ||
*#*# ''' | *#*#'''Hyperchloremic, non-anion gap metabolic acidosis''' | ||
*#*# '''Hypercalcuria''' | *#*# </span>'''Hypercalcuria''' | ||
*#*# '''Hypocitraturia''' | *#*# '''Hypocitraturia''' | ||
*#*# '''Hypokalemia''' | *#*# '''Hypokalemia''' | ||
*#** '''Due to impaired acid (H+, hydrogen is first element in periodic table so type 1 ) excretion into the urine in the presence of systemic acidosis, from dysfunction of the alpha-type intercalated cells''', which secrete protons into the urine via an apical H+-ATPase | *#** '''<span style="color:#ff0000">Due to impaired acid (H+, hydrogen is first element in periodic table so type 1 ) excretion into the urine in the presence of systemic acidosis, from dysfunction of the alpha-type intercalated cells</span>''', which secrete protons into the urine via an apical H+-ATPase | ||
*#*** Metabolic acidosis may cause a negative calcium balance as a result of impaired renal tubular reabsorption of calcium in the proximal tubule, leading to excessive renal loss of calcium. In addition, intestinal calcium absorption is diminished in patients with persistent acidosis. Slow dissolution of bone mineral can also be identified as calcium and phosphate act as buffering mechanisms to correct the acidosis. Chronic acidosis has been cited as a major factor in the genesis of bone disease. | *#*** Metabolic acidosis may cause a negative calcium balance as a result of impaired renal tubular reabsorption of calcium in the proximal tubule, leading to excessive renal loss of calcium. In addition, intestinal calcium absorption is diminished in patients with persistent acidosis. Slow dissolution of bone mineral can also be identified as calcium and phosphate act as buffering mechanisms to correct the acidosis. Chronic acidosis has been cited as a major factor in the genesis of bone disease. | ||
*#** Patients with the incomplete form of distal RTA are not persistently acidemic despite their inability to lower urinary pH with an acid load. '''The diagnosis of incomplete distal RTA can be confirmed by inadequate urinary acidification''' after an ammonium chloride loading test. | *#** Patients with the incomplete form of distal RTA are not persistently acidemic despite their inability to lower urinary pH with an acid load. '''The diagnosis of incomplete distal RTA can be confirmed by inadequate urinary acidification''' after an ammonium chloride loading test. | ||
*#* '''Potassium citrate therapy is able to correct the metabolic acidosis and hypokalemia''' | *#* '''Potassium citrate therapy is able to correct the metabolic acidosis and hypokalemia''' | ||
*#* '''<span style="color:#ff0000">Most common stone composition associated with Type 1/distal RTA is calcium phosphate</span>''' as a result of increased urinary pH, hypercalciuria, and hypocitraturia | *#* '''<span style="color:#ff0000">Most common stone composition associated with Type 1/distal RTA is calcium phosphate</span>''' as a result of increased urinary pH, hypercalciuria, and hypocitraturia | ||
*# '''Type 2 (proximal) RTA''' | *#*'''<span style="color:#ff0000">Associated with nephrocalcinosis on imaging</span>''' | ||
*#* '''Due to impaired bicarbonate (bi=2, type 2) reabsorption''' | *# '''<span style="color:#ff0000">Type 2 (proximal) RTA</span>''' | ||
*#* '''<span style="color:#ff0000">Due to impaired bicarbonate (bi=2, type 2) reabsorption</span>''' | |||
*#* 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. 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).''' | *#* 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. 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).''' | ||
*#* '''Nephrolithiasis is uncommon in this disorder as urinary citrate levels are not decreased, in contrast to type 1 RTA''' | *#* '''Nephrolithiasis is uncommon in this disorder as urinary citrate levels are not decreased, in contrast to type 1 RTA''' | ||
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*#* Associated with hyperkalemia | *#* Associated with hyperkalemia | ||
*#* '''Nephrolithiasis is uncommon in this disorder''' | *#* '''Nephrolithiasis is uncommon in this disorder''' | ||
=== Hypomagnesiuria === | === Hypomagnesiuria === | ||
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=== Urine pH === | === Urine pH === | ||
* '''At low urine pH (<5.5), the undissociated form of uric acid predominates, leading to uric acid and/or calcium stone formation.''' | * '''<span style="color:#ff0000">At low urine pH (<5.5), the undissociated form of uric acid predominates, leading to uric acid and/or calcium stone formation.</span>''' | ||
** '''Any disorder leading to low urine pH may predispose to stone formation.''' | ** '''Any disorder leading to low urine pH may predispose to stone formation.''' | ||
** '''Calcium oxalate stones can form in low urine pH as a result of heterogeneous nucleation with uric acid crystals'''. | ** '''Calcium oxalate stones can form in low urine pH as a result of heterogeneous nucleation with uric acid crystals'''. | ||
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== Uric acid stones == | == Uric acid stones == | ||
'''Determinants of uric acid stone formation (3):''' | '''<span style="color:#ff0000">Determinants of uric acid stone formation (3):</span>''' | ||
# '''Low urine pH (<5.5) (most important)''' | # '''<span style="color:#ff0000">Low urine pH (<5.5) (most important)</span>''' | ||
#* Urine pH remains the most cost-effective means of screening for this condition and monitoring therapy. | #* Urine pH remains the most cost-effective means of screening for this condition and monitoring therapy. | ||
# '''Low urine volume''' | # '''<span style="color:#ff0000">Low urine volume</span>''' | ||
# '''Hyperuricosuria''' | # '''<span style="color:#ff0000">Hyperuricosuria</span>''' | ||
=== Causes === | === Causes === | ||
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==== Acquired ==== | ==== Acquired ==== | ||
# '''Diabetes''' | # '''<span style="color:#ff0000">Diabetes''' | ||
#* '''Diabetic stone formers have a lower urine pH''' compared with non-diabetic stone formers '''due to insulin resistance''' | #* '''Diabetic stone formers have a lower urine pH''' compared with non-diabetic stone formers '''due to insulin resistance''' | ||
#** In normal individuals, insulin stimulates ammoniagenesis in renal tubule cells by promoting gluconeogenesis from glutamine and by stimulating ammonium excretion by the proximal tubular sodium/hydrogen exchanger. Failure of the renal tubule cells to respond to insulin '''results in defective ammonia production and/or excretion, thereby leading to a reduction in urinary pH and uric acid stone formation'''. | #** In normal individuals, insulin stimulates ammoniagenesis in renal tubule cells by promoting gluconeogenesis from glutamine and by stimulating ammonium excretion by the proximal tubular sodium/hydrogen exchanger. Failure of the renal tubule cells to respond to insulin '''results in defective ammonia production and/or excretion, thereby leading to a reduction in urinary pH and uric acid stone formation'''. | ||
#* '''Diabetic stone formers are approximately 6x more likely to develop a uric acid stone'''. | #* '''Diabetic stone formers are approximately 6x more likely to develop a uric acid stone'''. | ||
#** Uric acid stones are found in 34% of stone-forming patients with diabetes mellitus compared to 6% of non-diabetic stone formers | #** Uric acid stones are found in 34% of stone-forming patients with diabetes mellitus compared to 6% of non-diabetic stone formers | ||
# '''Obesity''' | # '''<span style="color:#ff0000">Obesity</span>''' | ||
# '''Metabolic syndrome''' | # '''<span style="color:#ff0000">Metabolic syndrome</span>''' | ||
# '''Tumour lysis syndrome''' | # '''<span style="color:#ff0000">Tumour lysis syndrome</span>''' | ||
# '''Volume depletion''' | # '''<span style="color:#ff0000">Volume depletion</span>''' | ||
# '''High animal protein intake''' | # '''<span style="color:#ff0000">High animal protein intake</span>''' | ||
# '''Chronic diarrhea''' | # '''<span style="color:#ff0000">Chronic diarrhea</span>''' | ||
# '''Uricosuric drugs''' | # '''<span style="color:#ff0000">Uricosuric drugs</span>''' | ||
# '''Idiopathic''' | # '''<span style="color:#ff0000">Idiopathic</span>''' | ||
* '''All 11 conditions associated with hyperuricosuria listed above''' | * '''<span style="color:#ff0000">All 11 conditions associated with hyperuricosuria listed above</span>''' | ||
== | == Calcium Phosphate Stones == | ||
* '''Stones are considered poorly radioopaque on imaging'''§ | * '''<span style="color:#ff0000">Associated with (4):</span>''' | ||
#'''<span style="color:#ff0000">RTA Type 1</span>''' | |||
#'''<span style="color:#ff0000">Primary hyperparathyroidism</span>''' | |||
#'''<span style="color:#ff0000">Medullary sponge kidney</span>''' | |||
#'''<span style="color:#ff0000">Use of carbonic anhydrase inhibitors</span>''' | |||
== Cystine Stones == | |||
* '''Stones are considered poorly radioopaque on imaging'''[https://uroweb.org/guideline/urolithiasis/ §] | |||
=== Causes === | === Causes === | ||
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*** '''Used for screening purposes to identify patients with cystine stone disease''' who are undergoing a 24 hour urine collection for evaluation. | *** '''Used for screening purposes to identify patients with cystine stone disease''' who are undergoing a 24 hour urine collection for evaluation. | ||
== Infection | == Infection Stones (magnesium ammonium phosphate) == | ||
* '''Struvite stones occur only in association with urinary infection by urea-splitting organisms.''' | * '''<span style="color:#ff0000">Struvite stones occur only in association with urinary infection by urea-splitting organisms.</span>''' | ||
** '''Urease hydrolyzes urea, forming ammonium and carbon dioxide, which increases urinary pH.''' | ** '''Urease hydrolyzes urea, forming ammonium and carbon dioxide, which increases urinary pH.''' | ||
*** Alkaline urine promotes supersaturation and precipitation of crystals of magnesium ammonium phosphate and carbonate apatite. | *** Alkaline urine promotes supersaturation and precipitation of crystals of magnesium ammonium phosphate and carbonate apatite. | ||
* '''Most common urease-producing pathogens (4):''' | * '''<span style="color:#ff0000">Most common urease-producing pathogens (4):</span>''' | ||
*# '''Proteus (most common)''' | *# '''<span style="color:#ff0000">Proteus (most common)</span>''' | ||
*# '''Klebsiella''' | *# '''<span style="color:#ff0000">Klebsiella</span>''' | ||
*# '''Pseudomonas''' | *# '''<span style="color:#ff0000">Pseudomonas</span>''' | ||
*# '''Staphylococcus aureus''' | *# '''<span style="color:#ff0000">Staphylococcus aureus</span>''' | ||
** '''Some yeasts and mycoplasma species have the capacity to synthesize urease''' | ** '''Some yeasts and mycoplasma species have the capacity to synthesize urease''' | ||
** '''Although E. coli is a common cause of UTIs, only rare species of E. coli produce urease''' | ** '''<span style="color:#ff0000">Although E. coli is a common cause of UTIs, only rare species of E. coli produce urease</span>''' | ||
* '''Pathogenesis''' | * '''Pathogenesis''' | ||
** '''Occur more often in females''' than males by a ratio of 2:1 '''because infection stones occur most commonly in those prone to frequent UTIs.''' | ** '''Occur more often in females''' than males by a ratio of 2:1 '''because infection stones occur most commonly in those prone to frequent UTIs.''' | ||
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** '''Spinal cord–injured patients are at particular risk for both infection and metabolic stones owing to neurogenic urinary tract dysfunction and hypercalciuria related to immobility''' | ** '''Spinal cord–injured patients are at particular risk for both infection and metabolic stones owing to neurogenic urinary tract dysfunction and hypercalciuria related to immobility''' | ||
* '''Commonly produce staghorn stones; however, other crystals, including cystine, calcium oxalate monohydrate, and uric acid, can assume a staghorn configuration''' | * '''Commonly produce staghorn stones; however, other crystals, including cystine, calcium oxalate monohydrate, and uric acid, can assume a staghorn configuration''' | ||
== Other stones == | == Other stones == | ||
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* '''Predominately composed (65%) of organic proteins''', sugars, and glucosaminses, unlike other stones that have minimal organic material (2.5%) | * '''Predominately composed (65%) of organic proteins''', sugars, and glucosaminses, unlike other stones that have minimal organic material (2.5%) | ||
** Among the proteins incorporated into the matrix substance are Tamm-Horsfall protein, nephrocalcin, a γ-carboxyglutamic acid–rich protein, renal lithostathine, albumin, glycosaminoglycans, free carbohydrates, and a mucoprotein called matrix substance A | ** Among the proteins incorporated into the matrix substance are Tamm-Horsfall protein, nephrocalcin, a γ-carboxyglutamic acid–rich protein, renal lithostathine, albumin, glycosaminoglycans, free carbohydrates, and a mucoprotein called matrix substance A | ||
* ''' | * '''Risk factors (4)''' | ||
* '''Challenging to diagnose preoperatively, as they can mimic upper tract collecting system soft-tissue masses''' and require a high index of suspicion | *#'''Recurrent UTI by urea-splitting bacteria''' | ||
* '''Radiolucent on plain film x-ray''' | *#'''Previous stone formation''' | ||
*#'''Previous surgery due to urolithiasis''' | |||
*#'''Obstructive uropathy''' | |||
* '''Diagnosis and Evaluation''' | |||
**'''Imaging''' | |||
***'''Challenging to diagnose preoperatively, as they can mimic upper tract collecting system soft-tissue masses''' and require a high index of suspicion | |||
*** '''Radiolucent on plain film x-ray''' | |||
=== Xanthine stones === | === Xanthine stones === | ||
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** 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. | ** 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. | ||
=== Medication associated stones === | === Medication associated stones[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1508366] === | ||
*'''Lotta Good Drugs Cause Calculi FIT TEST (12):''' | *'''<span style="color:#0000ff">Lotta Good Drugs Cause Calculi FIT TEST (12):''' | ||
*# ''' | *# '''<span style="color:#0000ff">L<span style="color:#ff0000">axatives''' | ||
*# ''' | *# '''<span style="color:#0000ff">G<span style="color:#ff0000">uaifenesin''' | ||
*# '''Vitamin D''' | *# '''<span style="color:#ff0000">Vitamin <span style="color:#0000ff">D''' | ||
*# '''Vitamin C''' | *# '''<span style="color:#ff0000">Vitamin <span style="color:#0000ff">C</span>''' in high doses is converted to oxalate and may induce hyperoxaluria | ||
*# ''' | *# '''<span style="color:#0000ff">C<span style="color:#ff0000">arbonic anhydrase inhibitors''' | ||
*#* May be associated with the formation of calcium-based calculi, '''particularly calcium phosphate''' | *#*E.g. acetazolamide | ||
*# ''' | *#*May be associated with the formation of calcium-based calculi, '''particularly calcium phosphate''' | ||
*# '''<span style="color:#0000ff">F<span style="color:#ff0000">urosemide''' | |||
*#* '''Thiazides''' cause intracellular acidosis and '''subsequent hypocitraturia''' | *#* '''Thiazides''' cause intracellular acidosis and '''subsequent hypocitraturia''' | ||
*# ''' | *# '''<span style="color:#0000ff">I<span style="color:#ff0000">ndinavir''' | ||
*#* '''MOA: protease inhibitor''' | *#* '''MOA: protease inhibitor''' | ||
*#* '''Used in patients with HIV/AIDS.''' | *#* '''Used in patients with HIV/AIDS.''' | ||
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*#* '''Now infrequently used''', replaced with newer generation agents. Kidney stone formation has been associated with a number of newer anti-retroviral agents. | *#* '''Now infrequently used''', replaced with newer generation agents. Kidney stone formation has been associated with a number of newer anti-retroviral agents. | ||
*#* '''Radiolucent on plain film and may not be seen on CT''' | *#* '''Radiolucent on plain film and may not be seen on CT''' | ||
*# ''' | *# '''<span style="color:#0000ff">T<span style="color:#ff0000">opiramate''' | ||
*#* Used to treat epilepsy and prevent migraines | *#* '''MOA: carbonic anhydrase inhibitor''' | ||
*#*Used to treat epilepsy and prevent migraines | |||
*#* Creates a chronic intracellular acidosis resulting '''in a urinary milieu similar to distal RTA''' with hyperchloremic acidosis, high urine pH, extremely low urinary citrate, and hypercalciuria. | *#* Creates a chronic intracellular acidosis resulting '''in a urinary milieu similar to distal RTA''' with hyperchloremic acidosis, high urine pH, extremely low urinary citrate, and hypercalciuria. | ||
*#* '''Treatment may be potassium citrate''' or cessation of the medication if possible. | *#* '''Treatment may be potassium citrate''' or cessation of the medication if possible. | ||
*# ''' | *# '''<span style="color:#0000ff">T<span style="color:#ff0000">riamterene''' | ||
*#* MOA: potassium-sparing diuretic | *#* '''MOA: potassium-sparing diuretic''' | ||
*#* Used for the treatment of hypertension | *#* Used for the treatment of hypertension | ||
*#* '''Radiolucent''' | *#* '''Radiolucent''' | ||
*# ''' | *# '''<span style="color:#0000ff">E<span style="color:#ff0000">phedrine''' | ||
*# ''' | *# '''<span style="color:#0000ff">S<span style="color:#ff0000">ilicates''' | ||
*# ''' | *# '''<span style="color:#0000ff">T<span style="color:#ff0000">MP/SMX''' | ||
== Anatomic predisposition to stones == | == Anatomic predisposition to stones == | ||