2. Moderators:
Professors:
ā¢ Prof. Dr. G. Sivasankar, M.S., M.Ch.,
ā¢ Prof. Dr. A. Senthilvel, M.S., M.Ch.,
Asst Professors:
ā¢ Dr. J. Sivabalan, M.S., M.Ch.,
ā¢ Dr. R. Bhargavi, M.S., M.Ch.,
ā¢ Dr. S. Raju, M.S., M.Ch.,
ā¢ Dr. K. Muthurathinam, M.S., M.Ch.,
ā¢ Dr. D. Tamilselvan, M.S., M.Ch.,
ā¢ Dr. K. Senthilkumar, M.S., M.Ch.
Dept of Urology, GRH and KMC, Chennai. 2
3. ā¢ The causes of nephrolithiasis is classified as
a) Calcium based calculi ā Hypercalciuria
Hyperuricosuric calcium oxalate stones
Hyperoxaluria
Hypocitraturic calcium stones
Hypomagnesuric calcium stones
b) Uric acid based calculi
c) Cystinuria
d) Infective calculi (struvite)
e) Low urine volumes
3
Dept of Urology, GRH and KMC, Chennai.
4. HYPERCALCIURIA
Most common predisposing factor for stone formation
Patient with oxalate stone excrete higher fraction of dietary calcium
(nrml<4mg/kg/day) or >200mg/day
Hypercalciuria is seen in frequency dysuria synd,beckwith-wiedmann
synd & cystic fibrosis
Its of 4 types- Absorptive, Renal, Resorptive, Idiopathic
4
Dept of Urology, GRH and KMC, Chennai.
5. ā¢ Absorptive
-most common cause
-due to inc intestinal absorption of calcium
a)Due to overly aggressive vit D supplement
b)Excessive ingestion of calcium containing food
Two types
Type I-a)hyper calciuria with out calcium load
b)uncommon, most severe type
5
Dept of Urology, GRH and KMC, Chennai.
6. ā¢ Type II- hyper calciuria with high calcium intake
ā¢ Type III-a)rare
b)renal defect cause excess urinary phosphate excretion due to
inactivation of renal epithelial NaPi2(sodium phosphate co transporter)
-hypophosphatemia-activation of vitD3-increased absorption of Ca+ &
phosphate-hyper calciuria
6
Dept of Urology, GRH and KMC, Chennai.
7. ā¢ Renal
a)Defect in kidney āallows excess calcium excretion regardless of
SrCa+,body stores, calcium ingestion
b)Calcium creatinine ratio high(>.20)
c)Secondary parathyroidism
7
Dept of Urology, GRH and KMC, Chennai.
8. Resorptive Hypercalciuria
ā¢ is an infrequent abnormality
ā¢ most commonly associated with primary hyperparathyroidism.
ā¢ Primary hyperparathyroidism is due to parathyroid tumourā¦.
IDIOPATHIC Hypercalciuria
ā¢ found in normal people & stone formers
ā¢ Inc urine ca+ but no serum abnormalities
8
Dept of Urology, GRH and KMC, Chennai.
9. absorptive renal Resorptive
Serum calcium Normal normal Elevated
Parathyroid
function
Suppressed Stimulated Stimulated
Fasting urinay ca+ Normal Elevated Elevated
Intestinalca+
absorption
elevated Elevated Elevated
9
Dept of Urology, GRH and KMC, Chennai.
10. Hyperoxaluria
ā¢ > 40mg/day
ā¢ Causes of Hyperoxaluria
ā¢ primary Hyperoxaluria); disorders in biosynthetic pathways
ā¢ enteric Hyperoxaluria - intestinal malabsorptive states associated
with inflammatory bowel disease, celiac sprue, or intestinal resection
ā¢ dietary Hyperoxaluria excessive dietary intake or high substrat elevels
(vitamin C) .
10
Dept of Urology, GRH and KMC, Chennai.
11. Primary Hyperoxaluria
ā¢ Mutations of gene (AGXT) - primary enzyme alanine/glyoxalate
aminotransferase (AGT) - catalyzing glyoxalate conversion to glycine
ā¢ rare autosomal recessive disorder in glyoxalate metabolism -
conversion of glyoxalate to glycine is prevented,
ā¢ leading to preferential oxidative conversion of glyoxalate to oxalate,
an end product of metabolism result in primary Hyperoxaluria type 1,
11
Dept of Urology, GRH and KMC, Chennai.
12. ā¢ Primary Hyperoxaluria type 2 (PH2) - defect in glyoxalate reductase/
hydroxypyruvate reductase (GRHPR) in the liver, resulting in
Hyperoxaluria nephrolithiasis,
12
Dept of Urology, GRH and KMC, Chennai.
13. Enteric Hyperoxaluria
ā¢ The most common cause of acquired hyperoxaluria
ā¢ is associated with chronic diarrheal states, by which fat
malabsorption
ā¢ results in saponification of fatty acids with divalent cations such as
calcium and magnesium,
ā¢ thereby reducing calcium oxalate complexation and increasing the
pool of available oxalate for reabsorption
13
Dept of Urology, GRH and KMC, Chennai.
14. Dietary Hyperoxaluria
ā¢ Over eating nuts, chocolate, brewed tea, spinach, broccoli,
strawberries, and rhubarb
ā¢ increased animal protein can also increase urinary levels of calcium
and oxalate
ā¢ Severe cal restriction
ā¢ More supplementation of vit-c
14
Dept of Urology, GRH and KMC, Chennai.
15. Idiopathic Hyperoxaluria
ā¢ mild Hyperoxaluria is as important a factor as hypercalciuria in the
pathogenesis of idiopathic calcium oxalate stones
15
Dept of Urology, GRH and KMC, Chennai.
16. Hyperuricosuria
ā¢ uric acid > 600 mg/day.
ā¢ 10% of calcium stone formers have high urinary uric acid
ā¢ Hyperuricosuria increases urinary levels of monosodium urate, which in turn
promotes calcium oxalate stone formation.
ā¢ At pH less than 5.5, the undissociated form of uric acid predominates, leading
to uric acid and/or calcium oxalate stone formation.
ā¢ Uric acid may also reduce the effectiveness of naturally occurring inhibitors
of crystallization .
16
Dept of Urology, GRH and KMC, Chennai.
17. ā¢ The most common cause of hyperuricosuria is increased dietary
purine intake
.
ā¢ acquired disease - gout, myeloproliferative and lymphoproliferative
disorders, multiple myeloma, secondary polycythemia, pernicious
anemia, hemolytic disorders, hemoglobinopathies
ā¢ hereditary renal hypouricemia/hyperuricosuria is due to Mutations
in the gene encoding URAT1 [urate transporter in the proximal renal
tubule, the anion exchanger URAT1 ]
17
Dept of Urology, GRH and KMC, Chennai.
18. Hypocitraturia
ā¢ urinary citrate < 320 mg/day
ā¢ Acid-base state is the primary determinant of urinary citrate
excretion.
ā¢ Metabolic acidosis reduces urinary citrate levels secondary to
enhanced renal tubular reabsorption and decreased synthesis of
citrate in peritubular cells
18
Dept of Urology, GRH and KMC, Chennai.
19. ā¢ Citrate is an important Inhibitor
ā¢ mechanisms.
ā¢ First ---reduces urinary saturation of calcium
ā¢ Second --directly prevents spontaneous nucleation of calcium oxalate
ā¢ Third -- inhibits agglomeration and sedimentation of calcium oxalate
crystals , growth of calcium oxalate and calcium phosphate crystals
ā¢ Finally --normal urinary citrate levels can enhance the inhibitory
effect of Tamm-Horsfall glycoprotein
19
Dept of Urology, GRH and KMC, Chennai.
20. ā¢ Citrate levels in the urine increase in alkalotic states, as well as
ā¢ with elevated levels of PTH, estrogen, growth hormone, and vitamin
D.
20
Dept of Urology, GRH and KMC, Chennai.
21. Low Urine pH
ā¢ At low urine pH (<5.5), the undissociated form of uric acid
predominates,
ā¢ leading to uric acid and/or calcium stone formation.
ā¢ Calcium oxalate stones form as a result of heterologous nucleation
with uric acid crystals
21
Dept of Urology, GRH and KMC, Chennai.
22. Renal Tubular Acidosis
ā¢ RTA is a clinical syndrome characterized by metabolic acidosis
resulting from defects in renal tubular hydrogen ion secretion or
bicarbonate reabsorption.
ā¢ Types 1,2,4
22
Dept of Urology, GRH and KMC, Chennai.
23. ā¢ Type 1 (Distal) RTA. comprises a syndrome of
ā¢ abnormal collecting duct function characterized by inability to acidify
the urine in the presence of systemic acidosis.
ā¢ The classic findings include
ā¢ hypokalemic, hyperchloremic,
ā¢ nonāanion gap metabolic acidosis along with nephrolithiasis,
nephrocalcinosis, and elevated urine pH (>6.0)
23
Dept of Urology, GRH and KMC, Chennai.
24. ā¢ The most common stone is calcium phosphate as a result of
hypercalciuria, hypocitraturia, and increased urinary pH
ā¢ The metabolic acidosis promotes
ā¢ bone demineralization, which leads to secondary
hyperparathyroidism and hypercalciuria.
ā¢ Profound hypocitraturia the most important factor in stone
formation
24
Dept of Urology, GRH and KMC, Chennai.
25. ā¢ Type 2 (Proximal) RTA. is characterized by
ā¢ a defect in HCO3ā reabsorption associated with initial high urine pH
that normalizes as plasma HCO3ā decreases and the amount of
filtered HCO3ā falls
25
Dept of Urology, GRH and KMC, Chennai.
26. ā¢ Type 4 (Distal) is associated with chronic renal damage, interstitial
renal disease and diabetic nephropathy.
ā¢ Reduction in glomerular filtration results in hyperkalemic,
hyperchloremic metabolic acidosis due to loss of HCO3ā in the urine
and decreased excretion of ammonium
ā¢ Aldosterone resistance is commonly associated with type 4 RTA
26
Dept of Urology, GRH and KMC, Chennai.
27. Hypomagnesuria
ā¢ Hypomagnesuria is a rare cause of nephrolithiasis, affecting less than
1% of stone formers as an isolated abnormality,
ā¢ Low urinary magnesium is also associated with decreased urinary
citrate levels,
ā¢ Reduce inhibitory activity
27
Dept of Urology, GRH and KMC, Chennai.
28. Uric Acid Stones
ā¢ The three main determinants factors---
ā¢ low pH [most important pathogenetic factor ]
ā¢ low urine volume, [hot temperature]
ā¢ hyperuricosuria
ā¢ most patients with uric acid stones have normal uric acid excretion
with persistent low urine pH
28
Dept of Urology, GRH and KMC, Chennai.
29. ā¢ congenital, acquired, or idiopathic causes.
ā¢ Congenital - associated with uric acid stones involve renal tubular
urate transport or uric acid metabolism , leading to hyperuricosuria.
ā¢ Acquired - chronic diarrhea, volume depletion, myeloproliferative
disorders, high animal protein intake, and uricosuric drugs may affect
any of the three factors determining uric acid stone formation.
ā¢ āgouty diathesisā or idiopathic low urine ph
29
Dept of Urology, GRH and KMC, Chennai.
30. Low urine ph
ā¢ Higher prevalence in non āinsulin dependent diabetes
ā¢ Impaired ammonium production or excretion as a result of insulin
resistance could leave hydrogen ions unbuffered in the urine, thereby
leading to reduction in urine pH
30
Dept of Urology, GRH and KMC, Chennai.
31. Cystine Stones
ā¢ Cystinuria -autosomal recessive -characterized by a defect in
intestinal and renal tubular transport of dibasic amino acids, resulting
in excessive urinary excretion of Cystine
ā¢ the defect also results in high urinary concentrations of lysine,
ornithine, and arginine, the poor solubility of Cystine leads to stone
formation
31
Dept of Urology, GRH and KMC, Chennai.
32. ā¢ main contributor to Cystine crystallization is
supersaturation - no specific inhibitor of Cystine
crystallization in the urine. Because of the poor
solubility of Cystine in urine- precipitation of Cystine
and subsequent stone formation occur at physiologic
urine conditions.
32
Dept of Urology, GRH and KMC, Chennai.
33. Infection Stones
ā¢ Infection stones (Bichler et al, 2002) are composed primarily of
magnesium ammonium phosphate hexahydrate [MgNH4PO4 ]
ā¢ āstruviteā stones (magnesium ammonium phosphate) - urinary
infection by urea-splitting bacteria like proteus vulgaris
33
Dept of Urology, GRH and KMC, Chennai.
34. ā¢ Pathogenesis
ā¢ The process of urealysis by urease provides an alkaline urine and
sufficient concentrations of carbonate and ammonia to induce the
formation of infection stones.
34
Dept of Urology, GRH and KMC, Chennai.
35. ā¢ Urinary urea, a constituent of normal urine, is first hydrolyzed to
ammonia and carbon dioxide in the presence of bacterial urease:
ā¢ (NH2 )2CO+H2O =2NH3 + CO2
ā¢ The alkaline urine that results from this reaction (pH 7.2 to 8.0)
ā¢ favors the formation of ammonium:
ā¢ NH3 + H2O=NH4+ +OHā
35
Dept of Urology, GRH and KMC, Chennai.
36. ā¢ Under physiologic conditions, the alkaline urine prevent further
generation of ammonium.
ā¢ in the presence of urease, ammonia continues to be produced
despite alkaline urine, further increasing urinary pH.
ā¢ The alkaline environment also promotes the hydration of carbon
dioxide to carbonic acid, which then dissociates into HCO3ā and H+.
ā¢ Further dissociation of HCO3ā yields carbonate and two hydrogen
ions
36
Dept of Urology, GRH and KMC, Chennai.
37. ā¢ The dissociation of hydrogen phosphate under alkaline conditions provides
phosphate
ā¢ H2PO4 _= H + + HPO4
ā¢ HPO4 = H + PO 4
ā¢ with physiologic concentrations of magnesium, provides the constituents
necessary for precipitation of struvite.
ā¢ In addition, the concentrations of calcium, phosphate & carbonate allow
precipitation of carbonate apatite and hydroxyapatite, thereby comprising the
components of infection Stones
37
Dept of Urology, GRH and KMC, Chennai.
38. Bacteriology
ā¢ The most common urease-producing pathogens are Proteus, [Proteus
mirabilis], Klebsiella, Pseudomonas, and Staphylococcus
ā¢ Escherichia coli is a common cause of urinary tract infections, only
rare species of E.coli produce urease
38
Dept of Urology, GRH and KMC, Chennai.
39. ā¢ infection stones occur most commonly in those prone to frequent
urinary tract infections,[ struvite stones more often in women]
39
Dept of Urology, GRH and KMC, Chennai.
40. Xanthine and Dihydroxyadenine
ā¢ Xanthine stones comprise a rare stone type -- often confused with uric acid stones because both
are radiolucent.
ā¢ an inherited disorder in the catabolic enzyme xanthine dehydrogenase (XDH) or xanthine
oxidase, which catalyzes the conversion of xanthine to uric acid.
ā¢ xanthine is poorly soluble in urine, the high levels of xanthine that accumulate in XDH deficiency
lead to xanthine stones
Allopurinol, which inhibits XDH and is used to treat hyperuricemia and hyperuricosuria, can, at
high levels, predispose to xanthine stones.
This side effect is distinctly uncommon because the drug causes only partial inhibition of the
enzyme and rarely reduces
40
Dept of Urology, GRH and KMC, Chennai.
41. Ammonium Acid Urate Stones
ā¢ less than 1% of all stones
ā¢ Conditions associated include laxative abuse, recurrent urinarytract
infection, recurrent uric acid stone formation, and inflammatory
bowel disease
41
Dept of Urology, GRH and KMC, Chennai.
42. ā¢ postulated to be the result of dehydration due to gastrointestinal fluid
loss causing intracellular acidosis and enhanced ammonia excretion.
ā¢ Because urinary sodium is low in the setting of laxative use, urate
complexes with abundant ammonia, thereby leading to urinary
supersaturation of ammonium acid urate.
42
Dept of Urology, GRH and KMC, Chennai.
43. Matrix Stones
ā¢ these āstonesā are typically radiolucent and may be mistaken for
tumor or uric acid stones
ā¢ composition of matrix stones was approximately two-thirds
mucoprotein and one-third mucopolysaccharide
ā¢ The matrix substance in crystalline calculi is closely related to the
matrix substance found in matrix calculi.
ā¢ reduced urinary calcium levels may account for the preferential
formation of matrix stones
43
Dept of Urology, GRH and KMC, Chennai.
44. ā¢ In renal failure patients undergoing dialysis, proteinuria may
contribute to an increased risk of matrix stone formation. )
44
Dept of Urology, GRH and KMC, Chennai.
45. Medication-Related Stones
ā¢ Drug-induced stones form either directly due to precipitation and
crystallization of a drug or its metabolite or indirectly by altering the
urinary environment, making it favorable for metabolic stone
formation
ā¢ Medications That Directly Promote Stone Formation Indinavir Stones.
ā¢ Indinavir sulfate is a protease inhibitor
ā¢ Triamterene Stones. Triamterene is a potassium-sparing diuretic
commonly used for the treatment of hypertension.
45
Dept of Urology, GRH and KMC, Chennai.
46. ā¢ Guaifenesin and Ephedrine. Consumption of large quantities of
guaifenesin and ephedrine can lead to stones composed of their
Metabolites
ā¢ Silicate Stones.
ā¢ Silica is a common element seen in vegetables,whole grains,
seafood, and even drinking water that is easily excreted in the urine
ā¢ Silicate stones -extremely rare - associated with consumption of
large amounts of silicate-containing antacids such as magnesium
Trisilicate
46
Dept of Urology, GRH and KMC, Chennai.
47. ā¢ Medications That Indirectly Promote Stone Formation
Corticosteroids, vitamin D, and phosphate binding antacids can
induce hypercalciuria.
ā¢ Thiazides cause intracellular acidosis and subsequent hypocitraturia
ā¢ Carbonic anhydrase inhibitors such as acetazolamide
ā¢ Chronic use results in hypocitraturia, hypercalciuria, and increased
risk for calcium phosphate stones
47
Dept of Urology, GRH and KMC, Chennai.
48. ā¢ Lastly, cytotoxic agents promote a high cell turnover, resulting in
urinary excretion of large amounts of uric acid.
48
Dept of Urology, GRH and KMC, Chennai.