Post on 08-Dec-2015
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URINARY LITHIASIS Etiology, Epidemiology
and Pathogenesis
Urology Division, Surgery DepartmentMedical Faculty,
University of Sumatera Utara
References
EpidemiologyPrevalence of kidney stone 1 – 15 %, and in
hot area such as the mountains, desert & tropical
areas
: = 2 to 3 : 1, peak age onset 40 - 60 yrs
The third most common affliction of the urinary
tract, after UTI and pathologic conditions of the
prostate
Race : Whites > Asian > African
Individual occupations eg. manager and
professional risk of stone (unclear reason)
Epidemiology25% stone formers have a family history
Risk of stone correlates with weight and body mass index
Uric acid and Ca stones more frequent in, infectious stones more common in
The most common kinds of stones are calcium oxalate, uric acid, struvite and cysteine
Etiology1. Definitive causes :
Metabolic
Infection
Anatomic
Functional
2. Idiopathic
Definitive causesDefects in purine metabolism (uric acid related disorders)
Hyperoxaluric states
- Primary hyperoxaluria
- Enteric hyperoxaluria
Hypercalcemic states
- Primary hyperparathyroidism
- Hyperthyroidism
- Vitamin D abuse
Hypercalcemic states (cont.) - Immobilization - Disseminated malignancies
- Sarcoidosis- Renal tubular acidosis
Chronic diarrheal statesCystinuriaUrinary infection with urease producing microorganismsAnatomical and functional abnormalities
Risk factors Genetics : Cystinuria : autosomal recessive RTA (renal tubular acidosis) – type IMedullary sponge kidney
Geography : temperature & humidity
Diet : calcium / oxalate intake >>
Profession : sedentary
ClassificationDefenition
Non Calcium Stones Infection stones:• Magnesium ammonium phosphate• Carbonate apatite• Ammonium urateaUric acidAmmonium urateaSodium urateCystine
Calcium Stones
Stone Composition and Relative Occurrence
Stone Composition Occurrence (%)
Calcium-Containing Stones
Calcium oxalate 60
Hydroxyapatite 20
Brushite 2
Non–Calcium-Containing Stones
Uric acid 7
Struvite 7
Cystine 1–3
Triamterene <1
Silica <1
2,8-Dihyroxyadenine <1
Stone formation
Stone formationCrystallization
Stone salts that precipitate out of urine The point of saturation of a salt in solution is called the
solubility product (Ksp)
When the product of the components of a salt (e.g.
calcium and oxalate) exceeds Ksp, salt crystals will precipitate out of solution Crystallization is based on Ksp, pH, and the presence of stone inhibitors and promoters
Nucleation
- Is the process by which stones form around a
core, or nucleus
- Homogeneous stone nuclei form in solution
- Heterogeneous stone nuclei form around
existing structures, such as cellular debris
Aggregation
- Crystals join together to form larger clumps
Inhibitors and Promoters of Crystal Formation
Inhibitors : Nephrocalcin Uropontin Tamm-Horsfall protein Citrate Magnesium
Promoters : Calcium phospate Calcium oxalate
Urinary tract stone
AgeSexProfessionNutritionClimateRaceInheritance
Abnormal renal morphologyDisturbed urin flow UTIMetabolic abnormalGenetic factors
Increaseexcretion of : 1.Stone
forming constituents2. Crystallization promoters
Decrease :1.Urinary
volume2. Excretion of crystallization inhibitors
SUPERSATURATION
STONE
PathogenesisCALCIUM STONES1. Hipercalciuria : excretion of Ca > 4
mg/kg/day a. Absorptive : increased ca excretion (>0.2
mg/mg creatinine) after an oral calcium load
b. Renal : urinary ca levels >0.11 mg/dL glomerular filtration with a normal serum calcium
c. Resorptive : associated with primary hyperparathyroidism
2. Hyperoxaluria : urinary oxalate greater than 40 mg/day
a. Primary Hyperoxaluria (autosomal recessive disorder )
b. Enteric Hyperoxaluria : associated with chronic diarrheal states
c. Dietary Hyperoxaluria : oxalate-rich foods such as nuts, chocolate, brewed tea, spinach, broccoli, strawberries.
d. Idiopathic Hyperoxaluria
3. Hyperuricosuria
Urinary uric acid exceeding 600 mg/day
The most common cause increase purin intake
4. Hypocitraturia
Urinary citrate level less than 320 mg/day
Correctable abnormality
Associated with nephrolithiasis in up to 10% of
calcium stone
5. Hypomagnesuria
Rare cause, less than 1%
Magnesium complexes with oxalate and calcium,
mg levels decrease reduced inhibitory activity
Poor dietary intake Mg
URIC ACID STONES 5-10% of all stone 3 factors of uric acid stone formation :
1. Low pH, < 5,52. Low urine volume3. Hyperuricosuria urinary uric acid
less than 600 mg/day
Secondary causes : gout (20%),obesity , myeloproliferative cancer and congenital disorder
STRUVITE STONESInfection stones comprise 5% to 15% of all
stones Composed of Mg ammonium phosphate crystals
= infection stones or triple phosphate stoneStaghorn calculi are typically struvite stoneCaused by infection with urease-producing
bacteria :
- proteus is the most common
- urease hydrolized urea to form ammonia
alkalinizes the urine, pH and allows crystals to form
CYSTINE STONES
1% of all stones
Congenital disorders, autosomal recessive
Caused by a defect in cystine reabsorption
in the proximal tubule
Cystine poorly soluble at normal pH (pKa
8.3)
Crystal form benzene ring on microscopy
CALCIUM PHOSPHATE STONE Urine pH > 5.5
Hypocitraturia
70% of adults with type 1 RTA have stones
80% are women
Associated with renal cyst
Medications That directly Promote Stone Formation
Indinavir Stones
Triamterene Stones
Guaifenesin and Ephedrine
Silicate Stones
Anatomic Predisposition Ureteropelvic Junction Obstruction :
20 %
cases
Horseshoe Kidneys
Caliceal Diverticula
SUMMARY
The most common type is calcium oxalate
Uric acid stones form at pH <5.5
The most important determinant of uric acid stone formation is low urinary pH
Struvite stone are composed of magnesium
ammonium phosphate crystals
- They are classically caused by infection with
a urease-producing bacterium
- Urinary pH is >7.2 treatment is surgery &
antibiotics
Cystine stones caused by a congenital
autosomal recessive disorder
Calcium phosphate stones associated with
type 1 RTA