Transcript الشريحة 1

Urinary lithiasis
The 3rd most common disorder of urinary tract after
UTI & prostate disorders.
Without medical intervention stone recurrence rate
after surgery can be as high as 50% within 5yr
*Stone occurrence is relatively uncommon before
age 20 but peaks in incidence in the fourth to sixth
decades of life
*men are affected 2-3 times more frequently than
women
Etiology
If urinary constituents are similar in each kidney
and if there is no evidence of obstruction, why do
most stones present in a unilateral fashion?
Why don’t small stones pass uneventfully down the
ureter early in their development?
Why do some people form one large stone
and others form multiple small calculi?
The etiology remain speculative
The physical process of stone formation is 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 lead to crystal
formation.
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
pure aqueous solution of a salt is considered
saturated when it reaches the point at which further
added salt crystals will not dissolve
In urine, despite concentration products of stoneforming salt components, such as calcium oxalate,
that exceed the solubility product, crystallization
does not necessarily occur because of the presence
of inhibitors and other molecules
Nucleation and Crystal Growth, Aggregation, and
Retention
Crystal components are the main component of
urinary stone
the noncrystalline part or Matrix component only
2-10% of the weight. (mainly protein)
*Nuclei are the earliest crystal structure that will not
dissolve
Magnesium and citrate inhibit crystal aggregation.
Nephrocalcin, an acidic glycoprotein made in the
kidney, inhibits calcium oxalate nucleation, growth,
and aggregation
1- Mass precipitation theory
suggests that the distal tubules or collecting ducts, or
both, become plugged with crystals, thereby
establishing an environment of stasis, & further
stone growth.
This explanation is unsatisfactory; tubules are conical
in shape and enlarge as they enter the papilla, thereby
reducing the possibility of ductal obstruction.
2- Randalls hypothesis (fixed particle theory)
formed crystals are somehow retained within cells or
beneath tubular epithelium.
Randall noted whitish-yellow precipitations of
crystalline substances occurring on the tips of renal
papillae as submucosal plaques.
3- Carr hypothesis
calculi form in obstructed lymphatics and then
rupture into adjacent fornices of a calyx.
Arguing against Carr’s theory are the grossly visible
early stone elements in areas remote from fornices.
Urinary Ions
A. CALCIUM
major ion present in urinary crystals
over 95% of the calcium filtered at the glomerulus is
reabsorbed at both the proximal and distal tubules
and limited amounts in the collecting tube.
Less than 2% is excreted in the urine.
B. OXALATE
10–15% of oxalate found in the urine originates from
the diet; the vast majority is a metabolic by
product
C. PHOSPHATE
important buffer and complexes with calcium in
urine. It is a key component in calcium phosphate and
magnesium ammonium phosphate stones.
The excretion of urinary phosphate in normal adults
is related to the amount of dietary phosphate
(especially in meats, dairy products, and vegetables)
D. URIC ACID
Uric acid is the by-product of purine metabolism
E. SODIUM
sodium plays an important role in regulating the
crystallization of calcium salts in urine
F. CITRATE
key factor affecting the development of calcium
urinary stones. A deficiency commonly is associated
with stone formation in those with chronic diarrhea or
renal tubular acidosis type I (distal tubular defect) and
in patients undergoing chronic thiazide therapy
G. MAGNESIUM
lack of dietary magnesium is associated with
increased calcium oxalate stone formation and
calcium oxalate crystalluria
H. SULFATE
They can complex with calcium & may help prevent
urinary calculi.
stone varieties
A-Calcium calculi.
Calcification either orthtopic in normal places or
heterotopic in abnormal places which (dystrophic
normal s. calcium or meastatic elevated s calcium)
*80-85% of urinary stones are calcareous.
Usually due to elevated urinary calcium, uric acid or
oxalate or decreased level of urinary citrate.
Approximately 1/3rd of pt. undergo metabolic
evaluation have no identifiable metabolic defect.
Nephrocalcinossis.
Calcification within renal parenchyma, rarely cause
symptoms & not amenable to traditional therapy for
urinary stone disease.
May associated with nephrolithaiasis.
Causes;
RTA, hyperparathyrodism, medullary sponge kidney,
sarcoidosis, milke alkali syndrome, & multiple
myeloma.
Types of calcium stone
1-absorptive hypercalciuric nephrolithiasis
Due to increase calcium absorption from small bowel
predominantly the jejunum resulting in hypercalciuria
(>4mg/kg) or (>150-200mg/24hr).
Its of 3types;
type1-dietary independent (15%)
*Cellulose phosphate- binding ca. in bowel prevent its
absorption.
*hydrochlorothiazides-reduce renal excretion
of ca.
Type 2- dietary dependent
common cause calcium restricted diet (no specific
therapy)
Type3-phosphate renal leak (5%)
lead to decrease serum phosphate—increase V D3
synthesis—increase ca absorption &excretion.
2-resorptive hypercalciuria;
hyperparathyrodism 50% presented with renal stone.
suspected in Pt. with ca. phosphate stone, women with
recurrent ca. stones & those with both nephrocalcinosis
& nephrolithiasis .
Hypercalcemia is most consistent sign.
3-Renal induced hypercalciuria.
Intrinsic renal tubular defect in ca. excretion. lead to
secondary hyperparathyroidism
effectively treated by hydrochlorthiazide.
4-Hyperuricosuric calicium nephrolithiasis:
Due to either excessive dietary intake of purines or
increase endogenous uric acid production
*Monosodium urate absorb & adsorb urinary inhibitors
& facilitate heterogeneous nucleation.
*pt. have elevated urinary uric acid >600-750 mg/24hr.
& consistently ph >5.5. The urinary ph help to
differentiate hyperuricosuric calcium from
hyperuricosuric uric acid nephrolithiasis.
-Effectively treated by low purine diet
pot.cit. & allopurinol (xanthine oxidase inhibitor) for
both exogenous &endogenous respectively.
5-Hyperoxaluric calcium nephrolithiasis:
Increase urinary oxalate >40mg/24hr
In pt. with inflammatory bowel disease & chronic
diarrheal state —malabsorption increase luminal fat &
bile, ca bind fat (saponification) no more ca ready to
bind oxalate– increase absorption of oxalate (enteric
hyperoxaluria) treated by oral ca. or magnesium.
Primary hyperoxaluria. rare hereditary disease
(enzyme deficiency) ase ca. oxalate stone &
nephrocalcinosis. need combined liver &renal
transplant.
6-Hypocitrateuric ca.nephrolithiasis.
Increase metabolic demand on the renal cell
mitochondria decrease the excretion of citrate
(hypocitraturia <320mg/24hr) like metabolic acidosis
(in RTA), hypokalemia (thiazide therapy), fasting,
hypomagnesemia UTI & androgens.
In contrast alkalosis, estrogen ,growth h. & V D
increase urinary citrate. It complex with ca. ion
decreasing energy for crystallization.
Treated by potassium citrate.
B. Non calcium calculi.
1- Struvite.
composed of MAP (magnesium, ammonium, &
phosphate). Infection stone ase urea splitting
organisms (proteus, pseudomonas providencia,
klebsiella, staph. & mycoplasma.)
Most commonly in women & may recur rapidly.
usually staghorn calculus. The high ammonium
concentration derived from urea splitting lead to
alkaline urinary ph ranges from 6.8-8.3
*normal urinary ph=5-7 in which MAP crystal
soluble.
2- Uric acid stone
Less than 5% of all urinary stones usually in men.
Specially pt. with gout, myeloproliferative disease,
rapid weight loss, & those treated with cytotoxic
drugs.
Most of them have no hyperuricemia.
Urinary ph consistently < 5.5, in contrast to pt.
with hyperuricosuric calcium nephrolithiasis.
as urinary ph increase >5.75 it dissociates to soluble
urate ion.
Treated by increase fluid intake >2L/d & urinary
Ph > 6.0 (alkalinization) allopurinol also help reduce
uric acid excretion.
3-cystine
Secondary to inborn error of metabolism.
Resulting in an abnormal intestinal & renal absorption
of amino acid cystine, ornithine, lysine, & arginine.
Cystine lithiasis is the only clinical manifestation of
this defect.
The solubility of cystine is ph dependent with
dissociation constant pka of 8.1so treated by increase
fluid intake >3L & alkalinization.
there is no known inhibitor for cystine stone.
penicillamine can reduce urinary cystine level it
complexes with amino acid—more soluble.
4-Xanthine.
Are secondary to congenital deficiency of xanthine
oxidase. This enzyme normally catalyzes the
oxidation of hypoxanthine to xanthine & xanthine to
uric acid.
Treatment: high fluid intake, alkalinization
trial of allopurinol xanthine oxidase inhibitor??
5-Other rare
indinavir (protease inhibitor) used in treatment of
AIDS .
Long term used of antacid—silica stone.
Triamterene stone ase antihypertensive contain
triamterene such as diazyde.
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,
-primary hyperparathyroidism,
-enteric hyperoxaluria,
-cystinuria, and
-gouty diathesis.
medical therapy is indicated not only to prevent
further stone formation but also to correct the
underlying physiologic disturbance
Indications for a Metabolic Stone Evaluation
Recurrent stone formers
Strong family history of stones
Intestinal disease (particularly chronic diarrhea)
Pathologic skeletal fractures
Osteoporosis
History of urinary tract infection with calculi
Personal history of gout
Solitary kidney
Anatomic abnormalities
Renal insufficiency
Stones composed of cystine, uric acid, or struvite
Protocol for Low-Risk Single Stone Formers
medical history
any underlying conditions that may have contributed
to the stone disease
patient's dietary habits, including fluid consumption
and excessive intake of certain foods as well as all
medications taken
blood screen
calcium, sodium, potassium, chloride, carbon dioxide,
blood urea nitrogen, creatinine, PTH, uric acid
Urinalysis pH, crystalluria, urine culture
Radiography
Stone analysis
Extensive Diagnostic Evaluation
History and physical examination,
diet history,
radiologic evaluation,
two 24-hour urine specimens on random diet, and
dietary instruction for restricted diet
Urine for pH, Total Volume, Oxalate, Citrate,
Qualitative Cystine
Blood for PTH, Calcium, Uric Acid, Creatinine,
Sodium
CONSERVATIVE MEDICAL MANAGEMENT
Fluid Recommendations
increase in fluid intake to achieve a daily urine output
of 2 liters
Lemonade and orange juice increase urine volume as
well as increase urinary citrate excretion
Increase intake of soda can confer an increased risk of
subsequent stone recurrence
Protein Restriction
-the incidence of renal stones is higher in populations
in which there is an increased animal protein intake
-Protein intake increases urinary calcium, oxalate,
and uric acid excretion and increase probability of
stone formation even in normal subjects
-ingestion of protein is second only to ingestion of
vitamin D in enhancing intestinal absorption of
calcium
Sodium Restriction
-Sodium restriction has been widely recommended
as an important element of dietary prevention of
recurrent nephrolithiasis
-The net effect of a high sodium diet was an
increased propensity for the crystallization of
calcium salts in urine
-In combination with animal protein restriction and
moderate calcium ingestion, a reduced sodium diet
will decrease stone episodes by approximately 50%
Obesity
-increased body mass index, larger waist size, and
weight gain correlated with an increased risk of stone
episodes. This increased stone risk was still more
pronounced for women than for men
-urine pH appears to be directly correlated with body
size so the increased incidence of uric acid stone
formation in obese stone formers may be secondary to
the production of more acidic urine than in “normalsized” patients
-weight-reducing diet (low-carbohydrate) delivers a
marked acid load to the kidney & predispose to
increased stone risk
Dietary Calcium
Older recommendations to significantly restrict
calcium intake probably led to an increase in
available intestinal oxalate. As a result, increase
oxalate absorption, thereby raising the supersaturation
of calcium oxalate
Oxalate Avoidance
Since less than 10% to 15% of urinary oxalate is
usually derived from dietary sources, it is unclear
how helpful it is to promote the strict avoidance of
oral oxalate loading
-avoid foodstuffs that are rich in oxalate, such as
spinach, beets, chocolate, nuts, and tea