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M.Prasad NaiduMsc Medical Biochemistry,
Ph.D. research scholar
Renal calculi:The smooth epithileal tissue are formed the hardness
by the inorganic and organic substance like kidney--------- stone ( calcium) gall bladder---- stone ( cholesterol oxalates) intestine ------- jejunum (hard substance)Introduction: Urinary calculi are mainly composed of substance
normally in urine and may be found in any part of the urinary tract. Their size of an egg. These calculi can be divided into:
Simple calculi Mixed calculi Foreign body calculiFormatin: The nucleus for stone can be obtained by
the presence of a small lesion. The crystals get deposited on the nucleus and continue to grow. These can some times adhere to the renal papillae.
Substances found in calculi : They are mainly uric acid, urate , triple phosphate, calcium carbonate ,calcium phosphate, calcium oxalates, cholesterol. Cystine calculi have been reported but are extremly rare, and xanthin also form stones ( xanthinuria)
COMPARATIVE INCIDENCES OF FORMS OF URINARY LITHIASISStone analysis in Percentage
Form of Lithiasis India USA Japan UK
Pure Calcium Oxalate 86.1 33 17.4 39.4
Mixed Calcium Oxalate and 4.9 34 50.8 20.2
Phosphate
Magnesium Ammonium 2.7 15 17.4 15.4
Phosphate (Struvite )
Uric Acid 1.2 8.0 4.4 8.0
Cystine 0.4 3.0 1.0 2.8
Inhibitors & Promoters of Stone Formation in Urine
INHIBITORSInhibits crystal Growth - Citrate – complexes with
Ca Magnesium – complexes
with oxalates Pyrphosphate -
complexes with Ca ZincInhibits crystal Aggregation Glycosaminoglycans Tamm- Horsfall Protein
PROMOTERS Bacterial Infection Anatomic Abnormalities
– PUJ obst., MSK Altered Ca and oxalate
transport in renal epithelia
Prolonged immobilisation
Increased uric acid levels I.e taking increased purine subs– promotes crystalisation of Ca and oxalate
TYPES OF RENAL / URETER STONES
Common stones:
OXALATE (CALCIUM OXALATE)
PHOSPHATE
URIC ACID / URATE
CYSTINE
Uncommon StonesXANTHINE STONES
– (Autosomal Recessive . Def of Xanthine Oxidase leading to Xanthinuria)
DIHYDROXY ADENINE STONE
– ( Def. of enzyme adenine phospo ribosyl transferase )
SlLICATE STONES
– Rare in humans ( excess intake of Antacid with Mg Trisilicate. Mostly in cattle due to ingestion of Sand )
MATRIX
- Infection by Proteus - Radiolucent (all calculi have some amt ( 3%) of matrix but matrix calculus has 65% Matrix content in calculi)
Stones – BIO Chemical Constituents Whewelite – Calcium Oxalate Monohydrate – CaC2O4-H2O
Weddelite - Calcium Oxalate dihydrate – CaC2O4-2H2O
Brushite – Calcium Hydrogen phosphate dihydrate – CaHPO4 2H2O
Whitlockite - TriCalcium Phosphate – Ca2(PO4)2
Struvite – Magnesium Ammonium hexahydrate – MgNH4PO4-6H2O
D/D of Radiolucent filling defect on IVU in Ureter or KidneyMust Know
Uric Acid CalculusMatrix CalculusSloughed PapillaBlood ClotsTCC Renal CystsVascular Lesions
Know For Brownie Points
Xanthine Calculus Hydroxy adenine Calculus Ephederine Calculus Infection due to gas forming
Org. Fungal Ball Tuberculoma Malacoplakia Hyper trophied Papilla Renal pseudo-tumour
OXALATE (CALCIUM OXALATE) ALSO CALLED MULBERRY STONE
COVERED WITH SHARP PROJECTIONS
SHARP MAKES KIDNEY BLEED
(HAEMATURIA)
VERY HARD
RADIO - OPAQUEUnder microscope looks like Hourglass or Dumbbell shape if monohydrate and
Like an Envelope if Dihydrate
Bio chemical test for oxalate stone Procedure: Make fine powder Add 2 to 3 drops of 10% HclCool it and add pinch Mn O2- do not mix
Result: fomation of gas bubbles form bottom
PHOSPHATE STONE USUALLY CALCIUM PHOSPHATE
SOMETIMES CALCIUM MAGNESIUM
AMMONIUM PHOSPHATE OR TRIPLE
PHOSPHATE
SMOOTH MINIMUM SYMPTOMS
DIRTY WHITE
RADIO - OPAQUE
Calcium Phosphate also called ‘Brushite’ appears like Needle shape under microscope
Bio chemical test for phosphate stoneProcedure: Make fine powder Add o.5ml of ammonium molybdate warm over a
gas flame
Results: formation of yellow precipitate.
PHOSPHATE STONES IN ALKALINE URINE
ENLARGES RAPIDLY TAKE SHAPE OF CALYCES STAGHORN
CALCIUM PHOSPHATE STONESHyperparathyroidism Ca P
Renal Tubular Acidosis K CO2
Medullary Sponge Kidney -
PTH Hormone Promotes renal production of 1-25-dihyroxycholecalciferol – active Vit.D and also
increases absorption of Calcium and decreases Phosphorus absorption from Kidneys
URIC ACID & URATE STONE HARD & SMOOTH
MULTIPLE
YELLOW OR RED-BROWN
RADIO - LUCENT (USE
ULTRASOUND)
pKa of uric acid 5.75 at this pH 50% of uric acid insoluble.If pH falls further - uric acid more insoluble
Bio chemical test for urate stone Murexide test Procedure: Make fine powder of the stone by using mortorTake a pinch of the powder in a test tube Add 1 drop of 20g/dl Na2 Co3.Add 2drops of phopho tungstic acid reagent
Results : formation of deep blue color.Clinical significance: gout
CYSTINE STONE AUTOSOMAL RECESIVE DISORDER
USUALLY IN YOUNG GIRLS
DUE TO CYSTINURIA -
CYSTINE NOT ABSORBED BY TUBULES
MULTIPLE
SOFT OR HARD – can form stag-horns
PINK OR YELLOW
RADIO-OPAQUE
Under microscope appears like hexagonal or benezene ring – ask for first morning sample
CYSTINE STONE - Management High Fluid Intake and Alkalanise Urine – dissolve most
of the smaller cystine stones
D-Pencillamine or MPG (Mercaptopropionylglycine) binds to cystine that is soluble in urine
Side effects of Pencillamine restricts it use – Allergic rashes, GI problems- Nausea, Vomiting, Diarrhoea
MPG better tolerated
Large obstructive stones – Surgery required first
Cyanide Nitroprusside Calorimeteric Test for detecting Cystinuria. If positive do amino acid chromatography
Bio chemical test for cystine stone Procedure: Make fine powder Add 1 drop of ammonium hydrooxide reagent and
one drop of Na Cl reagent, wait for 5 min add 2-3 drops of sodium nitroprusside reagent
Result: beet red color changes to orange is standing Clinical significance: cystinuria
Cause of Stone Disease Supersaturation of urine is the key to stone
formation
Intermittent supersaturation - Dehydration
Crystal aggregation
Anatomic Abnormailities – PUJ , MSK
Bacterial Infection
Defects in transport of Calcium and Oxalate by Renal epitheliaE.Coli infection increases matrix content in urine . Proteus makes urine alkaline
Surgical Conditions and Stone Disease
Regional ileitis and Ileal Bypass Surgery for eg Obesity can lead to increase oxalate absorption and stone ds
ileostomies - In Chr. Diarrhoea with– Bicabonate loss – systemic acidosis and acidic urine – increases risk of Uric Acid stones
HISTORYA. IS PATIENT DRINKING ENOUGH ?
B. PROFESSION
C.ENQUIRE ABOUT UTI STONES
D. FAMILY HISTORY
E.LONG ILLNESS BEDRIDDEN STONES
MANAGEMENT OF STONESHISTORY :
A. FIND OUT IF DRINKING ENOUGH LIQUIDS
(NOT DRINKING ENOUGH IMPORTANT CAUSE
OF STONE FORMATION & GROWTH)
HISTORY (Cont...)B. ASK ABOUT THEIR PROFESSION
DEHYDRATION STONES CAN FORM e.g.
MARATHON
WORK NEAR A FURNACE,
BRICK - LAYER, LABOURERS & WEAVERS
TRUCK & BUS DRIVERS
CLINICAL FEATURES1. PAIN IN 75 % OF THE CASES
“RENAL COLIC” IF SEVERE AND ACUTE
A) KIDNEY STONE
FIXED PAIN IN THE LOIN
B) URETERIC STONE
PAIN RADIATES LOIN TO GROIN
CLINICAL FEATURES (Contd....)
2) HAEMATURIA
CAN BE FRANK
OR ONLY FOUND ON DIP - STICK OR LAB.
3) PYURIA - IF INFECTION CAN HAVE PUS IN
URINE
Clinical Featuresacute obstruction
of ureter---severe colic
flank pain referred to genitalia
nausea, vomiting may mislead and look like gi problem
microhematuria likely
chronic stone dis. tends to be associated with large or multiple stones
can be little or no pain
may have impaired renal function, anemia, weight loss etc.
concomitant infection more likely
Clinical Risk Factorsoccupationfamily historydiethydrationsmall bowel disease (i.b.d.)medical conditions causing hypercalcuriamedical conditions causing aciduria
ON EXAMINATION1. ACUTE PRESENTATION
ABDOMEN TENSE AND RIGID
TENDERNESS PRESENT IN THE LOIN
2. ASSYMPTOMATIC PRESENTATION
NO TENDERNESS, FINDINGS IN ABDOMEN
INVESTIGATIONS1. FULL BLOOD COUNT TO CHECK FOR
(ANAEMIA IF GOING FOR SURGERY)
2. SERUM ELECTROLYTES / UREA / CREATININE / CALCIUM / URIC ACID /
PHOSPHATE/ BICARBONATES
3. 24-HOURS URINE FOR ELECTROLYTES
(Only if recurrent stone former)
CALCIUM / OXALATE / URIC ACID /
CYSTINE / CITRATE/ URATES
INVESTIGATIONS (Cont...)
4. PLAIN KUB X-RAY OF ABDOMEN (Mandatory)
5. IVU OR IVP (INTRA VENOUS UROGRAM)
Not Mandatory Useful for radio-lucent stones & to detect Congenital Anomalies in Urinary
tracts
6. ULTRASOUND (Mandatory)
7. CT – TO LOOK AT UNUSUAL ANATOMY OF THE KIDNEY (To
differentiate cause of acute colic – stone or anuria Suspected due to
stone disease)
Bilateral Ureteric Calculus in a patient presenting with Anuria Bilateral Ureteric Calculus in a patient presenting with Anuria
Helical or Spiral CT provides 3D reconstruction. Helical refers to path the X ray follows on Gantry. These are rapidly performed and do not require contrast agents for reconstruction.
MANAGEMENT OF UROLITHIASISNon-invasive approach to urinary calculas-
HALLMARK of last 20 yrs.Lithotripters – 1.Extra Corporeal Shock wave
2.Intra Corporeal
Better fiber optics – Mini turisation of Telescopes Accessories - Innovative variety
Modern Management of Urolithiasis ESWL Ureterorenoscopy Percutaneous Nephrolithotomy Laparoscopic Approach to stones
Open Ureterolithotomy, Pyelolithotomy or Nephropyelolithotomy is required in less than 1 to 2% of modern stone management
EXTRA - CORPOREAL SHOCK WAVE LITHOTRIPSY(ESWL)
SHOCK WAVES GENERATED UNDER WATER CAN
TRAVEL THROUGH BODY WITHOUT ANY
APPRECIABLE LOSS OF ENERGY. WHEN THEY
ENCOUNTER STONES THE CHANGES IN DENSITY
CAUSES ENERGY TO BE ABSORBED AND
REFLECTED BY THE STONE & THIS RESULTS IN
FRAGMENTATION OF THE STONES.
ESWL – For Urinary Tract CalculusESWL – For Urinary Tract Calculus
ESWLAbsolute Contra-indication-Pregnancy
Relative Contra-Indications for ESWL – Renal Colic Urinary obstruction Infection Declining Renal Function Significant Hematuria
ESWL COMPLICATIONSHaematuria – is quite common ( short term
antibiotics Recommended ) Incomplete stone Fragmentation &
Obstruction“Stienstrasse” ( stone street ) usually due to
a large “ Leading fragment”( Stents Recommended prior to ESWL for Calculi > 1.5 cm )
Renal Lithiasis Blood Pressure Study (Patients treated 1984-1986 Dallus Study)
First Follow Up Second Follow Up1988 1990
No.Pts Annualized Rate No. Pts Annualized Rate of Hypertension of Hypertension
ESWL 771 2.5% 590 2.1% non-ESWL 195 3.8% 155 1.6% Total 966 745
Diet & Fluid AdviceHigh Fluid Intake
Restrict Salt (Na)
Oxalate Restrict
Avoid high intake of Purine food
Increased citrus fruits may help
If hypercalciuria restrict Ca intake
Role of Potassium Citrate in preventing Cal Oxalate stone ds – KCit lowers
urinary calcium whereas Na Citrate does not lower Calcium due to Sodium load
Moderate Amounts : High Amounts :
Apple Juice Cocoa
Beer Fresh Tea
Coffee
Cola
FOODS :
Almonds, Asparagus, Cashew Nuts, Currants, Greens,
Plums, Raspberries, Spinach
Clinical significance of Renal Stonesall urinary stones are composed of 98% crystalline material and
2% mucoproteinthe crystalline component(s) may be found “pure” or in
combination with each other.the common characteristic that all crystalline components
share, is that they have a very limited solubility in urine99% of renal stones (in western hemisphere) are composed of:
calcium oxalate 75% (mono or di hydrate)calcium hydroxyl phosphate (15%)(apatite)magnesium ammonium phosphate 10% (struvite)uric acid 5%cystine 1%
investigations show that the formation of a stone is similar to the development of a crystalline mass in vitro
given that stone formation is an example of crystallization one could predict:the necessity for a supersaturated state in urinethe occurrence of spontaneous crystallizationthe need for the earliest polycrystalline state to be
arrested in the u.t. allowing time for growth
Spontaneous Crystallization
normal urine has crystals (at times)normal urine is extremely effective in maintaining a
stable supersaturated statethere are certain components of urine that
enhance ability to maintain ss stateinhibit development of crystals
Principles of Stone Preventionprevent supersaturation
water! water and more water enough to make 2L of urine per day
prevent solute overload by low oxalate and moderate Ca intake and treatment of hypercalcuria
replace “solubilizers” i.e... citratemanipulate pH in case of uric acid and cystine
flush! forced water intake after any dehydration
Treatment Renal Stones> 2cm or multiple stones, percutaneous ultrasonic
lithotripsy (pul)large branched stones “staghorn” may require pul and
eswl.cystine stones pul or open nephrolithotomy
MAJORITY : 80 TO 85 % of all stones can be treated by -
EXTRA - CORPOREAL SHOCK WAVE LITHOTRIPSY (ESWL)
MINORITY : 15 TO 20 % SHOULD NEED MINIMALLY INVASIVE
SURGERY (PCNL / URETEROSCOPY)
(LESS THAN 1 % SHOULD NEED OPEN SURGERY)
Treatment:small ureteral
stones with good chance of passage (<7 mms)allow time to pass
(2-4 weeks)lower ureter-
ureteroscopic stone removal
mid-upper ureter eswl
large ureteral stones (>7mms)eswlureteroscopic
stone fragmentation
open surgery