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 PercentageForm of Lithiasis India USA Japan UKPure Calcium Oxalate86.13317.439.4Mixed Calcium Oxalate and4.93450.820.2 PhosphateMagnesium Ammonium 2.71517.415.4 Phosphate (Struvite )Uric Acid1.28.04.48.0Cystine0.43.01.02.8

Inhibitors & Promoters of Stone Formation in UrineINHIBITORSInhibits crystal Growth - Citrate complexes with CaMagnesium complexes with oxalatesPyrphosphate - complexes with CaZincInhibits crystal AggregationGlycosaminoglycansTamm- Horsfall Protein

PROMOTERSBacterial InfectionAnatomic Abnormalities PUJ obst., MSK Altered Ca and oxalate transport in renal epithelia Prolonged immobilisationIncreased uric acid levels I.e taking increased purine subs promotes crystalisation of Ca and oxalate

TYPES OF RENAL / URETER STONESCommon stones:OXALATE (CALCIUM OXALATE)PHOSPHATEURIC ACID / URATECYSTINE

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-H2OWeddelite - Calcium Oxalate dihydrate CaC2O4-2H2OBrushite Calcium Hydrogen phosphate dihydrate CaHPO4 2H2OWhitlockite - 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 CalculusHydroxy adenine CalculusEphederine CalculusInfection due to gas forming Org.Fungal BallTuberculomaMalacoplakiaHyper trophied PapillaRenal pseudo-tumour

OXALATE (CALCIUM OXALATE)ALSO CALLED MULBERRY STONECOVERED WITH SHARP PROJECTIONSSHARP MAKES KIDNEY BLEED (HAEMATURIA)VERY HARDRADIO - 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 STONEUSUALLY CALCIUM PHOSPHATESOMETIMES CALCIUM MAGNESIUM AMMONIUM PHOSPHATE OR TRIPLE PHOSPHATESMOOTH MINIMUM SYMPTOMSDIRTY WHITERADIO - OPAQUECalcium 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 KCO2

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 STONEHARD & SMOOTHMULTIPLEYELLOW OR RED-BROWNRADIO - 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 STONEAUTOSOMAL RECESIVE DISORDERUSUALLY IN YOUNG GIRLSDUE TO CYSTINURIA - CYSTINE NOT ABSORBED BY TUBULESMULTIPLESOFT OR HARD can form stag-hornsPINK OR YELLOWRADIO-OPAQUEUnder 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 stonesD-Pencillamine or MPG (Mercaptopropionylglycine) binds to cystine that is soluble in urineSide effects of Pencillamine restricts it use Allergic rashes, GI problems- Nausea, Vomiting, DiarrhoeaMPG better toleratedLarge 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 DiseaseSupersaturation of urine is the key to stone formationIntermittent supersaturation - Dehydration Crystal aggregationAnatomic Abnormailities PUJ , MSKBacterial Infection Defects in transport of Calcium and Oxalate by Renal epithelia

E.Coli infection increases matrix content in urine . Proteus makes urine alkaline

Surgical Conditions and Stone DiseaseRegional ileitis and Ileal Bypass Surgery for eg Obesity can lead to increase oxalate absorption and stone dsileostomies - In Chr. Diarrhoea with Bicabonate loss systemic acidosis and acidic urine increases risk of Uric Acid stones

HISTORYA.IS PATIENT DRINKING ENOUGH ?B. PROFESSIONC.ENQUIRE ABOUT UTI STONESD. FAMILY HISTORYE.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 & WEAVERSTRUCK & BUS DRIVERS

CLINICAL FEATURES1.PAIN IN 75 % OF THE CASES RENAL COLIC IF SEVERE AND ACUTEA)KIDNEY STONE FIXED PAIN IN THE LOIN B)URETERIC STONE PAIN RADIATES LOIN TO GROIN

CLINICAL FEATURES (Contd....)2)HAEMATURIA CAN BE FRANKOR ONLY FOUND ON DIP - STICK OR LAB.3)PYURIA - IF INFECTION CAN HAVE PUS IN URINE

Clinical Featuresacute obstruction of ureter---severe colicflank pain referred to genitalia nausea, vomiting may mislead and look like gi problemmicrohematuria likelychronic stone dis. tends to be associated with large or multiple stonescan be little or no painmay 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 PRESENTATIONABDOMEN TENSE AND RIGIDTENDERNESS PRESENT IN THE LOIN2.ASSYMPTOMATIC PRESENTATIONNO 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/ BICARBONATES3.24-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)IVU OR IVP (INTRA VENOUS UROGRAM)Not MandatoryUseful for radio-lucent stones & to detect Congenital Anomalies in Urinary tractsULTRASOUND (Mandatory) 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 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 UrolithiasisESWLUreterorenoscopyPercutaneous NephrolithotomyLaparoscopic Approach to stonesOpen 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 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 & ObstructionStienstrasse ( 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 HypertensionESWL 771 2.5%590 2.1%non-ESWL 195 3.8%155 1.6%Total 966 745

Diet & Fluid AdviceHigh Fluid IntakeRestrict Salt (Na)Oxalate RestrictAvoid high intake of Purine foodIncreased citrus fruits may helpIf 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 JuiceCocoaBeerFresh TeaCoffeeColaFOODS :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 vitrogiven 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 supersaturationwater! water and more water enough to make 2L of urine per dayprevent solute overload by low oxalate and moderate Ca intake and treatment of hypercalcuriareplace solubilizers i.e... citratemanipulate pH in case of uric acid and cystineflush! 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 nephrolithotomyMAJORITY : 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 (7mms)eswlureteroscopic stone fragmentationopen surgery

All stones grown in the urinary tract have a small proteinaceous component termed matrix. For many years the development of stones was felt to be similar to the development of bone from a pre-existing cartilaginous matrix. In the past 25 years it has been shown that the matrix is incorporated into the stone as the crystals grow in a passive manner. There is some evidence to show that the proteinaceous components may even be crystal inhibitors.The crystalline components may either be in a pure form or mixed with other stone forming elements. All stone forming elements have very limited solubility in water (or urine). One never has to worry about seeing a urea or a glucose stone since these materials are extremely soluble and therefor are never found in a supersaturated state in urine.