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