Renal calculi

1
Renal calculi

• M.Prasad Naidu
• Msc Medical Biochemistry,
• Ph.D. research scholar

2
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

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• Simple calculi
• Mixed calculi
• Foreign body calculi
• Formatin 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)

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COMPARATIVE INCIDENCES OF FORMS OF URINARY
LITHIASIS

• Stone 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 20.2Phosph
  ate
• Magnesium Ammonium 2.7 15 17.4 15.4Phosphate
  (Struvite )
• Uric Acid 1.2 8.0 4.4 8.0
• Cystine 0.4 3.0 1.0 2.8

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Inhibitors Promoters of Stone Formation in Urine

• 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

• INHIBITORS
• Inhibits crystal Growth -
• Citrate complexes with Ca
• Magnesium complexes with oxalates
• Pyrphosphate - complexes with Ca
• Zinc
• Inhibits crystal Aggregation
• Glycosaminoglycans
• Tamm- Horsfall Protein

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TYPES OF RENAL / URETER STONES

• Common stones
• OXALATE (CALCIUM OXALATE)
• PHOSPHATE
• URIC ACID / URATE
• CYSTINE

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Uncommon Stones

• XANTHINE 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)

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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

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D/D of Radiolucent filling defect on IVU in
Ureter or Kidney

• Must Know
• Uric Acid Calculus
• Matrix Calculus
• Sloughed Papilla
• Blood Clots
• TCC
• Renal Cysts
• Vascular 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

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OXALATE (CALCIUM OXALATE)

• ALSO CALLED MULBERRY STONE
• COVERED WITH SHARP PROJECTIONS
• SHARP MAKES KIDNEY BLEED (HAEMATURIA)
• VERY HARD
• RADIO - OPAQUE

Under microscope looks like Hourglass or Dumbbell
shape if monohydrate and Like an Envelope if
Dihydrate
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Bio chemical test for oxalate stone

• Procedure
• Make fine powder
• Add 2 to 3 drops of 10 Hcl
• Cool it and add pinch Mn O2- do not mix
• Result fomation of gas bubbles form bottom

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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
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Bio chemical test for phosphate stone

• Procedure
• Make fine powder
• Add o.5ml of ammonium molybdate warm over a gas
  flame
• Results formation of yellow precipitate.

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PHOSPHATE STONES

• IN ALKALINE URINE
  ENLARGES RAPIDLY
  TAKE
  SHAPE OF CALYCES
  STAGHORN

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CALCIUM PHOSPHATE STONES

• Hyperparathyroidism 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
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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
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Bio chemical test for urate stone

• Murexide test
• Procedure
• Make fine powder of the stone by using mortor
• Take 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

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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
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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
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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

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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 epithelia

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

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HISTORY

• A. IS PATIENT DRINKING ENOUGH ?
• B. PROFESSION
• C. ENQUIRE ABOUT UTI STONES
• D. FAMILY HISTORY
• E. LONG ILLNESS BEDRIDDEN STONES

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MANAGEMENT OF STONES

• HISTORY
• A. FIND OUT IF DRINKING ENOUGH LIQUIDS
• (NOT DRINKING ENOUGH IMPORTANT CAUSE OF STONE
  FORMATION GROWTH)

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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

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CLINICAL FEATURES

• 1. 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

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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

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Clinical Features

• acute 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

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Clinical Risk Factors

• occupation
• family history
• diet
• hydration
• small bowel disease (i.b.d.)
• medical conditions causing hypercalcuria
• medical conditions causing aciduria

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ON EXAMINATION

• 1. ACUTE PRESENTATION
• ABDOMEN TENSE AND RIGID
• TENDERNESS PRESENT IN THE LOIN
• 2. ASSYMPTOMATIC PRESENTATION
• NO TENDERNESS, FINDINGS IN ABDOMEN

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INVESTIGATIONS

• 1. 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

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INVESTIGATIONS (Cont...)

• 4. PLAIN KUB X-RAY OF ABDOMEN (Mandatory)
• IVU OR IVP (INTRA VENOUS UROGRAM)
• Not Mandatory
• Useful for radio-lucent stones to detect
  Congenital Anomalies in Urinary tracts
• ULTRASOUND (Mandatory)
• CT TO LOOK AT UNUSUAL ANATOMY OF THE KIDNEY
  (To differentiate cause of acute colic
  stone or anuria Suspected due to stone
  disease)

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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.
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MANAGEMENT OF UROLITHIASIS

• Non-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

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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
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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.

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ESWL For Urinary Tract Calculus
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ESWL

• Absolute Contra-indication-
• Pregnancy
• Relative Contra-Indications for ESWL
• Renal Colic
• Urinary obstruction
• Infection
• Declining Renal Function
• Significant Hematuria

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ESWL COMPLICATIONS

• Haematuria 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
  gt 1.5 cm )

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Renal Lithiasis Blood Pressure Study (Patients
treated 1984-1986 Dallus Study)

• First Follow Up Second
  Follow Up
• 1988 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

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Diet Fluid Advice

• High 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
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Moderate Amounts High Amounts Apple
Juice Cocoa Beer Fresh Tea Coffee Cola FOODS
Almonds, Asparagus, Cashew Nuts, Currants,
Greens, Plums, Raspberries, Spinach
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Clinical significance of Renal Stones

• all urinary stones are composed of 98
  crystalline material and 2 mucoprotein
• the 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 urine
• 99 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

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• 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
  urine
• the occurrence of spontaneous crystallization
• the need for the earliest polycrystalline state
  to be arrested in the u.t. allowing time for
  growth

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Spontaneous Crystallization

• normal urine has crystals (at times)
• normal urine is extremely effective in
  maintaining a stable supersaturated state
• there are certain components of urine that
• enhance ability to maintain ss state
• inhibit development of crystals

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Principles of Stone Prevention

• prevent 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... citrate
• manipulate pH in case of uric acid and cystine
• flush! forced water intake after any dehydration

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Treatment Renal Stones

• gt 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)

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Treatment

• small ureteral stones with good chance of passage
  (lt7 mms)
• allow time to pass (2-4 weeks)
• lower ureter- ureteroscopic stone removal
• mid-upper ureter eswl

• large ureteral stones (gt7mms)
• eswl
• ureteroscopic stone fragmentation
• open surgery

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Thank you