M.

Prasad Naidu
Msc 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 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)
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 20.2
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
INHIBITORS
Inhibits crystal Growth -
Citrate complexes with Ca
Magnesium complexes
with oxalates
Pyrphosphate - complexes
with Ca
Zinc
Inhibits 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 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)

Stones BIO Chemical Constituents
Whewelite Calcium Oxalate Monohydrate CaC
2
O
4
-H
2
O
Weddelite - Calcium Oxalate dihydrate CaC
2
O
4
-2H
2
O
Brushite Calcium Hydrogen phosphate dihydrate CaHPO
4
2H
2
O
Whitlockite - TriCalcium Phosphate Ca
2
(PO
4
)
2

Struvite Magnesium Ammonium hexahydrate MgNH
4
PO
4
-6H
2
O


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




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
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

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 stone
Procedure:
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 STONES
Hyperparathyroidism Ca P

Renal Tubular Acidosis K CO
2

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 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

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
epithelia

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

MANAGEMENT OF STONES
HISTORY :
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 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

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 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
Clinical Risk Factors
occupation
family history
diet
hydration
small bowel disease (i.b.d.)
medical conditions causing hypercalcuria
medical conditions causing aciduria
ON EXAMINATION
1. ACUTE PRESENTATION
ABDOMEN TENSE AND RIGID
TENDERNESS PRESENT IN THE LOIN
2. ASSYMPTOMATIC PRESENTATION
NO TENDERNESS, FINDINGS IN ABDOMEN

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


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
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 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
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 Calculus
ESWL
Absolute Contra-indication-
Pregnancy

Relative Contra-Indications for ESWL
Renal Colic
Urinary obstruction
Infection
Declining Renal Function
Significant Hematuria
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 >
1.5 cm )
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


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
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 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%

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

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

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
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)
eswl
ureteroscopic stone
fragmentation
open surgery