URINARY STONE DISEASE

Li, KingbherlyLichauco, RafaelLim, Imee LorenLim, Jason MorvenLim, John HaroldLim, MaryLim Phoebe Ruth

Dr. Jerry Santos

ETIOLOGY Polycrystalline aggregates composed of

varying amounts of crystalloid and organic matrix

Stone formation requires supersaturated urine Urinary pH, ionic strength, solute

concentration, complexation Urinary constituents change dramatically

during different physiologic states

ROLE OF SOLUTE CONCENTRATION Greater concentration of 2 ions The more likely they are to precipitate Solubility product (Ksp) = as ion

concentrations increase, their activity product reaches a specific point

Formation product (Kfp) = concentration above Ksp capable of initiating crystal growth and heterogeneous nucleation

NUCLEATION THEORY Urinary stones originate from crystals

or foreign bodies immersed in supersaturated urine

CRYSTAL INHIBITOR THEORY• Calculi form owing to absence or low

concentration of natural stone inhibitors–Magnesium, citrate, pyrophosphate,

trace metals

A. CRYSTAL COMPONENT

Stones are primarily composed of crystalline component

Crystal formation Nucleation, growth, aggregation

Theory of mass precipitation Distal tubules or collecting ducts

becomes plugged with crystals, establishing an environment of stasis, for further stone growth

Tubules enlarge as they entire papilla, transit time is only a few minutes

Fixed particle theory Formed crystals retained within cells or

beneath tubular epithelium

B. MATRIX COMPONENT Noncrystalline matrix component 2-

10% by weight Mainly protein with hexose and

hexosamine Matrix Calculus

assoc with previous kidney surgery or chronic UTI

Gelatinous texture May serve as a nidus for crystal

aggratation

URINARY IONS

Major ion present in urinary crystals

95% calcium filtered at glomerulus is reabsorbed at proximal and distal tubules

<2% excreted in urine Diuretics –

hypocalciuric effect, decrease calcium excretion

Normal waste product of metabolism, relatively insoluble

Enters large bowel, consumed by bacterial decomposition

Excreted by proximal tubule

Supersaturation of calcium oxalate

Hyperoxaluria – bowel disorders

Calcium Oxalate

URINARY IONS

Important buffer, complexes with calcium in urine

Filtered cy glomerulus, reabsorbed in proximal tubules

Parathyroid hormone inhibits reabsorption

By-product of purine metabolism

Any defect in purine metabolism = urinary stone disease

Defect in xanthine oxidase

Xanthine may ppt in urine

Phosphate Uric Acid

URINARY IONS

Important role in regulating crystallization of calcium salts in urine

High dietary calcium – increases urinary calcium excretion

Reduces ability of urine to inhibit calcium oxalate crystal agglomeration

Pivotal role in citric acid cycle in renal cells

Estrogen increases citrate excretion , factor that decreases incidence of stones in women

Alkalosis increases citrate excretion

Sodium Citrate

URINARY IONS

Lack of magnesium is associated with increased calcium oxalate stone formation

Prevent urinary calculi

Complex with calcium

Magnesium Sulfate

STONE VARIETIES

STONE VARIETIES Calcium Calculi

Absorptive hypercalciuric nephrolithiasis

Resorptive hypercalciuric nephrolithiasis

Renal induced hypercalciuric nephrolithiasis

Hyperuricosuric Ca nephrolithiasis

Hyperoxaluric Ca nephrolithiasis

Hypocitraturic Ca nephrolithiasis

Non-Calcium Calculi Struvite or Magnesium

Ammonium Phosphate Uric Acid Cystine Xanthine Indinavir Rare

Silicate Triamterene

CALCIUM CALCULI• Calcifications

accumulate in collecting system Nephrolithiasis (calcareous)– elevated urinary

calcium– elevated urinary uric

acid– elevated urinary oxalate– decreased level urinary

citrate

• Symptoms secondary to obstruction:– Pain– Infection– Nausea– Vomiting

• Asymptomatic hematuria or UTI urinary stone

ABSORPTIVE HYPERCALCIURIC NEPHROLITHIASIS

ABSORPTIVE HYPERCALCIURIC NEPHROLITHIASIS

RESORPTIVE HYPERCALCIURIC NEPHROLITHIASIS

typically found in hyperparathyroidism calcium is released from bone in response to the

increased activity of osteoclasts caused by excessive and inappropriate serum PTH levels causes significant hypercalcemia

PTH causes the kidney to limit calcium excretion, but, with the overwhelming serum calcium load produced with hyperparathyroidism, the kidneys are forced to excrete the extra calcium into the urine, causing the hypercalciuria.

RENAL INDUCED HYPERCALCIURIC NEPHROLOTHIASIS

HYPERURICOSURIC CALCIUM NEPHROLITHIASIS

Excessive purine Increased uric acid production

Increased urinary monosodium urates Management:

Diet modification DOC: allopurinol 300mg/day Potassium citrate

HYPEROXALURIC CALCIUM NEPHROLITHIASIS

HYPOCITRATURIC CALCIUM NEPHROLITHIASIS

NONCALCIUM CALCULI

STRUVITE Composed of

Magnesium, Ammonium, & Phosphate (MAP)

Most common in women

Frequently present as renal staghorn calculi

Struvite stones are associated with urea-splitting organisms Proteus Pseudomonas Providencia Klebsiella Staphylococci Mycoplasma

Alkaline Urinary pH Results from the high ammonium concentration

derived from the urea-splitting organisms pH >7.2 (NV: 5.85)

MAP crystals precipitate MAP crystals are soluble in the normal urinary pH

range (5-7) Foreign bodies and neurogenic bladders may

predispose patients to urinary infections and subsequent struvite stone formation

Stone removal is therapeutic

Long term management Optimized with removal of foreign bodies All stone fragments should be removed with

or w/o the aid of follow-up irrigations Acetohydroxemic acid

Inhibits the action of bacterial urease, thereby reducing the urinary pH and decreasing the likelihood of precipitations

URIC ACID <5% of all urinary calculi Usually found in men High incidence of Uric Acid Lithiasis

Gout Myeloproliferative disease Rapid weight loss Those treated for malignant conditions

with cytotoxic drugs

Treatment Centered on:

Maintaining a urine volume of >2L / dayand a urinary pH of 6

Reducing dietary purines or the administration of allopurinol helps reduce uric acid excretion

Alkalinization with oral sodium bicarbonate, potassium citrate,

or IV 1/6 normal sodium lactate May dissolve calculi and is dependent on the stone

surface area

CYSTINE Secondary to an inborn error of

metabolism resulting in abnormal intestinal mucosal absorption and renal tubular absorption of dibasic amino acids Cystine Ornithine Lysine Arginine

Genetic defects of cystinuria has been mapped to chromosome 2p.16 and 19q13.1

Cystine lithiasis Only clinical manifestation of this defect 1-2% of all urinary stones Suspected in patients with a (+) FH of urinary

stones and the radiographic appearance of a faintly opaque, ground-glass, smooth-edged stone

Urinalysis: hexagonal crystals

Medical Therapy◦ High fluid intake (>3L/day)◦ Urinary alkalinization◦ Penicillamine

Reduce urinary cystine levels Poorly tolerated by some patients (skin rashes, loss of taste,

nausea, vomiting, & anorexia)◦ Mercaptopropionylglycine

Forms soluble complex with cystine and can reduce stone formation

Surgical◦ Most stones are recalcitrant to ESWL

XANTHINE Secondary to a congenital deficiency of

xanthine oxidase Catalyzes the oxidation of hypoxanthine to

xanthine and of xanthine to uric acid Urinary stones develop on 25% of

patients with xanthine oxidase deficiency

Stones are radiolucent and are tannish yellow in color

Treatment Directed by symptoms and evidence of

renal obstruction High fluid intake Urinary Alkalinization Stone recurrence

Trial of Allopurinol Purine-restricted diet

INDINAVIR Protease inhibitors are a popular and effective

treatment in patients with AIDS Indinavir

◦ 6% of patients prescribed had radiolucent stones◦ Indinavir calculi > only urinary stones to be

radiolucent on non-contrast CT scans Associated with calcium components

Stones are tannish red Temporary cessation of the medication with

intravenous hydration frequently allows thes stones to pass

RARE Silicate

Associated with long term use of antacids containing silica

Surgical treatment Triamterene

Associated with anti-hypertensive medications containing triamterene (Dyazide)

Discontinuing the medication eliminates stone recurrence

Glafenine Antrafenine

SIGNS AND SYMPTOMS

PAIN Colicky Noncolicky

Usually acute in onset, relatively constant, unexpected and severe

Urinary obstruction due to a direct increase in intraluminal

pressure stretching nerve endings inflammation, edema, hyperperistalsis,

and mucosal irritation

Affected by: Stone size Location Degree of obstruction Variation of individual anatomy

Patients frequently move constantly into unusual positions in contrast to the lack of movement of someone with peritoneal signs

1. Renal calyx— deep, dull ache in the flank or back • Mild to severe• Frequently small • may be exacerbated after consumption of large

amounts of fluid• the presence of infection or inflammation in the

calyx or diverticulum may contribute to pain perception.

• occasionally result in spontaneous perforation with urinoma, fistula, or abscess formation

2. Renal pelvis >1 cm in diameter - obstruct the

ureteropelvic junction causing severe pain in the

costovertebral angle, just lateral to the sacrospinalis muscle and just below the 12th rib

dull to excruciatingly sharp, constant, boring

Radiates along the course of the ureter and into the testicle

Partial or complete staghorn calculi- are not necessarily obstructive, few symptoms, “silent”

can often lead to significant morbidity, including renal deterioration, infectious complications, or both

3. Upper and midureter severe, sharp back (costovertebral

angle) or flank pain progressing down the ureter – more

severe and intermittent lodged at a particular site - less pain,

especially if it is only partially obstructive

Upper ureteral - lumbar region and flank

• Midureteral - radiates caudally and anteriorly toward the mid and lower abdomen in a curved, band-like fashion (initially parallels the lower costal margin but deviates caudal toward the bony pelvis and inguinal ligament)

4. Distal ureter pain that radiates to the

groin or testicle in males and the labia majora in females (ilioinguinal or genital branch of the genitofemoral nerves)

This pain pattern is likely due to the similar innervation of the intramural ureter and bladder

Bladder – urgency and frequency with burning (inflammation of the bladder wall around the ureteral orifice)

HEMATURIA complete urinalysis : hematuria and

crystalluria and documenting urinary pH

intermittent gross hematuria or occasional tea-colored urine (old blood)

Rarely (in 10–15% of cases), complete ureteral obstruction presents without microhematuria.

INFECTION Magnesium ammonium phosphate (struvite) stones = infection

stones Proteus, Pseudomonas, Providencia, Klebsiella, and Staphylococcus

infections Calcium phosphate stones

urine pH <6.6 - brushite stones urinary pH >6.6 - infectious apatite stones

All stones, however, may be associated with infections secondary to obstruction and stasis proximal to the offending calculus.

Infection pain Uropathogenic bacterial exotoxins and endotoxins may alter ureteral

peristalsis Local inflammation chemoreceptor activation and perception of local

pain

1. Pyonephrosis—gross pus in an obstructed collecting system

extreme form of infected hydronephrosis Presentation: may range from

asymptomatic bacteriuria to florid urosepsis

Renal urine aspiration - definitive diagnosis

untreated renocutaneous fistula

EVALUATION

Differential Diagnosis mimic other retroperitoneal and peritoneal

pathologic states Peritoneal signs should be sought during

physical examination History

onset, character, potential radiation, activities that exacerbate or ease the pain, associated nausea and vomiting or gross hematuria, and a history of similar pain

RISK FACTORS1. Crystalluria

The rate of stone formation is proportional to the percentage of large crystals and crystal aggregates.

Crystal production is determined by the saturation of each salt and the urinary concentration of inhibitors and promoters.

Urine samples – fresh, centrifuged and examined immediately

2. Socioeconomic factors affluent, industrialized countries

3. Diet less energy-dense diet may decrease the incidence

of stones Vegetarians may have a decreased incidence of

urinary stones. High sodium intake is associated with increased

urinary sodium, calcium, and pH, and a decreased excretion of citrate;

Fluid intake and urine output

4. Occupation Physicians and other white- collar workers have an

increased incidence of stones compared with manual laborers.

may be related to differences in diet and physical activity; high temperatures may develop higher concentrations of

solutes 5. Climate

—hot climates are prone to dehydration Increased calcium and oxalate excretion has been

correlated with increased exposure time to sunlight

6. Family history Those with a family history of stones have an

increased incidence of multiple and early recurrences

7. Medications antihypertensive medication triamterene Long-term use of antacids containing silica Carbonic anhydrase inhibitors Protease inhibitors in immunocompromised

patients are associated with radiolucent calculi.

PHYSICAL EXAM acute renal colic Systemic components: tachycardia, sweating, and

nausea Costovertebral angle tenderness abdominal mass may be palpable in patients with

long-standing obstructive urinary calculi and severe hydronephrosis

Fever, hypotension, and cutaneous vasodilation: urosepsis

thorough abdominal examination should exclude other causes of abdominal pain

RADIOLOGIC INVESTIGATIONS Computed tomography

imaging modality of choice in patients presenting with acute renal colic

rapid and is less expensive than IVP It images other peritoneal and retroperitoneal

structures and helps when the diagnosis is uncertain There is no need for intravenous contrast. do not give anatomic details as seen on an IVP Uric acid stones are visualized no differently from

calcium oxalate stones. Matrix calculi have adequate amounts of calcium to be visualized easily by CT.

Intravenous Pyelogram IV injection of contrast to

visualize renal collecting systems, ureters and UB

gives a comprehensive view of the patient's anatomy 50 ml of a special dye is injected into the bloodstream

that is excreted by the kidneys and by its density helps outline any stone on a repeated X-ray

X ray images every few minutes to determine if there is any obstruction to the dye as it is excreted into the bladder

Tomography useful to identify calculi in the kidney when

oblique views are not helpful. visualizes the kidney in a coronal plane identify poorly opacified calculi, especially

when interfering abdominal gas or morbid obesity make KUB films suboptimal

KUB films and directed ultrasonography Plain frontal supine

radiograph of the abdomen Visualization of:

Renal shadows Psoas muscle shadow Calcification (stones, vascular,

lymph node or tumor UB shadow

Calcium radiopaque

About 10% of stones do not have enough calcium to be seen on standard X-rays (radiolucent stones)

The distal ureter is easily visualized through the acoustic window of a full bladder. Edema and small calculi missed on an IVP can be appreciated with such studies.

Ultrasound presence of hydronephrosis (swelling of

the kidney—suggesting the stone is blocking the outflow of urine)

detect stones during pregnancy when x-rays or CT are discouraged

Retrograde pyelography required to delineate upper-tract anatomy

and localize small or radiolucent offending calculi.

Visualization of urinary collecting system achieved via cystoscope, ureteral catherization and retrograde injection of contrast

Used when IVU failed to opcacify renal collecting system and ureters

Nuclear scintigraphy radioisotopes (here called

radiopharmaceuticals) are taken internally, and the emitted radiation is captured by external detectors (gamma cameras) to form two-dimensional images

Bisphosphonate markers can identify even small calculi that are difficult to appreciate on a conventional KUB film

INTERVENTION

INTERVENTIONS Conservative observation Dissolution agents Relief of Obstruction Extracorporeal Shockwave Lithotripsy (ESWL) Ureteroscopic stone extraction Percutaneous Nephrolithotomy Open stone surgery Pyelolithotomy Anatrophic Nephrolithotomy Radial Nephrotomy Ureterolithotomy others

Conservative management Majority of stones pass out within a 6 week period

after the onset of symptoms depends on the size of the calculi and its location

Dissolution agents Use alkalinizing agents Given oral, IV or intrarenal

Relief of the Obstruction Emergent drainage in patient with signs of

UTI

Extracorporeal Shockwave Lithotripsy (ESWL)

Extracorporeal Shockwave Lithotripsy (ESWL)

excessive weight (>300 lb) may severely limit or preclude ESWL.

Pregnant women and patients with large abdominal aortic aneurysms or uncorrectable bleeding disorders should not be treated with ESWL.

Individuals with cardiac pacemakers should be thoroughly evaluated by a cardiologist.

CONSIDERATION

URETEROSCOPIC STONE EXTRACTION

Highly effective for lower ureteral calculi

Stone may be extracted using a wire basket

Or lithotrites may be placed through the ureteroscope to fragment the calculi

PERCUTANEOUS NEPHROLITHOTOMY the treatment of choice for large

(>2.5 cm) calculi; renal and proximal ureteral calculi, those resistant to ESWL, select lower pole calyceal stones with a narrow, long infundibulum and an acute infundibulo- pelvic angle, and instances with evidence of obstruction

Rapid cure

OPEN STONE SURGERY

Classic way to remove calculi Mandatory to obtain a

radiograph before the incision is made

Not frequently used anymore because of the morbidity of the incision, the possibility of retained stone fragments, and the ease and success of less invasive techniques

PYELOLITHOTOMY Effective especially with

extrarenal pelvis Transverse pyelotomy -

effective and does not require interruption of the renal arterial blood supply

Flexible endoscope – ensures stone-free status

Coagulum – can retrieve multiple, small renal pelvic calculi and difficult- to-access caliceal calculi

Cryoprecipitate Injected into the renal pelvis,

endogenous clotting factors result in a Jelly-like coagulum of the collecting system.

Small stones are entrapped and removed with the coagu- lum.

ANATROPHIC NEPHROLITHOTOMY

Used with complex staghorn calculi Complete staghorn calculus Partial staghorn calculus

1. Incision made on the convex surface of the kidney posterior to the line of Brodel

2. Occlusion of the renal artery followed by renal cooling with slushed ice

3. Nerve hook is helpful to tease out calculi4. Repair of narrowed infundibula helps

reduce stone recurrence rates.

RADIAL NEPHROTOMY

Allows access to limited calyces of the collecting system Frequently used in blown-out calyces with thin overlying

parenchyma Intraoperative ultrasound to localize the calyx and the

calculi A shallow incision of the renal capsule can be followed

by puncture into the collecting system. Stones may be cut with heavy Mayo scissors, and

remaining fragments can be retrieved.

OTHER RENAL PROCEDURES

Partial nephrectomy – for large stones in a renal pole with marked parenchymal thinning Caution should be taken even with a normal contralateral

kidney as stones are frequently associated with a systemic metabolic defect that may recur in the contralateral kidney

Ileal ureter substitution – to decrease pain with frequent stone passage

Autotransplantation with pyelocystostomy – for patients with rare malignant stone disease

Partial nephrectomy

Ileal ureter substitution

URETEROLITHOTOMY

Long standing ureteral calculi1. Preoperative radiograph to document stone location2. Incision lateral to the sacrospinalis muscles to allow

medial retraction of the quadratus lumborum; anterior fascicle of the dorsal lumbar fascia must be incised to gain proper exposure

3. Vessel loop or Babcock clamp placed proximal to the stone to prevent frustrating stone migration

4. Longitudinal incision over the stone with a hooked blade to expose the calculus

5. Nerve hook to tease out the stone

PREVENTION

FLUID INTAKE

About 1.6 L/24 h Encouraged during mealtime Increased approximately 2 h after meals Encouraged to force a nighttime diuresis

METABOLIC INTERVENTION Stone analysis Outpatient urine collection during

typical activities & fluid intake Ca stone formers

Initial 24-h urine collection Include tests for Ca, uric acid, oxalate,

citrate, Na, volume, & pH Hypercalciuria: most common

abnormality

ORAL INTERVENTION Alkalinizing pH agents

Potassium citrate: oral agent that elevates urinary pH effectively by 0.7–0.8 pH units

Adverse effect: abdominal discomfort Indications: Ca oxalate calculi 2° to hypocitraturia

(<320 mg/day), including those with renal tubular acidosis; uric acid lithiasis & nonsevere forms of hyperuricosuric Ca nephrolithiasis.

Alternative alkalinizing agents: Na, potassium bicarbonate, orange juice, & lemonade

No effective long-term urinary acidifying agents

ORAL INTERVENTION Gastrointestinal absorption inhibitor

Cellulose phosphate binds Ca in the gut & inhibits Ca absorption & urinary excretion

Decreases urinary saturation of Ca phosphate & Ca oxalate

Phosphate supplementation Indicated for renal PO4 leak

ORAL INTERVENTION Diuretics

Thiazides can correct renal Ca leak associated with renal hypercalciuria

Prevents 2° hyperparathyroid state & its associated elevated vitamin D synthesis & intestinal calcium absorption

Hypokalemia hypocitraturia

ORAL INTERVENTION Calcium supplementation

Indication: Enteric hyperoxaluric Ca nephrolithiasis Ca gluconate & Ca citrate

Uric acid-lowering medications Allopurinol

Urease inhibitor Acetohydroxamic acid: effective adjunctive

treatment in chronic urea-splitting urinary tract infections associated with struvite stones

Prophylaxis after removal of struvite stone

ORAL INTERVENTION Prevention of cystine calculi

Penicillamine: reduces the amount of urinary cystine that is relatively insoluble

Mercaptopropionylglycine (Thiola)

BLADDER STONES

BLADDER STONES Manifestation of an underlying pathologic

condition, including voiding dysfunction or a foreign body

Most seen in men Developing countries: frequently found in

prepubescent boys Stone analysis: ammonium urate, uric acid, or

Ca oxalate stones Irritative voiding symptoms, intermittent

urinary stream, UTI, hematuria, or pelvic pain

PROSTATIC STONES Prostatic calculi: found within prostate gland

per se & are found uncommonly within the prostatic urethra

Represent calcified corpora amylacea & rarely found in boys

Usually of no clinical significance, rarely they are associated with chronic prostatitis

Large prostatic calculi: may be misinterpreted as a carcinoma

Dx: radiograph or transrectal ultrasound

SEMINAL VESICLE STONES Smooth & hard Associated with hematospermia PE: stony hard gland; multiple stones

present with crunching sensation Confused with tuberculosis of the

seminal vesicle

URETHRAL STONES Originate from bladder Develop 2° to urinary stasis, urethral

diverticulum, near urethral strictures, or at sites of previous surgery

Females: rarely develop urethral calculi due to short urethra & lower incidence of bladder calculi; associated with urethral diverticula

Symptoms : intermittent urinary stream, terminal hematuria, & infection

Dx: palpation, endoscopic visualization, or radiographic study

PREPUCIAL STONES Occur in adults Develop 2° to a severe obstructive

phimosis or poor hygiene with inspissated smegma

Dx confirmed by palpation Tx: dorsal prepucial slit or formal

circumcision