Urinary tract obstruction & Stones

Loin pain & hematuria

Principal sites of pathology leading to loin pain Spinal nerve roots Vertebral column Paraspinal & lumbar muscles Kidneys Renal pelvis / ureters Abdominal aorta Pancreas

Renal pain arises because of rapid stretching or inflammation of renal capsule Pain from the renal pelvis / ureter is caused by distention & excessive peristaltic contractions Any back / retroperitoneal structure may give rise to back pain

Macroscopic hematuria May arise from lesions anywhere within the urinary system, kidney, renal pelvis, ureter, bladder, urethra As few as 5 x 10 RBC/ml ; 1ul blood/ml urine can be detected visually as red-coloured urine Macroscopic hematuria needs to be distinguished from Red discolouration of urine caused by certain dyes & some drugs Presence of Haem pigment : intravascular hemolysis (Hb), rhabdomyolysis (myoglobin) Bleeding from outside the urinary tract; perineum, vagina 6

Bleeding from the bladder or above cause uniform discoloration of urine Bleeding from the urethra may cause bleeding separate from the urine or mixed with urine Hematuria from the renal parenchyma – glomeruli or interstitium – tends to be accompanied by proteinuria, casts, & dismorphic RBC (abnormal morphology) Bleeding from renal tumors or from lesions in the renal pelvis or below may be isolated or associated with pyuria – particularly with infections. Macroscopic hematuria from tumors are usually painless, whereas that from calculi / infection is usually associated with pain

Pyelonephritis/infections

Physical factors of stone formation The formation of stone is usually the result of many metabolic and physiologic disorders contributing to stone formation Stones in the urinary tract are composed of crystals and matrix skeleton. Physical factors of stone formation Supersaturation of the urine with respect to a particular solute, e.g. uric acid, due to increase in excretion or decrease in urine volume. At some point spontaneous nucleation and crystal growth occur – homogenous nucleation. Urine pH, determines the solubility of ccompounds in the urine. Uric acid & cystine are poorly soluble in acidic media, whereas calcium salts are poorly soluble at an alkaline pH. Crystalization inhibitors; normal urine contain factors that inhibit formation & growth of crystals – Mg, citrate, pyrophosphate, TPH, glucosamine, nephrocalcin. Heterogenous nucleation appears to be a major mechanism in stone formation. A small crystal, e.g. uric acid, serves as a nidus on which another compound, e.g. ca-oxalate, precipitates Infection with urea splitting / urease producing microorganisms

Disorders causing stone disease Gastrointestinal disorders; Fat malabsorption, IBD, small bowel resection & bypass can cause decreased urinery volumes, hyperoxaluria, hyperuric-aciduria, hypocitrateuria, acidic urine. Hyperparathyroidism / hypercalcemia Causes of hypercalcemia (& hypercalciuria) are # Cancer, immobilization, endocrinopathies, dietary, granulomatous disease, renal, drugs Vit D increases Ca absorption from intestine Idiopathic Hypercalciuria. 24h urine[Ca] > 300mg/24h (men), >250mg/24h (women) Gout & hyperuricosuria. May promote Ca-oxalate stones Epitaxy, ca-oxalate deposits on uric acid / Na-urate crystals as nidus Urate in urine binds glycosamineglycans, an inhibitor of stone formation Uric acid promotes the degree of aggregation of precipitated crystals Uric acid lithiasis; elevated urinary uric acid (24h urinary uric acid), acid urine; Gout, myeloproliferative disorders Treatment: alkalinization of urine to pH 6-7 , fluids, allopurinol Infection with urease producing bacteria urea splitting struvite stones Proteus in majority; Klebsiella, Pseudomonas, Providencia, Staphylococcus, Ureaplasma urealyticum, rarely E. coli. More common in patients with ileal conduits, hyperchloremic metabolic acidosis, ureteral dilatation, increased volume of residual urine, decreased renal function

Obstruction & anatomic abnormalities Drugs. Acetazolamide causes hyperchloremic metabolic acidosis, transiently elevates urine pH, and reduces citrate excretion Allopurinol increases xanthine excretion and may produce xanthine stones Several drugs have limited urine solubility, May promote stone formation or are absorbed into the crystal matrix of other stone Triamterene, ceftriaxone, sulfonamides, bactrim, sulindac, phenazopyridine Other : laxatives, vit D, calcium, Renal tubular disorders. Cystinuria, Inherited disorder of amino acid transport, associated with increased urinary excretion of cystine, ornithine, lysine, & arginine (COLA) Limited soloubility of cystine promotes recurrent stones, which are radioopaque, homogeneous, may assume staghorn form Therapy: high fluid intake, alkalinization of urine to pH 7.5 or more; reduce cystine excretion by low Na diet, D-penicillamine, trioponine, captopril (drugs with sulfhydryl) Distal RTA Alkaline urine, hypocitrateuria,hypercalciuria Hyperphosphaturia, causing hypophosphatemia & elevated 1,25-(OH)2D3, hypercalcemia Idiopathic hypercalciuria; reduced tubular reabsorption of Ca

Idiopathic Urolithiasis Enzymatic defects Xanthinuria. Deficiency xanthine oxidase Radiolucent xanthine stones 2,8-dihydroxyadenine. Deficiency adeninephosphoribosyl transferase (APRT) Radiolucent stones, requires infrared / crystallographic analysis Treatment with allopurinol Primary hyperoxaluria, Idiopathic Urolithiasis Majority of patients Risk factor profile Abnormally high excretion of Ca (>4mg/kg/d), uric acid, oxalate, Na Decrease in several inhibitory solutes Decreased urine volume! Ability of urine to inhibit agglomeration improves after treatment with alkali, which increase urinary citrate Excretion of citrate is decreased by systemic acidosis, depletion of kalium & magnesium, starvation acetazolamide, Most patients with low urinary citate have RTA, chronic diarrhea, hypokalemia, malabsorption, or high intake of animal protein

Urinary risk assessment First stone episode Dietary advice: meat, dairy, salt Fluids; f/u 6-12 months No growth Metabolically active Monitor 1-2 years Urinary risk assessment Dietary/fluid hypercalciuria hyperuricosuria hypocitric aciduria hyperoxaluria Factors persist Evaluate diet Evaluate for Evaluate for Meat, Ca, Na acidosis, RTA dietary excess GI malabsorption Dietary, meat GI disorders measure oxalate/ glycoliate Treatment options Repeat specific Reduce meat dietary fat / Dietary advice dietary Rx & / excess oxalate restriction Thiazides allopurinol K-Citrate B6, PO4 ?thiazides

Calcium stones Mg/NH4/PO4 Cystine (cannot Uric acid Asymptomatic  No Rx Symptomatic Acute colic: analgetics, fluids Calcium stones Mg/NH4/PO4 Cystine (cannot Uric acid stones dissolve, or (cannot dissolve/ obstructive obstructive) Symptomatic obstructive Percutaneous extraction + ESWL Small <2cm >2cm New stones old stones ESWL Perc ESWL Often requires Urography Usg <2cm >3cm ureteric stones ESWL Perc upper1/3 lower1/3 ESWL ESWL Extraction laser Rx

Metabolic activation of vit.D The result is an increase in 7-dehydrocholesterol Diet Skin UV Cholecalciferol liver Metabolic activation of vit.D The result is an increase in Ca & PO4 concentration 25-hydroxycholecalciferol kidney PTH Hypophosphatemia Calcitriol 24,25 D Small intestine Bone Kidney +PTH Increase Increase Decrease CaHPO4 Ca & Po4 Ca & PO4 absorption release excretion

Plasma Ca PTH Bone Kidney Vit.D Reabsorption Phosphate Ca Calcitriol Excretion reabsorption formation Release of Calcium & phosphate Intestinal CaHPO4 absorption Effect of PTH on Ca & phosphate metabolism. Net effect is increase in plasma Ca, with no change or decrease in plasma phosphate concentration

Plasma Ca [2+] PTH Cacitriol Increased Ca increased Ca increased phosphate increased phosphate From bone from intestine from bone & intestine excretion in urine Plasma Ca Plasma Phosphate increase unchanged

Plasma phosphate Calcitriol PTH Ca from intestine Decreased decrease increase phosphate Ca from bone phosphate from intestine excretion in urine Plasma [Ca] Plasma [PO4] Slight increased increased

Serum [calcium] Increased = systemic disease normal Normal Hyperuricosuria Hyperoxaluria No abnormality Urinary calcium = idiopathic hypercalciuria RTA

Laboratory investigation Serum electrolytes, BUN, Cr, Ca, PO4, Uric acid Urinalysis; microscopic exam of fresh specimen Urine culture Nitroprusside test for cystine Urine pH, first AM urine, under oil Stone analysis 24h urine for Cr, Ca, PO4, uric acid, Cystine, oxalate Radiologic studies, USG, BNO, IVP Special test as indicated; PTH, Thyroid, Cortisol, etc