inflammation • Hallmark of PYELONEPHRITIS and ACUTE INTERSTITIAL NEPHRITIS and may accompany RBC casts in cases of glomerulonephritis • Primary marker for distinguishing pyelonephritis (upper UTI) from cystitis (lower UTI) WBC CASTS • Appearance: mostly composed of neutrophils, appear granular, cast matrix containing WBC • Reporting: average number/lpf • Clinical correlation: (+) protein, leucocyte esterase in the strip and observation of adjacent free WBC’s • Supravital stains can also be used to demonstrate the nuclei. It is helpful in differentiating RTE from WBC • Clinical correlations: – WBC, protein, and LE strip – Bacteria (pyelonephritis) – Eosinophil casts in stained specimens (AIN) BACTERIAL CASTS • Appearance: bacilli bound in the protein matrix • Clinical significance: Pyelonephritis (may be pure bacterial casts or mixed with WBC) • Sources be correlated with the presence of WBC casts, many free WBCs and bacteria in the urine sediment • Confirmation: Gram stain EPITHELIAL CELL CASTS • RTE Cells attached to a protein matrix • Clinical significance: Advanced Tubular Destruction. Also associated with heavy metal/chemical or drug-induced toxicity, viral infections and allograft rejection • If pyelonephritis is suspected, it should be accompanied by WBC casts • Since they are formed in the DCT, cells visible on the cast matrix are the smaller, round and oval cells • May be difficult to differentiate from WBCs particularly if degeneration has occurred. • Staining and phase microscopy can be helpful to enhance the nuclear detail needed for identification • Bilirubin stained RTE cells: Hepatitis FATTY CASTS • Appearance: Fat droplets and Oval Fat bodies attached to a protein matrix. Highly refractile (due to lipids) • Seen in cases of LIPIDURIA and are also associated with nephrotic syndrome, toxic tubular necrosis, diabetes mellitus and crush injuries • Confirmation is done by staining Sudan III and Oil Red O or the use of polarized microscope Mixed Cellular Casts • Most commonly encountered are: – RBC and WBC casts in cases of glomerulonephritis – WBC and RTE cell casts or WBC and bacterial casts in cases of pyelonephritis GRANULAR CASTS • Two types • Coarse granular casts • Fine granular casts • Could be pathologic or non pathologic • Non pathologic origin of the granules are from the lysosomes of RTE during normal metabolism (Strenous exercise) • Pathologic causes represent disintegration of cellular casts and tubular cells or protein agreggates filtered by glomerulus – Pyelonephritis – glomerulonephritis WAXY CASTS • Representative of extreme stasis indicating Chronic Renal Failure • Appearance: brittle, highly refractive cast matrix with JAGGED ENDS OR NOTCHES • Supravital stains- they appear pink BROAD CASTS • Often referred to as Renal Failure Casts (also represent extreme urine statis) • Indicates destruction (widening) of the tubular walls • Reflection of highly compromised kidneys • Bile stained broad casts are indicative of tubular necrosis caused by viral hepatitis Cast formation • Hyaline casts- beginning; PROTOTYPE OF ALL CASTS at first made up of entirely Tamm-Horsfall protein • Cellular casts- (WBC, RBC, Epithelial cell cast) which will undergo degeneration and dissolution • Coarse granular casts- will be formed and later on will disintegrate • Fine granular casts- will be formed and will degenerate to form: • Waxy casts- FINAL DEGENERATIVE FORM OF ALL CAST URINARY CRYSTALS Urinary Crystals • Usual crystals are rarely of clinical significance • Primary reason for identification: – Detect abnormal crystals indicative of liver disease, inborn errors of metabolism and renal damage caused by crystallization of iatrogenic compounds Normal Crystals in Acid Urine Amorphous Urates • Seen in acid urine and appear as yellow brown granules • If seen in clumps- resemble granular casts • Frequently encountered in specimens that had been preserved after refrigeration and may appear as pink sediment due to uroerythrin • Usually seen in higher pH higher that 5.5 but lower than 7.0 • Soluble in heat and alkali URIC ACID (Monosodium Urates) • Are seen in variety of shapes: rhombic, four sided flat plates (whet stones), wedges and rosettes, barrel-shaped/lemon shaped crystals • Soluble in alkali; appear yellow brown in color but may also be colorless and have a six sided hexagonal shape similar to cystine • Increased amounts are seen in cases of: – Increased nuclei acid and purine metabolism – Leukemic patients receiving chemotherapy – Lesch-nyhan syndrome (orange sand in diapers) – gout Acid Urates and Sodium Urates • Rarely encountered • Seen in less acidic rine • Have little or no clinical significance • Acid urates appear as large granules with spicules • Sodium urates appear as needle shaped and are seen in synovial fluid during episodes of gout • If seen in urine, they appear slender prisms in fan-like manner and are called peacock-tail crystals Calcium Oxalate • Frequently seen in acidic urine but can also be seen in neutral or alkaline urine • Occur in two forms: – Monohydrate calcium oxalate (whewellite crystals) – Appear oval or dumbbell shaped – Birefringent under polarized light – Clinically significant in cases of ethylene glycol poisoning – Dihydrate calcium oxalate (weddelite crystals) – Appear colorless, octahedral envelope – Two pyramids joined at their bases – Enveloped-shaped crystals – More commonly observed than the monohydrate and are also birefringent under polarized light Normal Crystals in Alkaline Urine Amorphous Urates • Seen in alkaline urine and appear as white or colorless granules • Frequently encountered in specimens that had been preserved after refrigeration and may appear as white sediment • An be differentiated from a urates by the color of the sediment and the pH of urine • Soluble in dilute acetic acid Triple Phosphate • Also known as ammonium magnesium phosphate or struvite crystals • Colorless, prism that resembles “coffin-lid’’ • Birefringent under polarized light • No clinical significance but are often seen in alkaline urine associated with urea-splitting bacteria • Soluble in dilute acetic acid Calcium Phosphate • Appear colorless, flat rectangular plates or thin prisms often in rosette formation • The rosette form may be confused with sulfonamide crystals • Calcium phosphate will be dissolved in dilute acetic acid but sulfonamides will not • No clinical significance although it is a common constituent of renal calculi Calcium Carbonate • Appear as small, colorless dumbbell or spherical shape crystals • Some may appear in clumps that resemble amorphous material but produce gas after the addition of acetic acid • They are also birefringent and have no clinical significance Ammonium Biurate • Appear as yellow brown crystal with a characteristic “thorny apples” appearance (spicule-covered spheres) • Commonly encountered in old specimens and may be associated with the presence of ammonia produced by urea splitting enzymes • The only urate found in alkaline urine Abnormal Urine Crystals Abnormal Urine Crystals • Usually found in acid urine, but rarely in neutral urine • Most have very characteristic shapes but should be confirmed using chemical tests • Manner of reporting of abnormal crystals: • Average and reported/lpf CYSTINE • Appear in cases of cystinuria (defective tubular reabsorption of four amino acids) • Lysine • Ornithine • Cystine- least soluble that is why prone to crystallization • May appear as colorless hexagonal plates and may be thick or thin • They may be difficult to distinguish from uric acid CYSTINE VS. URIC ACID Substance CYSTINE URIC ACID
Solubility Ammonia-soluble Ammonia-soluble
Soluble to dilute HCl Insoluble to dilute HCl
Birefringence NEGATIVE POSITIVE
(thick cystine are the only positive) CYANIDE NITROPRUSSIDE POSITIVE NEGATIVE TEST Formation of Red-purple color Cholesterol crystals • Rarely seen unless specimens have been refrigerated because lipids remain in droplet form • They appear as rectangular plates with a notch in one or more corners • Also described as “staircase pattern” or “stair step crystals” or “notched crystals” • Associated with lipiduria such as nephrotic syndrome and can be seen together with an oval fat body or fatty casts • Highly birefringent in polarized light Radiographic Dye Crystals • Similar to cholesterol crystals and are also highly birefringent • Seen in patients who had undergone xrays using contrast media • Usually manifests high specific gravity; higher than 1.040; measured via refractometer Tyrosine • Appear as fine colorless to yellow needles that form clumps or rosettes • Clinically significant in cases of liver disease in conjunction with leucine crystals • Can also be encountered in some cases of defective amino acid metabolism Leucine • Appear as yellow brown spheres that demonstate concentric circles with radial striations • Usually described as “scallop-lily” crystals • Often mistaken as fat globules • Add ether to differentiate leucine and fat globules • Fat globules are dissolved; leucine remains • Tyrosine+leucine= chronic liver disease Bilirubin crystals • Present in hepatic disorders that produced large amounts of bilirubin in urine • They appear as clumped needles or granules with characteristic yellow color of bilirubin • Should be accompanied with positive chemical test for bilirubin • In disorders that produce renal tubular damage; such as viral hepatitis, bilirubin crystals may be seen incorporated into the matrix of casts • Bilirubin stained RTE cell cast seen in cases of hepatitis • Bile stained broad cast caused by severe hepatitis Miscellaneous/Iatrogenic Crystals • Sulfonamide crystals • Seen in patients with UTI and inadequate fluid hydration • Appear as rhombic; needles; whetstones, sheaves of wheat, rosettes ranging from colorless to yellow brown (may resemble calcium phosphate) • Check patient’s medication history • May resemble bilirubin crystals; check for reagent strip reaction (diazo) to confirm identity of crystal • Ampicillin crystals – Encountered when the patient had taken massive doses of penicillin w/out adequate hydration – Appear as colorless needles that appear in bundles after refrigeration – Check patient’s medication history to aid in the identification of the crystal URINARY SEDIMENT ARTIFACTS Artifacts/Contaminants • Are commonly observed in specimens collected under improper conditions usually from contaminated specimen bottles • commonly encountered artifacts include: starch, oil droplets, air bubbles, pollen grains, fibers and fecal contamination • They may resemble cells and casts and should be properly observed when necessary • Artifacts are never reported in the result form Starch granules • Frequent contaminant from gloves • Appear as highly refractile spheres usually with a dimpled cente • Resemble RBC and FAT DROPLETS • Fat droplets manifest maltese cross and RBC’s (should be correlated with chemical tests) Oil Droplets • Highly refractile • Usually from contamination by immersion oils; lotions and cream • They resemble RBC Air bubbles • Occur when specimen is placed under a cover slip • They also resemble RBC Pollen grains • Seasonal contaminants • Appear as spheres with a cell wall and occasional concentric circles Hair and fibers • Usually diaper fibers that resemble casts (much longer and more refractile) • Under polarized light; fibers will polarize; casts will not • Fecal contamination such as plant and meat fibers may also be seen as artifacts in the urine sediment
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