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PA22.1-2 | Urine & Body Fluid Analysis — SDL Guide (Part 2)

Urine Microscopy — Casts

Casts are cylindrical moulds of the renal tubule lumen, formed by precipitation of Tamm-Horsfall protein (uromodulin) secreted by the thick ascending loop and early DCT. Low urine flow, high salt, and acidic pH promote cast formation. Their composition and shape carry diagnostic weight.

Cast type	Composition	Disease association
Hyaline	Pure Tamm-Horsfall protein, transparent	Normal in small numbers; dehydration, fever, vigorous exercise — benign
RBC casts	Tamm-Horsfall + red blood cells	Glomerulonephritis (post-streptococcal GN, IgA, lupus nephritis, Goodpasture's) — pathognomonic of glomerular bleeding
WBC casts	Tamm-Horsfall + neutrophils	Pyelonephritis (upper UTI), acute interstitial nephritis
Granular casts	Degenerated cellular casts ('muddy brown')	Acute tubular necrosis — the 'muddy brown granular cast' is ATN until proven otherwise
Waxy/broad casts	Highly refractive, wide diameter	Chronic kidney disease (advanced, slow urine flow in dilated tubules)
Fatty casts / oval fat bodies	Lipid-laden tubular cells; Maltese cross under polarised light	Nephrotic syndrome (massive lipiduria)
Epithelial cell casts	Desquamated tubular cells	ATN, heavy metal toxicity, viral nephritis

Memory peg: Hypertension = Hyaline (benign), Red = gloRmis (glomerulonephritis), White = pyelo (Whiteblood/pyelonephritis), Granular = ATN (Granular/muddy), Waxy = CKD (Waxy = wasted kidneys).

Diagram showing how Tamm-Horsfall protein forms urinary casts and comparing hyaline, RBC, WBC, and granular casts with their key disease associations. — **Panel A:** Renal tubule lumen, thick ascending limb, early distal convoluted tubule, Tamm-Horsfall protein / uromodulin secretion, low urine flow, high salt, acidic pH, protein precipitation, cylindrical cast mould. **Panel B:** Hyaline cast, pure Tamm-Horsfall protein, transparent smooth cylinder, benign associations: small numbers in normal urine, dehydration, fever, vigorous exercise. **Panel C:** RBC cast, red blood cells embedded in Tamm-Horsfall protein matrix, glomerulonephritis, pathognomonic glomerular bleeding. **Panel D:** WBC cast, neutrophils with multilobed nuclei embedded in Tamm-Horsfall matrix, pyelonephritis, acute interstitial nephritis. **Panel E:** Granular cast, muddy-brown degenerated cellular debris, coarse granules, acute tubular necrosis.

SELF-CHECK

Phase-contrast microscopy of urine from a 28-year-old with acute oliguria after an episode of haemolysis shows numerous 'muddy-brown' granular casts. WBC casts and RBC casts are absent. Which diagnosis does this best support?

A. Post-streptococcal glomerulonephritis

B. Acute pyelonephritis

C. Acute tubular necrosis

D. Lupus nephritis class IV

Reveal Answer

Answer: C. Acute tubular necrosis

Muddy-brown granular casts are the classic finding of acute tubular necrosis (ATN). They represent degenerated epithelial cells and cellular debris entrapped in Tamm-Horsfall protein, appearing as opaque brown cylinders. RBC casts are pathognomonic of glomerulonephritis; WBC casts indicate pyelonephritis. In ATN, the glomeruli are structurally intact — the injury is tubular — hence no RBC or WBC casts.

Urine Crystals

Crystals form when solutes exceed their solubility at the urine pH. Most crystals are incidental; a few are diagnostically critical.

Calcium oxalate (monohydrate — envelope/dumbbell; dihydrate — envelope/square):
• Most common crystal, seen at any pH.
• Monohydrate form: dumbbell or spindle-shaped — more associated with hyperoxaluria and stone disease.
• Dihydrate: classic envelope (octahedron). Seen after eating oxalate-rich foods (spinach, rhubarb), ethylene glycol poisoning (massive monohydrate crystals in ATN), or primary hyperoxaluria.

Uric acid (yellow-orange rhomboid/rosette, acid pH):
• Seen in gout, hyperuricaemia, myeloproliferative disorders, Lesch-Nyhan syndrome, high purine diet.
• Dissolve if urine is alkalinised — useful therapeutic manoeuvre.

Triple phosphate / struvite (coffin-lid, alkaline pH):
• Magnesium ammonium phosphate. Form only in alkaline urine produced by urease-splitting organisms (Proteus, Klebsiella).
• Grow to fill the renal pelvis → staghorn calculi (also called infection stones).

Cystine (hexagonal plates, acid pH):
• Pathognomonic of cystinuria — autosomal recessive defect in tubular reabsorption of dibasic amino acids (COAL: Cystine, Ornithine, Arginine, Lysine).
• Positive sodium nitroprusside (Brand's) test on urine. Treat by alkalinisation + high fluid intake.

Cholesterol (notched rectangular plates): Nephrotic syndrome, chyluria.

Leucine (yellow spheroids with radial striations) and Tyrosine (fine needles in sheaves): Severe hepatic failure (overflow aminoaciduria).

A six-panel medical diagram compares major urine crystals by microscopic shape, urine pH, and key clinical associations. — **Panel A:** Calcium oxalate monohydrate dumbbell/spindle crystals; calcium oxalate dihydrate envelope/octahedral crystals; any urine pH; hyperoxaluria; stone disease; ethylene glycol poisoning.. **Panel B:** Uric acid yellow-orange rhomboids and rosettes; acid urine pH; gout; hyperuricaemia; myeloproliferative disorders; Lesch-Nyhan syndrome; dissolves with alkalinisation.. **Panel C:** Triple phosphate / struvite coffin-lid crystals; alkaline urine pH; magnesium ammonium phosphate; urease-splitting organisms Proteus and Klebsiella; staghorn calculus.. **Panel D:** Cystine hexagonal plates; acid urine pH; cystinuria; COAL amino acids; positive sodium nitroprusside test; treatment with alkalinisation and high fluid intake.. **Panel E:** Cholesterol notched rectangular plates; nephrotic syndrome; chyluria.. **Panel F:** Leucine yellow spheroids with radial striations; tyrosine fine needles in sheaves; severe liver disease and aminoaciduria..

CLINICAL PEARL

Gout vs pseudogout: In synovial fluid analysis, polarised-light microscopy is the key discriminator. Monosodium urate (MSU) crystals (gout) are needle-shaped and negatively birefringent — they appear yellow when parallel to the slow axis of the compensator (mnemonic: gout = yellow when parallel = 'y-ellow p-arallel'). Calcium pyrophosphate dihydrate (CPPD) crystals (pseudogout/chondrocalcinosis) are rhomboid-shaped and positively birefringent — blue when parallel. The shape difference alone (needle vs rhomboid) distinguishes them under ordinary light if polarisation is unavailable.

SELF-CHECK

Urine microscopy from a 45-year-old with recurrent renal calculi shows flat hexagonal crystals that are birefringent under polarised light. Urine pH is 5.5. Which metabolic disorder does this finding indicate?

A. Primary hyperoxaluria

B. Xanthinuria

C. Cystinuria — autosomal recessive defect in dibasic amino acid transport

D. Hyperuricosuria from gout

Reveal Answer

Answer: C. Cystinuria — autosomal recessive defect in dibasic amino acid transport

Hexagonal (benzene-ring shaped) crystals in acid urine are pathognomonic of cystinuria. The defect is in the SLC3A1/SLC7A9 transporter responsible for tubular reabsorption of cystine, ornithine, arginine, and lysine (COAL). Calcium oxalate crystals are envelope-shaped; uric acid crystals are rhomboid/rosette in acid urine; xanthine crystals are amorphous yellow-brown.

Urine Patterns in Disease — Nephritic vs Nephrotic

Side-by-side medical diagram comparing nephritic urine with haematuria and RBC casts against nephrotic urine with heavy proteinuria, froth, oval fat bodies, fatty casts, and Maltese-cross lipid bodies. — **Panel A:** Nephritic syndrome: smoky-brown or cola-red urine, blood 2–3+, protein 1–2+, inflamed glomerulus, capillary wall breach, dysmorphic RBCs, RBC cast, WBC cast, post-streptococcal GN, IgA nephropathy, lupus nephritis, anti-GBM disease, MPGN.. **Panel B:** Nephrotic syndrome: pale-yellow frothy urine, protein 3–4+, blood negative, selective filtration barrier damage, albumin/protein leakage, oval fat bodies, fatty casts, waxy casts, Maltese-cross birefringence, minimal change disease, FSGS, membranous GN, diabetic nephropathy, amyloidosis.. **Bottom diabetic strip:** Diabetic urine pattern: glucose positive above renal threshold, ketones positive in DKA, microalbuminuria progressing to macroalbuminuria and nephrotic-range proteinuria.. **Bottom UTI strip:** UTI urine pattern: leukocyte esterase positive, nitrites positive, WBCs, bacteria, epithelial cells, and WBC casts in upper tract infection or pyelonephritis..

Two syndromic patterns are the cornerstone of nephrology interpretation:

Nephritic syndrome urine:
• Colour: smoky-brown, cola, or frank red haematuria
• Dipstick: blood 2–3+, protein 1–2+ (non-selective, moderate)
• Microscopy: dysmorphic RBCs, RBC casts (hallmark), WBC casts (if proliferative inflammation)
• Causes: post-streptococcal GN, IgA nephropathy, lupus nephritis, anti-GBM disease, MPGN
• Mechanism: glomerular inflammation → capillary wall breach → RBCs pass into tubule → casts form

Nephrotic syndrome urine:
• Colour: frothy (foam test for protein), pale-yellow
• Dipstick: protein 3–4+ (selective in minimal change disease — mostly albumin; non-selective in others), glucose absent unless DM
• Microscopy: oval fat bodies (lipid-laden tubular cells), fatty casts, waxy casts, Maltese-cross birefringence under polarised light
• RBCs and RBC casts are typically absent (glomerular wall is damaged selectively for charge/size — not torn)
• Causes: minimal change disease (children), FSGS, membranous GN, diabetic nephropathy, amyloidosis

DM urine pattern: Glucose positive (above threshold), ketones positive in DKA, protein positive when diabetic nephropathy develops (microalbuminuria → macroalbuminuria → nephrotic range).

UTI urine pattern: Dipstick LE+, nitrites+; microscopy WBCs, bacteria, WBC casts if upper tract (pyelonephritis); epithelial cells from trigone.