Bladder - Tamm-Horsfall protein

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Bladder

Acquired non-neoplastic anomalies

Tamm-Horsfall protein

Reviewer: Monika Roychowdhury, M.D., University of Minnesota Medical Center - Fairview (see Reviewers page)
Revised: 3 July 2011, last major update June 2011
Copyright: (c) 2003-2011, PathologyOutlines.com, Inc.

Definition
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● Tamm-Horsfall protein (THP) is a high molecular weight glycoprotein discovered by Tamm and Horsfall (J Exp Med 1952;95:71)
● Normally synthesized by thick ascending limb of loop of Henle, possibly distal convoluted tubules
● Most abundant protein in urine of healthy individuals
● May accumulate in renal parenchyma, perirenal soft tissue, renal hilar lymph nodes or bladder with pathologic conditions

Terminology
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● Also known as uromodulin, from UMOD gene on #16 (Wikipedia)

Pathophysiology
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● Inserted into luminal cell surface of renal tubules by glycosyl-phosphatidylinositol (GPI)-anchor, then excreted in urine at a rate of 50 - 100 mg/day
● Stones may form due to defective urinary Tamm Horsfall protein, due to lack of sialic acid (Int J Biol Sci 2008;4:215)
● Has a strong tendency to form macroaggregates of several million Daltons, particularly in highly tonic solutions
● Forms the matrix of urinary casts and stones

Epidemiology
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● THP deposits are present in 60% of cystectomy specimens, 4% of bladder biopsies
● In bladder specimens with THP deposits, mean age is 61 years, range 45-78 years, 85% are men (Am J Surg Pathol 1994;18:615)

Etiology / clinical features
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● Deposited in areas of necrosis, inflammation, fibrinous exudates, ulcer, crystalline material
● May be host defense factor against Proteus mirabilis urinary tract infections (J Urol 2009;181:2332)
● May have role in pathophysiology of interstitial cystitis (BJU Int 2009;103:1085)
● Comprises matrix of urinary casts formed during acute kidney injury (Webpath tutorial) and matrix of urinary stones
● Also present in deposits associated with interstitial kidney disease
● Also associated with urothelial carcinoma, nephrogenic adenoma

Gross description
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● Large, waxy, pale or weakly eosinophilic mass

Micro description
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● Glassy, PAS+ acellular material
● May also appear as strands of eosinophilic material obscured by fibrinous exudates or necrotic tissue

Micro images
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Diagram of Tamm-Horsfall protein secretion (green dots), forming a hyaline cast in the collecting duct

Pelvic granulomatous inflammation is focally associated with Tamm–Horsfall protein (asterisks) in the pelvic lumen

No thumbnails: Nephronophthisis: end-stage renal disease; lymphatics; pyelonephritis #1-protein cylinder; #2-protein cylinder; #3-immunostain

Positive stains
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● PAS, trichrome (pale blue)
● Anti Tamm-Horsfall protein antibody

EM description
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● Nonbranching 4 nm wide parallel fibrils

EM images
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No thumbnail: In lymphatics

End of Bladder > Acquired non-neoplastic anomalies > Tamm-Horsfall protein

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