Uric acid, Serum
This is one of the serum analytes commonly present in general laboratory
chemistry panels or profiles.
Gout is actually diagnosed with: (1) findings of diagnostic crystals in synovial fluid or (2) surgically excised
joint or other tissue tissue containing tophi or (3) flecks of fibrinoleukocytic exudate containing urate crystals. Pathologists should be aggressive in finding rounded voids in H&E tissue & alerting as to crystallosis likelihood, even if findings are not histologically diagnostic [L13-3592]. But, don't over diagnose as crystalosis. The void-like pseudocrystallosis foci sometimes seen in chondromalacia [here]. And, there can be a nonspecific chronic fibrinous osteoarthritis with the fibrin containing degenerative, H&E pale, cartilagenous, "pseudo-gouty" foci in the fibrin [L14-2122]. We may also be asked to search joint fluid for evidence of
difficult to prove septic prosthesis failure [here].
- urate: Crystallosis (clinically occult or obvious) found in tissue is important because it may indicate gout or may indicate that the patient has it due to the atherogenic metabolic syndrome or gout. Monosodium urate (MSU) crystals are thin needles. Gouty histological deposits are usually or often faintly basophilic with H&E histology, if any stain uptake at all, and may be surrounded by a giant cell reaction, often deceptively poorly expressed. In October 2003, Dr. Armstrong found
that a best-sensitive histological technique for rapid intra-operative diagnosis in soft
tissue is to frozen-section the suspect area and do polarized light exam without any staining of the slide. Or, one might do a non-FS cover-slipped wet prep or even a squash prep of exudate without coverslip [L13-14888]. Or one can process for histology with alcohol fixation and
bypass as much aqueous processing & staining as possible so that the urate needles polarize. November 2009, Dr. Spalding discovered that following up on incidentally found, suspicious foci in permanently processed arthroscopic or other tissue can be, by way of an unstained but xylene-deparafinized recut [some parafin formulations have polarizable content such that deparafinization is mandatory], found to reveal most of the deposits under polarized light exam [L10-10126]). This means that the crystals had originally been lost and only the nonpolarizable H&E shadows or voids are left behind (lost mainly during the aqueous slide-staining process)! Sometimes, even this maneuver fails, & one must make a decision based on the H&E fibrillar-crytalline grey or ghost-like voids left behind with associated histiocytes [L10-10530; L10-10735; L10-141,50] or as pink rounded crystalline-like deposits in acute septic like exudate, sometimes surrounded by nuclear debris from the polys [L13-14888]. DDX: Chondromalacia may manifest (never with surrounding histiocytes) histologically in H&E preps as similar rounded or hazy pale single or fused areas of granular or slightly fibrillar cartilage degeneration (on high power...even oil immersion exam, there are no crystal shapes [L13-14089]...a sort of pseudocrystallosis). In other instances, the H&E features are so powerfully persuasive that a diagnosis is made routinely [L10-10587]. You may see a tophus or tophi in skin specimens suspected as a cyst or such (most commonly on the ear helix [S10-939]). I recently had a case in a Crohn's disease patient thought arthroscopically to be a urate arthropathy knee which showed an unusually exuberant histiocytic surface synovitis that, at first looked like a brisk hyperplasia of plump synovial surface cells (was this a rare form of highly active urate arthritis, or was it prdominantly an enteropathic arthritis, or was it an overlap of both [L10-10530]).
- calcium pyrophosphate: pseudogout, when crystallosis is heavy, dense, enough, may cause characteristic radiological features (articular surface deposits or intrameniscal deposits). Chondrocalcinosis (pseudogout) of articular surfaces
can cause an "acute joint" with neutrophil exudate but negative Mirra frozen section criteria for septic joint [L07-9036]). Calcium pyrophosphate dihydrate (CPPD...pseudogout) [L07-2681; L08-12251] has a more
brownish-purple deposit by H&E (rhomboid- to rod-shaped pleomorphic CPPD crystals) when retains some calcium & it tends to polarize (calcium pyrophosphate normal H&E color of granular deposits may be lacking when decalcification and/or too long of an acid H&E stain6 has entirely removed the calcium component [L11-373; L12-5270; L13-3592] so that only rounded to oval, colorless, intra-soft-tissue, crystal-containing voids are seen [L13-7850]).
- wear & tear (detritic synovitis, detritic arthropathy):
tumoral calcinosis: nonrefractile H&E basophilic, globular structures (basophilic psammoma body–like calcospherites of calcium hydroxyapatite [CHA]) with surrounding giant cell reaction. Can reflect CREST syndrome & produce a chalky effusion.
fibrin: and, a recently "irritated"...by surgery or other...joint can appear to have focal
crystallosis arthroscopically but the whitish foci be inspissated, degrading tissue-surface fibrin [L07-9422]).
artifact: don't be fooled by palarizable sponge fragments or other debris that just happens to cling to the specimen.
- osteoarthritic fragments: bone microfragments likely still calcified & bone with characteristic H&E & polarized light morphology.
- prosthetic debris: the polyethylene (PE) debris is refractile [L09-5227] under polarized light exam (as silicone may be), remindful of crystallosis, & generates a histiocytic aseptic synovopathy & can be complexified by a complicating hemorrhagic arthrosis which organizes into siderotic macrophages & then some spindled histiocytes to further amplify the synovopathy & even make the surgeon have concern for early VNPS [L09-3745]; due to differing weight bearing forces, the debris tends to be much finer in total hip replacement (THR) cases & coarser & with giant cells in total knee (TKR) cases3; cobalt-chromium, titanium detritus may cause a black color5; can see in joint effusion sample as well as in synovectomy tissue. The debris can even migrate & cause lymphadenopathy4 with sinus histiocytosis, the node cut surface maybe even being black in the case of metallic debris.
Causes of Decreased Values/Levels
Causes of Increased Values/Levels
- asymptomatic hyperuricemia is common & more common with advancing age & most
never develop gout
- gout (many cases negative for uric acid elevation)
- post-therapeutic rise after cytotoxic treatment of some malignancies (additional
coordinated treatment may be done to prevent injury from crystal deposits)
- medications (low-dose salicylates; thiazide diuretics; niacin; ethanol)
- renal insufficiency
- assoc. with type II diabetes
- assoc. with dyslipidemia
- assoc. with hypertension
- assoc. with coronary atherosclerotic heart disease
- assoc. with obesity...primarily truncal (metabolic syndrome)
- a marker of increased risk for death by all causes in Japanese railroad
Other names for this exact or approximate agent are:
- Rott KT, Agudelo CA, Gout Editorial, JAMA 289(21):2857-2860, 4 June 2003.
- Shidham V, et. al., "Evaluation of Crystals in Formalin-Fixed, Paraffin-Embedded Tissue Sections for the Differential Diagnosis of Pseudogout, Gout, and Tumoral Calcinosis", Modern Pathology 14:806 - 810 (01 Aug 2001), [HERE].
- Schmalzried TP, et. al., "Polyethylene wear debris and tissue reactions in knee as compared to hip replacement prostheses", J. Applied Biomaterials 5(3):185-190, 30 Aug. 2004.
- Benz EB, et. al., "Lymphadenopathy Associated with Total Joint Prostheses. A Report of Two Cases and a Review of the Literature", The Journal of Bone and Joint Surgery 78:588-93 (1996).
- Albores-Saavedra J, et. al., "Sinus histiocytosis of pelvic lymph nodes after hip replacement. A histiocytic proliferation induced by cobalt-chromium and titanium", The American journal of surgical pathology 1994;18(1):83-90.
- Ohira T and Ishikawa K, "Concise report. Preservation of calcium pyrophosphate dihydrate crystals: effect of Mayer's haematoxylin staining period", Ann Rheum Dis 60(1):80-82, 2001.
(posted 8 June 2003; latest addition 6 April 2014)