Progress Of Gout Flare

Recent advances in the understanding of acute gouty attack are illustrated (left). The attack is primarily neutrophil-dependent and initiated by the capacity of urate crystals to activate complements and to stimulate synovial lining cells and resident in?ammatory cells to induce a variety of in?ammatory mediators. As depicted (right), self-resolution of acute gout is mediated by several mechanisms, including coating of monosodium urate crystals with proteins and clearance by differentiated macrophages, neutrophil apoptosis, clearance of apoptotic cells, inactivation of in?ammatory mediators, and the release of anti-in?ammatory mediators. Dots represent humoral in?ammatory mediators, including cytokines and chemokines. Apo B = apolipoprotein B; Apo E = apolipoprotein E; C1q, C3a, C3b, C5a, C5b-9 complement membrane attack complex; IL = interleukin; LDL = low-density lipoprotein; LTB4 = leukotriene B4; MCP-1 = monocyte chemoattractant protein-1/CCL2; MIP-1 = macrophage in?ammatory protein-1/CCL3; MMP-3 = matrix metalloproteinase-3; NO = nitrous oxide; PAF = platelet-activating factor; PGE2 = prostaglandin E2; PLA2 = phospholipase A2; PPAR-? = peroxisome proliferator-activated receptor-? ligand; PPAR? = peroxisome proliferator-activated receptor-? ligand; TGF-? = transcription growth factor-? ; TNF-? =  tumor necrosis factor- ?; S100A8/A9 = myeloid-related protein; sTNFr = soluble tumor necrosis factor receptor.

Diagram showing the cellular effects of gout flares during and after an episode of acute gout.

Progress Of Gout Flare

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Uric Acid Levels & Gout

Annual incidence of gout was less than 0.1% for men with serum uric acid levels less than 416 ?mol/L, 0.4% for men with levels of 416 to 475 ?mol/L, 0.8% for men with levels of 476 to 534 ?mol/L, 4.3% for men with levels of 535 to 594 ?mol/L, and 7.0% for men with levels greater than 595 ?mol/L, according to the Normative Aging Study (13). The solid line denotes these data points; the dotted line shows an exponential projection of the data points.

This chart emphasizes how the risk of gout rises with higher uric acid levels. The data comes from “Asymptomatic hyperuricemia. Risks and consequences in the Normative Aging Study.” report, from which, the abstract states:

To quantify the consequences of asymptomatic hyperuricemia, this study examined rates for a first episode of gouty arthritis based on 30,147 human-years of prospective observation. A cohort of 2,046 initially healthy men in the Normative Aging Study was followed for 14.9 years with serial examinations and measurement of urate levels. With prior serum urate levels of 9 mg/dl or more, the annual incidence rate of gouty arthritis was 4.9 percent, compared with 0.5 percent for urate levels of 7.0 to 8.9 mg/dl and 0.1 percent for urate levels below 7.0 mg/dl. With urate levels of 9 mg/dl or higher, cumulative incidence of gouty arthritis reached 22 percent after five years. Incidence rates were three times higher for hypertensive patients than for normotensive patients (p less than 0.01). The strongest predictors of gout in a proportional hazards model were age, body mass index, hypertension, and cholesterol level, and alcohol intake. When the serum urate level became a factor in the model, none of these variables retained independent predictive power. At the final examination, only 0.7 percent of participants had a serum creatinine level of 2.0 mg/dl or more, with no evidence of renal deterioration attributable to hyperuricemia. These data support conservative management of asymptomatic hyperuricemia.

Uric Acid Levels & Gout Chart

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Development Of Gout Overview

Gout is mediated by the supersaturation and crystallization of uric acid within the joints. The amount of urate in the body depends on the balance between dietary intake, synthesis, and excretion. Hyperuricemia results from the overproduction of urate (10%), from underexcretion of urate (90%), or often a combination of the two. Approximately one third of urate elimination in humans occurs in the gastrointestinal tract, with the remainder excreted in the urine.

Diagram showing that, if excretion of gout through kidneys and the gut is less than food intake and natural metabolism, then uric acid becomes too concentrated, and crystallization may lead to gout

Development Of Gout Overview

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Uric Acid: Antioxidant Protection For Heart, Cancer, Aging

Uric Acid: Antioxidant Protection For Heart, Cancer, Aging

Title
Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis.
Published
Nov 1981
Author(s)
Ames BN, Cathcart R, Schwiers E, Hochstein P.

Uric Acid investigation describing the valuable properties of urate as an antioxidant. Reports how uric acid fights against the toxic oxygen radicals that might be responsible for heart disease, cancer, and aging.

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Uric Acid & Evolution

Uric Acid & Evolution

Title
Loss of urate oxidase activity in hominoids and its evolutionary implications.
Author(s)
Oda M, Satta Y, Takenaka O, Takahata N.
Published
Mol Biol Evol. 2002 May;19(5):640-53.

Investigation of the genetic changes that caused humans to evolve without urate oxidase. Our lack of oxidase, present in most other animals, prevents uric acid breakdown. This gives us several advantages, with the disadvantage that if the levels of uric acid rise too high, gout and other diseases will affect us.

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Serum Urate And Recurrent Gout Attacks

Serum Urate And Recurrent Gout Attacks

A retrospective study of the relationship between serum urate level and recurrent attacks of gouty arthritis: evidence for reduction of recurrent gouty arthritis with antihyperuricemic therapy. Jun 2004. Shoji A et al. Gout study showing the relationship between persistent reduction of blood uric acid below the saturation point, and the reduction in frequency of acute gouty attacks.

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Serum Uric Acid In Acute Gout

Serum Uric Acid In Acute Gout

Serum uric acid in acute gout. Nov 1997. Logan JA et al. Gout study showing how uric acid often falls during an acute gout flare. In this study, the average fell from 9.4mg/dL to 7.4mg/dL (0.56mmol/L to 0.44mmol/L)

The authors emphasize that this increases the risk of mis-diagnosis and poor patient management.

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