Gout

Rheumatology‎ > ‎Crystal Induced Arthropathy‎ > ‎

2020 ACR Gout Management Guideline

Gout:

UA Pathogenesis:

AIXG
As the name suggest, HGPRT acts on Hypoxanthine and Guanine and not on Xanthine . Analogous is case of Adenosine, with APRT. Note: there is no Xanthien PRT.
Enzyme : PRPP acts on both HGPRT and AGPRT
Enzymes; 5 nucleotides, PNP, XO, GDA

Most people maintain a relatively stable uric acid level between 4 and 6.8 mg/dL and a total body uric acid pool of approximately 1000 mg. Persons with serum uric acid levels greater than 6.8 mg/dL, even without clinical gout, may deposit uric acid crystals either occultly or in the form of appreciable masses (tophi), with the consequence that the total body urate pool may be significantly higher than in persons who are not hyperuricemic. Ref: KF Pg. 1599

Name 2 inborn errors of metabolism leading to increased Urate production.

PRPP increased activity. Usually, this level is limited. Increased activity means more Purine synthesis (AMP, IMP, GMP), leads to subsequent increased metabolism of Purine and increased UA formation.
HGPRT deficiency leads to inability to salvage purine from Hypoxanthine or Guainine and hence, there is more UA production.

Complete HGRPT deficiency : Lesch-Nyhan syndrome, is an X-linked recessive disorder characterized by extremely high levels of serum urate, gout flares, nephrolithiasis, mental retardation, movement disorders, and behavioral disorders, including self-mutilation.The disorder can occasionally arise by de novo mutation; female carriers are generally asymptomatic but may have elevated serum urate levels. In contrast to the gout flares and nephrolithiasis, the neurologic findings in Lesch-Nyhan syndrome are independent of hyperuricemia and unresponsive to urate-lowering drugs.
Partial deficiency of HGPRT1. Kelley-Seegmiller syndrome have a partial deficiency of HGPRT1

Increased ATP consumption leading to increased AMP formation.

Persons with glucose-6-phosphatase deficiency (type I glycogen storage, or von Gierke’s disease) demonstrate a high rate of both purine and ATP turnover. The lactic acidemia that secondarily occurs in patients with glucose-6-phosphatase deficiency may also contribute to hyperuricemia by promoting decreased renal urate excretion (discussed in a subsequent section).
Persons with fructose-1-phosphate aldolase deficiency lack the capacity to metabolize fructose-1-phosphate. Fructose-1-phosphate accumulation causes feedback inhibition of fructokinase and fructose accumulation in the blood. As an apparent consequence of these changes, AMP accumulates and promotes hyperuricemia. Need to understand this both.

AAA

IIHX

XXX

GGG

Mechanism of Inflammation in Gout

Gout NEJM 2011

Types of Gout

Acute Gouty Arthritis
Intercritical or IntervalGout
Recurrent Gouty Arthritis or Chronic Tophaceous gout

https://www.cdc.gov/nchs/ppt/icd9/att7croftsep08.pdf

Acute Gout Attack

2012 ACR Guidelines for Management of Gout. Part 2: Therapy and Antiinflammatory Prophylaxis of Acute Gouty Arthritis

Diagnosis:

YeLLow light - ParaLLeLL when light passes through the crystal
If acute, unless able to rule out Septic arthritis with reasonable certainty, will need Arthrocentesis
If Interval or Recurrent - Confirm the diagnosis of Gout - know the DDx - Classify patient on etiology of hyperuricemia (Primary vs. Secondary - overproduction / under excretor)