The pathogenesis of gout — Journal of Rheumatic Diseases

Claims

1. crystallization-factors
   Low temperature, pH 7–9 and high sodium concentration reduce urate solubility, and damaged joints (for example from injury or osteoarthritis) are more prone to crystal deposition and gout.

   "Low temperatures, pH 7~9 and high concentration of sodium ions are known factors that reduce urate solubility and promote MSU crystallization. And joints that are damaged, such as those injured or affected by osteoarthritis, tend to have MSU crystal deposition and are more likely to develop gout"

   Locator: section: Monosodium urate crystallization and deposition · Quote language: en
2. diet-vs-genes
   Eating purine-rich meat and seafood (but not purine-rich plant foods), alcohol and high fructose intake are associated with gout risk, but diet appears to affect serum urate less than genetic variants do.

   "Increased consumption of purine-rich foods such as meat or seafood, rather than high-purine foods of plant origin, is associated with an increased risk of gout. Alcohol and high fructose intake are also associated with the risk of gout. However, diet appears to have a smaller effect on serum uric acid levels than genetic variants on serum urate levels or the risk of gout"

   Locator: section: Hyperuricemia · Quote language: en
3. flare-course
   A typical gout flare is a sudden onset of severe pain and swelling, usually in a lower-limb joint, that resolves within 7–14 days and is followed by a symptom-free period until the next flare.

   "The typical presentation of gout is an acute onset of severe pain and swelling, usually in a joint of the lower limb, which can also involve periarticular tissues (bursa, tendons), resolving within 7~14 days. After resolution, there is a pain-free asymptomatic period until another gout flare occurs"

   Locator: section: Introduction · Quote language: en
4. nets
   Neutrophils recruited to the joint ingest urate crystals and release their chromatin and proteins as neutrophil extracellular traps (NETs).

   "Attracted and activated, neutrophils ingest MSU crystals and eject their chromatin along with cytosolic and granule proteins, resulting in the formation of neutrophil extracellular traps (NETs). This process is called NETosis"

   Locator: section: Acute gout flare · Quote language: en
5. not-all-hyperuricemia
   Hyperuricemia is necessary for gout, but most people with it do not develop gout: about 22% of men with serum urate above 9.0 mg/dL develop gout within five years, and only 24% of people with asymptomatic hyperuricemia had urate deposits on dual-energy CT.

   "Hyperuricemia is essential for the development of gout but not all individuals with hyperuricemia develop gout. About 22% of males who had serum urate level greater than 9.0 mg/dL develop gout in 5 years ... only 24% of participants with asymptomatic hyperuricemia had urate deposits in joints or tendons detected on DECT"

   Locator: section: Hyperuricemia; Monosodium urate crystallization and deposition · Quote language: en
6. no-uricase
   Most mammals convert uric acid to soluble allantoin with the enzyme uricase, but humans and other apes lack uricase, so uric acid is the end product of purine metabolism.

   "Uric acid can be metabolized into allantoin by uricase in most mammals, and allantoin is highly water-soluble and readily excreted. However, humans and certain other primates, including chimpanzees, gorillas, orangutans and gibbons, lack uricase, so uric acid is the end product of purine metabolism"

   Locator: section: Hyperuricemia · Quote language: en
7. saturation-6-8
   Because extracellular fluid is rich in sodium, urate is present mostly as monosodium urate, which begins to crystallize at a serum urate of about 6.8 mg/dL.

   "Because of the high concentration of sodium in the extracellular compartment, urate is largely present as MSU, and a serum urate level of approximately 6.8 mg/dL is the concentration at which MSU crystals begin to precipitate"

   Locator: section: Monosodium urate crystallization and deposition · Quote language: en
8. tophi
   Advanced gout is marked by tophi, chronic inflammation and structural joint damage; tophi usually appear after at least 10 years of gout, in joints, bone, cartilage, tendons and skin, and are closely linked to bone erosion.

   "Advanced gout is characterized by tophi, chronic inflammatory responses, and structural joint damage. Tophi usually appear clinically in people with a longer duration of gout (at least 10 years) and higher serum uric acid levels. Tophi are commonly found in articular, periarticular, and subcutaneous areas such as joints, bone, cartilage, tendons, and skin. ... There is a close relationship between the presence of tophi and structural damage in joints affected by gout."

   Locator: section: Advanced gout · Quote language: en
9. transporter-genes
   Variants in the urate transporter genes SLC2A9, SLC22A12, SLC17A1 and ABCG2 are most strongly associated with variation in serum urate.

   "The urate transporter genes SLC2A9 (encoding GLUT9), SLC22A12 (encoding URAT1), SLC17A1 (encoding NPT1) and ABCG2 are most strongly associated with variation in serum urate levels"

   Locator: section: Hyperuricemia · Quote language: en
10. underexcretion
    Underexcretion of urate by the kidneys or intestine is the main cause of hyperuricemia in most people; about two-thirds of urate is excreted by the kidneys and one-third by the intestine.

    "Underexcretion of urate, either through decreased renal or intestinal excretion, is the main mechanism of hyperuricemia in most people. ... Approximately two-thirds of urate excretion occurs in the kidneys, while the remaining one-third occurs in the intestine"

    Locator: section: Hyperuricemia · Quote language: en