Gout Pathophysiology
The clinical symptoms of gout occur in response to the formation of monosodium urate (MSU) crystals. Gout becomes a serious health condition after the deposition of monosodium urate (MSU) crystals. Several pathophysiological checkpoints are important for the development of gout in a person. At first, elevation of urate concentrations occurs which further contributes to the urate under-excretion and urate overproduction increasing the total balance of urate. Overproduction of urate levels occur due to changes in the degradation and synthesis pathways of purine. Under-excretion through kidneys is also an important reason behind the elevated serum urate levels leading to hyperuricemia. There are changes in the urate transporters within the tubules of nephron which are collectively known as urate transportasome. [4]
Under-excretion by gut or extra-renal urate under-excretion also adds to the development of gout or hyperuricemia. The next checkpoint for the formation of MSU crystals in some individuals is the symptomatic gout along with crystal deposition. There is an acute inflammatory response to the MSU crystals which is a sterile and self-limiting acute auto-inflammatory response which mediate by the innate activation of immune system. The key cytokine causing the acute inflammatory response is interleukin 1 beta which works in response to the MSU crystals. In certain patients, there is advancement of gout along with structural joint damage. Structural joint damage in gout occurs along with the direct influence of MSU crystals on joint tissues and there is indirect effect of joint inflammation. Moreover, along with their central role in the pathogenesis of gout, the MSU crystals play a physiological role especially as a danger signal or adjuvant in immune surveillance.
There are several interacting checkpoints involving in the pathophysiology of gout. High uric acid level is the integral risk factor for the development of gout and is one of the prerequisite for the formation of monosodium urate (MSU) crystal formation. Urate under-excretion through gut and renal mechanisms is the great process for hyperuricemia in a majority of the people. Multiple metabolic, genetic, and environmental factors have an association with serum urate and change the urate synthesis or transport in one or other way. Urate super-saturation is the most crucial factor in the formation of MSY crystals. Other factors like connective tissue components, temperature, and pH also play a major role in crystal formation.
Alterations in the regulatory processes of the inflammatory response to MSU crystal formation might affect the susceptibility of an individual in the development of gout. Leucine-rich nucleotide causes more binding oligomerization with pyrin protein 3 inflammasome. Formation of tophus is the fundamental feature of the advancing gout and both the inflammatory tissue component and MSU crystals of the tophus involve in the development of joint damage leading to gout. Interleukin 1 beta is an important cytokine which plays a major role in the inflammatory response to crystal formation along with other components of immune system. Extreme levels of structural joint damage leads to the appearance and onset of symptoms which greatly affects the quality of life of a gout patient. [5]