Background: Gout is the most common inflammatory arthropathy among adults and develops due to hyperuricemia and the long-term deposition of monosodium urate (MSU) crystals in the joints and tissues. Hyperuricemia results either from increased production of uric acid or decreased renal and intestinal excretion, with impaired urate excretion being the predominant underlying cause in most individuals. Although genetic variations in urate transporters significantly influence serum urate levels, not all individuals with hyperuricemia develop MSU crystal deposition or gout. Aim: To review and analyze the pathophysiology of gout arising from normal and disrupted purine metabolism. Materials and Methods: Using a narrative literature review approach, we examined published research on purine metabolism and the pathophysiological mechanisms of gout. Sources included Thomson Reuters, PubMed Central, Cochrane Library, Medline, Web of Science, and Google Scholar. A total of more than 670 publications were screened, of which 31 key studies relevant to the pathophysiology of gout were included in the final analysis. Results: The inflammatory response triggered by MSU crystals is primarily driven by activation of the NLRP3 inflammasome, which converts IL-1β (pro-IL-1β) and IL-18 (pro-IL-18) into their active forms, IL-1β and IL-18, thereby initiating inflammation. IL-1β and IL-18 further enhance cytokine and chemokine expression, recruiting neutrophils and other immune cells to the site of inflammation. Neutrophils not only amplify the inflammatory response but also contribute to its resolution through the formation of neutrophil extracellular traps (NETosis), which capture and degrade inflammatory mediators. Severe gout is characterized by tophus formation, chronic inflammation, and structural joint damage. Tophaceous deposits consist of aggregated MSU crystals surrounded by inflammatory cells and connective tissue and are closely associated with persistent inflammation and tissue injury. Conclusion A clear, logically structured understanding of disease pathophysiology—including cause-and-effect mechanisms— is essential for making evidence-based decisions in diagnosis and treatment.

The pathogenesis of chronic obstructive pulmonary disease (COPD) encompasses a number of injurious processes, including an abnormal inflammatory response in the lungs to inhaled particles and gases. Other processes, such as failure to resolve inflammation, abnormal cell repair, apoptosis, abnormal cellular maintenance programs, extracellular matrix destruction (protease/antiprotease imbalance), and oxidative stress (oxidant/antioxidant imbalance) also have a role. The inflammatory responses to the inhalation of active and passive tobacco smoke and urban and rural air pollution are modified by genetic and epigenetic factors. The subsequent chronic inflammatory responses lead to mucus hypersecretion, airway remodeling, and alveolar destruction. This article provides an update on the cellular and molecular mechanisms of these processes in the pathogenesis of COPD. During the past decade a plethora of studies have unravelled the multiple roles of nitric oxide (NO) in airway physiology and pathophysiology. In the respiratory tract, NO is produced by a wide variety of cell types and is generated via oxidation ofL-arginine that is catalyzed by the enzyme NO synthase (NOS). NOS exist in three distinct are forms: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). NO derived from the constitutive are forms of NOS (nNOS and eNOS) and other NO-adduct molecules (nitrosothiols) have been shown to be modulators of bronchomotor tone. On the other hand, NO derived from iNOS seems to be a proinflammatory mediator with immunomodulatory effects. Finally, the production of NO under oxidative stress conditions secondarily generates strong oxidizing agents (reactive nitrogen species) that may modulate the development of chronic inflammatory airway diseases and/or amplify the inflammatory response.