Local supersaturation is a common trigger of crystallization, and when the nucleus of the crystalline structure is formed, crystals can self-perpetuate and cause more crystallization and aggregation. Main mechanisms by which the formed crystals and aggregates cause pathological states and ultimately disease are acute necroinflammation, chronic tissue remodelling, and mechanical obstruction. Necroinflammation is an autoamplifying process where crystals are toxic to cells (cytotoxicity) and cause cell death (necrosis and regulated cell death) and a local and systemic inflammatory response. Cytotoxicity includes actin depolymerization, free radical and reactive oxygen species synthesis, and autophagy. Crystals can also directly activate inflammation via Mincle receptors, calcium and potassium signalling, calpains, cathepsin beta, proteases, and NLPR3 inflammasomes. Cells undergo cell death via three main mechanisms: nectoptosis via RIPK1, FADD, RIPK3, and MLKL, ferroptosis via GPX4 suppression, system Xc suppression, and NAPDH loss, as well as apoptosis via RIPK1 and caspase 8. These distressed cells then excrete alarmins, proteases, and damage-associated molecular patterns including HMGB1, histones, mitochondrial DNA, demethylated DNA and RNA, ATP, uric acid, and double-stranded DNA, which further activates Toll-like receptors and inflammasomes. Finally, this activates the inflammatory response including the release of pro-inflammatory interleukin 1 alpha, interleukin 1 beta, cytokines, kinins, lipid inflammatory mediators, complement system activation, vasodilation, an increase in endothelial permeability and leukocyte influx, and pain. Macrophages are key cells that try to remove crystals from tissues by phagocytosis. As part of the inflammatory response, they undergo polarization into a pro-inflammatory state called M1. Macrophages can ingest particles at most a few microns in diameter. If digestion of the crystalline material fails in the lysosomes however, macrophages undergo autophagy, form foam cells and giant cells, and try to do extracellular digestion in a process called frustrated phagocytosis. Crystals do not always cause acute inflammation but instead lead to chronic tissue remodelling. This process is possible because crystals get shielded from pro-inflammatory processes by compartmentalization (e.g. granuloma formation, fibrosis, and wound-healing) or molecular coating, or because inflammatory responses are suppressed with direct anti-inflammatory signalling (e.g. CLEC12A and NETosis). Crystals can attach to membranes via annexin II, CD44, and osteopontin.
Crystallopathy
Bisalbuminemia
Pica 
Lipiduria
Necrobiosis
Sialuria
Calcification
Neutrophilia