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When injury is sublethal and sustained, cells and tissues tend to accumulate substances in abnormal quantities. This phenomenon was referred to as "infiltration" in the older literature. Usually such accumulations consist of molecule that are normally present such as triglycerides, glycogen, calcium, uric acid, melanin, and bilirubin. In some rare cases the accumulated substances are abnormal, as in amyloidosis, or more rarely in diseases attributable to defective genes in which abnormal metabolites accumulate because of faulty synthetic or degradative pathways. In addition, exogenous materials such as mineral dusts, pigments, and certain heavy metals may accumulate in the cytoplasm of cells after their introduction into the body by inhalation, ingestion, or injection. The basic process of ingestion, digestion, and storage of materials by cells involves their complex interactions of cell membranes and their fusion with lysosomes. Ingestion involves the inward flow of plasma membrane, which eventually encloses either fluid (pinocytosis) or particulate material (heterophagocytosis) that is internalized in the cytoplasm though still enclosed in a membrane-limited vacuole. As the vacuole (phagosome) moves inward, its membrane fuses with that of a pre-existing lysosome whereupon hydrolytic enzymes are released into the phagosome, interacting with and digesting the enclosed material. Because of the rapidity of pinocytosis, phagocytosis, phagosome movement, and fusion with lysosomes, certain types of cells may ingest and digest prodigious amounts of material. When the material is ingested in amounts so large that they exceed the capacity of lysosomes to digest them, or if the material is degraded slowly or not at all, it tends to accumulate in the cytoplasm, a condition referred to as "lysosomal overloading". Lysosomal overloading may occur rapidly if not all the digested material is subject to attack by digestive enzymes or more slowly, sometimes a matter of years, if only a small proportion of ingested material is undigested. Digestion of biologic material leads to the formation of soluble substances such as small peptides, amino acids, and sugars, which are reutilized by the cell.
Accumulation of material may cause the organs involved to become enlarged and firm. In the case of pigments the tissue may be strikingly coloured. When the storage of material is excessive, cells may be mechanically compromised and their functions may be impaired to the point that cell death occurs. Lysosomal overloading can also result from material originating within the cell, for example, the indigestible material resulting from focal cytoplasmic degradation, a process referred to as autophagy ("self-eating"). Autophagy is probably a normal cellular event responsible for the turnover of cell organelles and membranes.
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