Metaplasia:changeinphenotypeofdifferentiatedcells,ofteninresponsetochronicirritation,thatmakescellsbetterabletowithstandthestress;usuallyinducedbyaltereddifferentiationpathwayoftissuestemcells;mayresultinreducedfunctionsorincreasedpropensityformalignanttransformation
Under some circumstances, cells may accumulate abnormal amounts of various substances, which may be harmless or may cause varying degrees of injury. The substance may be located in the cytoplasm, within organelles (typically lysosomes), or in the nucleus, and it may be synthesized by the affected cells or it may be produced elsewhere.
The main pathways of abnormal intracellular accumulations are inadequate removal and degradation or excessive production of an endogenous substance, or deposition of an abnormal exogenous material (
Fig. 2.24 ). Selected examples of each are described as follows.
Fatty Change. Fatty change, also called steatosis, refers to any accumulation of triglycerides within parenchymal cells. It is most often seen in the liver, since this is the major organ involved in fat metabolism, but also may occur in heart, skeletal muscle, kidney, and other organs. Steatosis may be caused by toxins, protein malnutrition, diabetes mellitus, obesity, or anoxia. Alcohol abuse and diabetes associated with obesity are the most common causes of fatty change in the liver (fatty liver) in industrialized nations. This process is discussed in more detail in Chapter 16.
Cholesterol and Cholesteryl Esters. Cellular cholesterol metabolism is tightly regulated to ensure normal generation of cell membranes (in which cholesterol is a key component) without significant intracellular accumulation. However, phagocytic cells may become overloaded with lipid (triglycerides, cholesterol, and cholesteryl esters) in several different pathologic processes, mostly characterized by increased intake or decreased catabolism of lipids. Of these, atherosclerosis is the most important. The role of lipid and cholesterol deposition in the pathogenesis of atherosclerosis is discussed in Chapter 10.
Proteins. Morphologically visible protein accumulations are less common than lipid accumulations; they may occur when excesses are presented to the cells or if the cells http://ebooksmedicine.net 52CHAPTER 2 Cell Injury, Cell Death, and Adaptations
Defect in protein folding, transport
Accumulation of abnormal proteins
Lack of enzyme
Lysosomal storage disease: accumulation of endogenous materials
Ingestion of indigestible materials
Accumulation of exogenous materials
Fig. 2.24 Mechanisms of intracellular accumulation: (1) Abnormal metabolism, as in fatty change in the liver. (2) Mutations causing alterations in protein folding and transport, so that defective molecules accumulate intracellularly. (3) A deficiency of critical enzymes responsible for breaking down certain compounds, causing substrates to accumulate in lysosomes, as in lysosomal storage diseases. (4) An inability to degrade phagocytosed particles, as in carbon pigment accumulation.