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All tissues in the body are composed of parenchymal cells, which are specialized to perform the functions of that particular tissue, and interstitial connective tissue elements, which act as the supporting framework of the tissue (Figure I-1). Human disease results from the action of various injurious agents on tissues. Injurious agents may act on parenchymal cells or interstitial connective tissue, causing biochemical or structural damage. Biochemical damage may result in abnormal function and disease without producing any structural alteration in tissue. Structural damage may sometimes be recognized only by microscopic examination of the tissue. In parenchymal cells, it results either in reversible changes short of cell death (cell degeneration) or in irreversible cell death (necrosis). These are discussed in Chapter 1: Cell Degeneration & Necrosis. Interstitial tissue damage results in interstitial abnormalities (Chapter 2: Abnormalities of Interstitial Tissues). Parenchymal cell damage may result from interstitial abnormalities and vice versa.

Figure I–1.
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General causes and effects of tissue injury. Many different types of injuries act on tissues ① to cause direct parenchymal cell injury ② or interstitial injury ③. Interstitial abnormalities may cause indirect parenchymal cell injury ④.


A variety of injurious agents act on human tissues (Figure I-1) to produce tissue damage either directly or indirectly.


Direct Injury


A noxious agent may act directly on the tissue and interfere with its structure or biochemical function. An example is a burn, in which the heat causes immediate direct destruction of cell membranes and other tissue components and coagulation of intracellular proteins.


Indirect Injury


An injurious agent may act at some site other than the tissue in question to produce an abnormality in the immediate environment of the cell or cause accumulation of some toxic substance, which in turn causes cell damage. Representative causes of indirect injury include accumulation of toxic products in kidney and liver failure or a change in extracellular pH, electrolyte concentrations, or core body temperature. These indirect injuries may result in cell damage in many different tissues throughout the body, eg, structural and functional abnormalities in the brain in liver failure (hepatic encephalopathy).

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