The field of pathology is devoted to understanding the causes of disease and the changes in cells, tissues, and organs that are associated with disease and give rise to the presenting signs and symptoms in patients. There are two important terms that students will encounter throughout their study of pathology and medicine:
Etiology refers to the underlying causes and modifying factors that are responsible for the initiation and progression of disease. It is now clear that many common diseases, such as hypertension, diabetes, and cancer, are caused by a combination of inherited genetic susceptibility and various environmental triggers. Elucidating the genetic and environmental factors underlying diseases is a major theme of modern medicine.
Pathogenesis refers to the mechanisms of development and progression of disease, which account for the cellular and molecular changes that give rise to the specific functional and structural abnormalities that characterize any particular disease. Thus, etiology refers to why a disease arises and pathogenesis describes how a disease develops (
Fig. 2.1
Defining the etiology and pathogenesis of disease not only is essential for understanding disease but also is the basis for developing rational treatments and effective preventive measures. Thus, pathology provides the scientific foundation for the practice of medicine.
To render diagnoses and guide therapy in clinical practice, pathologists identify changes in the gross or microscopic appearance (morphology) of cells and tissues, and biochemical alterations in body fluids (such as blood and urine). Pathologists also use a variety of morphologic, molecular, and other techniques to define the biochemical, structural, and functional changes that occur in cells, tissues, and organs in response to injury. We begin, in this chapter, with a discussion of cellular abnormalities induced by a variety of internal (e.g., genetic) and external (e.g., environmental) abnormalities and stresses.
Cells actively interact with their environment, constantly adjusting their structure and function to accommodate changing demands and extracellular stresses. The intracellular milieu of cells is normally tightly regulated such that it remains fairly constant, a state referred to as homeostasis. As cells encounter physiologic stresses (such as increased workload in the heart) or potentially injurious conditions (such as nutrient deprivation), they can undergo adaptation, achieving a new steady state and preserving viability and function. If the adaptive capability is exceeded or if the external stress is inherently harmful or excessive, cell injury develops (
Fig. 2.2 ). Within certain limits, injury is reversible, and cells return to their stable baseline; however, if the stress is severe, persistent, or rapid in onset, it results in irreversible injury and death of the affected cells. Cell death is one of the most crucial events in the evolution http://ebooksmedicine.net
MOLECULAR, FUNCTIONAL, AND MORPHOLOGIC ABNORMALITIES IN CELLS AND TISSUES CLINICAL MANIFESTATIONS: SIGNS AND SYMPTOMS OF DISEASE
Fig. 2.1 Stepsintheevolutionofdisease.Onlyselectedmajorcauses(etiologies)areshown.
of disease in any tissue or organ. It results from diverse causes, including ischemia (lack of blood flow), infections, toxins, and immune reactions. Cell death also is a normal and essential process in embryogenesis, the development of organs, and the maintenance of tissue homeostasis.
Because damage to cells is the basis of all disease, in this chapter we discuss first the causes, mechanisms, and consequences of the various forms of acute cell injury, including reversible injury and cell death. We then consider cellular adaptations to stress and conclude with two other processes that affect cells and tissues: the deposition of abnormal substances and cell aging.
NORMAL CELL (homeostasis) REVERSIBLE INJURY Injurious stimulus Severe, progressive IRREVERSIBLE INJURY
Fig. 2.2 Sequenceofreversiblecellinjuryandcelldeath.Necrosisandapoptosisarethetwomajorpathwaysofcelldeathandarediscussedindetaillater.