A long tradition defines the scope of pathology as both a clinical specialty and an area of biomedical research. Although rooted in the correlation of anatomical and histological changes with clinically apparent disease (and hence the iconic images of autopsy and microscope), modern pathology studies the causes of disease (etiology) and their expression/evolution (pathogenesis) at the molecular level using the tools of molecular genetics and biochemistry as well as analysis at the cellular and organ system levels. Because the first symptoms and signs of disease are often those of the body’s response to injury, the pathologist uses this response to provide critical clues as to the etiological agent and the likely mode of pathogenesis.
As a clinical endeavor, pathology is both a diagnostic and prognostic specialty, which by defining and classifying the disease process, suggests (and helps to evaluate) therapeutic approaches to the physician. But in a broad sense, pathology seeks to understand the basis of the disease process. At times, this broad scope of interest leads to a “pathocentric” view of medicine (Figure 2-1).
“Pathocentric” view of medicine.
This chapter will present an overview of how the pathologist views mechanisms of irreversible cell injury (cell death), reversible cell injury, and the organism’s response to both. Oxygen deprivation to tissue (ischemia) leading to a form of tissue damage termed an infarct is of notable clinical significance (e.g., in myocardial infarcts, “heart attacks”) and will serve as an important model. Second, this chapter will briefly consider injury resulting from the process of host defense, either as appropriately targeted to tissue injury or inappropriately directed toward self-components either as “bystander effects” or “autoimmunity.” Finally, the chapter will consider changes due to the aging process. A simplistic, but nevertheless useful overview of this chapter is presented in Figure 2-2.
A simplified but useful overview.
CELL INJURY AND CELL DEATH: AN INTRODUCTION
An interest in the effects of disease and trauma is nothing new. People have been pathologists observing the effects of disease since the dawn of recorded history, likely before. Egyptian medical texts described infectious diseases (tetanus is an often-quoted example). The Tanach (Hebrew Bible) tells of a disease visited upon the Philistines that may have been bubonic plague. The Iliad describes the surgeon Machaon treating Menaleus’ arrow wound. Egyptian physicians described the host reaction to wounds (suppuration, inflammation) as early as the third millennium BC and may have treated them with antiseptic agents. Pathologists now study the etiology, pathogenesis, and host reaction to disease to diagnose illness, prognosticate, help suggest the best therapy, and ultimately discover the cause of death.