A deleterious set of responses which occurs at the subcellular level, stimulated by some injury, and which is often manifested in altered structure or functioning of the affected organism. With advances in understanding and the development of sensitive probes, it has become clear that the fundamental causes of diseases are based on biochemical and biophysical responses within the cell. These responses are now being categorized and, slowly, the mechanisms are being understood.

The term homeostasis refers to functionàl equilibrium in an organism and to the processes that maintain it. There is a range of responses that is considered normal. If cells are pushed to respond beyond these limits, there may be an increase, a decrease, or a loss of normal structure or function. These changes may be reversible or irreversible. If irreversible, the cells may die. Thus, subcellular changes may be reflected in altered tissues, organs, and consequently organisms, and result in a condition described as diseased.

Lesions are the chemical and structural manifestations of disease. Subjective manifestations of a disease process such as weakness, pain, and fatigue are called symptoms. The objective measurable manifestations such as temperature, blood pressure, and respiratory rate changes are called signs or physical findings. Changes in the chemical or cellular makeup of an organ, tissue, or fluid of the body or its excretory products are called laboratory findings. To make a diagnosis is to determine the nature of the pathologic process by synthesizing information from these sources evaluated in the light of the patient's history and compared with known patterns of signs and symptoms. In common usage, the term disease indicates a constellation of specific signs and symptoms attributable to altered reactions in the individual which are produced by agents that affect the body or its parts.

Etiology is the study of the cause or causes of a disease process. Although a disease may have one principal etiologic agent, it is becoming increasingly apparent that there are several factors involved in the initiation of a disease process. Susceptibility of the individual is an ever present variable. The etiologic factors can conveniently be divided into two categories (see table). One group consists of endogenous (internal; within the body) factors, and may originate from errors in the genetic material. The other category of etiologic factors is exogenous (environmental). These account for the majority of disease reactions. Exogenous factors include physical, chemical, and biotic agents.

Pathogenesis refers to the mechanisms by which the cell, and consequently the body, responds to an etiologic agent. It involves biochemical and physiological responses which are reflected in ultrastructural, microscopic, or gross anatomic lesions. There are a limited number of ways in which cells respond to injury. The nature of the response is modified by the nature of the agent, dose, portal of entry, and duration of exposure, as well as many host factors such as age, sex, nutritional state, and species and individual susceptibility.

The diseases which are important in causing human death have changed in the last 80 years. In 1900 six of the ten leading causes of death in the United States were infectious (biotic) agents. At present, only one of the ten leading causes of death in the United States, influenza and pneumonia, is due to biotic agents. While most of the biotic causes of diseases were being brought under control, continued population growth (in large part, a consequence of the control of infectious disease) and the remarkable growth of industrialization have been associated with an increased prevalence of diseases caused by physical and chemical agents. These include cancer, cirrhosis, and cardiovascular disease.

General principles of the organism's response to toxic substances, some of which occur naturally in the environment, have evolved from a great number of investigations of agent-host interaction. They are: (1) All substances entering the organism are toxic; none is harmless. Dose rate of exposure and route of entry into the body determine whether a toxic response will occur or not. (2) All agents evoke multiple responses. (3) Most of the biological responses are undesirable, leading to the development of pathological changes. (4) A given dose of an agent does not produce the same degree of response in all individuals. Thus, when disease is viewed as interaction between the environment and the individual, the control of disease is largely the management of the environmental causes of disease.