Pathophysiology

Pathophysiology (or physiopathology) is a branch of study, at the intersection of pathology and physiology, concerning disordered physiological processes that cause, result from, or are otherwise associated with a disease or injury. Pathology is the medical discipline that describes conditions typically observed during a disease state, whereas physiology is the biological discipline that describes processes or mechanisms operating within an organism. Pathology describes the abnormal or undesired condition (symptoms of a disease), whereas pathophysiology seeks to explain the functional changes that are occurring within an individual due to a disease or pathologic state.

The term pathophysiology comes from the Ancient Greek πάθος (pathos) and φυσιολογία (phisiologia).

The origins of pathophysiology as a distinct field date back to the late 18th century. The first known lectures on the subject were delivered by Professor August Friedrich Hecker [de] at the University of Erfurt in 1790, and in 1791, he published the first textbook on pathophysiology, Grundriss der Physiologia pathologica, spanning 770 pages. Hecker also established the first academic journal in the field, Magazin für die pathologische Anatomie und Physiologie, in 1796. The French physician Jean François Fernel had earlier suggested in 1542 that a distinct branch of physiology should study the functions of diseased organisms, an idea further developed by Jean Varandal [de] in 1617, who first coined the term "pathologic physiology" in a medical text.

In Germany in the 1830s, Johannes Peter Müller led the establishment of physiology research as autonomous from medical research. In 1843, the Berlin Physical Society was founded in part to purge biology and medicine of vitalism, and in 1847, Hermann von Helmholtz, who joined the Society in 1845, published the paper "On the conservation of energy", highly influential in reducing physiology's research foundation to physical sciences. In the late 1850s, German anatomical pathologist Rudolf Virchow, a former student of Müller, directed focus to the cell, establishing cytology as the focus of physiological research. He also recognized pathophysiology as a distinct discipline, arguing that it should rely on clinical observation and experimentation rather than purely anatomical pathology. Virchow’s influence extended to his student Julius Cohnheim, who pioneered experimental pathology and the usage of intravital microscopy, further advancing the study of pathophysiology.

By 1863, motivated by Louis Pasteur's report on fermentation to butyric acid, fellow Frenchman Casimir Davaine identified a microorganism as the crucial causal agent of the cattle disease anthrax, but its routinely vanishing from blood left other scientists inferring it a mere byproduct of putrefaction. In 1876, upon Ferdinand Cohn's report of a tiny spore stage of a bacterial species, the fellow German Robert Koch isolated Davaine's bacterides in pure culture—a pivotal step that would establish bacteriology as a distinct discipline—identified a spore stage, applied Jakob Henle's postulates, and confirmed Davaine's conclusion, a major feat for experimental pathology. Pasteur and colleagues followed up with ecological investigations confirming its role in the natural environment via spores in soil.

Also, as to sepsis, Davaine had injected rabbits with a highly diluted, tiny amount of putrid blood, duplicated disease, and used the term ferment of putrefaction, but it was unclear whether this referred as did Pasteur's term ferment to a microorganism or, as it did for many others, to a chemical. In 1878, Koch published Aetiology of Traumatic Infective Diseases—unlike any previous work—in which, in 80 pages, Koch, as noted by a historian, "was able to show, in a manner practically conclusive, that a number of diseases, differing clinically, anatomically, and in aetiology, can be produced experimentally by the injection of putrid materials into animals." Koch used bacteriology and the new staining methods with aniline dyes to identify particular microorganisms for each. Germ theory of disease crystallized the concept of "cause" as presumably identifiable by scientific investigation.

The American physician William Henry Welch trained in German pathology from 1876 to 1878, including under Julius Cohnheim, and opened America's first scientific laboratory—a pathology laboratory—at Bellevue Hospital in New York City in 1878. Welch's course drew enrollment from students at other medical schools, which responded by opening their own pathology laboratories. Once appointed by Daniel Coit Gilman, upon advice by John Shaw Billings, as founding dean of the medical school of the newly forming Johns Hopkins University that Gilman, as its first president, was planning, Welch traveled again to Germany for training in Koch's bacteriology in 1883. Welch returned to America but moved to Baltimore, eager to overhaul American medicine, while blending Virchow's anatomical pathology, Cohnheim's experimental pathology, and Koch's bacteriology. Hopkins medical school, led by the "Four Horsemen"—Welch, William Osler, Howard A. Kelly, and William Stewart Halsted—opened in 1893 as America's first medical school devoted to teaching German scientific medicine.

The first biomedical institutes, Pasteur Institute and Berlin Institute for Infectious Diseases, whose first directors were Louis Pasteur and Robert Koch, were founded in 1888 and 1891, respectively. America's first biomedical institute, The Rockefeller Institute for Medical Research, was founded in 1901 with Welch, nicknamed "dean of American medicine", as its scientific director, who appointed his former Hopkins student Simon Flexner as director of the pathology and bacteriology laboratories. Through the influence of World War I and World War II, the Rockefeller Institute emerged as the world's leading institution in biomedical research.^{[citation needed]}