Pathophysiology refers to the physiological processes associated with a disease or injury. In the<unk>  of medicine, diseases became better understood as human anatomy became better understood. The development of autopsy in the 15th and 16th centuries was key to this learning. As anatomists detailed the complex structures of the human body, they began to pay more attention to the pathological structures associated with diseases, their causes and effects, and mechanisms of progress. By the 18th century, many such pathologic observations were being published in textbooks and journals. This work lay important foundations for advances in medical treatment and intervention.<unk> cally, various notions of present-day<unk> " have described some general mix of excessive urine (polyuria), excessive thirst (polydipsia), and weight loss (see:<unk> #Early accounts). Over the past few centuries, these symptoms have been linked to updated understandings of how the disease works, and how it manifests differently across cases. This section outlines these developments as various diabetic conditions have become better understood.<unk>  mellitus Today, the term<unk> " most commonly refers to<unk>  mellitus.<unk>  mellitus is itself an umbrella term for a number of different diseases involving problems processing sugars that have been consumed (glucose metabolism).<unk> cally, this is the<unk> " which has been associated with sugary urine (glycosuria). Role of the pancreas In 1683, a surgical experiment by Johann Conrad Brunner almost led to a medical breakthrough. He excised the pancreas of a neighbour's hunting dog, causing polyuria and polydipsia. Brunner very clearly described these classic symptoms in pancreatectomized dogs, but made no association with<unk> . In 1788, Thomas Cawley published a case study in the London Medical Journal based on an autopsy of a diabetic patient. He observed stones and signs of tissue damage in the patient's pancreas, noting that the "right extremity of the pancreas was very hard, and appeared to be scirrhous." Considering the idea that<unk>  "be not a disease of the kidneys", he suggested that "a cure may have been effected... provided the stomach and organs subservient to digestion had retained their digestive power". In the decades that followed, Richard Bright (1831) and Von Recklinhausen (1864) also reported gross changes in the pancreas of diabetic patients. Claude Bernard demonstrated the function of pancreatic juice in digestion between 1849 and 1856, clarifying an important link in the pathophysiology of<unk> . Plaque in Strasbourg commemorating the 1889 discovery by Minkowski and Von Mering In 1889, Joseph von Mering and Oskar Minkowski excised the pancreas of a dog, which soon developed the symptoms of<unk> . According to some accounts, Minkowski was taught by his supervisor, Bernhard Naunyn, to test for sugar in urine whenever he noticed polyuria. According to some other accounts, a laboratory attendant pointed out that only the urine of the pancreatectomized dogs attracted flies, prompting the researchers to test for sugar. Ultimately, the pair tested for sugar in the urine and confirmed the connection with<unk>  mellitus. This event is commonly credited as the formal discovery of a role for the pancreas in<unk> . While the researchers continued to work on obtaining a pancreatic extract, they were unable to obtain the presumed anti-diabetic substance. In 1893, Edouard Hédon in Montpellier conducted a pancreatectomy in two stages. In the first, he took out almost all of the pancreas, cutting off the supply of pancreatic juice entirely. He then left a small remnant of pancreas grafted under the dog's skin. The dog did not become diabetic until the remaining graft was also excised, leading Hédon to the conclusion that the pancreas must have two functions: digestion via an external secretion, and carbohydrate metabolism via some internal secretion that was released directly into the bloodstream. J.J.R. MacLeod, among the Toronto group that later isolated and purified insulin for clinical use, cited this finding as the most convincing proof of an internal secretion in his 1913 book,<unk> : Its Pathological Physiology. Also in 1893, Édouard Laguesse suggested that the islet cells of the pancreas, described as "little heaps of cells" by Paul Langerhans in 1869, might play a regulatory role in digestion. These cells were named Islets of Langerhans after the original discoverer. Soon after, it was established that the role of the pancreas in carbohydrate metabolism could be localized to the islets; Eugene Lindsay Opie (1901) confirmed this connection in relation to<unk>  mellitus. In 1909, Belgian physician Jean de Mayer hypothesized that the islets secrete a substance that plays this metabolic role, and termed it "insulin", from the Latin insula ("island"). Sir Edward Albert Sharpey-Schafer independently proposed the same in 1916, not knowing at the time that de Meyer had made the same suggestion a few years prior. The endocrine role of the pancreas in metabolism, and indeed the existence of insulin, was further clarified between 1921-1922 when a group of researchers in Toronto, including Frederick Grant Banting, Charles Herbert Best, J.J.R. MacLeod, and James Collip, were able to isolate and purify the extract. Types of<unk>  mellitus Between 1850 and 1875, French researchers Apollinaire Bouchardat and E. Lancereux acknowledged a need for classification. They distinguished between those diabetics that were lean, had severe symptoms, poor outcomes, and pancreatic lesions at autopsy<unk>  maigre), and those that were overweight, presented later in life with a milder form of the disease and had a better prognosis if put on a low calorie diet<unk>  gras). These descriptions are comparable to the two types identified by Ayurvedic physicians Sushruta and Charaka (400–500 AD), with one type being associated with youth and the other with being overweight. Harold Percival Himsworth established a clearer distinction in 1936, differentiating two types of<unk>  based on sensitivity to insulin (both injected and pancreatic). In 1950, R. D. Lawrence observed that some diabetics were deficient in insulin and that some were not. Philip Hugh-Jones, while working in Jamaica in 1955, clarified Lawrence's classification and coined the terms "type 1" and "type 2"<unk> . He also noted a rarer variety observed in insulin-resistant youth (whose condition could not be placed into the two types). He called this third group "type J", where J stood for Jamaica. The terms type 1 and 2 were for some time forgotten. In 1976, they were revived and popularized by Andrew Cudworth after he discovered the link between type 1<unk>  and a specific genetic marker.<unk>  insipidus thumb In 1794, Johann Peter Frank gave a relatively clear description of<unk>  insipidus, as a "long continued abnormally increased secretion of non-saccharine urine which is not caused by a diseased condition of the kidneys". This remained the general state of knowledge for another century. William Osler, in the first edition of his textbook (1892), summarized the pathophysiology of the condition as follows: "The nature of the disease is unknown. It is doubtless of nervous origin. The most reasonable view is that it results from a vasomotor disturbance of the renal vessels... giving rise to continuous renal congestion." thumb In 1912, Alfred Eric Frank, then working on<unk>  mellitus in the department of Oskar Minkowski in Breslau, reported a specific link to the pituitary gland upon observing a case of a man who had survived after shooting himself in the temple. Morris Simmonds drew the same connection in 1913. Thereafter, numerous reports documented cases of<unk>  insipidus associated with pituitary lesions, steadily accumulating evidence favouring the hypothesized connection. George Oliver and Edward Albert Schafer were among the first researchers to document its endocrine functions. In the first two decades of the 20th century, however, a number of conflicting reports on the diuretic versus anti-diuretic properties of the pituitary extract caused confusion in the field. A general agreement was reached that some of the results that reported diuresis was due to increased pressure and blood flow to the kidney, while the posterior pituitary extract had an antidiurectic effect. By the 1920s, accumulated findings defined<unk>  insipidus as a disorder of the pituitary. The main question now became whether the cause of<unk>  insipidus lay in the pituitary gland or the hypothalamus, given their intimate connection. In 1920, Jean Camus and Gustave Roussy summarized a number of years of research, reporting that they had produced polyuria in dogs by puncturing the hypothalamus while leaving the pituitary intact. These results were later replicated by many others. Over the next few decades, various competing hypotheses arose as to where and how the "posterior lobe hormones" were produced, transported, and stored. Finally in 1954, Berta and Ernst Scharrer concluded that the hormones were produced by the nuclei of cells in the hypothalamus. Types of<unk>  insipidus Since about 1850 it had been known that<unk>  insipidus might be a hereditary disorder. In 1945, it was noted that vasopressin had no effect on treating some patients with familial<unk> . Based on this clue, it soon came to light that there exist two types of hereditary<unk>  insipidus. In 1947, the anti-diuretic hormone (ADH)-insensitive variety was termed nephrogenic<unk>  insipidus (NDI), and attributed to a defect in the loop of Henle and the distal convoluted
History of diabetes
History of hypertension
History of aspirin
History of invasive and interventional cardiology
History of general anesthesia
History of chemical warfare
History of HIV/AIDS
History of cardiopulmonary resuscitation