| BMP/ELECTROLYTES: | |||
| Na+ = 140 | Cl− = 100 | BUN = 20 | / Glu = 150 \ |
| K+ = 4 | CO2 = 22 | PCr = 1.0 | |
| ARTERIAL BLOOD GAS: | |||
| HCO3− = 24 | paCO2 = 40 | paO2 = 95 | pH = 7.40 |
| ALVEOLAR GAS: | |||
| pACO2 = 36 | pAO2 = 105 | A-a g = 10 | |
| OTHER: | |||
| Ca = 9.5 | Mg2+ = 2.0 | PO4 = 1 | |
| CK = 55 | BE = −0.36 | AG = 16 | |
| SERUM OSMOLARITY/RENAL: | |||
| PMO = 300 | PCO = 295 | POG = 5 | BUN:Cr = 20 |
| URINALYSIS: | |||
| UNa+ = 80 | UCl− = 100 | UAG = 5 | FENa = 0.95 |
| UK+ = 25 | USG = 1.01 | UCr = 60 | UO = 800 |
| PROTEIN/GI/LIVER FUNCTION TESTS: | |||
| LDH = 100 | TP = 7.6 | AST = 25 | TBIL = 0.7 |
| ALP = 71 | Alb = 4.0 | ALT = 40 | BC = 0.5 |
| AST/ALT = 0.6 | BU = 0.2 | ||
| AF alb = 3.0 | SAAG = 1.0 | SOG = 60 | |
| CSF: | |||
| CSF alb = 30 | CSF glu = 60 | CSF/S alb = 7.5 | CSF/S glu = 0.6 |
Pathophysiology (orphysiopathology) is a branch of study, at the intersection ofpathology andphysiology, concerning disorderedphysiological processes that cause, result from, or are otherwise associated with adisease orinjury. Pathology is the medical discipline that describes conditions typicallyobserved during adisease state, whereas physiology is the biological discipline that describes processes or mechanismsoperating within anorganism. 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.[1]
The termpathophysiology comes from theAncient 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 ProfessorAugust Friedrich Hecker [de] at theUniversity of Erfurt in 1790, and in 1791, he published the first textbook on pathophysiology,Grundriss der Physiologia pathologica,[2] spanning 770 pages.[3] Hecker also established the first academic journal in the field,Magazin für die pathologische Anatomie und Physiologie, in 1796.[4] The French physicianJean François Fernel had earlier suggested in 1542 that a distinct branch of physiology should study the functions of diseased organisms, an idea further developed byJean Varandal [de] in 1617, who first coined the term "pathologic physiology" in a medical text.[4]
In Germany in the 1830s,Johannes Peter Müller led the establishment of physiology research as autonomous from medical research. In 1843, theBerlin Physical Society was founded in part to purge biology and medicine ofvitalism, 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, Germananatomical pathologistRudolf Virchow, a former student of Müller, directed focus to the cell, establishingcytology 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.[4] Virchow’s influence extended to his studentJulius Cohnheim, who pioneeredexperimental pathology and the usage ofintravital microscopy, further advancing the study of pathophysiology.[4]
By 1863, motivated byLouis Pasteur's report on fermentation tobutyric acid, fellow FrenchmanCasimir Davaine identified a microorganism as the crucial causal agent of the cattle diseaseanthrax, but its routinely vanishing from blood left other scientists inferring it a mere byproduct ofputrefaction.[5] In 1876, uponFerdinand Cohn's report of a tiny spore stage of a bacterial species, the fellow GermanRobert Koch isolated Davaine'sbacterides inpure culture—a pivotal step that would establishbacteriology as a distinct discipline—identified a spore stage, appliedJakob Henle's postulates, and confirmed Davaine's conclusion, a major feat forexperimental pathology. Pasteur and colleagues followed up withecological investigations confirming its role in the natural environment via spores in soil.
Also, as tosepsis, Davaine had injected rabbits with a highly diluted, tiny amount of putrid blood, duplicated disease, and used the termferment of putrefaction, but it was unclear whether this referred as did Pasteur's termferment to a microorganism or, as it did for many others, to a chemical.[6] In 1878, Koch publishedAetiology 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 inaetiology, can be produced experimentally by the injection of putrid materials into animals."[6] Koch used bacteriology and the new staining methods withaniline dyes to identify particular microorganisms for each.[6]Germ theory of disease crystallized the concept of "cause" as presumably identifiable by scientific investigation.[7]
The American physicianWilliam Henry Welch trained in German pathology from 1876 to 1878, including underJulius Cohnheim, and opened America's first scientific laboratory—a pathology laboratory—atBellevue Hospital in New York City in 1878.[8] Welch's course drew enrollment from students at other medical schools, which responded by opening their own pathology laboratories.[8] Once appointed byDaniel Coit Gilman, upon advice byJohn Shaw Billings, as founding dean of the medical school of the newly formingJohns Hopkins University that Gilman, as its first president, was planning, Welch traveled again to Germany for training in Koch's bacteriology in 1883.[8] 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.[9] Hopkins medical school, led by the "Four Horsemen"—Welch,William Osler,Howard A. Kelly, andWilliam Stewart Halsted—opened in 1893 as America's first medical school devoted to teaching German scientific medicine.[8]
The first biomedical institutes,Pasteur Institute andBerlin Institute for Infectious Diseases, whose first directors wereLouis Pasteur andRobert 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 studentSimon Flexner as director of the pathology and bacteriology laboratories. Through the influence ofWorld War I andWorld War II, the Rockefeller Institute emerged as the world's leading institution in biomedical research.[citation needed]
The1918 pandemic triggered a frenzied search for its cause, although most deaths were vialobar pneumonia, already attributed topneumococcal invasion. In London, in 1928, a pathologist from the Ministry of Health namedFred Griffith documented pneumococcaltransformation, showing how it could change from virulent to avirulent and shift between antigenic types—almost as if it was a different species—questioning pneumonia's straightforward causation.[10][11] The laboratory of Rockefeller Institute'sOswald T. Avery, an early pneumococcal expert, was so troubled by the report that they refused to attempt repetition.[12]
During Avery's summer vacation,Martin Henry Dawson, a British-Canadian who believed everything from England was correct by default, repeated Griffith's results and achieved transformationin vitro, making it a more precise investigation.[12] Having returned, Avery kept a photo of Griffith on his desk while his researchers followed the trail. In 1944, Avery,Colin Munro MacLeod, andMaclyn McCarty reported the transformation factor asDNA, widely doubted amid estimations that something must act with it.[13] At the time of Griffith's report, it was unrecognized that bacteria even had genes.[14]
The first genetics,Mendelian genetics, began in 1900, yet inheritance of Mendelian traits was localized tochromosomes by 1903, thuschromosomal genetics.Biochemistry emerged in the same decade.[15] In the 1940s, most scientists viewed the cell as a "sack of chemicals"—a membrane containing only loose molecules inBrownian motion—and the only especial cell structures as chromosomes, which bacteria lack as such.[15] Chromosomal DNA was presumed too simple, so genes were sought inchromosomal proteins. Yet in 1953, American biologistJames Watson, British physicistFrancis Crick, and British chemistRosalind Franklin inferred DNA's molecular structure—adouble helix—and conjectured it to spell a code. In the early 1960s, Crick helped crack thegenetic code in DNA thus establishingmolecular genetics.
In the late 1930s, the Rockefeller Foundation had spearheaded and funded themolecular biologyresearch program—seeking a fundamental explanation of organisms and life—led largely by physicistMax Delbrück atCaltech andVanderbilt University.[16] Yet the reality oforganelles in cells was controversial amid unclear visualization with conventionallight microscopy.[15] Around 1940, largely via cancer research at Rockefeller Institute,cell biology emerged as a new discipline filling the vast gap betweencytology andbiochemistry by applying new technology—ultracentrifuge andelectron microscope—to identify and deconstruct cell structures, functions, and mechanisms.[15] The two new sciences interlaced,cell and molecular biology.[15]
Mindful of Griffith and Avery,Joshua Lederberg confirmedbacterial conjugation—reported decades earlier but controversial—and was awarded the 1958Nobel Prize in Physiology or Medicine.[17] AtCold Spring Harbor Laboratory in Long Island, New York, Max Delbrück andSalvador Luria led thePhage Group—hosting Watson—discovering details of cell physiology by tracking changes to bacteria upon infection withtheir viruses, the processtransduction. Lederberg led the opening of a genetics department atStanford University's medical school, and facilitated greater communication between biologists and medical departments.[17]
In the 1950s, research onrheumatic fever, a complication ofstreptococcal infections, revealed it was mediated by the host's own immune response, stirring investigation by pathologistLewis Thomas that led to identification of enzymes released by theinnate immune cellsmacrophages and that degrade host tissue.[18] In the late 1970s, as president ofMemorial Sloan–Kettering Cancer Center, Thomas collaborated with Lederberg, soon to become president ofRockefeller University, to redirect the funding focus of the USNational Institutes of Health toward basic research into the mechanisms operating during disease processes, which at the time medical scientists were all but wholly ignorant of, as biologists had scarcely taken interest in disease mechanisms.[19][20]
Thepathophysiology of Parkinson's disease (PD) involves theapoptosis, orprogrammed cell death, ofdopaminergic neurons as a consequence of alterations in biological activity within the brain related to the disorder. Several mechanisms have been proposed to explain neuronal apoptosis in PD; however, not all of these mechanisms are fully understood. The five primary mechanisms believed to contribute to neuronal death in PD includeprotein aggregation withinLewy bodies, disruption ofautophagy processes, alterations incellular metabolism andmitochondrial function,neuroinflammation, and breakdown of theblood-brain barrier, resulting in vascular compromise.[21]
Thepathophysiology of heart failure involves areduction in the efficiency of thecardiac muscle through damage or overloading. As such, it can be caused by a wide number of conditions, includingmyocardial infarction (in whichischemia of the heart muscle leads to its death),hypertension (which increases the force of contraction needed to pump blood), andamyloidosis (in which misfolded proteins are deposited in the heart muscle, causing it to stiffen). Over time, these increase the workload of the heart, leading to changes in the heart muscle itself.
Thepathophysiology of multiple sclerosis (MS) is that of an inflammatorydemyelinating disease in which activatedimmune cells invade thecentral nervous system and causeneuroinflammation,neurodegeneration, andtissue damage. The underlying precipitators of MS are incompletely defined. Current research inneuropathology,neuroimmunology,neurobiology,neuroimaging,clinical neurology, andpsychiatry provides support for the notion that MS is not a single disease but rather a spectrum.[22]
Thepathophysiology of hypertension is that of a chronic disease characterized by elevation ofblood pressure. Hypertension can be classified by cause as eitheressential (also known as primary oridiopathic hypertension) orsecondary. About 90–95% of hypertension is essential hypertension.[23][24][25][26]
Thepathophysiology of HIV/AIDS involves the acquisition ofHIV and thereplication of the virus insideT helper cells, causinglysis. T helper cells are required for almost alladaptive immune system responses. There is typically an initial period ofinfluenza-like illness following acquisition, and then a latent, asymptomatic phase. When theCD4 lymphocyte count falls below 200 cells/ml of blood, the HIV host has progressed toAIDS,[27] a condition characterized by deficiency incell-mediated immunity and resultant increase in susceptibility toopportunistic infections and somecancers.
Thepathophysiology of spider bites involves the effect of injectedvenom. A spider envenomation occurs when a spider injects venom into the skin. Not all spider bites deliver venom—a dry bite—and the amount of venom injected can vary depending on the type of spider and the circumstances of the encounter. The mechanical injury from a spider bite is generally not a serious concern for humans.
Thepathophysiology of obesity involves many developmental and maintenance processes.[28][29]
Research onobesity, as well as clinicalobesity medicine, and had been almost unapproached until theleptin gene was discovered in 1994 inJeffrey M. Friedman's laboratory.[30] The investigators hypothesized that leptin functions as asatiety factor. In theob/ob mouse, mutations in the leptin gene led to the obesephenotype, suggesting potential for leptin-based therapies for human obesity. However, shortly after,Jose F. Caro's team failed to find any leptin gene mutations in humans with obesity. Instead, they observed increased leptin expression, indicating potential leptin resistance in human obesity.[31]
