Pathophysiology

Pathophysiologysample values

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 ofpathologyandphysiology,concerning disorderedphysiological processesthat cause, result from, or are otherwise associated with adiseaseorinjury.Pathology is the medical discipline that describes conditions typicallyobservedduring adiseasestate, whereas physiology is the biological discipline that describes processes or mechanismsoperatingwithin anorganism.Pathology describes the abnormal or undesired condition, whereas pathophysiology seeks to explain the functional changes that are occurring within an individual due to a disease or pathologic state.

Etymology

The termpathophysiologycomes from theAncient Greekπάθος (pathos) and φυσιολογία (phisiologia).

History

Nineteenth century

Reductionism

In Germany in the 1830s,Johannes Müllerled the establishment of physiology research autonomous from medical research. In 1843, theBerlin Physical Societywas founded in part to purge biology and medicine ofvitalism,and in 1847Hermann von Helmholtz,who joined the Society in 1845, published the paper "On the conservation of energy", highly influential to reduce physiology's research foundation to physical sciences. In the late 1850s, Germananatomical pathologistRudolf Virchow,a former student of Müller, directed focus to the cell, establishingcytologyas the focus of physiological research, whileJulius Cohnheimpioneeredexperimental pathologyin medical schools' scientific laboratories.

Germ theory

By 1863, motivated byLouis Pasteur's report on fermentation tobutyric acid,fellow FrenchmanCasimir Davaineidentified 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.In 1876, uponFerdinand Cohn's report of a tiny spore stage of a bacterial species, the fellow GermanRobert Kochisolated Davaine'sbacteridesinpure culture—a pivotal step that would establishbacteriologyas 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 withecologicalinvestigations 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 termfermentto a microorganism or, as it did for many others, to a chemical.In 1878, Koch publishedAetiology of Traumatic Infective Diseases,unlike any previous work, where 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. "Koch used bacteriology and the new staining methods withaniline dyesto identify particular microorganisms for each.Germ theory of diseasecrystallized the concept of cause—presumably identifiable by scientific investigation.

Scientific medicine

The American physicianWilliam Welchtrained in German pathology from 1876 to 1878, including underCohnheim,and opened America's first scientific laboratory —a pathology laboratory— atBellevue Hospitalin 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 byDaniel Coit Gilman,upon advice byJohn Shaw Billings,as founding dean of the medical school of the newly formingJohns Hopkins Universitythat 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 Vichow's anatomical pathology, Cohnheim's experimental pathology, and Koch's bacteriology.Hopkins medical school, led by the "Four Horsemen" —Welch,William Osler,Howard Kelly,andWilliam Halsted— opened at last in 1893 as America's first medical school devoted to teaching German scientific medicine, so called.

Twentieth century

Biomedicine

The first biomedical institutes,Pasteur InstituteandBerlin Institute for Infectious Diseases,whose first directors werePasteurandKoch,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 Flexneras director of pathology and bacteriology laboratories. By way ofWorld War IandWorld War II,Rockefeller Institute became the globe's leader in biomedical research.

Molecular paradigm

The1918 pandemictriggered frenzied search for its cause, although most deaths were vialobar pneumonia,already attributed topneumococcalinvasion. In London, pathologist with the Ministry of Health,Fred Griffithin 1928 reported pneumococcaltransformationfrom virulent to avirulent and between antigenic types —nearly a switch in species— challenging pneumonia's specific causation.The laboratory of Rockefeller Institute'sOswald Avery,America's leading pneumococcal expert, was so troubled by the report that they refused to attempt repetition.

When Avery was away on summer vacation,Martin Dawson,British-Canadian, convinced that anything from England must be correct, repeated Griffith's results, then achieved transformationin vitro,too, opening it to precise investigation.Having returned, Avery kept a photo of Griffith on his desk while his researchers followed the trail. In 1944, Avery,Colin MacLeod,andMaclyn McCartyreported the transformation factor asDNA,widely doubted amid estimations that something must act with it.At the time of Griffith's report, it was unrecognized that bacteria even had genes.

The first genetics,Mendelian genetics,began at 1900, yet inheritance of Mendelian traits was localized tochromosomesby 1903, thuschromosomal genetics.Biochemistryemerged in the same decade.In the 1940s, most scientists viewed the cell as a "sack of chemicals" —a membrane containing only loose molecules inchaotic motion— and the only especial cell structures as chromosomes, which bacteria lack as such.Chromosomal DNA was presumed too simple, so genes were sought inchromosomal proteins.Yet in 1953, American biologistJames Watson,British physicistFrancis Crick,and British chemistRosalind Franklininferred DNA's molecular structure —adouble helix— and conjectured it to spell a code. In the early 1960s,Crickhelped crack agenetic codeinDNA,thus establishingmolecular genetics.

In the late 1930s,Rockefeller Foundationhad spearheaded and funded themolecular biologyresearch program—seeking fundamental explanation of organisms and life— led largely by physicistMax DelbrückatCaltechandVanderbilt University.Yet the reality oforganellesin cells was controversial amid unclear visualization with conventionallight microscopy.Around 1940, largely via cancer research at Rockefeller Institute,cell biologyemerged as a new discipline filling the vast gap betweencytologyandbiochemistryby applying new technology —ultracentrifugeandelectron microscope— to identify and deconstruct cell structures, functions, and mechanisms.The two new sciences interlaced,cell and molecular biology.

Mindful ofGriffithandAvery,Joshua Lederbergconfirmedbacterial conjugation—reported decades earlier but controversial— and was awarded the 1958Nobel Prize in Physiology or Medicine.AtCold Spring Harbor Laboratoryin Long Island, New York,DelbrückandSalvador Lurialed thePhage Group—hostingWatson— 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.

Disease mechanisms

In the 1950s, researches onrheumatic fever,a complication ofstreptococcalinfections, revealed it was mediated by the host's own immune response, stirring investigation by pathologistLewis Thomasthat led to identification of enzymes released by theinnate immunecellsmacrophagesand that degrade host tissue.In the late 1970s, as president ofMemorial Sloan–Kettering Cancer Center,Thomas collaborated withLederberg,soon to become president ofRockefeller University,to redirect the funding focus of the USNational Institutes of Healthtoward 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.Thomas became for Americanbasic researchersapatron saint.

Examples

Parkinson's disease

Thepathophysiology of Parkinson's diseaseisdeathofdopaminergicneuronsas a result of changes in biological activity in the brain with respect toParkinson's disease(PD). There are several proposed mechanisms forneuronaldeathin PD; however, not all of them are well understood. Five proposed major mechanisms for neuronal death in Parkinson's Disease include protein aggregation inLewy bodies,disruption ofautophagy,changes in cell metabolism ormitochondrialfunction,neuroinflammation,andblood–brain barrier(BBB) breakdown resulting in vascular leakiness.

Heart failure

Thepathophysiology of heart failureis a reduction in the efficiency of the heart muscle, through damage or overloading. As such, it can be caused by a wide number of conditions, including myocardial infarction (in which the heart muscle isstarved of oxygenand dies), 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 increases in workload will produce changes to the heart itself.

Multiple sclerosis

Thepathophysiology of multiple sclerosisis that of aninflammatory demyelinating disease of the CNSin which activated immune cells invade the central nervous system and cause inflammation, neurodegeneration and tissue damage. The underlying condition that produces this behaviour is currently unknown. Current research in neuropathology, neuroimmunology, neurobiology, and neuroimaging, together with clinical neurology provide support for the notion that MS is not a single disease but rather a spectrum

Hypertension

Thepathophysiology of hypertensionis that of a chronic disease characterized by elevation ofblood pressure.Hypertension can be classified by cause as eitheressential(also known as primary oridiopathic) orsecondary.About 90–95% of hypertension is essential hypertension.

HIV/AIDS

Thepathophysiology of HIV/AIDSinvolves, upon acquisition of the virus, that the virus replicates inside and killsT helper cells,which are required for almost alladaptive immune responses.There is an initial period ofinfluenza-like illness,and then a latent, asymptomatic phase. When theCD4lymphocyte count falls below 200 cells/ml of blood, the HIV host has progressed to AIDS,a condition characterized by deficiency incell-mediated immunityand the resulting increased susceptibility toopportunistic infectionsand certain forms ofcancer.

Spider bites

Thepathophysiology of spider bitesis due to the effect of itsvenom.A spider envenomation occurs whenever a spider injectsvenominto the skin. Not all spider bites inject venom – a dry bite, and the amount of venom injected can vary based on the type of spider and the circumstances of the encounter. The mechanical injury from a spider bite is not a serious concern for humans.

Obesity

Thepathophysiology of obesityinvolves many possible pathophysiological mechanisms involved in its development and maintenance.

This field of research had been almost unapproached until theleptingene was discovered in 1994 by J. M. Friedman's laboratory.These investigators postulated that leptin was a satiety factor. In the ob/ob mouse, mutations in theleptingene resulted in the obese phenotype opening the possibility of leptin therapy for human obesity. However, soon thereafterJ. F. Caro'slaboratory could not detect any mutations in the leptin gene in humans with obesity. On the contraryLeptinexpression was increased proposing the possibility of Leptin-resistance in human obesity.

See also

• Pathogenesis
• Pathology
• Physiology