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Pathophysiology ( physiopathology) – a convergence of
pathology Pathology is the study of the causes and effects of disease or injury. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in ...
with
physiology Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical ...
 – is the study of the disordered physiological processes that cause, result from, or are otherwise associated with a
disease A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
or injury. Pathology is the medical discipline that describes conditions typically ''observed'' during a
disease A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
state, whereas physiology is the biological discipline that describes processes or mechanisms ''operating'' within an
organism In biology, an organism () is any living system that functions as an individual entity. All organisms are composed of cells (cell theory). Organisms are classified by taxonomy into groups such as multicellular animals, plants, and ...
. 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.


History


Etymology

The term ''pathophysiology'' comes from the
Ancient Greek Ancient Greek includes the forms of the Greek language used in ancient Greece and the ancient world from around 1500 BC to 300 BC. It is often roughly divided into the following periods: Mycenaean Greek (), Dark Ages (), the Archaic p ...
πάθος (''pathos'') and φυσιολογία (''phusiologia'').


Nineteenth century


Reductionism

In Germany in the 1830s, Johannes Müller led the establishment of physiology research autonomous from medical research. In 1843, the Berlin Physical Society was founded in part to purge biology and medicine of
vitalism Vitalism is a belief that starts from the premise that "living organisms are fundamentally different from non-living entities because they contain some non-physical element or are governed by different principles than are inanimate things." Wher ...
, and in 1847
Hermann von Helmholtz Hermann Ludwig Ferdinand von Helmholtz (31 August 1821 – 8 September 1894) was a German physicist and physician who made significant contributions in several scientific fields, particularly hydrodynamic stability. The Helmholtz Associatio ...
, 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, German anatomical pathologist
Rudolf Virchow Rudolf Ludwig Carl Virchow (; or ; 13 October 18215 September 1902) was a German physician, anthropologist, pathologist, prehistorian, biologist, writer, editor, and politician. He is known as "the father of modern pathology" and as the founder ...
, a former student of Müller, directed focus to the cell, establishing
cytology Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living an ...
as the focus of physiological research, while
Julius Cohnheim Julius Friedrich Cohnheim (20 July 1839 – 15 August 1884) was a German-Jewish pathologist. Biography Cohnheim was born at Demmin, Pomerania. He studied at the universities of Würzburg, Marburg, Greifswald, and Berlin, receiving his doctora ...
pioneered experimental pathology in medical schools' scientific laboratories.


Germ theory

By 1863, motivated by Louis Pasteur's report on fermentation to butyric acid, fellow Frenchman
Casimir Davaine Casimir-Joseph Davaine (19 March 1812 – 14 October 1882) was a French physician known for his work in the field of microbiology. He was a native of Saint-Amand-les-Eaux, department of Nord. In 1850, Davaine along with French pathologist Pierr ...
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 Putrefaction is the fifth stage of death, following pallor mortis, algor mortis, rigor mortis, and livor mortis. This process references the breaking down of a body of an animal, such as a human, post-mortem. In broad terms, it can be view ...
. In 1876, upon Ferdinand Cohn's report of a tiny spore stage of a bacterial species, the fellow German
Robert Koch Heinrich Hermann Robert Koch ( , ; 11 December 1843 – 27 May 1910) was a German physician and microbiologist. As the discoverer of the specific causative agents of deadly infectious diseases including tuberculosis, cholera (though the bacteri ...
isolated Davaine's ''bacterides'' in
pure culture A microbiological culture, or microbial culture, is a method of multiplying microbial organisms by letting them reproduce in predetermined culture medium under controlled laboratory conditions. Microbial cultures are foundational and basic diagn ...
—a pivotal step that would establish
bacteriology Bacteriology is the branch and specialty of biology that studies the morphology, ecology, genetics and biochemistry of bacteria as well as many other aspects related to them. This subdivision of microbiology involves the identification, classificat ...
as a distinct discipline— identified a spore stage, applied
Jakob Henle Friedrich Gustav Jakob Henle (; 9 July 1809 – 13 May 1885) was a German physician, pathologist, and anatomist. He is credited with the discovery of the loop of Henle in the kidney. His essay, "On Miasma and Contagia," was an early argument for ...
's postulates, and confirmed Davaine's conclusion, a major feat for experimental pathology. Pasteur and colleagues followed up with
ecological Ecology () is the study of the relationships between living organisms, including humans, and their physical environment. Ecology considers organisms at the individual, population, community, ecosystem, and biosphere level. Ecology overlaps wi ...
investigations confirming its role in the natural environment via spores in soil. Also, as to
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
, 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.Bulloch, William
''The History of Bacteriology''
(Oxford: Oxford University Press, 1938 & 1960 / New York: Dover Publications, 1979), p 143–144, 147-148
In 1878, Koch published ''Aetiology of Traumatic Infective Diseases'', unlike any previous work, where in 80 pages Koch, as noted by an historian, "was able to show, in a manner practically conclusive, that a number of diseases, differing clinically, anatomically, and in
aetiology Etiology (pronounced ; alternatively: aetiology or ætiology) is the study of causation or origination. The word is derived from the Greek (''aitiología'') "giving a reason for" (, ''aitía'', "cause"); and ('' -logía''). More completely, e ...
, can be produced experimentally by the injection of putrid materials into animals." Koch used bacteriology and the new staining methods with
aniline dye Aniline is an organic compound with the formula C6 H5 NH2. Consisting of a phenyl group attached to an amino group, aniline is the simplest aromatic amine. It is an industrially significant commodity chemical, as well as a versatile starting m ...
s to identify particular microorganisms for each.
Germ theory of disease The germ theory of disease is the currently accepted scientific theory for many diseases. It states that microorganisms known as pathogens or "germs" can lead to disease. These small organisms, too small to be seen without magnification, invade ...
crystallized the concept of cause—presumably identifiable by scientific investigation.


Scientific medicine

The American physician William Welch trained in German pathology from 1876 to 1878, including under Cohnheim, and opened America's first scientific laboratory —a pathology laboratory— at
Bellevue Hospital Bellevue Hospital (officially NYC Health + Hospitals/Bellevue and formerly known as Bellevue Hospital Center) is a hospital in New York City and the oldest public hospital in the United States. One of the largest hospitals in the United States ...
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 Daniel Coit Gilman (; July 6, 1831 – October 13, 1908) was an American educator and academic. Gilman was instrumental in founding the Sheffield Scientific School at Yale College, and subsequently served as the second president of the University ...
, upon advice by John Shaw Billings, as founding dean of the medical school of the newly forming
Johns Hopkins University Johns Hopkins University (Johns Hopkins, Hopkins, or JHU) is a private research university in Baltimore, Maryland. Founded in 1876, Johns Hopkins is the oldest research university in the United States and in the western hemisphere. It consi ...
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 Vichow's anatomical pathology, Cohnheim's experimental pathology, and Koch's bacteriology. Hopkins medical school, led by the "Four Horsemen" —Welch,
William Osler Sir William Osler, 1st Baronet, (; July 12, 1849 – December 29, 1919) was a Canadian physician and one of the "Big Four" founding professors of Johns Hopkins Hospital. Osler created the first residency program for specialty training of phys ...
, Howard Kelly, and
William Halsted William Stewart Halsted, M.D. (September 23, 1852 – September 7, 1922) was an American surgeon who emphasized strict aseptic technique during surgical procedures, was an early champion of newly discovered anesthetics, and introduced several ...
— 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 Institute The Pasteur Institute (french: Institut Pasteur) is a French non-profit private foundation dedicated to the study of biology, micro-organisms, diseases, and vaccines. It is named after Louis Pasteur, who invented pasteurization and vaccines ...
and Berlin Institute for Infectious Diseases, whose first directors were
Pasteur Louis Pasteur (, ; 27 December 1822 – 28 September 1895) was a French chemist and microbiologist renowned for his discoveries of the principles of vaccination, microbial fermentation and pasteurization, the latter of which was named after ...
and 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 Simon Flexner, M.D. (March 25, 1863 in Louisville, Kentucky – May 2, 1946) was a physician, scientist, administrator, and professor of experimental pathology at the University of Pennsylvania (1899–1903). He served as the first director ...
as director of pathology and bacteriology laboratories. By way of
World War I World War I (28 July 1914 11 November 1918), often abbreviated as WWI, was one of the deadliest global conflicts in history. Belligerents included much of Europe, the Russian Empire, the United States, and the Ottoman Empire, with fightin ...
and
World War II World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the vast majority of the world's countries—including all of the great powers—forming two opposing ...
, Rockefeller Institute became the globe's leader in biomedical research.


Molecular paradigm

The
1918 pandemic The 1918–1920 influenza pandemic, commonly known by the misnomer Spanish flu or as the Great Influenza epidemic, was an exceptionally deadly global influenza pandemic caused by the H1N1 influenza A virus. The earliest documented case was ...
triggered frenzied search for its cause, although most deaths were via
lobar pneumonia Lobar pneumonia is a form of pneumonia characterized by inflammatory exudate within the intra-alveolar space resulting in consolidation that affects a large and continuous area of the lobe of a lung. It is one of three anatomic classifications ...
, already attributed to
pneumococcal ''Streptococcus pneumoniae'', or pneumococcus, is a Gram-positive, spherical bacteria, alpha-hemolytic (under aerobic conditions) or beta-hemolytic (under anaerobic conditions), aerotolerant anaerobic member of the genus Streptococcus. They are ...
invasion. In London, pathologist with the Ministry of Health, Fred Griffith in 1928 reported pneumococcal
transformation Transformation may refer to: Science and mathematics In biology and medicine * Metamorphosis, the biological process of changing physical form after birth or hatching * Malignant transformation, the process of cells becoming cancerous * Tran ...
from virulent to avirulent and between antigenic types —nearly a switch in species— challenging pneumonia's specific causation. The laboratory of Rockefeller Institute's
Oswald Avery Oswald Theodore Avery Jr. (October 21, 1877 – February 20, 1955) was a Canadian-American physician and medical researcher. The major part of his career was spent at the Rockefeller Hospital in New York City. Avery was one of the first molecula ...
, America's leading pneumococcal expert, was so troubled by the report that they refused to attempt repetition.Dubos, René
"Memories of working in Oswald Avery's laboratory"
Symposium Celebrating the Thirty-Fifth Anniversary of the Publication of "Studies on the chemical nature of the substance inducing transformation of pneumococcal types", 2 Feb 1979
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 transformation ''
in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology ...
'', 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, and Maclyn McCarty reported the transformation factor as DNA, 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 Mendelian inheritance (also known as Mendelism) is a type of biological inheritance following the principles originally proposed by Gregor Mendel in 1865 and 1866, re-discovered in 1900 by Hugo de Vries and Carl Correns, and later populari ...
, began at 1900, yet inheritance of Mendelian traits was localized to
chromosomes A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
by 1903, thus chromosomal genetics.
Biochemistry Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology and ...
emerged in the same decade.Bechtel, William
''Discovering Cell Mechanisms: The Creation of Modern Cell Biology''
(New York: Cambridge University Press, 2005)
In the 1940s, most scientists viewed the cell as a "sack of chemicals" —a membrane containing only loose molecules in chaotic motion— and the only especial cell structures as chromosomes, which bacteria lack as such. Chromosomal DNA was presumed too simple, so genes were sought in chromosomal proteins. Yet in 1953, American biologist James Watson, British physicist Francis Crick, and British chemist Rosalind Franklin inferred DNA's molecular structure —a
double helix A double is a look-alike or doppelgänger; one person or being that resembles another. Double, The Double or Dubble may also refer to: Film and television * Double (filmmaking), someone who substitutes for the credited actor of a character * ...
— and conjectured it to spell a code. In the early 1960s, Crick helped crack a
genetic code The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...
in DNA, thus establishing
molecular genetics Molecular genetics is a sub-field of biology that addresses how differences in the structures or expression of DNA molecules manifests as variation among organisms. Molecular genetics often applies an "investigative approach" to determine the ...
. In the late 1930s, Rockefeller Foundation had spearheaded and funded the
molecular biology Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...
research program A research program (British English: research programme) is a professional network of scientists conducting basic research. The term was used by philosopher of science Imre Lakatos to blend and revise the normative model of science offered by Ka ...
—seeking fundamental explanation of organisms and life— led largely by physicist
Max Delbrück Max Ludwig Henning Delbrück (; September 4, 1906 – March 9, 1981) was a German–American biophysicist who participated in launching the molecular biology research program in the late 1930s. He stimulated physical scientists' interest int ...
at
Caltech The California Institute of Technology (branded as Caltech or CIT)The university itself only spells its short form as "Caltech"; the institution considers other spellings such a"Cal Tech" and "CalTech" incorrect. The institute is also occasional ...
and
Vanderbilt University Vanderbilt University (informally Vandy or VU) is a private research university in Nashville, Tennessee. Founded in 1873, it was named in honor of shipping and rail magnate Cornelius Vanderbilt, who provided the school its initial $1-million ...
. Yet the reality of
organelles In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' th ...
in cells was controversial amid unclear visualization with conventional light microscopy. Around 1940, largely via cancer research at Rockefeller Institute, cell biology emerged as a new discipline filling the vast gap between
cytology Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living an ...
and
biochemistry Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology and ...
by applying new technology —
ultracentrifuge An ultracentrifuge is a centrifuge optimized for spinning a rotor at very high speeds, capable of generating acceleration as high as (approx. ). There are two kinds of ultracentrifuges, the preparative and the analytical ultracentrifuge. Both cla ...
and
electron microscope An electron microscope is a microscope that uses a beam of accelerated electrons as a source of illumination. As the wavelength of an electron can be up to 100,000 times shorter than that of visible light photons, electron microscopes have a hi ...
— to identify and deconstruct cell structures, functions, and mechanisms. The two new sciences interlaced, ''cell and molecular biology''. Mindful of Griffith and Avery,
Joshua Lederberg Joshua () or Yehoshua ( ''Yəhōšuaʿ'', Tiberian: ''Yŏhōšuaʿ,'' lit. 'Yahweh is salvation') ''Yēšūaʿ''; syr, ܝܫܘܥ ܒܪ ܢܘܢ ''Yəšūʿ bar Nōn''; el, Ἰησοῦς, ar , يُوشَعُ ٱبْنُ نُونٍ '' Yūšaʿ ...
confirmed bacterial conjugation —reported decades earlier but controversial— and was awarded the 1958
Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...
. At
Cold Spring Harbor Laboratory Cold Spring Harbor Laboratory (CSHL) is a private, non-profit institution with research programs focusing on cancer, neuroscience, plant biology, genomics, and quantitative biology. It is one of 68 institutions supported by the Cancer Centers ...
in Long Island, New York, Delbrück and
Salvador Luria Salvador Edward Luria (August 13, 1912 – February 6, 1991) was an Italian microbiologist, later a Naturalized citizen of the United States#Naturalization, naturalized U.S. citizen. He won the Nobel Prize in Physiology or Medicine in 1969, with ...
led the Phage Group —hosting Watson— discovering details of cell physiology by tracking changes to bacteria upon infection with their viruses, the process transduction. Lederberg led the opening of a genetics department at Stanford University's medical school, and facilitated greater communication between biologists and medical departments.


Disease mechanisms

In the 1950s, researches on rheumatic fever, a complication of streptococcal infections, revealed it was mediated by the host's own immune response, stirring investigation by pathologist
Lewis Thomas Lewis Thomas (November 25, 1913 – December 3, 1993) was an American physician, poet, etymologist, essayist, administrator, educator, policy advisor, and researcher. Thomas was born in Flushing, New York and attended Princeton University ...
that led to identification of enzymes released by the innate immune cells
macrophages Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...
and that degrade host tissue. In the late 1970s, as president of
Memorial Sloan–Kettering Cancer Center Memorial Sloan Kettering Cancer Center (MSK or MSKCC) is a cancer treatment and research institution in the borough of Manhattan in New York City, founded in 1884 as the New York Cancer Hospital. MSKCC is one of 52 National Cancer Institute� ...
, Thomas collaborated with Lederberg, soon to become president of Rockefeller University, to redirect the funding focus of the US
National Institutes of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
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. Thomas became for American
basic research Basic research, also called pure research or fundamental research, is a type of scientific research with the aim of improving scientific theories for better understanding and prediction of natural or other phenomena. In contrast, applied rese ...
ers a
patron saint A patron saint, patroness saint, patron hallow or heavenly protector is a saint who in Catholicism, Anglicanism, or Eastern Orthodoxy is regarded as the heavenly advocate of a nation, place, craft, activity, class, clan, family, or perso ...
.


Examples

* The pathophysiology of Parkinson's disease is
death Death is the irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain ...
of dopaminergic
neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. ...
s as a result of changes in biological activity in the brain with respect to
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
(PD). There are several proposed mechanisms for
neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. ...
al
death Death is the irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain ...
in PD; however, not all of them are well understood. Five proposed major mechanisms for neuronal death in Parkinson's Disease include protein aggregation in Lewy bodies, disruption of autophagy, changes in cell metabolism or mitochondrial function,
neuroinflammation Neuroinflammation is inflammation of the nervous tissue. It may be initiated in response to a variety of cues, including infection, traumatic brain injury,Ebert SE, Jensen P, Ozenne B, Armand S, Svarer C, Stenbaek DS ''et al.'' Molecular imaging of ...
, and blood–brain barrier (BBB) breakdown resulting in vascular leakiness. * The pathophysiology of heart failure is 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 is starved of oxygen and dies), hypertension (which increases the force of contraction needed to pump blood) and amyloidosis (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. * The pathophysiology of multiple sclerosis is that of an inflammatory demyelinating disease of the CNS in 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 * The pathophysiology of hypertension is that of a chronic disease characterized by elevation of blood pressure. Hypertension can be classified by cause as either essential (also known as primary or
idiopathic An idiopathic disease is any disease with an unknown cause or mechanism of apparent spontaneous origin. From Greek ἴδιος ''idios'' "one's own" and πάθος ''pathos'' "suffering", ''idiopathy'' means approximately "a disease of its own kin ...
) or secondary. About 90–95% of hypertension is essential hypertension. * The pathophysiology of HIV/AIDS involves, upon acquisition of the virus, that the virus replicates inside and kills
T helper cells The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considere ...
, which are required for almost all adaptive immune responses. There is an initial period of influenza-like illness, and then a latent, asymptomatic phase. When the CD4 lymphocyte count falls below 200 cells/ml of blood, the HIV host has progressed to AIDS, a condition characterized by deficiency in
cell-mediated immunity Cell-mediated immunity or cellular immunity is an immune response that does not involve antibodies. Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in ...
and the resulting increased susceptibility to
opportunistic infections An opportunistic infection is an infection caused by pathogens (bacteria, fungi, parasites or viruses) that take advantage of an opportunity not normally available. These opportunities can stem from a variety of sources, such as a weakened immune ...
and certain forms of
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
. * The pathophysiology of spider bites is due to the effect of its
venom Venom or zootoxin is a type of toxin produced by an animal that is actively delivered through a wound by means of a bite, sting, or similar action. The toxin is delivered through a specially evolved ''venom apparatus'', such as fangs or a st ...
. A spider envenomation occurs whenever a spider injects
venom Venom or zootoxin is a type of toxin produced by an animal that is actively delivered through a wound by means of a bite, sting, or similar action. The toxin is delivered through a specially evolved ''venom apparatus'', such as fangs or a st ...
into 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. * The pathophysiology of obesity involves many possible pathophysiological mechanisms involved in its development and maintenance. This field of research had been almost unapproached until the leptin gene 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 the leptin gene resulted in the obese phenotype opening the possibility of leptin therapy for human obesity. However, soon thereafter J. F. Caro's laboratory could not detect any mutations in the leptin gene in humans with obesity. On the contrary Leptin expression was increased proposing the possibility of Leptin-resistance in human obesity.


See also

*
Pathogenesis Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pat ...
*
Pathology Pathology is the study of the causes and effects of disease or injury. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in ...
*
Physiology Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical ...


References

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