Pathophysiology

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Pathophysiology sample values

BMP/ELECTROLYTES:

Na+ Cl−
 = 140  = 100 BUN = 20 /

Glu = 150

K+
 = 4 CO2  = 22 PCr = 1.0 \

ARTERIAL BLOOD GAS:

HCO
3
−
 = 24 paCO2 = 40 paO2 = 95 pH = 7.40

ALVEOLAR GAS:

pACO2 = 36 pAO2 = 105 A-a g = 10

OTHER:

Mg2+
Ca = 9.5  = 2.0  = 1
PO4

CK = 55 BE = −0.36 AG = 16

SERUM OSMOLARITY/RENAL:

PMO = 300 PCO = 295 POG = 5 BUN:Cr = 20

URINALYSIS:

UNa+ UCl−
 = 80  = 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 = 0.4

Pathophysiology (a.k.a. physiopathology) – a convergence
of pathology with physiology – is the study of the 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, whereas pathophysiology seeks to explain the functional changes
that are occurring within an individual due to a disease or pathologic state. [1]

Contents

 1History
o 1.1Etymology
o 1.2Nineteenth century
 1.2.1Reductionism
 1.2.2Germ theory
 1.2.3Scientific medicine
o 1.3Twentieth century
 1.3.1Biomedicine
 1.3.2Molecular paradigm
 1.3.3Disease mechanisms
o 1.4Examples
 2See also
 3References

History[edit]
Etymology[edit]
The term pathophysiology comes from the Ancient Greek πάθος (pathos) and
φυσιολογία (phusiologia).
Nineteenth century[edit]
Reductionism[edit]
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, and in 1847 Hermann 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, German anatomical pathologist Rudolf Virchow, a former student of Müller,
directed focus to the cell, establishing cytology as the focus of physiological research,
while Julius Cohnheim pioneered experimental pathology in medical schools' scientific
laboratories.
Germ theory[edit]
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.[2] 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.[3] 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, can be produced
experimentally by the injection of putrid materials into animals." [3] Koch used
bacteriology and the new staining methods with aniline dyes to identify particular
microorganisms for each.[3] Germ theory of disease crystallized the concept of cause—
presumably identifiable by scientific investigation. [4]
Scientific medicine[edit]
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 in New York City in 1878.[5] Welch's course
drew enrollment from students at other medical schools, which responded by opening
their own pathology laboratories.[5] 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. [5] 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.[6] Hopkins medical school, led by the "Four Horsemen" —
Welch, William Osler, Howard Kelly, and William Halsted— opened at last in 1893 as
America's first medical school devoted to teaching German scientific medicine, so
called.[5]
Twentieth century[edit]
Biomedicine[edit]
The first biomedical institutes, Pasteur Institute and Berlin Institute for Infectious
Diseases, whose first directors were Pasteur 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 as director of pathology and bacteriology laboratories. By way of World War
I and World War II, Rockefeller Institute became the globe's leader in biomedical
research.
Molecular paradigm[edit]
The 1918 pandemic triggered frenzied search for its cause, although most deaths were
via lobar pneumonia, already attributed to pneumococcal invasion. In London,
pathologist with the Ministry of Health, Fred Griffith in 1928 reported
pneumococcal transformation from virulent to avirulent and between antigenic types —
nearly a switch in species— challenging pneumonia's specific causation. [7][8] The
laboratory of Rockefeller Institute's Oswald Avery, America's leading pneumococcal
expert, was so troubled by the report that they refused to attempt repetition. [9]
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, too, opening it to precise investigation.[9] 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. [10] At the
time of Griffith's report, it was unrecognized that bacteria even had genes. [11]
The first genetics, Mendelian genetics, began at 1900, yet inheritance of Mendelian
traits was localized to chromosomes by 1903, thus chromosomal
genetics. Biochemistry emerged in the same decade.[12] 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.[12] 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— and conjectured it to spell a code. In the early
1960s, Crick helped crack a genetic code in DNA, thus establishing molecular genetics.
In the late 1930s, Rockefeller Foundation had spearheaded and funded the molecular
biology research program —seeking fundamental explanation of organisms and life—
led largely by physicist Max Delbrück at Caltech and Vanderbilt University.[13] Yet the
reality of organelles in cells was controversial amid unclear visualization with
conventional light microscopy.[12] Around 1940, largely via cancer research at Rockefeller
Institute, cell biology emerged as a new discipline filling the vast gap
between cytology and biochemistry by applying new technology —
ultracentrifuge and electron microscope— to identify and deconstruct cell structures,
functions, and mechanisms.[12] The two new sciences interlaced, cell and molecular
biology.[12]
Mindful of Griffith and Avery, Joshua Lederberg confirmed bacterial conjugation —
reported decades earlier but controversial— and was awarded the 1958 Nobel Prize in
Physiology or Medicine.[14] At Cold Spring Harbor Laboratory in Long Island, New
York, Delbrück and Salvador Luria 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. [14]
Disease mechanisms[edit]
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 that led to identification of enzymes released by the innate
immune cells macrophages and that degrade host tissue.[15] In the late 1970s, as
president of Memorial Sloan–Kettering Cancer Center, Thomas collaborated
with Lederberg, soon to become president of Rockefeller University, to redirect the
funding focus of the US National 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.[16] Thomas became for American basic researchers a patron saint.[17]
Examples[edit]

 The pathophysiology of Parkinson's
disease is death of dopaminergic neurons as a result of changes in biological
activity in the brain with respect to Parkinson's disease (PD). There are
several proposed mechanisms for neuronal death 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, and blood-brain barrier (BBB)
breakdown resulting in vascular leakiness.[18]
 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 [19]
 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)
or secondary. About 90–95% of hypertension is essential hypertension. [20][21][22][23]
  The pathophysiology of HIV/AIDS involves, upon acquisition of the virus,
that the virus replicates inside and kills T helper cells, 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,[24] a condition characterized by deficiency in cell-
mediated immunity and the resulting increased susceptibility to opportunistic
infections and certain forms of cancer.
 The pathophysiology of spider bites is due to the effect of its venom. A
spider envenomation occurs whenever a spider injects venom 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. [25] This field of
research had been almost unapproached until the leptin gene was discovered
in 1994 by J. M. Friedman's laboratory.[26] 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.[27]

See also[edit]
 Pathogenesis
 Pathology
 Physiology

References[edit]
1. ^ "Pathophysiology – Medical dictionary".  TheFreeDictionary.com. Farlex, Inc.
2. ^ Théodoridès J (1966). "Casimir Davaine (1812-1882): A precursor of Pasteur". Medical
History.  10  (2): 155–65.  doi:10.1017/S0025727300010942.  PMC 1033586. PMID 5325873.
3. ^ Jump up to:a b c Bulloch, William, The History of Bacteriology (Oxford: Oxford University Press,
1938 & 1960 / New York: Dover Publications, 1979), p 143–144, 147-148
4. ^ Carter KC (1980).  "Germ theory, hysteria, and Freud's early work in
psychopathology". Medical History.  24  (3): 259–
74.  doi:10.1017/S002572730004031X. PMC  1082654.  PMID  6997653.
5. ^ Jump up to:a b c d Silverman BD (2011). "William Henry Welch (1850-1934): The road to Johns
Hopkins". Proceedings. 24 (3): 236–
42.  doi:10.1080/08998280.2011.11928722.  PMC 3124910. PMID 21738298.
6. ^ Benson KR (1999).  "Welch, Sedgwick, and the Hopkins model of hygiene".  The Yale
Journal of Biology and Medicine.  72  (5): 313–20.  PMC 2579023. PMID 11049162.
7. ^ "In the bacteriology of the 1920s, the conversion of the R to the S form could be regarded
as an adaptation to the environment. However, the transformation of Type I to Type II was the
equivalent of the transformation of one species into another, a phenomenon never before
observed. Avery was initially skeptical of Griffith's findings and for some time refused to
accept the validity of his claims, believing that they were the result of inadequate
experimental controls. Avery's research on therapeutic sera led him to conclude that
pneumococcal types were fixed and that specific therapeutic agents could thus be developed
to combat the various types. A transformation from type to type in vivo presented a disturbing
clinical picture, as well as a challenge to the theoretical formulations of contemporary
bacteriology" [Oswald T Avery Collection, "Shifting focus: Early work on bacterial
transformation, 1928-1940", Profiles in Science, US National Library of Medicine, Web: 24
Jan 2013].
8. ^ Dubos, René J, Oswald T Avery: His Life and Scientific Achievements (New York:
Rockefeller University Press, 1976), pp 133, 135-136
9. ^ Jump up to:a b 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
10. ^ Lederberg J (1956). "Notes on the biological interpretation of Fred Griffith's
finding".  American Scientist. 44 (3): 268–269.
11. ^ Lacks SA (Jan 2003). "Rambling and scrambling in bacterial transformation—a historical
and personal memoir".  J Bacteriol. 185 (1): 1–6.  doi:10.1128/jb.185.1.1-
6.2003.  PMC 141969. PMID 12486033.
12. ^ Jump up to:a b c d e Bechtel, William, Discovering Cell Mechanisms: The Creation of Modern Cell
Biology (New York: Cambridge University Press, 2005)
13. ^ Kay, Lily, Molecular Vision of Life: Caltech, the Rockefeller Foundation, and the Rise of the
New Biology (New York: Oxford University Press, 1993)
14. ^ Jump up to:a b Institute of Medicine  Forum on Microbial Threats (2009). "The Life and Legacies
of Joshua Lederberg".  Microbial Evolution and Co-Adaptation: A Tribute to the Life and
Scientific Legacies of Joshua Lederberg: Workshop Summary. Washington DC: National
Academies Press. ISBN 978-0-309-13121-6.
15. ^ Sauerwald A, Hoesche C, Oschwald R, Kilimann MW (2007).  "Lewis Thomas and droopy
rabbit ears".  Journal of Experimental Medicine. 204 (12):
2777.  doi:10.1084/jem.20412fta. PMC  2118519.
16. ^ Letter: Lewis Thomas (MSKCC) to Joshua Lederberg (Stanford Univ), 7 Aug 1978, p 1
17. ^ Weissmann G (2006).  "Planning science (a generation after Lewis Thomas)".  Journal of
Clinical Investigation. 116 (6):
1463.  doi:10.1172/JCI28895.  PMC 1449953. PMID 16648878.
18. ^ Tansey M. G., Goldberg M. S. (2010). "Neuroinflammation in Parkinson's disease: Its role in
neuronal death and implications for therapeutic intervention".  Neurobiology of
Disease. 37 (3): 510–518. doi:10.1016/j.nbd.2009.11.004. PMC  2823829.  PMID  19913097.
19. ^ Golan, Daniel; Staun-Ram, Elsebeth; Miller, Ariel (2016). "Shifting paradigms in multiple
sclerosis". Current Opinion in Neurology.  29  (3): 354–
361.  doi:10.1097/WCO.0000000000000324. PMID 27070218.
20. ^ Carretero OA, Oparil S (January 2000).  "Essential hypertension. Part I: definition and
etiology". Circulation. 101 (3): 329–35. doi:10.1161/01.CIR.101.3.329. PMID 10645931.
Retrieved 2009-06-05.
21. ^ Oparil S, Zaman MA, Calhoun DA (November 2003). "Pathogenesis of hypertension".  Ann.
Intern. Med.  139  (9): 761–76.  doi:10.7326/0003-4819-139-9-200311040-
00011. PMID 14597461.
22. ^ Hall, John E.; Guyton, Arthur C. (2006). Textbook of medical physiology. St. Louis, Mo:
Elsevier Saunders. p.  228. ISBN 0-7216-0240-1.
23. ^ "Hypertension: eMedicine Nephrology". Retrieved  2009-06-05.
24. ^ Doitsh, G; Greene, WC (2016). "Dissecting How CD4 T Cells Are Lost During HIV
Infection". Cell Host Microbe.  19: 280–
91.  doi:10.1016/j.chom.2016.02.012.  PMC 4835240. PMID 26962940.
25. ^ Flier JS (2004). "Obesity wars: Molecular progress confronts an expanding
epidemic". Cell(Review).  116  (2): 337–50.  doi:10.1016/S0092-8674(03)01081-
X.  PMID  14744442.
26. ^ Zhang, Y; Proenca, R; Maffei, M; Barone, M; Leopold, L; Friedman, JM (Dec 1, 1994).
"Positional cloning of the mouse obese gene and its human homologue". Nature  (Research
Support).  372  (6505): 425–32. doi:10.1038/372425a0. PMID 7984236.
27. ^ Considine, RV; Considine, EL; Williams, CJ; Nyce, MR; Magosin, SA; Bauer, TL; Rosato,
EL; Colberg, J; Caro, JF (Jun 1995).  "Evidence against either a premature stop codon or the
absence of obese gene mRNA in human obesity".  The Journal of Clinical
Investigation(Research Support).  95  (6): 2986–
8. doi:10.1172/jci118007. PMC  295988.  PMID  7769141.