Editing Inflammation (section)

=== Acute ===
Acute inflammation is a short-term process, usually appearing within a few minutes or hours and begins to cease upon the removal of the injurious stimulus.<ref name="robspath" /> It involves a coordinated and systemic mobilization response locally of various immune, endocrine and neurological mediators of acute inflammation. In a normal healthy response, it becomes activated, clears the pathogen and begins a repair process and then ceases.<ref>{{Cite journal |vauthors=Kumar R, Clermont G, Vodovotz Y, Chow CC |date=September 2004 |title=The dynamics of acute inflammation |journal=Journal of Theoretical Biology |volume=230 |issue=2 |pages=145–55 |arxiv=q-bio/0404034 |bibcode=2004PhDT.......405K |doi=10.1016/j.jtbi.2004.04.044 |pmid=15321710 |s2cid=16992741}}</ref>

Acute inflammation occurs immediately upon injury, lasting only a few days.<ref name="pmid32310543">{{Cite journal |vauthors=Hannoodee S, Nasuruddin DN |year=2020 |title=Acute Inflammatory Response |url=https://www.ncbi.nlm.nih.gov/books/NBK556083/ |url-status=live |journal=[[EMedicine#History|StatPearls]] |pmid=32310543 |archive-url=https://web.archive.org/web/20220615132211/https://www.ncbi.nlm.nih.gov/books/NBK556083/ |archive-date=15 June 2022 |access-date=28 December 2020}}</ref> [[Cytokine]]s and [[chemokine]]s promote the migration of [[neutrophil]]s and [[macrophage]]s to the site of inflammation.<ref name="pmid32310543" /> Pathogens, allergens, toxins, burns, and frostbite are some of the typical causes of acute inflammation.<ref name="pmid32310543" /> [[Toll-like receptor]]s (TLRs) recognize microbial pathogens.<ref name="pmid32310543" /> Acute inflammation can be a defensive mechanism to protect tissues against injury.<ref name="pmid32310543" /> Inflammation lasting 2–6 weeks is designated subacute inflammation.<ref name="pmid32310543" /><ref name="pmid29630225" />

==== Cardinal signs ====
{| width="230" align="right" class="wikitable" style="text-align:center; margin-left:0.67em"
|+ The classic signs and symptoms of acute inflammation:{{efn|1=All these signs may be observed in specific instances, but no single sign must, as a matter of course, be present.<ref name="Stedman">{{Cite book |title=Stedman's Medical Dictionary |publisher=Williams & Wilkins |year=1990 |edition=Twenty-fifth}}</ref>
These are the original, or [[cardinal signs]] of inflammation.<ref name="Stedman" />}}
!English || Latin
|-
| Redness || ''[[Rubor]]''
|-
| Swelling || ''[[Swelling (medical)|Tumor]]''
|-
| Heat || ''[[Human body temperature|Calor]]''
|-
| Pain || ''[[Pain|Dolor]]''
|-
| style="border-bottom:2px solid grey;" | Loss of function|| style="border-bottom:2px solid grey;" | ''[[Functio laesa]]''{{efn|1=''Functio laesa'' is an antiquated notion, as it is not unique to inflammation and is a characteristic of many disease states.<ref name="Rather">{{Cite journal |vauthors=Rather LJ |date=March 1971 |title=Disturbance of function (functio laesa): the legendary fifth cardinal sign of inflammation, added by Claudius Galen to the four cardinal signs of Celsus |journal=Bulletin of the New York Academy of Medicine |volume=47 |issue=3 |pages=303–22 |pmc=1749862 |pmid=5276838}}</ref>}}
|}

Inflammation is characterized by five [[cardinal signs]],<ref name="ConcisePathology-Signs">{{Cite book |url=http://www.accessmedicine.com/resourceTOC.aspx?resourceID=7 |title=Concise Pathology |vauthors=Chandrasoma P, Taylor CR |publisher=McGraw-Hill |year=2005 |isbn=978-0-8385-1499-3 |edition=3rd |chapter=Part A. "General Pathology", Section II. "The Host Response to Injury", Chapter 3. "The Acute Inflammatory Response", sub-section "Cardinal Clinical Signs" |oclc=150148447 |access-date=2008-11-05 |chapter-url=http://www.accessmedicine.com/content.aspx?aID=183351 |archive-url=https://web.archive.org/web/20081005091840/http://accessmedicine.com/resourceTOC.aspx?resourceID=7 |archive-date=5 October 2008 |url-status=live}}</ref><ref name="auto">{{cite journal | vauthors = Rather LJ | title = Disturbance of function (functio laesa): the legendary fifth cardinal sign of inflammation, added by Galen to the four cardinal signs of Celsus | journal = Bulletin of the New York Academy of Medicine | volume = 47 | issue = 3 | pages = 303–322 | date = March 1971 | pmid = 5276838 | pmc = 1749862 }}</ref> (the traditional names of which  come from Latin):
* [[Pain|Dolor]] ([[pain]])
* Calor (heat)
* [[Rubor]] (redness)
* Tumor ([[swelling (medical)|swelling]])
* [[Functio laesa]] (loss of function)<ref>{{Cite book |url=http://thepoint.lww.com/Book/ShowWithResource/2931?resourceId=16419 |title=A massage Therapist Guide to Pathology |vauthors=Werner R |publisher=Wolters Kluwer |year=2009 |isbn=978-0-7817-6919-8 |edition=4th |access-date=6 October 2010 |archive-url=https://web.archive.org/web/20151221050601/http://thepoint.lww.com/Book/ShowWithResource/2931?resourceId=16419 |archive-date=21 December 2015 |url-status=live}}</ref>

The first four (classical signs) were described by [[Aulus Cornelius Celsus|Celsus]] ({{circa|30 BC}}–38 AD).<ref>{{Cite book |url=https://books.google.com/books?id=t_5pzrF1QocC&pg=PA97 |title=Brief History of Vision and Ocular Medicine |vauthors=Vogel WH, Berke A |publisher=Kugler Publications |year=2009 |isbn=978-90-6299-220-1 |page=97}}</ref>

[[Pain]] is due to the release of chemicals such as bradykinin and histamine that stimulate nerve endings.<ref name="ConcisePathology-Signs" /> Acute inflammation of the lung (usually in response to [[pneumonia]]) does not cause pain unless the inflammation involves the [[parietal pleura]], which does have [[nociceptor|pain-sensitive nerve endings]].<ref name="ConcisePathology-Signs" /> Heat and redness are due to increased blood flow at body core temperature to the inflamed site. Swelling is caused by accumulation of fluid.

=====Loss of function=====
The fifth sign, ''loss of function'', is believed to have been added later by [[Galen]],<ref name="isbn0-7817-7087-4">{{Cite book |title=Essentials of pahtophysiology: concepts of altered health states |vauthors=Porth C |publisher=Lippincott Williams & Wilkins |year=2007 |isbn=978-0-7817-7087-3 |location=Hagerstown, MD |pages=270}}</ref> [[Thomas Sydenham]]<ref name="isbn0-300-11322-6">{{Cite book |url=https://archive.org/details/worstofevilsmans00dorm/page/22 |title=The worst of evils: man's fight against pain |vauthors=Dormandy T |publisher=Yale University Press |year=2006 |isbn=978-0-300-11322-8 |location=New Haven, Conn |pages=[https://archive.org/details/worstofevilsmans00dorm/page/22 22] |url-access=registration}}</ref> or [[Rudolf Ludwig Karl Virchow|Rudolf Virchow]].<ref name="robspath">{{Cite book |title=Robbins Pathologic Basis of Disease |vauthors=Robbins SL, Cotran RS, Kumar V, Collins T |publisher=W.B Saunders Company |year=1998 |isbn=978-0-7216-7335-6 |location=Philadelphia}}</ref><ref name="ConcisePathology-Signs" /><ref name="auto" /> Examples of loss of function include  pain that inhibits mobility, severe swelling that prevents movement, having a worse sense of smell during a cold, or having difficulty breathing when bronchitis is present.<ref>{{Cite book |url=https://www.ncbi.nlm.nih.gov/books/NBK279298/ |title=InformedHealth.org [Internet] |date=22 February 2018 |publisher=Institute for Quality and Efficiency in Health Care (IQWiG) |via=www.ncbi.nlm.nih.gov}}</ref><ref>{{Cite web |date=11 March 2024 |title=Inflammation &#124; Definition, Symptoms, Treatment, & Facts &#124; Britannica |url=https://www.britannica.com/science/inflammation |website=www.britannica.com}}</ref>  Loss of function has multiple causes.<ref name="ConcisePathology-Signs" />

==== Acute process ====
{{More medical citations needed|section|date=April 2023}}
[[File:Events in Acute Inflammation.pdf|thumb|569x569px|A flowchart depicting the events of acute inflammation.<ref>{{Cite book |title=Pathologic basis of disease |vauthors=Robbins S, Cotran R, Kumar V, Abbas A, Aster J |date=2020 |publisher=Saunders Elsevier |edition=10th |location=Philadelphia, PA}}</ref>]]
[[File:Granulation tissue low power.jpg|thumb|[[Micrograph]] showing granulation tissue. [[H&E stain]].]]
The process of acute inflammation is initiated by resident immune cells already present in the involved tissue, mainly resident [[macrophages]], [[dendritic cells]], [[histiocytes]], [[Kupffer cells]] and [[mast cell]]s. These cells possess surface receptors known as ''[[pattern recognition receptor]]s'' (PRRs), which recognize (i.e., bind) two subclasses of molecules: [[pathogen-associated molecular pattern]]s (PAMPs) and [[damage-associated molecular pattern]]s (DAMPs). PAMPs are compounds that are associated with various [[pathogen]]s, but which are distinguishable from host molecules. DAMPs are compounds that are associated with host-related injury and cell damage.

At the onset of an infection, burn, or other injuries, these cells undergo activation (one of the PRRs recognize a PAMP or DAMP) and release inflammatory mediators responsible for the clinical signs of inflammation. Vasodilation and its resulting increased blood flow causes the redness (''rubor'') and increased heat (''calor''). Increased permeability of the blood vessels results in an exudation (leakage) of [[blood plasma|plasma]] proteins and fluid into the tissue ([[edema]]), which manifests itself as swelling (''tumor''). Some of the released mediators such as [[bradykinin]] increase the sensitivity to pain ([[hyperalgesia]], ''dolor''). The mediator molecules also alter the blood vessels to permit the migration of leukocytes, mainly [[neutrophils]] and [[macrophages]], to flow out of the blood vessels (extravasation) and into the tissue. The neutrophils migrate along a [[chemotactic]] gradient created by the local cells to reach the site of injury.<ref name="robspath" /> The loss of function (''functio laesa'') is probably the result of a neurological reflex in response to pain.

In addition to cell-derived mediators, several acellular biochemical cascade systems—consisting of preformed plasma proteins—act in parallel to initiate and propagate the inflammatory response. These include the [[complement system]] activated by bacteria and the [[coagulation system|coagulation]] and [[fibrinolysis system]]s activated by [[necrosis]] (e.g., burn, trauma).<ref name="robspath" />

Acute inflammation may be regarded as the first line of defense against injury. Acute inflammatory response requires constant stimulation to be sustained. Inflammatory mediators are short-lived and are quickly degraded in the tissue. Hence, acute inflammation begins to cease once the stimulus has been removed.<ref name="robspath" />