Editing Diabetic ketoacidosis (section)

==Mechanism==
Diabetic ketoacidosis arises because of a lack of insulin in the body.<ref>{{Citation |last1=Ghimire |first1=Pranita |title=Ketoacidosis |date=2024 |work=StatPearls |url=http://www.ncbi.nlm.nih.gov/books/NBK534848/ |access-date=2024-04-27 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30521269 |last2=Dhamoon |first2=Amit S.}}</ref> The lack of insulin and corresponding elevation of [[glucagon]] leads to increased release of glucose by the [[liver]] (a process that is normally suppressed by insulin) from [[glycogen]] via [[glycogenolysis]] and also through [[gluconeogenesis]].<ref>{{Cite journal |date=November 2010 |title=The Physiology of Glucagon |journal= Journal of Diabetes Science and Technology|pmc=3005043 |volume=4 |issue=6 |pages=1338–1344 |doi=10.1177/193229681000400607 |pmid=21129328 | vauthors = Taborsky GJ Jr }}</ref> High glucose levels spill over into the urine, taking water and solutes (such as [[sodium]] and [[potassium]]) along with it in a process known as [[osmotic diuresis]].<ref name=ADA2009/> This leads to [[polyuria]], dehydration, and [[polydipsia]]. The absence of insulin also leads to the release of free [[fatty acid]]s from [[adipose tissue]] ([[lipolysis]]), which the liver converts into acetyl CoA through a process called [[beta oxidation]]. 

Acetyl CoA is metabolised into ketone bodies under severe states of energy deficiency, like starvation, through a process called [[ketogenesis]], whose final products are aceto-acetate and β-Hydroxybutyrate. These ketone bodies can serve as an energy source in the absence of insulin-mediated glucose delivery, and is a protective mechanism in case of starvation. The ketone bodies, however, have a low [[Acid dissociation constant|pKa]] and therefore turn the blood acidic ([[metabolic acidosis]]). The body initially [[buffer solution|buffers]] the change with the [[bicarbonate buffering system]], but this system is quickly overwhelmed and other mechanisms must work to compensate for the acidosis.<ref name=ADA2009/> One such mechanism is [[hyperventilation]] to lower blood [[carbon dioxide]] levels (a form of compensatory [[respiratory alkalosis]]). This hyperventilation, in its extreme form, may be observed as [[Kussmaul respiration]].<ref name=Powers2005/>

In various situations such as infection, insulin demands rise but are not matched by the failing pancreas. Blood sugars rise, dehydration ensues, and [[insulin resistance|resistance to the normal effects of insulin]] increases further by way of a [[Virtuous circle and vicious circle|vicious circle]].<ref name=ADA2009/><ref name=Eledrisi/>

As a result of the above mechanisms, the average adult with DKA has a total body water shortage of about 6&nbsp;liters (or 100&nbsp;mL/kg), in addition to substantial shortages in sodium, [[potassium]], [[chloride]], [[phosphate]], [[magnesium]] and [[calcium]]. Glucose levels usually exceed 13.8&nbsp;mmol/L or 250&nbsp;mg/dL.<ref name=ADA2006>{{cite journal | vauthors = Kitabchi AE, Umpierrez GE, Murphy MB, Kreisberg RA | title = Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association | journal = Diabetes Care | volume = 29 | issue = 12 | pages = 2739–2748 | date = December 2006 | pmid = 17130218 | doi = 10.2337/dc06-9916 | url = http://care.diabetesjournals.org/content/29/12/2739.full | url-status = live | doi-access = free | archive-url = https://web.archive.org/web/20100327082010/http://care.diabetesjournals.org/content/29/12/2739.full | archive-date = 2010-03-27 }}</ref>

[[File:beta-Hydroxybutyric acid-2D-skeletal.svg|right|thumb|[[beta-Hydroxybutyric acid|β-hydroxybutyrate]] (the conjugate base of β-hydroxybutyric acid, drawn above) despite chemically containing a carboxylate group instead of a ketone, is the principal "ketone body" in diabetic ketoacidosis.]]
DKA is common in type 1 diabetes as this form of diabetes is associated with an absolute lack of insulin production by the [[islets of Langerhans]]. In type 2 diabetes, insulin production is present but is insufficient to meet the body's requirements as a result of end-organ insulin resistance. Usually, these amounts of insulin are sufficient to suppress ketogenesis. If DKA occurs in someone with type 2 diabetes, their condition is called "ketosis-prone type 2 diabetes".<ref name=Umpierrez2006/> The exact mechanism for this phenomenon is unclear, but there is evidence both of impaired insulin secretion and insulin action.<ref name=ADA2009/><ref name=Umpierrez2006/> Once the condition has been treated, insulin production resumes and often the person may be able to resume diet or tablet treatment as normally recommended in type 2 diabetes.<ref name=ADA2009/>

The clinical state of DKA is associated, in addition to the above, with the release of various [[counterregulatory hormone]]s such as [[glucagon]] and [[adrenaline]] as well as [[cytokine]]s, the latter of which leads to increased markers of [[inflammation]], even in the absence of [[infection]].<ref name=ADA2009/><ref name=ESPE>{{cite journal | vauthors = Dunger DB, Sperling MA, Acerini CL, Bohn DJ, Daneman D, Danne TP, Glaser NS, Hanas R, Hintz RL, Levitsky LL, Savage MO, Tasker RC, Wolfsdorf JI | display-authors = 6 | title = European Society for Paediatric Endocrinology/Lawson Wilkins Pediatric Endocrine Society consensus statement on diabetic ketoacidosis in children and adolescents | journal = Pediatrics | volume = 113 | issue = 2 | pages = e133–e140 | date = February 2004 | pmid = 14754983 | doi = 10.1542/peds.113.2.e133 | url = http://pediatrics.aappublications.org/cgi/content/full/113/2/e133 | url-status = live | doi-access =  | archive-url = https://web.archive.org/web/20090912041227/http://pediatrics.aappublications.org/cgi/content/full/113/2/e133 | archive-date = 2009-09-12 }}</ref>

Cerebral edema, which is the most dangerous DKA complication, is probably the result of a number of factors. Some authorities suggest that it is the result of overvigorous fluid replacement, but the complication may develop before treatment has been commenced.<ref name=Glaser2006 /><ref name=Brown2004 /> It is more likely in those with more severe DKA,<ref name=ESPE/> and in the first episode of DKA.<ref name=Glaser2006 /> Likely factors in the development of cerebral edema are dehydration, acidosis and low carbon dioxide levels; in addition, the increased level of inflammation and [[coagulation]] may, together with these factors, lead to decreased blood flow to parts of the brain, which then swells up once fluid replacement has been commenced.<ref name=Glaser2006 /> The swelling of brain tissue leads  to raised [[intracranial pressure]] ultimately leading to death.<ref name=ESPE/><ref name=Brown2004/>