Editing Shock (circulatory) (section)

==Pathophysiology==
[[Image:Shock-cell2.svg|500px|thumb|Effects of inadequate perfusion on cell function]]

Shock is a complex and continuous condition, and there is no sudden transition from one stage to the next.<ref name="Armstrong">{{Cite book |last=Armstrong |first=D.J. |title=Shock |publisher=Edinburgh: Churchill Livingstone |year=2004 |edition=2nd |location=In: Alexander, M.F., Fawcett, J.N., Runciman, P.J. ''Nursing Practice. Hospital and Home. The Adult.''}}</ref> At a cellular level, shock is the process of oxygen demand becoming greater than oxygen supply.<ref name=Tint10/>

One of the key dangers of shock is that it progresses by a [[positive feedback]] loop. Poor blood supply leads to cellular damage, which results in an inflammatory response to increase blood flow to the affected area. Normally, this causes the blood supply level to match with tissue demand for nutrients. However, if there is enough increased demand in some areas, it can deprive other areas of sufficient supply, which then start demanding more. This then leads to an ever escalating cascade.{{cn|date=February 2025}}

As such, shock is a [[chain reaction|runaway]] condition of [[homeostasis|homeostatic]] failure, where the usual corrective mechanisms relating to oxygenation of the body no longer function in a stable way. When it occurs, immediate treatment is critical in order to return an individual's metabolism into a stable, self-correcting trajectory. Otherwise the condition can become increasingly difficult to correct, surprisingly quickly, and then progress to a fatal outcome. In the particular case of anaphylactic shock, progression to death might take just a few minutes.<ref name="Guyton">{{Cite book |last1=Guyton |first1=Arthur |title=Textbook of Medical Physiology |last2=Hall |first2=John |publisher=Elsevier Inc. |year=2006 |isbn=978-0-7216-0240-0 |editor-last=Gruliow |editor-first=Rebecca |edition=11th |location=Philadelphia, Pennsylvania |pages=278–88 |chapter=Chapter 24: Circulatory Shock and Physiology of Its Treatment}}</ref>

===Initial===
During the Initial stage (Stage 1), the state of [[hypoperfusion]] causes [[Hypoxia (medical)|hypoxia]]. Due to the lack of oxygen, the cells perform [[lactic acid fermentation]]. Since oxygen, the terminal electron acceptor in the [[electron transport chain]], is not abundant, this slows down entry of [[pyruvate]] into the [[Citric acid cycle|Krebs cycle]], resulting in its accumulation. The accumulating pyruvate is converted to [[Lactic acid|lactate (lactic acid)]] by [[lactate dehydrogenase]]. The accumulating lactate causes [[lactic acidosis]].{{cn|date=February 2025}}

===Compensatory===
The Compensatory stage (Stage 2) is characterised by the body employing physiological mechanisms, including neural, hormonal, and bio-chemical mechanisms, in an attempt to reverse the condition.  As a result of the [[acidosis]], the person will begin to [[hyperventilation|hyperventilate]] in order to rid the body of carbon dioxide (CO<sub>2</sub>) since it indirectly acts to acidify the blood; the body attempts to return to [[acid–base homeostasis]] by removing that acidifying agent. The [[baroreceptors]] in the [[artery|arteries]] detect the [[hypotension]] resulting from large amounts of blood being redirected to distant tissues, and cause the release of [[epinephrine]] and [[norepinephrine]]. Norepinephrine causes predominately [[vasoconstriction]] with a mild increase in [[heart rate]], whereas [[epinephrine]] predominately causes an increase in [[heart rate]] with a small effect on the [[Blood vessel|vascular]] tone; the combined effect results in an increase in [[blood pressure]]. The [[Renin–angiotensin system|renin–angiotensin axis]] is activated, and [[arginine vasopressin]] (anti-diuretic hormone) is released to conserve fluid by reducing its excretion via the [[renal]] system. These hormones cause the vasoconstriction of the [[kidney]]s, [[gastrointestinal tract]], and other organs to divert blood to the heart, [[lungs]] and [[brain]]. The lack of blood to the renal system causes the characteristic low [[urine]] production. However, the effects of the renin–angiotensin axis take time and are of little importance to the immediate [[homeostatic]] mediation of shock.{{citation needed|date=June 2011}}

===Progressive/decompensated===
The Progressive stage (stage 3) results if the underlying cause of the shock is not successfully treated. During this stage, compensatory mechanisms begin to fail. Due to the decreased perfusion of the cells in the body, [[sodium]] ions build up within the intracellular space while [[potassium]] ions leak out. Due to lack of oxygen, [[cellular respiration]] diminishes and [[Anaerobic respiration|anaerobic metabolism]] predominates. As anaerobic metabolism continues, the arteriolar smooth muscle and precapillary [[sphincters]] relax such that blood remains in the [[capillaries]].<ref name="Robbins">{{Cite book |last1=Kumar |first1=Vinay |url=https://www.worldcat.org/oclc/69672074 |title=Robbins Basic Pathology |last2=Abbas |first2=Abul K. |last3=Fausto |first3=Nelson |last4=Mitchell |first4=Richard N. |date=2007 |publisher=Saunders/Elsevier |isbn=978-1-4160-2973-1 |edition=8th |location=Philadelphia, PA |pages=102–103 |oclc=69672074 |archive-date=2020-06-05 |access-date=2022-09-02 |archive-url=https://web.archive.org/web/20200605131552/https://www.worldcat.org/title/robbins-basic-pathology/oclc/69672074 |url-status=live }}</ref> Due to this, the [[Hydrostatics#Medicine|hydrostatic pressure]] will increase and, combined with [[histamine]] release, will lead to [[Extravasation|leakage of fluid]] and [[protein]] into the surrounding tissues.  As this fluid is lost, the blood concentration and [[viscosity]] increase, causing sludging of the micro-circulation. The prolonged vasoconstriction will also cause the vital organs to be compromised due to [[ischemia|reduced perfusion]].<ref name=Robbins/> If the bowel becomes sufficiently [[ischemic]], bacteria may enter the blood stream, resulting in the increased complication of [[septic shock|endotoxic shock]].<ref name=Guyton/><ref name=Robbins/>

===Refractory===
At Refractory stage (stage 4), the vital [[organ failure|organs have failed]] and the shock can no longer be reversed. [[Brain damage]] and cell death are occurring, and death will occur imminently. One of the primary reasons that shock is irreversible at this point is that much of the cellular [[Adenosine triphosphate|ATP]] (the basic energy source for cells) has been degraded into [[adenosine]] in the absence of oxygen as an electron receptor in the [[mitochondrial matrix]]. Adenosine easily perfuses out of cellular membranes into extracellular fluid, furthering capillary [[vasodilation]], and then is transformed into [[uric acid]]. Because cells can only produce adenosine at a rate of about 2% of the cell's total need per hour, even restoring oxygen is futile at this point because there is no adenosine to [[phosphorylate]] into ATP.<ref name=Guyton/>