Editing Exercise physiology (section)

== Metabolic changes ==
[[File:Ergospirometry laboratory.jpg|thumb|Ergospirometry laboratory for the measurement of metabolic changes during a graded exercise test on a treadmill]]

=== Rapid energy sources ===
Energy needed to perform short lasting, high intensity bursts of activity is derived from [[Bioenergetic systems#Anaerobic metabolism|anaerobic metabolism]] within the [[cytosol]] of muscle cells, as opposed to [[aerobic respiration]] which utilizes oxygen, is sustainable, and occurs in the [[mitochondria]]. The quick energy sources consist of the [[phosphocreatine]] (PCr) system, fast [[glycolysis]], and [[adenylate kinase]]. All of these systems re-synthesize [[adenosine triphosphate]] (ATP), which is the universal energy source in all cells. The most rapid source, but the most readily depleted of the above sources is the PCr system which utilizes the enzyme [[creatine kinase]]. This enzyme catalyzes a reaction that combines [[phosphocreatine]] and adenosine diphosphate (ADP) into ATP and [[creatine]]. This resource is short lasting because oxygen is required for the resynthesis of phosphocreatine via mitochondrial creatine kinase. Therefore, under anaerobic conditions, this substrate is finite and only lasts between approximately 10 to 30 seconds of high intensity work. Fast glycolysis, however, can function for approximately 2 minutes prior to fatigue, and predominantly uses intracellular glycogen as a substrate. Glycogen is broken down rapidly via [[glycogen phosphorylase]] into individual glucose units during intense exercise. Glucose is then oxidized to pyruvate and under anaerobic conditions is reduced to lactic acid. This reaction oxidizes NADH to NAD, thereby releasing a hydrogen ion, promoting acidosis. For this reason, fast glycolysis can not be sustained for long periods of time.{{cn|date=April 2025}}

=== Plasma glucose ===
Plasma glucose is said to be maintained when there is an equal rate of glucose appearance (entry into the blood) and glucose disposal (removal from the blood). In the healthy individual, the rates of appearance and disposal are essentially equal during exercise of moderate intensity and duration; however, prolonged exercise or sufficiently intense exercise can result in an imbalance leaning towards a higher rate of disposal than appearance, at which point glucose levels fall producing the onset of fatigue. Rate of glucose appearance is dictated by the amount of glucose being absorbed at the gut as well as liver (hepatic) glucose output. Although glucose absorption from the gut is not typically a source of glucose appearance during exercise, the liver is capable of catabolizing stored [[glycogen]] ([[glycogenolysis]]) as well as synthesizing new glucose from specific reduced carbon molecules (glycerol, pyruvate, and lactate) in a process called [[gluconeogenesis]]. The ability of the liver to release glucose into the blood from glycogenolysis is unique, since skeletal muscle, the other major glycogen reservoir, is incapable of doing so. Unlike skeletal muscle, liver cells contain the enzyme [[(glycogen-synthase-D) phosphatase|glycogen phosphatase]], which removes a phosphate group from glucose-6-P to release free glucose. In order for glucose to exit a cell membrane, the removal of this phosphate group is essential. Although gluconeogenesis is an important component of hepatic glucose output, it alone cannot sustain exercise. For this reason, when glycogen stores are depleted during exercise, glucose levels fall and fatigue sets in. Glucose disposal, the other side of the equation, is controlled by the uptake of glucose by the working skeletal muscles. During exercise, despite decreased [[insulin]] concentrations, muscle increases [[GLUT4]] translocation  and glucose uptake. The mechanism for increased GLUT4 translocation is an area of ongoing research.{{cn|date=April 2025}}

'''glucose control''':
As mentioned above, insulin secretion is reduced during exercise, and does not play a major role in maintaining normal blood glucose concentration during exercise, but its counter-regulatory hormones appear in increasing concentrations. Principle among these are [[glucagon]], [[epinephrine]], and [[growth hormone]]. All of these hormones stimulate liver (hepatic) glucose output, among other functions. For instance, both epinephrine and growth hormone also stimulate adipocyte lipase, which increases non-esterified fatty acid (NEFA) release. By oxidizing fatty acids, this spares glucose utilization and helps to maintain blood sugar level during exercise.{{cn|date=April 2025}}

'''Exercise for diabetes''':
Exercise is a particularly potent tool for glucose control in those who have [[diabetes mellitus]]. In a situation of elevated blood glucose ([[hyperglycemia]]), moderate exercise can induce greater glucose disposal than appearance, thereby decreasing total plasma glucose concentrations. As stated above, the mechanism for this glucose disposal is independent of insulin, which makes it particularly well-suited for people with diabetes. In addition, there appears to be an increase in sensitivity to insulin for approximately 12–24 hours post-exercise. This is particularly useful for those who have type II diabetes and are producing sufficient insulin but demonstrate peripheral resistance to insulin signaling. However, during extreme hyperglycemic episodes, people with diabetes should avoid exercise due to potential complications associated with [[ketoacidosis]]. Exercise could exacerbate ketoacidosis by increasing ketone synthesis in response to increased circulating NEFA's.{{cn|date=April 2025}}

Type II diabetes is also intricately linked to obesity, and there may be a connection between type II diabetes and how fat is stored within pancreatic, muscle, and liver cells. Likely due to this connection, weight loss from both exercise and diet tends to increase insulin sensitivity in the majority of people.<ref>{{Cite journal |last=Boutcher |first=Stephen H. |date=2011 |title=High-Intensity Intermittent Exercise and Fat Loss |journal=Journal of Obesity |language=en |volume=2011 |pages=868305 |doi=10.1155/2011/868305 |pmc=2991639 |pmid=21113312 |doi-access=free}}</ref> In some people, this effect can be particularly potent and can result in normal glucose control. Although nobody is technically cured of diabetes, individuals can live normal lives without the fear of diabetic complications; however, regain of weight would assuredly result in diabetes signs and symptoms.{{cn|date=April 2025}}

=== Oxygen ===

Vigorous physical activity (such as exercise or hard labor) increases the body's demand for oxygen. The first-line physiologic response to this demand is an increase in [[heart rate]], [[breathing rate]], and [[deep breathing|depth of breathing]].{{cn|date=April 2025}}

Oxygen consumption (VO<sub>2</sub>) during exercise is best described by the [[Fick Equation]]: VO<sub>2</sub>=Q x (a-vO<sub>2</sub>diff), which states that the amount of oxygen consumed is equal to [[cardiac output]] (Q) multiplied by the difference between arterial and venous oxygen concentrations. More simply put, oxygen consumption is dictated by the quantity of blood distributed by the heart as well as the working muscle's ability to take up the oxygen within that blood; however, this is a bit of an oversimplification. Although cardiac output is thought to be the limiting factor of this relationship in healthy individuals, it is not the only determinant of VO2 max. That is, factors such as the ability of the lung to oxygenate the blood must also be considered. Various pathologies and anomalies cause conditions such as diffusion limitation, ventilation/perfusion mismatch, and pulmonary shunts that can limit oxygenation of the blood and therefore oxygen distribution. In addition, the oxygen carrying capacity of the blood is also an important determinant of the equation. Oxygen carrying capacity is often the target of exercise ([[ergogenic aids]]) aids used in endurance sports to increase the volume percentage of red blood cells ([[hematocrit]]), such as through [[blood doping]] or the use of [[erythropoietin]] (EPO). Furthermore, peripheral oxygen uptake is reliant on a rerouting of blood flow from relatively inactive [[viscera]] to the working skeletal muscles, and within the skeletal muscle, capillary to muscle fiber ratio influences oxygen extraction.{{cn|date=April 2025}}

=== Dehydration ===
[[Dehydration]] refers both to hypohydration (dehydration induced prior to exercise) and to exercise-induced dehydration (dehydration that develops during exercise). The latter reduces aerobic endurance performance and results in increased body temperature, heart rate, perceived exertion, and possibly increased reliance on carbohydrate as a fuel source. Although the negative effects of exercise-induced dehydration on exercise performance were clearly demonstrated in the 1940s, athletes continued to believe for years thereafter that fluid intake was not beneficial. More recently, negative effects on performance have been demonstrated with modest (<2%) dehydration, and these effects are exacerbated when the exercise is performed in a hot environment. The effects of hypohydration may vary, depending on whether it is induced through diuretics or sauna exposure, which substantially reduce plasma volume, or prior exercise, which has much less impact on plasma volume. Hypohydration reduces aerobic endurance, but its effects on muscle strength and endurance are not consistent and require further study.<ref>{{Cite journal |last=Barr |first=SI |year=1999 |title=Effects of dehydration on exercise performance |journal=Canadian Journal of Applied Physiology |volume=24 |issue=2 |pages=164–72 |doi=10.1139/h99-014 |pmid=10198142}}</ref>  Intense prolonged exercise produces metabolic waste heat, and this is removed by [[sweat]]-based [[thermoregulation]]. A male [[marathon]] runner loses each hour around 0.83 L in cool weather and 1.2 L in warm (losses in females are about 68 to 73% lower).<ref name="cheuvront">{{Cite journal |vauthors=Cheuvront SN, Haymes EM |year=2001 |title=Thermoregulation and marathon running: biological and environmental influences |journal=Sports Med |volume=31 |issue=10 |pages=743–62 |doi=10.2165/00007256-200131100-00004 |pmid=11547895 |s2cid=45969661}}</ref> People doing heavy exercise may lose two and half times as much fluid in sweat as urine.<ref>{{Cite journal |last=Porter |first=AM |year=2001 |title=Why do we have apocrine and sebaceous glands? |journal=Journal of the Royal Society of Medicine |volume=94 |issue=5 |pages=236–7 |doi=10.1177/014107680109400509 |pmc=1281456 |pmid=11385091}}</ref> This can have profound physiological effects. Cycling for 2 hours in the heat (35&nbsp;°C) with minimal fluid intake causes body mass decline by 3 to 5%, blood volume likewise by 3 to 6%, body temperature to rise constantly, and in comparison with proper fluid intake, higher heart rates, lower stroke volumes and cardiac outputs, reduced skin blood flow, and higher systemic vascular resistance. These effects are largely eliminated by replacing 50 to 80% of the fluid lost in sweat.<ref name="cheuvront" /><ref>{{Cite journal |last=González-Alonso |first=J |last2=Mora-Rodríguez |first2=R |last3=Below |first3=PR |last4=Coyle |first4=EF |year=1995 |title=Dehydration reduces cardiac output and increases systemic and cutaneous vascular resistance during exercise |journal=Journal of Applied Physiology |volume=79 |issue=5 |pages=1487–96 |doi=10.1152/jappl.1995.79.5.1487 |pmid=8594004}}</ref>

=== Other ===
* Plasma [[catecholamine]] concentrations increase 10-fold in whole body exercise.<ref>{{Cite journal |last=Holmqvist |first=N |last2=Secher |first2=NH |last3=Sander-Jensen |first3=K |last4=Knigge |first4=U |last5=Warberg |first5=J |last6=Schwartz |first6=TW |year=1986 |title=Sympathoadrenal and parasympathetic responses to exercise |journal=Journal of Sports Sciences |volume=4 |issue=2 |pages=123–8 |doi=10.1080/02640418608732108 |pmid=3586105}}</ref>
* [[Ammonia]] is produced by exercised skeletal muscles from ADP (the precursor of ATP) by [[AMP deaminase|purine nucleotide deamination]] and [[amino acid]] [[catabolism]] of [[myofibrils]].<ref name="Nybo, L. 2005">{{Cite journal |last=Nybo |first=L |last2=Dalsgaard |first2=MK |last3=Steensberg |first3=A |last4=Møller |first4=K |last5=Secher |first5=NH |year=2005 |title=Cerebral ammonia uptake and accumulation during prolonged exercise in humans |journal=The Journal of Physiology |volume=563 |issue=Pt 1 |pages=285–90 |doi=10.1113/jphysiol.2004.075838 |pmc=1665558 |pmid=15611036}}</ref>
* [[interleukin-6]] (IL-6) increases in blood circulation due to its release from working skeletal muscles.<ref>{{Cite journal |last=Febbraio |first=MA |last2=Pedersen |first2=BK |year=2002 |title=Muscle-derived interleukin-6: Mechanisms for activation and possible biological roles |journal=FASEB Journal |volume=16 |issue=11 |pages=1335–47 |doi=10.1096/fj.01-0876rev |pmid=12205025 |s2cid=14024672 |doi-access=free}}</ref> This release is reduced if glucose is taken, suggesting it is related to energy depletion stresses.<ref>{{Cite journal |last=Febbraio |first=MA |last2=Steensberg |first2=A |last3=Keller |first3=C |last4=Starkie |first4=RL |last5=Nielsen |first5=HB |last6=Krustrup |first6=P |last7=Ott |first7=P |last8=Secher |first8=NH |last9=Pedersen |first9=BK |year=2003 |title=Glucose ingestion attenuates interleukin-6 release from contracting skeletal muscle in humans |journal=The Journal of Physiology |volume=549 |issue=Pt 2 |pages=607–12 |doi=10.1113/jphysiol.2003.042374 |pmc=2342952 |pmid=12702735}}</ref>
* Sodium absorption is affected by the release of interleukin-6 as this can cause the secretion of [[arginine vasopressin]] which, in turn, can lead to exercise-associated dangerously low sodium levels ([[hyponatremia]]). This loss of sodium in [[blood plasma]] can result in swelling of the brain. This can be prevented by awareness of the risk of drinking excessive amounts of fluids during prolonged exercise.<ref>{{Cite journal |last=Siegel |first=AJ |last2=Verbalis |first2=JG |last3=Clement |first3=S |last4=Mendelson |first4=JH |last5=Mello |first5=NK |last6=Adner |first6=M |last7=Shirey |first7=T |last8=Glowacki |first8=J |last9=Lee-Lewandrowski |first9=E |last10=Lewandrowski |first10=Kent B. |display-authors=8 |year=2007 |title=Hyponatremia in marathon runners due to inappropriate arginine vasopressin secretion |journal=The American Journal of Medicine |volume=120 |issue=5 |pages=461.e11–7 |doi=10.1016/j.amjmed.2006.10.027 |pmid=17466660}}</ref><ref>{{Cite journal |last=Siegel |first=AJ |year=2006 |title=Exercise-associated hyponatremia: Role of cytokines |journal=The American Journal of Medicine |volume=119 |issue=7 Suppl 1 |pages=S74–8 |doi=10.1016/j.amjmed.2006.05.012 |pmid=16843089}}</ref>