Physiological Changes in Exercise (YR1 Lecture 1H - Dr Alex Burton 2022 PDF)

physiological changes in exercise Alexander Burton Adjunct Fellow School of Medicine Western Sydney University Learning objectives: To recall that exercise is associated with large increases in metabolism and the generation of heat, which must be liberated through sweat release To recognise that blo...

physiological changes in exercise Alexander Burton Adjunct Fellow School of Medicine Western Sydney University Learning objectives: To recall that exercise is associated with large increases in metabolism and the generation of heat, which must be liberated through sweat release To recognise that blood flow to contracting muscles increases during exercise due to the actions of metabolites on local blood vessels, but that blood flow to non-contracting muscles decreases due to the increase in muscle sympathetic nerve activity (MSNA) To recognise that central command is responsible for the increase in heart rate, but that both central command and reflex inputs from the contracting muscles contribute to the sympathetically mediated increase in blood pressure To recall the central pathways involved in these changes in muscle blood flow during exercise Skeletal muscle metabolism At rest, metabolism within relaxed skeletal muscle blood flow is very low: ~1.5 ml O2/min.kg During exercise metabolism can increase 100-fold: ~150 ml O2/min.kg This high metabolism requires a high blood flow to supply O2 and energy substrates and to remove CO2 and metabolites Adrenaline (epinepherine) turns on energy production Skeletal muscle metabolism At rest, metabolism within relaxed skeletal muscle blood flow is very low: ~1.5 ml O2/min.kg During exercise metabolism can increase 100-fold: ~150 ml O2/min.kg This high metabolism requires a high blood flow to supply O2 and energy substrates and to remove CO2 and metabolites The high metabolism also generates large amounts of heat, which needs to be liberated through sweat release Human thermogenesis during exercise Physical activity increases energy expenditure (and hence heat production), largely from active skeletal muscle Heat production increases from ~80 kcal/h at rest to ~600 kcal/h during moderate exercise (e.g. jogging) Unless this excess heat is dissipated core temperature will increase by 1 oC every 10 min, limiting the duration of exercise to 30 min (core temperature 40 oC) Evaporative heat loss in humans: Evaporation of sweat can liberate most of the heat produced during exercise Sweating occurs immediately prior to exercise in trained athletes, thereby offsetting the increase in body temperature Loss of water places significant demands on the body, particularly when exercising in hot, humid conditions: unless the water and solutes are replaced plasma volume decreases and the viscosity of the blood increases During exercise sweating is the most important means of liberating heat Cutaneous vasodilatation In normothermic conditions skin blood flow is approximately 5% of cardiac output During heating blood flow in non-glabrous skin increases due to withdrawal of active noradrenergic cutaneous vasoconstriction As heating increases sweat release and active cholinergic vasodilatation occurs in non-glabrous skin In heat stress skin blood flow can increase to ~60% of cardiac output, which needs to be balanced by the demands of increased blood flow to contracting muscles Exercise-induced changes in muscle blood flow Blood flow to exercising muscle increases via the vasodilatory effects of metabolites, despite an increase in muscle sympathetic nerve activity (vasoconstrictor drive) to the contracting muscle Muscle Sympathetic Nerve Activity (MSNA) increases to the contracting muscle, as does sensory feedback from the muscle muscle afferent feedback increases rest MSNA increases contraction Boulton D, Taylor CE, Macefield VG & Green S (2014) Frontiers in Physiology 5: 194(1-9) Exercise-induced changes in muscle blood flow Blood flow to exercising muscle increases via the vasodilatory effects of metabolites, despite an increase in muscle sympathetic nerve activity (vasoconstrictor drive) to the contracting muscle Blood flow to non-exercising muscles decreases via an increase in muscle vasoconstrictor drive This increase in muscle vasoconstrictor drive - coupled with an increase in splanchnic vasoconstrictor drive to the gut - raises blood pressure This offsets the fall induced by cutaneous vasodilation and increases overall perfusion pressure How are these changes brought about? Central command - the motor commands to the muscles Reflex inputs from the contracting muscles Central command The “will” to exercise engages motor planning and motor execution areas of the cerebral cortex and cerebellum The set of motor commands to the skeletal muscles is transmitted from the primary motor cortex to the spinal motoneurones via the corticospinal tracts A parallel route - “a corollary discharge” - also engages areas of the brain involved in autonomic control, leading to sympathetically-mediated increases in blood pressure and heart rate, and withdrawal of parasympathetic drive to the heart Central command Watching a first-person video of a person running increases muscle sympathetic nerve activity, heart rate, skin blood flow and respiration Brown R, Kemp U & Macefield VG (2013) Frontiers in Autonomic Neuroscience 7: 102 (1-6) Central command Mental imagery - without actual muscle activation - can also bring about cardiovascular adjustments The cardiovascular changes associated with motor command can be observed in experimental paralysis No muscles are activated but increases in heart rate and blood pressure still occur - the greater the effort (motor command) the greater the responses Central command Pharmacologically paralyzed subject performing four attempted contractions of the leg muscles at different intensities Gandevia, Killian, McKenzie, Crawford, Allen, Gorman & Hales, J. Physiol. 470: 85-107, 1993 Central command Pharmacologically paralyzed subject performing four attempted contractions of the leg muscles at different intensities Same data on expanded time-base The arrows indicate the onset of the voluntary command Heart rate and blood pressure increase rapidly with effort Gandevia, Killian, McKenzie, Crawford, Allen, Gorman & Hales, J. Physiol. 470: 85-107, 1993 Reflex inputs The accumulation of metabolites in exercising muscle dilates local blood vessels and activates group III (thinly myelinated) and group IV (unmyelinated) muscle afferents These sensory axons (metaboreceptors) project to the nucleus tractus solitarius (NTS) in the medulla, which provides excitatory synapses to the rostral ventrolateral medulla (RVLM) - the primary output nucleus for muscle vasoconstrictor neurones Preventing the removal of metabolites (by inflating a sphygmomanometer cuff proximal to the exercised muscle) maintains activation of the metaboreceptors and sustains the increase in blood pressure in the absence of central command - the metaboreflex (pressor response) MSNA to non-contracting muscle increases during contraction and during post-exercise ischaemia central command reflex inputs (metaboreflex) MSNArms ECG grip pressure (%) 2 min static exercise 6 min post-exercise ischaemia cuff inflation 150mmHg exercise post-exercise ischaemia PEI Heart Rate (beats·min-1) Mean Arterial Pressure (mmHg) MSNA burst freq (bursts·min-1) MSNA total activity (%) Sander M, Macefield VG & Henderson LA (2010) Journal of Applied Physiology 108: 1691-1700 Increases in Blood Oxygen Level Dependent (BOLD) signal intensity during static hand-grip exercise Sander M, Macefield VG & Henderson LA (2010) Cortical and brainstem changes in neural activity during static handgrip and post-exercise ischemia in humans. Journal of Applied Physiology 108: 1691-1700 there is a progressive increase in effort during a sustained submaximal isometric contraction to overcome the muscular fatigue forearm flexor EMGrms grip force (40% MVC) primary somatosensory cortex (SI) insular cortex Sander M, Macefield VG & Henderson LA (2010) Journal of Applied Physiology 108: 1691-1700 Mid-cingulate cortex Anterior cingulate cortex Sander M, Macefield VG & Henderson LA (2010) Journal of Applied Physiology 108: 1691-1700 sustained increases in signal intensity within nucleus tractus solitarius and rostral ventrolateral medulla during static handgrip exercise and post-exercise ischaemia NTS RVLM Sander M, Macefield VG & Henderson LA (2010) Cortical and brainstem changes in neural activity during static handgrip and post-exercise ischemia in humans. Journal of Applied Physiology 108: 1691-1700 The increases in activity within the insular cortex may reflect the increase in sensory input from the baroreceptors and from the metaboreceptors in the contracting muscle The decrease in activity within the anterior cingulate and midcingulate cortex may be related to the affective components of the muscle pain The increase in muscle sympathetic nerve activity may be reflexly generated by excitatory projections from the nucleus tractus solitarius (NTS) to the rostral ventrolateral medulla (RVLM) Excitatory projections from metabosensitive neurones in NTS to barosensitive neurones in NTS may reduce the gain of the baroreflex, contributing to the increase in MSNA Conclusions: Exercise results in the production of large amounts of metabolic heat by the exercising muscles This heat is liberated by an increase in sympatheticallymediated sweating, associated with cutaneous vasodilatation Because of the increased metabolic load, blood flow to the exercising muscle needs to increase, brought about by the actions of muscle metabolites on local blood vessels Blood flow to non-exercising muscle and to the gut decreases through muscle and splanchnic vasoconstriction, causing an increase in blood pressure and hence perfusion pressure to the blood vessels of contracting muscles Conclusions: Central command is responsible for the increase in heart rate Both central command and reflex inputs from metaboreceptors in the contracting muscle contribute to the increase in blood pressure The metaboreflex can cause an increase in blood pressure in the absence of central command Both central command and the metaboreflex engage nucleus tractus solitarius and rostral ventrolateral medulla, bringing about increases in muscle sympathetic nerve activity Questions? [email protected]