Thermoregulation_-_2023.pptx

Thermoregulation Guyton and Hall Textbook of Medical Physiology Chapter 74 CVS-1 – Fall 2023 1° - Kristin L. Gosselink, Ph.D. 2° - Thomas P. Eiting, Ph.D. body is a unit; the person is a unit of body, mind, and spirit. body is capable of self-regulation, self-healing, and health maintenance. Lear...

Thermoregulation Guyton and Hall Textbook of Medical Physiology Chapter 74 CVS-1 – Fall 2023 1° - Kristin L. Gosselink, Ph.D. 2° - Thomas P. Eiting, Ph.D. body is a unit; the person is a unit of body, mind, and spirit. body is capable of self-regulation, self-healing, and health maintenance. Learning Objectives • Diagram the thermal balance for the body, including heat production (metabolism, exercise, shivering) and heat loss (convection, conduction, radiation, and evaporation). Identify those mechanisms that shift from heat production to heat loss when environmental temperature exceeds body core temperature. • Define the thermoregulatory set point. Diagram the negative feedback control of body core temperature, including the role of the hypothalamic set point. • Contrast the stability of body core with that of skin temperature. Include the control and mechanisms of cutaneous blood flow and sweating on skin temperature. • Explain how the change in core temperature that accompanies exercise differs from the change in core temperature produced by influenza, which alters the thermoregulatory set point. • List and describe the physiological changes that occur as a result of acclimatization to heat and cold. COMLEX • Temperature regulation • Temperature-sensitive neurons in anterior hypothalamus; firing rate reflects regional blood temperature • Normal set point and circadian rhythm • Fever – still regulated but at higher set point • Heat-conserving and -generating mechanisms (shivering, cutaneous vasoconstriction) • Heat dissipating mechanisms (cutaneous vasodilation, sweating – sympathetic cholinergic) • Cutaneous circulation almost entirely controlled by sympathetic adrenergic nerves and varies with the need to exchange heat with the environment Exceptio n to the rule! Metabolic heat production • Mostly generated in deep organs – liver, brain, heart; skeletal muscle during exercise • Rate of metabolism is affected by: • Metabolism of all cells of the body • Muscle activity • Thyroid hormone, growth hormone, testosterone • Sympathetic stimulation (Epi, Norepi) • Chemical activity in the cells (especially with increased temperature) • Metabolism needed for digestion, absorption, and storage of food Overview and basic principles Heat production from metabolism pothalamic set-point Heat exchange with the environment y mperature sensors in skin re temp < Set point  Heat conserving mechanisms x y x y (or heat generating… posterior hypothalamus) re temp > Set point  Heat dissipating mechanisms (anterior hypothalamus) resolved hyperthermia… >40°C  heat exhaustion, then heat stroke eat exhaustion: excessive sweating; volume depletion and ↓BP, syncope eat stroke: normal countermeasures cease; tissue damage Normal and pathological hypothalamic temperature ranges 96 - 104 °F Skin temperature sensors are free nerve endings with a range of transient receptor potential (TRP) cation channels that open and change conductance based on hotter or colder temperatures Sense Integrate Respond Skin temperature varies considerably Heat release to the environment depends on the gradient Hypothalamic and other brain regions involved in thermoregulation anterior anterior Paraventric ular nucleus * posterior hypothala mus * * anterior hypothala mus Supraoptic nucleus Organum Vasculosum of the Lamina Terminalis (OVLT) is a circumventricular organ; contains fenestrated capillaries, allowing communication between the brain and the peripheral circulation. Vasopressin/ADH Hypothalamus, CVOs, endocrine regulation will be seen in Endo/Repro-1 and Neu Core body temperature is not totally static, either Changes in core temperature generate more significant responses Rest Temperaturesensitive neurons in the anterior hypothalamus (preoptic area) change firing rate based on temperature Excitation Body temperature exhibits diurnal variation, and is impacted by internal and external stimuli, exercise, illness, etc. Inhi Blood flow to skin from core allows heat transfer Environmental temperature affects blood flow from core to skin Inflow of blood to venous plexus from skin capillaries Can be nearly zero flow or ~30% of cardiac output Arteriovenous anastomoses in “exposed” areas (hands, feet, ears) Heat dissipating mechanisms • Radiation and Convection (anterior hypothalamus) • Reduced sympathetic tone in cutaneous vessels • Arteriovenous shunting of blood to venous plexus near skin surface Radiation, Conduction and Convection can sometimes seem like the same thing. • Evaporation – sweat glands (*sympathetic ACh/muscarinic*) Duct cells Coil cells Thermoregulation in hot environments • Is it hot? Or hot and humid? >41°C (core temperature)  irreversible brain damage • Sweat (eccrine) is an ultrafiltrate of plasma, but is typically modified in the sweat glands • Cool-acclimated, at rest in the shade: 20 mL/h of 5 mmol/L Na+ limited volume; Na+ reabsorption • Cool-acclimated, exercising heavily: 1000 mL/h of 50 mmol/L Na+ limited production, less reabsorption time • Hot-acclimated, exercising heavily: 2000 mL/h of 5 mmol/L Na+ glandular hypertrophy; aldosterone • Exercise has the potential to cause overheating • Moderate workload can increase metabolic heat production 4- to 5-fold • Can raise body temp by 4°C per hour; increased body temperature increases cellular metabolic rate • Body fluids can store heat • Moderate, transient hyperthermia can be managed (39.5°C with endurance exercise?) • Increases thermal gradient and facilitates heat loss • High temperature, humidity, and solar radiation all decrease the efficiency of heat loss Factors affecting heat loss Heat intolerance with aging can be multifactorial • • • • Age and Gender Subcutaneous adipose is an Fitness insulator Acclimation Hydration • Temperature, Humidity, Wind • Clothing • Levothyroxine SSRIs MedicationsAnticholinergics • Chronic disease states • Thyroid • Type 2 Diabetes Mellitus • Dermatological Heat generating mechanisms, in response to cold • Shivering (posterior hypothalamus  α- and γ-motor neuron activation) • Involuntary, asynchronous skeletal muscle contraction • Facilitation of the stretch reflex remember our muscle spindles? • Activation of brown adipose • (sympathetic, norepi, β-adrenergic) • Thyroid hormone (Na+/K+-ATPase) • Chronic cold exposure increases thyroxine (T4); increased metabolic rate • EndoRepro-1 – we’ll see the hypothalamic-pituitary-thyroid axis; cold increases TRH release Thermoregulation in cold environments • Atmospheric temperature decreases by 1°C for every 500’ (150m) above sea level • ↓ water vapor and ↓ pollution increases exposure to solar radiation – individuals may feel hot while the temperature gradient predisposes to cooling • Mild hypothermia leads to: • Cerebral depression; impaired function (33°C = confusion and loss of shivering; 2932°C = loss of consciousness; 25-27°C = cardiac arrest) – variable by individual and may depend on timecourse of hypothermia • Ambient temperatures ~0°C cause arteriovenous shunts to open in digits, ears, and nose – warming of tissue but increased heat loss • If the individual is also exercising, depleted glycogen stores can lead to fatigue and reduced metabolic heat production in response to the exercise • Action potential conduction velocity is highly temperature-dependent Role of the hypothalamus in regulating body temperature Heat production is minimal and stable Small window Heat loss begins Core temperature of unclothed person exposed to varying environmental temperatures (DRY air) for a Hypothalamic temperature impacts evaporative heat loss Hypothalamic set point can be slightly altered by other temperature signals Sweating is initiated when the temperature of the anterior hypothalamus/preoptic area rises above the set point. Sweating increases further as temperature continues to rise. Reductions in skin temperature can shift this response to the right … sweating is initiated at higher temperatures. Decreasing skin temperature shifts this effect to the right. Hypothalamic temperature affects the rate of body heat production And other thermal sensors can modify… Shivering is initiated when the temperature of the anterior hypothalamus/preoptic area drops below the set point. (see slide #5) Shivering increases further as temperature continues to drop. Increases in skin temperature limit the shivering response and subsequently the amount of heat production. What happens when you change the hypothalamic set point? Raising the set point makes the body feel cold, inducing heatgenerating mechanisms Lowering the set point makes the body feel hot, inducing heat-dissipating mechanisms Heat intolerance with aging, and roles of the reproductive hormones We’ll see this again in EndoRepro-1 • Progesterone • Increased progesterone increases the hypothalamic set point and raises body temperature • Post-ovulatory temperature increase (basis of determining fertility) • Dissipation of excess heat during gestation • Estrogen • Estrogens decrease the hypothalamic set point and promote lower body temperatures • Augment vasodilation in peripheral vessels • Menopausal hot flashes and night sweats • Testosterone • Anabolic; increase body heat production • Along with growth hormone and thyroid hormone With aging, reduced sex steroids and growth hormone Also tend to lose muscle mass Age-related changes in autonomic function impaired ability Range narrows with age and declining hormone levels Fever and pyrogens • Pyrogens, resulting from infection, increase phagocyte interleukin-1 (IL1) production (IL-1β, IL-6, TNF-α) • IL-1 increases prostaglandin E2 synthesis in anterior hypothalamus • Hypothalamic set point is increased, stimulating heat-generating mechanisms inhibits cyclooxygenase and prevents prostaglandin formation – prevent prostaglandin synthesis by reducing arachidonic acid availability Recent research: Proc Natl Acad Sci USA 2022 119 (43) e2122562119 October 17, BRIEF REPORT – PHYSIOLOGY Prostaglandin production selectively in brain endothelial cells is both necessary and sufficient for eliciting fever Kiseko Shionoya, Anna Eskilsson, and Anders Blomqvist https://doi.org/10.1073/pnas.2122562119 Fever is known to be elicited by prostaglandin E acting on the brain, Malignant hyperthermia and other patient care • Reaction to inhaled anesthetics by susceptible individuals • Skeletal muscle massively increases heat production and O2 consumption • Rapid rise in body temperature Most common = genetic defect in RYR1 Patient groups susceptible to hyperthermia: obese, burn victims, fluid-depleted, impaired ability to increase cardiac output and peripheral perfusion Hypothermia often seen in outdoor environments (exposure) – but in urban medical setting is linked with advanced age, fixed income, poor nutritional status (slow onset and progression) – aging population may also have impaired autonomic/baroreflex function, and volume depletion as cutaneous vasoconstriction sends more blood to kidney and GFR increases Neurological issues can disrupt thermoregulation • Stroke • Infection / Inflammation • Traumatic Brain Injury (TBI) Many potential mechanisms involved in the damage You don’t need to know the details here… Additional research examples Regional variation in nitric oxide-dependent cutaneous vasodilatation during local heating in young adults. Exp Physiol. 2021 doi: 10.1113/EP089671 Online ahead of print Gregory W McGarr, Kelli E King, Samah Saci, Daphnee Leduc, Ashley P Akerman, Naoto Fujii, Glen P Kenny (edited)… We explored whether regional differences in nitric oxide (NO) dependent cutaneous vasodilatation during local skin heating are present in young adults. NO-dependent cutaneous vasodilatation varied across the body. The abdomen demonstrated larger NO contributions, while the chest demonstrated smaller NO contributions, compared to other regions. This exploratory work is an important first step in characterizing regional heterogeneity of cutaneous microvascular control across the torso and limbs. Equally, it serves as hypotheses generating for future studies examining regional cutaneous microvascular control in ageing and disease. Climate change and neurodegenerative diseases Environ Res. 2021 Jun 11;111511. doi: 10.1016/j.envres.2021.111511. Online ahead of print. Paolo Bongioanni, Renata Del Carratore, Silvia Corbianco, Andrea Diana, Gabriella Cavallini, Silvia M Masciandaro, Marco Dini, Roberto Buizza (edited)… Climate change, and the increased frequency and intensity of heat waves, have been linked to health problems. Increased incidence of neurological diseases are being reported, [including] Alzheimer's, Parkinson's, and Motor Neuron Diseases. Our work aims to examine the connection between high temperature exposure and neurodegenerative diseases. Firstly, we evaluate the influence of high temperature exposure on the pathophysiology of these disorders. Secondly, we discuss its effects on the thermoregulation, already compromised in affected patients, and its interference with processes of excitotoxicity, oxidative stress and