THERMOREGULATION

1. THERMOREGULATION Ginus Partadiredja The Department of Physiology UGM, Yogyakarta

2. Normal Body Temperature • Skin temperature  rise and falls  surroundings • Core temperature  constant (36C – 37.5C) • Body Temperature = Heat Production >< Heat Loss

3. Heat Production • Metabolic rate of the body: • Basal rate of metabolism of cells • Muscle activity • Thyroxine • Epinephrine, norepinephrine, sympathetic stimulation • Chemical activity in cells • Extra metabolism for digestion, absorption, storage of food

4. Heat Loss • Heat is mostly produced in the liver, brain, heart, exercised skeletal muscle • The rate of heat lost: • Conduction from the body core to the skin • The degree of vasoconstriction (sympathetic nerves) • Transfer from the skin to the surroundings • Insulator system (skin, subcutaneous tissue, fat) • Fat  transfer 1/3 heat • Women = better insulation • Clothing; wet clothing

5. Heat Loss • Radiation  infrared heat rays (60% total heat loss) • Conduction to solid objects (3%) •  to air (15%)  to water 30x of air • Convection conduction to the air first  convection (air • currents)  heat loss  wind speed •  heat conductivity in water >> than in air • Evaporation insensible evaporation (lungs + skin) = 600 • – 700 ml/ day  cannot be controlled •  sweating evaporation can be controlled •  the only means to get rid of heat in high • temperature environment

6. Respiration evaporation (water droplets evaporated) •  contribute to hypothermia in cool, windy, and dry environments

8. Sweating • Stimulation of the anterior hypothalamus-preoptic area  sympathetic nerves  cholinergic  sweat glands

9. Sweat secretion • coiled/ glandular portion  primary secretion≈ plasma (except protein); Na = 142 mEq/L, Cl = 104 mEq/L • duct portion • slight stimulation  low level salt • strong stimulation  high level salt (50 – 60 mEq/L) • Aldosterone  15– 30 g/day salt excreted (unacclimatized) •  3 – 5 g/day salt

10. Role of the Hypothalamus • Anterior hypothalamic-preoptic area  heat-sensitive neurons & 1/3 cold-sensitive neurons (temperature sensors) • Skin receptors: 10x cold receptors > warmth receptors  preventing hypothermia • Chilled body causes: • shivering • sweating inhibition • skin vasoconstriction • Deep tissue receptors (spinal cord, abdominal viscera, great veins around upper abdomen & thorax) • Posterior hypothalamus  combine & integrate temperature sensory signals

13. Temperature – Decreasing Mechanisms: • Vasodilation of skin blood vessels • Inhibition of the sympathetic center (posterior hypothalamus) • Sweating • Decrease in heat production

14. Temperature – Increasing Mechanisms: • Skin vasoconstriction • Stimulation of sympathetic centers (posterior hypothalamus) • Piloerection • Entrapping “insulator air” • Increase in thermogenesis • Shivering • Sympathetic excitation • Thyroxine

15. Shivering • Heat center (anterior hypothalamic-preoptic area) • inhibition • Primary motor center for shivering (dorsomedial portion of posterior hypothalamus) • stimulation • Cold signals (skin & spinal cord) • brain stem • facilitating the activity of anterior motor neuron • increasing tone

16. Sympathetic excitation of heat production • Sympathetic stimulation  the rate of cellular metabolism increase (chemical thermogenesis; excess foodstuff oxidized) • Brown fat (animals, not adult humans) large number of special mitochondria • Infants  brown fat in interscapular space  the rate of heat production increase 100%

17. Thyroxine Cooling anterior hypothalamic-preoptic area Thyrotropin-releasing hormone (hypothalamus) Thyroid stimulating hormone (anterior pituitary) Thyroxine Increase the rate of cellular metabolism (several weeks)

21. Behavioral Control of Body Temperature • Feeling hot or cold due to the changes of internal body temperature  moving into heated room or wearing well-insulated clothing • Local Skin Temperature Reflexes • Local vasodilatation or sweating

22. Set Point for Temperature Control • 37.1°C  set point of the temperature control mechanism • The set point  the degree of activity of the heat temperature receptors in the anterior hypothalamic-preoptic area • Skin & deep body tissues (spinal cord & abdominal viscera) also affect body temperature regulation  change of hypothalamic set point • Set point increase as skin temperature decrease (sweating at high skin temperature & low hypothalamic temperature)

23. Abnormalities of Body Temperature Regulation • Fever • Abnormalities in the brain (brain tumor)  increase body temperature • Toxic substances on temperature-regulating centers (pyrogens)  rising the set-point • Pyrogens: proteins, breakdown products of proteins, lipopolysaccharide toxins of bacteria or degenerating body tissues • The increase of set-point  heat conservation & heat production increase

24. Bacterial pyrogens (endotoxins of gram-negative bacteria)  several hours • Bacteria • Leukocytes, macrophages, large granular killer lymphocytes • Interleukin 1 (leukocyte pyrogen/ endogenous pyrogen) • E.g. Arachidonic acid  Prostaglandins (E2)  hypothalamus • Aspirin

25. Characteristics of Febrile Conditions The set-point increase & blood temperature < set-point Chills & cold feeling cold skin(vasoconstriction), shivering, piloerection, epinephrine secretion Body temperature reaches the high temperature hypothalamic set-point Neither feel cold or hot

26. The factor (e.g. pyrogens) removed The set-point reduced to a lower value Hypothalamus attempt to reduce body temperature Intense sweating, hot skin (vasodilatation) = “flush”/”crisis”

27. Hyperthermia • Hyperthermia: • Thermoregulatory failure (excessive heat production, excessive environmental heat, impaired heat dissipation) • Hypothalamic set-point is normal • Peripheral mechanisms unable to match the set point • Fever: • - Intact homeostasis responses • - Hypothalamic set-point increases due to pyrogenic cytokines • Peripheral mechanisms are competent  conserve heat

28. Causes of Hyperthermia * Mixed pathogenesis

29. Exertional Hyperthermia • Acclimatized athletes  2 L sweat/ hour  evaporation of 900 kcal/ hour • Heat dissipation  skin vasodilatation & sweating  limited by volume depletion, ambient temperature & humidity • Intense, prolonged exercise in humid weather  hyperthermia • Exertional hyperthermia usually self-limited & asymptomatic • Adverse effects: muscle cramps, heat exhaustion, heatstroke • Prevention: Acclimatization (athlete), light clothing, avoid direct sunlight, hydration • Treatment: Rest, oral rehydration, IV fluids, evacuation to cool environment

30. Heatstroke • One can withstand several hours 130F in dry air (convection) • One can only tolerate up to 94F in 100% humidified air • Heatstroke  if body temperature > 105F - 108F

31. Heatstroke • Heatstroke: - Exertional heat stroke (athletes & military) • - Classic heat stroke (sedentary, elderly) • Exertional heat stroke: Lack of acclimatization, lack of cardiovascular conditioning, dehydration, heavy clothing, excessive exertion • Classic heat stroke: Impaired heat dissipation (anhidrosis), cardiovascular diseases, neurologic disorders, impaired consciousness, obesity, anticholinergic or diuretic agents, dehydration, very old/ young • Prevention: Hydration, minimizing anticholinergic or diuretic agents, cool environments

32. Symptoms & signs: Dizziness, abdominal distress, vomiting, delirium/ stupor/ coma, hypotension, tachycardia, hyperventilation, hemorrhages, degeneration, in brain, liver, kidneys • Laboratory findings: Hemoconcentration, proteinuria, microscopic hematuria, abnormal liver function, elevated muscle enzymes levels, rhabdomyolysis (exertional), disseminated intravascular coagulation (exertional), hypoglycemia (exertional), electrolyte & acid-base disturbance; respiratory alkalosis & hypokalemia (early phase)  lactic acidosis & hyperkalemia (later phase)

33. Mortality: shock, arrhythmias, myocardial ischemia, renal failure, neurologic dysfunction • Treatment: • - Removal of clothing • - Sponge/ spray cooling/ cold water bath/ ice  body surface • - Oral hydration • - Intravenous hydration with room temperature fluids • - Correction of electrolyte/ acid-base disturbance • - Cardiovascular monitoring & support

34. Malignant Hyperthermia of Anesthesia • Excessive release of calcium from the sarcoplasmic reticulum (in response to anesthetic drugs) severe muscle hypermetabolism • Hereditary, autosomal dominant • Most anesthetic drugs, especially halogenated inhalation & depolarizing muscle relaxants • Symptoms & signs: > 41°C, severe muscle rigidity, hypotension, hyperpnea, tachycardia, arrhythmias, hypoxia, hypercapnia, lactic acidosis, hyperkalemia, rhabdomyolysis, disseminated intravascular coagulation • Treatment: Dantrolene sodium IV (inhibit the release of calcium), interruption of anesthesia, correction of hypoxia & metabolic disturbance, cardiovascular support, physical cooling

35. Neuroleptic Malignant Syndrome • Neuroleptic agents: phenotiazines, butyrophenones, thioxanthenes, haloperidol (most often) • Blockade of dopaminergic receptors in the corpus striatum • Symptoms & signs: > 41°C, skeletal muscle rigidity  excessive heat  impairs hypothalamic thermoregulation, extrapyramidal abnormalities, altered consciousness, autonomic dysfunction (labile blood pressure, tachyarrhythmias, incontinence)  impairs heat dissipation • Laboratory findings: Hemoconcentration, leukocytosis, hypernatremia, acidosis, electrolyte disturbances, rhabdomyolysis, abnormal renal & hepatic functions • Treatment: Neuroleptic withdrawal, metabolic & cardiovascular support, dantrolene sodium, bromocriptine mesylate (dopamine agonist)

36. Hormonal Hyperthermia • Thyrotoxicosis (most common) • Pheochromocytoma crisis: High level of norepinephrine  skin vasoconstriction & hypermetabolism • Adrenal insufficiency • Hypoglycemia • Hyperparathyroidism

37. Miscellaneous Causes of Hyperthermia • Simple dehydration  volume depletion  vasoconstrition & decreased sweating  impair heat dissipation • Extensive occlusive dressings • Infections • Anticholinergic drugs • Cocaine • Amphetamine • Alcohol abuse & withdrawal • Salicylate intoxication • Therapeutic Hyperthermia • Nasal hyperthermia for viral nasopharyngitis • Adjunctive therapy for cancers

38. The Consequences of Hyperthermia • Extreme hyperthermia: Confusion, delirium, stupor, coma • Metabolic abnormalities: Hypoxia, respiratory alkalosis, metabolic acidosis, hypokalemia, hyperkalemia, hypernatremia, hypophosphatemia, hypomagnesemia, hypoglycemia • Hematologic abnormalities: Hemoconcentration, leukocytosis, thrombocytosis, disseminated intravascular coagulation • Azotemia, elevated serum levels of liver and muscle enzymes

39. Management of Hyperthermia • Diagnose & treat underlying disoder • Cardiovascular & metabolic support • Antipyretic therapy (39C, young, elderly, underlying diseases)  mandatory in heat stroke, malignant hyperthermia; indicated in neuroleptic malignat syndrome, thyrotoxic crisis • Pharmacologic agents to lower hypothalamic set-point (in fever)  acetaminophen, aspirin • Physical cooling (in hyperthermia)  removing bedclothes, bedside fans, sponging with tepid water/ alcohol, hypothermic mattresses, ice packs, ice water immersion (most effective) • IP cool fluid, gastric lavage or ice water enema, extracorporeal circulation

40. Exposure of the Body to Extreme Cold Frostbite • Temperature regulation greatly impaired < 94F; lost < 85F due to the depression of the rate of chemical heat production, sleepiness (depresses the activity of CNS) • Exposure to ice water 20΄ death caused by heart standstill/ fibrillation

41. Hypothermia Common causes of hypothermia:

42. Stages of Hypothermia and Clinical Features: Mild

43. Stages of Hypothermia and Clinical Features: Moderate

44. Stages of Hypothermia and Clinical Features: Severe

45. Laboratory Findings in Hypothermia • Renal failure (secondary to rhabdomyolysis/ acute tubular necrosis • Rapid changes of electrolyte levels (potassium, due to rewarming) • Coagulopathies  self limited • Inaccurate leukocytes count  antibiotics in neonates, elderly, immunocompromised patients

46. Management of Hypothermia • Glucose (most patients  depleted glycogen stores) • Thiamine (a possibility of alcohol abuse) • Remove wet clothing, replaced with blankets • Avoid excessive movement and nasogastric tube • Aggressive resuscitation with warm fluid • Restricted steroids for adrenal insufficiency & failure of temperature normalization • Defibrillation for ventricular fibrillation (many electrocardiographic changes: tachycardia, bradycardia, atrial fibrillation, ventricular fibrillation, asystole, prolongation of PR, QRS, and QT intervals, J waves)

47. Rewarming 1. Mild hypothermia, intact thermoregulatory mechanisms, normal endocrine function, adequate energy stores  passive rewarming (insulation, moving patient to warm, dry environment) 2. Intact circulation  active external rewarming (hot water bottles, heating pads, forced-air warming system, immersion of hands or feet in 45°C water, negative pressure to forearm inserted in device containing heated air in a vacuum of -40 mmHg) Complications: core temperature afterdrop, rewarming acidosis (lactic acid from the periphery  central circulation, rewarming shock (peripheral vasodilatation)

48. 3. Active core rewarming  moderate & severe hypothermia: • Airway rewarming with humidified oxygen at 40°C (increases core temperature by 1°C- 2.5°C/ hour) • Intravenous fluids (5% dextrose and normal saline) heated to 40°C - 45°C • Extracorporeal blood rewarming  most effective (cardiopulmonary bypass, arteriovenous rewarming, venovenous rewarming, hemodialysis)  increases core temperature by 1°C - 2°C/ 3-5 minutes • Warm lavage (gastric, colonic, bladder lavage, peritoneal dialysis). Peritoneal dialysis  normal saline, lactated ringers, dialysate solution heated 40°C - 45°C, 6 – 10 L/ hour combined with O2 increases body temperature 1°C - 3°C/ hour

49. Active core rewarming: • Closed thoracic lavage: thoracostomy tube  mediastinal irrigation  increases core body temperature by 8°C/ hour • Disposition: • Lowest temperature survived: 14.2°C (child) & 13.7°C (adult) • Resuscitation SHOULD NOT BE DISCONTINUED (even if appears to be dead) until the core temperature > 30°C-32°C and no signs of life

50. Summary of Management of Hypothermia • Passive external warming (removal of cold, wet clothing; movement to a warm environment) • Active external rewarming (insulation with warm blankets) • Active core rewarming (warmed intravenous fluid infusions, heated humidified oxygen, body cavity lavage, extracorporeal blood warming)