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Module 12: Thermoregulation

Module 12: Thermoregulation. AnS 536 Spring 2012. Thermoregulation in the Neonate. Three principal modes of heat production in response to cold stress 1) Voluntary muscle activity 2) Involuntary tonic or rhythmic muscle activity

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Module 12: Thermoregulation

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  1. Module 12: Thermoregulation AnS 536 Spring 2012

  2. Thermoregulation in the Neonate • Three principal modes of heat production in response to cold stress • 1) Voluntary muscle activity • 2) Involuntary tonic or rhythmic muscle activity • (low intensity, not visible or high intensity, visible shivering) • 3) Non-shivering thermogenesis

  3. Thermoregulation in the Neonate • In most mature mammals • Shivering is quantitatively the most important involuntary mechanism for thermoregulation • Non-shivering thermogenesis develops only after long-term cold exposure • In neonates • Non-shivering thermogenesis is quantitatively important and an effective mechanism for heat production • Preferred mode of thermogenesis in neonates • Will suppress shivering • Elicitation mediated by sympathetic nervous system • Can be blocked by β-receptor antagonists (propranolol)

  4. Thermoregulation in the Neonate • Metabolically active brown fat is major site of thermogenesis • Comprises 5-7% of body weight in neonates • Except pig, which lacks brown fat • Comprises approx 1% of human adult body mass; metabolically inactive white fat functions as fat storage • Brown fat cells contain sympathetic nerve fibers which synapse with the cell membrane • Nerve fibers release norepinephrine to stimulate thermogenesis and activate lipase

  5. Thermoregulation in the Neonate • Brown fat cells have centrally located nucleus, surrounded by multiple fat lobules, surrounded by mitochondria • Thermogenin is the “uncoupling protein” • Specialized function depends on 32 kDa protein in mitochondrial inner membrane • Acts to short circuit the electrochemical gradient generated by the respiratory chain

  6. Thermoregulation in the Neonate • In tissues except brown fat • Substrate oxidation and ADP phosphorylation is coupled by the development of an electrochemical gradient within the mitochondria • Gradient is only discharged at specific sites where ATP-synthase is located • Controlled discharge generates energy used for ATP production • In mitochondria in brown adipose tissue • Thermogenin allows discharge across gradient without ATP generation • Energy is released as heat

  7. Thermoregulation in the Neonate • Thermoregulation is relatively inefficient in the neonate • Shivering thermogenesis • Shivering is an involuntary function with a tremor rate ~10 per second • Neonates have the inability to shiver • Non-shivering thermogenesis • Most of heat gain comes from metabolism of Brown Adipose Tissue (BAT)

  8. Thermoregulation in the Neonate • Postnatal development of respiratory enzymes and UCP occurs during the first few hours after birth • Development is accelerated and enhanced by cold stress • UCP synthesis is under noradrenergic control • UCP gene acutely regulated at the level of transcription after activation of plasma membrane β-adrenoreceptors • Rapid increase in ICP found in brown adipose tissue mitochondria most likely due to rapid increase in the rates of transcription of the UCP gene

  9. Thermoregulation in the Neonate • During cold exposure, blood flow through intrascapular brown fat deposits in the newborn rabbit increase • 90 ml/100 g·min to over 700 ml/100 g·min • Accounts for up to 25% cardiac output • Under maximal stimulation, brown adipose tissue can provide up to 2/3 of the total heat provided from non-shivering thermogenesis

  10. Thermoregulation in the Neonate • Thermoregulatory efficiency of non-shivering thermogenesis is greater than that of shivering • Extensive brown fat deposits at birth may be compensatory mechanism for smaller body size • In precocial newborns non-shivering thermogenesis disappears within a few weeks • Cold exposure at this time prevents disappearance • As age increases, the extent to which it can be evoked or maintained decreases • Altricial newborns gradually increase non-shivering thermogenesis through the first few weeks of life

  11. Thermoregulation in the Neonate • Cold stress and O2 consumption • If heat loss exceeds capability of heat production, body temperature begins to decrease • As body temperature falls, cold-induced heat production and basal heat production also decrease • Oxygen uptake decreases by a 2- to 3-fold per 10°C change in body temp • Thermoregulatory drive generated in the thermointegrative area of the CNS is reduced with increasing hypothermia

  12. Neonatal Hypothermia • Hypothermia • Increases morbidity and mortality significantly • Oxygen consumption decreases  hypoxia • Neonates need energy (glucose) to produce heat • ↑ glucose consumption  hypoglycemia • Vasoconstriction of blood supply to GI tract reduce ability to transport/absorb nutrients

  13. Neonatal Hypothermia • ↓ Body temp, solubility of gases such as oxygen and carbon dioxide ↑ • ↑ Solubility leads to a ↓ in pO2 and pCO2, and causes pH to rise • ↓ temp shifts hemoglobin saturation curve to the left = less unloading of O2 occurs at a given partial pressure

  14. Neonatal Hypothermia • Hypothermia ↓ total body metabolism and O2 consumption • ↓ in core body temperature can result in acidosis and ↓ kidney and liver function

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