Thermoregulation

Thermoregulation Maintenance of internal body temperature regardless of environmental temperature In utero: Maternal temperature Heat produced dissipated through the placenta High thermal diffusion capacity At birth Ineffective insulating layer

Thermoneutral zone Range of temperatures within which metabolic rate is at a minimum and temperature regulation can be achieved through nonevaporative physical processes alone Adults 26-28° C Infants 32-34° C Premature Infants Minimum of 35° C

Mechanisms for Heat Production Physical Shivering thermogenesis Important for adult thermogenesis Chemical Nonshivering thermogenesis Most effective and efficient source of heat production in the neonate

Norepinephrine and Epinephrine Adult shivering response mediated by epinephrine Neonate nonshivering response mediated through norepinephrine Infusion of norepinephrine Increase in plamsa nonesterified fatty acids (NEFA) Increased oxygen consumption Rise in body temperature Norepinephrine plays a large role in a newborn infant’s defense against cold and also has effects on intermediary lipid metabolism

Premature infants and norepinephrine levels 6 of 9 showed increased excretion of norepinephrine 6 infants: mean temperature fall 2.4° C 3 infants (no increase): temperature fall 3-5° C Two weeks later All 9 infants exhibited increased norepinephrine levels Mean temperature fall for all infants 0.9° C

Premature infants and norepinephrine levels Second Study Norepinephrine levels examined at 12 and 47 days Difference between ages may suggest : Norepinephrine response is a major component of infant’s response to cold Maturation of the infant may parallel the development of thermal stability Norepinephrine Level Mean Fall in Rectal Temperature Day 12 No apparent rise 4.5° C Day 47 Striking increase in levels 1.5° C

Brown Adipose Tissue (BAT) BAT is main site of nonshivering thermogenesis in neonate Human adult: BAT comprises 1% body weight Infant: BAT comprises 5-7% body weight BAT contains: Sympathetic nerve fibers which maintain synaptic contact with cell membrane These fibers trigger release of norepinephrine Initiates thermogenesis Activates lipase

Brown Adipose Tissue (BAT) BAT cells have central nucleus with fat lobules and mitochondria Mitochondria has specialized protein “Uncoupling protein” Short circuits the electrochemical gradient of respiratory chain Uncoupling protein discharges the chemical gradient in substrate oxidation and ADP phosphorylation without the generation if ATP Energy generated by uncoupling oxidative phosphorylation is simply released as heat

Brown Adipose Tissue (BAT) Postnatal development of respiratory enzymes and uncoupling protein in BAT occurs within the first hours of birth Accelerated by cold stress through increase in rates of transcription of the uncoupling gene BAT overall provides up to 2/3 of total heat produced through nonshivering thermogenesis. Nonesterified fatty acids (NEFA) (which rise in response to an increase in norepinephrine) appear to reflect the increased lipolytic activity of BAT

Nonshivering Thermogenesis Precocial species Non-shivering thermogenesis greatest at birth and disappears within a few weeks Exposure to cold prevents this disappearance Altricial species Gradual increases in non-shivering thermogenesis for the first few weeks of life Infants Gradual disappearance of brown fat stores within the first year This correlates with the conversion from non- shivering to shivering thermogenesis when an infant is exposed to the cold

Thermal imbalance Hyperthermia Hypothermia Neonates exhibit increased oxygen consumption Only slightly elevated temperatures Hypothermia Constriction of blood vessels in infants Increase tissue insulation to maximal value by increasing internal temperature gradient Maximally constricted – tissue insulation is low in comparison to the adult

hypothermia Increase in metabolic rate in infants Poses extraordinary challenges, infant already has difficulty in respiration Challenge of increased oxygen consumption may exceed physiological limits Protective mechanism in place against the effects of hypoxia due to cold stress Moderate acute hypoxia shows no effect on minimal oxygen consumption Reduced metabolic response to cold Results in reduction of increase in metabolic demand for a hypoxic infant but also makes it more difficult to maintain thermal equilibrium

Hypothermia Effects on acid-base balance Restrictions to adaptation Drives pH down – more acidic Drop in pH hypothesized to trigger action of norepinephrine in response to hypothermia Restrictions to adaptation Body temperature is maintained as long as heat loss doesn’t exceed capacity for heat production With continued increasing hypothermia the thermoregulatory drive induced in thermo- integrative area of the central nervous system is eventually reduced

Hypothermic Effects on Passive Transfer of Antibodies Cold stress delays onset and significantly decreases rate of absorption of immunoglobulins up to 15 hours after first feeding of colostrum Net absorption of IgG not affected In dogs hypothermia causes decreased venous outflow from the small intestine, decreased overall intestinal motility, and net reduction in transport of substances from the intestinal lumen into the blood

Hyperthermia and Passive Transfer Similar mechanism thought to be responsible for delay and decrease in rate of absorption of IgG in calves and other farm species Absence of an effect on net absorption of colostral immunoglobulins in calves may be due to the short duration of the cold stress Cold stressed calves also exhibited muscular weakness and reluctance to stand and nurse Therefore caused a decrease in total amounts of colostrum ingested and absorbed

Thermoregulation and thriftiness at birth Time it takes to stand and suckle are tied to ability to maintain temperature in newborn lambs Heavier lambs, blackface lambs, and single or twin lambs were quicker to stand and suckle from their mothers then lightweight, Suffolk, or triplet lambs Low birth weight lambs had lower rectal temperatures Lambs slow to suckle also had lower temperatures that persisted for 3 days

Thermoregulation and Lambs Energy needed to sustain body temperature supplied from brown adipose tissue (BAT) Oxidation of BAT for energy accomplished through triiodothyronine (T3) and thyrodine (T4) Heavier lambs and blackface lambs exhibited higher T3 and T4 levels Lower weight lambs exhibited lower T3 and T4 levels Indicates maturity at birth may play role in T3 and T4 levels

Thermoregulation and Lambs Overall: lighter weight/smaller size and slower ability to suckle resulted in reduced ability of efficient heat regulation Thermoregulation also believed to be affected by the fat content in colostrum High fat content provides greater energy supply for thermoregulation Allows for species differences in thermoregulating ability