TEMPERATURE REGULATION

Homeostasis and Allostasis

  • Cannon introduced homeostasis (temperature regulation and other biological processes that keep body variables within fixed range
  • The range is so narrow that we refer to it as a set point (single body that body works to maintain)
  • Negative feedback  processes that reduce discrepancies from the set point; something causes disturbance, and behavior proceeds until it relieves disturbance
  • Your body maintains a higher temperature during the day than at night (even if room temperature stays constant)
  • Allostasis  adaptive way in which the body changes its set points depending on the situation

Controlling Body Temperature

  • Basal metabolism  energy used to maintain constant body temperature while at rest (requires twice as much energy as do all other activities combined)
  • Poikilothermic  amphibians, reptiles, and most fish; their body temperature matches the temperature of their environment (sharks and tuna exception); lack physiological mechanisms of temperature regulation (shivering, sweating); “cold-blooded”
  • Homoeothermic  mammals, and birds; some species become poikilothermic during hibernation; use physiological mechanisms to maintain nearly constant body temperature despite changes in temperature of the environment
  • An animal generates heat in proportion to its total mass, but it radiates heat in proportion to its surface area
  • To cool ourselves when air is warmer than body temperature, we have only one physiological mechanism  evaporation (sweat to expose water for evaporation)
  • If you sweat without drinking, you start becoming dehydrated, then protect your body water by decreasing your sweat (despite risk of overheating)
  • Several physiological mechanisms increase body heat in cold envy;
    1. Shivering; muscle contractions generate heat
    2. Decreased blood flow to skin prevents blood from cooling
    3. Mammals but not humans; fluff out fur to increase insulation; “goose bumps” (for humans)
  • Behavioural mechanisms regulate temperature (less energy needed to spend physiologically); shade, put on/take off clothing, active to get warmer, less active to avoid overheating, huddle others, etc.

The Advantage of Constant High Body Temperature

  • 2/3 of total energy maintain body temperature (basal metabolism)
  • Maintain high metabolism so even when weather is cold, still run as fast as we need to (keep muscles warm at all the time, regardless of air temperature so stay always ready for activity)
  • Body temp of 37°C (trade-off between rapid movement and protein stability)
  • Advantage by being as warm as possible (warmer muscles  runs with less fatigue than a cooler animal)
  • Why don-t we heat to a warmer temperature?
    • Requires more fuel and energy o Beyond 40/41 degrees, proteins break bonds and are no longer useful
  • Possible to evolve proteins that are stable at higher temperatures  need many extra chemical bonds to stabilize protein (more rigid, inactive at more moderate temperatures)
  • Reproductive cells need cooler environment
    • Ex: birds lay eggs and sit on them because internal temperature too high, scrotum hangs outside body because sperm production requires cooler temp than the rest of body

Brain Mechanisms

  • Physiological changes that defend body temperature (shiver, sweat, change in blood flow to skin) depend on areas in/near hypothalamus (mainly anterior hypothalamus and pre optic area  just anterior to the anterior hypothalamus) o Called preoptic because it is near the optic chiasm, where optic nerves cross
  • Preoptic area/anterior hypothalamus (POA/AH)  close relationship between them; mainly treated as single area; important for temperature regulation, thirst, and sexual behavior o This area and a couple other hypothalamic areas send output to the hindbrain-s raphe nucleus (controls the physiological mechanisms)
  • POA/AH monitors body temperature partly by monitoring its own temperature
  • The hypothalamus is well insulated on interior of head; if it-s hot/cold, rest of interior of body is too
  • Cells of the POA/AH also receive input from temperature receptors in the skin and spinal cord; feel most intense when both the POA/AH and the other receptors feel the same way
  • POA/AH is primary area to control physiological mechanisms of temperature regulation; separate cells within it and a few other hypothalamic areas regulate different aspects of temperature regulation o Damage can impair one area and not others; after damage to all, regulate body temperature by same mechanisms a coldblooded animal may use.

Fever

  • Bacterial and viral infections cause fevers (increase body temperature); part of defense against illness; represents increased set point for body temperature; shiver or sweat when deviating from it o When bacteria, viruses, fungi, other intruders invade body, they mobilize leukocytes (white blood cells) to attack  release small proteins (cytokines) to attack intruders and stimulate vagus nerve that sends signals to hypothalamus, increasing release on prostaglandins
  • Stimulation of a certain prostaglandin receptor in one nucleus of the hypothalamus is needed for a fever; without those receptors, illnesses would not give you a fever
  • Animals that lack a mature hypothalamus don-t shiver in respond to infections, but select a spot that warms their body temperature

(develop fever by behavioural means)

  • Some bacteria grows less strongly at high temperatures; fever enhances immune system activity
  • A fever above 39 degrees can be dangerous, above 41 degrees is life-threatening

THIRST

Mechanisms of Water Regulation

  • Beavers and species living in lakes: drink much water, eat moist foods, excrete dilute urine; gerbils and desert animals don-t drink, they gain water from food and have adaptations to avoid losing water (excrete dry feces, concentrated urine); can-t sweat so avoid heat by burrowing underground; convoluted nasal passages minimize water loss when they exhale
  • For humans, if can-t find enough water  conserve by excreting concentrated urine and decreasing sweat (almost like gerbils)
  • Posterior pituitary releases hormone vasopressin (raises blood pressure by constricting blood vessels); increased pressure compensates for decreased blood volume
  • Vasopressin known as antidiuretic hormone (ADH)  allows kidneys to reabsorb water from urine to make it more concentrated; increased secretion while sleeping to preserve body water when you can-t drink

Osmotic Thirst

  • 2 types of thirst:
    1. Osmotic  eating salty foods
    2. Hypovolemic  losing fluid by bleeding or sweating
  • Combined concentration of all solutes in mammalian body fluids remains at almost constant level of 0.15M (molar)
    • This fixed concentration of solutes is a set point; any deviation activates mechanisms to restore concentration of solutes to set point
  • Osmotic pressure  tendency for water to flow across semipermeable membrane from area of low solute concentration to are of higher concentration
  • Membrane surrounding a cell almost semipermeable because water flows freely across and solutes slowly or not at all between intracellular fluid (ICF) inside cell and extracellular fluid (ECF) outside cell
  • Osmotic pressure occurs when solutes are more concentrated on one side of the membrane
  • Eating salty food  Na ions spread through blood and ECF (doesn-t cross membrane into cells)  high concentration of solutes outside cells than inside  resulting osmotic pressure draws water from the ICF to ECF
  • Some neurons can detect own loss of water and trigger osmotic thirst (helps restore normal state); kidneys excrete more concentrated urine to rid body of excess Na and maintain as much water as possible
  • Brain detects osmotic pressure  gets part of information from receptors around 3rd ventricle, which have the leakiest blood-brain barrier (helps monitor blood contents)
  • Important areas for detecting osmotic pressure and salt content of the blood
    • OVLT (organum vasculosum laminae terminalis)  receives input from receptors in the brain itself and in the digestive tract to allow brain to anticipate an osmotic need before rest of the body experiences it,
    • Subfornical organ (SFO)
  • Receptors in the OVLT, subfornical organ, stomach and elsewhere relay information to several parts of the hypothalamus including the supraoptic nucleus and the paraventricular nucleus (PVN) (controls the rate at which the posterior pituitary release vasopressin)
  • Receptors relay information to lateral preoptic area and surrounding parts of hypothalamus that control drinking
  • After osmotic pressure triggers thirst, when to stop drinking  water absorbed through digestive system then pumped through blood to the brain (takes around 15 min)  body monitors swallowing and detects distension of stomach and upper part of small intestine  messages to limit drinking to not more than you need at given time

Hypovolemic Thirst and Sodium-Specific Hunger

  • If you lose body fluid by bleeding, diarrhoea, sweating  osmotic pressure stays the same; heart has trouble pumping blood to head, nutrients don-t flow well into cells
  • Body reacts with hormones that constrict blood vessels (vasopressin and angiotensin II)
  • When blood volume drops  kidneys release enzyme (renin) which splits portion of angiotensinogen (large protein in blood) to form angiotensin I (which other enzymes convert to angiotensin II) o Angiotensin II constricts blood vessels to compensate for drop in blood pressure; also helps trigger thirst, in conjunction with receptors that detect blood pressure in large veins
  • This thirst different from osmotic thirst because you need to restore lost salts/water  hypovolemic thirst (thirst based on low volume)
  • When angiotensin II reaches brain, stimulates neurons in adjoining 3rd ventricle;

o    Neurons send axons to hypothalamus, where they release angiotensin II as neurotransmitter (neurons surrounding 3rd ventricle both respond to angiotensin II and release it; brain uses a chemical that was already performing a related function elsewhere in the body)

  • Animal with osmotic thirst needs water, one with hypovolemic thirst can-t drink pure water (if it did  dilute body fluids); therefore increases preference for salty water  if animal offered both water and salt, it alternated between them to yield appropriate mixture  strong craving for salty tastes  sodium-specific hunger (hungers for other vitamins and minerals learned by trial and error)
  • Sodium-specific hunger partly depends on hormones; when body-s sodium reserves low  adrenal glands produce hormone aldosterone (causes kidneys, salivary/sweat glands to retain salt)

 

Aldosterone and angiotensin II together change properties of taste receptors on tongue, neurons in nucleus of tractus solitaries (part of taste system) and neurons elsewhere in the brain to increase salt intake

  • Aldosterone indicates low Na; angiotensin low blood volume (either one by itself has small effect on salt intake; combined effect is increase in preference for salt over anything else)

Low blood volume  Kidneys release renin into blood  proteins in blood form Angiotensin I  Angiotensin I converted to Angiotensin II  Angiotensin II constricts blood vessels and stimulates cells in Subfornical organ to increase drinking

 HUNGER

Digestion and Food Selection

  • Digestion begins in mouth (saliva enzymes break down carbs)  swallowed food travels down esophagus to stomach (mixes with hydrochloric acid and enzymes that digest proteins)  stomach stores food, then round sphincter muscle opens at the end of the stomach to release food to small intestine  small intestine has enzyme to digest proteins, fats and carbs, also site to absorb digested materials into bloodstream  blood carries those chemicals to body cells that either use/ store them for later use  large intestine absorbs water and minerals, and lubricates the remaining material to pass as feces

Consumption of Dairy Products

  • As newborns grow older they stop nursing because milk supply declines, mother pushes them away, begin to eat other foods

o    Age of weaning lose intestinal enzyme lactase (necessary to metabolize lactose); milk consumption  stomach cramps and gas

  • Adult humans have enough lactase levels to consume milk and dairy throughout life, but some populations may lack gene that allows adults to metabolize lactose
  • Overeating of dairy  result depending on the bacteria in the digestive system (diarrhoea, cramps, gas pains)
  • Genes for lactose digestion evolved independently in different places in response to domestication of cattle; when cow-s milk available, pressure in favour of gene that enabled people to digest it

Food Selection and Behaviour

  • No significant effect of sugar on children-s activity level, play behaviours, school performance; belief that sugar causes hyperactivity is an illusion based on peoples tendency to remember observations that fit expectations a disregard other
  • Another misconception  eating turkey increase-s body-s supply of tryptophan (enables body to make chemicals that make you sleepy; sleepiness from overeating, not turkey itself); increased tryptophan does help brain produce melatonin (induces sleepiness)
  • Tryptophan enters brain by active transport protein that shares with phenylalanine and other large amino acids; when you eat carbs  body increases insulin secretion (moves sugars and phenylalanine to storage; in liver cells and elsewhere); by reducing competition from phenylalanine, tryptophan reaches brain easily (inducing sleepiness)
  • Many fish contain oil helpful for brain functioning, memory and reasoning

Short and Long Term Regulation of Feeding

Oral Factors

  • Strong urge to eat, taste and chew even when not hungry; most untasted meals, while getting nutrients you need, not satisfying
  • Sham-feeding  experiments; anything swallowed leaks out of tube connected to esophagus/stomach; eat and swallow continuously without being satiated
    • Taste and other mouth sensations contribute to satiety, but aren-t sufficient

The Stomach and Intestines

  • End meal before food reaches blood, muscles, other cells; signal to end a meal is stomach distension (promotes satiety)
  • Stomach conveys satiety messages to brain via vagus nerve and splanchnic nerves
  • Vagus nerve(cranial nerve X)  conveys information about stretching of stomach walls; provide basis for satiety
  • Splanchnic nerves  conveys information about nutrient contents of stomach; people who have had their stomachs removed still report satiety  stomach distension not necessary for satiety
  • Meals end after distension of stomach or duodenum (part of small intestine adjoining the stomach); it is the 1st digestive site to absorb significant amounts of nutrients
  • Fat in duodenum releases oleoylethanolamide (OEA)  hormone that stimulates vagus nerve, sending a message to the hypothalamus that delays the next meal
  • Any food in duodenum also releases hormone cholecystokinin (CCK), which limits food size in 2 ways:
    1. CCK constricts sphincter muscle between stomach and duodenum, causing stomach to hold its contents and fill more quickly than usual  facilitates stomach distension
    2. CCK stimulates vagus nerve send signals to hypothalamus, causing cells to release a neurotransmitter (shorter version of

CCK) o  CCK in intestines can-t cross blood-brain barrier, but it stimulates cells to release something almost like it; produces short-term effects only

Glucose, Insulin, Glucagon

  • Most digested food enters bloodstream as glucose; when glucose levels are high  liver cells convert excess to glycogen, and fat cells converts some into fat; when glucose level falls  liver converts some glycogen back to glucose  steady blood glucose level
  • Glucose in blood isn-t equally available to cells at all times; 2 pancreatic hormones, insulin and glucagon regulate glucose flow
  • Insulin  enables glucose to enter cells (except for brain cells), where glucose doesn-t need insulin to enter
    • When levels high  glucose enters cells easily; increase levels increase in anticipation of meal; increases during and after meal to handle the extra intake of glucose; high insulin decreases appetite because insulin allows so much glucose to enter the cells o As time passes after meal, blood glucose falls, insulin drops, glucose enters cells slow, hunger increases
  • Glucagon  stimulates liver to convert some stored glycogen to glucose to replenish low supplies in the blood
    • If insulin level constantly high, body moves glucose into cells (liver and fat cells); blood glucose will drop as glucose leaving blood without new glucose entering; despite high insulin  hunger increases
  • Animal preparing for hibernation  constantly high insulin; rapidly deposit much of each meal as fat and glycogen, hungry again, continue to gain weight to prepare for the season where the animal lives off fat reserves
  • Humans eat more in fall because we have evolved drive to increase reserves in preparation for winter

If the insulin level always low (people with diabetes), blood glucose extremely high, little enters cells; eat more than usual as cells starving, but excrete most glucose and lose weight

  • Either prolonged high or low insulin levels increase eating, but for different reasons and with different effects on body weight

Leptin

  • Body needs to compensate for daily mistakes of eating too much or too little with long-term regulation; does so by monitoring fat supplies
  • Leptin is in vertebrates
    • In normal mice and humans, the body-s fat cells produce leptin; more fat cells  more leptin.
  • Leptin signals brain about fat reserves, long-term indicator of whether you over or under eat; each meal also releases leptin, so the amount of circulating leptin indicates about short-term nutrition as well
  • When leptin high, act like you have a lot of nutrition  eat less, more active, increase activity of immune system (if you have enough fat supply, you can afford to devote energy to the immune system)
  • In the teens, a certain leptin level triggers puberty (if fat supply is too low to provide for your own needs, don-t have enough to supply for a baby)
  • If a mouse lacks the ability to produce leptin  brain acts as if body has no fat stores, must be starving, eats a lot, conserves energy by not moving, doesn-t enter puberty
  • Leptin sensitivity declines in people overweight, pregnant, preparing for hibernation
  • When consistent overeating leads to obesity, it damages the ER in neurons of the hypothalamus, seeing in motion a series of outcomes that lead to decreased leptin sensitivity

Brain Mechanisms

  • Hunger depends on contents of stomach, availability of glucose to the cells, fat supply, health/body temperature; appetite depends on more than need for food (seeing a picture of appealing food increases appetite; can eat just to be social)
  • Brain combines many kinds of information to decide when to eat and how much
  • Key brain areas include several nuclei of the hypothalamus
  • Many kinds of information impinge onto 2 kinds of cells in the arcuate nucleus of the hypothalamus  called “master area (for controlling appetite); axons extend from the arcuate nucleus to other areas of the hypothalamus

The Arcuate Nucleus and Paraventicular Hypothalamus

  • Arcuate nucleus of hypothalamus has 1 set of neurons sensitive to hunger signals, another to satiety signals

o    Hunger-sensitive cells receive input from taste pathway, other input from axons releasing neurotransmitter ghrelin (stomach releases during food deprivation, triggers stomach contractions, acts on hypothalamus to decrease appetite, acts on hippocampus to enhance learning)  only known hunger hormone

  • Signals of short-term/long-term satiety give input to satiety-sensitive cells of arcuate nucleus

 

Distension of intestines triggers neurons to release neurotransmitter CCK (short-term signal)

  • Blood glucose (short-term signal) directly stimulates satiety cells in the arcuate nucleus and leads to increases secretion of insulin that also stimulates the satiety cells; body fat (long-term signal) release leptin, which provides more input
  • Much of the output from the arcuate nucleus goes to the paraventricular nucleus of the hypothalamus; inhibits the lateral hypothalamus

(area for eating) o   PVN important for satiety

  • Axons from satiety-sensitive cells of arcuate nucleus deliver an excitatory message to PVN, releasing the neuropeptide alphamelanocyte stimulating hormone (alpha MSH), type of chemical  melanocortin o Melanocortin receptors in the PVN are important to limit food intake
  • Input from hunger-sensitive neurons of arcuate nucleus is inhibitory to both PVN and satiety-sensitive cells of arcuate nucleus itself
  • Inhibitory transmitters combination of  GABA, neuropeptide Y, agouti-related peptide; these transmitters block satiety according to

PVN, by provoking over-eating

  • Another pathway leads to cells in the lateral hypothalamus that release orexin/hypocretin; role in wakefulness and 2 roles in feeding
    1. Increases persistence to seek food
    2. Responds to incentives or reinforcement generally. Stimulation increases activity and motivation
  • Many chemicals contribute to the control of appetite  control of feeding can go wrong in many ways but when something does go wrong  the brain has many mechanisms to compensate or can develop specific drugs to work on many routes o Ex: melanocortin receptors  insulin, diet drugs and other procedures can affect eating by altering input to them

The Lateral Hypothalamus

  • Output from the paraventricular nucleus acts on the lateral hypothalamus (neuron clusters and passing axons); controls insulin secretion, alters taste responsiveness and facilitates feeding in other ways; stimulation increases the drive to eat
  • Many axons containing dopamine pass through the LH, so damages interrupts these fibres; with damage, there is loss with feeding without loss of arousal and activity; LH contributes to feeding by:
    1. Axons from LH to NTS (nucleus of tractus solitaries  part of taste pathway) alter taste sensation and salivation response to tastes; when LH detects hunger, sends messages to make food taste better
    2. Axons from LH extend to several parts of cerebral cortex, facilitating ingestion and swallowing, causing cortical cells to increase their response to taste, smell or sight of food
    3. LH increases pituitary gland-s secretion of hormones that increase insulin secretion
    4. LH sends axons to spinal cord, control autonomic responses such as digestive secretion, damage has trouble digesting foods

Medial Areas of the Hypothalamus

Output from ventromedial hypothalamus (VMH) inhibits feeding, damage  overeating and weight gain; eventually body weight levels off at a stable but high set point, and total food intake declines to nearly normal levels

  • Damage limited to VMH doesn-t consistently increase eating or body weight; to produce large effect, lesion extend outside VMH to invade nearby axons, especially ventral noradrenergic bundle
  • Damage in and around VMH  increased appetite compared to undamaged rats; eat normal-sized meals, but more frequently

(increased stomach motility/secretions, stomach empty faster  sooner animal ready for next meal

  • Another reason is age increases insulin production, much of each meal is stored as fat; high insulin levels keep moving blood glucose into storage, even when blood glucose level is low)
  • Damage: preoptic area (deficit in physiological mechanisms of temp regulation); lateral preoptic area (deficit in osmotic thirst due to cell damage and interruption of passing axons); lateral hypothalamus (under eat, weight loss, low insulin level from cell body damage, under arousal, under responsiveness from damage to passing axons); ventromedial hypothalamus (increased meal frequent, weight gain, high insulin level); paraventricular nucleus (increased meal size, increased carb intake during the 1st meal of the active period of the day)

Eating Disorders

  • Anorexia  refuse to eat to survive; bulimia  alternate between eating too much/too little
  • Increasing prevalence of obesity  increased availability of food so lose interest in rewards other than food, sedentary lifestyle, weak relationship between mood and weight gain in long-term, prenatal environment o Ex: mother with high-fat diet  larger lateral hypothalamus, produce more orexin and transmitters that facilitate increased eating and larger body weight

Genetics and Body Weight

  • Children-s weight correlated with biological parents due to genetics or prenatal environment
  • Obesity related to 1 gene (few cases)  mutated gene for receptor to melanocortin (neuropeptide responsible for hunger  overeat and become obese from childhood on), variant for FTO gene (weigh a few pounds more than others, 2/3 more chance to be obese)
  • Syndromal obesity  results from medical condition; severe early-onset obesity  deletions of chromosome part; includes  leptin receptors, insulin receptors or other elements in eating regulation  obesity and other problems o Ex: Prader-Willi syndrome  blood levels of ghrelin 4x more than normal  over eat because body thinks its being deprived
  • Many cases from genes and environment

o    Ex: Pima Natives  genes lead to obesity; used to have a diet with plants that ripen in short rainy season, eat food when was available to carry them through scarcity, conserve energy by limiting activity; now, with US diet, overeating and little activity isn-t adaptive

  • Genes affect weight gain  differences in hunger, digestion, lack of exercise, sedentary lifestyle

Weight Loss

  • Obesity viewed as a disease in the US; no longer see obese people as morally guilty and the insurance company may help pay for treatment but people may feel helpless to change
  • Dieting by itself isn-t very effective  most people don-t stick to the diet, as many people don-t lose weight as do lose weight on a plan, few maintain significant weight loss for long-term; small changes in diet is more likely to stick

Successful treatment requires  change of lifestyle, increased exercise, decreased eating; helps to get the weight off, not maintain weight loss

  • Need to reduce/eliminate soft drink intake as they are sweetened with fructose (sugar that doesn-t increase insulin/leptin as much as other sugars  gain calories without feeling full)
  • Diet soft drinks  more weight gain; when eating sweets learn to limit yourself; but with theses, taste is a poor predictor of energy, so overeat and stop compensating, less active
  • Weight-loss drugs  fenfluramine increases serotonin release/block reuptake; phentermine blocks reuptake of norepinephrine and dopamine prolonging activity o Combination leads to brain effects similar to complete meal but medical complications; sibutramine blocks reuptake of serotonin and norepinephrine, decreases meal size and binge eating; xenical prevents intestines from absorbing up to 30% of fats in the diet, but there is intestinal discomfort from globs of undigested fats, bowel movements thick with fat
  • Gastric bypass surgery for severe cases  part of stomach removed or sewed off so food can-t enter  smaller meal produces satiety; usually go from morbidly obese to obese o Side effects  infections, bowel obstruction, leaking food, nutritional deficiency

Bulimia Nervosa

  • Alternate between binges of overeating and strict dieting, may induce themselves to vomit
  • Most also suffer from depression, anxiety and other emotional problems; 1.5% of women; 1% of men; common with young people due to availability of good tasting high-calorie foods
  • Biochemical abnormalities  increased production of ghrelin (increase appetite); result of binges and purges; therapy decreases symptoms  ghrelin, body chemicals return to normal
  • Resembles drug addiction  eating good food activates same areas as addictive drugs; drug addicts who can-t get drugs overeat, fooddeprived people more likely to use drugs
  • Eating after deprivation  release dopamine and opioid compounds in brain, similar to effects of addictive drugs, increased level of dopamine 3 receptors in the brain; when deprived of food, show withdrawal symptoms; can be addicted to sugar and cycles of binging and purging