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Chapter 26

Lecture Outline

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Nutrition and Metabolism

• Nutrition

• Carbohydrate Metabolism

• Lipid and Protein Metabolism

• Metabolic States and Metabolic Rate

• Body Heat and Thermoregulation

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Body Weight

• Stable with equal energy intake and output– around a homeostatic set point

• Determined by combination of environmental and hereditary factors– 30-50% of variation between individuals due to

heredity – rest due to eating and exercise habits

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Gut-Brain Peptides

• Appetite regulators– short term

• effects last minutes to hours

– long term• effects last weeks to years

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Short-term Appetite Regulators

• Ghrelin – produces hunger

• Peptide YY – satiety

• Cholecystokinin – satiety

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Short-term Appetite Regulators

• Ghrelin – hunger– from parietal cells of empty stomach– also stimulates hypothalamus release of

human growth hormone releasing hormone

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Short-term Appetite Regulators

• Peptide YY (PPY) – satiety– from enteroendocrine cells in ileum and colon– secreted in proportion to calories consumed– acts as ileal break

• slows stomach emptying

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Short-term Appetite Regulators

• Cholecystokinin (CCK) – satiety– from enteroendocrine cells of duodenum and

jejunum– appetite-suppressing effect on brain

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Long-term Appetite Regulators

• Leptin – secreted by adipocytes in proportion to body fat stores

• Insulin – pancreatic beta cells– effect similar to leptin (but weaker)

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Hypothalamus

• Receptors for gut-brain peptides that regulate release of:

1. neuropeptide Y (hunger)• stimulated by gherlin• inhibited by PYY, leptin, and insulin

2. melanocortin (satiety)• stimulated by leptin, and CCK

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Appetite Regulation

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Other Factors in Appetite Regulation

• Appetite is briefly satisfied by– chewing– swallowing– stomach filling

• Neurotransmitters stimulate desire for different foods– norepinephrine – carbohydrates– galanin – fats – endorphins – protein

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Calories

• One calorie - amount of heat required to raise temperature of 1 g of water 1 °C– 1000 calories is a kilocalorie or Calorie

• Fats contain about 9 kcal/g

• Carbohydrates and proteins, about 4 kcal/g– sugar and alcohol are “empty” calories -- few

nutrients

• Substance used for fuel is oxidized primarily to make ATP

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Nutrients

• Ingested chemical used for growth, repair or maintenance

• Macronutrients consumed in large amounts – proteins, fats and carbohydrates

• Micronutrients needed in small amounts

• Recommended daily allowances (RDA) – safe estimate of daily intake for standard needs

• Essential nutrients can not be synthesized– minerals, vitamins, 8 amino acids and 1-3 fatty

acids must be consumed in the diet

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Carbohydrates

• Carbohydrates found in 3 places in body– muscle and liver glycogen; blood glucose

• Most carbohydrate serves as fuel– neurons and RBCs depend on glucose

• Sugars do serve as structural components– nucleic acids, glycoproteins and glycolipids,

ATP

• Blood glucose carefully regulated by insulin and glucagon

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RDA and Dietary Sources of Carbs

• Carbohydrates are rapidly oxidized, RDA greater than any other nutrient (175 g/day)

• Dietary sources:– monosaccharides = glucose, galactose and fructose

• liver converts galactose and fructose to glucose– outside hepatic portal system, only blood sugar is glucose

– normal blood sugar concentration ranges 70 to 110 mg/dL

– disaccharides = table sugar (sucrose), maltose, lactose

– polysaccharides = starch, glycogen and cellulose

• Nearly all dietary carbohydrates come from plants

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Dietary Fiber

• Fibrous material that resists digestion

• Fiber is important to diet (RDA is 30 g/day)– excess interferes with mineral absorption - iron

• Water-soluble fiber (pectin) blood cholesterol and LDL levels

• Water-insoluble fiber (cellulose, lignin)– absorbs water in intestines, softens stool,

gives it bulk, speeds transit time

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Lipids

• Average adult male 15% fat; female 25% fat– body’s stored energy

• hydrophobic, contains 2X energy/g, compact storage

• glucose and protein sparing (no protein utilized for energy)

– fat-soluble vitamins (A,D,E,K) absorbed with dietary fat

• ingest less than 20 g/day risks deficiency

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Functions of Lipids

• Diverse functions– structural

• phospholipids and cholesterol are components of plasma membranes and myelin

– chemical precursors • cholesterol - a precursor of steroids, bile salts and

vitamin D• fatty acids - precursors of prostaglandins and other

eicosanoids

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Fat Requirements and Sources

• Should be less than 30% of daily calorie intake– typical American gets 40-50%

• Most fatty acids synthesized by body– essential fatty acids must be consumed

• Saturated fats – animal origin -- meat, egg yolks and dairy products

• Unsaturated fats – found in nuts, seeds and most vegetable oils

• Cholesterol – found in egg yolks, cream, shellfish, organ meats and

other meats

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Serum Lipoproteins

• Lipids transported in blood as lipoproteins– protein and phospholipid coat around a

hydrophobic cholesterol and triglyceride core– soluble in plasma; bind to cells for absorption

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Serum Lipoproteins

• Categorized into 4 groups by density: more protein = higher density– chylomicrons– very low-density (VLDLs)– low-density (LDLs)– high-density (HDLs)

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Serum Lipoproteins

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Chylomicrons

• Form in absorptive cells of small intestine– enter lymphatic system, then blood– capillary endothelium has lipoprotein lipase

to hydrolyze monoglycerides– resulting free fatty acids (FFAs) and glycerol

enter fat cells to be resynthesized into triglycerides for storage

– chylomicron remnant degraded by liver

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VLDL and LDL

• VLDL – produced by liver to transport lipids to

adipose tissue for storage– when triglycerides removed become LDLs

(mostly cholesterol)

• LDL – absorbed by cells in need of cholesterol for

membrane repair or steroid synthesis

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HDL

• Production and function– liver produces an empty protein shell– travels through blood, picks up cholesterol– delivers cholesterol to liver, for elimination in

bile

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Total Cholesterol• Desirable to maintain total cholesterol

concentration of < 200 mg/dL– most cholesterol is endogenous– dietary restrictions lower blood cholesterol levels

• by 5% with restriction of dietary cholesterol• by 15 to 20% with restriction of certain saturated fats

– vigorous exercise lowers blood cholesterol

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Desirable Lipoprotein Levels

• High levels of HDL – indicate cholesterol is being removed from arteries

• Low levels LDL– high LDL correlates with cholesterol deposition in

arteries

• Recommendations– exercise regularly– avoid smoking, saturated fats, coffee and stress

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Lipoprotein Processing

• Three pathways

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Proteins

• 12-15% of body mass – mostly in skeletal muscles

• Functions– muscle contraction

• movement of body, cells, cell structures

– cell membranes (receptors, cell identity, pumps)

– fibrous proteins (collagen, keratin) • structural

– globular proteins (antibodies, myoglobin, enzymes)

• functional

– plasma proteins: blood osmolarity and viscosity

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Requirements for Protein

• RDA - 44-60 g/day• Nutritional value depends on proportions

of amino acids– 8 essential amino acids can not be

synthesized• isoleucine, leucine, lysine, methionine,

phenylalanine, threonine, tryptophan and valine

• Cells do not store surplus protein• Complete proteins (dietary)

– supply all amino acids in right amount needed to synthesize protein

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Dietary Sources

• Animal proteins (meat, eggs and dairy) are complete proteins – closely match human proteins in amino acid

composition

• Plant sources must be combined in the right proportions– beans and rice are a complementary choice

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Nitrogen Balance

• Rate of nitrogen ingestion equals rate of excretion– proteins are chief dietary source of nitrogen– excretion chiefly as nitrogenous wastes

• Positive nitrogen balance – occurs in children; they ingest more than they excrete– promoted by growth and sex hormones

• Negative nitrogen balance – body proteins being broken down for fuel (muscle

atrophy)– glucocorticoids promote protein catabolism in states

of stress

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Functions of Minerals• Calcium and phosphorus

– bones and teeth

• Phosphorus– phospholipids, ATP, CP, buffers, nucleic acids

• Calcium, iron, magnesium and manganese – cofactors for enzymes

• Iron - essential for hemoglobin and myoglobin

• Chlorine - component of stomach acid (HCl)

• Mineral salts – electrolytes; govern function of nerve and muscle

cells; regulate distribution of body water

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Dietary Sources of Minerals

• Vegetables, legumes, milk, eggs, fish and shellfish

• Animal tissues contain large amounts of salt– carnivores rarely lack salt in their diets– herbivores often supplement by ingesting soils

• Recommended sodium intake is 1.1 g/day

• Typical American diet contains 4.5 g/day

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Vitamins

• Body synthesizes some vitamins from precursors– niacin, vitamin A and D– vitamin K, pantothenic acid, biotin, folic acid

• produced by intestinal bacteria

• Water-soluble vitamins (C, B) – absorbed with water in small intestine; not

stored

• Fat-soluble vitamins (A, D, E, K)– absorbed with dietary lipids; stored

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Vitamins

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Carbohydrate Metabolism

• Dietary carbohydrate burned as fuel within hours of absorption (glucose catabolism)

C6H12O6 + 6O2 6CO2 + 6H2O

• Transfers energy from sugar to ATP

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Glucose Catabolism

• Series of small steps to efficiently transfer energy to ATP (reduces energy lost as heat)

• Three major pathways– glycolysis (yields 2 ATP)

• glucose (6C) split into 2 pyruvic acid molecules (3C)

– aerobic respiration (yields 34-36 ATP)

• completely oxidizes pyruvic acid to CO2 and H2O

– anaerobic fermentation (if no O2 available)• pyruvic acid reduced to lactic acid

– replenishes NAD+ so glycolysis can continue

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Overview of ATP Production

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Coenzymes

• Capture energetic electrons from glucose during its catabolism– coenzymes reduced

• gains energy (electron)• charge reduced (electrons have negative charge)

• NAD+ (nicotinamide adenine dinucleotide)– derived from niacin (B vitamin)– NAD+ + H- + H+ NADH + H+

• FAD (flavin adenine dinucleotide)– derived from riboflavin– FAD + H- + H+ FADH2

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Steps of Glycolysis (1)

• Phosphorylation– glucose enters cell has phosphate added - ATP

used– maintains favorable concentration gradient,

prevents glucose from leaving cell

• Priming – isomerization occurs– phosphorylation further activates molecule -

ATP used

• Cleavage– molecule split into 2 three-carbon molecules

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Steps of Glycolysis (2)

• Oxidation – removes H+ and H- – NAD+ + H- NADH

• Dephosphorylation– transfers phosphate groups to ADP to form

ATP– 4 ATP produced (2 ATP used) for a net gain of

2 ATP– produces pyruvic acid

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Anaerobic Fermentation

• Fate of pyruvic acid depends on oxygen availability

• In an exercising muscle, demand for ATP > oxygen supply; ATP produced by glycolysis– glycolysis can not continue without supply of NAD+

– NADH reduces pyruvic acid to lactic acid, restoring NAD+

• Lactic acid travels to liver to be oxidized back to pyruvic when O2 is available (oxygen debt)– then stored as glycogen or released as glucose

• Fermentation is inefficient, not favored by brain or heart

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Aerobic Respiration

• Most ATP generated in mitochondria, require oxygen as final electron acceptor

• Principle steps– matrix reactions occur in fluids of

mitochondria– membrane reactions whose enzymes are

bound to the mitochondrial membrane

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Mitochondrial Matrix Reactions

• Three steps prepare pyruvic acid to enter citric acid cycle– decarboxylation so that a 3-carbon becomes a

2-carbon compound– convert that to an acetyl group (remove H)– bind it to coenzyme A

• Known as formation of acetyl-coenzyme A

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Mitochondrial Matrix Reactions

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Mitochondrial Matrix Reactions

• Citric Acid Cycle• Acetyl-Co A (a C2 compound) combines with a

C4 to form a C6 compound (citric acid)-- start of cycle

• Water is removed -- NAD+ is reduced to NADH -- CO2 is removed to form a C5 compound-- NAD+ is reduced to NADH -- CO2 is removed to form a C4 compound

• FAD is reduced to FADH2 -- water is added -- NAD+ is reduced to NADH

• Original C4 compound is reformed – ready to restart cycle

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Summary of Matrix Reactions

2 pyruvate + 6H2O 6CO2

2 ADP + 2 Pi 2 ATP8 NAD+ + 8 H- + 8 H+ 8 NADH + 8 H+

(2 NADH produced during formation of acetyl-CoA)

2 FAD + 2 H2 2 FADH2

• Carbon atoms of glucose have all been carried away as CO2 and exhaled.

• Energy lost as heat, stored in 2 ATP, 8 reduced NADH, 2 FADH2 molecules of the matrix reactions and 2 NADH from glycolysis

• Citric acid cycle is a source of substances for synthesis of fats and nonessential amino acids

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Membrane Reactions

• Purpose - to oxidize NADH and FADH2, transfer their energy to ATP and regenerate them

• Reactions carried out by series of compounds attached to inner mitochondrial membrane called electron transport chain– FMN is derivative of riboflavin, iron-sulfur centers,

Coenzyme Q, Copper ions bound to membrane proteins and cytochromes (5 enzymes with iron cofactors)

• As electrons are transferred along transport chain, their potential orbital energy is released

• Final electron acceptor is oxygen: accepts 2 electrons and 2 H+ to form a water molecule

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Electron Transport Chain

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Chemiosmotic Mechanism

• Electron transport chain energy fuels enzyme complexes – pump protons from matrix into space between

inner and outer mitochondrial membranes– creates steep electrochemical gradient for H+

across inner mitochondrial membrane

• Inner membrane is permeable to H+ at channel proteins called ATP synthase

• Chemiosmotic mechanism - H+ flow rushing back through these channels drives ATP synthesis

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Chemiosmotic ATP Synthesis

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Overview of ATP Production

• NADH releases an electron pair to electron transport system and H+ to prime pumps– enough energy to synthesize 3 ATP

• FADH2 releases its electron pairs further along electron-transport system – enough energy to synthesize 2 ATP

• Complete aerobic oxidation of glucose to CO2 and H2O produces 36-38 ATP

– efficiency rating of 40% -- rest is body heat

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ATP Generated by Oxidation of Glucose

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Glycogen Metabolism

• ATP is quickly used after it is formed -- it is not a storage molecule– extra glucose will not be oxidized, it will be stored

• Glycogenesis -- synthesis of glycogen– stimulated by insulin (average adult contains 450 g)

• Glycogenolysis -- glycogen glucose– stimulated by glucagon and epinephrine– only liver cells can release glucose back into blood

• Gluconeogenesis -- synthesis of glucose from noncarbohydrates, such as fats and amino acids

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Glucose Storage and Use

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Lipids• Triglycerides are stored in adipocytes

– constant turnover of molecules every 3 weeks • released into blood, transported and either oxidized or

redeposited in other fat cells

• Lipogenesis = synthesizing fat from other sources– amino acids and sugars used to make fatty acids and

glycerol

• Lipolysis = breaking down fat for fuel– glycerol is converted to PGAL and enters glycolysis– fatty acids are broken down 2 carbons at a time to

produce acetyl-CoA (beta oxidation)

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Lipogenesis and Lipolysis Pathways

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Ketogenesis

• Fatty acids catabolized into acetyl groups (by beta-oxidation in mitochondrial matrix) may – enter citric acid cycle as acetyl-CoA– undergo ketogenesis

• metabolized by liver to produce ketone bodies– acetoacetic acid -hydroxybutyric acid– acetone

• rapid or incomplete oxidization of fats raises blood ketone levels (ketosis) and may lead to a pH imbalance (ketoacidosis)

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Proteins• Amino acid pool - dietary amino acids plus 100 g

of tissue protein broken down each day into free amino acids

• May be used to synthesize new proteins• As fuel -- first must be deaminated (removal of

NH2)--what remains is converted to pyruvic acid, acetyl-CoA or part of citric acid cycle– during shortage of amino acids, the reverse occurs for

protein synthesis

– the NH2 become ammonia (NH3) which is toxic and which the liver converts to urea (excreted in urine)

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Pathways of Amino Acid Metabolism

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Urea Synthesis

• Liver converts ammonia (NH3) to urea which is removed from blood by kidneys

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Absorptive State• Lasts about 4 hours during and after a meal

– time of nutrient absorption and use for energy needs

• Carbohydrates– blood glucose is available to all cells for ATP synthesis– excess is converted by liver to glycogen or fat

• Fats– taken up by fat cells from chylomicrons in the blood– primary energy substrate for liver, fat and muscle cells

• Amino acids– most pass through the liver and go onto other cells– in liver cells, may be used for protein synthesis, used

for fuel for ATP synthesis or used for fatty acid synthesis

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Regulation of Absorptive State• Regulated by insulin secreted in response to

elevated blood glucose and amino acid levels and the hormones gastrin, secretin and cholecystokinin

• Insulin– increases the cellular uptake of glucose by 20-fold– stimulates glucose oxidation, glycogenesis and

lipogenesis but inhibits gluconeogenesis– stimulates active transport of amino acids into cells

and promotes protein synthesis• high protein, low carbohydrate meals stimulate release of

both insulin and glucagon preventing hypoglycemia

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Postabsorptive State• Homeostasis of blood glucose critical to brain

– when stomach and small intestine are empty- stored fuels are used

• Carbohydrates– glucose is drawn from glycogen reserves for up to 4

hours and then synthesized from other compounds

• Fat– adipocytes and liver cells convert glycerol to glucose– free fatty acids are oxidized by liver to ketone bodies

• other cells use for energy-- leaving glucose for brain

• Protein metabolism– used as fuel when glycogen and fat reserves depleted– wasting away occurs with cancer and other diseases

from loss of appetite and altered metabolism

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Regulation of Postabsorptive State

• By sympathetic nervous system and glucagon

• Blood glucose drops, glucagon secreted– glycogenolysis and gluconeogenesis raise

glucose levels– lipolysis raises free fatty acid levels

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Regulation of Postabsorptive State

• Sympathoadrenal effects– promotes glycogenolysis and lipolysis under

conditions of injury, fear, anger and stress– adipose, liver cells and muscle cells are richly

innervated and also respond to epinephrine from adrenal medulla

– Cortisol from adrenal cortex promotes blood glucose

• fat and protein catabolism and gluconeogenesis

– Growth hormone – opposes rapid in blood glucose

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Metabolic Rate

• Amount of energy used in the body in a given period of time (kcal/hr or kcal/day)– measured directly in calorimeter (water bath)– measured indirectly by oxygen consumption

• Basal metabolic rate (BMR) – relaxed, awake, fasting, room comfortable

temperature– adult male BMR is 2000 kcal/day(slightly less female)

• Factors affecting total MR– pregnancy, anxiety, fever, eating, thyroid hormones,

and depression

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Body Heat and Thermoregulation

• Homeostasis requires heat loss to match heat gain

• Hypothermia - excessively low body temperature– can slow metabolic activity and cause death

• Hyperthermia - excessively high body temperature– can disrupt enzymatic activity and metabolic

activity and cause death

• Thermoregulation - ability to balance heat production and heat loss

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Body Temperature

• “Normal” body temperature varies about 1.8 degrees F. in a 24-hour cycle– low in morning and high in late afternoon

• Core body temperature is temperature of organs in cranial, thoracic and abdominal cavities– rectal temperature is an estimate– adult varies normally from 99.0 - 99.7 degrees F.

• Shell temperature is temperature closer to the surface (oral cavity and skin)– adult varies normally from 97.9 - 98.6 degrees F.

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Heat Production

• Comes from energy-releasing chemical reactions such as nutrient oxidation and ATP use

• From brain, heart, liver, endocrine and muscles– exercise greatly heat production in muscle

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Modes of Heat Loss

• Radiation - loss of body heat to objects around us– caused by molecular motion producing infrared

radiation

• Conduction - loss of body heat to the air which when warmed rises to be replaced by cooler air

• Evaporation - heat loss as sweat evaporates – extreme conditions as much as 2L of sweat lost per

hour, dissipating heat by as much as 600 kcal/hour

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Thermoregulation• Hypothalamic thermostat monitors

temperature of blood and skin, signals– heat-losing center to stimulate

• cutaneous vasodilation• sweating

– signals heat-promoting center to stimulate

• cutaneous vasoconstriction• arrector pili muscle contraction• shivering thermogenesis (if needed)• nonshivering thermogenesis - thyroid

hormone and BMR (seasonal adjustment)

• Behavioral thermoregulation– get out of sun, remove heavy clothing

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Disturbances of Thermoregulation

• Fever– normal protective mechanism that elevates BMR

which produces more heat elevating the BMR, etc.

• Hyperthermia - exposure to excessive heat– heat cramps are muscle spasms due to electrolyte

imbalance from excessive sweating– heat exhaustion -- severe electrolyte imbalance

producing fainting, dizziness, hypotension– heat stroke -- body temperature > 104 °F, may cause

delirium, convulsions, coma, and death

• Hypothermia - exposure to excess cold– as core body temperature , BMR causing a further

body temperature decrease, etc. (fatal if body temperature 75 °F)