regulation of organic metabolism growth and energy balance 0524
DESCRIPTION
By: Hsiao-Fung Pu 1 •Catabolism breakdown storage molecules and provision of energy for cell functions, and disposing of the waste products of these reaction Metabolism 2 • Carbohydrate →monosaccharides • Protein →amino acids (GI tract →hepatic portal vein→Liver→venous system) • Minerals • Vitamins • Water • Lipid →triglycerides 3 (Bern RM & Levy MN., Physiology, 5 th Edition, 2004, Fig. 40-3) 4 (Bern RM & Levy MN., Physiology, 5 th Edition, 2004, Fig. 40-1) 5TRANSCRIPT
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Regulation of Organic Metabolism, Growth, and
Energy BalanceBy: Hsiao-Fung Pu
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Metabolism
• Anabolismsynthesis of the molecules required for cell structure and function
• Catabolismbreakdown storage molecules and provision of energy for cell functions, and disposing of the waste products of these reaction
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Compositions of Foods
• Carbohydrate → monosaccharides• Protein → amino acids
(GI tract → hepatic portal vein →Liver → venous system)
• Lipid → triglycerides(GI tract → chylomicrons → Lymph → venous system)
• Minerals• Vitamins• Water
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Caloric Stores in Human
(Bern RM & Levy MN., Physiology, 5th Edition, 2004, Fig. 40-3)
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Overview of Energy Balance
(Bern RM & Levy MN., Physiology, 5th Edition, 2004, Fig. 40-1)
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Absorptive State
• Ingested nutrients are entering the blood from the gastrointestinal tract
• Energy: (1) metabolic heat(2) work(3) storage
(an average meal requires approximately 4 h forcomplete absorption)
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Postabsorptive State
• Gastrointestinal tract is empty of nutrients and energy must be supplied by the body’s own stores (maintain blood glucose, because the brain normally utilize glucose for energy only)
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Major Metabolic Pathways of the Absorptive State
(Widmaier EP et al., Vander’s Human Physiology, 11st Edition, 2008, Fig. 16-1)
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Lipoprotein Lipase
• Located on the blood-facing surface of the capillary endothelium
• Hydrolyze the very-low density lipoprotein (VLDL) to monoglycerides and fatty acids
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10(Widmaier EP et al., Vander’s Human Physiology, 11st Edition, 2008, Fig. 16-2)
Major Metabolic Pathways of the Postabsorptive State
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“Feasting” “Fasting”(insulin present) (insulin absent)
Synthesis CatabolismFuel is glucose Diverse fuels
Storage molecules Gluconeogenesis
(Widmaier EP et al., Vander’s Human Physiology, 11st Edition, 2008, Fig. 16-3)
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• Normal total energy expenditure for an average adult equals 1500 to 3000 kcal/day.
• The 180 g of glucose per day produced by gluconeogenesis in the liver and kidneys during fasting supplies 720 kcal: 180 g/day × 4 kcal/g = 720 kcal/day
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Glucose Sparing (Fat Utilization)• Most organs & tissues markedly reduced
their glucose catabolism increase their fat utilization. This metabolic adjustment, termed glucose sparing, “spare” the glucose produced by the liver for use by the nervous system.
• Many areas of the brain are capable of utilizing ketones for energy, and so as these substances being to build up in the blood after the first few days of a fast, the brain beings to utilize them, as well as glucose, for its energy source.
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Sources of Blood Glucose During the Postabsorptive Period
(Bern RM & Levy MN., Physiology, 5th Edition, 2004, Fig. 40-5)
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Endocrine and Neural Control of the Absorptive and Postabsorptive States
• Insulin• Glucagon (effect on Liver)• Epinephrine (from the adrenal medulla)• Other hormones (cortisol, GH, thyroid
hormone, sex steroids, etc.)• Sympathetic nerves to liver and adipose
tissues
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Effects of Insulin on Various Tissues
(Widmaier EP. et al., Vander’s Human Physiology, 11st Edition, 2008, Fig. 16-6)
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Summary of Glucose-CounterregulatoryControls
(Widmaier EP. et al., Vander’s Human Physiology, 11st Edition, 2008, Table 16-4)
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Diabetogenic Effect of Thyroid Hormones
• Increase absorption of glucose from the intestine
• Cause some degree of hepatic glycogen depletion
• Glycogen-depleted liver cells are damaged
• Liver take up less of the absorbed glucose
• Accelerate the degradation of insulin
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Effect of Starvation on Plasma Levels of Thyroid Hormones
(Ganong WF. Review of Medical Physiology, 20th Edition, Fig. 18-10)
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20(Widmaier EP. et al., Vander’s Human Physiology, 11st Edition, 2008, Table 16-3)
Effects of Cortisol on Organic Metabolism
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Fuel Homeostasis in Prolonged Moderate Exercise
Duration time: > 90 min
SNS activity↑
EP secretion ↑
Insulin secretion↓
Glucagon secretion↑
Liver: ↑glycogenolysis & gluconeogenesis
Adipose tissues: ↑lipolysis
GH secretion ↑
Cortisol secretion↑
Muscle: ↑glucose uptake
(Widmaier EP et al., Vander’s Human Physiology, 11st Edition, 2008, Fig. 16-11)
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Oral Glucose Tolerance Test (OGTT)
• Fasting > 12 hPlasma Glucose: 70-105 mg/dlOral 75 glucose/300 ml H2OWithin 2 h: < 140 mg/dl
• DM:Plasma Glucose: > 140 mg/dl (twice)Glucose in Urine (> 180 mg/dl in plasma)Plasma Glycohemoglobin: >7%
(Ganong WF. Review of Medical Physiology, 22nd Edition, 2005, Fig. 19-8)
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OGTT
(Fox SI., Human Physiology, 5th Edition, 1996, Fig. 19-11)
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Effects of Chronic, Intense Exercise on the Human Body
• Non-essential function (reproduction) shut down, so that nutrients can be directed primarily to muscle
• Delay puberty• Exercise-induced amenorrhea
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Cholesterol
• Precursor of plasma membranes, bile salts, steroid hormones
• High plasma concentrations →atherosclerosis
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Plasma Cholesterol (Women vs. Men)
(Widmaier EP et al., Vander’s Human Physiology, 5th Edition, 1990, Fig. 17-13)
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Cholesterol
• Normal range: 20 – 200 mg/dl• Borderline high: 200 – 239 mg/dl• High: above 240 mg/dl
• Ingesting saturated FA (animal fat – red meats, most cheeses, and whole milk)→↑plasma cholesterol
• Ingesting polyunsaturated FA (plant), or monounsaturated FA (olive or peanut oil)→↓plasma cholesterol
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Low Density Lipoprotein (LDL)
• Main cholesterol carriers• Deliver cholesterol to cells• ↑deposition of cholesterol in arterial walls• LDL-cholesterol complex: “BAD” cholesterol• Estrogen: ↓plasma LDL (by increasing the LDL
receptors in the liver)• Normal: < 150 mg/dl
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Cellular Uptake & Metabolism of Cholesterol
(Ganong WF. Review of Medical Physiology, 22nd Edition, 2005, Fig. 17-29)
(↓Cholesterol Synthesis)(acetyl-CoA:cholesterol acyltransferase)
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High Density Lipoproteins (HDL)
• Acceptors of cholesterol from various tissues• Removal of cholesterol from cells and its
secretion into the bile by the liver• HDL-Cholesterol complex: “GOOD”
cholesterol• Smoking: ↓plasma HDL• Weight reduction & exercise: ↑plasma HDL• Estrogen: ↑plasma HDL• EPA (eicosapentaenoic acid): ↑plasma HDL• Norml: > 35 mg/dl
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Growth (Involves Cell Division and Net Protein Synthesis)
• Genetics• Endocrine function
growth hormone, IGF-I, IGF-II, thyroid hormone, sex hormone, insulin, cortisol, etc.
• Growth factors (mitogen → cell division) and growth inhibiting factors
• Environmental factorsnutrients (AA, FA, Vit., minerals) and Infection
maternal malnutrition:growth retardation in the fetus, low birth weight,↑infant mortality, stunting brain development, mental retardation
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Growth of Different Tissues at Various Ages
(Ganong WF, Review of Medical Physiology, 22nd Edition, 2005, Fig. 22-12)
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Intrauterine Growth (from Conception to Delivery)
• Fetal mass increases 44 x 107 timesAfter birth: 20-fold
• Body length increases 3850 timesAfter birth: 3-4 fold
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IGFs
• Growth during early gestation: IGF-II• Growth during later gestation: IGF-I
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Growth Hormone Secretion throughout the Day
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Effect of GH and Insulin on Growth
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Growth hormone & IGF-I interact on theEpiphyseal Plates of Bone are as follows:
(1) GH stimulates the chondrocyte precursor cells (prechondrocytes) and/or young differentiating chondrocytes) in the epiphyseal plates to differentiate into chondrocytes
(2) the cells begin both to secrete IGF-I and to become responsive to IGF-I
(3) IGF-I then acts as an autocrine or paracrineagent to stimulate the differentiating chondrocytes to undergo cell division
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Fetal
• Little or no effect• IGF-II, the secretion is independent of GH,
is also a crucial mitogen during the prenatal period (for total body growth, for maturation of nervous system)
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During childhood
• Excess: gigantism• Deficiency: dwarfism• Normal or elevated
Laron Dwarfism (GH insensitivity syndrome)--- gene deletion or point mutation--- GH-R fail to respond to GH--- plasma IGF-I is markedly reduced
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Gigantism
(Widmaier EP et al., Vander’s Human Physiology, 11st Edition, 2008, Fig. 11-29a)
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Adult (after epiphyseal closure)
• Excess: acromegaly (almost pituitary tumor)Deficiency: fat distribution randomly
IGF-I and GH↑amino acid uptake↑synthesis of RNA and ribosomes↑protein synthesis
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Acromegaly (I)
(Widmaier EP et al., Vander’s Human Physiology, 11st Edition, 2008, Fig. 11-29b, c)
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43(Fox SR, Human Physiology, 5th Edition, 1996, Fig. 19.17)
Acromegaly (II)
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Epidermal Growth Factor• Lung maturation• Birth weight is not affected• ↑Adrenal and gut weight • Stimulates gut muscle, enzyme maturation,
gut size and content, improving the ability of the infant to absorb nutrients
• Maturation of the fetal adrenal cortex, ↑expression of 3-hydroxysteroid dehydrogenase
• Somker (mother) →↓EGFRs and affinity for EGF
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Genetic, Maternal & Uterine Factors• The height of the mother correlates better with fetal
size than the height of the father.• First-born infants are on the average 100 g heavier
than subsequent infants• Maternal alcohol ingestion: fetal length and mental
development• Fetal alcohol syndrome: microcephaly, mental
retardation, midfacial hypoplasia, short palpebralfissures, wide-bridge nose, long philtrum (人中), and narrow vermilion border of the lips
• Smoking causes not only retarded intrauterine growth but also decreased postnatal growth for as long as 5 years after parturition.
• Maternal infection: toxoplasmosis, rubella, cytomegalovirus infection, herpes
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46(Grossman A, Clinical Endocrinology, 1st Edition, 1992, Fig. 59.2)
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Relative Importance of Hormones in Human Growth at Various Ages
(Ganong WF, Review of Medical Physiology, 22nd Edition, 2005, Fig. 22-13)
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Effect of Thyroid Hormone on Metabolism of Thyroidectomized Rats
(Ganong WF, Review of Medical Physiology, 22nd Edition, 2005, Fig. 18-10)
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49(Ganong WF, Review of Medical Physiology, 22nd Edition, 2005, Fig. 22-14)
Normal and Abnormal Growth
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The First Law of Thermodynamics
• Energy can be neither created nor destroyed but can be converted from one form to another
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• ΔE = H + W
ΔE: energy liberateH: heat (60%)
--- maintain body temperature--- enzyme activity--- membrane permeability
W: biological work (40%)--- external work: the movement of external
objects by contracting skeletal muscles--- internal work : all other forms of work, including
skeletal muscle activity not used in movingexternal objects
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Calories
• the amount of heat energy necessary to raise the temperature of 1 L water 1 degree: 1 kcal
• 1000 cal = 1 kcal = 4184 joules
• The heat capacity of human tissue is similar to that of water. If 1 kcal of heat is added to one kg of body tissue, the temperature of that tissue increases nearly 1℃.
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• If the cellular temperature were to drop 10 ℃, however, cellular enzymatic reaction rates would decreased by a factor of approximately 2.5
• Human metabolic activity, therefore, changes about 12% for every degree centigrade of change in body temperature
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Metabolic Rate
• the amount of energy liberated per unit of time
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Basal Metabolic Rate (BMR)• the metabolic rate determined at rest in a room at a
comfortable temperature in the thermoneutral zone (25 – 30 ℃) 12 – 14 h after the last meal
• Falls about 10% - 15% during sleep• Adult human of average size is about 20 - 25 kcal/Kg
BW/day, and requires the use of approximately 200 –250 ml O2/min
• ~40% of BMR is accounted for by the CNS~20-30% of BMR by the skeletal muscle mass
• absolute BMR: large animal > small animal• BMR/BW: large animal < small animal• women is slightly lower than man
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Correlation Between Body Weight vs. Surface Area (black line) and Heat Production vs. Body Weight (red line)
(Ganong WF. Review of Medical Physiology, 22nd Edition, 2005, Fig 17-2)
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Surface Area in Human
• S = 0.007184 x W 0.425 x H 0.725
• S: surface area in m2
W: body weight in kgH: height in cm
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Caloric Value• In vitro:
Carbohydrate: 4.1 kcal/gFat: 9.3 kcal/gProtein: 5.3 kcal/g
• In vivo:Carbohydrate: 4.1 kcal/gFat: 9.3 kcal/gProtein: 4.1 kcal/g (exclude urea andrelated nitrogenous compounds)
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Direct Method for Measuring Metabolic Rate
(Widmaier EP et al., Vander’s Human Physiology, 8th Edition, 1990, Fig. 17-17)
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Indirect Method for Measuring Metabolic Rate(Except O2 Debt is Being Incurred or Repaid)
(Widmaier EP. et al., Vander’s Human Physiology, 8th Edition, 1990, Fig. 17-18)
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61(Widmaier EP. et al., Vander’s Human Physiology, 11st Edition, 2008, Table 16-5)
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Thyroxine
• Increases oxygen consumption and heat production of most body tissues except brain
• Thyroxine increases proteins in inner mitochondrial membrane and reduce the amount of ATP to increase cell respiration and generate heat
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Body Mass Index (BMI)
Weight (Kg)/Heigh2 (M2)
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Classification of Overweight and Obesity Based on Body Mass Index (BMI)
• Underweight < 18.5• Normal 18.5 – 24.9• Overweight 25.0 – 29.9• Obesity
Class I 30.0 – 34.9Class II 35.0 – 39.9Class III (extreme) > 40.0
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Health Consequences of Overweight & Obesity
• Diabetes Mellitus Type 2• Hypertension• Hyperlipidemia and Dyslipidemia• Arteriosclerotic heart disease & stroke• Gallbladder disease, Osteoarthritis • Cancers: uterine endometrium, breast,
prostate, and colon• Sleep apnea: BMI > 30• Menstrual irregularity, infertility, and
polycystic ovarian syndrome
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• Abdominal fat (“apples”, central or visceral-abdominal obesity) are at greater risk for developing serious conditions such as diabetes and cardiovascular diseases than people whose fat is mainly in the lower body (“pears”, gluteal-femoral obesity) – on the buttocks and thighs.
• High-risk abdominal obesity is defined as a waist measurement of >102 cm (>40 inches) in men and >88 cm (>35 inches) in women.
• Adipose tissue cells in the abdomen are much more adept at breaking down fat stores and releasing the products into the blood.
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67(Widmaier EP. et al., Vander’s Human Physiology, 11st Edition, 2008, Fig. 16-14)
Fat cells, synthesize and secrete a protein called leptin, which is a putative hormone that acts on the Central Nervous System to reduce appetite inpersons with adequate energy reserves.
↓NPY Release
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Long-term Fasting
• ↓sex steroids secretion• ↓thyroid hormones secretion• ↑adrenal glucocorticoids secretion
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Overview of a Current Concept of Regulation of Energy Stores
(Bern RM & Levy MN, Physiology, 4th Edition, 1998, Fig. 46-13)
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Drugs Treatment (BMI > 30)• 食慾抑制劑 (刺激serotonine or adrenaline分泌或抑制
回收)(A) PPA (phenylpropanolamine)
感冒藥中成份,已被禁用,會增加年輕女性中
風機率,約可減6 Kg(B) prozao: 抗憂鬱劑,約可減12 Kg(C) dexfenfluramine: 會造成心瓣膜疾病及肺部
高壓之危險性
(D) fen-fen:會造成心瓣膜疾病,已禁用
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Drugs Treatment (BMI > 30)
• 熱量消耗劑
主要成份: ephedrine與caffiene, 約可減 16 Kg• 消化抑制劑
(A) xenical: lipase inhibitor, 約可減4 Kg, 會有
腹瀉產生
(B) 纖維素: 主要用於DM及高血脂病人,約可減
4 Kg
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Eating Disorders(almost in adolescent girls & young women)
• Anorexia Nervosaafraid of gaining weight and reduced food intake so severely< 25 years old↓15% BW↓heart rate (< 60/min)Loss of menstrual periods ( 3 times)Low blood pressureLow body temperatureAltered secretion of many hormonesDie of starvation
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73(Wilson JD, et al., Williams Textbook of Endocrinology, 9th Edition, 1998, Table 22-4)
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74(Wilson JD, et al., Williams Textbook of Endocrinology, 9th Edition, 1998, Table 22-6)
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Eating Disorders(almost in adolescent girls & young women)
• Bulimia Nervosa:Recurrent episodes of being eatingSelf-induced vomiting, laxatives ordiureticsStrict dieting, fasting or vigorous exercise in order to prevent weight gain
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76(Wilson JD, et al., Williams Textbook of Endocrinology, 9th Edition, 1998, Table 22-5)
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77(Wilson JD, et al., Williams Textbook of Endocrinology, 9th Edition, 1998, Table 22-7)
(自殘)
(自殺)
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78
Endocrine Changes in Anorexia Nervosa and Bulimia Nervosa
(Wilson JD, et al., Williams Textbook of Endocrinology, 9th Edition, 1998, Table 22-8)
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Gastric Bypass Operation for Morbid Obesity
(Wilson JD, et al., Williams Textbook of Endocrinology, 9th Edition, 1998, Fig. 22-14)
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80From: 聯合報
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Effect of Starvation on the Food Stores of the Body
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• Exercise plus caloric restriction causes lose more fat and less protein than with caloric restriction alone
• Fat: 9.3 kcal/g1000 kcal/day ÷ 9.3 kcal/g = 107.5 g/day107.5 g/day × 7 day = 752.7 g/weekanother 75.3 g water lostTotal: 828 g/week
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83
Summary of National Research Council Dietary Recommendations
(Widmaier EP. et al., Vander’s Human Physiology, 11st Edition, 2008, Table 16-8)
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84
Mechanisms of Heat Exchange between the Body and the Environment
(Rhoades R and Pflanzer R, Human Physiology, 4th Edition, 2003, Fig. 27-4)
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85
Relationship of Skin’s Insulating Capacity to Skin Blood Flow
(Widmaier EP. et al., Vander’s Human Physiology, 5th Edition, 1990, Fig. 17-24)
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86
Static Discharge Frequency of Cold and Warm Nerve Fibers as a Function of Skin Temperature
(Rhoades R and Pflanzer R, Human Physiology, 4th Edition, 2003, Fig. 27-2)
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Summary of Thermoregulatory Effector Responses to Decreased Core and Skin
Temperature
(Rhoades R and Pflanzer R, Human Physiology, 4th Edition, 2003, Table 27-1)
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Involuntary Muscle Activity• The upper limit of shivering-induced
heat production is perhaps only a 3-fold increase above resting levels, and shivering is inefficient for two reasons:1. shivering → ↑ activated muscle’s blood flow → ↑ local skin surface temperature → ↑ heat loss2. shaking motions of shivering increase heat loss by convection
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Summary of Thermoregulatory Effector Responses to Increased Core and Skin
Temperature
(Rhoades R and Pflanzer R, Human Physiology, 4th Edition, 2003, Table 27-2)
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90
Summary of Temperature-regulating Mechanisms
(Widmaier EP. et al., Vander’s Human Physiology, 11st Edition, 2008, Fig. 16-18)
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91
Sweating
• 2-3 million sweat glands distributed over most of the body surface
• The rate of sweat evaporation depends upon environmental humidity and the rate of air movement at the skin surface (2L/h).
(Rhoades R and Pflanzer R, Human Physiology, 4th Edition, 2003, Fig. 27-8)
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92
Thermoneutral Zone : 25 - 30 ℃(Environmental Temperature)
Thermoneutral Zone: 36.8 – 37.2 ℃(Hypothalamus Temperature)
at this range, without either sweating or shivering being initiated
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Measurement of Core Temperature
• Both the tympanic membrane temperature and the rectal temperature are reasonably accurate estimates of core temperature.
• The oral (sublingual) temperature is also representative, averaging approximately 0.6 ℃lower than rectal or tympanic membrane temperature.
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94
Survival Range of Body Temperature in Humans
(Rhoades R and Pflanzer R, Human Physiology, 4th Edition, 2003, Fig. 27-9)
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Circadian Rhythm in Core Temperature
(Rhoades R and Pflanzer R, Human Physiology, 4th Edition, 2003, Fig. 27-11)
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Menopause — Hot Flashes• Estrogen deficiency narrows the
hypothalamic thermoneutral zone from 0.4 to less than o.1℃
(Rhoades R and Pflanzer R, Human Physiology, 4th Edition, 2003, Fig. 27-12)
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Tolerance
• Dry air: 130 ℃ for 20 min or longer• Very moist air: 46 ℃ for only few min
• Body temperature tolerance range: 21-24 ℃
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Long Term Acclimatization
• Heat:↑mineralocorticoid hormone secretion (aldosterone)↓sodium concentration in sweat
• Cold:↑metabolic rate
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Fever
• Fever is an elevation of body temperature due to a “resetting of the thermostat” in the hypothalamus.
• The most common cause of fever is infection, but physical trauma and stress can also induce fever.
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100(Widmaier EP et al., Vander’s Human Physiology, 11st Edition, 2008, Fig. 16-19)
Fever Pathway
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Hyperthermia
• Hyperthermia is defined as an increase in core temperature that does not represent a new set point for control of hypothalamic temperature.
• Exercise increases energy expenditure and heat production, and despite activation of heat loss mechanisms, core temperature increases.
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Factors Affecting Heat Production• Diet-induced thermogenesis: ↑10-20%• Hormones: EP, NE, thyroid hormone• Exercise: ↑voluntary skeletal muscle contraction• Drug-induced malignant hyperthermia: most
common in patients receiving antipsychotic medications (alter brain neurotransmitter levels and can provoke inappropriate catecholamine-induced vasoconstriction and increased heat production)
• Malignant hyperthermia (during anesthesia): rare genetic disorder; muscle rigidity and increased energy expenditure develop from interaction of specific anesthetics with skeletal muscle proteins involved with calcium release and storage
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Comparison of Thermoregulatory Responses to Fever and Exercise at
Matched Core Temperature
(Rhoades R and Pflanzer R, Human Physiology, 4th Edition, 2003, Table 27-5)
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Benefit of Fever
• Antibody production ↑• Inhibits microorganisms growth• Slow the growth of some tumors
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Heat ExhaustionCore temperature ↑
→ vasodilation and sweating ↑→ CO and peripheral resistance ↓→ blood volume, BP & body
temperature↓
Symptoms: dizziness and nausea
Therapy: oral fluid replacement
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Heat stroke• Exposure to hot & humid environment• Conduction and convection of heat from
the skin to the environment decrease(Sweating ↓)
• Body temperature ↑↑↑ ( 41-42℃)• Symptoms: dizziness, abdominal
distress, absence of sweating, delirium, loss of consciousness or death