Physiology 215 Week 14 Notes
Physiology 215 Week 14 Notes phys 215
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This 18 page Class Notes was uploaded by Maddie Butkus on Sunday April 17, 2016. The Class Notes belongs to phys 215 at Ball State University taught by Dr. Kelly-Worden in Summer 2015. Since its upload, it has received 12 views.
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Date Created: 04/17/16
Energy and Heat 50 % of energy is transferred to ATP 50 % is lost as heat Metabolic rate- the rate at which energy is expanded by the body during both external and internal work Metabolic rate = energy expenditure (kcal)/time (hr) Calorie- basic unit of heat, equals the amount of heat necessary o to raise the temperature of 1 gram of water by 1 C 1 kilocalorie (Kcal) = 1000 Calories Basil Metabolic Rate Metabolic activity needed to maintain the body at rest Measured 1. person at rest for at least 30 minutes 2. mental rest, no stress 3. comfortable temperature 4. 12 hours without food Calorimetry Three types of calorimetry; bomb, direct and indirect Indirect calorimetry (respiration calorimetry) Food + O2 à CO2 + H2O + energy - Measures heat production based on gaseous exchange (O2, CO2) - Uses the concept of R.Q., Respiratory quotient, (CO2/O2) - Heat produced is based on caloric equivalent of O2 at a particular RQ - Caloric energy equivalent of O2 = 1L O2 = 4.839 kcal 15 L/hr = O2 consumption X 4.8 kcal = energy equivalent of O2 72 kcal/hr = estimated metabolic rate Hypothalamic Regulation of Body Fat Lipostatic hypothesis- brain monitors the amount of body fat Lateral hypothalamus believed to be in control of feeding Lateral hypothalamic syndrome- anorexia caused by lateral hypothalamic lesion Ventromedial hypothalamus believed to control satiety (feeling of fullness) Ventromedial hypothalamic syndrome- overeating as a result of a lesion to the ventromedial hypothalamus Adipose tissue (fat cells)- release leptin which regulates body mass by acting on neurons of the hypothalamus. Leptin receptors- found in the arcuate nucleus near the base of the third ventricle of the hypothalamus Involvement of Peptide Neurotransmitters Release of peptide neurotransmitters, MSH (- melanocyte-stimulating hormone) and CART (cocaine- and amphetamine-regulated transcript) from the arcuate nucleus Humoral response- activation of neurons in the paraventricular nucleus of the hypothalamus, results in increased secretion of TSH and ACTH from the anterior pituitary, increased metabolic rate of cells in the body Visceromotor response- increase in the tone of the ANS which increases metabolic rate as well in part by raising body temperature Somatic motor response decreases feeding behavior orchestrated by the MSH and CART neurons which project into the spinal cord The Arcuate Nucleus A decrease in leptin stimulates NPY (neuropeptide Y) and AgRP (agouti-related peptide) release from the neurons of the arcuate nucleus NPY and AgRP neurons have connections with the paraventricular nucleus and the lateral hypothalamus inhibit the secretion of TSH and ACTH activate the parasympathetic division of the ANS and stimulate feeding behavior. Both AgRP and MSH both bind the same (MC4) receptor MSH is activating (receptor agonist) AgRP is inhibiting (receptor antagonist) Activation of the MC4 receptor inhibits feeding MCH (melanin- concentrating hormone)- also found in the arcuate nucleus Involved in organization and initiation of goal directed feeding behaviors (going to the fridge) So, a rise in leptin, an increase in MSH and CART, inhibition of feeding, increase in metabolism Glucose and Insulin Rise in glucose Release of insulin from B-cells Cellular uptake and storage of glucose and other nutrients Insulin enhances leptin gene expression Indirectly stimulates leptin release by mediating nutrient transport Cholecystokinin (CCK) Released in the small intestine by chyme that is rich in fat or protein Causes satiety, may act by: Activating CCK A-type receptors on neurons Stimulating enzyme release from the pancreas, facilitating digestion and absorption Stimulation of insulin secretion Obesity Calorie intake exceeds calories burned up Common Psychological Causes Of Obesity: Eating everything on your plate Feeling pressure to eat what has been prepared Eating at a certain time, hungry or not Eating too many tasty foods Depression, anxiety, stress and boredom Physical Causes of Obesity Disturbances in leptin signaling- lack of satiety Lack of exercise Differences in the “fidget factor” (nonexercise activity thermogenisis, NEAT) Differences in extracting energy from food- leaner people use more food energy for heat Hereditary tendencies- differences in energy balance Development of too many fat cells Hypothyroidism- thyroid hormone deficiency Anorexia Nervosa Anorexia nervosa- obsessed with being thin An illness that usually occurs in teenage girls, but it can also occur in teenage boys, and adult women and men. Lose a lot of weight and are terrified of gaining weight. Believe they are fat even though they are very thin. Anorexia isn't just a problem with food or weight, but use of food and weight to deal with emotional problems. May starve themselves to death May have altered hormone secretions, absence of menstrual periods, low body temperature Temperature Regulation Body temperature- 98.6 F or 37 C o Measured in the mouth (oral) or under the armpit o (auxiliary) can range from 96-99.9 F throughout the day Central Core temperature of internal organs, CNS and skeletal muscle is 100 F Core temperature may vary due to exercise, exposure to extreme temperatures, during a woman’s menstrual cycle and naturally due to biological rhythm Hypothermia- too low body temperature, caused by excessive cooling of the body or prolonged exposure to cold Hyperthermia- elevation in core temperature, caused by sustained exercise, high levels of thyroid hormone or epinephrine, damage to control centers in the hypothalamus Heat Exchange For balance heat input should equal heat output Radiation- emission of heat energy from the surface of a body as heat waves (EM waves), when the body is in its resting state, the primary method the body utilizes for discharging extra heat is radiation Conduction- transfer of heat between objects of different temperatures Convection- transfer of heat energy by air currents Evaporation- loss of water from the skin surface resulting in the loss of heat energy needed to convert water into a gas, major heat loss during activity Sweating- evaporative heat loss under sympathetic control Hypothalamic Regulation of Temperature Central thermoreceptors monitor the temperature of the blood as it circulates throughout the brain. sensitive to temperature changes as little as .018°F. Peripheral receptors are located in the skin. These receptors provide the hypothalamus and cerebral cortex with information about external temperature, allowing the individual to perceive temperature so that the he or she can control exposure to heat and cold. Overheating When either the skin or blood is overheated, the hypothalamus will initiate impulses to the sweat glands, instructing them to actively secrete sweat that moistens the skin smooth muscle tissue in the walls of the arterioles that supply the skin with blood, causing them to vasodilate Exposure to Cold (Burrrr) In a cold environment, The peripheral thermoreceptors will relay the signal to the hypothalamus. The central thermoreceptors will also notify the hypothalamus if blood temperature drops below normal. The hypothalamus will activate brain centers that control muscle tone. These centers will stimulate small and rapid neuromuscular reactions (shivering). Shivering increases muscle activity and will generate heat Fever Endogenous pyrogen released form neutrophils Release of prostaglandins Reset of hypothalamic temperature Initiation of cold response Heat production The Digestive System Motility- muscular contractions that mix and move the contents of the digestive tract Secretion- release of digestive juices into the digestive tract Digestion- the biological breakdown of complex food substances Absorption- the movement of substances from the digestive tract into the blood or lymph Food Substances Carbohydrates- neutral compounds of carbon, hydrogen, and oxygen such as sugars, starches, and cellulose Proteins- any of numerous naturally occurring extremely complex substances that consist of amino-acid residues joined by peptide bonds Fats- any substance of plant or animal origin that is nonvolatile, insoluble in water, and oily or greasy to the touch, lipids Carbohydrates End product of carbohydrate breakdown is monosaccharides (glucose, galactose, fructose) Polysaccharides (starch or glycogen) – Broken down by amylase first, then maltase – Disaccharides – Have the ending “ose” – The enzyme that breaks them down will end in “ase” – Example Lactose is broken down by Lactase Proteins Broken down by enzymes that cleave between specific amino acid groups into peptides and amino acids Examples of enzymes that cleave proteins – Chymotrypsin – Carboxypeptidase – Pepsin – Trypsin – Aminopeptidase- an enzyme that cleaves peptides into individual amino acids Fats Trigycerides (lipids) – Broken down by Lipase into monoglycerides and free fatty acids Components of the Digestive System The Mouth Motility- chewing Secretions- in saliva (pH about 6) – Amylase (breaks down starch in sugars) – Mucus – Lysozymes (breaks down cell walls/membranes) – Digestion- carbohydrates Absorption- some medicines – Example; nitroglycerin Pharynx and Esophagus Motility- swallowing Secretion- mucus Exocrine Pancreas Secretion- – Trypsin- stored as trypsinogen until release Activated by enterokinase and trypsin (itself) – Chymotrypsin-stored as chymotrypsinogen Activated by trypsin – Carboxypeptidase- stored as procarboxypeptidase Activated by trypsin – Amylase- secreted in its active form – Lipase- secreted in its active form – Digestion- by these enzymes accomplishes digestion in the duodeum Liver Secretion- Bile – Bile salts (composed of cholesterol related compounds) – Alkaline secretion (bicarbonate solution- buffers acid from the stomach for enzymes to work properly) – Bilirubin Digestion – Bile salts aid in fat digestion Bile Salts Promote Emulsification Bile Salts have both hydrophilic and hydrophobic domains (amphipathic). On exposure to a large aggregates of triglyceride, the hydrophobic portions of bile salts go into the lipid, with the hydrophilic domains remaining at the surface. Such coating with bile salts aids in breakdown of large aggregates or droplets into smaller and smaller droplets (micelles). Roles of the Liver Metabolic processing of nutreints Detoxification or degradation of body wastes and hormones Synthesis of plasma proteins Storage of glycogen Activation of vitamin D (with the kidneys) Removal of bacteria Excretion of cholesterol and bilirubin Small Intestine Motility- segmentation, migrating motility complex Secretions – Mucus – Salt – Digestion- in lumen by pancreatic enzymes and bile, carbohydrates and proteins are digested along with the completion of fat digestion Absorption- all nutrients along with most electrolytes and water The Brush Border Epithelial cells that form the luminal surface of the small intestine Plasma membrane contains 3 types of enzymes – Enterokinase- activates trypsinogen – disaccharidases (maltase, sucrase, and lactase)- carbohydrate digestion – Aminopeptidases- hydrolyze small peptide fragments into amino acids Large Intestine Motility- Haustral contractions, mass movement Secretion- mucus Absorption- salt and water, conversion of contents into feces Autonomous smooth-muscle function Pace setter cells- produce spontaneous, rhythmic, sub-threshold fluctuations in membrane potential – slow wave potentials – basic electrical rhythm (BER) – pacesetter potential slow wave potentials- not action potentials – Do not induce contractions without help – spread to adjacent muscle cells via gap junctions (protein pores) – bring the membrane closer to the threshold potential – caused by cyclic changes in Ca and K currents – rate is characteristic for each organ Smooth Muscle Contraction Depolarization caused by slow wave exceeds threshold for action potential and Ca2+ enters the cell ; voltage-gated Ca channels open Ca inflow depolarizes the membrane, causing an action potential Ca also initiates contraction by binding with calmodulin Relationship between Slow Wave and AP Slow waves are always present in smooth muscle – In the “resting” state, only the slow waves occur Stimulation from nerves or exposure to hormones may result in depolarization to threshold – As the muscle becomes active, action potentials begin to appear on the positive peaks of the slow waves & muscle contraction follows The rate of slow waves will determine the frequency of contractions The number of action potentials on each slow wave peak determines the strength of muscle contraction The Enteric Nervous System Intrinsic Nerve Plexus- relays information to and from the GI tract via the parasympathetic and sympathetic nervous systems - relays information within the GI tract by local reflexes - controls most functions of the GI tract Two parts: a. Myenteric plexus- primarily controls the motility of GI smooth muscles b. Submucosal plexus - primarily controls secretion and blood flow - receives sensory information from chemoreceptors and mechanoreceptors of the GI tract. Extrinsic Nerves (Parasympathetic) In general, excitatory in the GI tract, increases smooth muscle motility and promotes secretion of digestive enzymes carried via vagus and pelvic nerves - preganglionic fibers synapse in the myenteric and submucosal plexuses. - cell bodies in the ganglia of the plexuses send information to the smooth muscle, secretory cells, endocrine cells of the GI tract. Vagus nerve carries information to the esophagus, stomach, pancreas and upper large intestine. The pelvic nerve carries information to the lower large intestine, rectum and anus. Extrinsic Nerves (Sympathetic) Inhibitory, decreases GI motility and secretion Preganglionic cholinergic (achetylcholine secreting) fibers synapse in prevertebral ganglia Postganglionic adrenergic fibers leave the prevertebral ganglia and synapse in the myenteric and submucosal plexuses direct postganglionic adrenergic innervation of blood vessels and some smooth muscles also occurs Enteric Endocrine (Hormone) System More Gastrointestinal Hormones The Stomach Motility- receptive relaxation; peristalis Secretion- gastric juice HCl Pepsin Mucus Intrinsic factor Digestion- continuation of carbohydrate digestion beginning of protein digestion in the antrum of the stomach Absorption of alcohol and aspirin Function of the Stomach Storage of Food in the body Secretion of hydrochloric acid (HCl) and enzymes to begin protein digestion Production of chyme by mixing of the food in the antrum of the stomach The Stomach (Protective Mechanisms) Protected from gastric secretion by the gastric mucosal barrier – Cells are almost impermeable to H+ – Edges of cells form tight junctions, preventing the movement of acid between cells – Lining of stomach is replaced every 3 days Peptic ulcer- breakdown in the barrier and erosion of the stomach wall – Gastric Secretion Gastric mucosa- 2 areas 1. Oxyntic mucosa- lines the body and fundus 1. Pyloric gland area- lines the antrum 2. Gastric pits- foldings in the gastric mucosa containing gastric glands Gastric Secretory Cells Surface epithelial cells- line the walls between the pits and secrete thick mucus Mucus cells- line the gastric pits and gland entrance, secrete watery mucus Chief cells- line the gastric gland and secrete pepsinogen Parietal cells- line the outer wall of the gastic pits, secrete HCl and intrinsic factor All arise from gastric stem cells Receptive Relaxation Empty stomach has deep folds and holds about 50 mL As food fills the stomach the folds get smaller and flatten as the stomach relaxes Full stomach holds about 1 Liter Over eating leads to discomfort from over- distending the stomach. Vomiting Coordinated by a vomiting center in the medulla Achieved by contraction of the diaphragm and abdominal muscles Deep inspiration and closure of the glottis Diaphragm descends down onto the stomach while contraction of the abdominal muscles compresses the abdominal cavity As the stomach is squeezed, the contents move upward through the relaxed sphincters and esophagus and out the mouth Excessive vomiting can lead to dehydration, circulatory problems and metabolic alkalosis Small Intestine Absorption (Carbohydrate Absorption) Remember, disaccharides must first be converted into monosaccharides (glucose, galactose and fructose) Glucose and galactose are taken up by secondary active transport Fructose is taken up by facilitated diffusion Small Intestine Absorption (Protein Absorption) Absorbed as amino acids by secondary active transport Absorbs amino acids from – Food – Digestive enzymes – Cellular protein last during mucosal turnover – Plasma proteins that leak from the capillaries – Fat Absorption Micelle comes into contact with the epithelial surface cells Monoglycerides and fatty acids passively diffuse through the cell membrane (lipid bilayer) The monoglycerides and fatty acids are synthesizes back into triglycerides inside the cells Triglycerides aggregate to form chylomicrons which are extruded from the cell by exocytosis Chylomicrons enter the lymph system because they cannot enter the blood vessels Vitamin Absorption Vitamin B12 requires intrinsic factor for absorption Fat soluble vitamins – Vitamin E is absorbed passively. The vitamin is cleaved by esterases located in the stomach lining. – It is then packaged into very low-density lipoproteins (VLDL) by the addition of lipid-like substances – Water soluble vitamins – Believed to be taken up passively or via transporters Iron Absorption In the United States adults ingest up to 20 mg of iron daily. Of this amount, about 0.5 to 1.0 mg in men, 1.0 to 1.5 mg in women. Iron is taken up by active transport into intestinal epithelial cells Iron in food may exist primarily as inorganic (ferrous) iron and a smaller portion as ferric iron. After uptake by the intestinal cell, iron is stored as protein-bound ferric iron or eventually transferred from the cell. Iron needed for production of red blood cell is transported in the blood by transferin Calcium Absorption Absorption of calcium occurs mainly in the duodenum. Vitamin D facilitates active transport of calcium Vitamin D must first be activated in the liver and kidneys, which is enhanced by parathyroid hormone A decrease in calcium concentration results in the secretion of parathyroid hormone Large Intestine and Bacteria Slow colonic movement so bacteria have time to grow Colon does not secrete antibacterial agents Surviving bacteria thrive and help the body by – Synthesizing vitamin K – Preventing the growth of potentially harmful bacteria – Promoting colonic motility – Maintaining colonic mucosal integrety Diarrhea Helpful in elimination of harmful material Harmful if excessive loss of intestinal contents results in: – Dehydration – Loss of nutrients – Metabolic acidosis The Endocrine System 1. Regulating metabolism and water and electrolyte balance 2. Adaptive changes to help the body cope with stress 3. Growth and development 4. Controlling reproduction 5. Regulating red blood cell production 6. Digestion and absorption Complexity of Hormones A single gland can release multiple hormones A single hormone may be secreted by more than one gland A single hormone can have more than one target A hormone may be released at different rates over time A single target cell may be influenced by more than one hormone Complexity of Hormones (continued) The same chemical messenger may be considered a hormone or a neurotransmitter depending on how it is released and where it acts Some organs only release hormones Classifications of Hormones Protein or Peptide hormones Made from two or more amino acids Majority of all hormones Dissolved in and carried by the plasma Steroid Hormones Made from cholesterol Transported in the plasma bound to plasma proteins Amine Hormones Derived from tyrosine Can be, in the case of catecholamines, both dissolved in plasma and bound to plasma proteins Activation by Hormones Hydrophilic (water loving) hormones Act through second messenger pathways G-protein receptors Lipophilic (lipid loving) hormones Enhance synthesis of enzymatic or structural proteins Act on receptors inside the cell, commonly in the nucleus Hormone with receptor binds to DNA at the “Hormone Response Element” site Binding activates specific genes Protein synthesis begins Improper Hormone Secretion Hyposecretion- decreased release or loss of a particular hormone Treated by replacement therapy Hypersecretion- oversecretion of a given hormone Can be caused by tumors or over stimulation Treated by Surgical removal of the tumor or radiation or chemotherapy Or in the case of over stimulation by drugs that block synthesis or inhibit secretion Pineal Gland Secretes melatonin Circadian rhythm- biological cycle for night and day regulated by the SCN (suprachiasmic nucleus) Melatonin secretion increases at night in the absence of light Induces sleep Inhibits hormones that stimulate reproductive activity Is an antioxidant Enhances the immune system Hypothalamic Hormones TRH-thyrotropin releasing hormone Stimulates release of TSH and prolactin CRH-corticotropin releasing hormone Stimulates release of ACTH GnRH-gonadotropin releasing hormone Stimulates release of FSH and LH GHRH-growth hormone releasing hormone Stimulates release of growth hormone GHIH-growth hormone inhibiting hormone Inhibits the release of growth hormone Hypothalamic Hormones (cont.) PRH- prolactin releasing hormone Stimulates release of prolactin PIH-prolactin inhibiting hormone Inhibits the release of prolactin Hypothalamus and the Pituitary The hypothalamus is directly connected to the posterior pituitary The pituitary has two parts Anterior pituitary (adenohypophysis) which buds off from the roof of the mouth Posterior pituitary (neurohypophysis) which is formed as an outgrowth of the brain The hypothalamus and the posterior pituitary form a neurosecretory system The neurosecretory cell bodies lie in the supraoptic and paraventricular nuclei of the hypothalamus Posterior Pituitary Hormones Made up of the axon terminals of the hypothalamic neurons Stores 2 hormones produced by the hypothalamus Oxytocin- contraction of the uterus during childbirth and ejection of milk from the mammary glands Vasopressin (again!)- aka ADH, enhances retention of water by incorporation of water channels in the distal tubules and collecting ducts and causes contraction of arteriole smooth muscle Hypothalamus and the Anterior Pituitary Hypothalamic hormones enter the hypothalamic capillaries The hypothalamic capillaries rejoin the hypophyseal portal system In the anterior pituitary the hypophyseal portal branches into anterior pituitary capillaries The hormones leave the blood stream and enter the anterior pituitary The hormones interacts with targets and alter the release of hormones stored in the anterior pituitary If the hypothalamic hormone is stimulatory for a given anterior pituitary hormone(s), that hormone(s) is released and travels through the anterior pituitary capillaries that rejoin to form a vein Target Hormones Hormones that are secreted by the pituitary will act on a target gland That gland may also secrete hormones These hormones may produce Negative Feedback They act on a site in the hypothalamus or pituitary to stop the secretion of the hypothalamic or pituitary hormone in the pathway Example: CRH acts on the anterior pituitary à stimulates ACTH secretion à acts at the adrenal cortex to stimulate cortisol secretion à acts at the hypothalamus to stop CRH secretion Anterior Pituitary Hormones Growth Hormone (GH) Responsible for body growth and involved in metabolism Thyroid-stimulating Hormone (TSH) Stimulates release of thyroid hormone and thyroid growth Adrenocorticotropic hormone (ACTH) Stimulates cortisol secretion and promotes growth of the adrenal cortex Anterior Pituitary Hormones (cont.) Follicle-stimulating hormone (FSH) Females- stimulates growth and development of the ovarian follicles and promotes secretion of estrogen by the ovaries Males- sperm production Luteinizing hormone (LH) Females- ovulation and luteinization (we will discuss this in the next chapter) and regulates secretion of estrogen and progesterone Males- secretion of testosterone from the Leydig cells of the testes Prolactin (PRL) Females- production of milk and development of the breasts Growth Genetic determination Adequate diet Health Emotional balance cortisol released from prolonged stress inhibits growth by blocking secretion of GH and breaking down proteins Hormone balance Rapid Growth Periods Fetal growth is dependent on placental hormones GH acts only after birth Postnatal growth spurt- first 2 years of life Pubertal growth spurt- during adolescence Increased release of GH Lengthening of the long bones Increase in androgen release (testosterone) Promotion of protein synthesis Testosterone and estrogen halt bone growth by the end of puberty Actions of GH Direct effect- binds it’s receptor at the target cell GH receptors on adipose tissue promoting the breakdown of triglycerides into fatty acids Indirect effect- binds a receptor on the liver or other tissue which generally releases IGF-1 (insulin growth factor 1) which acts at the target tissue GH and Growth The major role of growth hormone in stimulating body growth is to stimulate the liver and other tissues to secrete IGF-1. IGF-1 stimulates proliferation of chondrocytes (cartilage cells), resulting in bone growth. Growth hormone does seem to have a direct effect on bone growth in stimulating differentiation of chondrocytes. IGF-1 also appears to be the key player in muscle growth. stimulates both the differentiation and proliferation of myoblasts. stimulates amino acid uptake and protein synthesis in muscle and other tissues. Bone Development Bones grow in length at the epiphyseal plate Cartilage in the region of the epiphyseal plate next to the epiphysis continues to grow by mitosis. The chondrocytes, in the region next to the diaphysis, age and degenerate. Osteoblasts move in and ossify the matrix to form bone. The process continues throughout childhood and the adolescent years until the cartilage growth slows and finally stops. Metabolic Effects of GH Protein metabolism: Increased amino acid uptake Protein synthesis Fat metabolism: Stimulates triglyceride breakdown in adipocytes Increases free fatty acids Carbohydrate metabolism: Maintains blood glucose within a normal range Suppresses the abilities of insulin to stimulate uptake of glucose in peripheral tissues Saves glucose for the brain Enhances glucose synthesis in the liver Control of GH Secretion Growth hormone-releasing hormone (GHRH) stimulates both the synthesis and secretion of growth hormone. GHIH (Somatostatin; SS) inhibits growth hormone release in response to GHRH and to other stimulatory factors such as low blood glucose concentration. Ghrelin (peptide hormone secreted from the stomach). binds receptors and potently stimulates secretion of growth hormone. Abnormal GH Secretion Deficiency in growth hormone or receptor defects Growth retardation or dwarfism Short stature due to retarded skeletal growth Poorly developed musculature and excess fat Excessive secretion of growth hormone- two distinctive disorders: Giantism- excessive growth hormone secretion that begins in young children or adolescents. very rare disorder, usually resulting from a tumor One of the most famous giants was a man named Robert Wadlow. He weighed 8.5 pounds at birth, but by 5 years of age was 105 pounds and 5 feet 4 inches tall. Robert reached an adult weight of 490 pounds and 8 feet 11 inches in height. He died at age 22. Acromegaly- excessive secretion of growth hormone in adults. overgrowth of bone and connective tissue leads to a change in appearance, obvious in the face . excessive growth hormone and IGF-1 also lead to metabolic derangements, including glucose intolerance.
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