The Endocrine System - Advanced Anatomy & Physiology - PDF

The Endocrine System Advanced Anatomy & Physiology The Endocrine System Chapter 21 (McCance-Heuther) Dr. Joseph Curione 17-1 Endocrine System Overview Hypothalamus and pituitary gland Other endocrine glands Hormones and their actions Stress and adaptation Eicosanoids and paracrine signaling Endocrin...

The Endocrine System Advanced Anatomy & Physiology The Endocrine System Chapter 21 (McCance-Heuther) Dr. Joseph Curione 17-1 Endocrine System Overview Hypothalamus and pituitary gland Other endocrine glands Hormones and their actions Stress and adaptation Eicosanoids and paracrine signaling Endocrine disorders 17-2 Overview 17-3 Overview of Cell Communications Includes both endocrine and nervous systems Necessary for integration of cell activities Mechanisms of communication via: – gap junctions pores in cell membrane allow signaling chemicals to move from cell to cell – neurotransmitters released from neurons to travel across gap to 2nd cell – hormones chemical messengers that travel in the bloodstream – paracrine (local) hormones secreted into interstitial fluid to affect nearby cells 17-4 Endocrine System Components Hormone – chemical messenger secreted into bloodstream, stimulates response in another tissue or organ Target cells – have receptors for hormone Endocrine glands – produce hormones Endocrine system – endocrine organs (thyroid, pineal, etc) – hormone producing cells in organs (brain, heart and small intestine) 17-5 Endocrine vs. Exocrine Glands Exocrine glands – secrete their products through a duct and onto an open surface or organ cavity – extracellular effects (food digestion) Endocrine glands – Secrete their products directly into the bloodstream, no ducts – intracellular effects, alter target cell metabolism 17-6 Nervous vs. Endocrine Systems Communication – nervous - both electrical and chemical – endocrine - only chemical Speed and persistence of response – nervous - reacts quickly (1 - 10 msec), stops quickly – endocrine - reacts slowly (hormone release in seconds or days), effect may continue for weeks Adaptation to long-term stimuli – nervous - response declines (adapts quickly) – endocrine - response persists Area of effect – nervous - targeted and specific (one organ) – endocrine - general, widespread effects (many organs) 17-7 Communication by the Nervous and Endocrine Systems 17-8 Nervous and Endocrine Systems Several chemicals function as both hormones and neurotransmitters – NE, cholecystokinin, thyrotropin-releasing hormone, dopamine and ADH Some hormones secreted by neuroendocrine cells (neurons) – oxytocin and catecholamines Both systems with overlapping effects on same target cells – NE and glucagon cause glycogenolysis in liver Systems can regulate each other – neurons can trigger hormone secretion – hormones can stimulate or inhibit neurons 17-9 Hypothalamus Shaped like a flattened funnel, forms floor and walls of third ventricle Regulates homeostasis mechanisms and some endocrine functions 17-10 Pituitary Gland Hypophysis Suspended from hypothalamus by stalk (infundibulum) – housed in sella turcica of sphenoid bone – 1.3 cm diameter Anterior pituitary (Adenohypophysis) – arises from hypophyseal pouch (outgrowth of pharynx) Posterior pituitary (Neurohypophysis) – arises from brain 17-11 Embryonic Development 17-12 Histology of Pituitary Gland “Adenohypophysis” “Neurohypophysis” 17-13 Pituitary Gland Anatomy and Hormones of Neurohypophysis 17-14 Hypothalamo-Hypophyseal Portal System 17-15 Control of Pituitary: Hypothalamic and Cerebral Control Anterior lobe control - releasing hormones and inhibiting hormones of hypothalamus Posterior lobe control - neuroendocrine reflexes – hormone release in response to nervous system signals suckling infant® stimulates nerve endings ® hypothalamus ® posterior lobe ® oxytocin ® milk ejection – hormone release in response to higher brain centers milk ejection reflex can be triggered by a baby's cry 17-16 Control of Pituitary: Feedback from Target Organs Negative feedback – ­ target organ hormone levels inhibits release of tropic hormones Positive feedback stretching of uterus ­ OT release, causes more contraction/ stretching of uterus, until delivery 17-17 Pituitary Hormones - Anterior Lobe Tropic hormones target other endocrine glands – gonadotropins target gonads FSH (follicle stimulating hormone) LH (luteinizing hormone) – TSH (thyroid stimulating hormone) – ACTH (adrenocorticotropic hormone) PRL (prolactin) GH (growth hormone) 17-18 Anterior Pituitary Hormones Principle hormones and target organs shown Axis - refers to way endocrine glands interact 17-19 Anterior Pituitary Hormones FSH – stimulates production of egg or sperm cells LH – mainly stimulates hormone production females - stimulates ovulation and secretion of Estrogen and Progesterone males – stimulates testes to secrete Testosterone TSH – stimulates growth of the thyroid and secretion of thyroid hormones 17-20 Anterior Pituitary Hormones ACTH (Adrenocorticotropic Hormone) – regulates response to stress, stimulates adrenal cortex corticosteroids regulate glucose, fat and protein metabolism Prolactin (prolactin-releasing factor from hypothalamus stimulates its release) – female - milk synthesis after delivery – male - ­ LH sensitivity and ­ testosterone secretion 17-21 GH (Growth Hormone) a.k.a. somatotropin Secreted by anterior pituitary Promotes tissue growth – mitosis and cellular differentiation – stimulates liver to produce IGF-I and II ­ protein synthesis – ­ DNA transciption for ­ mRNA production, proteins synthesized – enhances amino acid transport into cells, ¯ protein catabolism ­ lipid metabolism – stimulates FFA and glycerol release from adipocytes, protein sparing ­ CHO metabolism – glucose sparing effect = less glucose used for energy Electrolyte balance – promotes Na+, K+, Cl- retention, Ca 2+ absorption 17-22 Growth Hormone and Aging Childhood and adolescence – bone, cartilage and muscle growth – Stimulates growth at epiphyseal plates Adulthood – increase osteoblastic activity and appositional growth affecting bone thickening and remodeling – blood concentration decrease by age 75 to ¼ of that of adolescent Levels of GH (fluctuates throughout day) – higher during deep sleep, after high protein meals, after vigorous exercise – lower after high CHO meals 17-23 Posterior Pituitary Hormones (produced by hypothalamus) ADH – targets kidneys ­ water retention, reduce urine – also functions as neurotransmitter Oxytocin – Causes uterine contractions and milk ejection (let-down) [GnRH (Gonadotropin-releasing hormone) stimulates production of FSH and LH] 17-24 Pineal Gland Peak secretion ages 1-5; by puberty 75% lower Produces serotonin by day, converts it to melatonin at night Melatonin ­ in SAD + PMS; ¯ by phototherapy – depression, sleepiness, irritability and carbohydrate craving 17-25 Thymus Located in mediastinum, superior to heart Involution after puberty Secretes hormones that regulate development and later activation of Tlymphocytes Tcells become immunocompetent 17-26 Thyroid Gland Anatomy Fig. 17.9a Largest endocrine gland; high rate of blood flow – arises root of embryonic tongue Anterior and lateral sides of trachea – two large lobes connected by isthmus 17-27 Thyroid Hormones T3 (triiodothyronine) T4 (tetraiodothyronine) produced by thyroid follicles - filled with colloid and lined with simple cuboidal epithelial “follicular cells” ­ body’s metabolic rate, O2 consumption calorigenic effect - ­ heat production ­ heart rate and contraction strength ­ respiratory rate stimulates appetite and breakdown CHO, lipids and proteins Calcitonin produce by parafollicular “c” cells ¯ blood Ca2+ , promotes Ca2+ deposition, antagonistic to parathyroid hormone 17-28 Histology of the Thyroid Gland 17-29 Parathyroid Glands Parathyroid hormone: (PTH) – ­ blood Ca2+ levels 3 ways: ­ absorption of Ca2+ ¯ urinary excretion ­ bone resorption – promotes synthesis of calcitriol 17-30 Adrenal Gland 17-31 Adrenal Cortex 3 Layers – zona glomerulosa (outer) – zona fasciculata (middle) – zona reticularis (inner) 17-32 Adrenal Cortex Corticosteroids – Zona Glomerulosis produces mineralocorticoids control electrolyte balance, aldosterone promotes Na+ retention, water reabsorption and K+ excretion – Zona Fasiculata produces glucocorticoids especially cortisol, stimulates fat and protein catabolism, gluconeogenesis (from a.a.’s and FA’s) and ¯ lipogenesis (release of fatty acids and glucose into blood) anti-inflammatory effect; immunosuppressive long-term – Zona reticularis (sex hormones) androgens (including DHEA which other tissues convert to testosterone) and estrogen (important after menopause) 17-33 Adrenal Medulla Sympathetic ganglion innervated directly by sympathetic preganglionic fibers – consists of modified neurons called chromaffin cells – stimulation causes release of “catecholamines” (epinephrine, NE) Hormonal effect is longer lasting – Increases alertness, anxiety, or fear – increases BP, heart rate and air flow – raises metabolic rate inhibits insulin secretion stimulates gluconeogenesis and glycogenolysis Stress causes medullary cells to stimulate cortex 17-34 Adrenal Medulla Tumor Pheochromocytomas – caused by tumors derived from the chromaffin cells of the adrenal medulla. – Secrete catecholamines. – Clinical manifestations Hypertension, diaphoresis, tachycardia, palpitations, and severe headache 17-35 Pancreas Is both exocrine and endocrine 17-36 Endocrine tissue of Pancreas Clusters of endocrine cells called “Islets of Langerhans” The islets include 4 types of cells that secrete different hormones: – Alpha (a) cells - glucagon – Beta (b) cells - insulin – Delta (d) cells - somatostatin – F cells - pancreatic polypeptide 17-37 Pancreatic Hormones 1-2 million islets produce hormones – 98% of organ produces digestive enzymes (exocrine) Insulin (from b cells) – secreted after meal with carbohydrates that raise glucose blood levels – stimulates glucose & amino acid uptake – nutrient storage effect (promotes glycogenesis and lipogenesis) – antagonizes glucagon 17-38 Pancreatic Hormones Glucagon (from a alpha cells) – secreted when blood glucose is low, acts on liver cells to release glycogen, increases blood sugar – stimulates glycogenolysis, fat catabolism (release of FFA’s) and promotes absorption of amino acids for gluconeogenesis Somatostatin (from delta (d) cells) – secreted with rise in blood glucose and amino acids after a meal, inhibits GH – paracrine secretion = inhibits secretion of insulin, glucagon by a and b cells 17-39 Pancreatic Hormones Hyperglycemic hormones raise blood glucose – GH, epinephrine, NE, cortisol and corticosterone Hypoglycemic hormones lower blood glucose – insulin 17-40 Endocrine Functions of Other Organs Heart – – atrial natriuretic peptide released with an increase in BP – ¯ blood volume and ¯ BP by ­ Na+ and H2O loss by kidneys Skin - helps produce D3 Liver – 15% of erythropoietin (stimulates bone marrow) – angiotensinogen (a prohormone) precursor of angiotensin II – source of IGF-I (works with GH) – converts vitamin D3 to calcidiol – Hepcidin – inhibits intestinal absorption of iron into 17-41 bloodstream Endocrine Functions of Other Organs Kidneys – produces 85% of erythropoietin – stimulates bone marrow to produce RBC’s – Renin converts angiotensinogen to angiotensin I – converts calcidiol to calcitriol (active form of vitamin D) ­ absorption by intestine and inhibits loss in the urine more Ca2+ available for bone deposition Stomach and small intestines (10 enteric hormones) – coordinate digestive motility and secretion Placenta – secretes estrogen, progesterone and others regulate pregnancy, stimulate development of fetus and mammary glands 17-42 Fat soluble vs Water soluble Steroids – derived from cholesterol: – sex steroids, corticosteroids Peptides and glycoproteins – OT, ADH; all releasing and inhibiting hormones of hypothalamus; most of anterior pituitary hormones Monoamines (biogenic amines) – derived from amino acids catecholamines (norepinephrine, epinephrine, dopamine) and thyroid hormones 17-43 Oxytocin and ADH 17-44 Hormone Synthesis: Steroid Hormones Synthesized from cholesterol – differs in functional groups attached to 4-ringed steroid backbone 17-45 Hormone Synthesis: Peptides Cellular steps – RER removes segment, forms prohormone – Golgi complex further modifies it into hormone – e.g. insulin formation preproinsulin converted to proinsulin in RER proinsulin split into insulin and C peptide in golgi complex 17-46 Hormone Synthesis: Monoamines All are synthesized from tyrosine – except melatonin which is synthesized from tryptophan Thyroid hormone is unusual – composed of two tyrosine molecules – requires a mineral, iodine 17-47 Thyroid Hormone Synthesis Fig. 17.18 17-48 T3 and T4 Synthesis Follicular cells – absorb I- from blood and store in lumen as I– synthesize thyroglobulin and store in lumen contains tyrosine – tyrosine and Iodine form T3 and T4 TSH – stimulates follicular cells to remove T3 and T4 from thyroglobulin for release into plasma 17-49 Chemistry of Thyroid Hormone Fig. 17.19 MIT contains one iodine atom, DIT has two T3 = combination of MIT plus DIT T4 = combination of two DITs 17-50 Hormone Transport Monoamines and peptides are hydrophilic – protein hormones are transported in the bloodstream, transported free unbound as water soluble form Steroids and thyroid hormone are hydrophobic – must bind to transport proteins for transport – bound hormone - attached to transport protein, prolongs half-life to weeks protects from enzymes and kidney filtration – unbound hormone leaves capillary to reach target cell (half-life a few minutes) Transport proteins in blood plasma – albumin, and TGB (thyroxine binding globulin) bind to thyroid hormone – steroid hormones bind to globulins (ex. transcortin) 17-51 – aldosterone - no transport protein, 20 min. half-life Hormone Receptors Located on plasma membrane, mitochondria, other organelles, or in nucleus Usually thousands for given hormone – hormone binding turns metabolic pathways on or off 17-52 Hormone Mode of Action Hydrophobic hormones – penetrate plasma membrane – bind to intracellular receptors ie. Estrogen, T3, aldosterone Hydrophilic hormones – must bind to cellsurface receptors ie. epinephrine 17-53 Thyroid Hormone Effects TH binds to receptors on – mitochondria ­ rate of aerobic respiration – ribosomes and chromatin ­ protein synthesis Na+-K+ ATPase produced – generates heat 17-54 Hydrophilic Hormones: Mode of Action cAMP as Second Messenger ie. epinephrine 1) Hormone binding activates G(s) protein 2) Activates adenylate cyclase 3) Produces cAMP 4) Activates kinases 5) Activates enzymes 6) Metabolic reactions: – synthesis – secretion – change membrane potentials 17-55 Hydrophilic Hormones: Mode of Action Other 2nd and 3rd Messengers Hormones may use different second messengers in different tissues. (G coupled proteins) 17-56 G-coupled protein examples alpha 1 - Gq - PLC - PIP2 - DAG - (PKC - phosphorylates prots./enzymes); IP3 - in sm. mscle. - S.R.incrs. Ca++ - binds to Calmodulin - inhibits calponin & caldesmon; Calmodulin activates MLCK - phosphorylates Myosin = smooth mscle. contraction alpha 2 - Gi - inhibits A.C. (adenylyl cyclase) - dcrs. cAMP - dcrs. PKA - decrs. Ca++ influx = inhibitory; incrs. K+ efflux = hyperpolarizes cell = inhibitory beta 1 - Gs - stim. A.C. (adenylyl cyclase) - icrs. cAMP - incrs. PKA - incrs. Ca++ influx = excitatory; decrs. K+ efflux beta 2 - Gs - stim. A.C. (adenylyl cyclase) - icrs. cAMP - - in sm. mscle. inhibits MLCK = decrs. phosphorylation of myosin = inhibitory = smooth mscle. relaxation 17-57 Enzyme Amplification 17-58 Hormone Clearance Hormone signals must be turned off Hormones degraded by liver and kidney Excreted in bile or urine Varies w/ Metabolic clearance rate (MCR) “Half-life” - time required to clear 50% of hormone 17-59 Modulation of Target Cell Sensitivity Long-term high levels (ex. Insulin) can lead to down-regulation 17-60 Hormone Interactions Most cells sensitive to more than one hormone and exhibit interactive effects Synergistic effects (epi & NE) Permissive effects – one hormone enhances response to a second hormone Antagonistic effects (PTH & Calcitonin) 17-61 Stress and Adaptation Stress – caused by any situation that upsets homeostasis and threatens one’s physical or emotional well-being General adaptation syndrome – way body reacts to stress – occurs in 3 stages 1. alarm reaction 2. stage of resistance 3. stage of exhaustion 17-62 Alarm Reaction Initial response ­ epinephrine and norepinephrine levels ­ HR and ­ BP ­ blood glucose levels Sodium and water retention (aldosterone) 17-63 Stage of Resistance glycogen reserves later depleted ­ ACTH and cortisol levels Fat and protein breakdown Gluconeogenesis = ­ sugar Long term effects: – Depressed immune function – Susceptibility to infection and ulcers 17-64 Stage of Exhaustion Stress that continues until fat reserves are gone Protein breakdown and muscle wasting Loss of glucose homeostasis Hypertension and electrolyte imbalances (loss of K+ and H+) Hypokalemia and alkalosis leads to death – severe metabolic alkalosis secondary to glucocorticoid-induced excessive mineralocorticoid activity 17-65 Paracrine Secretions Chemical messengers that diffuse short distances and stimulate nearby cells – unlike neurotransmitters not produced in neurons – unlike hormones not transported in blood Examples and their functions – histamine from mast cells in connective tissue causes relaxation of blood vessel smooth muscle – nitric oxide from endothelium of blood vessels, causes vasodilation – somatostatin from delta cells, inhibits secretion of alpha and beta cells – catecholamines diffuse from adrenal medulla to cortex 17-66 Eicosanoids: a Paracrine Secretion Leukotrienes – converted from arachidonic acid (by lipoxygenase) – mediates allergic and inflammatory reactions Prostacyclin (by cyclooxygenase) – inhibits blood clotting and vasoconstriction Thromboxanes (by cyclooxygenase) – produced by blood platelets after injury; override prostacyclin, stimulates vasoconstriction and clotting Prostaglandins (by cyclooxygenase): diverse; includes – PGE: relaxes smooth muscle in bladder, intestines, bronchioles, uterus and stimulates relaxation of blood vessels (Gs) – PGE2 can be both vasodilatory & constrictive depending on which E-Prostinoid receptor it binds to (EP1/3 = Gq; EP2/4=Gs) – PGF: opposite effects (Gq) 17-67 Eicosanoid Synthesis 17-68 Endocrine Disorders Too Much or Too Little Hormone Variations in hormone concentration and target cell sensitivity have noticeable effects on body Hyposecretion – inadequate hormone release – tumor or lesion destroys gland head trauma affects pituitary gland’s ability to secrete ADH – diabetes insipidus = chronic polyuria Hypersecretion – excessive hormone release – tumors or autoimmune disorder toxic goiter (graves disease) – antibodies mimic effect of TSH 17-69 on the thyroid Pituitary Disorders Hypersecretion of growth hormones – acromegaly – thickening of the bones and soft tissues – problems in childhood or adolescence gigantism if oversecretion dwarfism if hyposecretion 17-70 Acromegaly vs Giantism 17-71 Thyroid Gland Disorders Congenital hypothyroidism (¯ TH) cretinism – infant suffers abnormal bone development, thickened facial features, low temperature, lethargy, brain damage Myxedema (adult hypothyroidism, ¯ TH) – low metabolic rate, sluggishness, sleepiness, weight gain, bradycardia, constipation, dry skin and hair, cold sensitivity, ­ blood pressure and tissue swelling Endemic goiter (goiter = enlarged thyroid gland) – dietary iodine deficiency, no TH, no - feedback, ­ TSH Toxic goiter (Graves disease) – antibodies mimic TSH, ­TH, exophthalmos 17-72 Hypothyroidism Same patient Before and After treatment 17-73 Goiter from iodine deficiency 17-74 Toxic Goiter “Graves Disease” with exopthalmos 17-75 Hyperthyroidism Hyperthyroidism: Thyrotoxicosis – Is a condition that results from any cause of increased level of thyroid hormone. – Excess amounts of thyroid hormone are secreted from the thyroid gland. – Clinical manifestations Increased metabolic rate with heat intolerance and increased tissue sensitivity to stimulation by the sympathetic nervous system; enlargement of the thyroid gland (goiter) – Treatment Methimazole or propylthiouracil: Antithyroid drugs Radioactive iodine therapy Surgery 17-76 Parathyroid Disorders Hypoparathyroid – surgical excision during thyroid surgery – fatal tetany 3-4 days Hyperparathyroid = excess PTH secretion – tumor in gland – causes soft, fragile and deformed bones – ­ blood Ca2+ – renal calculi 17-77 Adrenal Disorders Cushing syndrome - excess cortical secretion – hyperglycemia, hypertension, weakness, edema – muscle and bone loss occurs with protein catabolism – buffalo hump and moon face = fat deposition between shoulders or in face Adrenogenital syndrome (AGS) – adrenal androgen hypersecretion; accompanies Cushing – enlargement of external sexual organs in children and early onset of puberty – masculinizing effects on women (deeper voice and beard growth) 17-78 Cushing’s Syndrome Same patient Before and After Treatment 17-79 Diabetes Mellitus Signs and symptoms of hyposecretion of insulin – polyuria, polydipsia, polyphagia – hyperglycemia, glycosuria, ketonuria – osmotic diuresis blood glucose levels rise above transport maximum of kidney tubules, glucose remains in urine (ketones also present) increased osmolarity draws water into urine 17-80 Types of Diabetes Mellitus Type I (IDDM) - 10% of cases – some cases have autoimmune destruction of b cells, diagnosed about age 12 – treated with diet, exercise, monitoring of blood glucose and periodic injections of insulin Type II (NIDDM) - 90% – insulin resistance failure of target cells to respond to insulin – 3 major risk factors are heredity, age (40+) and obesity – treated with weight loss program of diet and exercise – oral medications improve insulin secretion or target cell sensitivity 17-81 Pathology of Diabetes Acute pathology: cells cannot absorb glucose, rely on fat and proteins (weight loss, weakness) – fat catabolism ­ FFA’s in blood and ketone bodies – ketonuria promotes osmotic diuresis, loss of Na+ and K+ – ketoacidosis occurs as ketones ¯ blood pH if continued causes dyspnea and eventually diabetic coma Chronic pathology – chronic hyperglycemia leads to neuropathy and cardiovascular damage from atherosclerosis retina and kidneys (common in type I), atherosclerosis leads to heart failure (common in type II), and gangrene 17-82 Hyperinsulinism From excess insulin injection or pancreatic islet tumor Causes hypoglycemia, weakness and hunger – triggers secretion of epinephrine, GH and glucagon side effects: anxiety, sweating and ­ HR Insulin shock – uncorrected hyperinsulinism with disorientation, convulsions or unconsciousness 17-83