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The Peripheral Endocrine Glands

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1 The Peripheral Endocrine Glands
Chapter 19 The Peripheral Endocrine Glands Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning

2 Peripheral Endocrine Glands
Outline Thyroid glands Anatomy and hormones Adrenal glands Stress response Fuel metabolism Calcium metabolism Pancreas

3 Arranged into hollow spheres Forms functional unit called a follicle
Follicular cells Arranged into hollow spheres Forms functional unit called a follicle Lumen filled with colloid Serves as extracellular storage site for thyroid hormone Produce two iodine-containing hormones derived from amino acid tyrosine Tetraiodothyronine (T4 or thyroxine) Tri-iodothyronine (T3) C cells Secrete peptide hormone calcitonin Figure 19.1: Anatomy of the thyroid gland. (b) Light-microscope appearance of the thyroid gland. The thyroid gland is composed primarily of colloid-filled spheres enclosed by a single layer of follicular cells. Fig. 19-1b, p. 684

4 Thyroid hormone synthesis and release
Tg = thyroglobulin Transport of Tg to colloid Iodine uptake to colloid Iodination of tyrosine Coupling Release Stored as Tg Phagocytes “bite” Tg containing colloid Phagocytes cleave T3 and T4 from Tg in the follicular cells T3 and T4 diffuse to blood (TBG carrier protein in blood) Iodine is recycled after metabolism Activity 90% T4 but T3 is 4X as potent

5 *Endoplasmic Colloid Blood Thyroid follicular cell reticulum/Golgi
complex Lysosome DIT = Di-iodotyrosine T3 = Tri-iodothyronine T4 = Tetraiodothyronine (thyroxine) TGB = Thyroglobulin I = Iodine MIT = Monoiodotyrosine Fig. 19-2, p. 685

6 Thyroid Gland Effects of thyroid hormone
Main determinant of basal metabolic rate and heat production Influences synthesis and degradation of carbohydrate, fat, and protein (intermediary metabolism) Increases target-cell responsiveness to catecholamines (sympathomimetic effect) Increases heart rate and force of contraction Essential for normal growth Plays crucial role in normal development of skeleton and nervous system (stimulates GH and IGF-1)

7 Thyroid Gland Secretion
Regulated by negative-feedback system between hypothalamic TRH, anterior pituitary TSH, and thyroid gland T3 and T4 Feedback loop maintains thyroid hormones relatively constant

8 Stress Cold in infants Hypothalamus Anterior pituitary Thyroid gland
Thyrotropin- releasing hormone (TRH) Anterior pituitary Thyroid-stimulating hormone (TSH) Thyroid gland Thyroid hormone (T3 and T4) Metabolic rate and heat production; enhancement of growth and CNS development; enhancement of sympathetic activity Fig. 19-3, p. 687

9 Thyroid Gland Dysfunction
Table 19-1, p. 687

10 Thyroid Gland Abnormalities Hyperthyroidism
Most common cause is Graves’ disease Autoimmune disease Body erroneously produces thyroid-stimulating immunoglobulins (TSI) Characterized by exopthalmos Treatment Surgical removal of a portion of the over-secreting thyroid Administration of radioactive iodine Use of antithyroid drugs

11 Graves disease Antibody that binds TSH receptors no negative FB
Figure 19.4: Role of long-acting thyroid stimulator in Graves’ disease. Long-acting thyroid stimulator (LATS), an antibody erroneously produced in the autoimmune condition of Graves’ disease, binds with the TSH receptors on the thyroid gland and continuously stimulates thyroid hormone secretion outside the normal negative-feedback control system. Fig. 19-4, p. 688

12 Hyperthyroidism - exopthalmos
Hypothyroidism Goiter Hyperthyroidism - exopthalmos Figure 19.5: Patient displaying exophthalmos. Abnormal fluid retention behind the eyeballs causes them to bulge forward. Fig. 19-5, p. 688

13 Thyroid Gland Abnormalities Hypothyroidism Causes Cretinism Myxedema
Primary failure of thyroid gland Secondary to a deficiency of TRH, TSH, or both Inadequate dietary supply of iodine Cretinism Results from hypothyroidism from birth Myxedema Term often used for myxedema in adults Treatment Replacement therapy Dietary iodine

14 Anatomy Adrenal cortex Adrenal medulla Zona glomerulosa Cortex
Zona fasciculata (See next slide) Zona reticularis Medulla Adrenal gland Embedded above each kidney in a capsule of fat Composed of two endocrine organs Adrenal cortex Outer portion Secretes steroid hormones Adrenal medulla Inner portion Secretes catecholamines

15 Adrenal Glands Adrenal cortex Consists of three layers or zones
Zona glomerulosa Zona fasciculata (See next slide) Zona reticularis Adrenal cortex Consists of three layers or zones Zona glomerulosa – outermost layer (Mineralocorticoids) Zona fasciculata – middle and largest portion (Glucocorticoids) Zona reticularis – innermost zone (Sex hormones) Categories of adrenal steroids Mineralocorticoids Mainly aldosterone Influence mineral balance, specifically Na+ and K+ balance Glucocorticoids Primarily cortisol Major role in glucose metabolism as well as in protein and lipid metabolism Sex hormones Identical or similar to those produced by gonads Most abundant and physiologically important is dehydroepiandosterone (male “sex” hormone) Medulla

16 Effects of Adrenal Cortical Hormones
Permissive actions on catecholamines Stress adaptation (releases building blocks of new tissue) Anti-inflamatory and immunosuppressive

17 POMC Stress Diurnal rhythm Hypothalamus Anterior pituitary
Corticotropin-releasing hormone (CRH) Anterior pituitary Adrenocorticotropic hormone (ACTH) POMC Adrenal cortex Cortisol Blood glucose (by stimulating gluconeogenesis and inhibiting glucose uptake) Metabolic fuels and building blocks available to help resist stress Blood amino acids (by stimulating protein degradation) Blood fatty acids (by stimulating lipolysis) Fig. 19-8, p. 692

18 Adrenal Glands Cortisol Stimulates hepatic gluconeogenesis
Zona fasciculata – middle and largest portion (Glucocorticoids) Stimulates hepatic gluconeogenesis Inhibits glucose uptake and use by many tissues, but not the brain Stimulates protein degradation in many tissues, especially muscle Facilitates lipolysis Plays key role in adaptation to stress At pharmacological levels, can have anti-inflammatory and immunosuppressive effects Long-term use can result in unwanted side effects Displays a characteristic diurnal rhythm (day hi night low) Secretion Regulated by negative-feedback loop involving hypothalamic CRH and pituitary ACTH

19 Adrenal Glands Secretes both male and female sex hormones in both sexes Dehydroepiandrosterone (DHEA) Zona reticularis – innermost zone (Sex hormones) Only adrenal sex hormone that has any biological importance Overpowered by testicular testosterone in males Physiologically significant in females where it governs Growth of pubic and axillary hair Enhancement of pubertal growth spurt Development and maintenance of female sex drive

20 Adrenal Glands Aldosterone Secretion is increased by
Zona glomerulosa – outermost layer (Mineralocorticoids) Secretion is increased by Activation of renin-angiotensin-aldosterone system by factors related to a reduction in Na+ and a fall in blood pressure Direct stimulation of adrenal cortex by rise in plasma K+ concentration Regulation of aldosterone secretion is largely independent of anterior pituitary control


22 Adrenal Medulla Modified part of sympathetic nervous system
Primary stimulus for increased adrenomedullary secretion activation of sympathetic nervous system by stress Releases epinephrine and norepinephrine Secreted into blood by exocytosis of chromaffin granules Vary in their affinities for the different adrenergic receptor types Epinephrine Reinforces sympathetic system in mounting general systemic “fight-or-flight” responses Maintenance of arterial blood pressure Increases blood glucose and blood fatty acids

23 Table 19-2, p. 697

24 fig 10-6, pg 343 Receptor type CNS PNS target cells Nicotinic
Alpha-receptors Beta receptors Muscarinic Somatic Preganglionic Postaganglionic Autonomic parasympathetic Autonomic sympathetic Norephinephrine Epinephrine Acetylcholine Autonomic sympathetic Autonomic paraysmpathetic Brainstem Nicotinic Cervical Somatic alpha-motor neuron Adrenal gland Skeletal muscle NE (15%) Blood stream Alpha E (85%) Thoracic Chromaffin cell Autonomic sympathetic Sympathetic ANS Beta Autonomic sympathetic Ganglia Lumbar Muscarinic Sacral Autonomic parasympathetic fig 10-6, pg 343 Parasympathetic ANS

25 Stress Response Pattern of reactions to a situation that threatens homeostasis Stress Generalized nonspecific response of body to any factor that overwhelms or threatens to overwhelm the body’s ability to maintain homeostasis Stressor Any noxious stimulus that brings about the stress response

26 General Adaptation Syndrome
Alarm reaction- fight or flight response,muscles tense, HR and BP increase Resistance or adaptation-nervous and endocrine systems deal with stressor. dangerous if long term. Exhaustion-resistance drops, immunity suppression, depletion of energy reserves, stress related disease.

27 Stressor Hypothalamus CRH Posterior pituitary Anterior pituitary ACTH
Sympathetic nervous system Anterior pituitary ACTH Vasopressin Adrenal medulla Activation of sympathetic nervous system accompanied by epinephrine secretion Prepares body for fight-or-flight response Adrenal cortex Epinephrine Cortisol Activation of CRH-ACTH-cortisol system Helps body cope by mobilizing metabolic resources Glucagon-secreting cells Insulin-secreting cells Endocrine pancreas Arteriolar smooth muscle Vasoconstriction Glucagon Insulin Elevation of blood glucose and fatty acids Decreased insulin and increased glucagon secretion Blood flow through kidneys Increased activity of renin-angiotensin-aldosterone system and increased vasopressin secretion Renin Angiotensin Aldosterone Fig , p. 700

28 Endocrine Control of Fuel Metabolism
All the chemical reactions that occur within the cells of the body Intermediary metabolism or fuel metabolism Includes reactions involving the degradation, synthesis, and transformation of proteins, carbohydrates, and fats Nutrient molecules are broken down through the process of digestion into smaller absorbable molecules Proteins → amino acids Carbohydrates → monosaccharides (mainly glucose) Dietary fats (triglycerides) → monoglycerides and free fatty acids

29 Anabolism and Catabolism
Buildup or synthesis of larger organic macromolecules from small organic subunits Reactions usually require ATP energy Reactions result in Manufacture of materials needed by the cell Storage of excess ingested nutrients not immediately needed for energy production or needed as cellular building blocks Catabolism Breakdown or degradation of large, energy-rich organic molecules within cells Two levels of breakdown Hydrolysis of large cellular molecules into smaller subunits Oxidation of smaller subunits to yield energy for ATP production

30 Food intake Dietary protein D I G E S T I O N Absorbable units Glucose
carbohydrate Dietary triglyceride fat D I G E S T I O N Absorbable units Amino acids Glucose Fatty acids Monoglycerides A B S O R P T I O N Metabolic pool in body Body proteins (structural or secretory products) Amino acids Urea Urinary excretion (elimination from body) Oxidation to CO2 + H2O + ATP (energy) Expired (elimination from body) Storage, structural, and functional macromolecules in cells Glycogen storage in liver and muscle Glucose Triglycerides in adipose tissue stores (fat) Fatty acids Use as metabolic fuel in cells Fig , p. 702

31 Stored Metabolic Fuel in the Body

32 Metabolic States Absorptive state Fed state
Glucose is plentiful and serves as major energy source Postabsorptive state Fasting state Endogenous energy stores are mobilized to provide energy Liver Primary role in maintaining normal blood glucose levels Principal site for metabolic interconversions such as gluconeogenesis Adipose tissue Primary energy storage site Important in regulating fatty acid levels in the blood Muscle Primary site of amino acid storage Major energy user Brain Normally can only use glucose as an energy source Does not store glycogen Mandatory blood glucose levels be maintained

33 Pancreas Alpha cell Beta cell Delta cell Capillaries
Endocrine cells – Islets of Langerhans Β (beta) cells Site of insulin synthesis and secretion Α (alpha) cells Produce glucagon D (delta) cells Pancreatic site of somatostatin synthesis PP cells Least common islet cells Secrete pancreatic polypeptide The function of PP is to self regulate the pancreas secretion activities (endocrine and exocrine). Insulin and glucagon Most important in regulating fuel metabolism Pancreas Alpha cell Beta cell Delta cell Capillaries Fig 15-3, pg 455

34 Pancreatic Hormones Somatostatin
Released from pancreatic D cells in direct response to increase in blood sugar and blood amino acids during absorption of a meal Prevents excessive plasma levels of nutrients Local presence of somatostatin decreases secretion of insulin, glucagon, and somatostatin itself Physiologic importance has not been determined Insulin Anabolic hormone Promotes cellular uptake of glucose, fatty acids, and amino acids and enhances their conversion into glycogen, triglycerides, and proteins, respectively Lowers blood concentration of these small organic molecules Secretion is increased during absorptive state Primary stimulus for secretion is increase in blood glucose concentration Glucagon Mobilizes energy-rich molecules from storage sites during postabsorptive state Secreted in response to a direct effect of a fall in blood glucose on pancreatic α cells Generally opposes actions of insulin No known clinical abnormalities caused by glucagon deficiency or excess Excess of glucose can aggravate hyperglycemia of diabetes mellitus

35 Diabetes Mellitus Most common of all endocrine disorders
Prominent feature is elevated blood glucose levels Urine acquires sweetness from excess blood glucose that spills into urine Two major types Type I diabetes Characterized by lack of insulin secretion Type II diabetes Characterized by normal or even increased insulin secretion but reduced sensitivity of insulin’s target cells

36 Endocrine Control of Calcium Metabolism
Plasma Ca2+ must be closely regulated to prevent changes in neuromuscular excitability Also plays vital role in a number of essential activities Excitation-contraction coupling in cardiac and smooth muscle Stimulus-secretion coupling Maintenance of tight junctions between cells Clotting of blood Neurotransmitter release Hypercalcemia Reduces excitability Hypocalcemia Brings about overexcitability of nerves and muscles Severe overexcitability can cause fatal spastic contractions of respiratory muscles

37 Endocrine Control of Calcium Metabolism
Three hormones regulate plasma concentration of Ca2+ (and PO43-) Calcitonin Hormone produced by C cells of thyroid gland Negative-feedback fashion Secreted in response to increase in plasma Ca2+ concentration Acts to lower plasma Ca2+ levels by inhibiting activity of bone osteoclasts Unimportant except during hypercalcemia Parathyroid hormone (PTH) Secreted by parathyroid glands Primary regulator of Ca2+ Raises free plasma Ca2+ levels by its effects on bone kidneys, and intestines Essential for life Prevents fatal consequences of hypocalcemia Facilitates activation of Vitamin D Vitamin D Stimulates Ca2+ and PO43- absorption from intestine Can be synthesized from cholesterol derivative when exposed to sunlight Amount supplemented by dietary intake Must be activated first by liver and then by kidneys before it can exert its effect on intestines

38 Negative-feedback Loops Controlling Parathyroid Hormone (PTH) and Calcitonin Secretion

39 Bone remodeling Bone deposition Bone resorption
Osteoblasts – secrete matrix for calcium phosphate Osteocytes – retired osteoblasts Osteoclasts – resorb bone Osteoporosis Bone thinning Increased osteoclast activity Reduced osteoblast activity

40 (Because of inverse relationship between plasma PO43- and Ca2+
Relieves Plasma PO43- (Because of inverse relationship between plasma PO43- and Ca2+ concentrations caused by solubility characteristics of calcium phosphate salt) Plasma Ca2+ Kidneys Parathyroid glands Activated vitamin D PTH PO43- reabsorption by kidneys Ca2+ reabsorption by kidneys Urinary excretion of Ca2+ Ca2+ absorption in intestine (Counteract each other) Urinary excretion of PO43- PO43- absorption in intestine No change in plasma Ca2+ Plasma PO43- Fig , p. 725

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