Endocrine System PDF

Endocrine System Hormones and Their Actions Eicosanoids and Paracrine Signaling Hypothalamus and Pituitary Other Endocrine Glands Stress and Adaptation Endocrine Disorders 17-1  Cell Communications internal communication is necessary for coordi...

Endocrine System Hormones and Their Actions Eicosanoids and Paracrine Signaling Hypothalamus and Pituitary Other Endocrine Glands Stress and Adaptation Endocrine Disorders 17-1  Cell Communications internal communication is necessary for coordination of cell activities four mechanisms of communication between cells – gap junctions pores in cell membrane allow signaling from cell- cell – neurotransmitters released from neurons – paracrine (local) secretions secreted into tissue fluids to affect nearby cells – hormones chemical messengers that travel in the bloodstream 17-2  Endocrine System endocrine system - glands, tissues, and cells that secrete hormones endocrinology – the study of this system and the diagnosis and treatment of its disorders endocrine glands – organs that produce hormones hormones - chemical messengers transported by the bloodstream that stimulate responses in another tissue or organ, often far away 17-3 Endocrine Organs Pineal gland Hypothalamus Pituitary gland Thyroid gland Thymus Adrenal gland Pancreas Parathyroid glands Trachea Posterior view Gonads: Ovary (female) Testis (male) 17-4  Comparison of Endocrine and Exocrine Glands exocrine glands – ducts carry secretion to an epithelial surface or the mucosa of the digestive tract – ‘external secretions’ – extracellular effects (such as food digestion) endocrine glands – no ducts – contain dense capillary networks to allow easy uptake of hormones into bloodstream – ‘internal secretions’ – intracellular effects such as altering target cell metabolism 17-5  Comparison of Nervous and Endocrine Systems (Differences) both serve for internal communication – nervous - both electrical and chemical – endocrine - only chemical speed and persistence of response – nervous - reacts quickly, stops quickly – endocrine - reacts slowly, effect may continue for weeks adaptation to long-term stimuli – nervous - response declines (adapts quickly) – endocrine - response persists (adapts slowly) area of effect – nervous - targeted and specific (one organ) 17-6 – endocrine - general, widespread effects  Communication by the Nervous and Endocrine Systems Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Neurotransmitter Nerve impulse Neuron Target cells (a) Nervous system EndocrineTarget cells cells Hormone in bloodstream (b) Endocrine system 17-7  Nervous and Endocrine Systems (Similarities) several chemicals function as both hormones and neurotransmitters some hormones are secreted by neuroendocrine cells (neurons) both systems can have overlapping effects on same target – norepinephrine and glucagon cause glycogen hydrolysis in liver systems regulate each other – neurons trigger hormone secretion – hormones stimulate or inhibit neurons 17-8  Hormone Chemistry Two broad chemical classes Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. H OH CH3 H2 N C COOH – steroids CH3 CH2 derived from cholesterol O Testosterone I O I estrogens, progesterone, OH testosterone, cortisol, CH3 I I OH corticosterone, aldosterone, Thyroxine OH DHEA, and calcitriol HO HO CH CH2 NH CH2 Estradiol HO Epinephrine – amino-acid based (a) Steroids (b) Monoamines Thr Tyr Asn Pro Cys Tyr Asn chains of amino acids Phe Glu Leu Lys Phe S Gln Gly Thr Gly Tyr lle – hypothalamus and pituitary Arg Leu S Val Glu Ser hormones Insulin Glu Gly Cys Cys S Gln S lle Cys derived from specific amino Val Ser Thr Cys Leu S Tyr acids (often tyrosine) Val Tyr Leu Arg S Ala Asp lle Glu His Val Leu His Ser Gly Cys Leu – epinephrine, norepinephrine, Pro Phe His Angiotensin II Gln melatonin, and thyroid hormone (c) Peptides Phe Asn Val 17-9  Paracrine Secretions paracrines - chemical messengers that diffuse short distances and stimulate nearby cells – unlike neurotransmitters, not produced in neurons – unlike hormones, not transported in blood – a single chemical can act as a hormone, paracrine, or even neurotransmitter in different locations 17-10  Paracrine Secretions – histamine from mast cells in connective tissue: causes relaxation of blood vessels – nitric oxide from endothelium of blood vessels, causes vasodilation – catecholamines (epinephrine, NE, dopamine) diffuse from adrenal medulla to cortex 17-11 Eicosanoids: a Family of Paracrine Secretions eicosanoids – important family of paracrines – derived from fatty acid called arachidonic acid arachidonic acid converted into various eicosanoids: – leukotrienes mediate allergic and inflammatory reactions – thromboxanes stimulates vasoconstriction and clotting – prostaglandins (a huge group) include: PGE: relaxes smooth muscle in bladder, intestines, bronchioles, uterus and stimulates contraction of blood vessels PGF: opposite effects 17-12  Control of Hormone Secretion Endocrine glands are usually controlled by a negative feedback loop – Hormone is released – Target cells respond – Level of original hormone or that of target cell hormone reaches a threshold, which stops secretion 17-13  Control of Hormone Secretion Humoral (body fluid) Stimuli – Some glands are regulated by the concentration of a substance in the ECF – e.g. pancreatic cells that release insulin respond to ECF glucose levels; parathyroid cells respond to ECF calcium levels Neural Stimuli – Some glands release hormones based on signals from the nervous system – Mainly the ANS (parasympathetic to pancreatic cells, sympathetic to adrenal medulla) 17-14  Hormone Interactions most cells sensitive to more than one hormone and exhibit interactive effects synergistic effects – multiple hormones act together for greater effect FSH and testosterone for sperm production permissive effects – one hormone enhances the target organ’s response to a second later hormone estrogen prepares uterus for action of progesterone antagonistic effects – one hormone opposes the action of another insulin lowers blood glucose & glucagon raises it 17-15  Enzyme Amplification Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction hormones are or display. Small stimulus extraordinarily potent chemicals Hormone one hormone molecule can Reaction cascade (time) cAMP and trigger the protein kinase synthesis of many Activated enzymes enzyme molecules very small stimulus Metabolic product can produce very large effect Great effect 17-16  Hormone Receptors hormones only stimulate cells that have receptors for them receptors are protein or glycoprotein molecules: – on plasma membrane, in cytoplasm, or in nucleus receptors act like switches, turning on metabolic pathways when hormone binds to them usually each target cell has a few thousand receptors for a given hormone receptor-hormone interactions exhibit specificity and saturation – specific receptor for each hormone – saturated when all receptor molecules are occupied by hormone 17-17  Hormone Mode of Action hydrophobic hormones Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. – penetrate plasma Hydrophilic Receptor in hormone plasma Target cell membrane and enter membrane nucleus Transport protein – act directly on the Second- genes Free hormones messenger activation – take several hours to days to show effect due to lag for protein synthesis Bound hormone Hydrophobic hydrophilic hormones hormone Receptor in – cannot enter target cell Tissue fluid nucleus Blood – must stimulate indirectly  Thyroid Hormone (Hydrophobic) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Thyroid hormone is really 2 forms: T3 and T4 TBG – both diffuse into cell T3 T Various metabolic effects in target cell, T4 is 4 Protein mRNA converted to more potent synthesis T3 DNA T3 binds to receptors on T4 I chromosomes T3 Activate genes – Increase metabolism, Blood Tissue fluid Target cell strengthen heartbeat, etc. 17-19  Action of Hydrophilic Hormones Since hydrophilic hormones can’t pass through the cell membrane, they must dock on a receptor on the outside and then cause a change inside – this is signal transduction: 1. Hormone docks on receptor and activates a G-protein inside the cell 2. G-protein causes cyclic AMP to be made (cAMP is a second messenger) 3. cAMP activates a protein kinase, which activates or deactivates specific cellular proteins 4. The specific proteins cause physiological changes in the cell 17-20 Action of Hydrophilic Hormones 17-21 Animations – Action of Both Types of Hormone Action of hydrophobic hormones: https://mediaplayer.pearsoncmg.com/assets/secs-ipweb-m echanism-of-hormone-action-direct-gene-activation Action of hydrophilic hormones: https://mediaplayer.pearsoncmg.com/assets/secs-mechanis m-of-hormone-action-second-messenger-system 17-22  Modulation of Target Cell Sensitivity Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or target cell sensitivity display. Hormone Receptor adjusted by changing the number of receptors; this Response can be a normal or abnormal response Low receptor density Increased receptor density Weak response Increased sensitivity Stronger response (a ) Up-regulation up-regulation: number of receptors is increased – sensitivity increased Response down-regulation reduces number of receptors High receptor density Reduced receptor density – less sensitive to hormone Strong response Reduced sensitivity (b ) Down-regulation Diminished response – happens with long-term exposure to high hormone concentrations 17-23 ? 17-24 Anatomy of Hypothalamus Link between nervous & endocrine systems regulates primitive functions of the body from water balance and thermoregulation to sex drive and childbirth many functions carried out by pituitary gland 17-25  Pituitary Gland (Hypophysis) suspended from hypothalamus by a stalk – infundibulum size and shape of kidney bean composed of two structures with independent origins and separate functions – adenohypophysis (anterior pituitary) – neurohypophysis (posterior pituitary) 17-26  Embryonic Development (FYI) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Telencephalon of brain Future hypothalamus Neurohypophyseal bud Hypophyseal pouch Pharynx Tongue Future thyroid gland Mouth (a) 4 weeks Hypothalamus Hypothalamus Optic chiasm Neurohypophyseal bud Pituitary stalk Posterior lobe Hypophyseal pouch Anterior lobe Sphenoid bone Pharynx Pharynx (b) 8 weeks (c) 16 weeks 17-27 Histology of Pituitary Gland Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chromophobe Basophil Acidophil (a) Anterior pituitary Unmyelinated nerve fibers Glial cells (pituicytes) (b) Posterior pituitary a: © Dr. John D. Cunningham/Visuals Unlimited; b: © Science VU/Visuals Unlimited 17-28 Anterior and Posterior Pituitary Anterior pituitary (AP) is anterior 3/4 of pituitary – links to hypothalamus by hypophyseal portal system set of capillaries in hypothalamus connected to a second set in AP hypothalamic hormones regulate AP cells Posterior pituitary (PP) is posterior 1/4 of pituitary – nerve tissue, not a true gland nerve cell bodies in hypothalamus pass down the stalk as hypothalamo-hypophyseal tract and end in posterior lobe hypothalamic neurons secrete hormones that are stored in PP until released into blood 17-29  Hypophyseal Portal System Axons to primary Neuron capillaries cell body Just Hypothalamic hormones recognize Gonadotropin-releasing hormone Thyrotropin-releasing hormone Hypophyseal these Corticotropin-releasing hormone portal system: Prolactin-inhibiting hormone Primary capillaries Growth hormone–releasing hormone Portal venules Somatostatin Secondary capillaries We will Anterior lobe hormones Anterior lobe learn these Follicle-stimulating hormone Luteinizing hormone Posterior lobe Thyroid-stimulating hormone (thyrotropin) Adrenocorticotropic hormone Prolactin Growth hormone hypothalamic hormones travel in hypophyseal portal system from hypothalamus to anterior pituitary 17-30  Hypothalamic Hormones Eight hormones produced in hypothalamus – six regulate the anterior pituitary (releasing or inhibiting hormones) – two stored in the posterior pituitary (oxytocin and antidiuretic hormone) posterior pituitary does not synthesize them 17-31 Anterior Pituitary Hormones anterior lobe of the pituitary synthesizes and secretes six principal hormones two gonadotropin hormones that target gonads 1) FSH (follicle stimulating hormone) stimulates secretion of ovarian sex hormones, development of ovarian follicles, and sperm production 2) LH (luteinizing hormone) stimulates ovulation, stimulates corpus luteum to secrete progesterone, stimulates testes to secrete testosterone 17-32 Anterior Pituitary Hormones 3) TSH (thyroid stimulating hormone) stimulates secretion of thyroid hormone 4) ACTH (adrenocorticotropic hormone) stimulates adrenal cortex to secrete glucocorticoids 5) PRL (prolactin) after childbirth, stimulates mammary glands to synthesize milk, enhances secretion of testosterone by testes 6) GH (growth hormone) stimulates mitosis and cellular differentiation 17-33 Hypothalamo-Pituitary- Target Organ Relationships Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Hypothalamus TRH GnRH CRH GHRH Liver PRL GH IGF Mammary Fat, gland muscle, bone TSH ACTH Thyroid Adrenal cortex LH FSH Figure 17.6 Testis Ovary principle hormones and target organs 17-34  Posterior Pituitary Hormones produced in hypothalamus – transported to posterior lobe – released when hypothalamic neurons are stimulated ADH (antidiuretic hormone) – increases water retention, thus prevents dehydration OT (oxytocin – the “love hormone”) – released during sexual arousal and orgasm – promotes feelings of sexual satisfaction and emotional bonding between partners – stimulates labor contractions during childbirth – stimulates flow of milk during lactation – promotes emotional bonding between mother and infant 17-35  Control of Pituitary Secretion rates of secretion are not constant – regulated by hypothalamus, other brain centers, and feedback from target organs Hypothalamic/Cerebral Control – anterior lobe control – by hormones from hypothalamus (which can be triggered by external factors) e.g., in cold weather, hypothalamus detects reduced body temp, releases more TSH, leads to generation of body heat – posterior lobe control - neuroendocrine reflexes hormone release in response to nervous system signals (can also be external) suckling infant stimulates nerve endings hypothalamus posterior lobe oxytocin milk ejection 17-36  Control of Pituitary: Feedback from Target Organs Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. negative 1 TRH  6 Negative feedback feedback -increased inhibition target organ hormone +  4 levels inhibits release 5 2 Target organs of hormones + TSH positive feedback - stretching of uterus Thyroid hormone increases OT release, + 3 causes contractions, causing more stretching Stimulatory effect of uterus, etc. until + –Inhibitory effect delivery 17-37  Growth Hormone GH has widespread effects on the body tissues – especially cartilage, bone, muscle, and fat induces liver to produce growth stimulants – insulin-like growth factors (IGF’s) stimulate target cells in diverse tissues protein synthesis increases lipid metabolism increases – provides energy for growing tissues carbohydrate metabolism –makes glucose available 17-38  Growth Hormone – bone growth, thickening, and remodeling influenced, especially during childhood and adolescence – secretion high during first two hours of sleep – can peak in response to vigorous exercise – GH levels decline gradually with age lack of protein synthesis contributes to aging of tissues and wrinkling of the skin 17-39  Pineal Gland pineal gland - attached to roof of third ventricle beneath the posterior end of corpus callosum may synchronize physiological function with 24- hour circadian rhythms of daylight and darkness – synthesizes melatonin from serotonin during the night may regulate timing of puberty in humans seasonal affective disorder (SAD) occurs in winter or northern climates – depression, sleepiness, irritability and carbohydrate craving – possibly from increased melatonin 17-40  Thymus plays a role in three systems: endocrine, lymphatic, and immune bilobed gland in the mediastinum superior to the heart hormones important in immune defense Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Thyroid Trachea Thymus Heart Diaphragm Liver (a) Newborn (b) Adult 17-41  Thyroid Gland Anatomy – Butterfly-shaped Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Thyroid secretes thyroxine (T4: 4 iodine cartilage atoms) and triiodothyronine (T3) – increases metabolic rate, O2 Thyroid gland consumption, heat production (calorigenic Isthmus effect), appetite, growth hormone secretion, alertness and quickens reflexes Trachea parafollicular (C or clear) cells (a) secrete calcitonin with rising blood calcium – stimulates bone formation – probably only important in children 17-42  Thyroid Gland – Only gland that stores its secretory product in large amounts (~ 100 day supply) – Synthesis 1. Iodide trapping by follicular cells 2. Follicular cells make thyroglobulin (TGB) 3. Amino acids in thyroglobulin are iodinated (making T1 or T2) 4. Two T2’s equals T4, T1 plus T2 equals T3 5. Follicular cells take in iodinated TGB by pinocytosis, then lysosomes break down the TGB 6. T3 and T4 are left: they diffuse out of the cell and into the blood 7. Most is transported in blood by thyroxine-binding globulin 17-43  Parathyroid Glands usually four glands partially embedded in posterior surface of thyroid gland Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Pharynx secrete parathyroid hormone (PTH) (posterior view) – increases blood Ca2+ levels promotes synthesis of calcitriol Thyroid gland (vitamin D) decreases urinary excretion of Parathyroid Ca2+ glands increases bone resorption (Ca2+ taken from bones) Esophagus Trachea (a) © John Cunningham/Visuals 17-44 Unlimited ? 17-45  Adrenal Gland Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Adrenal gland Suprarenal vein Kidney Connective Adrenal cortex tissue capsule Zona Adrenal medulla glomerulosa Adrenal cortex Zona fasciculata (a) Zona reticularis Adrenal medulla (b) small gland that sits on top of each kidney adrenal cortex and medulla formed by merger of two fetal glands with different origins and 17-46 functions  Adrenal Medulla adrenal medulla – inner core, 10% to 20% of gland Dual nature: endocrine gland and sympathetic ganglion – when stimulated, releases catecholamines (epinephrine and norepinephrine) and a trace of dopamine directly into the bloodstream (so they act as hormones) effect is longer lasting than neurotransmitters – increases alertness; prepares body for physical activity: mobilize high energy fuels, lactate, fatty acids, and glucose – increases blood pressure, heart rate, blood flow to muscles, pulmonary air flow and metabolic rate – decreases digestion and urine production 17-47  Adrenal Cortex surrounds adrenal medulla and produces more than 25 steroid hormones called corticosteroids or corticoids secretes 3 classes of steroid hormones – mineralocorticoids – glucocorticoids – sex steroids 17-48  Categories of Corticosteroids mineralocorticoids – aldosterone stimulates Na+ retention so blood volume and blood pressure are maintained glucocorticoids – regulate metabolism of glucose and other fuels – especially cortisol, stimulates release of fuels into blood – helps body adapt to stress and repair tissues (given as drugs to encourage healing – anti-inflammatory effect (can become immune suppression in long-term use) sex steroids – androgens – sets libido; large role in prenatal male development – estradiol – small quantity, but important after menopause for sustaining adult bone mass 17-49  Pancreas Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Tail of pancreas Bile duct (c) Pancreatic islet PancreaticDuodenum ducts Beta cell (a) Alpha cell Delta cell (b) Pancreatic islet c: © Ed Reschke exocrine digestive gland and endocrine cell clusters (pancreatic islets) found inferior & posterior to stomach. 17-50  Pancreatic Hormones 1-2 million pancreatic islets (Islets of Langerhans) produce hormones – other 98% of cells produce digestive enzymes insulin secreted by B or beta () cells – secreted during and after meal when glucose and amino acid blood levels are rising – stimulates cells to absorb these nutrients and store or metabolize them, lowering blood glucose levels promotes synthesis of glycogen, fat, and protein – insufficiency or inaction is cause of diabetes mellitus 17-51  Pancreatic Hormones glucagon – secreted by A or alpha () cells – released between meals when blood glucose concentration is falling – in liver, stimulates release of glucose into the circulation raising blood glucose level – in adipose tissue, stimulates fat catabolism 17-52  Pancreatic Hormones somatostatin secreted by D or delta () cells – partially suppresses secretion of glucagon and insulin – inhibits nutrient digestion and absorption which prolongs absorption of nutrients – modulates effects of insulin & glucagon 17-53 Hormones and the Pancreas hyperglycemic hormones raise blood glucose concentration – glucagon, growth hormone, epinephrine, norepinephrine, cortisol hypoglycemic hormones lower blood glucose – insulin 17-54  The Gonads ovaries and testes are both endocrine and exocrine – exocrine product – whole cells - eggs and sperm – endocrine product - gonadal hormones – mostly steroids ovarian hormones – Estradiol (an estrogen), progesterone, and inhibin testicular hormones – testosterone, weaker androgens, estrogen and 17-55 inhibin  Histology of Gonads Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. or display. Blood vessels Granulosa cells Seminiferous (source of tubule estrogen) Germ cells Connective tissue Egg nucleus wall of tubule Egg Sustentacular cells Interstitial cells Theca (source of testosterone) 50 µm 100 µm Testis (a) Ovary (b) © Manfred Kage/Peter Arnold, Inc. © Ed Reschke follicle - egg surrounded by granulosa cells 17-56 and a capsule (theca)  Ovary secrete estradiol (and related estrogens) after ovulation, the remains of the follicle become the corpus luteum – secretes progesterone for ~12 days following ovulation functions of estradiol and progesterone – development of female reproductive system and physique including adolescent bone growth – regulate menstrual cycle, sustain pregnancy – prepare mammary glands for lactation inhibin suppresses FSH secretion from anterior pituitary 17-57  Testes microscopic seminiferous tubules produce sperm – tubule walls contain sustentacular cells (Sertoli cells) – interstitial cells lie in clusters between tubules testicular hormones – testosterone and other steroids from interstitial cells stimulates development of male reproductive system in fetus and adolescent, and sex drive sustains sperm production – inhibin from sustentacular (Sertoli) cells limits FSH secretion to regulate sperm production 17-58  Endocrine Functions of Other skin Organs – keratinocytes make cholecalciferol using UV from sun liver – helps make at least five hormones – converts cholecalciferol into calcidiol – secretes angiotensinogen (for BP regulation) – secretes 15% of erythropoietin (stimulates bone marrow) – hepcidin – promotes intestinal absorption of iron – source of IGF-I that controls action of growth hormone kidneys – role in production of three hormones – converts calcidiol to calcitriol, active form of vitamin D – secrete renin that converts angiotensinogen to angiotensin I – produce 85% of erythropoietin 17-59  Endocrine Functions of Other Organs heart – cardiac muscle secretes atrial natriuretic peptide to lower blood pressure stomach and small intestine: at least ten enteric hormones – coordinate digestive motility and glandular secretion adipose tissue secretes leptin - slows appetite osseous tissue – osteocalcin secreted by osteoblasts – increases insulin sensitivity of body tissues – inhibits weight gain and onset of type II diabetes mellitus placenta – secretes estrogen, progesterone and others 17-60 regulate pregnancy, development of fetus  Stress Response Sequence of responses to stress: 1. Fight-or-flight (right away): Glucose and oxygen to vital organs, nonessential body function inhibited 2. Resistance reaction (days to weeks): Release of cortisol, HGH, and TSH – lypolysis, release and synthesis of glucose, increased use of glucose, increased blood pressure 3. Exhaustion (weeks to months) Wasting of muscle, immune suppression, gastric ulceration, failure of beta cells. Stress contributes to many chronic diseases. Anti-inflammatory Drugs cortisol and corticosterone – steroidal anti-inflammatory drugs (SAIDs) – inhibit inflammation by inhibiting synthesis of eicosanoids disadvantage – kidney damage over long term aspirin, ibuprofen, naproxen & celecoxib (Celebrex) – nonsteroidal anti-inflammatory drugs (NSAIDs) COX inhibitors since block cyclooxygenase (COX) useful in treatment of fever and clotting – inhibit prostaglandin and thromboxane synthesis 17-62  Endocrine Disorders variations in hormone concentration and target cell sensitivity have noticeable effects on body hyposecretion – inadequate hormone release – tumor or lesion destroys gland or interferes with its ability to receive signals from another gland e.g. head trauma affects pituitary gland’s ability to secrete ADH – diabetes insipidus - chronic polyuria autoantibodies fail to distinguish gland from foreign matter (and thus damage it) 17-63  Endocrine Disorders hypersecretion – excessive hormone release – proliferative tumors or autoimmune disorder pheochromocytoma – tumor of adrenal medulla; secretes excessive epinephrine and norepinephrine toxic goiter (Graves disease) – autoantibodies mimic effect of TSH on the thyroid causing thyroid hypersecretion 17-64  Pituitary Disorders hypersecretion of growth hormone (GH) – acromegaly - thickening of bones and soft tissues in adults (see pic below) especially hands, feet and face – problems in childhood or adolescence: gigantism if hypersecretion pituitary dwarfism if hyposecretion – growth hormone is now made by genetically engineered bacteria Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Age 9 Age 16 Age 33 Age 52 From Clinical Pathological Conference Acromegaly, Diabetes, Hypermetabolism, Protein Use and Heart Failure in American Journal of Medicine, 20:133, 1986. Copyright © 1986 by Excerpta Media, Inc. 17-65  Thyroid Gland Disorders congenital hypothyroidism (decreased TH) – hyposecretion present at birth (formerly cretinism) myxedema (decreased TH) – adult hypothyroidism – both treated with oral thyroid hormone goiter – any pathological enlargement of the thyroid gland – endemic goiter dietary iodine deficiency: no TH, no feedback, increased TSH stimulates hypertrophy – toxic goiter (Graves disease) autoantibodies mimic the effect of TSH on the thyroid causing hypersecretion overgrown thyroid produces functional TH 17-66 Endemic Goiter Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Figure 17.28 © CNR/Phototake 17-67  Parathyroid Disorders – hypoparathyroidism accidental surgical removal during thyroid surgery fatal tetany in 3 - 4 days due to rapid decline in blood calcium level – hyperparathyroidism - excess PTH secretion proliferative parathyroid tumor bones become soft, fragile, and deformed Ca2+ and phosphate blood levels increase causes kidney stones 17-68  Adrenal Disorders Cushing syndrome - excess cortisol secretion – hyperglycemia, hypertension, weakness, edema – rapid muscle and bone loss due to protein catabolism – abnormal fat deposition moon face and buffalo hump adrenogenital syndrome (AGS) – adrenal androgen hypersecretion – enlargement of external sexual organs in children and early onset of puberty newborn girls exhibit masculinized genitalia – masculinizing effects on women increased body hair, deeper voice and beard growth 17-69 Cushing Syndrome From: Atlas of Pediatric Physical Diagnosis, 3/e by Zitelli & Davis, fig 9-17 1997, with permission from Elsevier 17-70 ? 17-71  Diabetes Mellitus most prevalent metabolic disease in world – hyposecretion or inaction of insulin – symptoms: polyuria (excess urine output), polydipsia (intense thirst) and polyphagia (hunger) revealed by elevated blood glucose, glucose in urine and ketones in the urine – Too much glucose in kidneys means not all is reabsorbed excess glucose enters urine and water follows causes polyuria, dehydration, and thirst 17-72 Types of Diabetes Mellitus Type 1 – Insulin-Dependent (5 to 10% of cases in US) – insulin is always used to treat Type 1 – hereditary susceptibility if infected with certain viruses – autoantibodies attack and destroy pancreatic beta cells Type 2 – Non-Insulin-Dependent (90 to 95% of diabetics) – problem is insulin resistance – risk factors are heredity, age (40+),obesity, and ethnicity – Native American, Hispanic, and Asian – treated with weight loss program and exercise since: increased muscle mass improves regulation of glucose adipose signals interfere with glucose uptake – oral medications improve insulin secretion or target cell sensitivity 17-73  Pathology of Diabetes pathogenesis: cells cannot absorb glucose, must rely on fat and proteins for energy needs - weight loss and weakness – fat catabolism increases free fatty acids and ketones in blood Ketones in urine promote osmotic diuresis, loss of Na+ and K+, irregular heartbeat, and neurological issues ketoacidosis occurs b/c ketones decrease blood pH – deep, gasping breathing and diabetic coma are terminal result 17-74  Pathology of Diabetes chronic pathology (chronic hyperglycemia) – leads to neuropathy and cardiovascular damage from atherosclerosis and microvascular disease arterial damage in retina and kidneys (common in type I), atherosclerosis leads to heart failure (common in type II) diabetic neuropathy – nerve damage from impoverished blood flow can lead to erectile dysfunction, incontinence, poor wound healing, and loss of sensation from area 17-75