The Endocrine System PDF

602 UNIT 3 Regulation and Integration of the Body The endocrine system is one Pineal gland - - - - --...J of the body's two major control systems Learning Outcomes Pituitary gland - - - - -...

602 UNIT 3 Regulation and Integration of the Body The endocrine system is one Pineal gland - - - - --...J of the body's two major control systems Learning Outcomes Pituitary gland - - - - - -\- %--- ( Hypothalamus- - - - -- ! -.,;.~ jlt' --'· II- Indicate im po rta nt diffe rences between hormonal and Thyroid gland - - - - - ---f----, neural controls of body functioning. II- List the major endocrine organs, and describe their body Parathyroid glands - - - --::.-= -< locations. (on dorsal aspect II- Distinguish between hormones, paracrines, and of thyroid gland) autocrines. Thymus - - - - -t -- - - - -~~ As \Ve have seen, the nervous system regulates the activi ty of muscles and glands via electrochemical impulses delivered by neurons, and those organs respond withi n milliseconds. The means of control and speed of the endocri ne system are very different: The endocrine system influences metabolic activity by means of honno11es (horrnone = to excite). Hormones are c hem ical messengers secreted by cells into the extracellular fluids. These messengers travel through the blood and regu- late the metabolic funct ion of other cells in the body. Binding of a hormone to cell ular receptors init iates responses that typi- Gonads cally occur after a lag period of seconds or even days. But, once - ++~~----~~I --f~H'. _--~ Ovary (female) initiated, those responses tend to last much longer than those Testis (male) induced by the nervous system. Table 16.1 summarizes the dif- ferences between the nervous sytem and the endocrine system. Hormones ul timately target most cells of the body, produc- ing widespread and d iverse effects. The major processes that these "mighty molecules" control and integrate include: Reproduction Figure 16.1 Location of selected en docrine organs of t he Growth and development body. Maintenance of electrolyte, water, and nutrient balance of the blood Regulation of cellular rnetabolism and energy balance Unlike most organ systems, the endocrine organs are not Mobilization of body defenses grouped together but are widely scattered about the body. As we explained in Chapter 4 (~ pp. 123- 124), there are two As you can see, the endocrine system orchestrates processes kinds of glands: that go on for relatively Jong periods, in some instances con- tinuously. The scientific study of hormones and the endocrine Exocrine glands produce nonhormonal substances, such as organs is called endocrinology. sweat and saliva, and have ducts that carry these substances to Compared with other organs, the endocrine system's organs a membrane surface. are small and un impressive, but their influence is powerful. E ndocrine glands, also called ductless glands, produce hormones and lack ducts. They release their hormones into the surround ing tissue fluid (e11do = within; crine = to Table 16.1 Comparison of Nervous and Endocrine secrete), and typically have a rich vascular and lymphatic Systems drainage that receives their hormones. Most of the hormone- NERVOUS SYSTEM ENDOCRINE SYSTEM produci ng cells in endocrine glands are arranged in cords Initiates responses rapidly Initiates responses slowly and branching networks, which maximizes contact between them and the surrounding capillaries. Short-duration responses Long-duration responses Acts via action potent ials and Acts via hormones released into The endocrine glands include the pituitary, thyroid, parathy- neurotransmitters t he blood roid, adrenal, and pineal glands (Figure 16.1). The hypothala- Acts at specific locations Acts at d iffuse locations- mus, along with its neural functions, also produces and releases d etermined by axon pathways t argets can be anywhere blood hormones, so we consider the hypothalamus a neuroendocrine reaches organ. In addition, several organs, such as the pancreas, gonads Neurotransmitters act over very Hormones act over long (ovaries and testes), and placenta, contain endocri ne tissue. short d istances distances Most other organs also contai n scattered endocri ne cells or small clusters of endocrine cells.  Chapter 16 The Endocrine System 607 (a) Humoral Stimulus Hormone release caused by altered levels (b) Neural Stimulus Hormone release caused by neural input. - (c) Hormonal Stimulus Hormone release caused by another hormone of certain critical ions or nutrients. (a tropic hormone). CNS (spinal cord).. Hypothalamus Capillary (low Ca2 in blood) Thyroid gland (posterior view) Anterior----.~ pituitary ·- - - - - - - - -Preganglionic gland sympathetic fibers Thyroid Adrenal Gonad gland cortex (Testis) Medulla of adrenal gland.. l PTH.......:.... Stimulus: Low concentration of Ca2 in capillary blood. St imulus: Action potentials in preganglionic Stimulus: Hormones from hypothalamus. Response: Parathyroid glands secrete sympathetic fibers to adrenal medulla. Response: Anterior pituitary gland secretes parathyroid hormone (PTH), which Response: Adrenal medulla cells secrete hormones that stimulate other endocrine glands increases blood Ca2. epinephrine and norepinephrine. to secrete hormones. Figure 16.4 Three types of endocrine gland st imuli. Humoral Stimuli 16.4Three types of stimuli cause Some e ndocrine glands secrete their hormones in direct hormone release response to changing blood levels of certai n critical ions and nutrients. These stimuli are called hurnoraL sti,1111/i (from the Learning Outcome Latin term hurnor, which refers to moisture or bodily flu ids).... Explain how hormone release is regulated. Humoral stimul i are the simplest endocrine controls. For The synthesis and release of most hormones are regulated by example, cells of the parathyroid glands monitor the body's some type of negative feedback mecha nism (- Produce son dri nks e nough water to prevent dehy- dration. However, it can be life threatening Insulin-like growth in unconscious or comatose patients, so factors (IGFs) accident victims with head trauma must c:t>- Effects be carefully monitored. c:t>- Effects The opposite problem, hypersecre- Metabolic actions: Growth-promoting actions: tion of ADH, can occur in children \vith Increases blood glucose and Increases skeletal growth meningitis, or in adults who have neuro- has other anti-insulin effects Increases ca rtilage growth surgery, hypothalamic injury, or cancer Increases fat breakdown At extraskeletal tissues, promotes (particularly lu ng cancer) in which can- and release ,1fd / \ protein synthesis and cell growt :J cer cells are additional sources of ADH. and proliferation It also may occur after general anesthesia '--- or adm inistration of certai n drugs. The resulting condition, syndro,ne of inappro-..,..._ Increases, stimulates priate ADH secretion (SIADH), is marked Reduces, inhibits by retention of fluid, headache and disori- D lnrtiaJ stimulus e ntation due to brain edema, weight gain, O Physiological response and decreased solute co ncentration in O Result the blood. SIADH management requires restricting flu ids and carefully monitoring Figure 16.5 Growth-promoting and metaboli c actions of growth hormone (GH). blood soditun levels. Dri nking alcoholic beverages inhibits ADH secretion and Anterior Pituitary Hormones causes copious urine output. The dry mouth and intense thirst The a nterior pituitary has trad itionally been called the "mas- of a "hangover" reflect this dehydrating effect. Drinking Jots of ter endocrine gland" because rnany of the numerous hormones water also inhibits ADH release. it produces regulate the activity of other endocri ne glands. In  Chapte r 16 The Endocrine System 615 recent years, however, it has been dethroned by the hypothala- Regulation o f SecretionSecretion of GH is regulated chiefly mus, which is now known to control the activity of the anterior by two hypothalamic hormones with antagonistic effects. pituitary. Gro,vth hor1n on e-releasin g hormone (GHRH) stimulates The anterior pitu itary releases six hormo nes, all of them GH release. Typically, GHRH , and therefore GH, secretion peptides or proteins-growth hormone, thyroid-stimulating has a daily cycle with the highest levels occurring duri ng hormone, adrenocorticotropic hormone, follicle-stimulating evening sleep. The total amount secreted daily peaks dur- hormone, lu teiniz ing hormone, and prolact in (Table 16.3). ing adolescence and then declines with age. There are also a When the anterior pituitary receives an appropriate chem ical number of secondary triggers that cause GHRH secretion (see stimulus from the hypothalamus, it releases o ne or more of its Table 16.3 on p. 612). hormones. Although many different hormones pass from the Gro,vth h o r ,n on e- inhibitin g hormone (GHIH), also hypothalamus to the anterior lobe, each target cell distingu ishes called somatosta tin (so"mah-to-stat'i n), inhibits GH release. the messages d irected to it and responds in ki nd-secreti ng the proper hormone in response to specific releasing hormones, and GHIH release is triggered by the feedback of GH and IGFs. shutting off hormone release in response to specific inhibiting Rising levels of GH also feed back to inhibit its own release. GHIH is also produced in various locations in the gut, where hormones. Four of the six anterior pituitary hormones-thyroid-stimulating it inhibits the release of virtually all gastroi ntestinal and pan- hormone, adrenocorticotrop ic hormo ne, foll icle-st imulating creatic secretions-both endocri ne and exocrine. hormone, and luteinizing hormone-are trop ic hor ,n ones or tropins that regulate the secretory actio n of other endocrine HOMEOSTATIC glands (tropi = turn on, change). All anterior pitu itary hor- ~--..4~- IMBALANCE 16.2 mo nes except growth hormone affect their target cells via a Both hypersecretion and hyposecretion of GH may result in cyclic AMP second-messenger system. structural ab normalities. Hypersecretion in children resul ts in gigan tis1n because GH targets the still -active epiphyseal Growth Hormone (GH) (growth) plates. The person becomes abnormally tall, often Soma totrop ic cells of the anterior lobe produce gro,vth h or- reaching a he ight of 2.4 m (8 feet), but has relatively normal 1n on e (GH, also called so,natotropin). GH is essentially an body proportions (Figure 16.6). anabol ic (tissue building) hormone that has both metabolic and growth-promoti ng actions (Figure 16.5). Dir ect Actions on M et abolism Acting d irectly, GH exerts metabolic effects. It mobilizes fats from fat depots for transport to cells, increasing blood levels of fatty acids and e ncouraging their use for fuel. It also decreases the rate of glucose uptake and rnetabolisrn, conserving glucose. In the liver, it e ncourages glycogen breakdow n and release of glucose to the blood. This glucose sparing action, which raises blood glucose levels, is called the a11ti-i11suli11 effect of GH because its effects oppose those of insulin. In addition, GH increases am ino acid uptake into cells and their incorporation into proteins. Indirect Actions on Growth GH mediates most of its growth- enhancing effects indirectly via a family of growth-promoting prote ins called insulin-lik e growth fa ctors (IGFs). The liver, skeletal muscle, b one, and other tissues produce IGFs in response to GH. IGFs produced by the liver act as hormones, while IGFs rnade in other tissues act locally within those tissues (as paracrines). IGFs stimulate actions requ ired for growth: Uptake of nutrie nts from the blood and their incorporation into proteins and DNA, allowing growth by cell division Formation of collagen and deposition of bone matrix Although GH stimulates most body cells to enlarge and divide, its major targets are bone and skeletal muscle. Stimulation of the epiphyseal plate leads to long bone growth, and stimulation Figure 16.6 Disorders of pituitary g rowth hormone. An of skeletal muscles increases muscle mass. individual exhibit ing gigantism (center) is flanked by a pituitary dwarf (left) and a woman of normal height (right). 616 UNIT 3 Regulation a nd Integration of the Body If excessive GH is secreted after the epiphyseal plates have closed, acro1negaly (ak"ro-meg' ah-le) resul ts. Literall y....... Hypothalamus translated as "enlarged extrem ities," this condition is c harac- TRH terized by overgrowth of bones of the hands, feet, and face. ' Hypersecretion usually results from an anterior pituitary tumor Anterior pituitary that churns out excessive GH. The usual treatment is surgical rernoval of the turnor, but th is surgery does not reverse anatomi- TSH cal changes that have already occurred. Hyposecret ion of GH in adults usually causes no problems, but GH deficiency in ch ildren slows long bone growth, a condi- : L Thyroid gland j tion called pituita ry dwarfJSm (Figure 16.6). Such individuals !.......~ raid hormones attain a max imum height of 1.2 m (4 feet), but usually have fairly normal body proportions. Lack of GH is often accompa- [ Target cells j Cl '4 Stimulates Inhibits nied by deficiencies of other anterior pituitary hormones, and if thyroid-stirnulating honnone and gonadotropins are lacking, the Fi gure 16.7 Reg ulation of thyroid hormon e secretion. individual will be malproportioned and will fail to mature sexu- (TRH = thyrotropin-releasing hormone, TSH = thyroid-stimulating ally as well. Fortunately, human GH is produced commercially hormone) by genetic engineering techniques. When pi tuitary dwarfism is diagnosed before puberty, growth hormone replacernent therapy can promote nearly normal growth. ACTH release. Internal and external factors that alter the normal The availability of synthet ic GH also has a downside. Ath- ACTH rl1ythm by triggeri ng CRH release include fever, hypogly- letes and the elderly have been tempted to use GH for its body- cemia (low blood glucose levels), and stressors of all types. building properties, and some parents seek to give their children the hormone in an attempt to make them taller. However, while Gonadot ropins (FSH and LH) muscle mass increases, there is no objective evidence for an Follicle-stimula ting hormone (FSH) a nd luteinizing hor - increase in muscle strength in either athletes or the elderly, and m one (LH) (lu' te-in-Iz"ing) are referred to collectively as only minimal increases in stature occur in normal children. go nadot ropins. They regulate the fu nc tion of the gonads Moreover, taking GH can lead to fluid retention, joint and mus- (ovaries and testes). In both sexes, FSH stimulates production cle pain, diabetes, and may promote cancer. of gametes (sperm or eggs) and LH promotes production of gonadal hormones. In females, LH works with FSH to cause an egg-contai ning ovarian follicle to mature. LH then triggers Thyroid-Stimulating Hormone (TSH) ovulation and promotes synthesis and release of ovarian hor- Thyroid-s tim ula ting hor 1none (TSH ), or thyr otrop in, is mones. In males, LH stimulates the interstitial cells of the testes a tropic hormone that sti mulates normal development and to produce the male hormone testosterone. secretory activi ty of the thyroid gland. Its release follo\vs Gonadotropins are virtually absent from the blood of prepu- the hypothalamic-pituitary-target endocrine organ feedback bertal boys and girls. During puberty, the gonadotropic cells of loop described earlier and s hov, n specifically for TS H in the anterior pituitary are activated and gonadotropin levels rise, Fi gure 16.7. causing the gonads to mature. In both sexes, gonadotropin- The hypothalamic peptide thyrotropin-releasing hormone releasing hormone (G nRH) produced by the hypothalamus (TRH) triggers the release of TSH from thyr otropic cells of prompts gonadotropin release. Gonadal hormones, produced the anterior pitui tary. Rising blood levels of thyroid hormones in response to the gonadotropins, feed back to suppress FS H act on both the pituitary and the hypothalamus to inhibit TSH a nd LH release. (Chapter 27 covers these hormones in more secretion. GHIH also inhibits TSH secretion. detail.) A d renocorticotropic Hormone (ACTH) Prolact in (PRL) Adrenocor ticotropic hormone (ACTH) (ah-dre"no-kor"ti- Prolactin (PRL) is a protei n hormone structurally similar to ko-trop' ik), or cor ticotropin, is secreted by the cor ticotropic GH. Produced by prolactin cells, PRL's only well-documented cells of the anterior pitu itary. It is split from a prohorrnone effect in humans is to stimulate milk production by the breasts (a large precursor molecule) with the to ngue-twisting name (pro = for; !act = milk). The role of prolactin in males is not pro-opiomelanocortin (POMC) (pro"o"pe-o-rnah-lan"o-kor' tin). well understood. ACTH sti mulates the adrenal cortex to release corticosteroid Unlike other a nterior pituitary hormones, PRL release is honnones, most importantly glucocorticoids that help the body controlled primarily by an inhibitory hormone, prolactin - resist stressors. inhibiting hor m one (PIH), now k nown to be dopamine, ACTH release, elicited by hypothalam ic corti cotr opin- which prevents prolactin secretion. Decreased PIH secretion releasing hor mone (CRH ), has a daily rhyth m, \Vi th levels leads to a surge in PRL release. There are a number of prolac- peaking in the morning, shortly before awakening. Rising levels tin-releasing factors, including TRH, but their exact roles are of glucocorticoids feed back and block secretion of CRH and not well understood.  Chapte r 16 The Endocrine System 617 In females, prolacti n levels rise and fall in rhythm with 12. List the four a nterior pituitary hormones that a re tropic estrogen blood levels. Estrogens stimulate prolactin release, hormones and name their ta rget glands. both directly and indirectly. A brief rise in prolactin levels just - - - - - - - - - - For answers, see A nswers Appendix. before the menstrual period partially accounts for the breast swell ing and tenderness some women experience at that time, but because this PRL stimulation is so brief, the breasts do not The thyroid gland controls 16. 7 produce milk. In pregnant women, PRL blood levels rise dra- matically toward the end of pregnancy, a nd milk production metabolism becomes possible. After birth , the infant's suckling stimulates Learning Outcomes release of prolactin-releasing factors in the mother, encouraging Ill> Describe the effects of t he two groups o f hormones continued milk production. prod uced by the t hyroid gland. Ill> Follow t he process of thyroxine format ion and release. -, HOMEOSTATIC CLINICAi.! Location and Structure ~--. ~ - IMBALANCE 16. 3 Hypersecretion of prolactin is more common than hyposecre- The butterfly-shaped thyroid glan d is located in the anterior tion (which is not a problem in anyone except women who neck, on the trachea just inferior to the larynx (Figure 16. J choose to nurse). In fact, hyperprolactine,nia is the most fre- and Figu re 16.Sa). A median tissue mass called the isthmus querlt abnormality of anterior pituitary tumors. Clinical signs (is'mus) connects its l\vo lateral lobes. The thyroid gland is the include inappropriate lactatio n, lack of menses, inferti lity in largest pure endocrine gland in the body. Its prodigious blood females, and impotence in males. supply (from the superior and inferior thyroid arteries) makes thyroid surgery a painstaking (and bloody) endeavor. Internall y, the gl and is comp osed of holl ow, spherical Check Your Understanding follicles (Figure 16.Sb). The \Valls of each foll icle are formed 10. What is the key difference between the way the hypothalamus largely by cuboidal or squamous epithelial cells called fol- comm unicates with the anterior pituitary and the way it licular cells, \vh ich produce the glycoprote in thyroglob ulin comm unicates with the posterior pituitary? (thi"ro-glob'u-lin). The central cavity, or lumen, of the follicle 11. Zoe drank too much alcohol one night and suffered from a stores colloid , an amber-colored, sticky material consisting of headache and nausea the next morning. What ca used these thyroglobulin molecules with attached iodine atoms. Thyroid " hangover" effects? hormone is derived frorn this iodinated thyroglobulin. Hyoid bone - - -, Superior thyroid Parafollicular cells -=~ Common carotid - ~ artery (secrete calcitonin) artery Inferior thyroid artery Follicular cells (secrete thyroid hormone) i==;-- Colloid· filled follicles Aorta - - - - - - ~ (a) Gross anatomy of the thyroid gland, anterior view (b) Photomicrograph of thyro id gland follicles (31 5x) Figure 16.8 The thyroid gland. Practice Histology questions: MasteringA&P' > Study Area > Lab Tools > PAL  Chapte r 16 The Endocrine System 619 - -Rough ER ;fTyrosines (part of thyroglobulin molecule) Golgi - - -.... ) ~{ @ Iod ine is attached to tyrosi ne apparatus ~ lloid, forming DIT and MIT. G) Thyrog lobu lin is synthesized and I I discharged into the foll icle lumen. I Iodine lDIT 1 MIT Thyro · globulin @iodide colloid is oxid ized., to iodine. @ iodide (I-) is trapped.. (actively transported in). ~.,::;,.,....- @ Iodinated tyrosines are - linked together to form T3 Lysosome __,( and T4. ® Thyroglobulin colloid is endocytosed and combined 0cleaveLysosoma l enzymes T and T from with a lysosome. Colloid in 4 3 lumen of thyroglobulin and hormones d iffuse into bloodstream. follicle Figure 16.9 Synthesis of thyroid hormone. Only a few tyrosines of the thyroglobulins in the colloid are illustrated. The unstructured yellow substance in the follicle lumen is colloid. (MIT = monoiodotyrosine; DIT = diiodotyrosine) more colloid to "restock" the follicle lumen. As a general rule, higher ins ide the cell than in blood.) Once trapped inside TS H levels are lower during the day, peak just before sleep, and the follicular cell, iodide then moves into the follicle lumen remain high during the nig ht. Consequently, thyroid hormone by facilitated diffusion. release and synthesis follows a similar pattern. @ Iodide is oxidized to iodine. At the border of the follicular Let's examine ho\v follicular cells synthesize thyroid hor- cell and colloid, iodides are ox idized (by removal of elec- mone (Figure 16.9): trons) and converted to iodine (12). G) Thyrog lobulin is synthesized and d ischarged into the @ Iodine is attached to tyrosine. Iodine is attached to tyro- follicle lumen. After being synthesized on the ribosomes si ne amino acids that are part of the thyroglobulin molecule. of the follicular cell's rough endoplasrnic reticulum, thy- This iodination reaction, mediated by peroxidase enzymes, roglobulin is transported to the Golgi apparatus, where sugar occurs at the junction of the follicular cell and the colloid. molecules are attached and the thyroglobulin is packed into Attachment of one iodine to a tyrosine produces mon o- transport vesicles. These vesicles move to the apex of the iodotyrosine (MIT), and attachment of two iodines pro- follicular cell, where they discharge their contents into the duces diiodotyr osine (DIT). follicle lumen to become part of the stored colloid. @ Iodinated tyrosines are linked together to form T3 and @ Iodid e is trapped. To produce the functional iod inated hor- T4 Enzymes in the colloid link MIT and DIT together. Two mones, the follicular cells must accumulate iod ides (anions linked DITs result in T4 , and coupling of MIT and DIT of iodine, 1-) from the blood. Iodide trappi ng depends on produces T3. At this point, the hormones are sti ll part of the active transport. (The concentration of r- is over 30 times thyroglobulin colloid. 620 UNI T 3 Regulation a nd Integration of the Body ® Thyroglobulin colloid is endocytosed. To secrete the Thyroid hormone is critically important for normal growth hormones, the follicular cells must reclaim iodinated thy- and brain development in early childhood, so newborns are rou- roglobulin by e ndocytosis and combine the vesicles with tinely screened for hypothyroidism. Congenital hypothyroidis1n lysosomes. is usual ly caused by poor development of the thyroid gland. Cf) Lysosomal enzymes spl it T4 and T3 from thyroglobulin Rarely, a pi tuitary problem or maternal meclications may affect and t he hormones diffuse from the follicular cell into the baby's ability to make T H. In the first weeks of life, an infant the bloodstrea m. The main hormonal product secreted is with congenital hypothyroidism may have no symptoms at all, T4. Some T4 is converted to T3 before secretion, but most T 3 or may present with a weak cry, poor feeding, constipation, or is generated in the peripheral tissues. prolonged jaundice. Early treatment with oral thyroid hormone replacement is crucial and usually allows a normal, healthy life. Most affected children will require lifelong TH replacement. Tra nsport and Reg ulation The mos t common hyperthyroid pathology is G raves' Most T4 and T3 released into the blood immed iately binds to disease. In this autoimmune condi tion, a person makes abnor- thyroxine-binding globulins (TBGs) and other transport pro- mal antibod ies directed against thyroid foll icular cells. Rather teins produced by the liver. Both T4 and T 3 bind to target tissue than marking these cells for destruct ion as antibod ies normally receptors, but T 3 binds more tightly and is about l O tirnes more do, these antibodies paradoxically mim ic TSH and continu- active. Most peripheral tissues have the enzymes needed to con- ously stimulate T H release. vert T4 to T 3 by removing one iodine atom. Typical symptoms of Graves' clisease include elevated meta- Figure 16. 7 ( p. 616) shows the negative feedback loop that bolic rate; sweating; rapid, irregular heartbeat; nervousness; regulates blood levels of TH. Falling T H blood levels trigger and weight loss despite adequate food. Eyeballs may protrude release of thyroid-sti1nulating honno11e (TSH), and ultimately of more TH. Rising T H levels feed back to inh ibit the hypo- thalamic-anterior pituitary axis, temporarily shutting off the stimulus for TSH release. In infants, exposure to cold stimulates the hypothalamus to secrete thyrotropin-releasing hornwne (TRH), which triggers TS H release. The thyroid gland then releases larger amounts of thyroid hormones, enhancing body metabolism and heat pro- duction. Factors that inhibit TS H release include GHIH, dopa- mine, and rising levels of glucocorticoids. Excessively high blood iodide concentrations also inhibit TH release. , HOMEOSTATIC ~--. ~~ IMBALANCE 16.4 Both overactivity and underactivity of the thyroid gland can cause severe metabolic disturbances. Hypothyroid disorders may result from some thyroid gland defects or secondarily from inadequate TS H or TRH release. T hey also occur \vhen the thyroid gland is rernoved surgically and when dietary iodine (a) An enlarged thyroid (goiter); due to iodine deficiency is inadequate. In adults, the full-blown hypothyroid syndrome is called ,n yxed ema (mik"se-de' mah; "mucous swelling"). Symptoms include a low metabolic rate; feeling chilled; constipation; thick, dry skin and puffy eyes; edema; lethargy; and mental sluggish- ness. A goiter (an enlarged protruding thyroid gland) occurs if myxedema resul ts from lack of iod ine (Figure 16.10a). The follicular cells produce colloid but cannot iodinate it and rnake functional hormones. The pituitary gland secretes increasing amounts of TS H in a futile attempt to stimulate the thyroid to produce TH, but the only result is that the foll icles accu- mulate more and more unusable colloid. Depending on the cause, iodine supplernents or hormone replacement therapy can reverse rnyxedema. Before iodized sal t became available, the midwestern Un ited S tates \vas called the "goiter belt." Goiters were common (b) Bulging eyes (exophthalmos) of Graves' disease because this area had iodine-poor soil and no access to iodine- rich seafood. In places where goiters are especially common, Figure 16.10 Thyroid disorders. these goiters are called endemic goiters.  Chapte r 16 The Endocrine System 621 (exophthalinos) if the tissue behind the eyes becomes edema- Check Your Understanding tous and fibrous (Figure 16.l Ob). Treatments include surg ically 13. What is the difference between T3 and T4 ? Which one of these remov ing the thyroid gland or ingesting radioact ive iod ine is referred to as thyroxine? (1 311), which destroys the most active thyroid cells. 14. Why does TH require plasma proteins in order to move th rough blood? Where are the receptors for TSH located? - - - - - - - - - - For answers, see Answers Appendix. Calcitonin Calcitonin, a polypeptide hormone released by the p arafolli- cnlar, or C , cells of the thyroid gland in response to a rise in 16.8 The parathyroid glands bl ood Ca2 levels, does not have a known physiological role in humans. In fact, calcitonin does not need to be replaced in are primary regulators of patients whose thyroid gland has been removed. blood calcium levels However, at pharmacological doses ( doses higher than nor- mally found in the body), calcitonin has a bone-spari ng effect Learning Outcome and is given therapeut ically to patients to treat Paget's disease Ill> Indicate the general fu nctions of parathyroid hormone. and someti mes osteoporosis (bone diseases; ~ pp. 193- 194). At The tiny, yellow-brov,n par a thyroid glands are nearly hid- these high concentrations, calcitonin targets the skeleton, where den from vie\v in the posterior aspect of the thyroid gland it ( 1) inhibits osteoclast activity, inhibiti ng bone resorption and (Figure 16.11a). There are usually four of these glands, but release of Ca2 from the bony matrix, and (2) stimulates Ca2 the nu mber varies-as many as eight have been reported in uptake and incorporation into bone matrix. some individuals, and some may be located in other regions of the neck or even in the thorax. The parathyro id's g landu lar cells are arranged in th ick, branching cords containing scattered oxyphil cells and large numbers of smaller p arath yr oid cells (Figure 16.1 l b). The Pharynx--- (posterior aspect) Thyroid - -----r =--- Parathyroid gland cells (secrete r-"' '--"'--- Parathyroid parathyroid g lands hormone) (a) (b) Figure 16.11 The parathyroid g lands. (a) The pa rathyroid glands are located on the posterior aspect of the thyroid gland and are more inconspicuous than depicted. Practice Histology questions: MasteringA&P' > (b) Photomicrograph of parathyroid gland tissue (160x ). Study Area > Lab Tools > PAL 622 UNIT 3 Regulation a nd Integration of the Body parathyroid cells secrete parathyroid hormone. The function of for absorption of Ca2 + from food, but first the kidneys must the oxyphil cells is unclear. convert it to its active vitamin 0 3 form, calcitriol ( 1,25-dihy- P arathyr oid hormone (PTH), or parathormone, the protein droxycholecalciferol). PTH sti1n ulates this transformation. horrnone of these glands, is the single most important hormone controlling calciu1n balance in the blood. Precise control of cal- ~--a,,--- , HOMEOSTATIC cium levels is critical because Ca2+ homeostasis is essential for IMBALANCE 16.5 CLINICAi! so many functions, including transmission of nerve impulses, Hyperparathyroidis,n (excess PT H) is the third most common muscle contraction, and blood clotting. e ndocrine disorder. It is often caused by a parathyroid gland Falling blood Ca 2+ levels trigger PTH release, and rising tumor. Calcium leaches from the bo nes, whic h softe n a nd blood Ca2+ levels inhibit its release. PTH increases Ca2 + levels deform as fibrous connective tissue replaces their mineral salts. in blood by stimulating three target organs: the skeleton, the In osteitis fibrosa cystica, a severe form of this disorder, the kidneys, and the intestine (Figure 16.12). PTH release: bones have a moth-eaten appearance on X rays and tend to frac- Stimulates osteoclasts (bone-resorbing cells) to digest some ture spontaneously. The resulting hypercalcemia (abnormall y of the calcium-rich bony matrix and release ionic calcium and elevated blood Ca2+ level) has many outcomes, but the two most phosphates to the blood ( would increase plasma levels of glucose. Study Area > Lab Tools > PAL  Cha pte r 16 The Endocrine System 631 Stimulates glucose uptake by cells Insulin [ Stimulates glycogen formation Pancreas Blood glucose falls to normal range. Stimulus t Blood glucose level t BALANCE : Normal blood glucose level (about 90 mg/1 oo ml) ! Stimulus J Blood glucose level Blood glucose rises to normal range. Pancreas Stimulates glycogen Glucagon breakdown Fig ure 16.17 Insulin a nd glucago n f rom the pancreas reg ulate blood glucose levels. Insulin is not needed for glucose entry into liver, kidney, and to fat. Insulin also stimulates amino acid uptake and protein syn- brain tissue, all of \vhich have easy access to blood glucose thesis in rnuscle tissue. regardless of insulin levels. However, insuli n does have impor- tant roles in the brain-it participates in neuronal developrnent, Fact ors That Influence Insulin Release Pancreatic beta cells feeding behavior, and learning and memory. secrete insulin when stimulated by: Insuli n activates its receptor (a tyrosine kina~e enzyme), which Elevated blood glucose levels. This is the chief controlling factor. phosphorylates specific proteins, beginning the cascade that pro- Rising blood levels of amino acids and fatty acids. motes glucose uptake and insulin's other effects. After glucose Acetylchol ine released by parasympathetic nerve fibers. enters a target cell, insulin binding triggers enzymatic activities that: Hyperglycemic hormones (such as glucagon, epinephrine, Catalyze the oxidation of glucose for ATP production growth hormone, thyroxine, or glucocorticoids). This effect Join glucose molecules together to form glycogen is indirect and occurs because all of these hormones increase Convert glucose to fat (particularly in adipose tissue) blood glucose levels. As a rule, energy needs are met first, followed by glycogen for- Somatostatin and sympathetic nervous system activati on mation. Fi nally, if excess glucose is still available, it is converted depress insulin release. 632 UNIT 3 Regulation and Integration of the Body I Insulin All tissues Liver breaks down Skeletal muscle breaks - - - - -. - - - Adipocytes break down fat (lipolysis) glycogen to glucose down proteins ! I Glucose uptake Liver converts fats to ketone bodies ! (and usage) Liver converts amino L acids to glucose Blood I Blood glucose.,._ _ _ _____. I Blood pH due to ketone - - -- , (hyperglycemia) bodies (ketoacidosis) Urine f Glucose in urine (glycosuria) t Ketones in urine (ketonuria) ! ! Glucose "pulls" water Ketones "pull" cations into kidney tubules into kidney tubules Osmotic diuresis Loss of Na , K+, H+- in urine Signs and symptoms t Poly uria Polyphagia t Heart rhythm Acetone breath (I Urine output) (I Appetite) abnormalities I Rate and depth f Nausea, vomiting, abdominal pain of breathing Dehydration Central nervous f system depression, Polydipsia coma ( t Water intake) Figure 16.18 Conseque nces of insulin deficit (d iabetes mellitus). As you can see, blood glucose levels represent a balance of Pol yd ipsia. De hydration sti mulates hypothalamic thi rst humoral, neural , and hormonal influences. Insulin is the major centers, causi ng polydipsia, or excessive thirst. hypoglycemic factor that counterbalances the many hypergly- Polyphagia. Polyphagia refers to excessive hunger and food cemic hormones. consumption, a sig n that the person is "starvi ng in the land of plenty." Al though plenty of glucose is available, the body cannot use it. Instead, the body breaks down protein and fat.- HOMEOSTATI C to supply e nergy, and this is thought to stimulate appetite. ~--:&._,-.... I MBALANCE 16.10 Whe n sugars cannot be used as cellular fuel, more fats are Diabetes 1nellitus (OM) results from either hyposecretion or mobilized, resulting in hi gh fatty acid levels in the blood, a hypoactivity of insulin. When insulin is absent, the result is condition called lipidemia. In severe cases of diabetes mellitus, type I diabetes ,nellitus. If insulin is present, but its effects are blood levels of fatty acids a nd their meta bolites (acetoacetic deficient, the result is type 2 diabetes ,nellitus. In either case, acid, aceto ne, and o thers) rise dramaticall y. The fatty acid blood glucose levels remain high after a meal because glucose metabolites, collectively called ketones (ke' to nz) or ketone is unable to enter most tissue cells. bodies, are organic acids. Whe n they accumulate in the blood, Diab etes is so common that you will encounter many the blood pH drops, resulting in ketoacidosis, and ketone bod- patients with this disease in your career. It is described in more ies begin to spill into the urine (ketonuria). detail in A Closer Look. The three cardinal signs of diabetes Severe ketoacidosis is life threatening. The nervous system mellitus (outli ned in Figure 16.1 8) are: responds by initiating rapid deep breathing (hyperpnea) to Polyuria. Excessive glucose in the blood leads to excessive blow off carbon dioxide frorn the blood and increase blood pH. glucose in the kidney filtrate where it acts as an osmotic (We will explain the physiological basis of this mechanism in diuretic (that is, it inhibits water reabsorption by the kidney Chapter 22.) Serious electrolyte losses also occur as the body tubules). The e nd result is polyuria, a huge urine output that rids itself of excess ketone bodies. Ketone bodies are negatively decreases blood volume and causes dehydration. charged and carry positive ions out with them, so sodium and