Chapter 9, Stress and Adaptation, Canadian Edition pp. 190-203.
Seye rat expt changes manfestatons of the body's attempt to to adapt to stmu stress as a state manfested by a specc syndrome of the body deveoped n response to any stmu that made an ntense systemc demand on t. Constancy of the nterna envronment stabe nterna envt milieu interieur Water Cannon ths knds of stabty (homeostass) thru a system of carefuy coordnated physoogc processes that oppose change argey automatc nvoe resstance to nterna and externa dsturbances Contro systems homeostatc contro system - coecton of nterconnected components that fucton to keep a physca or chemca parameter or the body reatvey constant Homeostass: purposefu mantenance of a stabe nterna envronment by coordnated physoogc processes that oppose change physoogc contro systems that oppose change operate by negatve feedback mechansms consstng of a sensor that detects a change, an ntegrator/comparator that sums and compares ncomng data wth a set pont, and an ehector system that returns the sensed functon to wthn the range of the set pont Feedback systems negatve feedback mechansms postve feedback mechansms HPA (hypothaamc-ptutary-adrena) axs GAS (genera adaptaton syndrome) genera systemc rxn; adaptve n rxn to a stressor; syndrome coordnated and dependent physca manfestatons 3 stages: 1. aarm stage gen. Stmuaton of sym NS and HPA axs --> reease catechoamnes and cortso 2. resstance stage most ehectve/economc defense --> nc cortso eves drop 3. exhauston stage stressor proongs and overwhems body, depetes resources --> systemc damage Stressors endogenous vs. Exogenous 2 factors determnng nature of stress response: propertes of stressor, and condtonng of person beng stressed eustress vs. Dstress condtonng factors vary among peope; nterna vs. Externa Neuroendocrne response mmune system ahects and s ahected by stress response acton of hormones nvoved n the neuroendocrne responses to stress Hormones Source of the hormones Physoogc ehects Catechoamnes (NE, Ep) LC, adrena medua Dec n nsun reease and Inc n gucagon reease - Inc gycogenoyss, guconeogeness, poyss, proteoyss, Dec gu uptake by perphera tssues - Inc n HR, cardac contractty, vascuar smooth musce contracton, - reax'n of broncha smooth musce CRF hypothaamus - ACTH reease from APG - nc LC neurons actvty ACTH Ant. Ptutary (APG) - synthess & reease of cortso Gucocortcod hormones e. cortso Adrena cortex - potentates actons of Ep and gucagon - nhbt reease/acton of reproductve hormones and TSH - dec mmune ces & namm. medators Mneraocortcod hormones e. adosterone Adrena cortex Inc Na+ absorp'n by kdney Antduretc hormones (ADH, vasopressn) Hypothaamus, post. Ptutary (PPG) - Inc water absorp'n by kdney - vasoconstrct bood vesses - stmuates ACTH reease Aostass physoogc changes n neuroendocrne, autonomc, & mmune systems, n response to ether rea or perceved chaenges to homeostass aostatc oad accumuaton of aostatc changes Integraton of stress response components @ CNS eve cerebra cortex cognton, attenton mbc system - emotons thaamus reay center, sensory nput hypothaamus coordnates endocrne and ANS ptutary gand - RAS retcuar actvatng system moduates menta aertness, ANS actvty, skeeta musce tone (muscuoskeeta tenson) Locus Caerueus area of bran stem, densey popuated w/ neurons producng NE centra ntegratng ste for ANS response to stressfu stmu LC-NE system --> hypothaamus, mbc system, hpoocampus, cerebra cortex adaptve advantage durng stress --> ght-or-ght responses most rapd basc survva responses nc n sympathetc actvty Cortcotropn-reeasng factor CRF found n hypothaamus and extrahypothaamc structures (mbc sys, bran stem) CRF --> secreton of ACTH (from APG) --> synthesze and secrete gucocortcod hormones (cortso) cortso as medator, and nhbtor (overactvaton of stress response does not occur) antagonze nsun, supress osteobast act, hematopoess, proten & coagen synthess, and mmune responses Angotensn II Sym NS stmuaton --> perphera RAAS renn-angotensn-adosterone system nc n vascuar tone, rena retenton of Na+ and water CNS ehects AT1 receptors n hypothaamus and LC --> enhance CRF formaton & reease, reease of ACTH, enhance stress-nduced reease of vasopressn from PPG, stmuates reease of NE from LC Growth hormones proong cortso presence --> suppresson of growth hormones, IGF-1, other growth factors CRF --> nc somatostatn --> nhbt GH secreton thyrod hormones cortso --> dec TSH & nhbt T4 to T3 converson (energy-savng) reproductve hormones CRF nuence reease/nonreease of reproductve hormones anovuaton, amenorrhea, dec spermatogeness, dec testosterone ADH/vasopressn hypotensve stress nc water retenton by kdney --> vasoconstrct bood vesses Serotonn / 5HT receptor agonsts --> nc secreton of stress hormones Immune response endocrne-mmune nteractons stress response --> suppress mmune response causa roe of stress n mmune-reated dsease or reverse: manfestatons of stress response = reecton of aternatons n CNS resutng form the mmune response monocytes and ymphocytes produce cytoknes n the bran share common sgna pathways sym NS and reease of catechoamnes ymph nodes, thymus and speen are supped wth ANS CRF actvates ANS thru mutsynaptc descendng pathways Ep + CRF + cortso = nhbt fn of mmune sys Copng and adaptaton to stress adaptabty hghy deveoped NS and ntegence --> repertore of adaptng mechansms copng strateges / mechansms means used to attan baance (bet stressor and abty to dea wth t) emotona and behavoura responses used to manage threats to our physoogc and psychoogca homeostass how we cope = how we perceve Adaptve capacty physoogc and anatomc reserve tme adaptaton most emcent wth gradual change genetcs age gender physca and menta heath status nutrton manutrton vs. Obesty seep-wake cyces bo rhythms, crcadan hardness personaty characterstc (sense of contro over envt, sense of havng purpose n fe, abty to conceptuaze stressors as a chaenger rather than a threat) psychosoca factors cose reatonshps wth others Chapter 41, Disorders of Endocrine Control of Growth and eta!olis", pp. 99#-1003 $1293 % 1301 in non-Canadian ed&. Dsorders of adrena cortca functon Contro of adrena cortca functon adrena gands medua (nner porton, 20%) secretes Ep and NorEp; part of sym NS cortex (outer porton, 80%) zona gomeruosa (outer) -> mneraocortcods zona fasccuata (mdde) --> gucocortcods, androgens zona retcuars (nner) --> gucocortcods, adrena androgens oss of adrena CORTICAL fn fata Hormones prod. By adrena cortex a sterods and syntheszed from acetate & choestero secreted n unbound state and bnd to pasma protens Adosterone prncpa mneraocortcod bnd to abumn reguate K+ and Na+ eves, & water baance reguated by renn-angotensn mechansm, & bood eves of K+ So, nc adosterone = Na+ retenton by dsta tubues of kdney; nc urnary osses of K+ Excess adosterone ow K+, musce weakness Low amt of adosterone hgh K+, cardac toxcty Cortso (hydrocortsone) ma|or gucocortcod bnd to cortcosterod-bndng gobun, some abumn reg by negatve feedback mechansms of HPA system CRH --> ACTH --> cortso durna varaton n ACTH peak n AM reguate metaboc fn of bosy and contro nammatory responses stmuates gu prod'n by ver, promotes proten breakdown, mobzaton of fatty acds aa used for guconeogeness moderate resstance to nsun --> rase bood gu eve (dabetcs and dabetes prone) emotona behavour synthetc cortso --> ant-nammatory reduce humora and ce-medated mmunty adrena nsumcency on wthdrawa of drugs suppresson of HPA system --> atrophy abrupt wthdrawa of drug --> acute nsumcency Adrena Androgens sex hormones DHEA and DHEAS bnd to abumn tte ehect on norma sexua fn, but contrb to puberta har growth DHEAS treat Addson dsease (n women) and aduts w/ dec DHEAS eves adrenopause Lver man ste of metabosm of hormones Adrena cortca nsumcency mneraocortcod decency - mpared sat reguaton & water emnaton gucocortcod decency mpared bood gu reguaton & contro ehects of mmune and nammatory responses Adrena cortca excess derangements n gu metabosm dsorder of Na+ and K+ reguaton (nc Na+ retenton and K+ oss) mpared stress response due to nhbton of nammatory and mmune response nc androgen eves (hrsutsm) p. 1296 Tests of adrena functon Bood eves of cortso, adosterone, and ACTH can be measured usng mmunoassay 24-hour urne specmen measurng the excre- ton of varous metaboc end products of adrena hormones Cushng syndrome: 24-hour urnary free cortso, ate-nght (between 11 pm and mdnght) serum or savary cortso eves, & the overnght 1-mg dexamethasone suppresson test admnstraton of dexamethasone - measurng negatve feedback suppresson of ACTH adrena tumors, ectopc ACTH-producng tumors unresponsve to ths method CRH tests - ptutary ACTH-secretng tumor (.e., Cushng dsease) Cortcotropn (cosyntropn) stmuaton testng s the most frequenty used dagnostc test to assess testng responsveness of the HPA axs. Congenta adrena hyperpasa CAH or adrenogenta syndrome congenta dsorder caused by an autosoma recessve trat n whch a decency exsts n any of the enzymes necessary for the synthess of cortso ncreased eves of ACTH and adrena hyperpasa Mneraocortcods may be produced n excessve or nsumcent amounts femae nfants nc andronges = vrzaton syndrome (ambguous gentaa, enarged ctors, fused aba and urogenta snus) 21-hydroxyase decency states exsts smpe vrzng CAH - mpars the synthess of cortso compete sat-osng enzyme decency - decent producton of adosterone and ts ntermedate 11--hydroxyase defcency s rare excessve androgen producton and mpared converson of 11- deoxycortcosterone to cortcosterone excess 11-deoxycortcosterone --> hypertenson treatments: ora or parentera gucocortcod repacement sat-osers: Fudrocortsone acetate reconstructve surgery Adrena cortca nsumcency 1. Prmary (Addson dsease) adrenal cortical hormones are deficient and ACTH levels are elevated because of lack of feedback inhibition all the layers of the adrenal cortex are destroyed. Autoimmune destruction most common cause Other causes: TB, metastatic carcinoma, funal infection !"articularly histo"lasmosis#, cytomealovirus infection, amyloid disease, and hemochromatosis$ ac%uired immunodeficiency syndrome &anifestations: do not become a""arent until a""roximately '() of the land has been destroyed mineralocorticoid deficiency increased urinary losses of sodium, chloride, and *ater, alon *ith decreased excretion of "otassium ++, hy"onatremia, loss of extracellular fluid, decreased cardiac out"ut, and hy"erkalemia abnormal a""etite for salt Orthostatic hy"otension lucocorticoid deficiency "oor tolerance to stress hy"olycemia, lethary, *eakness, fever, and astrointestinal sym"toms hy"er"imentation resultin from elevated ACTH levels skin looks bron-ed or suntanned, ums and oral mucous membranes may become bluish+black Treatment: chronic metabolic disorder + lifetime hormone re"lacement thera"y oral re"lacement thera"y, *ith hiher doses bein iven durin "eriods of stress "harmacoloic aent . both lucocorticoid and mineralocorticoid activity usually Hydrocortisone /ludrocortisone 0H1A2 reular schedule for meals and exercise 2. Secondary (dsorder of HPA system) resut of hypoptutarsm or because the ptutary gand has been surgcay removed common cause(s): rapd wthdrawa of gucocortcods that have been admnstered therapeutcay for asthma or an exacerbaton of mutpe sceross --> suppress HPA system --> adrena cortca atrophy --> oss of cortso prod'n Acute Adrena Crss fe-threatenng onset of adrena crss may be sudden, or t may progress over a perod of severa days Massve batera adrena hemorrhage --> acute fumnatng form of adrena nsumcency Treatment: hormone repacement therapy (combnaton of gucocortcods and mneraocortcods) ve Ss of management shoud be foowed: (1) Sat repacement, (2) Sugar (dextrose) repacement, (3) Sterod repacement, (4) Support of physoogc functonng, and (5) Search for and treat the underyng cause (e.g., nfecton) Gucocortcod hormone excess (Cushng Syndrome) manfestatons of hypercortsosm from any cause 3 forms result from excess lucocorticoid "roduction by the body "ituitary + excessive "roduction of ACTH by a tumor of the "ituitary land adrenal formation + benin or malinant adrenal tumor ecto"ic Cushin 2yndrome + by non+"ituitary ACTH+secretin tumour &anifestations: 4fat5 abdomen, 4buffalo hum"5, 4moon face5, muscle *eakness, thin extremities, stretch marks, hy"okalemia !excessive 67 secretion# 8 hy"ertension !9a7 retention# inhibited inflammatory and immune res"onses inc astric acid secretion ++, astric ulceration, bleedin 0ianosis: :;+hour excretion of cortisol in urine "rovides a reliable and "ractical index of cortisol secretions loss of the diurnal "attern of cortisol secretion overniht <+m dexamethasone su""ression test is also used as a screenin tool for Cushin syndrome measure "lasma ACTH Treatment: remove or correct the source of hy"ercortisolism *ithout causin "ermanent "ituitary or adrenal damae Transs"henoidal removal of a "ituitary adenoma or a hemihy"o"hysectomy =emoval of only the tumor rather than the entire "ituitary land Cortisol re"lacement thera"y >ncidental adrenal mass incidentaloma is a mass lesion found unex"ectedly in an adrenal land by an imain "rocedure if they are malinant and if they are hormonally active ?rimary adrenal carcinoma is %uite rare, but other cancers, "articularly lun cancers, commonly metastasi-e to the adrenal land