curs endocrinologie intro final ro
TRANSCRIPT
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SISTEMUL ENDOCRIN
= sistem de glande ce secreta mesageri chimici (hormoni) in lichidele organismului
Alaturi de sistemul nervos, reprezinta cele 2 sisteme de reglare a functiilor organismului
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= substanta chimica secretata in lichidele organismului de catre o celula (grup de celule) si care exercita un efect de control fiziologic asupra altor celule din organism
O molecula se numeste hormon doar atunci cand este privita in contextul rolului acesteia intr-un sistem biologic de comunicatie
HORMONUL
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ReproducereCrestere si dezvoltareMobilizarea apararii organismului
Mentinerea homeostazieiReglarea metabolismului
ROLURILE HORMONILOR
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N.C.Paulescu
CONTRIBUTIA ROMANEASCA IN ENDOCRINOLOGIE
C.I.Parhon
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Gr.T.Popa
CONTRIBUTIA ROMANEASCA IN ENDOCRINOLOGIE
Gh.Marinescu
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Neurohormoni = Hormoni produsi si eliberati de catre neuroni
ex: TRH, GnRH, CRH, OTC, ADH, NAHormoni glandulari = Hormoni produsi si
eliberati in glandeex: EG,PG, MLT, Ins, DHEA, A
Hormoni locali = Hormoni secretati de neuroni sau glande cu rol local, paracrin/autocrin
ex: G, CCK, S, Ggn, VIP, GIP
CLASIFICAREA HORMONILOR (ORIGINE)
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Hormoni compusi din amino-aciziProteine Peptide Amine
Steroizi – compusi din colesterol Prostaglandine – compusi din lipide active
CLASIFICAREA HORMONILOR (STRUCTURALA)
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COMUNICAREA INTERCELULARA
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1. Sub forma de precursorEx: glandele secretoare de hormoni steroidieni(corticosuprarenala, ovare, testicule): granule de lipide cu colesterol
2. ExtracelularEx: glanda tiroida: tiroglobulina (glicoproteina) extracelular, cu molecule de hormon atasate; rolul foliculului
3. IntracelularMetoda predominantaEx: medulosuprarenala;in granule subcelulare(100-400μm)
STOCAREA HORMONILOR
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SECRETIA HORMONILOR
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Transportul substantelor catre tesuturile tinta se face prin fluxul sangvin (+limfatic)
Hormonii exista in 2 forme:Forma combinata de proteine transportoare specifice: Albumine Globuline
TBG – thyroid binding globulin CBG – cortisol binding globulin
Forma libera (mai putin reprezentata)Intre cele 2 forme exista un echilibru
dinamic
TRANSPORTUL HORMONILOR
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Concentratie foarte mica(de la 1pg/ml pana la cateva μg/ml)
Hidrosolubili – dizolvati in plasma, transportati de la locul secretiei spre celulele tinta
ex: peptide si catecolamineLiposolubili – legati de proteine
plasmatice in proportie > 90%ex: steroizi si tiroidieni
TRANSPORTUL HORMONAL
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MECANISMUL DE ACTUINE AL HORMONILOR (DUPA STRUCTURA)
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MECANISMUL DE ACTUINE AL HORMONILOR (DUPA STRUCTURA)
Alti mediatori intracelulari: IP3, DAG, Ca++
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Peptidici:Fagocitoza (intracelular)Hidroliza enzimatica (extracelular)
Aminoacizi:Oxidare (MAO, COMT) [catecolamine]
Steroizi:DehidrogenareConjugare
METABOLIZAREA HORMONILOR
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Prin procese metabolice:Proteoliza (hormoni peptidici)Transformare in ficat
Prin excretie:RenalBiliar
! Circuitul enterohepatic
ELIMINAREA HORMONILOR
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A. Reglarea hormonogenezei1. Neurogen2. Feed-back3. Bioritm
B. Reglarea la nivelul receptorilor
4. Down regulation5. Up regulation6. Reglare postreceptor
REGLAREA SECRETIEI HORMONALE
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1. Mecanismul neurogenHipotalamusMedulosuprarenalaGlanda pineala (epifiza)Pancreasul
REGLAREA HORMONOGENEZEI
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2. Mecanismul de feed-backLungScurtUltrascurt
REGLAREA HORMONOGENEZEI
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3. BioritmulUltradianCircadianCircatrigintanCircumanual
REGLAREA HORMONOGENEZEI
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Patologie legata de o secretie hormonalaInsuficientaExagerata
Posibilitatea de a suplini functia (hormonoterapie)
IMPLICATII PATOLOGICE SI FARMACOLOGICE
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Anatomice: Rx, US, CT, IRMFunctionale:
BiologiceChimiceImunologice
Morfofunctionale: Scintigrafia tiroidiana
METODE DE EXPLORARE IN ENDOCRINOLOGIE
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HIPOTALAMUSUL
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Hipotalamus-adenohipofiza = Sistem port hipotalamo-hipofizar(Gr.T.Popa & U. Fielding | 1930)
Hipotalamus-neurohipofiza = Tract hipotalamo-hipofizar
AXUL HIPOTALAMO-HIPOFIZAR
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ANTERIOR
POSTERIOR
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1. Neurotransmitatori2. Neuromodulatori3. Neurohormoni
HORMONII HIPOTALAMICI
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NoradrenalinaDopaminaSerotoninaAcetilcolinaGlutaminaGABAGlicinaATP
NEUROTRANSMITATORII
= Eliberati local, sinaptic, asigurand transmiterea impulsului nervos
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Peptide opioideEndorfineEnkefalineDinorfine
NeurotensinaAngiotensina cerebrala
NEUROMODULATORII (CIBERNINELE)
= Se elibereaza extrasinaptic, actionand asupra neuronilor vecini (local)
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GHRH/SomatoliberinaGIH/SomatostatinaTRH/TireoliberinaCRH/CorticoliberinaPRFPIF/DopaminaGnRH/LHRH/GonadoliberinaMRHOTCADHPOMC,Proenkefalina,Neurofizine,etc
NEUROHORMONII
Nucleii magnocelulari Neurohipofiza
RH=liberineIH=statine
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Secretate in hipotalamus (neuronii eminentei mediane) si apoi conduse in hipofiza anterioara prin sistemul port hipotalamo-hipofizar
Ele actioneaza pe celulele glandulare din hipofiza anterioara, modulandu-le secretia
Hipotalamusul integreaza informatii din mai multe surse
LIBERINELE SI STATINELE
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Terminatii nervoase ale tracturilor din nucleii supraoptic si paraventricular ajung prin tija pituitara in neurohipofiza
Hormonii sunt sintetizati in corpurile celulare si transportati legati de proteine carrier (neurofizine)
ADH (nSO), OTC (nPV)Hormonul se separa cu usurinta de
neurofizina (izolata nu are vreo functie cunoscuta)
NEUROHORMONII RETROHIPOFIZARI
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HIPOFIZA
= glanda pituitara• Glanda mica
endocrina (1 gram); dimensiuni milimetrice (10/12/6 mm)
• Localizata in saua turceasca a osului sfenoid
• =“master gland”
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= Adenohipofiza (adeno=glanda)Pars distalis anterioaraPars intermediaPars tuberalis (ce acopera tija pituitara)
LOBUL ANTERIOR
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= Adenohipofiza (adeno=glanda)Pars distalis anterioaraPars intermediaPars tuberalis
LOBUL ANTERIOR
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Formata din aglomerari neregulate de celule secretorii, inconjurate de o retea bogata de capilare sinusoide, cu endoteliul fenestrat
Celulele adenohipofizei contin granulele in care se gasesc hormonii secretati
Raspunde semnalelor transmise prin sistemul port hipotalamo-hipofizar
NU are BHE
ADENOHIPOFIZA
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1. STH2. TSH3. PRL4. FSH5. LH
HORMONII ADENOHIPOFIZEI
6. POMCA. ACTHB. β-LPHC. β-
endorfinaD. MSH αE. MSH βF. Enkefaline
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Glandulotropi:CSR: ACTHGonade: FSH,LH
Tiroida: TSH
HORMONII ADENOHIPOFIZEI
Nonglandulotropi:
STH PRL α,β,γ MSH LPH
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ACTH
• Polipeptid 39 aa• Clivat din POMC• Dupa o perioada
scurta de timp, este clivat la randul lui in
α MSH + CLIP• Se poate sintetiza in
laborator (23 aa), pentru testul de stimulare cu ACTH sau tratamentul de substitutie
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POMC
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Stimuleaza cresterea si productia de hormoni steroizi in suprarenala (in zonele fasciculata si reticulara)
Actioneaza prin mesageri secunzi ce activeaza enzime (desmolaza) ce convertesc CHOL pregnenolon
Creste transportul de CHOL in mitocondrie si stimuleaza hidroliza lui
Stimuleaza captarea de lipoproteine in celulele CSR
ACTHACTIUNI CSR
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Cresterea pigmentarii pielii (MSH)
Stimularea lipolizei (LPH)
Retentia hidrosalina(efect mineralocorticoid)
ACTHACTIUNI EXTRA-CSR
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Sistem complex de factori
CRH creste sinteza de ACTH (eliberare pulsatila)
Efectele stresului sunt mediate prin ADH, AT II, CRH, SNC
Cortizolul exercita feedback negativ (Hyp+H)
REGLAREA ACTH
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= constelatii de semne/simptome datorate expunerii cronice la exces de glucocorticoizi
ACTH dependent:Boala Cushing = adenom hipofizar (ACTH)Sindrom de ACTH ectopic
ACTH independent:Adenom CSRCarcinom CSRHiperplazie nodulara CSR
SINDROMUL CUSHING
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= insuficienta suprarenaliana cronica (scaderea secretiei de glucocorticoizi si adesea mineralocorticoizi)Majoritatea simptomelor: nespecifice, insidioaseHiperpigmentare in hipocorticismul primar(cauza suprarenaliana)
BOALA ADDISON
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Structura similaraRegleaza:
Dezvoltarea, cresterea, maturatia pubertara
Procesele reproductiveSecretia hormonilor sexosteroizi gonadici
HORMONII GONADOTROPIFSH + LH
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La femeiLH
folicul ovarian folicul galben
↑ Steroidogeneza (cel interstitiale)
↑ Productia de estrogeni din androgeni (cel granuloase)
FSH ↑ Cresterea ovarului in
greutate ↑ Dezvoltarea si maturatia
foliculului ovarian
FSH + LHROLURI
La barbatiLH
↑ Steroidogeneza (cel interstitiale = Leydig)
↑ Cresterea testiculara
FSH ↑ Cresterea testiculara
(dezvoltarea tubilor seminiferi)
↑ Productia de estrogeni din androgeni (cel granuloase = Sertoli)
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LA FEMEI
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LA BARBATI
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Hormon glicoproteicDepozitat in granulele secretoare citoplasmice din celulele tireotrofe (din aria anteromediala a glandei hipofize)
2 subunitati, α si β
TSH= H. TIREOTROP
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Regleaza cresterea, dezvoltarea si metabolismul glandei tiroide
Stimuleaza sinteza si secretia hormonilor tiroidieni
Actioneaza prin stimularea productiei de AMPc
TSHACTIUNI
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Mecanisme:TRH (+)T3,T4 TSH (-)T3,T4 TRH (-)Restrictia alimentara(-)
Expunerea la frig (+)
Ritmul circadian (noaptea +)
Cortizol, STH (-)
REGLAREA SECRETIEI DE TSH
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Polipeptid 191 aaSimilaritati cu PrlForme multiple (75 % = STH circulant)Specificitate de specieSe poate obtine industrial si comercial
STH= SOMATOTROPINA, GH
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Directe (STH)Indirecte (IGF-1)
Stimuleaza cresterea si dezvoltarea tesuturilor, organelor si intregului organism
Fenomene anabolizante + stimularea condrogenezei si osteosintezei
STHACTIUNI
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Creste preluarea aminoacizilor din plasma in celule incorporarea lor in noi proteine retentie de azot scade productia de uree
Amplifica rata de sinteza proteica in majoritatea celulelor
STHMETABOLISM PROTEIC
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Activeaza lipaza hormon-sensibila mobilizeaza grasimile neutre din tesutul adipos cresc AG in plasma creste preluarea si oxidarea AG in muschiul scheletic si ficat
Poate produce steatoza hepatica
STHMETABOLISM LIPIDIC
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Efect hiperglicemiantScade preluarea si utilizarea glucozei in muschiul scheletic si tesutul adipos (efect de crutare)
Glicogenoliza hepaticaScade sensibilitatea periferica la insulina
STHMETABOLISM GLUCIDIC
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REGLAREA SECRETIEI STH
GHIH(SS), GHRHHipoglicemie (+)Cresterea unor aminoacizi
(+)SomnulStresulExcercitiul fizic
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Hormon proteic 199 aa3 punti bisulfidiceProdusa:
Celule somatomamotrope (hipofiza)
HipotalamusUter, placenta, sanLimfocite
Concentratii serice bazale asemanatoare B ~ F
PROLACTINA
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Initierea si mentinerea lactatieiMamogeneza (cresterea si dezvoltarea gl mamare)
Lactogeneza (initierea lactatiei)Galactopoieza (mentinerea productiei de lapte)
Alte actiuni:Comportament prenatalReproducere (secretia crescuta de Prl = efect inhibitor)
PROLACTINAACTIUNI
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Inhibitie tonica din partea PIF (dopamina)
Controlata si de PRF
Stimuli:NastereaStimularea sanilorStres
PROLACTINAREGLAREA
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Nanismul (piticism, dwarfism)Deficienta de STH prepubertar
Bine proportionati Inteligenta normalaTendinta spre hipoglicemie In functie de restul hormonilor hipofizari, pot ajunge sau nu la maturitate sexuala
STHIMPLICATII PATOLOGICE
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Pigmeul AfricanNivele normale de STH sericLipseste cresterea IGF pubertara
Deficienta STH la adultScade greutatea corporala prin diminuarea depozitelor de lipide si proteine
Oboseala musculara si epuizare rapida
STHIMPLICATII PATOLOGICE
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GigantismProductia de STH inainte de pubertate
Asociaza si cresterea greutatii corporale
Alte complicatii Intoleranta la glucoza Cetoacidoza Probleme cardiovasculare
Cel mai frecvent datorita unor adenoame
STHIMPLICATII PATOLOGICE
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AcromegaliaSTH secretat excesiv dupa ce epifizele s-au inchis
Survine o crestere apozitionala
Cresc si tesuturile moiDe obicei datorita unei tumori secretante de STH
STHIMPLICATII PATOLOGICE
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HiperprolactinemiaIn prolactinoame (~ 70% din tumorile hipofizare)
Medicamente ce interfera cu secretia de dopamina (PIF)
Clinic:Oligomenoree / amenoree (femei)InfertilitateSemnele masei hipofizare
PROLACTINAIMPLICATII PATOLOGICE
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HipoprolactinemiaDe regula insoteste o hipofunctie hipofizara generala
Izolat, cu o componenta genetica familiala
PROLACTINAIMPLICATII PATOLOGICE
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HIPOPITUITARISMUL
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PanhipopituitarismulCauze multiple: hipotalamice, hipofizare
Semnele disfunctiei tuturor hormonilor
Apoplexia hipofizaraInfarct acut al hipofizei: tumori, traume, tulburari de coagulare, postpartum (Sheehan)
In general afectata adenohipofiza
HIPOPITUITARISMUL
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Sindromul de sa turceasca goalaSpatiul subarahnoidian se extinde in saua turceasca (mareste saua)
Adenohipofiza comprimata poate sa functioneze normal
HIPOPITUITARISMUL
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Functioneaza ca o glanda endocrina atipica (hormonii sunt sintetizati in hipotalamus, fiind doar stocati in lobul hipofizar posterior, de unde sunt eliberati la semnale hipotalamice)
nSO ADH nPV OTCVascularizatie extensiva cu capilare fenestrate
HH sintetizati ca pre-pro-hormoni, legati de neurofizine
ADH – NF II OTC – NF I
NEUROHIPOFIZA
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NonapeptidAsemanator cu OTC
(de aceea activitatea fiziologica prezinta suprapuneri)
Rol AntidiureticVasoconstrictorDe stimulare a secretiei ACTH
In invatare si memorie
ADH= VASOPRESINA
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ACTIUNI RENALE
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ACTIUNI CARDIOVASCULARE
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EFECTE FINALE CARDIOVASCULARE
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Stimuli:Cresterea osmolaritatii LEC. Osmoreceptorii centrali:Hipotalamusul medial In jurul Nso, NPV, aria AV3VFormatiuni hipotalamice vecine (OSF, NPO,OSC)
Sistemul osmoreglator este sensibil in intervalul 280-295 mOsm/kg
REGLAREA ADH
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Stimuli:Voloreceptori (Aparat cardiovascular)
Baroreceptori: Joasa presiune (Atrii, Vene mari, Vase pulmonare)
Inalta presiune (Arc aortic, sinus carotidian)
Schimbarea de volum devine un stimul semnificativ cand volumul sangvin circulant scade sub 8-10%
REGLAREA ADH
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Setea este stimulata de:Osmolaritate serica crescuta
Volum vascular scazutSecretia de ADHAT II e considerata una dincomponentele majore
REGLAREA ADH
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Nonapeptid ~ ADHActiuni:
Motilitatea uterina Ejectia laptelui Antidiuretic Contractia musculaturii
netede viscerale Vasodilatatie cutanata Creste concentratia
plasmatica a Prl Favorizeaza eliminarea
spermatozoizilor in canaliculele seminale
Neuromediator
OCITOCINA
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Diabetul insipid = deficit de ADHNeurogen
Idiopatic (25%)Dobandit (neurohipofiza)Genetic (rar – mutatie in gena NF II)
Tratament : ADH exogenNefrogen
Dobandit (rinichi)Genetic (rar – mutatie in gena V2, Aq2)
Tratament: Tiazide + Amilorid (diuretice)Psihogen
ADHIMPLICATII PATOLOGICE
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SIADHCarcinoame pulmonareTBC pulmonarTraumatismAnestezieDurere
Hormonii sunt produsifara controlul secretiei
ADHIMPLICATII PATOLOGICE
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SUCCES!