C2. Curs Hipotalamus Si Diabet Insipid 2014

Embed Size (px)

DESCRIPTION

medicina

Text of C2. Curs Hipotalamus Si Diabet Insipid 2014

  • Neuroimagistica seteiZece subiecti au efectuat PET-CT si o evaluare psihologica a setei (Denton, PNAS, 96, 5304-5309, 1999)

    Oxytocin-like peptides 1 2 3 4 5 6 7 8 9Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly (NH2) Oxytocine * * * * * * * Ile * Mesotocine * * * Ser * * * Ile * Isotocine * * * Ser * * * Glu * Glumitocine * * * * * * * Val * Valitocine * * * Asn * * * * * Aspargtocine

    Vasopressin-like peptides

    1 2 3 4 5 6 7 8 9Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly (NH2) Vasopressine * * * * * * * Lis * Lisine-vasopressine

    * Phe * * * * * * * Phenipressine

    * * Ile * * * * * * Vasotocine

    Structura hormonilor neurohipofizari

    TM ITM IIITM IITM IVTM VTM VITM VIIReceptor V1a

    Noyau paraventriculaire

    Noyau supraoptique

    Neurohypophyse de rat -ME

    VasopresinaOxitocinaUterSinGonade? AH?AdipociteCreierSuprarenaleFicatAHMuschi netedRinichiHipotalamusCreier

    SeteAVPSindroame poliuro-polidipsiceHipotalamus

    Polidipsie psihogena

    Absenta AVP

    Vasopresinaza

    Rinichi: rezistenta la AVPinsuficienta renala

    IRM normalLechan RM. Neuroendocrinology of Pituitary Hormone Regulation. Endocrinology and Metabolism Clinics 16:475-501, 1987

    Diabet insipid: Deficitul de AVPDeteriorarea hipotalamusului (site-ul de sinteza AVP), tijei pituitare (transportul AVP) sau a retrohipofizei (site-ul de stocare AVP), va duce la o boala cunoscut sub numele de diabet insipid central.Muli dintre aceti pacieni nu au hipersemnal in T1 in lobul posterior al hipofizei pe imagistica RMN a creierului.

    Diabet InsipidCaracteristici clinice sunt rezultatul deficientei de AVP Excreia unor volume mari de urin (poliurie) Excreia de urin diluat (OSM

  • Hipernatremia Na+> 145 mEq/L Hipodipsie primara, DI (central sau nefrogen)

    Diureza osmotica (DZ dezechilibrat)

    Neurologic: astenie, stare confuzionala, convulsii, deficit focal.

    Trat: Desmopresina 10 mg intranazal sau 0.12 mg x 3/zi slg (Minirin Melt)aport hidric po sau 5% glucoza: 1-2 L

  • Hiponatremia Neurologic: greata, edem cerebral, cefalee, obnubilare, coma

    Semnele afectiunii de baza (Addison, hipopituitarism, SIADH)

    Scadere Na+ hTaRapiditatea instalarii hNa+Na+ < 120 mEq/L: risc vital

  • Hiponatremia - tratamentEtiologicSIADH: Restrictie hidrica Antagonist Rec V2 AVP = Vaptan

    Substitutie corticoida (HHC Fludrocortizon, 2 x 0.1 mg/zi)

    Substitutie tiroidiana: LT4 in doze de la 25 la 100 mg/zi, sub protectie antiagreganta

    Cresterea capitalului de Na: < 10-15 mEq / 24h

    Solutii fiziologice sau saline hipertone 0.5 - 2 L/zi

    Creste> 15mEq/zi Risc de mielinoza pontina (sdr de demielinizare osmotica), mai sever in hNa+ cronica

    Reglarea i explorarea hipofizeiHipofiza: anatomie funcionalTipuri celulare i implicaii funcionaleComunicarea hipotalamo hipofizarAxa de cretere: reglare i explorare funcionalAxa tiroidian: reglare i explorare funcionalAxa suprarenal: reglare i explorare funcionalAxa gonadic: reglare i explorare funcional Explorarea: farmacologic / fiziologic ?

    Concluzii

    Cell types in pars distalis

    Cell Type Secretory ProductsCell Population %Somatotroph Growth hormone 50Lactotroph Prolactin15Corticotroph Adrenocorticotropic hormone 15Thyrotroph Thyroid stimulating hormone10GonadotrophLuteinizing hormone-Follicle-stimulating hormone10

    C-corticotroph: F -Folliculostellate cell; G-gonadotroph; L-Lactotroph; S-somatotroph, T -thyrotroph; UN-unknown.

    Substances

    Cell Types

    Peptides:

    Activin B, inhibin, follistatin

    F, G

    Aldosterone-stimulating factor

    UN

    Angiotensin II (angiotensinogen, angiotensin I-converting enzyme, cathepsin B, renin)

    C,G,L, S

    Atrial naturetic peptide

    G

    Corticotropin-releasing hormone-binding protein

    C

    Dynorphin

    G

    Galanin

    L, S,T

    GAWK (chromogranin B)

    G

    Growth hormone-releasing hormone

    UN

    Histidyl proline diketopiperazine

    UN

    Motilin

    S

    Neuromedin B

    T

    Neuromedin U

    C

    Neuropeptide Y

    T

    Neurotensin

    UN

    Protein 7B2

    G, T

    Somatostatin 28

    UN

    Substance P (Substance K)

    G,L,T

    Thyrotropin-releasing hormone

    G, L,S,T

    Vasoactive intestinal poltpeptide

    G,L,T

    Growth factors:

    Basic fibroblast growth factor

    C,F

    Chondrocyte growth factor

    UN

    Epidermal growth factor

    G,T

    Insulin-like growth factor I

    S,F

    Nerve growth factor

    UN

    Pituitary cytotropic factor

    UN

    Transforming growth factor alpha

    L,S,G

    Vascular endothelial growth factor

    F

    Cytokines:

    Interleukin-I beta

    T

    Interleukin-6

    F

    Leukemia inhibitory factor

    C,F

    Neurotransmitters:

    Acetylcholine

    C,L

    Nitric oxide

    F

    Disorders of the Endocrine SystemExcess or deficiencyImpaired synthesisTransport and metabolism of hormonesResistance to hormone action

    Reglarea Axei GH GHRH (44)SMS (14) GH IGF1 GHRP Ghrelin

    Insulin Tolerance Test0.1/0.15 UI/Kgc, i.v.Obese: 0,3 UI/Kgc

    Contraindicate Epileptic seizuresSevere heart ischemia

    Oral Glucose Tolerance TestOral glucose 75gGH peak level> 1 mg/LAcromegaly: positive & differential diagnosis Diabetes Mellitus

    IGF-1 : variation with age & sex

    Reglarea Axei CSR CRH / VP ACTH Cortisol Leptina Citokine GR, CRHR, V1b, ACTH R,

    Short ACTH Stimulation Test250 mg ACTH i.v.

    Screening in Cushing Syndrome

    Diagnosis in Cushing Syndrome

    Inferior Petrosal Sinus SamplingV. femurala ... IPSCRH 100 ug i.v.Control - VCIIPS: -5, 0, 2, 5, 10 min

    Reglarea Axei Tiroidiene TRH TSH T4 / T3 Type II deiodinase Leptina TR, TRH R, TSH R

    TRH test400 mg i.v. TRHTSH is measured each 30 mins, for 3 h

    Reglarea Axei Gonadice GnRH LH & FSH Prolactina Testosteron /E2, Pg Inhibina /activina

    GnRH este eliberat in sistemulport hipotalamo- hipofizar, pornind din eminena median i legnd vascular adeno-hipofiza.

    Eliberarea este pulsatil tonic, iniial nocturn, apoi i diurn, ulterior apare o descrcare major, pre-ovulatorie. Eliberarea tonic provine din MBA, cea pre-ovulatorie din AHPO

    Controlul sintezei LH i FSH de ctre GnRh

    Stage 1: Prepubertal, no pubic hair growthStage 2: Testes grow; scrotal skin becomes redder and coarser; sparse and fine hair develops at base of penisStage 3: Penis lengthens with small increase in diameter; scrotal skin reddens, thickens and crinkles, pubic hair thicker and coarserStage 4: Penis and testes continue to grow; pubic hair coarser, darker and more curlyStage 5: Penis at adult size; pubic hair covers symphysis pubis and extends to inner thighsStadiile dezvoltarii pubertare (Tanner)

    Pulsatile LH Pattern in Human

    Pulsatility in gonadal axis Pulsatile hormones: Mix & Measure

    CONCLUZII Evaluarea bazala pentru hormonii cu secreie cvasiconstanta. Evaluare dinamica pentru hormoni cu ritm, sau secretie pulsatila. Teste de inhibiie pentru sindroame de hipersecretie. Teste de stimulare pentru deficit hormonal. Integrarea rezultatelor clinice, biochimice, imagistice. Tineti cont de : hormoni, transport, metaboliozare, receptori, interferente de reglare (feed-back nespecific).

    *Slide Index CI0001L: A-F

    DISCUSSION POINTS:

    SLIDE BACKGROUND:Status as of March 2003.

    **Regulation of food intakeThe regulation of food intake involves a complex interaction of systems that determine the size, content, and frequency of feedings. Presumably, the brain is the final processing center that translates central and peripheral signals to initiate or stop feeding. Neuronal circuits have been identified in the hypothalamus that affect satiation (level of fullness during a meal which regulates the amount of food consumed) and satiety (level of hunger after a meal is consumed which regulates the frequency of eating). Regulatory mechanisms also must be present that integrate determinants of short-term energy intake with long-term energy requirements.

    The discovery of leptin, the protein product of the ob/ob gene, in 1995 [1] led to a marked increase in our understanding of the regulation of food intake. Leptin is produced by fat cells, released into the circulation, and it crosses the blood-brain barrier to bind to its receptor in the hypothalamus, which stimulates the expression of neuropeptides and neurotransmitters that inhibit food intake. Therefore, leptin provides a unique feedback signaling system that transmits information regarding adipose tissue energy stores to the central nervous system. Other peripheral organs also communicate with the brain about energy intake through neural signaling and endocrine pathways. The gastrointestinal system, which is responsible for digesting and absorbing ingested nutrients, is particularly involved. The gastrointestinal tract produces cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), apolipoprotein A-IV (apo A-IV), ghrelin, insulin, and glucose, which are likely involved in short-term, and possibly long-term, regulation of food intake. Central neuropeptides and neurotransmitter signals produced in hypothalamic nuclei stimulate 1) neuropeptide Y (NPY), 2) agouti-related protein (A