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Neonatal Endocrinology

Neonatal Endocrinology. Prof Dr. Oya Ercan. Transition to extrauterine life. - Hypothermia , hypoglycemia , hypocalcemia Adrenal cortex – autonomic nervous system including the paraaortic chromaffin system - essential !. Cortisol Surge : Occurs near term .

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Neonatal Endocrinology

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  1. NeonatalEndocrinology Prof Dr. Oya Ercan

  2. Transitiontoextrauterine life -Hypothermia, hypoglycemia, hypocalcemia • Adrenal cortex – autonomicnervoussystemincludingtheparaaorticchromaffinsystem- essential!

  3. CortisolSurge: Occursnearterm. • Increasedcortisolproductionbythefetal adrenal. • Decreased rate of conversion of cortisoltocortisone.

  4. CortisolSurge • Augmentssurfactantsynthesis in lungtissue. • Increasesadrenomedullaryphenylethanolamine N-methyl-transferaseactivityincreasesmethylation of norepinephrinetoepinephrine. • Increaseshepaticiodothyronineouter ring MDI activityincreasesconversion of T4 to T3. • Decreasessensitivity of theductusarteriosustoprostaglandinsfacilitatesductusclosure. • Inducesmaturation of severalenzymesand transport processes of thesmallintestine. • Stimulatesmaturation of hepaticenzymes.

  5. Secondaryeffectsof cortisolsurge • Increased T3 levelsstimulate ß-adrenergicreceptorbindingandpotentiatesurfactantsynthesisin lungtissueandincreasethesensitivity of brownadiposetissuetonorepinephrine.

  6. CatecholamineSurge: Norepinephrineepinephrinedopamine Plasmanorepinephrineconcentrationsexceedepinephrinelevels. • Criticalcardiovascularadaptations (increasedbloodpressure, increasedcardiacventricularinotropiceffects) • Increasedglucagonsecretion • Decreasedinsulinsecretion • Increasedbrownadiposetissuethermogenesiswithincreasedplasmafattyacidlevels. • Pulmonaryadaptation (includingmobilization of pulmonaryfluidandincreasedsurfactantrelease.)

  7. Most of thechromaffintissue in thefetus is representedbyextramedullaryparaganglia (derivedfrompreaorticcondensations of sympatheticneuronsandchromaffincells). • Thelargest of theseparaganglia; theorgans of Zuckerkandl, neartheorigin of theinferiormesentericarteries, enlargeto 10 to 15 mm in length at term. • Inparaaorticchromaffintissue, PNMT activity is low.

  8. Neonatalbrownadiposetissuethermogenesis Brown adiposetissue is themajor site forthermogenesisin thenewborn. • Largestmasses: envelopethekidneysand adrenal glands. • Smallermasses: surroundthebloodvessels of themediastinumandneck. • Norepinephrine, via ß-adrenergicreceptors, stimulatesbrownadiposetissuethermogenesisand optimal responsiveness of thistissueto NE is thyroidhormonedependent.

  9. Calciumhomeostasis • Highconcentrations of fetalcalciumaremaintainedbyactiveplacental transport frommaternalblood. • Fetalparathyroid PTHRP acts in theplacentatostimulatematernal-fetalcalcium transfer [1,25(OH)2D]. • Hightotal andionizedcalcium in fetalblood PTH levelsrelativelylow – CT concentrationshigh. • 25-hydroxycholecalciferoland 1,25-dihydroxycholecalciferolaretransportedaccrosstheplacenta, andfree vitamin D concentrations in thefetalcirculationaresimilartoorhigherthanmaternalvalues.

  10. Adaptation • Highcalciumenvironmentregulatedby PTHRP and CT Lowcalciumrequiringregulationby PTH and vitamin D withremoval of theplacenta, plasma total calciumconcentrationfallsandreaches a nadir of approximately 9 mg/dl in terminfantsby 24 hr of life. • Theionizedcalciumconcentrationreaches a lowlevel of about 1.2 mmol/L. Plasma PTH levels in theneonatearerelativelylow in theneonatalperiodandareminimallyresponsivetohypocalcemiaduringthefirst 2-3 days of life. (+CT increases)

  11. Glomerularfiltration is lowforseveraldays. • Renalresponsivenessto PTH is reducedforseveraldaysafterbirth limit phosphateexcretionandpredisposetheneonatetohyperphosphatemia, particularlyifthedietincludeshighphosphatemilksuch as unmodifiedcow’smilk.

  12. Calciumhomeostasisand PTH secretionusuallynormalizewithin 1-2 wk in full-terminfants but normalizationmayrequire 2-3 wk in thesmallprematureinfants.

  13. Glucosehomeostasis • Thelowglucoseandhighcatecholaminelevelsstimulateglucagonsecretionand a transientpeak in plasmaglucagonleveloccurswithin 2h afterbirth. • Plasmainsulinlevelsarelow at birthandtendtofallfurthersecondarytohypoglycemia. • Theearlyglucagonandcatecholaminesurgesrapidlydepletehepaticglycogenstoressothatreturn of plasmaglucoselevelsto normal after 12-18 h andrequiresmaturation of hepaticgluconeogenesisunderthestimulus of a highplasmaglucagon/insulinratio. • Glucagonsecretiongraduallyincreasesduringtheearlyhoursafterbirth, especiallywith protein feeding.

  14. Prematureinfantshavemore severe andprolongedhypocalcemiabecause of relativelyreducedglycogenstoresandimpairedhepaticgluconeogenesis. • Forthehealthyterminfant, glucosehomeostasis is achievedwithin 5 to 7 d of life, in prematureinfants 1-2 wkmay be required.

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