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Water metabolism disorders

Water metabolism disorders. Dr Olcay Evliyaoğlu. Plasma osmolality is t ightly between 275-295 mOsm /kg. Thirst enhance water ingestion. Both systems work together for the regulation of plasma osmolality. Arginin va s opre s sin (AVP) enhance water output. Extracellular fluid regulation.

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Water metabolism disorders

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  1. Watermetabolismdisorders Dr Olcay Evliyaoğlu

  2. Plasmaosmolality is tightly between 275-295 mOsm/kg Thirst enhance water ingestion Both systems work together for the regulation of plasma osmolality Arginin vasopressin (AVP)enhance water output

  3. Extracellular fluid regulation Renin-angiotensin-aldosterone Na reabsorbstion Osmolality regulation Thirstand AVP system Regulation of water intake and output

  4. Body water and electrolytes Term newborns and infants % 75-80 of body weight is water % 30 of body weight isintracellularwater % 45-50 of body weight is extracellular water In the first days of life 7 % of the total body water is excreted from extracellular compartment by rapid diuresis

  5. Adult type water distribution is achieved through childhood % 40 of BW is intracellular % 20 of BW is extracellular % 60 of BW is total water

  6. Daily water ingestion and excretion can be 10 times different between individuals. It also can be different at different times in the same individual. Water losses: respiratory system skin digestive system urine İnsensible losses

  7. Urine volume Solute load that should be excreted Urine concentration that should excrete the solute load Daily soluteexcretionapprox is 500 mOsm/m2 For urine with mean concentration of 500-600mOsm/kg 900ml/m2/dayurine is necessary Respiration and via skin750ml/m2/day Digestive system 100ml/m2/day Water oxidation occuring during enery metabolism250ml/m2/day 1500ml/m2/day

  8. Daily electrolyte needs

  9. If IV fluid therapy is planned for a short interval (hours- few days) anions with Na and K will be adequate If IV fluid therapy is for a long interval Ca, MgandPshould be added

  10. Osmolality differences between the compartments will be equalized Cell membranes are impermeable to electolytes like sodium and chloride Extracellular solute load Cell membranes are permeable to potassium and phosphate Intracellular solute load

  11. Osmotic gradient Water pass through compartments

  12. Chronic changes is cell osmolality Adaptation mech of cell Intracellular impermeabl solutesincrease ordecrease Attention to hyper and hyponatremia treatment

  13. Physiology of osmotic regulation Serum 275-295mOsm/kg Neurol and biochemical path ways to bring the osm to normal Sensitive mech that can sense osm changes

  14. Osmosensors in central nervous systemregulate to effector system Posterior pituitary AVP secretion Thirst

  15. Vasopressin • AVP cyclic nonapeptide. Structure is like oxytosin . • Synthesized as preprohormone. • Gene is onchromosome 20. • Synthesized in bilateral hypothalamic supraoptic and paraventricular nucleus neurons. • Magnocellular neuron’saxonsend at pituitary stalk and posterior pituitary. • AVP containing granulles are stored in nerve endings. • Nerve impulse results in Ca influx and exocitosis of granulles. • AVP is stored in a complex with neurophysin II in granulles • Neurophysin II is functional in AVP folding, oligomerization and transmission • In plasma neurophysin II seperates from AVP leaving it free.

  16. Vasopressin secretion and thirst regulation Osmotic regulation İncrease in plasma osmolality İncrease in intravascular volume Emesis Pharmocologic agents Vasopressin secretion Sodium Chloride Glucose (insulin def) Osmoticloads

  17. Osmorecactivated Hypertonic stimulus Depolarization of supra optic nucleus AVP secretion Osmo sensors and AVP secreting neurons are anatomically distinct Osmo sensors are outside of blood brain barrier Lamina terminalis- organ vasculosum (OVLT) Subfornical organ (SFO) Preoptic hypothalamus ( outside BBB) Osm res

  18. Serum osmolality < 280 mOsm /kg Plasma AVP secretion < 1 pg/ml Serum osmolality >283mOsm/kg (threshold for AVP secretion) AVP secretion increase according to serum Osm. At serum osm of 320 mOsm/kg AVP reaches it’s max con of 20pg/ml

  19. Emesis Hypotension Hypovolemia Vasovagal stimulus Hypoglycemia due to insulin Serum AVP > 5pg/ml Peak antidiuretic effect 5 pg/ml

  20. Morecomplicatedcorticalactivitiesareneededforthirst Osmoticstim Angiotensin II Stimulates thirst center For thirst and AVP secretion same osmo sensors are used Threshold for thirst is 10 mOsm/ kg more than AVP secretion Serum Osm 293 mOsm/kg Threshold for thirst

  21. Water balance AVP secretion Thirst mechanisms Decreasewaterloss İncreasewaterintake Bothsystemsworktogether. Onesystem is enoughforthemaintance of serum Osm. 5-10 ml/m2 urineoutput can be compensatedbywateringestion AVP deficient, thirstintact Thirstdisorder, AVP intact Compensatedby AVP secretion

  22. Vasopressin secretionandthirstregulation Nonosmoticregulation İncrease in intravascularvolumeandvascularwalltension Right andleftatrium Aorticarch (carotidsinus) Activatesbaroreceptors Vagus Glossofarengeal Brain stemnucleustractussolitarius Noradrenergicalbundles Hypothalamicparaventricularandsupraopticnucleus İnhibit AVP secretion

  23. Small changes (1%) in serumOsm Bigchanges in intravascularvolume Effect AVP secretion 8 % decrease in bloodvolume can increase AVP secretion

  24. İncreaseurineout put İnhibit AVP secretion Glucocorticoids Directlyincreasefreewaterexcretion Cortisoldeficiency AVP secretionincrease Freewaterexcretiondecrease Decreaseurineoutput

  25. AVP t1/2: 5-10 min Degradationbyvasopressinase Aminoterminalpart is resistantfordegradation t1/2 8-24 saat Desmopressin

  26. Vasopressinreceptors G protein associatedcellmembranereceptors Vascularsmoothmuscle (vascularcontraction) Hepatocytes V1 Anteriorpituitarycorticotrophs Increase ACTH (fofotidilinositol yolu ile) secretion Smiliarto V1 andoxytocinrecstructure V3 (V1b)

  27. Kidneycollectortubulles ThickasccendingHenleloop Periglomerullartubulles Somesystemicvesselendotelialcells (vasodilationvia NO synthasestimulation) Stimulation of VonWillebrandfactor Stimulation of factorVIIIa Stimulation of tissueplazminogenactivator V2 Consists of 370 aminoasits G protein associatedres. FunctionsviacAMP Gene on longarm of chromosome X (Xp28)

  28. AVP effect at kidnesys VP+VP2R İncreasecAMP Microflamendandcellularstucturalchanges in themicrotubules Waterchannelsenterthemembrane. Waterpermeability of themembraneincrease

  29. V1a andV1b JoinwithphospholipaseC andactsbyintracellularCaand phosphotidilinositolsignalpathways Joinswith Gαs andactsbycAMP V2

  30. Activation of V2 recaquoporinemoleculesenterapikalmembrane Waterpermeabilityincrease in luminalepithelialmembrane ( 100 times)

  31. Vasopressindeficiency • Polyuria ( >2L/m2/day) • Polydipsia • DiabetesInsipidus

  32. Serum Osm:(Serum Na + K)x2 + Gluc/18 +BUN/3 • Urine Osm: (1.86 x Na) + Glucose/16 + BUN/2.8 + 9 • Urine Osm/ Serum Osm <1,5  DI

  33. DiabetesInsipidus Primarypolidipsia Nephrogenic Central

  34. DI differentialdiagnosis

  35. DI differentialdiagnosis

  36. Central DI • Pituitary • Genetic • Otosomaldom (VP-neurophysin gene) • Otosomalrec (VP-nörofizin gen) • Otosomalrec (Wolframsynd)(chromosome 4p WFS 1 gene) • X-linkedres (chrom Xp28) • Congenitalmalformations • Midlinecraniofacialdisorders • Holoprosencephaly • Pituitaryhypogenesis • Acquired • Trauma • Neoplasms ( craniyofarengioma,disgerminoma,meningioma) • Granulomas • Infections • Inflamatory- lenphocyticinfundibuloneurohipophysitis • Vascular • İdiyopathic Clinical disorders of the posterior pituitary In Pediatric Endocrinology

  37. Nephrogenic DI • Genetic • X- linkedrec (AVP-V2 rec) • Ot rec (aquaporin-2) • Ot dom (aquaporine-2) • Acquired • Drugs • Lithyum • Foscarnet • Demeclocycline • others • Metabolic • Hiperglisemi • Hiperkalsemi • Hipokalemi • Protein malnütrisyonu • Renal • Chronicrenalfailure • İskemicinjury • Medullarydisfunction • Obstructions

  38. Primarypolydipsia • Psychogenicpolydipsia • Dipsogenicpolydipsia • Iatrogenicpolydipsia

  39. İnappropriate AVP secretion • ADH secretioninappropriatetoplasmaosm ( lowerthanthethreshold) • Dilutionalhyponatremia

  40. İnappropriate AVP secretion • Tumors (bronkogenicCa) • Drugs • CNS disorders • Nonmalignlungdisorders • Postoperative • Adrenal insufficiency • Hypothyroidism

  41. Cerebral salt loss • Any CNS disorder can result in hyponatremiaandincrease in urineNa • WithNathere is alsowaterloss, DH

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