water metabolism disorders dr olcay evliyaoğlu. plasma osmolality is tightly between 275-295...

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Water metabolism disorders Dr Olcay Evliyaolu Slide 2 Plasma osmolality is tightly between 275-295 mOsm/kg Thirst enhance water ingestion Arginin vasopressin (AVP)enhance water output Both systems work together for the regulation of plasma osmolality Slide 3 Extracellular fluid regulationRenin-angiotensin-aldosterone Na reabsorbstion Osmolality regulationThirst and AVP system Regulation of water intake and output Slide 4 Body water and electrolytes Term newborns and infants % 75-80 of body weight is water % 45-50 of body weight is extracellular water % 30 of body weight is intracellularwater In the first days of life 7 % of the total body water is excreted from extracellular compartment by rapid diuresis Slide 5 % 40 of BW is intracellular % 20 of BW is extracellular % 60 of BW is total water Adult type water distribution is achieved through childhood Slide 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 nsensible losses Slide 7 Urine volumeSolute load that should be excreted Urine concentration that should excrete the solute load Daily solute excretion approx is 500 mOsm/m2 For urine with mean concentration of 500-600mOsm/kg 900ml/m2/day urine is necessary Respiration and via skin 750ml/m2/day Digestive system 100ml/m2/day Water oxidation occuring during enery metabolism 250ml/m2/day 1500ml/m2/day Slide 8 Daily electrolyte needs ElectrolyteAmount Na20-50mEq/m2/day K20-50mq/m2/day Ca Term NB50-75mg/kg/day Infants600mg/day Children800mg/day Adolescents1200mg/day Slide 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, Mg and P should be added Slide 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 Slide 11 Osmotic gradient Water pass through compartments Slide 12 Chronic changes is cell osmolality Adaptation mech of cell Intracellular impermeabl solutes increase or decrease Attention to hyper and hyponatremia treatment Slide 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 Slide 14 Osmosensors in central nervous system regulate to effector system Thirst Posterior pituitary AVP secretion Slide 15 Vasopressin AVP cyclic nonapeptide. Structure is like oxytosin. Synthesized as preprohormone. Gene is on chromosome 20. Synthesized in bilateral hypothalamic supraoptic and paraventricular nucleus neurons. Magnocellular neurons axons end 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. Slide 16 Vasopressin secretion and thirst regulation Osmotic regulation ncrease in plasma osmolality ncrease in intravascular volume Emesis Pharmocologic agents Vasopressin secretion Sodium Chloride Glucose (insulin def) Osmotic loads Slide 17 Hypertonic stimulus Osmo rec activated 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 Slide 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 its max con of 20pg/ml Slide 19 Emesis Hypotension Hypovolemia Vasovagal stimulus Hypoglycemia due to insulin Serum AVP > 5pg/ml Peak antidiuretic effect 5 pg/ml Slide 20 More complicated cortical activities are needed for thirst Osmotic stim 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 Slide 21 Water balance AVP secretion Thirst mechanisms Decrease water loss ncrease water intake Both systems work together. One system is enough for the maintance of serum Osm. AVP deficient, thirst intact 5-10 ml/m2 urine output can be compensated by water ingestion Thirst disorder, AVP intactCompensated by AVP secretion Slide 22 Vasopressin secretion and thirst regulation Nonosmotic regulation Right and left atrium Aortic arch (carotid sinus) Activates baroreceptors ncrease in intravascular volume and vascular wall tension Brain stem nucleus tractus solitarius Vagus Glossofarengeal Hypothalamic paraventricular and supraoptic nucleus nhibit AVP secretion Noradrenergical bundles Slide 23 Small changes (1%) in serum Osm Big changes in intravascular volume Effect AVP secretion 8 % decrease in blood volume can increase AVP secretion Slide 24 Glucocorticoids nhibit AVP secretion Directly increase free water excretion Cortisol deficiency AVP secretion increase Free water excretion decrease Decrease urine output ncrease urine out put Slide 25 AVP t1/2: 5-10 min Degradation by vasopressinase Desmopressin Aminoterminal part is resistant for degradation t1/2 8-24 saat Slide 26 Vasopressin receptors G protein associated cell membrane receptors V1 V3 (V1b) Vascular smooth muscle (vascular contraction) Hepatocytes Anterior pituitary corticotrophs Increase ACTH (fofotidil inositol yolu ile) secretion Smiliar to V1 and oxytocin rec structure Slide 27 V2 Kidney collector tubulles Thick asccending Henle loop Periglomerullar tubulles Some systemic vessel endotelial cells (vasodilation via NO synthase stimulation) Stimulation of Von Willebrand factor Stimulation of factor VIIIa Stimulation of tissue plazminogen activator Consists of 370 aminoasits G protein associated res. Functions via cAMP Gene on long arm of chromosome X (Xp28) Slide 28 AVP effect at kidnesys VP+VP2Rncrease cAMP Microflamend and cellular stuctural changes in the microtubules Water channels enter the membrane. Water permeability of the membrane increase Slide 29 V1a andV1b Join with phospholipase C and acts by intracellular Ca and phosphotidilinositol signal pathways V2 Joins with Gs and acts by cAMP Slide 30 Activation of V2 recaquoporine molecules enter apikal membrane Water permeability increase in luminal epithelial membrane ( 100 times) Slide 31 Vasopressin deficiency Polyuria ( >2L/m2/day) Polydipsia Diabetes Insipidus Slide 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 Water deprivition test Response - yes Urine Osm > 1000 Urine Osm > 600(at least 2 meas) Primary polydipsia Partial nephrogenic DIPartial central DI Response - no Serum Osm > 300( Na>146mmol/L) Urine Osm < 600 Central DINefrogenic DI DI differential diagnosis Slide 35 AVP test Response-yes urine Osm > %50 Central DI Response-no urine Osm < %50 Nephrogenic DI Slide 36 Central DI Pituitary Genetic Otosomal dom (VP-neurophysin gene) Otosomal rec (VP-nrofizin gen) Otosomal rec (Wolfram synd)(chromosome 4p WFS 1 gene) X-linked res (chrom Xp28) Congenital malformations Midline craniofacial disorders Holoprosencephaly Pituitary hypogenesis Acquired Trauma Neoplasms ( craniyofarengioma,disgerminoma,meningioma) Granulomas Infections Inflamatory- lenphocytic infundibuloneurohipophysitis Vascular diyopathic Clinical disorders of the posterior pituitary In Pediatric Endocrinology Slide 37 Nephrogenic DI Genetic X- linked rec (AVP-V2 rec) Ot rec (aquaporin-2) Ot dom (aquaporine-2) Acquired Drugs Lithyum Foscarnet Demeclocycline others Metabolic Hiperglisemi Hiperkalsemi Hipokalemi Protein malntrisyonu Renal Chronic renal failure skemic injury Medullary disfunction Obstructions Slide 38 Primary polydipsia Psychogenic polydipsia Dipsogenic polydipsia Iatrogenic polydipsia Slide 39 nappropriate AVP secretion ADH secretion inappropriate to plasma osm ( lower than the threshold) Dilutional hyponatremia Slide 40 Tumors (bronkogenic Ca) Drugs CNS disorders Non malign lung disorders Postoperative Adrenal insufficiency Hypothyroidism nappropriate AVP secretion Slide 41 Cerebral salt loss Any CNS disorder can result in hyponatremia and increase in urine Na With Na there is also water loss, DH