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Water metabolism disorders
Dr Olcay Evliyaoğlu
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
Extracellular fluid regulation Renin-angiotensin-aldosterone
Na reabsorbstion
Osmolality regulation Thirst and AVP system
Regulation of water intake and output
Body water and electrolytesTerm 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
% 40 of BW is intracellular % 20 of BW is extracellular
% 60 of BW is total water
Adult type water distribution is achieved through childhood
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 systemskindigestive systemurine
İnsensible losses
Urine volume Solute load that should be excretedUrine concentration that should excrete the solute load
Daily solute excretion approx is 500 mOsm/m2For 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
Daily electrolyte needs
Electrolyte Amount
Na 20-50mEq/m2/day
K 20-50mq/m2/day
Ca
Term NB 50-75mg/kg/day
Infants 600mg/day
Children 800mg/day
Adolescents 1200mg/day
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
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
Osmotic gradient
Water pass through compartments
Chronic changes is cell osmolality
Adaptation mech of cell
Intracellular impermeabl solutes increase or decrease
Attention to hyper and hyponatremia treatment
Physiology of osmotic regulationSerum 275-295mOsm/kg
Neurol and biochemical path ways to bring the osm to normal
Sensitive mech that can sense osm changes
Osmosensors in central nervous system regulate to effector system
Thirst Posterior pituitary AVP secretion
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 neuron’s 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.
Vasopressin secretion and thirst regulation
Osmotic regulation
İncrease in plasma osmolality İncrease in intravascular volumeEmesis Pharmocologic agents
Vasopressin secretion
SodiumChlorideGlucose (insulin def)
Osmotic loads
Hypertonic stimulus Osmo rec activated
Depolarization of supra optic nucleus
AVP secretion
Osmo sensors and AVP secreting neurons are anatomically distinctOsmo sensors are outside of blood brain barrier
Lamina terminalis- organ vasculosum (OVLT)Subfornical organ (SFO)Preoptic hypothalamus ( outside BBB)
Osm res
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
Emesis Hypotension Hypovolemia Vasovagal stimulusHypoglycemia due to insulin
Serum AVP > 5pg/ml
Peak antidiuretic effect
5 pg/ml
More complicated cortical activities are needed for thirst
Osmotic stimAngiotensin 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
Water balance
AVP secretion Thirst mechanisms
Decrease water loss İncrease 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 intact Compensated by AVP secretion
Vasopressin secretion and thirst regulation
Nonosmotic regulation
Right and left atriumAortic arch (carotid sinus)
Activates baroreceptors
İncrease in intravascular volume and vascular wall tension
Brain stem nucleus tractus solitarius
Vagus Glossofarengeal
Hypothalamic paraventricular and supraoptic nucleus
İnhibit AVP secretion
Noradrenergical bundles
Small changes (1%) in serum Osm
Big changes in intravascular volume
Effect AVP secretion
8 % decrease in blood volume can increase AVP secretion
Glucocorticoids İnhibit AVP secretion
Directly increase free water excretion
Cortisol deficiency AVP secretion increase
Free water excretion decrease
Decrease urine output
İncrease urine out put
AVP t1/2: 5-10 minDegradation by vasopressinase
Desmopressin Aminoterminal part is resistant for degradationt1/2 8-24 saat
Vasopressin receptors
G protein associated cell membrane receptors
V1
V3 (V1b)
Vascular smooth muscle (vascular contraction)Hepatocytes
Anterior pituitary corticotrophsIncrease ACTH (fofotidil inositol yolu ile) secretionSmiliar to V1 and oxytocin rec structure
V2 Kidney collector tubullesThick asccending Henle loopPeriglomerullar tubullesSome systemic vessel endotelial cells (vasodilation via NO synthase stimulation)Stimulation of Von Willebrand factorStimulation of factor VIIIa Stimulation of tissue plazminogen activator
Consists of 370 aminoasitsG protein associated res.Functions via cAMP
Gene on long arm of chromosome X (Xp28)
AVP effect at kidnesys
VP+VP2R İncrease cAMP
Microflamend and cellular stuctural changes in the microtubules
Water channels enter the membrane.
Water permeability of the membrane increase
V1a andV1b Join with phospholipase C and acts by intracellular Ca andphosphotidilinositol signal pathways
V2 Joins with Gαs and acts by cAMP
Activation of V2 rec aquoporine molecules enter apikal membrane
Water permeability increase in luminal epithelial membrane ( 100 times)
Vasopressin deficiency
• Polyuria ( >2L/m2/day)• Polydipsia• Diabetes Insipidus
• 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
Diabetes Insipidus
Primary polidipsia
Nephrogenic
Central
Water deprivition test
Response - yesUrine Osm > 1000
Urine Osm > 600(at least 2 meas)
Primary polydipsi
a
Partial nephroge
nic DI
Partial central
DI
Response - noSerum Osm > 300( Na>146mmol/L)
Urine Osm < 600
Central DINefrogenic
DI
DI differential diagnosis
DI differential diagnosis
AVP test
Response-yesΔ urine Osm > %50
Central DI
Response-noΔ urine Osm < %50
Nephrogenic DI
Central DI• Pituitary
– Genetic • Otosomal dom (VP-neurophysin gene)• Otosomal rec (VP-nörofizin 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• İdiyopathic
Clinical disorders of the posterior pituitaryIn Pediatric Endocrinology
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 malnütrisyonu
– Renal • Chronic renal failure• İskemic injury• Medullary disfunction• Obstructions
Primary polydipsia
• Psychogenic polydipsia• Dipsogenic polydipsia• Iatrogenic polydipsia
İnappropriate AVP secretion
• ADH secretion inappropriate to plasma osm ( lower than the threshold)
• Dilutional hyponatremia
• Tumors (bronkogenic Ca)• Drugs • CNS disorders• Non malign lung disorders• Postoperative• Adrenal insufficiency• Hypothyroidism
İnappropriate AVP secretion
Cerebral salt loss
• Any CNS disorder can result in hyponatremia and increase in urine Na
• With Na there is also water loss, DH