1. Water metabolism disorders
Dr Olcay Evliyaoğlu

2. Plasma osmolality 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
Thirst and AVP system
Regulation of water intake and output

4. Body water and electrolytes
Term newborns and infants
% of body weight is water
% 30 of body weight is intracellularwater
% 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 solute excretion approx is 500 mOsm/m2
For urine with mean concentration of mOsm/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 ml/m2/day
1500ml/m2/day

8. Daily electrolyte needs
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

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

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 solutes increase or decrease
Attention to hyper and hyponatremia treatment

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

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

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 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.

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)
Osmotic loads

17. Osmo rec activated
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. 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

21. 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.
5-10 ml/m2 urine output can be compensated by water ingestion
AVP deficient, thirst intact
Thirst disorder, AVP intact
Compensated by AVP secretion

22. Vasopressin secretion and thirst regulation
Nonosmotic regulation
İncrease in intravascular volume and vascular wall tension
Right and left atrium
Aortic arch (carotid sinus)
Activates baroreceptors
Vagus
Glossofarengeal
Brain stem nucleus tractus solitarius
Noradrenergical bundles
Hypothalamic paraventricular and supraoptic nucleus
İnhibit AVP secretion

23. Small changes (1%) in serum Osm
Big changes in intravascular volume
Effect AVP secretion
8 % decrease in blood volume can increase AVP secretion

24. İncrease urine out put
Glucocorticoids
İnhibit AVP secretion
Directly increase free water excretion
Cortisol deficiency
AVP secretion increase
Free water excretion decrease
Decrease urine output

25. Degradation by vasopressinase
AVP t1/2: 5-10 min
Desmopressin
Aminoterminal part is resistant for degradation
t1/ saat

26. Vasopressin receptors
G protein associated cell membrane receptors
Vascular smooth muscle (vascular contraction)
Hepatocytes V1
Anterior pituitary corticotrophs
Increase ACTH (fofotidil inositol yolu ile) secretion
Smiliar to V1 and oxytocin rec structure
V3 (V1b)

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 V2
Consists of 370 aminoasits
G protein associated res.
Functions via cAMP
Gene on long arm of chromosome X (Xp28)

28. 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

29. V1a andV1b
Join with phospholipase C and acts by intracellular Ca and
phosphotidilinositol signal pathways V2
Joins with Gαs and acts by cAMP

30. Activation of V2 rec aquoporine molecules enter apikal membrane
Water permeability increase in luminal epithelial membrane ( 100 times)

31. Vasopressin deficiency
Polyuria ( >2L/m2/day)
Polydipsia
Diabetes Insipidus

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

33. Diabetes Insipidus
Primary polidipsia
Nephrogenic
Central

34. DI differential diagnosis
Water deprivition test
Urine Osm > 600(at least 2 meas)
Urine Osm > 1000
Response - yes
Primary polydipsia
Partial nephrogenic DI
Partial central DI
Urine Osm < 600
Serum Osm > 300( Na>146mmol/L)
Response - no
Central DI
Nefrogenic DI

35. DI differential diagnosis
AVP test
Δ urine Osm > %50
Response-yes
Central DI
Δ urine Osm < %50
Response-no
Nephrogenic DI

36. 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 pituitary
In Pediatric Endocrinology

37. Nephrogenic DI Genetic Acquired 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

38. Primary polydipsia Psychogenic polydipsia Dipsogenic polydipsia
Iatrogenic polydipsia

39. İnappropriate AVP secretion
ADH secretion inappropriate to plasma osm ( lower than the threshold)
Dilutional hyponatremia

40. İnappropriate AVP secretion
Tumors (bronkogenic Ca)
Drugs
CNS disorders
Non malign lung disorders
Postoperative
Adrenal insufficiency
Hypothyroidism

41. Cerebral salt loss
Any CNS disorder can result in hyponatremia and increase in urine Na
With Na there is also water loss, DH