water metabolism disorders

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