WATER AND ELECTROLYTE BALANCE DRANITZKI ELHALEL MICHAL, MD NEPHROLOGY AND HYPERTENSION SERVICES

Total Body Water (TBW) Intracellular space Interstitium } extracellular Vascular Space }

TBW = 60% of Body Weight 60% of TBW (36% of weight) - intracellular 40% of TBW (24% of weight) - extracellular

Exchange of water between cellular and extracellular fluids 1. OSMOTIC PRESSURE - generated by number of particles per unit volume 2. HYDROSTATIC PRESSURE

Main intracellular osmole  K + Main extracellular osmole  Na + Extracellular osmolarity ~2xNa + Extracellular osmolarity = Intracellular osmolarity Normal osmolarity ~280 mOsmol/Kg ~140 mEq/L of Na +

70 kg, male TBW - 42 liter Total Body Solute - 42 liter x 280 mOsmol/l = mOsmol Intracellular volume - 25 liter Intracellular osmoles - 25 liter x 280 mOsmol/l = 7000 mOsmol Extracellular volume - 17 liter Extracellular osmoles - 17 liter x 280 mOsmol/l = 4760 mOsmol

Substance Plasma Plasma Extracellular Intracellular added osmolarity sodium volume volume NaCl     Water     Isotonic NaCl 0 0  0

Plasma Na + concentration is a measure of concentration and not of volume, or of total body sodium

Plasma osmolarity  2 x plasma [Na+] + Glucose + Urea Normal values: P Na mEq/L Glucose mmol/L Urea mmol/L P osm mOsmol/kg Effective P osm mOsm/kg

Exchange of Water between Plasma and Interstitial Fluid - Oncotic pressure - Hydrostatic pressure

EFFECTIVE BLOOD VOLUME (EBV) 1.Volume in arterial system 2.Pressure perfusing the arterial baroreceptors (carotid, glomerular) REGULATION OF EFFECTIVE BLOOD VOLUME AFFECTS SODIUM STORES BY AFFECTING URINARY SODIUM EXCRETION

REGULATION OF EBV 1. SENSORS - volume/pressure receptors: - afferent arteriole - cardiopulmonary - atria - carotid

REGULATION OF EBV 2. EFFECTORS a. Sympathetic nervous system: - sympathetic nervous tone - secretion of catecholamines from adrenal medulla  Venous constriction Myocardial contractibility and heart rate Arteriolar constriction Renin secretion Renal tubular Na + reabsorption

REGULATION OF EBV b. Renin - Angiotensin - Aldosterone system: arteriolar vasoconstriction renal Na + retention (Angiotensin II, aldosterone) c. Atrial Natriuretic Peptide (ANP) d. Regulation of renal Na + excretion: varies directly with effective blood volume controlled by - GFR - Tubular reabsorption of Na +

VOLUME REGULATION Reduced EBV Elevated EBV Sympathetic tone   Renin, Angiotensin, Aldosterone   ANP   Renal sodium excretion  

60-70% 20-30% 5% 4%

OSMOREGULATION SENSING - Osmoreceptors in hypothalamus EFFECTORS - Thirst  Drinking - Antidiuretic Hormone (ADH)  water excretion

Water Balance Obligatory water output: Urine ml Skin ml Respiratory tract ml Stool ml

Obligatory Water Intake Drinking400 ml Water content of food850 ml Water pruduced by oxidation 350 ml

Excersice on a Hot Day A. Water loss  Osmolarity  B. Water + Sodium loss Volume  Osmolarity   Thirst  } water retention  ADH  Volume  Urinary sodium excretion  ADH water retention  Urine - Osmolarity  Na +, Cl - 

Half Isotonic Saline Infusion A. Osmolarity   ADH  B. Volume   Sodium excretion  ADH   Urine - Osmolarity  Na +, Cl - 

Isotonic Saline Infusion A. Osmolarity - no change B. Volume   Sodium excretion  ADH  Urine - Isosmotic urine

Congestive Heart Failure A. EBV   Urinary Sodium excretion  ADH   Total Body Sodium  (Edema) Total Body water  Plasma Osmolarity  Plasma Sodium  Urine Osmolarity  Urine Na +, Cl - 

Primary Renal Sodium Retention Total Body Sodium  Total Body Water 

Secretory Diarrheas = Isoosmotic Fluid containing Na + and K + as in the Plasma EBV - decreased P Osm - no change P Na - no change ADH - increased Renin + Aldosterone - increased ANP - decreased  Urinary Sodium Excretion - decreased Urine Osmolarity - increased

Hyponatremia and hypoosmolality = Impaired renal water excretion Hypernatremia and hyperosmolarity = Impaired thirst mechanism or no access to water

Hypoosmolarity and Hyponatremia - SYMPTOMS Nausea Malaise Headache Lethargy Seizures Coma Cause - Brain Edema

Hyponatremia – Etiology Disorders of impaired water excretion A. Effective blood volume depletion GI losses Renal losses: diuretics, hypoaldostronism, Na + -wasting nephropathy Skin losses: exercise, burns Edematous states: heart failure, hepatic cirrhosis, nephrotic syndrome, protein loosing enteropathy B. Diuretics: Thiazides, loop diuretics C. Renal failure

Hyponatremia – Etiology D. Non-hypovolemic states ofADH excess Syndrom of inappropriate ADH secretion Cortisol deficiency Hypothiroidism E. Decreased solute intake F. Cerebral salt wasting Disordders with normal water excretion A. Primary polydipsia B. Reset osmostat: pregnancy, psychosis, quadriplegia, malnutrition

Diuretics 1. Volume depletion 2. Inhibition of urinary dilution 3. K + depletion Most common - THIAZIDES

60-70% 20-30% 5% 4%

Syndrome of Inappropriate ADH Secretion = Impaired water excretion 1. Hypoosmolarity and Hyponatremia 2. Increased urine osmolarity NO DECREASED EBV Na + EXCRETION IS NORMAL

SIADH - ETIOLOGY 1. Neuropsychiatric disorders 2. Drugs 3. Pulmonary disease 4. Post-operative 5. Severe nausea 6. Ectopic production 7. Exogenous administration of ADH

PSEUDOHYPONATREMIA Low plasma Na + with normal P osm A. Severe hyperlipidemia B. Severe hyperproteinemia Low plasma Na + with elevated P osm A. Hyperglicemia B. Administration of hypertonic Manitol

Hyponatremia - DIAGNOSIS 1. Patient history 2. Estimate Volume status 3. Plasma Osmolarity 4. Urine Osmolarity 5. Urine Na + concentration

Hyponatremia – Treatment 1. Estimate neurological symptoms 2. Estimate volume status 3. Decide – water restriction or sodium load or both 4. Correct slowly!!!! ~ ½ meq/l/h TREAMENT COMPLICATION: CENTRAL PONTINE MYELINOLYSIS

Estimation of Sodium deficit Na + deficit = 0.5 x weight (125-plasma Na + ) Example: 70kg female, plasma Na + 113meq/l Na + deficit = 35( )=420 meq Time of correction: 12meq/l =24h 0.5meq/l/h Fluids: Hypertonic (3%) saline = 513meq/l 420 meq = 818 ml of hypertonic saline

If hypovolemia coexist: Treat with normal (0.9%) saline. First, Sodium will rise slowly in plasma.When hypovolemia will be corrected ADH levels will drop, and water excretion will correct plasma Na +.

Treatment of SIADH 1.Water restriction 2. Hypertonic saline or NaCl tablets 3. Loop diuretics 4. Demeclocycline

Hyperosmolarity and Hypernatremia - SYMPTOMS Lethergy Weakness Irritability Twitching Seizures Coma Cause - Brain Dehydration

Hypernatremia – Etiology w ater loss A. Insensible loss – Increased sweating, evaporation Burns Respiratory infection B. Renal loss – Central Diabetes Insipidus Nephrogenic Diabetes Insipidus Osmotic diuresis C. Gastrointestinal loss – Osmotic diarrhea D. Hypothalamic disoreders E. Water loss into cells – Seizures Rabdomyolysis

Hypernatremia – Etiology cont. Sodium retention A. Administration of hypertonic NaCl or NaHCO 3 B. Ingestion of sodium

Hypernatremia – DIAGNOSIS 1. Patient history 2. Estimate volume status 3. Plasma osmolarity 4. Urine volume 5. Urine osmolarity 6. Urine Na + concentration

DIABETES INSIPIDUS- CENTRAL-ETIOLOGY 1.Idiopathic – familial 2. Post surgery to hyopthalamus 3. Head trauma 4. Hypoxic or ischemic encephalopathy (shock, arrest, Sheehan’s syndrom) 5. Neoplastic 6. Histiocytosis X 7. Sarcoidosis 8. Anorexia nervosa 9. Cerebral aneurysm 10. Encephalitis or meningitis

DIABETES INSIPIDUS – NEPHROGENIC- ETIOLOGY 1.Decreased water permeability of the collecting tubule a. Congenital b. Hypercalcemia c. Hypokalemia d. Drugs (Lithium, Demeclocycline, Streptozocin) e. Sjogren’s syndrom f. Amyloidosis

Diabetes Insipidus – Nephrogenic Etiology – con. 2. Interference with countercurrent mechanism a. Osmotic diuresis b. Loop diuretics c. Renal failure d. Hypercalcemia e. Hypokalemia f. Sickle cell anemia 3. Increased periferal degradation of ADH a. Pregnancy 4. Unknown mechanism a. Isofamid b. Methoxyflurane

Hypernatremia – Treatment 1. Estimate neurological symptoms 2. Estimate volume status 3. Treat slowly ~ 0.5 meq/l/h

Estimate water deficit Water deficit = CBW[plasma Na + /140 – 1] CBW= Current Body Water For males 0.5 X weight For females 0.4 X weight Example: 50kg female has plasma Na + of 183meq/l

Example: 50kg female has plasma Na + of 183meq/l Water deficit = 0.4 X 50[183/140-1]=6 liters Time of treatment = ( )meq/l =86h 0.5 meq/l/h If no need for quick fluid replacment, treat with 5% glucose. Don’t forget to add insensible loss, ~700 ml/d Estimate continous loss of water and electrolites.

Hyponatremia and hypoosmolality = Impaired renal water excretion Hypernatremia and hyperosmolarity = Impaired thirst mechanism or no access to water

POLYURIA – D.D. 1.Water diuresis (urine osmolarity 300) Saline loading Postobstructive diuresis Hyperglycemia Very high protein diet Na + wasting nephropathy

POLYURIA – DIAGNOSIS 1. Patient history 2. Estimate volume status 3. Measure Glucose level in plasma 4. Plasma osmolarity 5. Urine osmolarity 6. If DI is suspected but no hyperosmolarity is present, perform water restriction test

Water restriction test Purpose – to induce hyperosmolarity to stimulate maximal ADH secretion Follow: 1. Plasma osmolarity 2. Urine volume 3. Urine osmolarity When plasma osmolarity > 295 mosmol/l or Urine osmolarity is stable, give exogenous ADH

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