Nephrology‎ > ‎

Sodium and Water Balance


    Molecular Physiology of Water Balance NEJM 2015
    Case Discussion: Supplement to: Molecular physiology of water balance. N Engl J Med 2015

  • HYPONATREMIA: Mild / Moderate / Profound: Na: Low:  check serum osmolality, urine osmolality, and urine sodium; We can also check for Uric Acid, and BUN/Cr; review medications; clinically decide if patient is euvolumic or not (BP, Heart Rate, Orthostatic, Skin Turgor, Mucous Membrane) If euvolumicr/o Hypothyroidism and Adrenal Insufficiency
    • Low ADH but low solute to get rid of excess water (U osm < 100, and  : Primary Polydipsia, 
    • Treatment in asymptomatic patient: Correction 5-6 meq/24 hr. Calculate total sodium needed in next 24 hr - 3 factors decide on the treatment strategy
      • Presence of and Severity of Symptoms
      • Chronicity (Higher risk of ODS)
      • Response to treatment is unpredictable; frequent Sodium monitoring is needed

a.     Hypovolumic (different from dehydration): You can give more fluid with RL (130 meq/L) than with NS (154 meq/L). If overcorrection occurs, then give DDAVP.

b.     Euvolumic: If SIADH: Volume Restriction; Salt and Furosemide (Lasix)

c.      Hypervolumic: Volume Restriction: AVP antagonist??

d.     Pseudo-hyponatremia: Glucose high, Mannitol, TG, Other Proteins etc.

5 Overall Concepts
1. Define Etiology (ADH mediated or NOT, Mechanism of ADH generation, Aldo is high or NOT)
2. Define Risk of ODS or CPD and Treatment goal
3. Treatment strategy depends on Etiology and acuity
4. Plasma Na is a function of total body Na and K and Water
5. Balance of Electrolytes "IN/L of fluid given" and "Electrolyte OUT/L of Urine Output" will define if Plasma Na is going to increase or not - i.e Understand the concept of Hypotonic Urine (more free water loss in Urine) in correction of hyponatremia. 


Utility and limitations of the traditional diagnostic approach to hyponatremia: a diagnostic study. Am J Med. 2010
Treatment of hyponatremia Curr Opin Nephrol Hypertens. 2010 

Disorders of Plasma Sodium — Causes, Consequences, and Correction NEJM 2014

Disorders of Plasma Sodium — Case Discussions NEJM 2014 

Central Pontine Myelinolysis NEJM 2016
  • HYPERNATREMIA: Na: High: Problem is with Free Water Deficit (i.e. dehydration, which is different from salt and water loss i e. hypovolumia2/2: Calculate Urine and Serum Osmolality - Calculate TOTAL Free Water Deficit (target Na of 140) - Calculate Water Deficit to replete in next 24 hour (with goal of no more than 10 mEq /day) - Calculate the rate of repleting D5W (free water) over 24 hour - If patient is symptomatic due to volume loss, give normal saline bolus to avoid rapid sodium correction during fluid repletion


Clinical Questions : Understanding Mechanisms: 
  1. Both Thiazides diuretics, and Loop Diuretics cause diuresis, and volume depletion. Loop Diuretics leads to Hypernatremia, while Thiazide Diuretics leads to Hyponatremia, Why? 
    • Ans: More free water loss than sodium in Loop Diuretics, and more Sodium Loss compared to free water in Thiazides. 
      • Both case due to fluid loss have more ADH, and Aldosterone. Both act distal to where Loop and Thiazide Diuretics act. Then why such a different in fluid loss in two situations. 
        • Ans: Na K 2Cl- Channel that loop diuretics block is needed to maintain the medullary concentration gradient. NaCl- channels that thiazides blocks does not have much role in medullary gradient. Medullary gradient is needed for ADH to retain free water. In the absence of gradient, even though there is plenty of ADH, no free water is retained in loop diuretics use, whereas that free water is retained with thiazide diuretics. Free water retention causes hyponatremia in Thiazide. Free water loss causes hypernatremia in Loop Diuretics. 
          • What effect does ADH do on NK2Cl- channels?
            • Increases the rate of expression of these channels - both short term, and long term. NEJM 2015
  2. How does oxcarbamazepine cause hyponatremia?
  3. What is Urine Osmolality in Euvolumic Hyponatremia? U-Na?
    • U-Som is High due to high ADH (SIADH). U-Na is high as low aldo causes loss of U-Na. 
Clinical Question 

22 yo M patient with Schizophrenia was for fall. Was found to have S-Na of 113. S-osm was 240. U-osm is 46. U-Na is 6. 

Describe the pathophysiology of Hyponatremia in this patient?

1. Low ADH: Hence, U-osm is low. 
2. Hyponatremia is due to lack of enough Salt to drive out the water from body. Hence, it is as low as it can be. 

This is a perfect example of hyponatremia due to Primary Polydipsia. 

How would you treat this patient?

1. Fluid restriction. 
2. Salt repletion. 

Ans: While fluid restriction alone with regular diet (that has salt) will work, Salt repletion is the best answer, as that can drive out the water. This is highly affective since ADH is very low. Do not replete a lot of salt, as that will lead to rapid diuresis, and rapid correction of S-Na. 

He also had hypokalemia when he presented. He was given NS at 75 cc / hr,  

At, around 4 am, it was 116. Hence, IV fluid was changed to 1/2NS with K+. Fluid continued at 75 cc / hr. 

Subsequent changes are as above. At, 730 am it was changed to 1/4 NS with K+. Na, continued to increase.

What could have been done upfront to minimize the risk of such a rapid correction of Na. 

1) Instead of 75 c / hr, NS could have been run at 25 cc / hr. That limits amount of Na, and amount of diuresis it can cause, and decreases the rate of correction. 
2) At 730 am, since Na continued to go up, instead of changing the 1/4NS with K+, it should have been changed fully to D5, and needed to be given at a rate more than what kidney can handle. i.e @ 250 cc / hr. That would cause hyponatremia, and make sure it reverses. 

What is the role of S-K+ in hyponatremia, and how does its correction affect S-Na. 

Further explanation on how hypokalemia causes hyponatremia, and how potassium repletion causes correction of hyponatremia.

Hypokalemia is an independent predictive factor for the development of hyponatremia. Because intracellular and extracellular osmolality are always equal, loss of either sodium or potassium, unless accompanied by loss of water, would result in hypotonicity. Although it is intuitively evident why changes in body sodium and water levels should determine serum sodium concentration, the role of potassium is less obvious, but  nevertheless is very important. Edelman et al  showed that serum sodium concentration is a function not only of total exchangeable sodium and total-body water, but also of total exchangeable potassium. The primary mechanism is that potassium depletion results in a shift of sodium into the cell with a commensurate exit of potassium from the cell into extracellular fluidThe reverse occurs during potassium repletion and explains Laragh’s  observation that oral potassium chloride administration resulted in an increase in serum sodium levels in hyponatremic patients in the absence of administered sodium. A similar observation was reported by Fichman et al in patients with diuretic-induced hyponatremia and hypokalemia. This effect of potassium repletion to increase serum sodium concentration may be enhanced by the entry of chloride into cell along with the potassium, which renders the cell hypertonic and draws water from the extracellular fluid. Potassium entry also may be accompanied by the movement of hydrogen ions from the intracellular to extracellular space, where they are buffered and thereby made osmotically inactive. This would decrease effective extracellular tonicity, again causing water to move into the cells, increasing the extracellular concentration of sodium. Whichever mechanism is dominant, the important observation is that potassium depletion could be associated with hyponatremia, and potassium repletion results in an increase in serum sodium concentration. 

Note: Above paragraph is from the reference included here:

Hence, rapid correction of Na in this patient may very well have been partly related to the correction of hypokalemia. 

Case based discussion 

36 yo comes with following. 

EKG is as below. 

Patient received 1 L NS bolus in ER. Also, was repeated aggressively with K. Subsequent BMP are as follow.