Tuesday, October 1, 2013

Consult Rounds: Why does infusion of normal saline cause metabolic acidosis?

Why does infusion of normal saline cause metabolic acidosis?
This should be an easy answer but when you review the literature, the literature is all over the place( literally!!).Collection of responses I received when I asked few experts in the field:

1. “ The bicarbonate ions are diluted by the isotonic fluid, and acidosis occurs as a result.”
            2. “The fall in serum bicarbonate is due to the expansion of the extracellular fluid volume                                   with large IV fluids”

3.  The "strong ion difference" (SID) helps explain this that in order to maintain electroneutrality. Since there is diluting fluid, water must dissociate, providing excess protons which leads to metabolic acidosis. “- via the stewart method of acid base

4.  “Usually 60% of the filtered bicarbonate load is reabsorbed in euvolemia. When extracellular volume is low the proximal tubular absorption is increased, maybe to 80%,due to changes in oncotic pressure and hydrostatic pressure of peri tubular capillaries and glomerulus.  This results in increased reabsorption in setting of volume depletion.  When extracellular volume is increased then proximal tubular absorption of bicarbonate is decreased, thus an acidosis.”

5. “ The ph of normal saline is 5.5, won't that also lead to dissociation and use of Hco3 and cause an acidic environment”
6. “Nacl is a weak acid so despite the low ph it will not change systemic ph.”
7. “The PCT reabsorbs 80 to 90 % of filtered HCO3. When micropuncture needle is not inserted in the terminal PCT, just the last accessible PCT that can be seen on the cortical surface. When Walker et  al micro-disceted the entire PCT, the reabsorption was close to 90% of filtrate, which prevents bicarbonaturia and percipitation of CaHPO4 in the deepest bend of the LOH, as this would cause  obstructive nephron damage and kidney stone disease among our ancestors and we would not be alive.
8.  “With a pH of isotonic saline of 5.5, there are far too few H+ added to cause metabolic                           acidosis if infusion volumes are less than 50 L/day.”
Take your pick! 



  1. Another explanation is that increase in the amount of filtered chloride and delivery of chloride to the distal nephron caused by large infusions of normal saline provide the substrate for increased pendrin activity in intercalated type b cells. This would result in the reabsorption of chloride by the secretion of bicarbonate into the lumen leading to a metabolic acidosis.

    1. That would suggest that the effect would only occur in patients with functioning kidneys and we know that this is not the case. Also, why would there be an increase in pendrin activation in the absence of chloride depletion?

  2. Nothing about excessive chloride shifting the potassium/proton exchange?

  3. I think the SID theory could nicely explain that. 1 liter of Isotonic Saline contains 154 mEq of Na and 154 mEq of Cl. Normal values of chloride in plasma range from 95 to 105 mEq/L (or mmol/l). Isotonic saline increases chloride concentration in blood(and the overall negative charge) In order to maintain electroneutrality cells (probably not only kidney cells;lung cells perhaps) compensates lowering Hco3 production.(which ,like chloride is an anion)My guess is that a load of chloride could shift carbonic anhydrase reaction to the right producing more Co2 and less Hco3. this could help maintain electroneutrality. A higher Co2 level increasing respiratory rate would eventually remove the Co2 load.

  4. As with the majority of pathophysiology, probably a combination of multiple mechanisms mentioned.

  5. Thanks for the descriptions, as with most of pathophysiology it is probably a combination of all the mechanisms described.


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