Though this is to some degree controversial, volume expansion with normal saline has been associated with the development of a hyperchloremic, non-anion gap metabolic acidosis. What are the mechanisms associated with saline expansion-induced metabolic acidosis?
The rationale for why a metabolic acidosis should develop in response to saline infusion is not immediately apparent, as there should not be any excess protons being delivered in the infusate. There are three potential mechanisms which have been cited:
1. One of the earliest explanations for this phenomenon was simply that bicarbonate ions are diluted by the isotonic fluid, and acidosis occurs as a result. Thus, this entity is sometimes referred to as "dilutional acidosis."
2. The "Stewart approach" to acid-base metabolism rejected the dilutional explanation above, reasoning that BOTH bicarbonate ions and protons would be diluted by saline infusion equally, and therefore could not be the reason for the development of acidosis. Instead, a concept called "strong ion difference" (SID) is introduced to explain this: in order to maintain electroneutrality in the presence of diluting fluid, water must dissociate, providing excess protons that drive a metabolic acidosis. If I'm not explaining it well, check out this reference for more details.
3. A more recent paper by Doberer et al states that neither of the two mechanisms is true in practice: rather, acidosis develops because there is a dilution of bicarbonate ions (which due to its being in the blood is a "closed system") without there being a dilution of acid in the form of CO2 gas (which due to its ability to be exhaled can be considered an "open system").
Regardless of the explanation, many would argue that the degree of acidosis observed with saline expansion is relatively mild and potentially even clinically insignificant.