The two definitions for this are over-feeding, and the use of total parenteral nutrition. Only TPN, however, causes metabolic acidosis.  This chapter deals with the metabolic acidosis which results from parenteral supplementation with amino acid mixtures.

Hyperchloraemic metabolic acidosis due to the preservatives in TPN

The major role in this is again plaid by the chloride ion. There is the presence of the chloride ion in the hydrochloride preparations of lysine and arginine, which had historically formed a major part of the early TPN mixures. And casein hydrolysate had also contained a large amount of hydrochloride. Furthermore, hydrochloric acid is typically added to TPN amino acid mixtures in order to reduce the pH, and thus avoid the unpleasant Maillard reaction.

Let us consider the bag of TPN amino acids. At any given pH, amino acids may either be cationic or anionic. In the TPN bag, where the pH is 5.8,  the majority will be cationic. This positive charge is balanced by chloride ions.

Now, consider what happens to the TPN mixture once it has been infused into the patient. The cationic amino acids have an exit strategy- they can be metabolised and incorporated into proteins. The chloride, however, persists – it is a non-metabolisable anion.  As cationic amino acids leave the circulation, only chloride remains. The strong ion difference decreases. Hence the acidosis.

hyperchloraemic metabolic acidosis due to chloride being used as a preservative in TPN

Of course, this whole business can be avoided if only acetic acid were used to acidify the TPN mixture. Acetic acid is metabolisable, and will not contribute to the strong ion difference.

But what about oral overfeeding? This is a curious beast. Many pages have been devoted in the literature to the metabolic and physiological effects of starvation; however, gluttony has not enjoyed this much attention, though it is surely enjoyed by a large proportion of the population.  An attempt to address this imbalance was made during the tumultuous sixties in Scotland; Strong Shirling and Passmore persuaded “sixteen subjects, some thin and some fat” to ingest some 3000-7000 extra kcal per day, for 4 days. One of the subjects (Elizabeth) came to the hospital complaining of “thinness”.  Another was a sufferer of Klinefelters syndrome, and already happened to be at the hospital  having his hypogonadism treated. Several more were randomly selected skinny medical students, and eight were people who presented to the obesity clinic, complaining that they couldn’t lose weight. How binge-eating was negotiated with these people, the authors do not discuss.

Oral overfeeding is of course a no-joke issue in the ICU, and the critically ill patients tend to suffere some genuine complications as a result of excess macronutrients. This issue is dealt with elsewhere.


Klein, Catherine J., Gena S. Stanek, and CHARLES E. WILES. "Overfeeding macronutrients to critically ill adults: metabolic complications." Journal of the American Dietetic Association 98.7 (1998): 795-806.

Strong, J. A., D. Shirling, and R. Passmore. "Some effects of overfeeding for four days in man." Br. J. Nutr 21.90 (1967): 919.

Heird, William C., et al. "Metabolic acidosis resulting from intravenous alimentation mixtures containing synthetic amino acids." New England Journal of Medicine 287.19 (1972): 943-948.

Klein, Catherine J., Gena S. Stanek, and CHARLES E. WILES. "Overfeeding macronutrients to critically ill adults: metabolic complications." Journal of the American Dietetic Association 98.7 (1998): 795-806.

Kato, Katsuyoshi, et al. "The Latent Risk of Acidosis in Commercially Available Total Parenteral Nutrition (TPN) Products: a Randomized Clinical Trial in Postoperative Patients." Journal of clinical biochemistry and nutrition 45.1 (2009): 68.

Sugiura S., Inagaki K., Noda Y., Nagai T., Nabeshima T. Acid load during total parenteral nutrition: Comparison of hydrochloric acid and acetic acid on plasma acid-base balance. Nutrition. 2000;16:260–263.

Kushner, Robert F. "Total parenteral nutrition-associated metabolic acidosis."Journal of Parenteral and Enteral Nutrition 10.3 (1986): 306-310.