In metabolic acidosis with normal anion gap, why does a fall in bicarbonate cause a rise in serum chloride?

Answer 1

Excellent question... it's tricky because there is the book answer and the REAL answer, which sadly hasn't caught on outside of the critical care community.

The book answer is that the body holds on to chloride to maintain electroneutrality. Bicarb is a negative ion, so if its value falls, the body must compensate in other ways by raising the chloride level. This can be done in the kidney. In addition, the enzyme that breaks CO2 into carbonic acid (and ultimately bicarb) is found in the RBC. CO2 diffuses into the cell, where it reacts to create bicarb and hydrogen ion. The bicarb is transported out of the RBC. To maintain electroneutrality, for every bicarb that is pumped out of the cell, a chloride is pumped in. The chloride pumped into the RBCs are normally not picked up in serum assays.

So, if you're not pumping bicarb out of the RBCs (thus causing a fall in HCO3), you're not pulling chloride back into the RBC, leaving more chloride available to be detected in the serum. This is another mechanism, perhaps the more important for why the fall in HCO3 causes an increase in CL-.

The true answer lies in Stewart Acid-Base theory. Essentially, the dissociation of CO2 into HCO3 is determined by many factors, amongst them the chloride concentration. So, the chicken-and-egg situation is somewhat reversed. For further info, you can start by googling "Stewart Acid-Base" or "strong ion acid-base", or look at the website "http://acidbase.org". But, probably, for tests, you can ignore this last paragraph.