Delta gap and delta ratio: how to calculate and read them

What the delta gap and delta ratio measure

The delta gap and the delta ratio both start from one idea: when a strong acid such as lactic acid builds up, each hydrogen ion it releases is buffered by one bicarbonate ion, and the acid's anion stays behind as an unmeasured anion. So in a pure high anion gap metabolic acidosis, the rise in the anion gap (ΔAG) should roughly match the fall in bicarbonate (ΔHCO₃⁻). Wrenn described the difference between the two, ΔAG minus ΔHCO₃⁻, as the delta gap in 1990. The delta ratio divides the two instead, ΔAG / ΔHCO₃⁻, and expects a value near 1. When bicarbonate has fallen more than the gap has risen, a second, normal anion gap acidosis is probably adding chloride. When bicarbonate has fallen less, something is holding bicarbonate up, most often a metabolic alkalosis. Neither number diagnoses anything alone; both are prompts to look for a second process.

Which normal anion gap to subtract

The normal anion gap you subtract decides the answer. The best baseline is the patient's own anion gap from when they were well, because normal values differ between people. Without one, use the middle of your laboratory's reference range rather than a textbook figure: the anion gap calculator defaults to 3 to 11 mmol/L without potassium, the range quoted for ion-selective electrode analyzers, whose middle is 7, while older continuous-flow analyzers gave mean gaps near 12 mmol/L. Kraut and Nagami show why this matters with two hypothetical patients: with a baseline gap of 3 mmol/L, a lactate of 6 mmol/L still left the gap at 9, inside the normal range, while with a baseline of 10 the same lactate rise pushed the gap out of range. Correct the gap for a low albumin with the Figge equation before you calculate either delta, or a hypoalbuminemic patient will look like they have an extra normal gap acidosis.

How to read the delta gap

Wrenn's delta gap is read against a margin of 6 mmol/L either side of zero. A delta gap greater than +6 means the anion gap has risen more than bicarbonate has fallen, and Wrenn wrote that a metabolic alkalosis is then usually present, keeping bicarbonate higher than the added acid alone would allow. A delta gap less than −6 means bicarbonate has fallen more than the gap explains, and a hyperchloremic (normal anion gap) acidosis is usually present as well. Values between −6 and +6 fit a high anion gap acidosis on its own. The margin exists because neither the normal gap nor the normal bicarbonate is known exactly for any one patient, and an error of a few mmol/L in either baseline moves the delta gap by the same amount. The table below sums up the reading; it is a clue to check with the history, the blood gas and other tests.

How to read the delta ratio

The delta ratio carries the same information as the delta gap as a ratio, and its expected value depends on which acid is present. Kraut and Nagami summarise the human data: the ratio was close to 1:1 in ketoacidosis but averaged 1.5 in lactic acidosis, and in nephrectomized rats given lactic acid it reached 1.8:1. Two things explain the gap between the two acids. Lactate and protons spread through different volumes of the body, and the kidneys excrete ketone anions far faster than lactate: the fractional excretion was about 45.8% for ketones against 4.7% for lactate, so ketoacid anions leave the blood while the bicarbonate deficit stays. A ratio clearly below 1 therefore suggests a normal anion gap acidosis alongside the high gap one, or ketoacid anions lost in the urine. A ratio well above what lactic acidosis produces suggests that a metabolic alkalosis is holding bicarbonate up.

Because the denominator is the fall in bicarbonate, the ratio becomes unstable when bicarbonate is near normal: a fall of 1 or 2 mmol/L turns small errors into large ratios. The delta gap, a difference rather than a ratio, behaves better in that range.

Worked example: one high gap acidosis or two disorders?

Take sodium 140, chloride 104 and bicarbonate 12 mmol/L, albumin 4.0 g/dL, and a lab anion gap range of 3 to 11 mmol/L. The anion gap is 140 − (104 + 12) = 24 mmol/L, and normal albumin needs no correction. Using the middle of the lab range, 7, as the normal gap, ΔAG is 24 − 7 = 17. Bicarbonate has fallen from 24 to 12, so ΔHCO₃⁻ is 12. The delta gap is 17 − 12 = +5, inside Wrenn's ±6 margin, and the delta ratio is 17 / 12 = 1.4, in the range reported for lactic acidosis: this fits a high anion gap acidosis alone. Now change only the chloride to 112. The gap falls to 16, ΔAG to 9, while ΔHCO₃⁻ stays 12: the delta gap is −3 and the ratio 0.75. That points towards a normal gap acidosis on top, though the delta gap is still inside the margin, so the two readings are checked together.

Had this second patient's albumin been 2.0 g/dL, the corrected gap would be 16 + 2.5 × 2 = 21, ΔAG 14 and the delta gap +2, and the apparent second acidosis would disappear. Run the numbers through the albumin-corrected anion gap calculator first, then do the delta arithmetic.

Why the delta ratio can mislead

Rastegar's 2007 review in the Journal of the American Society of Nephrology concluded that the delta ratio should be used cautiously to diagnose mixed acid-base disorders: although the mean ratio in selected patients is close to 1, it varies widely from patient to patient. Every patient's normal anion gap is uncertain, and the normal range in a population spans 8 to 10 mmol/L. Protons and the acid's anion spread through different volumes of the body, and water leaving cells during buffering dilutes chloride, so the plasma fall in bicarbonate does not track the acid load exactly. Ketone anions are excreted in the urine, so in ketoacidosis the ratio falls over time even without a new disorder. The delta gap and delta ratio are best treated as prompts to look for a cause, such as vomiting or diuretic use behind a metabolic alkalosis, or diarrhea or a large volume of saline behind a hyperchloremic acidosis, and not as proof that a second disorder exists.