Nephrology Topic

Acid-base in five steps.

Five steps go further than a glance at a blood gas: pH, primary disorder, compensation, the albumin-corrected anion gap, then the delta ratio to catch a hidden second or third disorder.

Reviewed June 2026 · verify against current guidelines

The Method

Five steps, every time.

pH	Acidemia (<7.35) or alkalemia (>7.45)?
Primary disorder	Which way do HCO₃- and PaCO₂ point?
Compensation	Appropriate, or is a second disorder hiding?
Anion gap	Always calculate. Correct for albumin.
Delta ratio	In high-gap acidosis, find the hidden disorder. The step most people skip

Most stop too soon: Steps 3 to 5 are where mixed disorders hide.

A normal pH does not exclude a mixed disorder; opposite changes in HCO₃- and PaCO₂ can cancel out.

Steps 2-3

Name it, then check compensation.

The four primary disorders

Disorder	Marker	Expected compensation
Metabolic acidosis	↓ HCO₃-	PaCO₂ = 1.5 × HCO₃- + 8 ± 2 (Winter's)
Metabolic alkalosis	↑ HCO₃-	PaCO₂ ↑ ~0.7 per 1 mEq HCO₃-
Respiratory acidosis	↑ PaCO₂	HCO₃- ↑ 1 (acute) or 4 (chronic) per 10
Respiratory alkalosis	↓ PaCO₂	HCO₃- ↓ 2 (acute) or 5 (chronic) per 10

Acute vs chronic respiratory compensation depends on the clinical history, not the numbers alone.

Compensation rarely returns the pH fully to normal (chronic respiratory alkalosis can). An overshoot means a second disorder.

Step 4

Always gap the acidosis.

The calculation

Anion gap = Na - (Cl + HCO₃-). Normal is about 8 to 12.

Correct, then classify

Low albumin	Add 2.5 to the gap per 1 g/dL of albumin below 4.
High gap (HAGMA)	GOLD MARK: glycols, oxoproline, lactate, methanol, aspirin, renal, ketoacidosis.
Normal gap (NAGMA)	Bicarbonate loss: diarrhea, renal tubular acidosis, saline.

A normal gap can hide acidosis when albumin is low. Correct it first.

HAGMA high-anion-gap metabolic acidosisNAGMA normal-anion-gap metabolic acidosis

Step 5

Find the hidden disorder.

The delta ratio

In high-gap acidosis, compare the rise in gap to the fall in bicarbonate: (gap - 12) / (24 - HCO₃-).

Read the ratio

< 1	A normal-gap acidosis is also present.
1 to 2	Pure high-gap acidosis.
> 2	A metabolic alkalosis (or chronic respiratory acidosis) coexists.

The delta ratio is how you catch a second or third disorder on one gas.

Put It Together

One gas, five steps.

The gas

pH 7.30, PaCO₂ 30, HCO₃- 14, Na 140, Cl 110, albumin 4.

Walk the steps

Steps 1-2	Acidemic; low HCO₃- means a metabolic acidosis.
Step 3	Winter's: 1.5 × 14 + 8 = 29. PaCO₂ 30, so compensation is appropriate.
Step 4	Gap = 140 - (110 + 14) = 16. High gap.
Step 5	Ratio = (16 - 12) / (24 - 14) = 4/10 = 0.4.

Eyeballing says 'gap acidosis.' Step 5 reveals a second, normal-gap acidosis (ratio < 1).

Sources

Verify against current guidelines and local protocol before acting.

Berend K, de Vries AP, Gans RO. Physiological Approach to Assessment of Acid-Base Disturbances. NEJM 2014;371:1434-1445.
Seifter JL. Integration of Acid-Base and Electrolyte Disorders. NEJM 2014;371:1821-1831.
American Journal of Kidney Diseases (AJKD) Core Curriculum: Respiratory Acid-Base Disorders (2023) and Metabolic Acidosis.
Albert MS, Dell RB, Winters RW. Quantitative displacement of acid-base equilibrium in metabolic acidosis (Winter's formula). Ann Intern Med 1967.
Emmett M, Narins RG. Clinical use of the anion gap. Medicine 1977.

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