Approach to Metabolic Acidosis
Metabolic acidosis is a condition in which blood bicarbonate (HCO₃⁻) decreases,
causing the blood pH to fall below normal. When evaluating metabolic acidosis,
the first and most important diagnostic step is calculating the anion gap (AG). The
anion gap helps determine whether the acidosis is caused by accumulation of acids
or by bicarbonate loss.
The anion gap is calculated using the formula:
AG = Na⁺ − (Cl⁻ + HCO₃⁻)
Normal anion gap is approximately:
8–12 mEq/L
The anion gap represents the concentration of unmeasured anions in plasma. The
most important unmeasured anion is albumin, so the expected normal anion gap
depends partly on albumin concentration.
If albumin is low, the normal anion gap also becomes lower. Clinically, the
expected normal anion gap can be estimated as:
Normal AG ≈ Albumin × 3
For example:
● Albumin = 4 g/dL → normal AG ≈ 12
● Albumin = 2 g/dL → normal AG ≈ 6
Therefore, failure to adjust for albumin may cause clinicians to miss a true high
anion gap acidosis.
If the anion gap is elevated, the patient has high anion gap metabolic acidosis.
This means additional acids have accumulated in the blood.
,The mechanism is:
● Acid enters the blood
● The acid releases H⁺
● H⁺ is buffered by bicarbonate
● Bicarbonate concentration falls
● The acid’s negatively charged anion remains in plasma
● The anion gap increases
Common causes include:
● Diabetic ketoacidosis
● Lactic acidosis
● Chronic kidney disease
● Toxin ingestion such as methanol or ethylene glycol
In diabetic ketoacidosis, ketone bodies accumulate. In lactic acidosis, lactate
accumulates. In renal failure, sulfate, phosphate, and organic acids accumulate
because the kidneys cannot excrete them effectively.
If metabolic acidosis is present but the anion gap remains normal, the disorder is
called normal anion gap metabolic acidosis or hyperchloremic metabolic
acidosis.
In this situation:
● Bicarbonate is lost from the body
● Chloride increases to maintain electrical neutrality
● Therefore, the anion gap stays normal
Common causes include:
● Diarrhea
● Renal tubular acidosis (RTA)
To distinguish between gastrointestinal bicarbonate loss and renal acidification
defects, clinicians calculate the urine anion gap (UAG).
, The formula is:
UAG = (Na⁺ + K⁺) − Cl⁻
Urine bicarbonate is not included in the calculation.
The urine anion gap indirectly estimates urinary ammonium (NH₄⁺) excretion. This
is important because ammonium is a major mechanism for acid excretion by the
kidneys. Since NH₄⁺ is usually excreted with chloride, high urinary ammonium
causes high urine chloride concentration.
If the urine anion gap is negative (for example −10 or −20), urine chloride is high.
This suggests increased NH₄Cl excretion and indicates that the kidneys are
responding appropriately to acidosis.
In this case, the kidneys are functioning normally, so the metabolic acidosis is
likely due to bicarbonate loss from the gastrointestinal tract, especially diarrhea.
In diarrhea:
● Bicarbonate is lost in stool
● Metabolic acidosis develops
● Kidneys compensate by increasing ammonium excretion
● Urine chloride rises
● UAG becomes negative
If the urine anion gap is positive (for example +10 or +20), urine chloride is
relatively low. This indicates reduced ammonium excretion and suggests impaired
renal acid secretion.
In this setting, the cause is usually renal tubular acidosis (RTA).
Thus:
● Negative UAG → kidneys functioning properly → diarrhea likely
● Positive UAG → impaired renal acid excretion → RTA likely
The kidneys also play a major compensatory role during metabolic acidosis.
Metabolic acidosis is a condition in which blood bicarbonate (HCO₃⁻) decreases,
causing the blood pH to fall below normal. When evaluating metabolic acidosis,
the first and most important diagnostic step is calculating the anion gap (AG). The
anion gap helps determine whether the acidosis is caused by accumulation of acids
or by bicarbonate loss.
The anion gap is calculated using the formula:
AG = Na⁺ − (Cl⁻ + HCO₃⁻)
Normal anion gap is approximately:
8–12 mEq/L
The anion gap represents the concentration of unmeasured anions in plasma. The
most important unmeasured anion is albumin, so the expected normal anion gap
depends partly on albumin concentration.
If albumin is low, the normal anion gap also becomes lower. Clinically, the
expected normal anion gap can be estimated as:
Normal AG ≈ Albumin × 3
For example:
● Albumin = 4 g/dL → normal AG ≈ 12
● Albumin = 2 g/dL → normal AG ≈ 6
Therefore, failure to adjust for albumin may cause clinicians to miss a true high
anion gap acidosis.
If the anion gap is elevated, the patient has high anion gap metabolic acidosis.
This means additional acids have accumulated in the blood.
,The mechanism is:
● Acid enters the blood
● The acid releases H⁺
● H⁺ is buffered by bicarbonate
● Bicarbonate concentration falls
● The acid’s negatively charged anion remains in plasma
● The anion gap increases
Common causes include:
● Diabetic ketoacidosis
● Lactic acidosis
● Chronic kidney disease
● Toxin ingestion such as methanol or ethylene glycol
In diabetic ketoacidosis, ketone bodies accumulate. In lactic acidosis, lactate
accumulates. In renal failure, sulfate, phosphate, and organic acids accumulate
because the kidneys cannot excrete them effectively.
If metabolic acidosis is present but the anion gap remains normal, the disorder is
called normal anion gap metabolic acidosis or hyperchloremic metabolic
acidosis.
In this situation:
● Bicarbonate is lost from the body
● Chloride increases to maintain electrical neutrality
● Therefore, the anion gap stays normal
Common causes include:
● Diarrhea
● Renal tubular acidosis (RTA)
To distinguish between gastrointestinal bicarbonate loss and renal acidification
defects, clinicians calculate the urine anion gap (UAG).
, The formula is:
UAG = (Na⁺ + K⁺) − Cl⁻
Urine bicarbonate is not included in the calculation.
The urine anion gap indirectly estimates urinary ammonium (NH₄⁺) excretion. This
is important because ammonium is a major mechanism for acid excretion by the
kidneys. Since NH₄⁺ is usually excreted with chloride, high urinary ammonium
causes high urine chloride concentration.
If the urine anion gap is negative (for example −10 or −20), urine chloride is high.
This suggests increased NH₄Cl excretion and indicates that the kidneys are
responding appropriately to acidosis.
In this case, the kidneys are functioning normally, so the metabolic acidosis is
likely due to bicarbonate loss from the gastrointestinal tract, especially diarrhea.
In diarrhea:
● Bicarbonate is lost in stool
● Metabolic acidosis develops
● Kidneys compensate by increasing ammonium excretion
● Urine chloride rises
● UAG becomes negative
If the urine anion gap is positive (for example +10 or +20), urine chloride is
relatively low. This indicates reduced ammonium excretion and suggests impaired
renal acid secretion.
In this setting, the cause is usually renal tubular acidosis (RTA).
Thus:
● Negative UAG → kidneys functioning properly → diarrhea likely
● Positive UAG → impaired renal acid excretion → RTA likely
The kidneys also play a major compensatory role during metabolic acidosis.
