Anion Gap and acidosis

Anion Gap is of 2 types, plasma Anion gap and urinary anion gap

Plasma Anion Gap

Plasma Anion Gap refers to the amount of unmeasured anions present in the plasma.

Calculated by:[ Na+]     –     [Cl-]+[HCO3-]  or

[Na+] + [K+] – [Cl-]  + [HCO3-]

Normal Anion Gap- 10-12 meq

Delta Gap= Anion gap-12

Unmeasured anions-Proteins,phosphate,Sulfate,organic anions.

Points to be noted

  1. When the ion added is chloride, anion gap remains the same.
  2. Eg:Adding HCl leads to decrease in HCO3-(used for buffering H+) but the decrease in HCO3- is balanced by an increase in Cl-.So it leads to normal anion gap metabolic acidosis,also called hyperchloremic metabolic acidosis.
  3. When the ion added is not chloride, anion gap widens.

Urine Anion Gap


In normal subjects urine anion gap is usually zero or positive.

Urine anion gap is negative if there is no distal acidification of urine.

In Renal Tubular acidosis Urine anion gap is normal.

High anion gap metabolic acidosis

A high anion gap indicates acidosis. e.g. In uncontrolled diabetes, there is an increase in ketoacids (i.e. an increase in unmeasured anions) and a resulting increase in the anion gap. In these conditions, bicarbonate concentrations decrease, in response to the need to buffer the increased presence of acids (as a result of the underlying condition). The bicarbonate is replaced by the unmeasured anion resulting in a high anion gap.

  • Methanol
  • Uremia
  • DKA/Alcoholic KA
  • Paraldehyde/propylene glycol(used in diazepam injns)
  • Isoniazid
  • Lactic Acidosis
  • Ethylene Glycol
  • Rhabdo/Renal Failure
  • Salicylates


Normal Anion gap Metabolic acidosis

In patients with a normal anion gap the drop in HCO3 is compensated for almost completely by an increase in Cl and hence is also known as hyperchloremic acidosis.

The HCO3 lost is replaced by a chloride anion, and thus there is a normal anion gap.

  • Gastrointestinal loss of HCO3 (i.e., diarrhea) (vomiting causes hypochloraemic alkalosis)
  • Renal loss of HCO3 (i.e. proximal renal tubular acidosis(RTA) also known as type 2 RTA)
  • Renal dysfunction (i.e. distal renal tubular acidosis also known as type 1 RTA)
  • Ingestions
    • Ammonium chloride and Acetazolamide.
    • Hyperalimentation fluids (i.e. total parenteral nutrition)
  • Some cases of ketoacidosis, particularly during rehydration with Na+ containing IV solutions.
  • Mineralocorticoid deficiency (Addison’s disease)

FUSEDCARS (fistula (pancreatic), uretogastric conduits, saline administration, endocrine (hyperparathyroidism), diarrhea, carbonic anhydrase inhibitors (acetazolamide), ammonium chloride, renal tubular acidosis, spironolactone)

Summed up as:

Anion Gap Metabolic Acidosis: MUDPILERS

  • Methanol
  • Uremia
  • DKA/Alcoholic KA
  • Paraldehyde
  • Isoniazid
  • Lactic Acidosis
  • Ethylene Glycol
  • Rhabdo/Renal Failure
  • Salicylates

Non-Anion Gap Acidosis: HARDUPS

  • Hyperalimentation
  • Acetazolamide
  • Renal Tubular Acidosis
  • Diarrhea
  • Uretero-Pelvic Shunt
  • Post-Hypocapnia
  • Spironolactone

Acute Respiratory Acidosis  any hypoventilation state

  • CNS Depression (drugs/CVA)
  • Airway Obstruction
  • Pneumonia
  • Pulmonary Edema
  • Hemo/Pneumothorax
  • Myopathy
Chronic Respiratory Acidosis = COPD/restrictive lung dz

Metabolic Alkalosis: CLEVER PD

  • Contraction
  • Licorice
  • Endocrine:Conns
  • Cushing’s/Bartter’s
  • Vomiting
  • Excess Alkali
  • Refeeding Alkalosis

Respiratory Alkalosis: CHAMPS (think speed up breathing)

  • CNS disease
  • Hypoxia
  • Anxiety
  • Mech Ventilators
  • Progesterone
  • Salicylates/Sepsis

Low anion gap

A low anion gap is frequently caused by hypoalbuminemia. Albumin is a negatively charged protein and its loss from the serum results in the retention of other negatively charged ions such as chloride and bicarbonate. As bicarbonate and chloride anions are used to calculate the anion gap, there is a subsequent decrease in the gap.

In hypoalbuminaemia the anion gap is reduced from between 2.5 to 3 mmol/L per g/dL decrease in serum albumin.Common conditions that reduce serum albumin in the clinical setting are hemorrhage, nephrotic syndrome, intestinal obstruction and liver cirrhosis.

The anion gap is sometimes reduced in multiple myeloma, where there is an increase in plasma IgG (paraproteinaemia).

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