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Normal Anion Gap Metabolic Acidosis

what is a normal anion gap

Reviewed and revised 20th August 2013

Normal Anion Gap Metabolic Acidosis (NAGMA)

  • HCO3 loss and replaced with Cl- -> anion gap normal
  • if hyponatraemia is present the plasma [Cl-] may be normal despite the presence of a normal anion gap acidosis -> this could be considered a ‘relative hyperchloraemia’.


  • Chloride
  • Acetazolamide/Addisons
  • GI Loss
  • Extras – RTA, ingestion of oral acidifying salts, recovery phase of DKA


  • Addisons
  • Bicarb loss (GI or renal, incl RTA)
  • Chloride
  • Drugs (e.g. acetazolamide, acids)

Expanded Causes (HARDUP)

  • Hyperchloraemia
  • Acetazolamide, Addison’s disease
  • Renal tubular acidosis
  • Diarrhoea, vomiting, ileostomies, fistulae
  • Ureteroenterostomies
  • Pancreatoenterostomies


  • Ureteroenterostomies
  • Small bowel fistula
  • Excess Chloride
  • Diarrhoea
  • Carbonic anhydrase inhibitors
  • Renal tubular acidosis
  • Addisson’s disease
  • Pancreatoenterostomies


  • loss of bicarbonate with chloride replacement -> hyperchloraemic acidosis

Loss of base via the bowel

  • secretions into the large and small bowel are mostly alkaline with a bicarbonate level higher than that in plasma.
  • some typical at risk clinical situations are:
  • severe diarrhoea
  • villous adenoma
  • external drainage of pancreatic or biliary secretions (eg fistulas)
  • losses via NG tubes
  • urinary diversions
  • chronic laxative abuse
  • administration of acidifying salts

Loss of base via the kidney

Gain of mineral acid

  • eg HCl infusion
  • this should be easily established by history


  • normally 85% of filtered bicarbonate is reabsorbed in the proximal tubule and the remaining 15% is reabsorbed in the rest of the tubule
  • in patients receiving acetazolamide (or other carbonic anhydrase inhibitors), proximal reabsorption of bicarbonate is decreased resulting in increased distal delivery and HCO3-

    appears in urine

  • this results in a hyperchloraemic metabolic acidosis and is essentially a form of proximal renal tubular acidosis but is usually not classified as such.
  • see HCO3 loss above

Recovery phase of DKA

  • hyperchloraemic metabolic acidosis commonly develops during therapy of diabetic ketoacidosis with normal saline

Oral ingestion of Acidifying Salts

  • oral administration of CaCl2 or NH4Cl is equivalent to giving an acid load
  • both of these salts are used in acid loading tests for the diagnosis of renal tubular acidosis
  • CaCl2 reacts with bicarbonate in the small bowel resulting in the production of insoluble CaCO3 and H+
  • the hepatic metabolism of NH4+ to urea results in an equivalent production of H+


1. Increase in anions may be too low to push the anion gap out of the reference range

  • in lactic acidosis, the clinical disorder can be severe but the lactate may not be grossly high (eg lactate of 6mmol/l) and the change in the anion gap may still leave it in the reference range
  • administration of IV saline solution may replace lost acid anion with chloride so that treatment may result in the acidosis converting to a hyperchloraemic type

2. Intracellular movement of acid anions in exchange for chloride

  • in lactic acidosis, the movement of lactate intracellularly in exchange for chloride occurs via an antiport
  • example: tonic seizure leads exchange of lactate for Cl- so on presentation it looks like a NAGMA

3. Wide normal range of the anion gap

  • this could result in a situation where the anion gap is only elevated slightly or still within the normal range due to the combination of small errors in the measurement of the component electrolytes

Category: Forex

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