Normal Anion Gap Metabolic Acidosis

OVERVIEW

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’.

CAUSES

CAGE

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

ABCD

  • 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, ileostomies, fistulae
  • Ureteroenterostomies
  • Pancreatoenterostomies

or USEDCRAP

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

CHLORIDE GAIN/BICARBONATE LOSS

  • 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

ACETAZOLAMIDE THERAPY

  • 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.

GI LOSS

  • see HCO3 loss above

EXTRAS

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+

REASONS WHY ANION GAP MAY BE NORMAL DESPITE A ‘HIGH ANION GAP METABOLIC ACIDOSIS’

  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
    1. in lactic acidosis, the movement of lactate intracellularly in exchange for chloride occurs via an antiport
    2. 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
    1. 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
  4. Hypoalbuminaemia

References and Links


CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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