ANION GAP METABOLIC ACIDOSISMore then just a mud pile

Anne Peery, MDJuly 29, 2008

Metabolic acidosis

Overproduction or ingestion of fixed acid or loss of base which produces an increase in arterial pH (an acidemia)

HCO3 is used to buffer the extra fixed acid.

As a result, the arterial HCO3 decreases. Acidemia causes hyperventilation

(Kussmaul breathing), which is the respiratory compensation for metabolic acidosis.

The anion gap

An estimate of the unmeasured anions. Used to determine if a metabolic

acidosis is due to an accumulation of non-volatile acids (e.g. lactic acid) OR a net loss of bicarbonate (e.g. diarrhea)

Anion gap = Na – (Cl + HCO3)

The influence of albumin

Albumin is a major source of unmeasured anions!

If a patient’s serum albumin is low, then the patient has more unmeasured anions then the anion gap predicts.

Corrected AG = Observed AG + 2.5 x (4.5 – measured albumin)

More then one problem?

The “gap-gap” or “delta-delta” In the presence of a high AG metabolic

acidosis, it is possible to detect another metabolic acid base disorder by comparing the AG excess to the HCO3 deficit

Delta-Delta = (Measured AG – 12)/(24-measured HCO3)

Mixed Disorders

When a fixed acid accumulates in extracelluar fluid, the decrease in serum HCO3 is equivalent to the increase in AG and the gap-gap ratio = 1

When a hypercholemic acidosis appears, the decrease in HCO3 is greater then the increase in AG, and the gap-gap <1 (i.e. coexistent metabolic acidosis)

When alkali is added in presence of high AG acidosis, the decrease in bicarbonate is less then increase in AG and the gap-gap > 1 (i.e. coexistent metabolic alkalosis)

Differential for AG Metabolic Acidosis

1. Ketoacidosis2. Lactic acid acidosis3. Toxin-induced metabolic acidosis4. Renal failure acidosis

Ketosis

Occurs in conditions of reduced nutritient intake, adipose tissues release free fatty acids, which are taken up in the liver and metabolized to form the ketones, acetoacetate and B-hydroxybutyrate.

The ACETEST a nitroprusside reaction detects acetoacetate NOT hydroxybutyrate.

Ketosis

Diabetic ketoacidosis Alcoholic ketoacidosis Starvation ketosis

Alcoholic Ketoacidosis

Some chronic alcoholics, esp binge drinkers, who discontinue solid food intake while continuing EtOH consumption develop this form of ketoacidosis when EtOH ingestion is curtailed abruptly.

Metabolic acidosis may be severe but is accompanied by only a modest derangement in glucose levels (usually low but may be slightly elevated).

Alcoholic Ketoacidosis

Presentation may be complex because a mixed disorder is often present Metabolic alkalosis from emesis Respiratory alkalosis from EtOH liver

disease Lactic acid acidosis from hypoperfusion

Therapy includes IV glucose and saline Check electrolytes frequently High potential for refeeding syndrome

Lactic Acid Acidosis

Lactic acid can exist in two forms: L-lactate and D-Lactate. In mammals, only the levorotary form is a product of metabolism.

D-Lactate can accumulate in humans as a byproduct of metabolism by bacteria, which accumulate and overgrow in the GI tract with jejunal bypass or short bowel syndrome.

The lab measures only L-lactate!

L-Lactic Acidosis

Tissue underperfusion (Type A) Shock, shock, shock Hypoxia Asthma CO poisoning Severe anemia

L-Lactic Acidosis

Medical conditions (w/o tissue hypoxia) Hepatic failure Thiamine deficiency (co-factor for pyruvate

dehyrogenase) Malignancy Bowel ischemia Seizures Heat stroke Tumor lysis Drugs/Toxins

Metformin (particulary associated with hypovolemia and dye)

NRTI (especially stavudine and zidovudine) Propofol Nitroprusside

L-Lactic Acidosis

Propylene Glycol toxicity An alcohol used to enhance water solubility of

many hydrophobic IV medications (lorazepam, diazepam, esmolol, nitroglycerin)

Propylene glycocol toxicity from solvent accumulation has been reported in 19% to 66% of ICU patients receiving high dose lorazepam or diazepam for more then 2 days.

Signs of toxicity—agitation, coma, seizures, tachycardia, hypotension

Toxic-Induced Metabolic Acidosis Salicylates

More common in children then in adults May result in high AG metabolic acidosis Most commonly associated with respiratory

alkalosis due to direct stimulation of the respiratory center

Osmolar Gap

Under most physiologic conditions, Na, urea and glucose generate the osmotic pressure of blood .

Serum OSM = 2 (Na) + BUN/2.8 + glc/18 Calculated and determined OSM should agree

within 10 to 15 mOsm/kg. If not, then serum Na may be spuriously low

OR osmolytes other then Na, glc or urea have accumulated.

The osmolar gap is a reliable and helpful tool when screening for toxin-associated high AG acidosis.

Toxic-Induced Metabolic Acidosis Ethanol

In general does not cause high AG metabolic acidosis

Oxidized to acetaldehyde, acetyl CoA and CO2

Acetaldehyde levels increase significantly if acetaldehyde dehydrogenase inhibited by disulfiram, insecticides or a sulfonurea.

Paraldehyde Very rare

Toxic-Induced Metabolic Acidosis Methanol

Causes metabolic acidosis in addition to severe optic nerve and CNS manifestations

High osmolar gap

Ethylene Glycol Leads to high AG metabolic acidosis in addition to

severe CNS, cardiopulmonary and renal damage. Recognizing oxalate crystals in urine facilitates

diagnosis. High osmolar gap

Uremia

At a GFR < 20 mL/min, the inability to excrete H+ with retention of acid anions such as phosphate and sulfate results in an increased anion gap acidosis, which RARELY is severe.

The unmeasured anions “replace” bicarbonate (which is consumed as a buffer).

Hyperchloremic normal anion gap acidosis develops in milder cases of renal insufficiency.

References

Marino, P. 2007. The ICU Book. 3rd Edition. Philadelphia. Lippincott.

Brenner and Rector. 2007. The Kidney. 8th Edition. New York. Saunders.

McPhee S andPapadakis M. 2007. Current Medial Diagnosis and Treatment. New York. McGraw-Hill.

Up to Date 2008.