ANION GAP METABOLIC

ACIDOSIS
More then just a mud pile

Anne Peery, MD
July 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. Ketoacidosis
2. Lactic acid acidosis
3. Toxin-induced metabolic acidosis
4. 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.