Transcript Anion gap metabolic acidosis

ANION GAP METABOLIC ACIDOSIS
More then just a mud pile
Anne Peery, MD
July 29, 2008
Metabolic acidosis
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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
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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
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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?
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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
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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
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Ketoacidosis
Lactic acid acidosis
Toxin-induced metabolic acidosis
Renal failure acidosis
Ketosis
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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
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Diabetic ketoacidosis
Alcoholic ketoacidosis
Starvation ketosis
Alcoholic Ketoacidosis
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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
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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
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Therapy includes IV glucose and saline
Check electrolytes frequently
High potential for refeeding syndrome
Lactic Acid Acidosis
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Lactic acid can exist in two forms: L-lactate and DLactate. 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
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Tissue underperfusion (Type A)
 Shock,
shock, shock
 Hypoxia
 Asthma
 CO poisoning
 Severe anemia
L-Lactic Acidosis
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Medical conditions (w/o tissue hypoxia)
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Hepatic failure
Thiamine deficiency (co-factor for pyruvate dehyrogenase)
Malignancy
Bowel ischemia
Seizures
Heat stroke
Tumor lysis
Drugs/Toxins
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Metformin (particulary associated with hypovolemia and dye)
NRTI (especially stavudine and zidovudine)
Propofol
Nitroprusside
L-Lactic Acidosis
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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
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Salicylates
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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
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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
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Ethanol
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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.
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Paraldehyde
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rare
Toxic-Induced Metabolic Acidosis
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Methanol
Causes metabolic acidosis in addition to severe optic nerve
and CNS manifestations
 High osmolar gap
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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
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Uremia
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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
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Marino, P. 2007. The ICU Book. 3rd Edition. Philadelphia. Lippincott.
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Brenner and Rector. 2007. The Kidney. 8th Edition. New York. Saunders.
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McPhee S andPapadakis M. 2007. Current Medial Diagnosis and
Treatment. New York. McGraw-Hill.
Up to Date 2008.