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1.(MeSH)The balance between acids and bases in the BODY FLUIDS. The pH (HYDROGEN-ION CONCENTRATION) of the arterial BLOOD provides an index for the total body acid-base balance.
Chemistry, Physical, Physical Chemistry - Physiological Processes, Physiologic Processes - Blood Physiology, Physiology, Blood - Biochemical Phenomena, Metabolism, and Nutrition, Metabolism, Nutrition, and Biochemical Phenomena[Hyper.]
Anion Gap (n.) [MeSH]
||This article may be too technical for most readers to understand. (April 2010)|
|Na+ = 140||Cl− = 100||BUN = 20||/|
|Glu = 150|
|K+ = 4||CO2 = 22||PCr = 1.0||\|
|ARTERIAL BLOOD GAS:|
|HCO3- = 24||paCO2 = 40||paO2 = 95||pH = 7.40|
|pACO2 = 36||pAO2 = 105||A-a g = 10|
|Ca = 9.5||Mg2+ = 2.0||PO4 = 1|
|CK = 55||BE = −0.36||AG = 16|
|PMO = 300||PCO = 295||POG = 5||BUN:Cr = 20|
|UNa+ = 80||UCl− = 100||UAG = 5||FENa = 0.95|
|UK+ = 25||USG = 1.01||UCr = 60||UO = 800|
|PROTEIN/GI/LIVER FUNCTION TESTS:|
|LDH = 100||TP = 7.6||AST = 25||TBIL = 0.7|
|ALP = 71||Alb = 4.0||ALT = 40||BC = 0.5|
|AST/ALT = 0.6||BU = 0.2|
|AF alb = 3.0||SAAG = 1.0||SOG = 60|
|CSF alb = 30||CSF glu = 60||CSF/S alb = 7.5||CSF/S glu = 0.4|
The anion gap   is the difference in the measured cations and the measured anions in serum, plasma, or urine. The magnitude of this difference (i.e. "gap") in the serum is often calculated in medicine when attempting to identify the cause of metabolic acidosis. If the gap is greater than normal, then high anion gap metabolic acidosis is diagnosed.
However, omission of potassium has become widely accepted, as potassium concentrations, being very low, usually have little effect on the calculated gap. This leaves the following equation:
Anion gap is an 'artificial' and calculated measure that is representative of the unmeasured ions in plasma or serum (serum levels are used more often in clinical practice).
Commonly measured cations include sodium (Na+), Potassium (K+), Calcium (Ca2+) and Magnesium (Mg2+). Cations that are generally considered 'unmeasured' include a few normally occurring serum proteins, and some pathological proteins (e.g., paraproteins found in multiple myeloma). Likewise, commonly 'measured' anions include chloride (Cl−), bicarbonate (HCO3−) and phosphate (H2PO4−), while commonly 'unmeasured' anions include sulphates and a number of serum proteins.
By definition, only Na+, Cl− and HCO3− (+/- K) are used when calculating the anion gap.
In normal health there are more measurable cations compared to measurable anions in the serum; therefore, the anion gap is usually positive. Because we know that plasma is electro-neutral we can conclude that the anion gap calculation represents the concentration of unmeasured anions. The anion gap varies in response to changes in the concentrations of the above-mentioned serum components that contribute to the acid-base balance. Calculating the anion gap is clinically useful, as it helps in the differential diagnosis of a number of disease states.
Modern analyzers make use of ion-selective electrodes which give a normal anion gap as <11 mEq/L. Therefore according to the new classification system a high anion gap is anything above 11 mEq/L and a normal anion gap is often defined as being within the prediction interval of 3–11 mEq/L, with an average estimated at 6 mEq/L.
In the past, methods for the measurement of the anion gap consisted of colorimetry for [HCO3−] and [Cl−] as well as flame photometry for [Na+] and [K+]. Thus normal reference values ranged from 8 to 16 mEq/L plasma when not including [K+] and from 10 to 20 mEq/L plasma when including [K+]. Some specific sources use 15 and 8–16 mEq/L.
A reference range provided by the particular lab that performs the testing should be used to determine if the anion gap is outside of the normal range. A certain proportion of normal individuals may have values outside of the 'normal' range provided by any lab.
Anion gap can be classified as either high, normal or, in rare cases, low. Laboratory errors need to be ruled out whenever anion gap calculations lead to results that do not fit the clinical picture. Methods used to determine the concentrations of some of the ions used to calculate the anion gap may be susceptible to very specific errors. For example, if the blood sample is not processed immediately after it is collected, continued leukocyte cellular metabolism may result in an increase in the HCO3− concentration, and result in a corresponding mild reduction in the anion gap. In many situations, alterations in renal function (even if mild, e.g., as that caused by dehydration in a patient with diarrhea) may modify the anion gap that may be expected to arise in a particular pathological condition.
A high anion gap indicates that there is loss of HCO3− without a concurrent increase in Cl−. Electroneutrality is maintained by the elevated levels of anions like lactate, beta-hydroxybutyrate and acetoacetate, PO4−, and SO4−. These anions are not part of the anion-gap calculation and therefore a high anion gap results. Thus, the presence of a high anion gap should result in a search for conditions that lead to an excess of these substances.
The anion gap is affected by changes in unmeasured ions. A high anion gap indicates acidosis. e.g. In uncontrolled diabetes, there is an increase in ketoacids (i.e. an increase in unmeasured anions) and a resulting increase in the anion gap. In these conditions, bicarbonate concentrations decrease, in response to the need to buffer the increased presence of acids (as a result of the underlying condition). The bicarbonate is consumed by the unmeasured anion (via its action as a buffer) resulting in a high anion gap.
Note: a useful mnemonic to remember this is MUDPILES (methanol, uremia, diabetic ketoacidosis, propylene glycol, isoniazid, lactic acidosis, ethylene glycol, salicylates). MUDPILERS is a variation with the addition of "R" for rhabdomyolysis. Another variation is MUDPALES which is the same as previous only with the "A" representing alcoholic ketoacidosis, a common emergency department presenting condition. A newer mnemonic CUTE DIMPLES includes "C" for Cyanide, "T" for Toluene, and a second "E" for ethanol (alcoholic ketoacidosis) (cyanide, uremia, toluene, ethanol, diabetic ketoacidosis, isoniazid, methanol, propylene glycol, lactic acidosis, ethylene glycol, salicylates). Historically, the "P" in MUDPILES was for paraldehyde. As paraldehyde is no longer used medically, the "P" in the MUDPILES mnemonic currently refers to propylene glycol, a substance common in race car radiator fluid and in pharmaceutical injections such as diazepam or lorazepam as a preservative. Accumulation of propylene glycol is converted into lactate and pyruvate, which causes lactic acidosis.
In patients with a normal anion gap the drop in HCO3− is compensated for almost completely by an increase in Cl− and hence is also known as hyperchloremic acidosis.
The HCO3− lost is replaced by a chloride anion, and thus there is a normal anion gap.
Note: a useful mnemonic to remember this is FUSEDCARS (fistula (pancreatic), uretero-enterostomy, saline administration, endocrine (hyperparathyroidism), diarrhea, carbonic anhydrase inhibitors (acetazolamide), ammonium chloride, renal tubular acidosis, spironolactone)
A low anion gap is frequently caused by hypoalbuminemia. Albumin is a negatively charged protein and its loss from the serum results in the retention of other negatively charged ions such as chloride and bicarbonate. As bicarbonate and chloride anions are used to calculate the anion gap, there is a subsequent decrease in the gap.
In hypoalbuminaemia the anion gap is reduced from between 2.5 to 3 mmol/L per 1 g/dL decrease in serum albumin. Common conditions that reduce serum albumin in the clinical setting are hemorrhage, nephrotic syndrome, intestinal obstruction and liver cirrhosis.
Corrections can be made for hypoalbuminemia to give an accurate anion gap.