Unmeasured anions

As previously discussed, in anion gap metabolic acidosis, the isoelectric state is maintained because unmeasured anions are present. With a normal anion gap metabolic acidosis, the isoelectric state is maintained by an increase in the measured... 

Normally, the sum of the cations exceeds the sum of the anions by no more than 12-16 mEq/L (or 8-12 mEq/L if the formula used for estimating the anion gap omits the potassium level). A larger-than expected anion gap is caused by the presence of unmeasured anions (lactate, etc) accompanying metabolic acidosis. This may occur with numerous conditions, such as diabetic ketoacidosis, renal failure, or shock-induced lactic acidosis. Drugs that may induce an elevated anion gap metabolic acidosis (Table 58-1) include aspirin, metformin, methanol, ethylene glycol, isoniazid, and iron. 

The pathogenesis of ketoacidosis is discussed in detail in Chapter 25. Ketoacids such as P-hydroxybutyrate and 2-oxoglutarate accumulate and represent the unmeasured anions. Accumulation of these ketone bodies causes a decrease in HCOJ, a normal or low serum chloride, and a liigh anion gap. Ketoacids also accumulate in states of starvation and alcoholic malnutrition. 

This generally occurs with blood salicylate concentrations above 30 mg/dL. Salicylate, itself an unmeasured anion, alters peripheral metabolism, leading to the production of various organic acids without dominance of any specific acid. The processes eventually result in a metabohc acidosis with a high anion gap. Saficylate also stimulates the respiratory center to increase the rate and depth of respiration, resulting in a low PCO2, low HCOj, and respiratory alkalosis (see the section entitled Respiratory Alkalosis). In adults, mijced respiratory aUcalosis and metabolic acidosis are more common, whereas in children, metabolic acidosis predominates. 

The unmeasured anion is commonly known as the anion gap, which is normally 12 4 mEq/L. This value is useful in assessing the acid-base status of a patient and in diagnosing metabolic acidosis. Disorders that cause a high anion gap are metabolic acidosis, dehydration, therapy with sodium salts of strong acids, therapy with certain antibiotics (e.g., carbenicillin), and alkalosis. A decrease in the normal anion gap occurs in various plasma dilution states, hypercalcemia, hypermagnesemia, hypernatremia, hypoalbuminemia, disorders associated with hyperviscosity, some paraproteinemias, and bromide toxicity. 

Arterial blood gases and serum electrolytes should be measured regularly in patients with CKD. These patients should also have a complete medical history and review of medications to determine if there are other potential causes of acid-base disturbances (e.g., diabetic ketoacidosis, ingestion of toxins, or GI disorders). The anion gap, indicating the differences in unmeasured anions and cations, should also be calculated (see Chap. 51). An elevated anion gap (>17 mEq/L) is often present in those with CKD due to the accumulation of organic anions, phosphates, and sulfates. 

The cation concentration is equal to the sodium concentration plus that of unmeasured cations (UCs), predominantly magnesium, calcium, and potassium. The anion concentration is equal to the concentrations of chloride, bicarbonate, and unmeasured anions (UAs), including proteins, sulfates, phosphates, and organic anions. Therefore, as the result of the combination of the two equations above the SAG can be expressed as ... 

The normal SAG is approximately 9 mEq/L, with a range of 3 to 11 mEq/L. This value is lower than the value of 12 mEq/L cited in the literature in the past because of changes in the instrumentation for measurement of serum electrolytes during the past decade. Increases in the anion gap to values in excess of 17 to 20 mEq/L are indicative of the accumulation of unmeasured anions in ECF. 

These unmeasured anions are generated as the result of the consumption of HCOJ by endogenous organic acids such as lactic acid, acetoacetic acid, or / -hydroxybutyric acid or from the ingestion of toxins such as methanol or ethylene glycol. The degree of elevation in the SAG is dependent on the clearance of the anion, as well as the multiple factors that influence HCOJ concentrations. Thus the SAG is a relative rather than an absolute indication of the cause of metabolic acidosis. The SAG may also be elevated in the metabolic acidosis due to renal failure, as the result of the accumulation of various organic anions, phosphates, and sulfates. 

The anion gap (AG) is calculated by subtracting the sum of plasma chloride and bicarbonate concentrations from the sum of the sodium and potassium it represents the balance between the plasma anions and cations (Feldman and Rosenberg 1981 Kraut and Madias 2007). The unmeasured anions that contribute to the anion gap... 

Anion gap is calculated by subtracting measured serum anions (bicarbonate plus chloride) from cations (potassium plus sodium). Increases in anion gap above normal are due to the presence of unmeasured anions that accompany acidosis. The gap in this case (38 meq/L) is well in excess of the normal gap (12-16 meq/L). The answer is (C). 

C. Anion gap metabolic acidosis. The normal anion gap of 8-12 mEq/L accounts for unmeasured anions (eg, phosphate, sulfate, and anionic proteins) In the plasma. Metabolic acidosis is usually associated with an elevated anion gap. 

An anion gap acidosis (anion gap >16 mEq/L) suggests an increase in unmeasured anion(s), and a significantly elevated anion gap (>20 mEq/L) should always be evaluated further as there are no physiologic processes to generate unmeasured anions [2]. An anion gap acidosis is highly... 

Unmeasured anions (acids) are elevated Elevated acid results in a loss of bicarbonate... 

In addition to proteins, the plasma contains a large number of other anions, the most predominant of which are chloride and hydrogencarbonate. Smaller amounts of phosphate, sulfate, and organic acids are also present. Plasma also contains a number of cations, most predominantly sodium, and lesser quantities of potassium, calcium, and magnesium. The total cation concentration is 150 mmol 1 , and since electrical neutrality must be maintained, the total anion concentration is similar. However, when subtracting the concentration of the major anions (Cl and HCOi") from the major cations (Na and K ), the result is not zero, but usually between 10 and 20 mmol 1 . This is known as the anion gap and represents the unmeasured anions (e.g., POl , S04, and organic acids). 

The anion gap is increased by lower amounts of unmeasured cations or by increased amounts of unmeasured anions. Lactic adt, gfycolatcy gPyoxalalcy and oxalate can significantly increase the concentratitmtrfraimeasui anions. 

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