Normal anion gap acidosis

In contrast to high anion gap acidoses, m which bicarbonate is consumed in buffering excess the cause of acidosis in the presence of a norma anion gap is the loss of bicarbonate-rich fluid from eitlrer the kidney or gastrointestinal tract. As bicarbonate is lost, more Cl ions are reabsorbed with Na or to maintain electrical neutrality so that hyperchloremia ensues (see Figure 46-14). Normal anion gap acidosis can be divided into hypokalemic and normokalemic acidoses, which can be helpful in the differential diagnosis of this type of disorder (see Table 46-4). 

Hyperkalemic Normal Anion Gap Acidosis (Renal Tubular Acidosis Type IV)... 

All patients developed a compensatory metabolic acidosis due to chronic hyperventilation. Respiratory alkalosis was thought to have developed because of capillary leak into the lungs producing borderline or frank pulmonary edema. After several days a superimposed normal anion gap acidosis developed from dilution by large volumes of saline fluid resuscitation. The authors found no defects in renal handling of calcium, phosphorous, or magnesium. There was no evidence of a renal acidification defect or renal tubular acidosis. 

Metabolic acidosis is characterized by a decrease in serum HC03. The anion gap is used to narrow the differential diagnosis, as this acidosis may be caused by addition of acids (increased anion gap) or loss of HC03 (normal anion gap). The compensation for metabolic acidosis is an increase in ventilation with a decrease in arterial C02. 

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... 

In patients with a normal anion gap metabolic acidosis it is ... 

Because clove cigarettes also contain tobacco, they carry all of the hazards of regular tobacco smoking (Council on Scientific Affairs 1988). Several cases of serious medical illness have been associated with clove cigarettes in the United States (Guidotti et al. 1989). These include cases of hemorrhagic pulmonary edema, pneumonia, bronchitis, and hemoptysis. Because eugenol anesthetizes the respiratory tract, it inhibits the normal gag reflex and has led to aspiration pneumonia in at least one case. Accidental overdoses in children have led to CNS depression, urinary abnormalities, and anion-gap acidosis. These cases were treated successfully with supportive measures (Lane et al. 1991). 

DKA is a positive anion gap metabolic acidosis associated with the accumulation of P-hydroxy-butyrate and acetoacetate. Lactic acidosis secondary to cardiac or renal failure, hypoxia, poor tissue perfusion, shock, or sepsis may also contribute to the anion gap in DKA. A normal anion gap (AG) is 12 2 mEq/L.The anion gap (AG) is calculated using the following formula AG = ([Na+ + K+] - [Cl- + HCO,]). In our illustrative case, the anion gap was 28, indicating severe metabolic acidosis. 

A 76-year-old woman developed quadriparesis associated with hyperkalemia after taking diclofenac lOOmg/day for 10 months for gouty arthritis. She had a metabolic acidosis with a normal anion gap and mild renal impairment. Her weakness resolved after withdrawal of diclofenac and correction of the hyperkalemia. 

Figure 46-14 Simple Gambeigram depiction of normal gap, anion gap acidosis, and nonanion gap acidosis. Cations, Na and are in left bar for each condition, whereas measured (Cl and HCOj) and unmeasured (U ) anions are in right bar for each condition.

Diarrhea may cause acidosis as a result of loss of Na, Kfi and HCOJ. One of the primary exocrine functions of the pancreas is production of HCOs to neutralize gastric contents on entry into the duodenum. If the water, K", and HCO7 in the intestine are not reabsorbed, a hypokalemic, normal anion gap metabolic acidosis will develop. The resulting hyperchloremia is due to the replacement of lost bicarbonate with Cr to maintain electrical balance. 

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. 

The answer is d. (Murray, pp 238-249. Scriver, pp 2165-2194. Sack, pp 121-144. Wilson, pp 287-324.) Propionic acidemia (232000) results from a block in propionyl CoA carboxylase (PCC), which converts propionic to methylmalonic acid. Excess propionic acid in the blood produces metabolic acidosis with a decreased bicarbonate and increased anion gap (the serum cations sodium plus potassium minus the serum anions chloride plus bicarbonate). The usual values of sodium (-HO meq/L) plus potassium ( 4 meq/T) minus those for chloride (-105 meq/L) plus bicarbonate (—20 meq/L) thus yield a normal anion gap of -20 meq/L. A low bicarbonate of 6 to 8 meq/L yields an elevated gap of 32 to 34 meq/L, a gap of negative charge that is supplied by the hidden anion (propionate in propionic acidemia). Biotin is a cofactor for PCC and its deficiency causes some types of propionic acidemia. Vitamin B deficiency can cause methylmalonic aciduria because vitamin Bn is a cofactor for methylmalonyl coenzyme A mutase. Glycine is secondarily elevated in propionic acidemia, but no defect of glycine catabolism is present. 

Megarbane B, Bruneel F, Bedos JP, et al. 2000. Ammonium chloride poisoning a misunderstood cause of metabolic acidosis with normal anion gap. Intensive Care Med 26(12) 1869. 

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. 

Laboratory studies Laboratory studies noted a acidosis with a pH of 7.08. The resident calculated an anion gap of 32, which confirmed an anion gap acidosis as the bicarbonate was 6 mmol/L, sodium was 145 nunol/L, and chloride was 107 mmol/L (Box 8.1). Due to the anion gap acidosis, the resident requests both a lactate (which was relatively normal at 2.2 mmol/L) and urine organic acids (Fig. 8.1). 

Mathews KD, Stark JE. Hyperchloremic, normal anion-gap, metabolic acidosis due to topiramate. Am J Health Syst Pharm 2008 65(15) 1430-4. 

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. 

Five patients with metformin-associated severe lactic acidosis, seen between 1 September 1998 and 31 May 2001, have been reported (58). Two had attempted suicide. All had severe metabolic acidosis with a high anion gap and raised blood lactate concentrations. Four developed profound hypotension and three had acute respiratory failure. Three had normal preceding renal function. Three required conventional hemodialysis and two continuous renal replacement therapy. 

The major concern of the emergency department physicians was the lethargy, hypotonia, and seizure activity. Initial laboratory studies revealed that the child had a normal complete blood count and smear. Other blood tests revealed metabolic acidosis with a bicarbonate concentration of 11 mEq/L (normal is 20-25 mEq/L) and an anion gap of 22 mEq/L (normal is < 15 mEq/L). His serum glucose, calcium, and magnesium concentrations were normal. To exclude the diagnosis of meningitis, a spinal tap was performed. The cell counts and chemistries of the cerebrospinal fluid were normal. The physicians considered that the child might have sepsis and administered antibiotics and intravenous fluids. Prior to administration of antibiotics, blood, urine, and cerebrospinal fluid were sent for bacterial culture. 

The diagnosis of D-lactic acidosis is suspected in patients with disorders of the small intestine causing malabsorption and when the serum anion gap (Chapter 39) is elevated in the presence of normal serum levels of L-lactate and other organic acids. Measurement of serum D-lactate requires special enzymatic procedures utilizing D-lactate dehydrogenase and NADH. As D-lactate is converted to pyruvate, NADH is oxidized to NAD+ which is detected spectrophotometrically (Chapter 8). 

Acid-base disturbances frequently coexist with two or more simple disorders (Table 39-2). In these settings, blood pH is either severely depressed (e.g., a patient with metabolic acidosis and respiratory acidosis) or normal. Both plasma HCOj and pH may be within normal limits when metabolic alkalosis and metabolic ketoacidosis coexist, as in a patient with diabetic ketoacidosis who is vomiting. In this situation, an elevated anion gap may be the initial abnormality that can be detected in the underlying mixed acid-base disturbance. 

I 07. A child presents with severe vomiting, dehydration, and fever. Initial blood studies show acidosis with a low bicarbonate and an anion gap (the sum of sodium plus potassium minus chloride plus bicarbonate is 40 and larger than the normal 20 to 25). Preliminary results from the blood amino acid screen show two elevated amino acids, both with nonpolar side chains. A titration curve performed on one of the elevated species shows two ionizable groups with approximate pKs of 2 and 9.5. The most likely pair of elevated amino acids consists of... 

In the conditions discussed above (diabetic ketoacidosis, lactic acidosis, uremia, and ingestion of salicylate, ethylene glycol, or methanol) metabolic acidosis is associated with an increased anion gap. In the face of excess metabolic acids, bicarbonate is depleted in the process of buffering excess hydrogen ions. Provided that the renal functions is normal, the kidney attempts to compensate by secreting an acid urine and retaining bicarbonate. 

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