His medications included hydroxyurea and deferasirox. He was treated for painful sickle crisis and community-acquired pneumonia with analgesics, oxygen and antibiotics. He showed an initial improvement in clinical condition. He received repeated blood transfusions for his worsening anemia but did not show a subsequent increase in his hematocrit.
His refractory anemia workup did not support any active bleeding or hemolysis. His reticulocyte count was 1. A peripheral smear showed anisocytosis and Howell-Jolly bodies, but no schistocytes. Our patient deteriorated four days after admission, with drowsiness, disorientation and slurred speech. A physical examination was unrevealing and a neurological examination showed no focal deficits. His electrolytes, blood urea nitrogen, creatinine, blood and urine cultures and brain imaging were indeterminate.
His opioid medications were decreased and he was given naloxone without improvement in his mental status. By the seventh day, he was stuporous. His family began to consider a 'comfort measures only' goal of care. This case was a diagnostic quandary. To decipher the cause of the refractory anemia, bone pain and change in mental status we focused on the surprising finding of a serum anion gap AG of zero Table 1.
His outpatient AG over the last six months had been between three and four. Immunofixation showed an immunoglobulin G monoclonal protein with kappa light chain specificity. He was treated with dexamethasone Decadron and melphalan hydrochloride and made significant improvement, returning to his baseline functional status within 14 days.
Routinely measured cations and anions include sodium, potassium, chloride and bicarbonate. The sum of all circulating cations must equal the sum of all circulation anions [ 1 ]. The AG exists because the total unmeasured anions exceed the total unmeasured cations. Population studies using contemporary measurements of serum electrolytes suggest the normal range of AG to be between six and ten [ 1 , 2 ].
Furthermore, the concentration of potassium in the blood is usually negligible compared to that of sodium, chloride and bicarbonate. Therefore, the AG equals the sum of sodium ions minus the sum of the chloride ions and bicarbonate ions.
A low AG or a negative AG is uncommon in clinical medicine. There are very few clinical conditions associated with a low AG. Additionally, laboratory error may be a possible cause of a low AG finding. Thus, the test was repeated in our patient. The AG was still between zero and minus one.
Normally, the majority of the serum AG is due to the sum of the anionic charges on circulating proteins. Albumin being the most abundant of all circulating proteins, hypoalbuminemia can result in a low AG. In our patient, the serum albumin was 2. Since the s, ion-selective electrodes for specific ionic species were used for the measurement of serum electrolytes. The difference between the ionic concentration in the electrode known and the sample creates an electrical potential measured and the sample ionic concentration can be calculated.
Why do we use the anion gap? It is important because an increased anion gap usually is caused by an increase in unmeasured anions, and that most commonly occurs when there is an increase in unmeasured organic acids, that is, an acidosis 3 , 4. Acids eg, lactate and pyruvate are protons donors and must be buffered by bicarbonate.
The consumption of bicarbonate by the unmeasured anions will increase the anion gap by lowering the serum bicarbonate level. The total numbers of anions and cations are still equal, but the gap is increased because of a lowering of a measured anion, serum bicarbonate. The etiologies of an increase in organic acids have been well outlined. The most common ones can be remembered by the mnemonic MUDPILES : methanol, metformin, uremia, diabetic ketoacidosis, ethylene glycol, salicylates and starvation 5 , 6.
These conditions produce an acid load that consumes bicarbonate, increases the anion gap, and lowers serum pH. If the patient is acidotic and has an elevated anion gap, it is almost certainly caused by one of these conditions, each one with us characteristic signs, symptoms, and laboratory values. Whereas the presence for a high anion gap educes the consideration of a differential diagnosis by reflex in daily clinical practice, a low anion gap often does not elicit the same warning to clinicians and hence often remains either undiscovered or neglected.
The classical differential diagnosis of a low anion gap has changed since the ion-selective electrode has been introduced. A low anion gap has several utilities. First, it can be an early and sometimes only sign of an underlying disease process such as paraproteinemia. In addition to displacement of sodium-containing water from serum by large amounts of non-sodium-containing paraproteins, some paraproteins eg, IgG in multiple myeloma can have a net positive charge at physiological pH.
This leads to an increase in unmeasured cations and a low anion gap 7 , 8. Concomitant severe hypercalcemia and hypoalbuminemia are often contributing factors to a low anion gap in multiple myeloma 9. Since the only cation included in the anion gap calculation is sodium, severe hyperkalemia, hypercalcemia, hypermagnesemia or lithium intoxication theoretically can also lead to a significantly decreased anion gap.
Second, at normal serum pH of 7. Staging for MM patients were performed based on Salmon-Durie method. AGs were compared by independent sample t-test. Pearson coefficient of correlation was used to correlate paraprotein IgG concentration and anion gap. The mean ages of MM and controls were So AG has proven helpful in the differential diagnosis of metabolic acidosis. Conditions associated with reduced AG are relatively few and individually rare but the finding of reduced AG can, like increased AG, be diagnostically useful as a recently published case history demonstrates.
The case concerns a 50 year old African American gentleman with sickle cell disease and chronic kidney disease who was admitted to hospital because of his deteriorating condition. This was assumed to be due to a sickle cell crisis evidenced by severe anaemia and increasing bone pain.
The anemia did not however appear to be haemolytic in nature as would be expected in sickle cell crisis, and despite blood transfusion, grew worse. After four days in hospital his condition further deteriorated with change in mental status drowsiness, disorientation and slurred speech that progressed to stupor. There was concern that this man was dying.
0コメント