This article may be too technical for most readers to understand.(April 2010) |
BMP/ELECTROLYTES: | |||
Na+ = 140 | Cl− = 100 | BUN = 20 | / Glu = 150 \ |
K+ = 4 | CO2 = 22 | PCr = 1.0 | |
ARTERIAL BLOOD GAS: | |||
HCO3− = 24 | p a CO2 = 40 | p a O2 = 95 | pH = 7.40 |
ALVEOLAR GAS: | |||
p A CO2 = 36 | p A O2 = 105 | A-a g = 10 | |
OTHER: | |||
Ca = 9.5 | Mg2+ = 2.0 | PO4 = 1 | |
CK = 55 | BE = −0.36 | AG = 16 | |
SERUM OSMOLARITY/RENAL: | |||
PMO = 300 | PCO = 295 | POG = 5 | BUN:Cr = 20 |
URINALYSIS: | |||
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: | |||
CSF alb = 30 | CSF glu = 60 | CSF/S alb = 7.5 | CSF/S glu = 0.6 |
The anion gap [1] [2] (AG or AGAP) is a value calculated from the results of multiple individual medical lab tests. It may be reported with the results of an electrolyte panel, which is often performed as part of a comprehensive metabolic panel. [3]
The anion gap is the quantity difference between cations (positively charged ions) and anions (negatively charged ions) in serum, plasma, or urine. The magnitude of this difference (i.e., "gap") in the serum is calculated to identify metabolic acidosis. If the gap is greater than normal, then high anion gap metabolic acidosis is diagnosed.
The term "anion gap" usually implies "serum anion gap", but the urine anion gap is also a clinically useful measure. [4] [5] [6] [7]
The anion gap is a calculated measure. It is computed with a formula that uses the results of several individual lab tests, each of which measures the concentration of a specific anion or cation.
The concentrations are expressed in units of milliequivalents/liter (mEq/L) or in millimoles/litre (mmol/L).
The anion gap is calculated by subtracting the serum concentrations of chloride and bicarbonate (anions) from the concentrations of sodium and potassium (cations):
Because potassium concentrations are very low, they usually have little effect on the calculated gap. Therefore, omission of potassium has become widely accepted. This leaves the following equation:
Normal AG = 8-16 mEq/L
Expressed in words, the equation is:
(Bicarbonate may also be referred to as "total CO2" or "carbon dioxide".) [3]
Calculating the anion gap is clinically useful because it helps in the differential diagnosis of a number of disease states.[ citation needed ]
The total number of cations (positive ions) should be equal to the total number of anions (negative ions), so that the overall electrical charge is neutral. However, routine tests do not measure all types of ions. The anion gap is representative of how many ions are not accounted for by the lab measurements used in the calculation. These "unmeasured" ions are mostly anions, which is why the value is called the "anion gap." [3]
By definition, only the cations sodium (Na+) and potassium (K+) and the anions chloride (Cl−) and bicarbonate (HCO−
3) are used to calculate the anion gap. (As discussed above, potassium may or may not be used, depending on the specific lab.)[ citation needed ]
The cations calcium (Ca2+) and magnesium (Mg2+) are also commonly measured, but they aren't used to calculate the anion gap. Anions that are generally considered "unmeasured" include a few normally occurring serum proteins, and some pathological proteins (e.g., paraproteins found in multiple myeloma).[ citation needed ]
Similarly, tests do often measure the anion phosphate (PO3−
4) specifically, but it isn't used to calculate that "gap," even if it is measured. Commonly 'unmeasured' anions include sulfates and a number of serum proteins.[ citation needed ]
In normal health there are more measurable cations than measurable anions in the serum; therefore, the anion gap is usually positive. Because we know that plasma is electro-neutral (uncharged), 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.[ citation needed ]
Different labs use different formulas and procedures to calculate the anion gap, so the reference range (or "normal" range) from one lab isn't directly interchangeable with the range from another. The reference range provided by the particular lab that performed the testing should always be used to interpret the results. [3] Also, some healthy people may have values outside of the "normal" range provided by any lab.[ citation needed ]
Modern analyzers use 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. A normal anion gap is often defined as being within the prediction interval of 3–11 mEq/L, [8] with an average estimated at 6 mEq/L. [9]
In the past, methods for the measurement of the anion gap consisted of colorimetry for [HCO−
3] 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 [10] and 8–16 mEq/L. [11] [12]
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 cellular metabolism by leukocytes (also known as white blood cells) may result in an increase in the HCO−
3 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.[ citation needed ]
A high anion gap indicates increased concentrations of unmeasured anions by proxy. Elevated concentrations of unmeasured anions like lactate, beta-hydroxybutyrate, acetoacetate, PO3−
4, and SO2−
4, which rise with disease or intoxication, cause loss of HCO−
3 due to bicarbonate's activity as a buffer (without a concurrent increase in Cl−). Thus, finding a high anion gap should result in a search for conditions that lead to excesses of the unmeasured anions listed above.[ citation needed ]
The anion gap is affected by changes in unmeasured ions. In uncontrolled diabetes, there is an increase in ketoacids due to metabolism of ketones. Raised levels of acid bind to bicarbonate to form carbon dioxide through the Henderson-Hasselbalch equation resulting in metabolic acidosis. In these conditions, bicarbonate concentrations decrease by acting as a buffer against the increased presence of acids (as a result of the underlying condition). The bicarbonate is consumed by the unmeasured cation(H+) (via its action as a buffer) resulting in a high anion gap.[ citation needed ]
Causes of high anion gap metabolic acidosis (HAGMA):[ citation needed ]
Note: a useful mnemonic to remember this is MUDPILES – Methanol, Uremia, Diabetic Ketoacidosis, Paraldehyde, Infection, Lactic Acidosis, Ethylene Glycol and Salicylates[ citation needed ]
In patients with a normal anion gap the drop in HCO−
3 is the primary pathology. Since there is only one other major buffering anion, it must be compensated for almost completely by an increase in Cl−. This is therefore also known as hyperchloremic acidosis.[ citation needed ]
The HCO−
3 lost is replaced by a chloride anion, and thus there is a normal anion gap.[ citation needed ]
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 often due to hypoalbuminemia. Albumin is an anionic protein and its loss 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.[ citation needed ]
The anion gap is sometimes reduced in multiple myeloma, where there is an increase in plasma IgG (paraproteinaemia). [14]
The calculated value of the anion gap should always be adjusted for variations in the serum albumin concentration. [15] For example, in cases of hypoalbuminemia the calculated value of the anion gap should be increased by 2.3 to 2.5 mEq/L per each 1 g/dL decrease in serum albumin concentration (refer to Sample calculations, below). [9] [16] [17] Common conditions that reduce serum albumin in the clinical setting are hemorrhage, nephrotic syndrome, intestinal obstruction and liver cirrhosis. Hypoalbuminemia is common in critically ill patients.[ citation needed ]
The anion gap is often employed as a simple scanning tool by clinicians at the bedside to detect the presence of anions such as lactate, which can accumulate in critically ill patients. Hypoalbuminemia can mask a mild elevation of the anion gap, resulting in failure to detect an accumulation of unmeasured anions. In the largest study published to date, featuring over 12,000 data sets, Figge, Bellomo and Egi [18] demonstrated that the anion gap, when used to detect critical levels of lactate (greater than 4 mEq/L), exhibited a sensitivity of only 70.4%. In contrast, the albumin-corrected anion gap demonstrated a sensitivity of 93.0%. Therefore, it is important to correct the calculated value of the anion gap for the concentration of albumin, particularly in critically ill patients. [18] [19] [20] Corrections can be made for the albumin concentration using the Figge-Jabor-Kazda-Fencl equation to give an accurate anion gap calculation as exemplified below. [17]
Given the following data from a patient with severe hypoalbuminemia suffering from postoperative multiple organ failure, [21] calculate the anion gap and the albumin-corrected anion gap.
Data:
Calculations:
In this example, the albumin-corrected anion gap reveals the presence of a significant quantity of unmeasured anions. [21]
In inorganic chemistry, bicarbonate is an intermediate form in the deprotonation of carbonic acid. It is a polyatomic anion with the chemical formula HCO−
3.
An arterial blood gas (ABG) test, or arterial blood gas analysis (ABGA) measures the amounts of arterial gases, such as oxygen and carbon dioxide. An ABG test requires that a small volume of blood be drawn from the radial artery with a syringe and a thin needle, but sometimes the femoral artery in the groin or another site is used. The blood can also be drawn from an arterial catheter.
Alkalosis is the result of a process reducing hydrogen ion concentration of arterial blood plasma (alkalemia). In contrast to acidemia, alkalemia occurs when the serum pH is higher than normal. Alkalosis is usually divided into the categories of respiratory alkalosis and metabolic alkalosis or a combined respiratory/metabolic alkalosis.
Electrolyte imbalance, or water-electrolyte imbalance, is an abnormality in the concentration of electrolytes in the body. Electrolytes play a vital role in maintaining homeostasis in the body. They help to regulate heart and neurological function, fluid balance, oxygen delivery, acid–base balance and much more. Electrolyte imbalances can develop by consuming too little or too much electrolyte as well as excreting too little or too much electrolyte. Examples of electrolytes include calcium, chloride, magnesium, phosphate, potassium, and sodium.
Hyperchloremia is an electrolyte disturbance in which there is an elevated level of chloride ions in the blood. The normal serum range for chloride is 96 to 106 mEq/L, therefore chloride levels at or above 110 mEq/L usually indicate kidney dysfunction as it is a regulator of chloride concentration. As of now there are no specific symptoms of hyperchloremia; however, it can be influenced by multiple abnormalities that cause a loss of electrolyte-free fluid, loss of hypotonic fluid, or increased administration of sodium chloride. These abnormalities are caused by diarrhea, vomiting, increased sodium chloride intake, renal dysfunction, diuretic use, and diabetes. Hyperchloremia should not be mistaken for hyperchloremic metabolic acidosis as hyperchloremic metabolic acidosis is characterized by two major changes: a decrease in blood pH and bicarbonate levels, as well as an increase in blood chloride levels. Instead those with hyperchloremic metabolic acidosis are usually predisposed to hyperchloremia.
Hypochloremia is an electrolyte disturbance in which there is an abnormally low level of the chloride ion in the blood. The normal serum range for chloride is 97 to 107 mEq/L.
Metabolic acidosis is a serious electrolyte disorder characterized by an imbalance in the body's acid-base balance. Metabolic acidosis has three main root causes: increased acid production, loss of bicarbonate, and a reduced ability of the kidneys to excrete excess acids. Metabolic acidosis can lead to acidemia, which is defined as arterial blood pH that is lower than 7.35. Acidemia and acidosis are not mutually exclusive – pH and hydrogen ion concentrations also depend on the coexistence of other acid-base disorders; therefore, pH levels in people with metabolic acidosis can range from low to high.
Respiratory acidosis is a state in which decreased ventilation (hypoventilation) increases the concentration of carbon dioxide in the blood and decreases the blood's pH.
Ringer's lactate solution (RL), also known as sodium lactate solution,Lactated Ringer's (LR), and Hartmann's solution, is a mixture of sodium chloride, sodium lactate, potassium chloride, and calcium chloride in water. It is used for replacing fluids and electrolytes in those who have low blood volume or low blood pressure. It may also be used to treat metabolic acidosis and to wash the eye following a chemical burn. It is given by intravenous infusion or applied to the affected area.
In clinical chemistry, the osmol gap is the difference between measured blood serum osmolality and calculated serum osmolality.
Metabolic alkalosis is an acid-base disorder in which the pH of tissue is elevated beyond the normal range (7.35–7.45). This is the result of decreased hydrogen ion concentration, leading to increased bicarbonate, or alternatively a direct result of increased bicarbonate concentrations. The condition typically cannot last long if the kidneys are functioning properly.
In physiology, base excess and base deficit refer to an excess or deficit, respectively, in the amount of base present in the blood. The value is usually reported as a concentration in units of mEq/L (mmol/L), with positive numbers indicating an excess of base and negative a deficit. A typical reference range for base excess is −2 to +2 mEq/L.
Hyperchloremic acidosis is a form of metabolic acidosis associated with a normal anion gap, a decrease in plasma bicarbonate concentration, and an increase in plasma chloride concentration. Although plasma anion gap is normal, this condition is often associated with an increased urine anion gap, due to the kidney's inability to secrete ammonia.
Normal anion gap acidosis is an acidosis that is not accompanied by an abnormally increased anion gap.
High anion gap metabolic acidosis is a form of metabolic acidosis characterized by a high anion gap. Metabolic acidosis occurs when the body produces too much acid, or when the kidneys are not removing enough acid from the body. Several types of metabolic acidosis occur, grouped by their influence on the anion gap.
In clinical chemistry, the urine anion gap is calculated using measured ions found in the urine. It is used to aid in the differential diagnosis of metabolic acidosis.
Winters's formula, named after R. W. Winters, is a formula used to evaluate respiratory compensation when analyzing acid-base disorders in the presence of metabolic acidosis. It can be given as:
Chloride is an anion in the human body needed for metabolism. It also helps keep the body's acid-base balance. The amount of serum chloride is carefully controlled by the kidneys.
Distal renal tubular acidosis (dRTA) is the classical form of RTA, being the first described. Distal RTA is characterized by a failure of acid secretion by the alpha intercalated cells of the distal tubule and cortical collecting duct of the distal nephron. This failure of acid secretion may be due to a number of causes. It leads to relatively alkaline urine, due to the kidney's inability to acidify the urine to a pH of less than 5.3.
In nephrology, the delta ratio, or "delta-delta", is a formula that can be used to evaluate whether a mixed acid–base disorder is present, and if so, assess its severity. The anion gap (AG) without potassium is calculated first and if a metabolic acidosis is present, results in either a high anion gap metabolic acidosis (HAGMA) or a normal anion gap acidosis (NAGMA). A low anion gap is usually an oddity of measurement, rather than a clinical concern.