Anion Gap: Low, Normal & High Levels + Causes, Symptoms

Anion Gap

Anion Gap: Low, Normal & High Levels + Causes, Symptoms


Concept of electroneutrality or the gamblegram

The body strives to maintain electroneutrality at all times by keeping the concentrations of anions equivalent to cations in serum (or plasma).

In a healthy individual, sodium and potassium (also called “measured” cations) account for about 95% of total cations, whereas chloride and bicarbonate (also called “measured” anions) account for about 85% of the total anions.

“Unmeasured” cations (UC+) and anions (UA–, see below) account for the differences. This concept of electroneutrality can also be demonstrated graphically in a gamblegram.

Concept of electroneutrality

Sum of cations = Sum of anions


(Na+ + K+ + UC+) = (Cl– + HCO3– + UA–)

The anion gap reflects the difference in the serum (plasma) concentrations of the “measured” cations and “measured” anions and is calculated using the following formula:

Anion gap = (Na+ + K+) – (Cl– + HCO3–)

However, we need to incorporate “unmeasured” cations and “unmeasured” anions in the above equation, as follows:

Anion gap = (Na+ + K+ + UC+) – (Cl–+ HCO3– + UA–)

or (rearranging the above equation)

Anion gap = UA– – UC+ = (Na+ + K+) – (Cl– + HCO3–)


Anion gap = UA– – UC+

Thus, the anion gap is calculated using “measured” cations (sodium, potassium) and anions (chloride and bicarbonate) in mEq/L, but actually is an indicator of the difference between “unmeasured” anions and cations.

Since “unmeasured” anions are more abundant than unmeasured cations and are more important in terms of disease than “unmeasured” cations, the anion gap is essentially a marker of the amount of “unmeasured” anions in circulation.

“Unmeasured” cations (UC+)

These include proteins that are positively charged at physiologic pH (γ-globulins) and the free or ionized forms of calcium (Ca2+) and magnesium (Mg2+). The latter are not seen in high enough concentrations to make much impact on the anion gap.

“Unmeasured” anions (UA–)

These include proteins that are normally negatively charged at physiologic pH (particularly albumin, which is the largest contributor to the anion gap in health) and noncarbonic acids that are produced during physiologic and pathologic processes, including lactate, phosphates, sulfates, and ketones. Some exogenous toxins and drugs, including methanol, salicylate and ethylene glycol (and its metabolites), are also “unmeasured” anions. Because “unmeasured” anions are found in higher concentrations than “unmeasured” cations, they have a far greater impact on the anion gap.

Note that the term “unmeasured” is really a misnomer, as many of these anions and cations are actually or can be measured, however they are not included in the anion gap equation (and are “unmeasured” for this purpose).

Use of anion gap for determining causes of metabolic acidosis

Changes in anion gap are used primarily to distinguish between causes of a metabolic acidosis, i.e. due to titration of bicarbonate or loss of bicarbonate.

Titration acidosis

  • Metabolic acidosis due to titration: There will be accumulation of a noncarbonic acid, whose proton (H+) is being buffered by bicarbonate (HCO3–), leading to a decrease in bicarbonate and an increase in the anion of the acid. The anion of the acid is an “unmeasured” anion (UA–) and will thus increase the anion gap. This concept is illustrated in the image to the right.
  • Acidosis due to bicarbonate loss: In contrast, with bicarbonate loss there is no accumulation of a non carbonic acid and electroneutrality is maintained by chloride (which increases, offsetting the decrease in bicarbonate), thus the anion gap is usually normal in a bicarbonate loss acidosis (but there is a corrected hyperchloremia).

The table below summarizes the changes seen in the anion gap in these two forms of metabolic acidosis:

Mechanism of low bicarbonateExpected anion gapCorrected chloride
Titration by excess noncarbonic acidIncreasedNormal
Loss of bicarbonateNormalHigh

Method of measurement

Refer to individual anions/cations homepage ( Na+, K+, Cl–, and HCO3–)

Sample considerations

Refer to individual anions/cations homepage ( Na+, K+, Cl–, and HCO3–)

Increased anion gap

This indicates increased unmeasured anions (more common) or decreased unmeasured cations (less common).

  • Artifact: Any artifactual cause of increased sodium or potassium or decreased chloride or bicarbonate (e.g. storage of blood on cells with lactate production by cells, which consumes bicarbonate in the tube) may increase the anion gap. This is an uncommon cause of a high anion gap.
  • Iatrogenic: Administration of sodium-containing drugs such as sodium salts and penicillin may increase the anion gap because their sodium content is measured as part of the sodium concentration on a chemistry panel.
  • Pathophysiologic:
    • Titration or high anion gap metabolic acidosis: This is the most common cause of an increased anion gap and is due to accumulation of an noncarbonic (nonvolatile) acid, such as L- or D-lactate, ketones and uremic acids (e.g. sulfates, phosphates). Some toxins and drugs are also acids (methanol, salicylate, ethylene glycol metabolites) and toxicity with these compounds is characterized by a high anion gap (or titration) metabolic acidosis. This type of acidosis is always a primary metabolic acid-base disturbance. In one study of neonatal foals (within one week of age) with various disorders (sepsis, neonatal encephalopathy, enterocolitis etc), an anion gap of >27 mEq/L had a sensitivity of 80% and specificity of 85% for detecting a high L-lactate (> 7 mmol/L) in a subsample of 81 foals. However, the change in the anion gap explained only about 46% of the change in L-lactate by linear regression analysis, indicating other unmeasured anions in these sick foals contribute to the anion gap (Gomez et al 2015).
    • Alkalemia: Loss of protons (H+) from plasma proteins (particularly albumin) in an attempt to buffer the increase in bicarbonate, increases their net negative charge. Alkalemia also stimulates lactic acid production (a high intracellular pH stimulates phosphofructokinase in cells which drives anaerobic metabolism). The lactate may move into plasma (from within cells), which can increase the anion gap. The increase in AG in both situations is usually mild (


    Low anion gap: Definition, causes, and symptoms

    Anion Gap: Low, Normal & High Levels + Causes, Symptoms

    An anion gap is calculated by using the results of an electrolyte blood test. This test can help determine what is causing a pH imbalance.

    For the body to function normally, it needs to maintain a normal pH balance, or balanced levels of acid and alkali or base in the blood.

    When these levels are balance, a person may experience symptoms of high acid, otherwise known as acidosis, or high base, known as alkalosis, depending on the underlying cause.

    Electrolytes have an electrical charge that helps them maintain the body’s pH level. They are vital for many bodily functions and include substances such as sodium, potassium, chloride, bicarbonate, and other minerals.

    Normally, anion gap results range from 3 to 10 milliequivalents per liter (mEq/L).

    Several underlying conditions can result in a pH imbalance and cause an abnormal anion gap.

    A low anion gap is very rare. If an electrolyte test shows a low anion gap, a doctor will usually order a second test, as the results may be due to a laboratory error.

    Other than a laboratory error, a less common cause of a low anion gap is hypoalbuminemia.


    Hypoalbuminemia is when a person has too little albumin in their blood. Albumin is an essential protein.

    Hypoalbuminemia usually occurs because of inflammation throughout the body.

    Causes of hypoalbuminemia include:

    • sepsis
    • recent surgery
    • malnutrition
    • severe burns
    • liver or kidney disease

    Hypoalbuminemia is also considered a contributing factor to having a low anion gap in people with multiple myeloma. It is not known, however, if testing a person’s anion gap is a useful tool for monitoring the progression of the disease.

    When a person has too much acid or too little base in their blood, the anion gap will be higher than normal. This is called acidosis and can be life-threatening in some situations.

    Acidosis can be caused by a variety of conditions, including:

    • some lung disorders, such as severe asthma, sleep apnea, pneumothorax, myasthenia gravis, botulism, amyotrophic lateral sclerosis (ALS), and Guillain-Barre syndrome
    • uncontrolled diabetes or diabetic ketoacidosis
    • kidney damage or failure
    • prolonged diarrhea
    • starvation
    • excessive alcohol use that causes alcoholic ketoacidosis
    • lactic acidosis, which is a buildup of lactic acid
    • exposure to high levels of salicylates (aspirin), methanol, ethylene glycol, or antifreeze
    • drug overdose

    Share on PinterestDrowsiness and fatigue can be symptoms of acidosis.

    Depending on the cause of the pH imbalance, a person may experience a variety of symptoms.

    Conditions associated with a low anion gap are unly to cause symptoms. In most cases, the result is from a mistake in the calculation.

    Anyone with a low anion gap due to an underlying medical condition will experience the symptoms of that condition.

    A person with acidosis may not experience any symptoms or may have nonspecific symptoms related to the underlying medical condition, such as:

    When a person has alkalosis or higher levels of base in their blood, they may experience symptoms related to the underlying medical condition, such as:

    • low calcium levels
    • a headache
    • lethargy
    • seizures, muscle spasms, and delirium
    • heart palpitations
    • weakness

    Treatment for an abnormal anion gap will focus on the underlying cause.

    A low or high anion gap alone cannot diagnose a medical condition, so a doctor will perform a variety of other tests before making a treatment plan.

    Anyone concerned about a high or low anion gap in their blood test results may find it helpful to speak with a doctor about the potential cause.

    A range of underlying medical conditions can affect the body’s pH levels. Calculating the anion gap can help a doctor determine the underlying cause of the abnormality.

    A low anion gap is very rare and is often caused by a laboratory error. In this case, a person will require a repeat blood test.

    High anion gaps are often associated with serious conditions, such as lung disorders, uncontrolled diabetes, and drug overdose. These conditions need prompt treatment to prevent severe complications, including death.

    Anyone who does not understand the underlying cause of a low or high anion gap results should speak to their doctor.


    Metabolic Acidosis

    Anion Gap: Low, Normal & High Levels + Causes, Symptoms

    What is metabolic acidosis?

    The buildup of acid in the body due to kidney disease or kidney failure is called metabolic acidosis. When your body fluids contain too much acid, it means that your body is either not getting rid of enough acid, is making too much acid, or cannot balance the acid in your body.

    What causes metabolic acidosis?

    Healthy kidneys have many jobs. One of these jobs is to keep the right balance of acids in the body. The kidneys do this by removing acid from the body through urine. Metabolic acidosis is caused by a build-up of too many acids in the blood. This happens when your kidneys are unable to adequately remove the acid from your blood.

    What are the signs and symptoms?

    Not everyone will have signs or symptoms.  However, you may experience:

    • Long and deep breaths
    • Fast heartbeat
    • Headache and/or confusion
    • Weakness
    • Feeling very tired
    • Vomiting and/or feeling sick to your stomach (nausea)
    • Loss of appetite

    If you experience any of these, it is important to let your healthcare provider know immediately.

    What are the complications of metabolic acidosis if I have kidney disease or kidney failure?

    • Increased bone loss (osteoporosis): Metabolic acidosis can lead to a loss of bone in your body. This can lead to a higher chance of fractures in important bones your hips or backbone.
    • Progression of kidney disease:  Metabolic acidosis can make your kidney disease worse.  Exactly how this happens is not clear. As acid builds up, kidney function lowers; and as kidney function lowers, acid builds up. This can lead to the progression of kidney disease.
    • Muscle loss: Albumin is an important protein in your body that helps build and keep muscles healthy. Metabolic acidosis lowers the amount of albumin created in your body, and leads to muscle loss, or what is called “muscle wasting.”
    • Endocrine disorders: Metabolic acidosis interferes with your body’s ability to maintain normal functions of your endocrine system (the collection of glands that produce hormones). This can cause your body to build a resistance to insulin (the hormone in your body that helps keep your blood sugar level from getting too high or too low). If left untreated for too long or not corrected in time, it can lead to diabetes.

    How is it treated?

    We all need bicarbonate (a form of carbon dioxide) in our blood. Low bicarbonate levels in the blood are a sign of metabolic acidosis.  It is a base, the opposite of acid, and can balance acid. It keeps our blood from becoming too acidic. Healthy kidneys help keep your bicarbonate levels in balance.

      Low bicarbonate levels (less than 22 mmol/l) can also cause your kidney disease to get worse.   A small group of studies have shown that treatment with sodium bicarbonate or sodium citrate pills can help keep kidney disease from getting worse.

    However, you should not take sodium bicarbonate or sodium citrate pills unless your healthcare provider recommends it.


    Anion Gap: Low, Normal & High Levels + Causes, Symptoms

    Anion Gap: Low, Normal & High Levels + Causes, Symptoms

    The anion gap is a value calculated from the results of an electrolyte blood test which informs clinicians about the balance of positively and negatively charged particles in the blood. This is a useful measure to diagnose diseases and disorders associated with an acid/base imbalance in the body.

    What Is the Anion Gap?

    The anion gap is a value that represents the difference between positively charged ions (cations) and negatively charged ions (anions) in the blood.

    The anion gap cannot be directly measured, instead, it is calculated from the results of an electrolyte panel, another type of blood test.

    The anion gap is calculated using the concentrations of the major anions in the blood, chloride and bicarbonate, and the major cations, sodium and potassium.

    However, the concentration of potassium in the blood is usually much lower compared to sodium, chloride, and bicarbonate. Therefore, it is common practice to not use potassium when calculating the anion gap, as it usually has little effect [1].

    In the body, the total positive charge from cations should equal the total negative charge from anions in the blood to maintain overall neutrality.

    However, blood tests usually do not measure all types of ions. This means the anion gap gives us a picture of the unmeasured anions and cations in the blood. There are normally more unmeasured anions than cations, hence there is usually an anion gap [2].

    Clinically, the anion gap value is primarily used to help evaluate acid-base disorders, which occur when the concentration of acids and bases in the blood becomes unbalanced [2].

    Although the term anion gap usually refers to the concentrations of cations and anions in the blood, it can also refer to their concentrations in the urine, which is also clinically useful [3].

    Normal Range

    Normal ranges can vary between laboratories due to differences in equipment, techniques, and chemicals used. If your results are outside of the normal range, it may not necessarily mean there is something wrong. However, a normal result also doesn’t mean a particular medical condition is absent. Always talk with your doctor to learn more about your test results.

    The value of the anion gap is reported in milliequivalents per liter (mEq/L).

    Normal values are 3 to 11 mEq/L [4, 2].

    Some older types of tests used different techniques to measure electrolytes, which give different results. The normal range for these older tests is 8 to 16 mEq/L [5, 6, 7].


    It’s important to note that a number of factors may cause a high anion gap. Test results should be interpreted by a doctor who can take into account your medical history and other test results.

    The anion gap is primarily used to determine the cause of metabolic acidosis, a condition where the body is producing too much acid or not enough acid is being removed from the body.

    The list below details some potential causes of metabolic acidosis that is associated with a high anion gap. A normal anion gap during metabolic acidosis may indicate a different set of causes [8].


    1. Lactic acidosis – a condition where the body produces too much lactic acid [9, 10, 11]
    2. Diabetic ketoacidosis – a serious, life-threatening complication of diabetes resulting from excess production of ketones, which are byproducts of fat breakdown used as an alternative energy source [12, 13]
    3. Kidney failure – reduces the amount of acid removed from the body, while increasing the excretion of bicarbonate [14, 15]
    4. Uremia – the presence of urea in the blood is associated with kidney failure
    5. Thiamine (vitamin B1) deficiency [16, 17, 18]
    6. Hyperphosphatemia – High levels of phosphate ions in the blood [19, 2]
    7. Starvation [20]


    1. Carbon monoxide [21, 22]
    2. Cyanide [23, 24]
    3. Ethylene glycol (antifreeze) poisoning [25, 26, 27]
    4. Propylene glycol [28]
    5. Isopropyl alcohol [28]
    6. Toluene [29, 30]
    7. Methanol [31]
    8. Paraldehyde [22]


    1. Metformin [20]
    2. 5-Oxoproline/pyroglutamic acid – a byproduct of Tylenol (acetaminophen, paracetamol) [32, 33, 34, 35]
    3. Overdose with salicylates such as aspirin [20]
    4. Gamma-hydroxybutyrate (GHB) [36]
    5. Ibuprofen [28]


    A high anion gap itself does not produce symptoms, but it may indicate an imbalance in blood acid levels, such as metabolic acidosis. Some symptoms of metabolic acidosis include [9]:

    1. Nausea
    2. Vomiting
    3. Rapid and shallow breathing
    4. Fatigue
    5. Rapid/abnormal heartbeat
    6. Low blood pressure
    7. Confusion
    8. Headaches
    9. Lack of appetite


    Talk with your doctor if your anion gap test results are high. A high anion gap may indicate metabolic acidosis, which requires medical management.

    The treatment of metabolic acidosis typically requires addressing the underlying cause. Some possible treatments for metabolic acidosis include detoxification if caused by drugs or toxins and insulin if the condition is caused by diabetes [9].

    Symptoms and Treatment

    A low anion gap may be caused by a number of different conditions. Symptoms will depend on the underlying cause.

    Treatment will depend on the underlying cause as well. It is worthwhile to repeat the electrolyte blood test and recalculate the anion gap value to ensure that the low anion gap value is not an outcome of a laboratory error in measurement.


    Clinical Usefulness of the Serum Anion Gap

    Anion Gap: Low, Normal & High Levels + Causes, Symptoms

    Division of Nephrology, Department of Internal Medicine, Chonbuk National University Medical School, Chonbuk, Korea.

    Division of Nephrology, Department of Internal Medicine, Chonbuk National University Medical School, Chonbuk, Korea.

    Find articles by Kyung Pyo Kang

    Division of Nephrology, Department of Internal Medicine, Chonbuk National University Medical School, Chonbuk, Korea.

    Find articles by Sung Kyew KangAuthor information Copyright and License information DisclaimerCopyright © 2006 The Korean Society of Electrolyte and Blood Pressure Research

    The anion gap in the serum is useful in the interpretation of acid-base disorders and in the diagnosis of other conditions. In the early 1980s, ion-selective electrodes for specific ionic species were introduced for the measurement of serum electrolytes. This new method has caused a shift of the anion gap from 12±4 mEq/L down 6±3 mEq/L.

    It is worthy for clinicians to understand the range of normal anion gap and the measuring methods for serum sodium and chloride in the laboratories that support their practice. While an increase in the anion gap is almost always caused by retained unmeasured anions, a decrease in the anion gap can be generated by multiple mechanisms.

    Keywords: Anion gap, Ion-selective electrode

    The serum anion gap is a helpful parameter in the clinical diagnosis of various conditions. The commonest application of the anion gap is to classify cases of metabolic acidosis into those that do and those that do not have unmeasured anions in the plasma (Table 1). In this article, we briefly review the significance of the anion gap and the approach to the use of the serum anion gap.

    Anion Gap in Major Causes of Metabolic Acidosis

    As charge balance precluded the existence of any gaps, the more accurate term should really be 'difference between unmeasured anions and unmeasured cations' which obviously lacks the brevity requisite for practical communication.

    Clinically, anion gap is equal to the difference between the plasma concentrations of the major cation (Na+) and the major measured anions (Cl-+HCO3-). It is important to understand that this entity actually equals [anionic proteins+inorganic phosphate+sulphate+organic anions]-[potassium+calcium+magnesium+cationic proteins] (Fig. 1)1).

    Since there are more unmeasured anions than unmeasured cations, the value of anion gap is usually positive. The classical value of a normal anion gap is considered 12±4 mEq/L, when sodium was determined by flame photometry ( the principle of flame atomic emission spectrometry) and chloride by a colorimetric assay (mercuric-nitrate-thiocyanate colorimetric assay).

    Since the 1980s, 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.

    The measurement by ion-selective electrodes has caused a shift of the anion gap from 12±4 mEq/L down 6±3 mEq/L2). It is worthy for clinicians to understand the range of normal anion gap and the measuring methods for serum sodium and chloride in the laboratories that support their practice.

    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 acidosis3, 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 starvation5, 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 gap7, 8).

    Concomitant severe hypercalcemia and hypoalbuminemia are often contributing factors to a low anion gap in multiple myeloma9). 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.

    4, the majority of plasma proteins are anionic. Albumin with an average negative charge of 18 per mole at physiological pH has been shown to be responsible for approximately 75% of the unmeasured anions of the normal anion gap. A drop in albumin by 10 g/L therefore will cause the anion gap to fall by approximately 2.5 mEq/L at constant pH10, 11).

    Hypoalbuminemia is probably the commonest cause of a clinically relevant lowered anion gap. Third, a low anion gap can mask an underlying high anion gap acidosis and potentially delay intervention. While an increase in the anion gap is almost always caused by retained unmeasured anions, a decrease in the anion gap can be generated by multiple mechanisms.

    In this short review, emphasis is placed on the fact that the serum anion gap is the difference between the unmeasured anions and the unmeasured cations, and any numerical analysis of this entity needs to take this equation into consideration.

    By exploring all the possible factors that can influence unmeasured cations and unmeasured anions can one truly extract useful information from the serum anion gap.

    It is advisable for the clinician to know the normal range of the anion gap and the assays used in measuring Na+ and Cl- in the laboratories supporting their practice.

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    Low Anion Gap: Symptoms, Causes, Diagnosis

    Anion Gap: Low, Normal & High Levels + Causes, Symptoms

    The anion gap is a value that’s calculated using the results of an electrolyte blood test.

    Electrolytes are elements and compounds that occur naturally in the body and control important physiological functions. Calcium, chloride, magnesium, and sodium, among others, are electrolytes.

    Electrolytes have an electrical charge — some are positive and others are negative. They help to control the balance of acids and bases in your body.

    The anion gap value is the difference between the negatively and positively charged electrolytes. If the calculated value for the anion gap is too high or too low, it may be a sign of a disorder.

    If your doctor suspects that you have an electrolyte imbalance in your blood, they’ll order an anion gap blood test.

    Symptoms may include:

    • shortness of breath
    • nausea or vomiting
    • edema (accumulation of fluid)
    • abnormal heartbeat
    • weakness
    • confusion

    The anion gap value is reported in units of milliequivalents per liter (mEq/L). Normal results generally fall between 3 and 10 mEq/L. However, normal ranges may vary by lab.

    A high anion gap value means that your blood is more acidic than normal. It may indicate that you have acidosis. Conditions that can cause acidosis (and therefore a high anion gap value) include:

    • diabetic ketoacidosis, a condition requiring immediate medical attention
    • overdose of salicylates, such as aspirin
    • uremia (urea in the blood)
    • ethylene glycol (antifreeze) poisoning

    Having a low anion gap value is very rare. The most common causes of low anion gap results may include the following.

    Laboratory error

    If your test indicates a low anion gap value, your doctor may order a second test to account for laboratory error.

    Because the anion gap is calculated from the results of the electrolyte panel, accurate measurement of the individual electrolytes is necessary.

    A published review found that 67,000 calculations of anion gap, a low anion gap was calculated less than 1 percent of the time.

    Within this small percentage, over 90 percent of the results were due to laboratory error in calculating one of the electrolyte values.

    Monoclonal and polyclonal gammopathy

    This condition refers to an overabundance of proteins (immunoglobulins) in your blood. Immunoglobulins, also known as antibodies, play a critical role in your immune system. There are many types of immunoglobulins, but one type, called IgG, is positively charged. Overproduction of IgG can sometimes lead to a low anion gap value.

    Monoclonal gammopathies can be associated with conditions such as multiple myeloma. Polyclonal gammopathies are often associated with various inflammatory diseases.

    Your doctor may order a blood test to assess the levels of immunoglobulins in your blood. They may also order a serum or urine protein electrophoresis test to help monitor and diagnose your condition.

    Other factors

    There are a few more rare causes of low anion gap. These include:

    • Bromide intoxication. Bromide is present in some sedative drugs, medication for myasthenia gravis, and some herbal medications. High concentrations of bromide can lead to neurologic or dermatologic symptoms. Although negatively charged, bromide can interfere with the calculation of chloride. This affects the calculation of the anion gap and gives a falsely low anion gap result.
    • Lithium. Lithium is positively charged and is sometimes prescribed for treatment of bipolar disorder. In high concentrations, it can lower the anion gap.
    • Increase in other positively charged ions. A large increase in other positively charged ions, such as calcium and magnesium, can also lower the anion gap.

    Treatment for low anion gap is focused on treating the underlying cause.

    If your test results come back indicating a low anion gap, your doctor may want to repeat the test to account for laboratory error. Once a low anion gap has been confirmed, your doctor will order additional tests to determine the underlying cause of the result.

    If you’re taking medication that can lead to a low anion gap, such as lithium or medication containing bromide, you can talk to your doctor about adjusting the dosage, if possible.

    If you seek out and get the treatment that you need for the underlying cause, the outlook for having a low anion gap is good. Following the proper treatment, your anion gap value should normalize.


    What Is an Anion Gap Test?

    Anion Gap: Low, Normal & High Levels + Causes, Symptoms

    The anion gap test tells you how much acid is in your blood. Acid levels that are higher or lower than normal can tip your doctor off to a health problem and help them find the right treatment for you.

    Too much acid in your blood can be a sign of short-term problems dehydration and diarrhea, or long-term conditions diabetes. It's not common, but too little acid may point to a serious problem heart disease.

    Your doctor might order the anion gap test if you have symptoms of high blood acid levels, :

    You'll go to your doctor's office to get a blood test. Before your appointment, your doctor will tell you if you need to avoid food and certain drinks. Let them know if you're taking any medicines — especially an antibiotic — because that can affect your test results.

    Your doctor will use a needle to take some blood from a vein in your arm. They'll send the blood sample to a lab for testing. You may have a bit of pain, soreness, or bruising in the area afterward.

    The lab will take a close look at electrically charged minerals in your blood called electrolytes. These help keep your blood from becoming too acidic — or not acidic enough.

    Electrolytes can carry a positive or negative charge. The anion gap test measures how balanced these charges are. The result is a number that can help your doctor figure out if you have a condition that's throwing off your acid levels.

    If your doctor says you have a high anion gap, you may have a higher than normal amount of acid in your blood. The doctor may call this “acidosis.”

    Acidosis can be a symptom of conditions :

    • Dehydration
    • Diarrhea
    • Kidney disease
    • Ketoacidosis (diabetes complication)

    Acidosis can also be brought on by too much exercise.

    If your doctor says you have a low anion gap, you might have a lower than normal amount of acid in your blood. This result isn't common, and sometimes it's due to a lab error. Your doctor may ask the lab to do the test again to double-check the numbers.

    If you really do have a low anion gap, it could mean your blood doesn't have enough of a protein called abumin. That can be a sign of conditions :

    • Kidney problems
    • Heart disease
    • Certain types of cancer

    If your doctor diagnoses you with a condition a high or low anion gap result, they'll come up with a treatment plan that helps you take charge of it.

    Once you get your test result, ask the doctor to explain exactly what it means. Keep in mind that even if your anion gap is high or low, that doesn't necessarily mean you have a serious health problem.

    An anion gap number between 3 and 10 is considered normal. But the “normal” range can vary from person to person, and it may also depend on the methods your lab used to do the test.


    Clinical Journal of the American Society of Nephrology: “Serum Anion Gap: Its Uses and Limitations in Clinical Medicine.”

    MedlinePlus: “Anion Gap Blood Test.”

    University of Rochester Medical Center: “Anion Gap (Blood).”

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