Anion Gap Metabolic Acidosis – Low & High Causes, Symptoms

What is Anion Gap Metabolic Acidosis?

The Anion gap is the difference in the cations and anions in the body. Cations are positively-charged ions while anions are negatively-charged ions. The serum anions and cations are usually used, but urine measurements can also be used. The degree of the gap in the serum electrolytes is calculated to determine reasons for metabolic acidosis. When the gap is higher than normal, high anion gap metabolic acidosis is revealed, whereas if the gap is low, low anion gap metabolic acidosis is concluded.

The anion gap refers to all the unmeasured anions in plasma. Commonly measured cations include sodium, potassium, calcium and magnesium. Cations that are normally unmeasured include some pathological proteins. Commonly measured anions include chloride, phosphate, and bicarbonate and commonly unmeasured ones include sulphates, lactate and acetoacetate. The unmeasured anions account for about 10% of anions in the plasma. The anion gap represents these unmeasured anions which are not part of the usual laboratory tests.

When metabolic acidosis occurs, the hydrogen ions (cations) reacts with bicarbonate anions, resulting in decreased concentration of the measured anion and increased concentration in the unmeasured anions, leading to a gap.

Anion gap is used for the following reasons:

1. To signal the presence of metabolic acidosis and confirm other findings
2. To differentiate the causes of metabolic acidosis
3. To assess the extent of metabolic acidosis and help in treatment choice.

Anion Gap Levels

Anion gap is subdivided into levels depending on the symptoms and cause.

Low Anion Gap

A low anion gap includes a measurement of less than three mEq/L. It is an infrequent form of metabolic acidosis and accounts to only one to three percent of all cases.

Causes

A low anion gap is usually caused by hypoalbuminemia, a decrease in albumin in the blood. Albumin is an anion which when decreased, it allows other anions such as bicarbonate and chloride to be retained. This causes the gap to decrease.

Common conditions that lead to a low anion gap are hemorrhage, liver cirrhosis, nephritic syndrome, and intestinal obstruction. Multiple myeloma also may cause a low anion gap because of an increase in plasma immunoglobulins that leads to hypoalbuminemia.

Symptoms

Symptoms include:

1. Hypoalbuminemia
2. Hypercalcemia/ Hypermagnesemia
3. Muscle weakness
4. Edema
5. Hypotension
6. Lethargy
7. Dysrhthmias or irregularities in the heart rate

Normal Anion Gap

In normal anion gap, the computed value is three mEq/L to 11 mEq/L.

Causes

In a normal anion gap, the drop in bicarbonate ions (HCO3¯) is compensated by an increase in chloride (Cl¯) which makes the gap remain normal despite of metabolic acidosis. It is also known as hyperchloremic acidosis

Common conditions that lead to a normal anion gap include:

1. Diarrhea
2. Alcoholic intoxication
3. Addison’s disease
4. Renal dysfunction (renal tubular acidosis)
5. Uretero-enterostomy
6. Saline administration
7. Hyperparatrhyroidism
8. Intake of carbonic anhydrase inhibitors (Acetazolamide) and ammonium chloride

Symptoms

Symptoms include:

1. Increased serum chloride levels
2. Fatigue
3. Postural hypotension
4. Emotional disturbances
5. Increased thirst
6. Anorexia
7. Polyuria
8. Restlessness
9. Weakness

High Anion Gap

A high anion gap is characterized by a gap of more than 10 to 11 mEq/L.

Causes

In a high anion gap, the presence of acidosis causes the bicarbonate ions to decrease. Common conditions that lead to a high anion gap include the following:

1. Lactic acidosis
2. Ketoacidosis as seen in diabetes and alcoholism
3. Dehydration
4. Salicylate toxicity that results in metabolic block
5. Medication overuse of isoniazid and Toluene
6. Ingestion of toxins such as ethylene glycol, paraldehyde, methanol, propyl alcohol, Phenformin, cyanide, iron
7. Renal failure because of a decrease in the ability of the kidneys to produce bicarbonates to buffer the acidosis.
8. Uremia
9. Rhabdomyolysis

Symptoms

Symptoms include:

1. Low bicarbonate levels (less than 22 mEq/L)
2. Fruity or acetone breath
3. Warm, dry skin
4. Abdominal pain
5. Polyuria or increased urination
6. Tachycardia
7. Nausea and vomiting
8. Diarrhea
9. Hyperventilation as a compensatory mechanism
10. Tinnitus or ringing of the ears as a result of salicylate toxicity

Diagnosis

Anion gaps are measured by computing the difference of the measured cations and anions in the body. Measurements are taken through blood tests. Anion gap is expressed in milliequivalents per liter (mEq/L) or millimoles per liter (mmol/L). By practice, only sodium, potassium, chloride and bicarbonate ions are used when calculating the anion gap.

Anion Gap Calculator- How to Calculate Anion Gap

The anion gap is calculated using two accepted formulas.

With Potassium:

Anion gap= ([Na+] + [K+]) ? ([Cl?] + [HCO3?])

Without Potassium:

Anion gap== [Na+] ? ([Cl?] + [HCO3?])

The calculation without potassium is usually used in daily practice. Since serum potassium is only low, the removal of it in the equation normally does not cause any significant result.

Blood Test for Anion Gap

In order to calculate the anion gap, blood testing for serum electrolytes (Na, K, Cl) and arterial blood gases (ABG) determination is used to check bicarbonate levels (HCO3). Patients should be instructed on monitoring electrolytes at regular intervals to assess extent of illness and efficacy of treatment. Specific electrolytes should be requested by the physician to be checked in order to keep costs down.

Treatment

Treatment of anion gap depends on the level and the underlying cause. Treatment goals are directed at managing the metabolic acidosis and include the following:

Administration of sodium bicarbonate therapy

To buffer the acidosis, bicarbonates need to be administered. The intravenous site needs to be checked because bicarbonates causes tissue irritation.

Electrolyte replacement of those with reduced levels

Serum sodium and potassium needs to be replaced in cases of hyponatremia or hypokalemia.

Administration of diuretics when dehydration is not present

This decreases serum calcium and magnesium levels. Diuretic used in cases of hypovolemis may further aggravate the condition.

Phosphate therapy

Phosphate enhances the elimination of excess calcium, magnesium, and chloride ions.

Albumin replacement therapy for hypoalbuminemia

Serum albumin is replaced by administering intravenous infusions.

Continuous monitoring of arterial blood gases, electrolytes, creatinine and BUN

Monitoring is done to determine treatment efficacy.

Prevention

Prevention of anion gap metabolic acidosis also depends on the cause. Prevention should be catered towards managing the disease to prevent metabolic acidosis. The following outlines the most common prevention for certain causes of metabolic acidosis.

Diabetic Ketoacidosis

1. Take insulin as prescribed
2. Monitor blood sugar frequently
3. Prevent infection to avoid increase in insulin requirements
4. Monitor hyperglycemia symptoms such as anorexia, nausea, vomiting and diarrhea for immediate management

Toxicity

1. Take salicylates, anhydrase inhibitor diuretics, iron and isoniazid as prescribed
2. Avoid exposure to cyanide and other toxins
3. Drink alcohol in moderation

Lactic acidosis

1. Avoid fatty foods to lower the risk of atherosclerosis that leads to anaerobic metabolism when it obstructs heart and brain circulation
2. Watch out for hyperglycemia
3. Exercise regularly to promote circulation

High Anion Gap Complications

Complications of anion gap usually involve the end results of metabolic acidosis such as:

1. Coma
2. Cerebral edema
3. Respiratory collapse
4. Cardiac dysrhythmias
5. Hypovolemic shock or circulatory collapse

High Anion Gap Remedies

Metabolic acidosis is a highly complicated condition that requires full medical management. Remedies are not sufficient to treat the disease; however, it may improve some of the signs and symptoms. They include:

1. Consume egg whites with every meal to replace albumin in case of albuminemia. Egg whites are a rich source of albumin.
2. Increase intake of potassium rich foods such as bananas, apples and apricot to restore potassium levels.
3. Consume sodium rich foods in the form of root crops.
4. Encourage pursed lip breathing to allow for maximum exhalation of carbon dioxide, reducing carbonic acid levels.
5. Increase fluid intake to manage hypovolemia.

Despite these remedies, patients with metabolic acidosis need medical management to prevent life-threatening complications. See for Anion gap calculation