Proximal renal tubular acidosis Distal renal tubular acidosis Hyperalimentation Addison disease Acetazolamide Spironolactone Saline infusion To distinguish between the main types of metabolic acidosis, a clinical tool called the anion gap is considered very useful. It is calculated by subtracting the sum of the chloride and bicarbonate levels from the sum of the sodium and potassium levels. As sodium is the main extracellular cation, and chloride and bicarbonate are the main anions, the result should reflect the remaining anions. Normally, this concentration is about 8–16 mmol/L (12±4). An elevated anion gap (i.e. > 16 mmol/L) can indicate particular types of metabolic acidosis, such as types caused by certain poisons, lactate acidosis, and ketoacidosis. It is important to note that the anion gap can be spuriously normal in sampling errors of the sodium level, e.g. in extreme hypertriglyceridemia. The anion gap can also be increased due to relatively low levels of cations other than sodium and potassium (e.g. calcium or magnesium). As a differential diagnosis is made, other tests may be necessary, including toxicological screening and imaging of the kidneys, along with testing of electrolytes (including chloride), glucose, kidney function, and a full blood count. Urinalysis can reveal acidity (salicylate poisoning) or alkalinity (renal tubular acidosis type I). In addition, it can show ketones in ketoacidosis. It is also important to differentiate between acidosis-induced hyperventilation and asthma; otherwise, treatment could lead to inappropriate bronchodilation. Pathophysiology Compensatory mechanisms Metabolic acidosis is characterized by a low concentration of bicarbonate (), which can happen with increased generation of acids (such as ketoacids or lactic acid), excess loss of by the kidneys or gastrointestinal tract, or an inability to generate sufficient . Thus demonstrating the importance of maintaining balance between acids and bases in the body for maintaining optimal functioning of organs, tissues and cells. The body regulates the acidity of the blood by four buffering mechanisms. Bicarbonate buffering system Intracellular buffering by absorption of hydrogen atoms by various molecules, including proteins, phosphates and carbonate in bone. Respiratory compensation. Hyperventilation will cause more carbon dioxide to be removed from the body and thereby increases pH. Kidney compensation Buffer The decreased bicarbonate that distinguishes metabolic acidosis is therefore due to two separate processes: the buffer (from water and carbon dioxide) and additional renal generation. The buffer reactions are: H+ + HCO3- <=> H2CO3 <=> CO2 + H2O The Henderson-Hasselbalch equation mathematically describes the relationship between blood