Changes in pH have been known for more than a century to be a predictor of tone. Gaskell (34) shown that acid solutions relax vascular smooth muscle, and more recent research has proven that lowering blood pH enhances blood flow (35). Increased blood flow is needed in areas of the body with high energy demands, such as the brain and heart. Acidosis is defined as a state of low serum bicarbonate concentration and high serum lactate concentration due to excessive loss or poor production of these anions. It can be caused by many diseases or other causes including trauma, infection, inflammation, etc. Acidosis impairs tissue perfusion and activates defensive mechanisms that protect against further damage - this is called "acid-base homeostasis". These mechanisms include increased breathing, which increases ventilation/perfusion ratio and thus oxygenation of blood, and decreased renal clearance of hydrogen ions (which increase urine pH). However, these same mechanisms that protect against further injury may also limit blood flow by increasing blood pressure through increased respiratory rate and vasoconstriction via activation of peripheral chemoreceptors and central nervous system (CNS) centers. Thus, acidosis can cause or contribute to reduced blood flow. The relationship between acid-base status and blood flow was first described over 100 years ago by Gaskell.