Lactic Acid · What Is It, What Increases It, and More

Lactic acid, also known as lactate, is a substance the body produces mainly by the breakdown of glucose under anaerobic conditions (i.e., without oxygen), like anaerobic glycolysis. Anaerobic glycolysis is one of the pathways responsible for supplying the cell with energy, both in the form of adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NADH). The tissues that produce the most lactic acid include muscle cells and red blood cells, with lesser production from brain tissue, skin, and in the gastrointestinal (GI) tract. Lactic acid is subsequently released into the bloodstream to be metabolized by the liver and kidneys, where it can be used in gluconeogenesis. Gluconeogenesis refers to glucose and energy synthesis from noncarbohydrate substrates, such as lactate. 

Typical lactate levels are usually low, less than 2 mmol/L, with a range between 0.5-1 mmol/L. Hyperlactatemia can occur when lactate levels rise to between 2-4 mmol/L. If the levels exceed 4 mmol/L, it is known as severe hyperlactatemia. Elevated serum lactate levels can indicate poor prognosis. 

Lactic acidosis refers to the combination of elevated lactate levels and a decreased pH of the individual's blood serum equal to or less than 7.35. It is considered the most common cause of metabolic acidosis identified in hospitalized individuals. 

There are two types of lactic acidosis; type-A and type-B. Type-A lactic acidosis is caused by hypoperfusion and long-term hypoxia of the tissues. It usually occurs when oxygen consumption is greater than oxygen delivery, resulting in cells undergoing anaerobic glycolysis for energy. Type-A lactic acidosis can be caused by all subtypes of shock (e.g., septic, cardiogenic, hypovolemic, obstructive), regional ischemia (e.g., limb, mesenteric), and anaerobic muscle activity (e.g., high intensity interval training, weightlifting).   

On the other hand, type-B lactic acidosis results from sources other than hypoperfusion and tissue hypoxia that result in impaired tissue function and an inability to process available pyruvate. Consequently, alternative metabolic pathways to generate pyruvate occur, activating the lactic acid cycle, thereby resulting in high levels of lactate. Causes of type-B lactic acidosis include liver disease, malignancies, medications (e.g., metformin, epinephrine), thiamine deficiency, excessive exercise, diabetic ketoacidosis, and alcohol intoxication. 

Lactic acidosis contributes to a worsening of underlying comorbidities and therefore impacts an individual’s mortality. For example, individuals with even mildly elevated levels of lactic acid along with sepsis have a greater risk of in-hospital mortality within 30 days. Similarly, severely elevated lactic acid levels can have profound hemodynamic consequences, as it has been shown to reduce the heart’s and blood vessels’ contractility. The higher the lactate levels and the longer their value remains elevated, the greater the risk of death.  

Elevated lactate can be the result of increased lactic acid production, decreased lactic acid clearance, or a combination of both. There are multiple causes for lactic acid build-up in the body, of which include septic shock, tissue hypoperfusion (e.g., due to carbon monoxide exposure), post-cardiac arrest, regional tissue ischemia, anaerobic muscle activity, diabetic ketoacidosis, toxins and pharmacological agents, thiamine deficiency, malignancies, and liver failure.  

Septic shock is often associated with cardiovascular dysfunction causing arterial hypotension, as well as decreased perfusion in the peripheral tissues for oxygen and nutrient exchange. As a result, lactic acid that has subsequently accumulated in the blood can be a useful monitoring marker for individuals in shock. Similarly, any form of ischemia (i.e., restricted or inadequate oxygen delivery) as seen in the other types of shock (e.g., cardiogenic, obstructive, hemorrhagic shock), cardiac arrest due to lack of flow during the arrest, carbon monoxide poisoning, or local tissue ischemia can cause lactic acid build-up. A very common and benign cause of lactic acid increase is anaerobic muscle activity, which results in muscle soreness after intense exercise. During exercise, the skeletal muscles produce more lactate than the liver can metabolize. In addition, diabetic ketoacidosis can affect lactate levels because of hypoperfusion and metabolic stress. Several medications and toxins, like alcohol, biguanides (e.g., metformin), nucleoside reverse transcriptase inhibitors, salicylates, and isoniazid, can also increase lactic acid levels. Thiamine deficiency shifts metabolism to increased anaerobic carbohydrate metabolism, as thiamine is a crucial co-factor for multiple cellular enzymes, including pyruvate dehydrogenase, an essential component of aerobic carbohydrate metabolism. Lastly, malignancies and liver failure mainly increase lactate due to the inability of the liver to remove excessive lactic acid.  

Under most circumstances, lactate is rapidly cleared by the liver, where it is reconverted into glucose by the processes of gluconeogenesis. A smaller amount of additional lactate is cleared by the kidneys.   

Treatment options for excessive lactic acid levels depend on how elevated the lactate levels are and what caused the increase. If medical history reveals strenuous exercise, health care professionals must ensure that the individual is adequately hydrated, is breathing sufficiently, is warm, and is resting. Lactic acidosis secondary to septic shock generally requires administering broad-spectrum antibiotics to manage the underlying infection. Equally important is administering crystalloid fluids, typically 30 mL/kg within three hours of the initial assessment. Hemodialysis can sometimes be used to manage severe lactic acidosis, especially in patients who have renal failure. In many cases, lactic acidosis is caused by inadequate blood flow, therefore tissue perfusion must be improved first. Initiation of inotropic medications (e.g., dobutamine, dopamine) and vasoconstrictors (e.g., epinephrine, vasopressin analogs) may be helpful, providing better circulation of the intravascular volume. Further supportive care must then be individualized.