What is metabolic acidosis?

Metabolic acidosis is a medical condition characterized by an imbalance in the body’s acid-base balance, resulting in an accumulation of acid or a loss of bicarbonate (a base) in the body. This disturbance in the acid-base balance leads to a decrease in the pH of the blood, making it more acidic.


There are several possible causes of metabolic acidosis, including:


  • Increased Production of Acid: This can occur due to conditions such as diabetic ketoacidosis (DKA), where the body produces excess ketones (acidic byproducts of fat metabolism) in response to insulin deficiency. Other conditions that can lead to increased acid production include lactic acidosis (due to inadequate oxygen delivery to tissues), ingestion of certain toxins or drugs, and disorders of amino acid metabolism.


  • Decreased Excretion of Acid: The kidneys play a crucial role in excreting excess acid from the body through the urine. Conditions that impair kidney function, such as renal failure or certain types of kidney disease, can lead to a buildup of acid in the body.


  • Loss of Bicarbonate: Bicarbonate is a buffer that helps regulate the body’s acid-base balance. Conditions that result in the loss of bicarbonate from the body, such as diarrhea or intestinal fistulas, can lead to metabolic acidosis.


What is the relationship between metabolic acidosis and oxidative stress?

The relationship between metabolic acidosis and oxidative stress is multifaceted and involves complex interactions between cellular metabolism, acid-base balance, and redox homeostasis. While direct evidence linking metabolic acidosis to oxidative stress is limited, several mechanisms suggest potential connections between these processes:


  • Mitochondrial Dysfunction: Metabolic acidosis can disrupt mitochondrial function, leading to impaired oxidative phosphorylation and ATP production. Mitochondria are major sources of reactive oxygen species (ROS) production in cells, and disruption of mitochondrial function can lead to increased ROS generation. Excess ROS production in mitochondria can overwhelm antioxidant defenses and lead to oxidative stress.


  • Inflammation and Immune Response: Metabolic acidosis can activate inflammatory pathways and trigger immune responses in cells and tissues. Inflammatory cells, such as macrophages and neutrophils, produce ROS as part of their antimicrobial defense mechanisms. Chronic inflammation associated with metabolic acidosis can lead to sustained ROS production and oxidative stress.


  • Acidosis-induced Tissue Damage: Acidosis can directly damage cells and tissues, leading to cellular injury and oxidative stress. Acidosis disrupts cell membrane integrity, alters intracellular pH, and impairs enzymatic function, all of which can contribute to oxidative damage. Oxidative stress resulting from tissue injury and damage can further exacerbate cellular dysfunction and contribute to the progression of metabolic acidosis.


  • Antioxidant Defenses: Metabolic acidosis may affect antioxidant defenses and redox signaling pathways in cells. Acidosis can alter the expression and activity of antioxidant enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase, leading to impaired antioxidant capacity. Dysregulation of antioxidant defenses can exacerbate oxidative stress and contribute to cellular damage in the context of metabolic acidosis.


  • Secondary Effects on Organ Function: Metabolic acidosis can have systemic effects on organ function, leading to tissue hypoxia, ischemia-reperfusion injury, and organ dysfunction. These secondary effects can further contribute to oxidative stress and tissue damage in affected organs, exacerbating the overall oxidative burden in the body.


Overall, while the precise mechanisms linking metabolic acidosis to oxidative stress are still being elucidated, evidence suggests that metabolic acidosis can disrupt cellular metabolism, activate inflammatory pathways, and impair antioxidant defenses, leading to increased ROS production and oxidative stress.