What is the pathophysiological mechanism by which inadequate tissue perfusion leads to lactic acidosis?

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From the Guidelines

Lactic acidosis occurs due to inadequate tissue perfusion because when tissues don't receive enough oxygen, cells must switch from aerobic to anaerobic metabolism to produce energy, resulting in the production of lactate and hydrogen ions, which cause acidosis. During normal aerobic metabolism, glucose is completely broken down to carbon dioxide and water, yielding 36 ATP molecules. However, in anaerobic conditions, glucose is only partially metabolized to lactate, producing just 2 ATP molecules. This process generates hydrogen ions, causing acidosis. The body normally clears lactate through the liver and kidneys, but when production exceeds clearance capacity, lactate accumulates in the bloodstream. Common causes of inadequate tissue perfusion include shock (cardiogenic, septic, or hypovolemic), severe hypoxemia, and carbon monoxide poisoning.

According to the Surviving Sepsis Campaign guidelines 1, treatment focuses on addressing the underlying cause of poor perfusion, such as fluid resuscitation for hypovolemia or antibiotics for sepsis, while supporting vital organ function and monitoring lactate levels to assess response to therapy. The guidelines recommend an initial target mean arterial pressure (MAP) of 65 mm Hg in patients with septic shock requiring vasopressors 1. Additionally, the guidelines suggest guiding resuscitation to normalize lactate in patients with elevated lactate levels as a marker of tissue hypoperfusion 1.

It is essential to note that sodium bicarbonate therapy is not recommended to improve hemodynamics or reduce vasopressor requirements in patients with hypoperfusion-induced lactic acidemia with pH ≥ 7.15 1. The use of sodium bicarbonate therapy may be associated with sodium and fluid overload, an increase in lactate and Paco2, and a decrease in serum ionized calcium.

Key points to consider in the management of lactic acidosis due to inadequate tissue perfusion include:

  • Addressing the underlying cause of poor perfusion
  • Supporting vital organ function
  • Monitoring lactate levels to assess response to therapy
  • Avoiding the use of sodium bicarbonate therapy in patients with hypoperfusion-induced lactic acidemia with pH ≥ 7.15
  • Guiding resuscitation to normalize lactate in patients with elevated lactate levels as a marker of tissue hypoperfusion.

From the Research

Lactic Acidosis and Tissue Perfusion

  • Lactic acidosis is often caused by tissue perfusion that is inadequate to meet metabolic demand 2.
  • Inadequate tissue perfusion leads to tissue hypoxia, which results in the accumulation of lactic acid 3, 4.
  • Tissue hypoxia is a major contributor to lactic acid accumulation in sepsis and low-flow states 4.

Mechanisms of Lactic Acid Accumulation

  • Two main mechanisms contribute to lactic acid accumulation in sepsis and low-flow states: tissue hypoxia and epinephrine-induced stimulation of aerobic glycolysis 4.
  • Lactic acidosis can also result from medications, organ dysfunction, and sepsis even in the absence of malperfusion 3.
  • Type B lactic acidosis should be considered in patients with persistently elevated lactate without evidence of inadequate oxygen delivery 5.

Consequences of Lactic Acidosis

  • Acidemia causes deleterious effects in almost every organ system, but it can also have positive effects, increasing localized blood flow and oxygen delivery, as well as providing protection against hypoxic cellular injury 3.
  • The cellular injury associated with lactic acidosis is partly due to activation of NHE1, a cell-membrane Na(+)/H(+) exchanger 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Lactic Acidosis: Current Treatments and Future Directions.

American journal of kidney diseases : the official journal of the National Kidney Foundation, 2016

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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