Lactic Acidosis: Symptoms, Types, Causes and Treatment

Lactic acidosis is a serious medical condition that arises when the body accumulates too much lactic acid, leading to a dangerous imbalance in blood pH. Though it is a familiar concept to many clinicians, it is often misunderstood or overlooked, especially in complex or critically ill patients. Early recognition and appropriate management are essential, as lactic acidosis is frequently associated with high mortality. This article offers a comprehensive breakdown of its symptoms, types, causes, and treatment strategies, drawing on up-to-date evidence from clinical research.

Symptoms of Lactic Acidosis

Lactic acidosis can sneak up on patients and clinicians alike, as its symptoms are often subtle at first but may rapidly progress to life-threatening severity. Recognizing the early warning signs is crucial for prompt diagnosis and intervention.

Symptom	Description	Typical Presentation	Source(s)
Nausea/Vomiting	Gastrointestinal upset, often persistent	Nausea, emesis, diarrhea	1 3 10
Respiratory	Shortness of breath, rapid breathing	Tachypnea, hyperventilation, dyspnea	1 3 4
Neurological	Mental status changes, confusion, weakness	Delirium, ataxia, encephalopathy	2 3 10
Other	Fatigue, malaise, hypotension, blindness	General malaise, shock, rare blindness	3 4 10

Table 1: Key Symptoms of Lactic Acidosis

Early and Common Manifestations

The initial symptoms often involve the gastrointestinal and respiratory systems. Patients may feel nauseous, vomit, or experience abdominal pain and diarrhea. These are nonspecific but should raise suspicion, especially in high-risk individuals such as those with diabetes, sepsis, or recent surgery 1 3 10.

Respiratory symptoms are also prominent. The body attempts to compensate for rising acid levels by increasing the breathing rate—patients may present with rapid, deep breathing (Kussmaul respirations), shortness of breath, and sometimes a feeling of air hunger 1 4.

Neurological and Severe Presentations

As acidosis worsens, neurological involvement becomes more evident. Symptoms can range from mild confusion and weakness to severe delirium, ataxia (loss of coordination), and, in rare cases, transient blindness or coma 2 3. Especially in D-lactic acidosis, neurological symptoms such as slurred speech, ataxia, and even cranial nerve palsies are notable 2.

Other Clinical Clues

Additional symptoms include general fatigue, malaise, and hypotension. In severe cases, lactic acidosis may rapidly progress to shock and multi-organ failure. Rarely, patients can develop dramatic symptoms like complete but reversible blindness, as reported in metformin-associated lactic acidosis (MALA) 3.

Types of Lactic Acidosis

Understanding the different types of lactic acidosis is essential for effective diagnosis and management. The primary distinction is based on the underlying mechanism—whether tissue oxygenation is impaired or not.

Type	Mechanism	Typical Causes	Source(s)
Type A	Tissue hypoxia	Shock, sepsis, cardiac arrest	1 4 6 7 9 12
Type B	No obvious hypoxia	Drugs, liver disease, cancer, D-lactic acidosis	1 2 5 6 7 8 9
D-Lactic	Bacterial overproduction	Short bowel, antibiotics	2

Table 2: Classification of Lactic Acidosis

Type A Lactic Acidosis

Type A is the most common and is linked to insufficient oxygen delivery to tissues. When cells lack adequate oxygen, they switch to anaerobic metabolism, generating excess lactic acid. Typical scenarios include:

• Shock (septic, cardiogenic, or hypovolemic)
• Severe hypoxemia (from respiratory failure)
• Cardiac arrest
• Major trauma or hemorrhage

These conditions are medical emergencies, and lactic acidosis here is a marker of severe physiological distress 1 4 6 9 12.

Type B Lactic Acidosis

In Type B lactic acidosis, there is no overt impairment in tissue oxygenation. Instead, the issue is either an increase in lactate production or a decrease in its clearance due to metabolic or toxic factors. Causes include:

• Medications and toxins (e.g., metformin, antiretrovirals, phenformin)
• Liver failure (impaired lactate metabolism)
• Malignancies (especially hematologic cancers)
• Thiamine deficiency (affecting pyruvate metabolism)
• Inborn errors of metabolism

Type B is often overlooked and may have a more insidious onset 1 5 6 7 8 9 10.

D-Lactic Acidosis: A Special Subtype

D-lactic acidosis is a less common but unique form, resulting from bacterial production of the D-isomer of lactic acid, which humans cannot efficiently metabolize. It typically occurs in patients with short bowel syndrome, following bowel surgery, or after antibiotic use that disrupts gut flora. Neurological symptoms are especially prominent in this variant 2.

Causes of Lactic Acidosis

The underlying causes of lactic acidosis are diverse and can be grouped based on whether they result from increased lactate production or decreased removal. Identifying the root cause is crucial for targeted therapy.

Cause	How It Contributes	Typical Scenario	Source(s)
Hypoperfusion	Increases anaerobic glycolysis	Shock, cardiac arrest	1 4 6 9 13
Sepsis/Infection	Both overproduction and underutilization	Severe infection, septic shock	1 4 9 13
Liver Failure	Impaired clearance	Cirrhosis, hepatic shock	4 6 7 12
Renal Failure	Decreased lactate removal	Chronic kidney disease, AKI	3 4 10 12
Drugs & Toxins	Mitochondrial dysfunction	Metformin, phenformin, antiretrovirals	3 5 6 8 10 12 16
Malignancy	Increased production & nutrient deficiency	Leukemia, lymphoma, thiamine deficiency	5 8
Inborn Errors	Enzymatic defects	Glycogen storage disease	1 6 7
D-Lactic Overgrowth	Bacterial fermentation	Short bowel, carb overload, antibiotics	2

Table 3: Major Causes of Lactic Acidosis

Impaired Tissue Oxygenation (Type A Causes)

The most frequent cause is tissue hypoperfusion. Any condition that reduces blood flow or oxygen delivery—such as shock (from bleeding, heart failure, or infection)—forces tissues into anaerobic metabolism, rapidly raising lactate levels 1 4 6 9 13.

Metabolic and Toxic Causes (Type B)

• Medications: Metformin and, historically, phenformin are notorious for causing lactic acidosis, especially in the presence of renal dysfunction 3 6 10 12 16. Antiretroviral drugs (e.g., zidovudine) can also impair mitochondrial function, increasing lactate 1 5.
• Liver and Renal Dysfunction: The liver is the primary organ for lactate clearance, while the kidneys also contribute. Failure of these organs leads to accumulation 4 6 7 12.
• Malignancies: Certain cancers, particularly hematologic types, can trigger lactic acidosis through high metabolic activity or by causing vitamin deficiencies (notably thiamine), further impairing lactate metabolism 5 8.
• Inborn Errors: Rare genetic defects in enzymes such as pyruvate dehydrogenase or those involved in glycogen storage can lead to chronic lactic acidosis 1 6 7.
• D-Lactic Acidosis: Seen in patients with short bowel syndrome or after specific antibiotic regimens, leading to overgrowth of D-lactate-producing bacteria. The resulting D-lactate is not easily metabolized, causing both metabolic and neurological symptoms 2.

Other Notable Triggers

Alcohol abuse, especially in diabetic patients, can precipitate lactic acidosis through multiple mechanisms, including increased lactate production and impaired clearance 10.

Treatment of Lactic Acidosis

Managing lactic acidosis requires a multifaceted approach, with the primary focus on addressing the underlying cause. Supportive care and, in select cases, adjunctive therapies may be necessary.

Treatment	Approach	Best Use Scenario	Source(s)
Underlying Cause	Treat and reverse	All forms—core principle	4 9 12 13
Oxygen/Perfusion	Restore tissue oxygen	Shock, hypoxemia	4 9 13
Renal Support	Dialysis, hemofiltration	Severe acidosis, drug toxicity	3 4 16
Drug Withdrawal	Discontinue offenders	Metformin, antiretrovirals, others	1 3 10 12
Thiamine	Supplement	Suspected deficiency, malignancy	5 8
Antibiotics/Diet	Modify flora, restrict carbs	D-lactic acidosis	2
Dichloroacetate	Stimulate metabolism	Experimental, not routine	15 17
Sodium Bicarbonate	Buffering agent	Severe acidosis (controversial)	14 16

Table 4: Main Treatment Modalities in Lactic Acidosis

Core Principle: Treat the Underlying Cause

The most crucial step in managing lactic acidosis is identifying and correcting the underlying trigger. This may involve:

• Treating shock (fluids, vasopressors)
• Managing sepsis (antibiotics, source control)
• Addressing hypoxemia (oxygen, ventilation)
• Discontinuing contributing drugs (especially metformin, phenformin, or antiretrovirals) 3 4 9 10 12 13

Supportive Therapies

• Optimizing Oxygen Delivery: Increase cardiac output and hemoglobin concentration to restore tissue perfusion 4 9 13.
• Renal Replacement Therapy: Dialysis or hemofiltration may be indicated in cases of severe acidosis, especially with drug-induced lactic acidosis or when renal failure is present. In metformin-associated cases, dialysis can be life-saving 3 4 16.
• Thiamine Supplementation: If deficiency is suspected (e.g., in cancer patients or those with poor nutrition), thiamine may help restore lactate metabolism, particularly in type B cases 5 8.

Special Considerations for D-Lactic Acidosis

Management involves restricting dietary carbohydrates and using antibiotics to suppress D-lactate-producing gut bacteria. Vancomycin, metronidazole, and ciprofloxacin are commonly effective; the choice depends on bacterial sensitivities 2.

Experimental and Controversial Therapies

• Dichloroacetate (DCA): DCA stimulates pyruvate dehydrogenase, enhancing lactate metabolism. While it improves laboratory values and may lower mortality in animal models, it has not consistently improved outcomes in human trials and is not widely used 15 17.
• Sodium Bicarbonate: Once a mainstay, sodium bicarbonate's role is now controversial. Evidence suggests it may not improve outcomes and can sometimes worsen acidosis by increasing lactate production or causing fluid overload. It may be considered in cases of life-threatening acidemia (pH <7.0) but should be used cautiously 14 16.

Adjuncts and Prevention

Other therapies (e.g., carbicarb, buffering agents) remain under investigation, and prevention—through early recognition, minimizing drug risks, and managing chronic conditions—remains the best strategy 4 9 12 13 14.

Conclusion

Lactic acidosis is a complex, life-threatening metabolic disturbance that demands rapid recognition and targeted intervention. Here are the key takeaways:

• Symptoms are wide-ranging but commonly include gastrointestinal distress, respiratory compensation, and neurological changes.
• Types are classified into Type A (hypoxic) and Type B (non-hypoxic), with D-lactic acidosis as a notable special form.
• Causes are diverse, spanning from shock and sepsis to medications, organ failure, and rare metabolic or bacterial disorders.
• Treatment is centered on reversing the underlying cause, with supportive measures and select adjunctive therapies. Controversial or experimental treatments should be reserved for specific indications or within clinical trials.

Summary Points:

• Early symptom recognition can prevent catastrophic outcomes.
• Understanding the type and cause directs appropriate management.
• Drug-induced and D-lactic acidosis require special attention.
• Supportive care is vital; controversial therapies should be used with caution.
• Prevention and prompt intervention remain the keys to improving survival.

By keeping these principles in mind, clinicians and patients alike can better navigate the challenging landscape of lactic acidosis, improving both short- and long-term outcomes.