Lactic Acidosis
Disease Details
Family Health Simplified
- Description
- Lactic acidosis is a medical condition characterized by the buildup of lactic acid in the body, causing a decrease in blood pH levels.
- Type
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Lactic acidosis can result from various causes, including genetic conditions, but it is not a single disease with a specific type of genetic transmission. However, when lactic acidosis is due to inherited metabolic disorders, it often follows:
- **Mitochondrial inheritance:** This type of genetic transmission occurs because of mutations in mitochondrial DNA, which is inherited exclusively from the mother.
- **Autosomal recessive inheritance:** Some enzyme deficiencies leading to lactic acidosis follow this pattern, where both parents must carry and pass on the defective gene.
The specific type of genetic transmission depends on the underlying disorder responsible for the lactic acidosis. - Signs And Symptoms
- Lactic acidosis is commonly found in people who are unwell, such as those with severe heart and/or lung disease, a severe infection with sepsis, the systemic inflammatory response syndrome due to another cause, severe physical trauma, or severe depletion of body fluids. Symptoms in humans include all those of typical metabolic acidosis (nausea, vomiting, generalized muscle weakness, and laboured and deep breathing).
- Prognosis
- Mild and transient elevations in lactate have limited impact on mortality, whereas sustained and severe lactate elevations are associated with a high mortality.The mortality of lactic acidosis in people taking metformin was previously reported to be 50%, but in more recent reports this was closer to 25%.
- Onset
- Lactic acidosis can have an onset that varies depending on the underlying cause. It can develop suddenly (acute) in cases such as severe infection, trauma, or certain medications, or it can develop more gradually (chronic) in conditions like chronic liver disease or heart failure.
- Prevalence
- The prevalence of lactic acidosis varies and is difficult to quantify precisely due to its association with a wide range of underlying conditions, such as severe infections, organ failure, and certain medications. It is considered a relatively rare but serious medical condition. Prevalence rates are not typically specified due to the condition being secondary to other primary illnesses.
- Epidemiology
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Lactic acidosis is a medical condition characterized by an accumulation of lactic acid in the body, leading to a lower pH in the bloodstream. It is often categorized into two types: Type A, which is associated with hypoxia (low oxygen levels), and Type B, which occurs without hypoxia and is often linked to metabolic conditions or drug interactions.
Epidemiologically, lactic acidosis can occur across various populations and is frequently seen in patients with conditions such as septic shock, cardiac arrest, or severe hypoxia. It can also be associated with chronic conditions like liver disease, diabetes (particularly with the use of metformin), and malignancies. The incidence in hospitalized patients is notably higher, particularly among those in intensive care units. The condition can significantly increase morbidity and mortality rates, thus prompt diagnosis and management are critical. - Intractability
- Lactic acidosis itself is not inherently intractable. It is a condition characterized by the buildup of lactic acid in the body, usually due to oxygen deprivation in tissues or metabolic disturbances. Effective management depends on addressing the underlying cause, such as sepsis, severe hypoxia, liver failure, or certain medications. Treatment typically involves measures to improve oxygenation, restore tissue perfusion, correct metabolic imbalances, and remove or address the precipitating factors. Early diagnosis and appropriate intervention can often lead to resolution of the condition.
- Disease Severity
- Lactic acidosis is a serious medical condition characterized by the buildup of lactic acid in the body, which can lead to a dangerously low pH level in the bloodstream. It can be life-threatening if not promptly diagnosed and treated.
- Healthcare Professionals
- Disease Ontology ID - DOID:3650
- Pathophysiology
- Glucose metabolism begins with glycolysis, in which the molecule is broken down into pyruvate in ten enzymatic steps. A significant proportion of pyruvate is converted into lactate (usually 10:1). The human metabolism produces about 20 mmol/kg of lactic acid every 24 hours. This happens predominantly in tissues (especially muscle) that have high levels of the "A" isoform of the enzyme lactate dehydrogenase (LDHA), which predominantly converts pyruvate into lactate. The lactate is carried by the bloodstream to other tissues where it is converted back to pyruvate by the "B" isoform of LDH (LDHB). Firstly there is gluconeogenesis in the liver (as well as the kidney and some other tissues), where lactate is converted into pyruvate and then into glucose; this is known as the Cori cycle. In addition, pyruvate generated from lactate can be oxidized to acetyl-CoA, which can enter the citric acid cycle allowing ATP production by oxidative phosphorylation.Elevations in lactate are either a consequence of increased production or of decreased metabolism. With regards to metabolism, this predominantly takes place in the liver (70%), which explains that lactate levels may be elevated in the setting of liver disease.In "type A" lactic acidosis, the production of lactate is attributable to insufficient oxygen for aerobic metabolism. If there is no oxygen available for the parts of the glucose metabolism that require oxygen (citric acid cycle and oxidative phosphorylation), excess pyruvate will be converted in excess lactate. In "type B" lactic acidosis the lactate accumulates because there is a mismatch between glycolysis activity and the remainder of glucose metabolism. Examples are situations where the sympathetic nervous system is highly active (e.g. severe asthma). There is controversy as to whether elevated lactate in acute illness can be attributed to tissue hypoxia; there is limited empirical support for this theoretical notion.
- Carrier Status
- Lactic acidosis refers to the buildup of lactic acid in the body, predominantly affecting metabolic processes. Carrier status is not applicable to lactic acidosis as it is not an inherited condition, but rather a result of metabolic dysfunction, underlying health issues, or external factors like medications or toxins.
- Mechanism
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Lactic acidosis refers to a condition characterized by the accumulation of lactate in the body, leading to a decrease in blood pH. Here's an overview of the mechanisms and molecular mechanisms involved:
**Mechanism:**
1. **Anaerobic Metabolism:** Lactic acidosis often results from anaerobic metabolism, where glucose is converted to lactate instead of being fully oxidized to carbon dioxide and water. This typically occurs when oxygen delivery to tissues is insufficient.
2. **Overproduction or Underutilization of Lactate:** Conditions that either increase the production of lactate (e.g., intense exercise, sepsis, shock) or impair the utilization of lactate (e.g., liver disease) can lead to lactic acidosis.
3. **Impaired Clearance:** The liver primarily clears lactate through gluconeogenesis and oxidation. Conditions impairing liver function can disrupt this process.
**Molecular Mechanisms:**
1. **Glycolysis Pathway:** Under anaerobic conditions, pyruvate (produced from glucose) is converted to lactate by the enzyme lactate dehydrogenase (LDH). This regeneration of NAD+ is necessary to sustain glycolysis.
2. **NAD+/NADH Ratio:** A shift in the cellular NAD+/NADH ratio towards NADH can favor the conversion of pyruvate to lactate, promoting lactic acidosis.
3. **Mitochondrial Dysfunction:** Impaired oxidative phosphorylation in mitochondria (due to hypoxia, toxins, or genetic disorders) can force cells to rely on anaerobic glycolysis, increasing lactate production.
4. **Hypoxia-inducible Factor 1 (HIF-1):** In response to hypoxia, HIF-1 is activated and can upregulate enzymes involved in glycolysis, including LDH, leading to increased lactate production.
5. **Transport Proteins:** Monocarboxylate transporters (MCTs) facilitate the export of lactate from cells into the bloodstream. Overactivity or upregulation of these transporters can exacerbate lactic acidosis.
Understanding these mechanisms is crucial for diagnosing and treating lactic acidosis, as interventions may target specific pathways involved in lactate production or clearance. - Treatment
- If elevated lactate is present in acute illness, supporting the oxygen supply and blood flow are key initial steps. Some vasopressors (drugs that augment the blood pressure) are less effective when lactate levels are high, and some agents that stimulate the beta-2 adrenergic receptor can elevate the lactate further.Direct removal of lactate from the body (e.g. with hemofiltration or dialysis) is difficult, with limited evidence for benefit; it may not be possible to keep up with the lactate production.Limited evidence supports the use of sodium bicarbonate solutions to improve the pH (which is associated with increased carbon dioxide generation and may reduce the calcium levels).Lactic acidosis caused by inherited mitochondrial disorders (type B3) may be treated with a ketogenic diet and possibly with dichloroacetate (DCA), although this may be complicated by peripheral neuropathy and has a weak evidence base.
- Compassionate Use Treatment
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Lactic acidosis involves the buildup of lactic acid in the body, leading to an excessively acidic environment. Treatment primarily focuses on addressing the underlying cause and supportive care. While specific off-label or experimental treatments are not typically first-line, some approaches have been explored:
1. **Dichloroacetate (DCA)**: This compound has been investigated as a treatment to stimulate pyruvate dehydrogenase, potentially reducing lactate production.
2. **Bicarbonate Therapy**: Used in some cases to neutralize the acid in the blood, although its use remains controversial.
3. **Extracorporeal Treatments**: Hemodialysis or continuous renal replacement therapy (CRRT) might be used to remove excess lactate, particularly in severe cases.
4. **Thiamine (Vitamin B1)**: Sometimes used off-label, especially in patients suspected of having a thiamine deficiency precipitating lactic acidosis.
These approaches are generally considered on a case-by-case basis and typically as adjuncts to more established treatments aimed at correcting the underlying cause of the lactic acidosis. - Lifestyle Recommendations
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For lactic acidosis, lifestyle recommendations include:
1. **Dietary Adjustments**: Monitor and manage your carbohydrate intake to prevent excessive lactic acid production. Consult a dietitian for a tailored diet plan.
2. **Regular Exercise**: Engage in moderate, regular physical activity. Avoid intense exercise that can exacerbate lactic acid buildup. Always consult your healthcare provider before starting any new exercise regimen.
3. **Hydration**: Maintain adequate hydration to help the body metabolize lactic acid more efficiently.
4. **Avoid Alcohol**: Limit or avoid alcohol consumption, as it can increase the risk of lactic acidosis.
5. **Medication Management**: Ensure proper management of any underlying conditions and medications that might contribute to lactic acidosis. Always follow your doctor’s guidance.
6. **Monitor Symptoms**: Be vigilant about any symptoms and seek medical advice if you experience muscle pain, weakness, fatigue, or other concerning signs.
Regular check-ups with your healthcare provider are essential for monitoring the condition and making necessary adjustments to your lifestyle. - Medication
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Lactic acidosis requires prompt medical attention to address the underlying cause. Medications may include:
1. Sodium Bicarbonate: Administered to neutralize the excess acid in the blood.
2. Dichloroacetate: Occasionally used to increase the removal of lactate by stimulating pyruvate dehydrogenase.
3. Intravenous fluids, including electrolytes, to help flush out the lactic acid and maintain hydration.
4. Insulin: Used in cases related to diabetes to improve glucose metabolism.
5. Antibiotics: If an infection is identified as the underlying cause, appropriate antibiotics may be administered.
It's important to treat the underlying condition causing the lactic acidosis, such as sepsis, trauma, or a metabolic disorder, along with these medications. - Repurposable Drugs
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Repurposable drugs for lactic acidosis might include:
1. Dichloroacetate (DCA) - Helps normalize lactate levels by stimulating pyruvate dehydrogenase.
Note: Treatments should always be administered under medical supervision. - Metabolites
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Lactic acidosis is characterized by an elevated concentration of lactate in the blood. Key metabolites involved include:
1. **Lactate**: Increased levels are a direct indicator.
2. **Pyruvate**: May also be elevated due to disrupted conversion processes.
3. **Bicarbonate**: Often decreased as the body attempts to buffer the increased acid.
4. **Glucose**: Fluctuations depending on the underlying cause (e.g., sepsis, diabetes).
It's important to investigate the underlying cause to manage the condition effectively. - Nutraceuticals
- Lactic acidosis is a medical condition where lactate builds up in the body, leading to an excessively acidic environment. As of now, there is no specific nutraceutical approved for the treatment of lactic acidosis. Management typically focuses on addressing the underlying cause, improving tissue oxygenation, and supportive care. Nutraceuticals could potentially offer indirect benefits, such as improving overall metabolic health, but they are not a primary treatment for this condition. Always consult a healthcare professional for proper diagnosis and treatment.
- Peptides
- Lactic acidosis is not typically associated directly with peptides. It is a condition characterized by the buildup of lactic acid in the body, leading to an acid-base imbalance in the blood. This can result from various causes, such as tissue hypoxia, certain medications, or metabolic disorders. Treatment focuses on addressing the underlying cause and managing symptoms. Peptides are not specifically used in the diagnosis or treatment of lactic acidosis.