Blood Lactic Acid

Aka: Blood Lactic Acid, Lactic Acidosis, Lactic Acidosis Definition, Lactic Acid

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II. Physiology

  1. See Glucose Metabolism
  2. Lactic Acid is generated when oxygen is unavailable to allow for Krebs Cycle related Oxidative Phosphorylation
    1. Occurs with both skeletal Muscle anaerobic metabolism as well as other physiologic stress (e.g. Sepsis)
    2. Lactic Acid may also be generated during aerobic conditions
  3. Glycolysis generates 7 net ATP/Glucose (compared with 25 for Kreb Cycle) and does not require oxygen
  4. However, Glycolysis does use NAD+ (for glyceraldehyde 3-P to 1,3P2-glycerate)
    1. Glycolysis.png
    2. NAD+ is typically replenished in the Krebs Cycle related Oxidative Phosphorylation
    3. When oxygen is unavailable, pyruvate is metabolized to Lactic Acid, regenerating NAD+
  5. Lactic Acid conversion back to Glucose (Gluconeogenesis) requires several additional steps
    1. gluconeogenesis.png
    2. Muscle Cells release generated Lactic Acid
    3. Lactate may be directly utilized by the Heart (up to 60% of energy demands) and brain (up to 25% of energy demands)
    4. Lactic Acid is transported via systemic circulation to liver and Kidney
      1. Liver (70-75%) and Kidney (25-30%) cells perform lactate metabolism (Gluconeogenesis)
      2. Three Enzymes required for Gluconeogenesis from Lactic Acid are only in cells of the liver and Kidney
        1. Pyruvate carboxylase
        2. Fructose Diphosphatase
        3. Glucose 6-Phosphatase

III. Causes: Tissue Hypoxia in Hypoperfusion States (Type A)

  1. Systemic hypoperfusion or shock
    1. Hypovolemia or Dehydration
    2. Cardiogenic Shock
    3. Seizure (transient)
    4. Septic Shock
      1. Lactic Acid is generated in lungs and Muscle, primarily with leukocyte Glycolysis
  2. Local hypoperfusion
    1. Testicular Torsion
    2. Intestinal Volvulus
    3. Acute Mesenteric Ischemia
    4. Arterial embolism (e.g. Cerebrovascular Accident)
    5. Epinephrine infusion (causing tissue Hypoxia)
  3. Decreased arterial oxygen
    1. Hypoxemia (e.g. Asthma)
    2. Severe Anemia
    3. Carbon Monoxide Poisoning

IV. Causes: No Tissue Hypoxia (Type B)

  1. Medical conditions (Type B1)
    1. Severe liver disease (related to Cori Cycle Lactic Acid generation)
    2. Cancer
    3. Thiamine deficiency
  2. Medications or toxins (Type B2, most are via mitochondrial cytopathy)
    1. Acetaminophen Overdose
      1. Acetaminophen Poisoning directly inhibits Electron Transport Chain in mitochondria
      2. Lactic Acidosis in Acute Hepatic Failure is associated with higher mortality
    2. Cyanide Poisoning
      1. Cyanide blocks Oxidative Phosphorylation
      2. Lactic Acid levels are typically very high (>10 mmol/L)
    3. MetforminOverdose
    4. Beta-2 Agonist (transient Lactic Acidosis)
      1. Via stimulated Glycolysis and pyruvate generation
      2. Albuterol 10 mg neb increases Lactic Acid 0.8 mmoL/L
      3. Zitek (2016) Acad Emerg Med 23(6): 718-21 +PMID:26857949 [PubMed]
    5. Isoniazid (via liver toxicity)
    6. Tetracycline
    7. Linezolid
    8. Alcohol and Toxic Alcohol ingestion
      1. Alcohol Intoxication
      2. Ethylene Glycol Poisoning
      3. Methanol Poisoning
    9. Propofol
      1. Causes Propofol Infusion Syndrome
    10. Propylene gylcol (solvent for many Parenteral drugs)
      1. Nitroglycerin
      2. Lorazepam
      3. Etomidate
      4. Phenytoin
    11. Nucleoside Reverse Transcriptase Inhibitor (NRTI agents)
      1. Zidovudine
      2. Lamivudine
      3. Didanosine
      4. Stavudine
  3. Congenital metabolic conditions (Type B3)
    1. Mitochondrial disorders
    2. Hypoglycemia

V. Labs: Collection

  1. Draw lactate samples in gray-top tube, cool in ice bag and run sample within 15 minutes
    1. RBC metabolism will otherwise falsely alter serum lactate levels

VI. Precautions

  1. Lactic Acid is primarily used as a Sepsis marker and tissue ischemia marker (e.g. Ischemic Bowel)
    1. However, differential diagnosis of Lactic Acidosis is broad (see above)
    2. Avoid ordering Lactic Acid in low risk patients (non-toxic, previously healthy)
    3. Consider superimposed factors resulting in Lactic Acidosis (Asthma, Albuterol)
  2. Lactic Acid clearance outside Sepsis does not uniformly improve with Intravenous Fluids
    1. Cardiogenic Shock can also increase Lactic Acid and will worsen with excess fluids
    2. Outside Sepsis, Exercise caution in aggressive fluid Resuscitation to lower Lactic Acid
  3. Lactic Acid is falsely elevated with improper collection
    1. Delayed Running of a sample (or a sample not kept on ice after blood draw)
    2. Non-free flowing sample (e.g. Tourniquet in place during blood draw)
      1. Arterial Line samples are most accurate (free flowing)
      2. Controversial as to whether Tourniquet use effects lactate level
  4. Lactic Acidosis is associated with increased mortality in specific conditions (esp. Lactic Acid >4 mmol/L)
    1. Septic Shock
    2. Cryptic Shock (occult hypoperfusion) with normal Blood Pressure, but increased Lactic Acid level
    3. Trauma
    4. Failure to clear Lactic Acid
      1. May indicate infectious disease complications, organ dysfunction and inadequate Resuscitation
  5. Expect Potassium to increase with severe Lactic Acidosis
    1. Severe Lactic Acidosis (typically >4) is associated with a Metabolic Acidosis with Anion Gap
    2. Cellular Potassium-hydrogen transporter drives hydrogen into cells in exchange for Potassium
    3. Potassium efflux from cells results in an increase in Serum Potassium
  6. References
    1. Claudius and Kallay in Swadron (2023) EM:Rap 23(5): 9-10
    2. Herbert and Crager in Herbert (2018) EM:Rap 18(4): 1-3

VII. Efficacy: Children

  1. Lactic Acid has historically not been used in children, as much as it has become a mainstay in adult evaluation
  2. Lactic Acid may have more evidence for use in sick children (esp. Sepsis, Trauma) and their disposition
    1. Increased organ dysfunction in children with elevated Lactic Acid >4 mmol/L
      1. Scott (2012) Acad Emerg Med 19(11): 1276-80 +PMID: 23167859 [PubMed]
    2. Predicted need for Critical Care in children with Trauma and pre-hospital elevated Lactic Acid >4 mmol/L
      1. Shah (2013) Pediatr Emerg Care 29(6): 715-9 +PMID: 23714761 [PubMed]
    3. Predicted in-hospital mortality for critically ill children
      1. Bai (2014) BMC Pediatr 14:83 +PMID: 24673817 [PubMed]

VIII. References

  1. Platzer and Ponce (2023) Crit Dec Emerg Med 37(5): 16-7
  2. (2013) Endo and Acid Base Disorders, EM Bootcamp, Las Vegas

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