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LACTIC ACIDOSIS by Mark Ramzy DO & Nick Mark MD ONE @MRamzyDO most
DEFINITIONS: @Nickmmark current
Muscles / Other Tissues version →
· Lactic acid is an endogenous substrate for gluconeogenesis, that is constantly
produced by muscle and other tissues and is increased with exercise/activity. Lactic Liver
acid is non-toxic, though it can cause a metabolic acidosis and importantly can be a Glucose Glucose H2O
marker for severity of underlying disease.
· Lactate is the conjugate base of lactic acid (this is why LR does not cause acidosis) GAPDH
+2 ATP

v1.0 (2020-01-25)
O
· Lactic Acidosis is defined as an arterial lactate level ≥ 2 mmol/L PLUS a pH < 7.35
Lactate Pyruvate O2

CC BY-SA 3.0
HO
Dehydrogenase
ROLE IN DISEASE:
(LDH) HO
Lactatic acid may be elevated in critical illness due to impaired O2 delivery (Type LDH
A lactic acidosis) or impaired O2 utilization by cells (Type B Lactic Acidosis).
Pyruvate Lactate
Rarely, an enantiomer of lactate (D-lactate) may be produced by gut bacteria in Occurs when
O2 is ABSENT
patients with bacterial overgrowth, causing another type of lactic acidosis. LACTATE
Elevation in serum lactic acid is associated with severe sepsis, but lactic acid CLEARANCE
clearance is unreliable as a resuscitation endpoint. · In sepsis & septic shock, Oxidative
Phosphorylation 70% Liver
Anaerobic Aerobic State
lactate elevations may be 20% Kidney
(DO2 < VO2) (VO2 < DO2) due to increased 𝛽2 10% Muscle
Type-A Type B
adrenergic tone rather than The Cori Cycle: Oxygen deprived
lactic acidosis lactic acidosis
end-organ hypoperfusion
O2 H2O cells produce lactate. In the Liver and Renal
· Septic patients with presence of O2, the liver/kidney dysfunction will
VO2

H+ +
elevated lactate typically convert lactate back to pyruvate, increase lactate due
have hyperdynamic repaying the “oxygen debt” of the to impaired clearance
circulation & O2 delivery Hydrogen Ion tissue
Importantly, in severe sepsis L-Lactate DELIVERY OF OXYGEN (DO2) is dependent on the following:
increasing oxygen delivery CARDIAC OUTPUT (CO) & BLOOD O2 CONTENT (CaO2)
(DO2) may not increase O2
consumption (VO2) nor does 𝐃𝑶𝟐 = 𝑯𝑹 × 𝑺𝑽 × 𝟏. 𝟑𝟒 × 𝑯𝒃 × 𝑺𝒂𝑶𝟐 + (𝑷𝒂𝑶𝟐 × 𝟎. 𝟎𝟎𝟑)
DO2 it affect lactate clearance.

TYPE A: IMPAIRED O2 DELIVERY (DO2) TYPE B: IMPAIRED O2 UTILIZATION (VO2) TYPE D: BACTERIAL
OVERGROWTH
D-Lactic Acid

DECREASED O2 DELIVERY
Consider etiologies that
impair adequate perfusion
- Hypotension &
Hypovolemia
- Trauma & burns
- Cardiogenic & Septic Shock
- Severe Anemia
- Cardiac Arrest
- Severe Hypoxemia
- Regional Ischemia
- Compartment Syndrome
INCREASED O2 DEMAND
Consider etiologies that
increase O2 consumption
- Stress / Pain / Exercise
- Fever
- Hypothermia & Shivering
- Seizures
- 𝜷eta-Agonists
- ↑ work of breathing
- Localized soft-tissue infection
- Mesenteric Ischemia
- Microcirculatory dysfunction
DRUGS / TOXINS IMPAIRED CLEARANCE - Presents as AG acidosis with negative
- Propofol (PRIS), - Systemic liver Failure lactate. Difficult to diagnosis as it
- Valproic Acid) - Renal failure requires separate D-lactate testing
- Biguanides (Metformin) - Mitochondrial dynsfxn - Seen in Short Bowel Syndrome,
- Linezolid, Lactulose - Inborn Errors of Metabolism where decreased carbohydrate
digestion leads to presence of
- HIV Antiretrovirals (esp. NRTIs)
- Acetaminophen additional sugars in the colon.
OTHER
- Ethanol, Methanol & Other - Bacteria ferment and convert these
- Infections (ie. HIV, Malaria, Late Sepsis)
toxic alcohols sugars into D-Lactate
- Sodium Nitroprusside - Malignancy (Leukemia/Lymphoma) - Diabetic Ketoacidosis and Propylene
- Others (ie. Ricin, Strychnine, Niacin, - Diabetes Mellitus +/- DKA Glycol administration have also been
Salicylates, Isoniazid) - Alcoholic lactic acidosis associated with D-Lactate
- Deficiencies (Thiamine & Biotin) accumulation