The Warburg Effect: A Case of Severe Lactic Acidosis and Hypoglycemia

Introduction: The Warburg effect, observed in cancer cells, is a type of cellular adaptation where lactate fermentation is favored for biosynthetic needs regardless of oxygen levels leading to type B lactic acidosis. Additionally, due to heightened glucose demand by malignant cells, hypoglycemia may be present. The Warburg effect is predominantly observed in aggressive lymphoproliferative disorders and is linked to a poor prognosis due to significant tumor burden. Case Description: We present a 36-year-old male with history of diffuse B-cell lymphoma, complicated by pulmonary embolism and deep vein thrombosis on anticoagulation. The patient was brought to ED with complaints of respiratory distress and altered mental status. On exam, the patient appeared disoriented and tachypneic (respiratory rate of 34) with a peripheral oxygen saturation of 95% on room air. Physical exam revealed a prominent mass in the right thigh. Laboratory showed hypoglycemia (45), elevated creatinine and azotemia consistent with non-oliguric acute kidney injury type 1, alongside severe metabolic acidosis (pH: 6.8, pCO2: 14, HCO3: 3.1) with high anion gap (31.9) (delta ratio: 1.2), attributed to lactatemia (151 mg/dL). Aggressive intravenous hydration and bicarbonate drip failed to improve acidosis, necessitating intermittent hemodialysis (IHD). Despite four days of daily IHD, severe lactic acidosis persisted (pH: 7.2, HCO3: 7, and lactic acid: 130 mg/dL), requiring intubation. Induction chemotherapy was initiated, leading to marked improvement in acidosis (HCO3: 16, pH: 7.3) by day two for which dialysis was discontinued. Discussion: The Warburg effect presents as a rare, complex, and challenging clinical situation in patients with hematologic malignancies, necessitating early identification and intervention to improve prognosis. Tachypnea without low oxygen levels is a characteristic manifestation. Treatment primarily focuses on prompt initiation of chemotherapy alongside supportive measures, yet efficacy of bicarbonate or hemodialysis is uncertain, often offering partial or no correction. Further research into kidney replacement therapy's potential benefits is warranted.