References Chapter 19, Part 12 Metabolic acidosis June 14, 2023 References Chapter 19, Part 2 Roger mentioned MELAS syndrome MELAS syndrome: Clinical manifestations, pathogenesis, and treatment options Josh mentioned this blog on lactate- Understanding lactate in sepsis & Using it to our advantage We discussed the Warburg effect The Warburg Effect: How Does it Benefit Cancer Cells? - PMC and here’s a case from skeleton key- Skeleton Key Group Case #28: Mysterious Acidosis in Cancer - Renal Fellow Network Otto Warburg won the Nobel Prize in Physiology and Medicine in 1931 for describing how animal tumors produce large quantities of lactic acid (Wikipedia) Joel calls it the Lactate saline reflex, but the accepted term of art is Lacto-Bolo reflex The origins of the Lacto-Bolo reflex: the mythology of lactate in sepsis Buffer agents do not reverse intramyocardial acidosis during cardiac resuscitation. Josh mentioned this article the BICAR-ICU Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial - The Lancet Roger shared 3 quotes to make the point that there has been little movement in our knowledge the past 40 years: Bicarbonate does not improve hemodynamics in critically ill patients who have lactic acidosis. A prospective, controlled clinical study from Cooper in the Annals Lactic Acidosis and Bicarbonate Therapy | Annals of Internal Medicine from Robert Hollander Lactic acidosis from Nick Madias Josh mentioned the use of sodium bicarbonate for CKD Eubicarbonatemic Hydrogen Ion Retention and CKD Progression - Kidney Medicine (Madias) Bicarbonate therapy for prevention of chronic kidney disease progression (from Wesson), Sodium Bicarbonate Prescription and Extracellular Volume Increase: Real‐world Data Results from the AlcalUN Study Amy’s VoG on metabolic acidosis/KDIGO guidelines Very nice JASN review that describes the mechanisms of how metabolic acidosis leads to CKD progression First description by THE Dr. Bright 1930 Lancet description of benefit 2009 RCT that the 2012 KDIGO guidelines sort of based their 2b recommendations off of 2020 BiCARB Study 2021 META Analysis We discussed methanol toxicity : Case Study: Methanol Poisoning from Adulterated Liquor | Food Safety, Acute methyl alcohol poisoning: a review based on experiences in an outbreak of 323 cases and josh poking at the osmolar gap: PulmCrit- Toxicology dogmalysis: the osmolal gap and shared these guidelines: METHANOL | extrip-workgroup and Roger loves this: Urine fluorescence using a Wood's lamp to detect the antifreeze additive sodium fluorescein: a qualitative adjunctive test in suspected ethylene glycol ingestions From China to Panama, a Trail of Poisoned Medicine - The New York Times (diethylene glycol) . The Accidental Poison That Founded the Modern FDA - The Atlantic Outline: Chapter 19 Metabolic Acidosis Etiologies and Diagnosis Lactic Acidosis Pyruvate → lactate (LDH; NADH → NAD+) Normal production: 15–20 mmol/kg/day Metabolized in liver/kidney → pyruvate → glucose or TCA Normal lactate: 0.5–1.5 mmol/L; acidosis if > 4–5 mmol/L Causes: ↑ production: hypoxia, redox imbalance, seizures, exercise ↓ utilization: shock, hepatic hypoperfusion Malignancy, alcoholism, antiretrovirals D-lactic acidosis Short bowel/jejunal bypass Glucose → D-lactate (not metabolized by LDH) Symptoms: confusion, ataxia, slurred speech Special assay needed Tx: bicarb, oral antibiotics Treatment Underlying cause Bicarb controversial: may worsen intracellular acidosis, overshoot alkalosis, ↑ lactate Target pH > 7.1; prefer mixed venous pH/pCO2 Ketoacidosis (Chapter 25 elaborates) FFA → TG, CO2, H2O, ketones (acetoacetate, BHB) Requires: ↑ lipolysis (↓ insulin) Hepatic preference for ketogenesis Causes: DKA (glucose > 400) Fasting ketosis (mild) Alcoholic ketoacidosis Poor intake + EtOH → ↓ gluconeogenesis, ↑ lipolysis Mixed acid-base (vomiting, hepatic failure, NAGMA) Congenital organic acidemias, salicylates Diagnosis: AG, osmolar gap (acetone, glycerol) Ketones: nitroprusside only detects acetone/acetoacetate BHB can be 90% of total (false negative) Captopril → false positive Treatment: Insulin +/- glucose Renal Failure ↓ excretion of daily acid load GFR 40–50 mg/dL Early: respiratory alkalosis → Later: metabolic acidosis Treatment: bicarb, dialysis (>80 mg/dL or coma) Methanol Metabolized to formic acid → retinal toxicity Osmolar gap elevated Tx: bicarb, ethanol/fomepizole, dialysis Ethylene glycol → glycolic/oxalic acid → renal failure Same treatment + thiamine/pyridoxine Other Toluene, sulfur, chlorine gas, hyperalimentation (arginine, lysine) GI Bicarbonate Loss Diarrhea, bile/pancreatic drainage → loss of alkaline fluids Ureterosigmoidostomy → Cl-/HCO3- exchange in colon Cholestyramine → Cl- for HCO3-
