Fasting ketosis and alcoholic ketoacidosis
- Ankit Mehta, MD
Ankit Mehta, MD
- Assistant Professor, Department of Internal Medicine, Texas A&M College of Medicine, Dallas
- Associate Program Director, Internal Medicine Residency, Baylor University Medical Center, Dallas
- Michael Emmett, MD
Michael Emmett, MD
- Editor-in-Chief — Nephrology
- Section Editor — Fluid and Electrolytes
- Chief of Internal Medicine
- Baylor University Medical Center
- Section Editors
- Richard H Sterns, MD
Richard H Sterns, MD
- Editor-in-Chief — Nephrology
- Section Editor — Fluid and Electrolytes
- Professor of Medicine
- University of Rochester School of Medicine and Dentistry
- Stephen J Traub, MD
Stephen J Traub, MD
- Section Editor — Toxicology
- Associate Professor of Emergency Medicine
- Mayo Medical School
Ketoacidosis is the term used for metabolic acidoses associated with an accumulation of ketone bodies. The most common cause of ketoacidosis is diabetic ketoacidosis. Two other causes are fasting ketosis and alcoholic ketoacidosis.
Fasting ketosis and alcoholic ketoacidosis will be reviewed here. Issues related to diabetic ketoacidosis are discussed in detail elsewhere. (See "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Epidemiology and pathogenesis" and "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Clinical features, evaluation, and diagnosis" and "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Treatment".)
PHYSIOLOGY OF KETONE BODIES
There are three major ketone bodies, with the interrelationships shown in the figure (figure 1):
●Acetoacetic acid is the only true ketoacid.
●The more dominant acid in patients with ketoacidosis is beta-hydroxybutyric acid, which results from the reduction of acetoacetic acid by NADH. Beta-hydroxybutyric acid is a hydroxyacid, not a true ketoacid.
- Rose BD, Post TW. Clinical physiology of acid-base and electrolyte disorders, 5th ed, McGraw-Hill, New York 2001. p.801.
- Foster DW, McGarry JD. The metabolic derangements and treatment of diabetic ketoacidosis. N Engl J Med 1983; 309:159.
- Reichard GA Jr, Owen OE, Haff AC, et al. Ketone-body production and oxidation in fasting obese humans. J Clin Invest 1974; 53:508.
- Cahill GF Jr. Fuel metabolism in starvation. Annu Rev Nutr 2006; 26:1.
- Owen OE, Caprio S, Reichard GA Jr, et al. Ketosis of starvation: a revisit and new perspectives. Clin Endocrinol Metab 1983; 12:359.
- Miles JM, Haymond MW, Nissen SL, Gerich JE. Effects of free fatty acid availability, glucagon excess, and insulin deficiency on ketone body production in postabsorptive man. J Clin Invest 1983; 71:1554.
- MADISON LL, MEBANE D, UNGER RH, LOCHNER A. THE HYPOGLYCEMIC ACTION OF KETONES. II. EVIDENCE FOR A STIMULATORY FEEDBACK OF KETONES ON THE PANCREATIC BETA CELLS. J Clin Invest 1964; 43:408.
- Balasse EO, Féry F. Ketone body production and disposal: effects of fasting, diabetes, and exercise. Diabetes Metab Rev 1989; 5:247.
- Owen OE, Morgan AP, Kemp HG, et al. Brain metabolism during fasting. J Clin Invest 1967; 46:1589.
- Owen OE, Reichard GA Jr. Human forearm metabolism during progressive starvation. J Clin Invest 1971; 50:1536.
- Yancy WS Jr, Olsen MK, Guyton JR, et al. A low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia: a randomized, controlled trial. Ann Intern Med 2004; 140:769.
- Toth HL, Greenbaum LA. Severe acidosis caused by starvation and stress. Am J Kidney Dis 2003; 42:E16.
- Rudolf MC, Sherwin RS. Maternal ketosis and its effects on the fetus. Clin Endocrinol Metab 1983; 12:413.
- Mahoney CA. Extreme gestational starvation ketoacidosis: case report and review of pathophysiology. Am J Kidney Dis 1992; 20:276.
- Shah P, Isley WL. Ketoacidosis during a low-carbohydrate diet. N Engl J Med 2006; 354:97.
- Chalasani S, Fischer J. South Beach Diet associated ketoacidosis: a case report. J Med Case Rep 2008; 2:45.
- Wrenn KD, Slovis CM, Minion GE, Rutkowski R. The syndrome of alcoholic ketoacidosis. Am J Med 1991; 91:119.
- Levy LJ, Duga J, Girgis M, Gordon EE. Ketoacidosis associated with alcoholism in nondiabetic subjects. Ann Intern Med 1973; 78:213.
- Dillon ES, Dyer WW, Smelo LS. Ketone acidosis of nondiabetic adults. Med Clin N Amer 1940; 24:1813.
- Jenkins DW, Eckle RE, Craig JW. Alcoholic ketoacidosis. JAMA 1971; 217:177.
- Cooperman MT, Davidoff F, Spark R, Pallotta J. Clinical studies of alcoholic ketoacidosis. Diabetes 1974; 23:433.
- Kreisberg RA. Diabetic ketoacidosis, alcoholic ketosis, lactic acidosis, and hyporeninemic hypoaldosteronism. In: Diabetes mellitus: Theory and practice, 3rd ed, Ellenberg M, Rifkin H (Eds), Medical Examination Publishing Co Inc, New York 1983. p.621.
- Palmer JP. Alcoholic ketoacidosis: clinical and laboratory presentation, pathophysiology and treatment. Clin Endocrinol Metab 1983; 12:381.
- Halperin ML, Hammeke M, Josse RG, Jungas RL. Metabolic acidosis in the alcoholic: a pathophysiologic approach. Metabolism 1983; 32:308.
- Ylikahri RH, Huttunen MO, Härkönen M. Hormonal changes during alcohol intoxication and withdrawal. Pharmacol Biochem Behav 1980; 13 Suppl 1:131.
- Linnoila M, Mefford I, Nutt D, Adinoff B. NIH conference. Alcohol withdrawal and noradrenergic function. Ann Intern Med 1987; 107:875.
- Laffel L. Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes. Diabetes Metab Res Rev 1999; 15:412.
- Umpierrez GE, DiGirolamo M, Tuvlin JA, et al. Differences in metabolic and hormonal milieu in diabetic- and alcohol-induced ketoacidosis. J Crit Care 2000; 15:52.
- Krebs HA, Freedland RA, Hems R, Stubbs M. Inhibition of hepatic gluconeogenesis by ethanol. Biochem J 1969; 112:117.
- Fulop M, Ben-Ezra J, Bock J. Alcoholic ketosis. Alcohol Clin Exp Res 1986; 10:610.
- Schelling JR, Howard RL, Winter SD, Linas SL. Increased osmolal gap in alcoholic ketoacidosis and lactic acidosis. Ann Intern Med 1990; 113:580.
- Aronson PS, Giebisch G. Effects of pH on potassium: new explanations for old observations. J Am Soc Nephrol 2011; 22:1981.
- Peters AL, Buschur EO, Buse JB, et al. Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium-Glucose Cotransporter 2 Inhibition. Diabetes Care 2015; 38:1687.
- Smith SW, Manini AF, Szekely T, Hoffman RS. Bedside detection of urine beta-hydroxybutyrate in diagnosing metabolic acidosis. Acad Emerg Med 2008; 15:751.
- Oster JR, Rietberg B, Taylor AL, et al. Can beta-hydroxybutyrate be detected at the bedside by in vitro oxidation with hydrogen peroxide. Diabetes Care 1984; 7:80.
- Schabelman E, Kuo D. Glucose before thiamine for Wernicke encephalopathy: a literature review. J Emerg Med 2012; 42:488.
- Hack JB, Hoffman RS. Thiamine before glucose to prevent Wernicke encephalopathy: examining the conventional wisdom. JAMA 1998; 279:583.
- Miller PD, Heinig RE, Waterhouse C. Treatment of alcoholic acidosis: the role of dextrose and phosphorus. Arch Intern Med 1978; 138:67.
- Young A. Inhibition of glucagon secretion. Adv Pharmacol 2005; 52:151.
- PHYSIOLOGY OF KETONE BODIES
- FASTING KETOSIS
- Fasting ketoacidosis
- ALCOHOLIC KETOACIDOSIS
- Clinical presentation
- Laboratory findings
- - Hypoglycemia or hyperglycemia
- - Potassium depletion and hypokalemia
- - Phosphate depletion and hypophosphatemia
- - Magnesium depletion and hypomagnesemia
- - Elevated serum osmolal gap
- - Combined acid-base disorders
- Detection of ketone bodies
- - Nitroprusside testing
- False-negative nitroprusside testing
- False-positive nitroprusside testing
- - Direct measurement of serum beta-hydroxybutyrate
- Differential diagnosis
- Thiamine before dextrose in alcoholic patients
- Dextrose and saline solutions
- Potassium administration
- Phosphate administration
- Magnesium administration
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS