1. Eric Niederhoffer SIU-SOM How does ethanol ingestion cause nutrition problems? A 38-year-old woman is brought to the physician because of frequent falls, increasing confusion, and incontinence

2. Alcoholic Ketoacidosis Ketone body processing overview Ketogenesis and ketone body utilization Clinical features

3. Ketone Body Processing Overview TAG FA Ketone Bodies adipose tissue muscle Leu Ile Lys Phe Tyr Trp αKA liver AT HSL Albumin Epinephrine Norepinephrine Energy for the Brain and Nerves β-oxidation ketogenesis Thr

4. Ketogenesis and Ketone Body Utilization TCA neuron mitochondrion TAG Acetyl CoA AACoA HMGCoA AA3HB β-oxidation AA CoA thiolase HMG CoA synthase HMG CoA lyase 3HBDH Acetone Ile, Thr Lys, Trp Leu Tyr, Phe hepatocyte mitochondrion AA3HB 3HBDH AACoA Acetyl CoA Generates lots of ATP AACoAT 3KACoAT SCoA Suc NADHNAD + NADHNAD +

5. Clinical Features (H&P) History (Typical symptoms reflect poor nutritional status from long-term alcohol abuse) poor nutrition volume depletion ketone bodies buildup Nausea, vomiting, and abdominal pain (each found in 60-75% of patients) Dyspnea, tremulousness, and/or dizziness (10-20% each) Muscle pain, diarrhea, syncope, and seizure (1-8% each) Physical examination Tachycardia, tachypnea, and/or abdominal tenderness (30-40% each) Hypotension, hypothermia, fever, abdominal distention, rebound tenderness, hepatomegaly, ascites, and/or heme-positive stools (1-15% each.)

6. Clinical Features (Laboratory Studies) Arterial blood gas Look for M acid, may have mixed acid-base disorder (M acid from ketone formation, M alk from vomiting/volume depletion, R alk secondary to hyperventilation) Serum ketones Order specific test of [3HB]; ([3HB]/[AA] > 5) Glucose and electrolytes Decreased, normal, or increased serum [Glc] (in DKA, serum [Glc] increased) Increased anion gap Increased serum [lactate] Increased serum [urea nitrogen] and [creatinine] Complete blood count Looking for anemia, intravascular volume depletion Liver and pancreatic function tests Total bilirubin, ALT, AST, LDH, AP, PA, PL Alcohol levels Patient may have decreased drinking; generally does not change approach

7. Review Questions What are ketone bodies? Which amino acids are ketogenic? How are ketone bodies generated (substrates, enzymes, pathways, location)? How are ketone bodies metabolized (enzymes, pathways, location)? What is the effect of NADH levels on ketone bodies? How does the metabolism of ketone bodies correlate with clinical findings?