A 38-year-old woman is brought to the physician
because of frequent falls, increasing confusion, and
incontinence
How does ethanol ingestion cause nutrition problems?
Eric Niederhoffer
SIU-SOM
Alcoholic Ketoacidosis
• Ketone body processing overview
• Ketogenesis and ketone body utilization
• Clinical features
Ketone Body Processing Overview
Energy for the Brain and Nerves
TAG
Epinephrine
Norepinephrine
HSL
Ketone Bodies
FA
adipose tissue
Thr
Leu Phe Tyr
Ile
Lys Trp
muscle
Albumin
ketogenesis
β-oxidation
AT
αKA
liver
Ketogenesis and Ketone Body Utilization
TAG
Generates lots of ATP
β-oxidation
hepatocyte
mitochondrion
Acetyl CoA
Ile, Thr
Acetyl CoA
AA CoA thiolase
AACoA
Lys, Trp
HMG CoA synthase
HMGCoA
AACoAT
Suc
AACoA SCoA
Leu
HMG CoA lyase
AA
TCA
3HBDH
Tyr, Phe
3HB
NADH NAD+
Acetone
3KACoAT
AA
3HBDH
3HB
NADH NAD+
neuron
mitochondrion
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.)
Clinical Features (Laboratory Studies)
•
Arterial blood gas
Look for Macid, may have mixed acid-base disorder (Macid from ketone formation, Malk from vomiting/volume
depletion, Ralk 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
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?