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

Alcoholic Ketoacidosis

• Ketone body processing overview

• Ketogenesis and ketone body utilization

• Clinical features

Ketone Body Processing Overview

TAG

FAKetone Bodies

adipose tissue

muscle

LeuIle

Lys

PheTyr

Trp αKAliverAT

HSL

Albumin

EpinephrineNorepinephrine

Energy for the Brain and Nerves

β-oxidation

ketogenesis

Thr

Ketogenesis and Ketone Body Utilization

TCA

neuronmitochondrion

TAG

Acetyl CoA

AACoA

HMGCoA

AA 3HB

β-oxidation

AA CoA thiolase

HMG CoA synthase

HMG CoA lyase

3HBDH

Acetone

Ile, Thr

Lys, Trp

Leu

Tyr, Phe

hepatocytemitochondrion

AA 3HB3HBDH

AACoA

Acetyl CoA

Generates lots of ATP

AACoAT

3KACoAT

SCoASuc

NADH NAD+ NADH NAD+

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 examinationTachycardia, 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?