STEPTRACKERBIOCHEMISTRY + PHARMACOLOGY + PEDIATRICS | NUTRITION | HIGH-YIELD REVIEW

Malnutrition & Ethanol Metabolism

Protein vs total-calorie starvation, the danger of feeding too fast, and how alcohol's extra NADH rewires the liver.

FOCUS ON
Kwashiorkor = protein deficiency with some calories → edema, fatty liver, flaky skin. Marasmus = total calorie deficiency → muscle wasting, no edema. Refeeding → ↓ PO₄, ↓ K⁺, ↓ Mg. Ethanol: alcohol dehydrogenase → acetaldehyde → aldehyde dehydrogenase → acetate, both make NADH → ↑ NADH/NAD⁺ → lactic acidosis, hypoglycemia, fatty liver, ketoacidosis.
TOPIC
MECHANISM
FINDINGS
CLUE · TREATMENT
Kwashiorkor
Inadequate protein, adequate carbs → ↓ albumin (oncotic pressure) and ↓ apolipoproteins (fat can't leave liver)
Pitting edema, distended abdomen, fatty liver, skin lesions, depigmented hair, anemia
Child weaned onto starchy diet
Marasmus
Total energy deficiency
Severe muscle and fat wasting, "old man" face, no edema
"Marasmus = muscle wasting"
Refeeding syndrome
Insulin surge on refeeding → cellular uptake of PO₄, K⁺, Mg²⁺; phosphate used for ATP
↓ PO₄ (cardiac/respiratory failure, rhabdomyolysis), ↓ K⁺, ↓ Mg, fluid overload, thiamine depletion
Anorexia, alcoholism, prolonged fasting · start slowly, replace electrolytes and thiamine
Alcohol dehydrogenase
Ethanol → acetaldehyde (cytosol); zero-order kinetics
Makes NADH
Fomepizole blocks it (methanol, ethylene glycol poisoning)
Aldehyde dehydrogenase
Acetaldehyde → acetate (mitochondria)
Makes NADH
Disulfiram blocks it → flushing, nausea, tachycardia · ALDH2*2 variant in East Asians (flushing)
MEOS (CYP2E1)
Induced by chronic drinking
↑ Metabolism of alcohol and some drugs; ↑ acetaminophen toxicity (NAPQI)
Tolerance in heavy drinkers
↑ NADH: hypoglycemia
Pyruvate → lactate and oxaloacetate → malate → ↓ gluconeogenesis substrates
Fasting hypoglycemia
Binge drinker found confused
↑ NADH: lactic acidosis
Pyruvate → lactate
Anion gap acidosis
Also ↓ uric acid excretion → gout
↑ NADH: fatty liver
DHAP → glycerol-3-P ↑ + ↓ β-oxidation → triglyceride synthesis
Hepatic steatosis (reversible)
First stage of alcoholic liver disease
Alcoholic ketoacidosis
↑ NADH shifts acetoacetate → β-hydroxybutyrate; acetyl-CoA → ketones, TCA inhibited
Anion gap acidosis, normal/low glucose
Urine dipstick (detects acetoacetate) may be falsely weak

Mechanism — ethanol and the NADH flood

Ethanol
→
ADH(fomepizole)
→
Acetaldehyde
→
ALDH(disulfiram)
→
Acetate
NAD⁺ → NADH at both steps
→
Pyruvate → lactate · OAA → malate · DHAP → G3P
→
Hypoglycemia, lactic acidosis, fatty liver, ketoacidosis

Kwashiorkor vs marasmus

FEATURE
KWASHIORKOR
MARASMUS
Deficit
Protein
Total calories
Edema
Yes
No
Fatty liver
Yes
No
Wasting
Masked by edema
Severe
Albumin
Very low
Near normal

How it's tested

COMMON CONFUSIONFomepizole blocks alcohol dehydrogenase (toxic alcohols); disulfiram blocks aldehyde dehydrogenase (aversion therapy).
THE TRAPA severely malnourished patient started on full feeds develops weakness and heart failure on day 2–3 — refeeding hypophosphatemia.
YOUR APPROACHFor alcohol, trace each problem back to excess NADH; for malnutrition, ask whether protein or total energy is missing and whether feeding just restarted.

If you see… think…

Swollen-bellied child with edema, fatty liver → kwashiorkor
Emaciated child, no edema → marasmus
Weakness, arrhythmia days after refeeding → hypophosphatemia (refeeding)
Flushing and vomiting when drinking on medication → disulfiram
Antidote for ethylene glycol or methanol → fomepizole
Binge drinker with fasting hypoglycemia → ↑ NADH blocks gluconeogenesis
Heavy drinker with acetaminophen hepatotoxicity at low dose → CYP2E1 induction
Alcoholic with anion gap acidosis, normal glucose → alcoholic ketoacidosis
Ketone that dominates in alcoholic ketoacidosis → β-hydroxybutyrate
Asian patient with facial flushing after one drink → ALDH2 variant