Malnutrition: Biochemical Consequences

Malnutrition Basics - Empty Tank Signals

• Malnutrition: Nutrient intake imbalance. PEM: Protein-Energy Malnutrition. Undernutrition: Low intake/infections.
• 📌 Marasmus = Muscle Wasting, Miserable.
• Key PEM types (Wellcome criteria):

  Feature	Marasmus	Kwashiorkor
  Edema	No	Yes (pitting)
  Body Wt % (age)	< 60%	60-80% (+edema)
  SC Fat	↓↓↓	↓ (preserved)
  Muscle Wasting	Severe	Severe (masked)
  Appetite	Good	Poor
  Hair	Sparse	Flag sign
  Mental	Irritable	Apathetic

⭐ Kwashiorkor, meaning “the sickness the older child gets when the next baby is born,” often develops after abrupt weaning to a low-protein, high-carbohydrate diet.

• Severe Acute Malnutrition (SAM): MUAC < 11.5 cm or Wt/Ht Z-score < -3 SD.

Marasmus - The Great Adaptation

• 📌 MARASMUS: Metabolic Adaptation, Reduced Adipose tissue, Severe wasting, Muscle breakdown, Usually alert, Starvation response.
• Biochemical Basis: Adaptive response to prolonged starvation, conserving protein.
• Hormonal Profile:
  • $Insulin \downarrow$ (decreased glucose uptake by peripheral tissues).
  • $Cortisol \uparrow$ (catabolic; permissive for gluconeogenesis, proteolysis).
  • $GH \uparrow$ (lipolytic; peripheral insulin resistance blunts anabolic effects).
  • $Glucagon \uparrow$ (stimulates glycogenolysis, gluconeogenesis, ketogenesis).
• Metabolic Changes (Adaptation):
  • Efficient fat mobilization: Lipolysis $\rightarrow$ FFAs, glycerol (primary fuel source).
  • Muscle protein breakdown $\rightarrow$ amino acids (substrate for gluconeogenesis).
  • Ketogenesis $\rightarrow$ ketone bodies (alternative brain fuel, sparing glucose).
  • Relative preservation of visceral protein synthesis (e.g., albumin) initially.
• Clinical: Severe wasting ('wizened old man' face), growth retardation, alert/irritable.

⭐ In marasmus, serum albumin levels are often near-normal or only slightly reduced due to adaptive conservation of visceral protein synthesis.

Kwashiorkor - Deceptive Swell

• Biochemical 'dysadaptation' to protein-energy malnutrition.
• Key Features:

  • Hypoalbuminemia (Serum albumin $< \textbf{2.8 g/dL}$): ↓Synthesis (essential AA deficiency, oxidative stress) → ↓oncotic pressure → edema.

  • Fatty liver (hepatomegaly): ↓Apolipoprotein B-100 synthesis → impaired VLDL export.

  • Oxidative stress: ↓Glutathione, ↓Vit E, C; ↑free radicals.

  • Electrolyte imbalance: Intracellular ↓K⁺, ↓Mg²⁺ (serum K⁺ normal/↑).

  • Immune dysfunction: ↓Lymphocytes, ↓cytokines.

  • Skin/Hair: 'Flaky paint' dermatosis, flag sign.

  • Hormonal: Insulin normal/↑ (ineffective), ↑cortisol, ↓IGF-1.

• 📌 Mnemonic: Kwashiorkor Has Low Protein Signs: K=↓K⁺ (intracellular), H=Hypoalbuminemia, L=Fatty liver, P=Edema/Psychomotor changes, S=Skin lesions.

⭐ Reduced synthesis of apolipoprotein B-100 is a key factor in the development of fatty liver in kwashiorkor, leading to impaired export of triglycerides from hepatocytes.

Starvation & Refeeding - Metabolic Tightrope

• Prolonged Starvation: Further $\downarrow$ BMR; brain adapts to ketone bodies (spares glucose/protein); micronutrient depletion.
• Refeeding Syndrome:
  • Pathophysiology: Insulin $\uparrow$ (refeeding) $\rightarrow$ catabolism to anabolism shift $\rightarrow$ massive intracellular uptake of $PO_4^{3-}$, $K^+$, $Mg^{2+}$. Thiamine (Vit B1) deficiency exacerbates (cofactor for CHO metabolism).
  • Biochemical Hallmarks:
    • Hypophosphatemia ($PO_4^{3-} \downarrow$): Key, < 0.5 mmol/L (severe).
    • Hypokalemia ($K^+ \downarrow$): < 3.5 mmol/L.
    • Hypomagnesemia ($Mg^{2+} \downarrow$): < 0.7 mmol/L.
  • Consequences: Cardiac (arrhythmias, failure), respiratory (failure), neurological (seizures, Wernicke's), hematological.
  • Prevention: Gradual refeeding; electrolyte monitoring & repletion; prophylactic thiamine (100-300 mg/day).
  • 📌 REFEEDING: Remember Electrolytes, Fluids, Especially Electrolytes, Don't Introduce Nutrients Greedily. Key ions: P, K, Mg.

⭐ Thiamine supplementation is crucial before initiating nutritional support in severely malnourished patients to prevent Wernicke’s encephalopathy, as carbohydrate refeeding increases thiamine demand.

High‑Yield Points - ⚡ Biggest Takeaways

• Kwashiorkor: Key features are edema, hypoalbuminemia, fatty liver, skin lesions (flaky paint dermatosis), and flag sign hair.
• Marasmus: Presents with severe muscle wasting, loss of subcutaneous fat (wizened face), no edema, and an alert, irritable state.
• PEM leads to impaired immune function (especially cell-mediated), increased susceptibility to infections, and critical electrolyte imbalances.
• Common micronutrient deficiencies include Iron (microcytic anemia), Iodine (goiter, hypothyroidism), and Vitamin A (xerophthalmia, Bitot's spots).
• Refeeding syndrome is a life-threatening risk: watch for hypophosphatemia, hypokalemia, hypomagnesemia, and potential cardiac/neurological complications during initial re-nutrition.
• Metabolic adaptation to starvation involves ↓ BMR, initial gluconeogenesis from amino acids, then reliance on fatty acid oxidation and ketone body production to spare protein.
• Chronic malnutrition results in stunted growth, delayed development, and impaired cognitive function in children, with long-lasting effects on health and productivity.