Fat-Soluble Vitamins: A, D, E, K

Fat-Soluble Vitamins Overview - The Fab Four Intro

• Vitamins A, D, E, K - "ADEK" 📌.
• Absorption: Requires dietary fats, bile salts, and micelle formation. Transported via chylomicrons.
• Storage: Primarily in liver and adipose tissue (Vitamin K has limited storage).
• Excretion: Slow, mainly fecal; potential for toxicity (esp. A & D).

⭐ Fat-soluble vitamins are stored in the body; deficiencies develop slowly, but toxicity is a greater risk compared to water-soluble vitamins due to accumulation.

Vitamin A - Vision & Vampires

• Forms & Roles: Retinol (storage), Retinal (vision - rhodopsin), Retinoic Acid (epithelial differentiation, immunity).
• Sources: Animal (e.g., liver), Plant (β-carotene, e.g., carrots).
• Vision Cycle: 11-cis-retinal + opsin ⇌ Rhodopsin. Light: 11-cis → all-trans-retinal → signal.
• Deficiency:
  • Nyctalopia (earliest).
  • Xerophthalmia (Bitot's spots, keratomalacia).
  • Squamous metaplasia.
  • Impaired immunity.
• Toxicity:
  • Acute: N/V, headache.
  • Chronic: alopecia, dry skin, hepatomegaly, ↑ICP, bone pain.
  • ⚠️ Teratogenic (isotretinoin).

⭐ Bitot's spots: Foamy, cheesy, triangular keratinized plaques on bulbar conjunctiva; pathognomonic for Vitamin A deficiency.

Vitamin D - Sunshine Powerhouse

• Forms & Sources:
  • • D3 (Cholecalciferol): Synthesized in skin (7-dehydrocholesterol + UV-B); fish oils, liver.
  • • D2 (Ergocalciferol): From ergosterol in plants/yeast; fortified foods.
• Activation (2-step hydroxylation):

*   - Calcidiol ($25-OH$ Vit D): Produced in liver; precursor to active form.
*   - Calcitriol: Active hormone; synthesis ↑ by PTH, ↓$Ca^{2+}$, ↓$PO_4^{3-}$.

• Functions (Calcitriol):
  • • ↑ Intestinal $Ca^{2+}$ & $PO_4^{3-}$ absorption.
  • • ↑ Renal $Ca^{2+}$ & $PO_4^{3-}$ reabsorption.
  • • Modulates bone mineralization & resorption.
• Deficiency: Rickets (children: bone deformities, growth retardation), Osteomalacia (adults: bone pain, fractures); due to impaired mineralization.
• Toxicity: Hypercalcemia, hypercalciuria, nephrocalcinosis, metastatic calcification (e.g., in kidneys, arteries).

⭐ $25-OH$ Vitamin D (Calcidiol) is the major circulating form and best indicator of Vitamin D status.

Vitamin E - Antioxidant Ace

• Forms: Tocopherols (α-tocopherol: most active) & Tocotrienols.
• Function: Major membrane-bound, lipid-soluble antioxidant.
  • Protects PUFAs in cell membranes from lipid peroxidation by free radicals.
  • Scavenges reactive oxygen species (ROS).
• Sources: Vegetable oils (sunflower), nuts (almonds), seeds (sunflower), wheat germ, green leafy veg.
• Deficiency: Rare.
  • Premature infants: Hemolytic anemia.
  • Adults: Spinocerebellar ataxia, myopathy, peripheral neuropathy, retinopathy.
• Toxicity: Least toxic fat-soluble vitamin.
  • High doses (> 1000 mg/day) may impair Vitamin K action (↑ bleeding risk).

⭐ Deficiency causes acanthocytosis (spur cells) and hemolytic anemia, especially in neonates.

Vitamin K - Clotting Kingpin

• Types & Sources:
  • K1 (Phylloquinone): Green leafy vegetables.
  • K2 (Menaquinone): Gut bacteria synthesis.
  • K3 (Menadione): Synthetic (risk of hemolysis in G6PD def.).
• Function: 📌 "K for Koagulation"
  • Coenzyme for γ-glutamyl carboxylase.
  • γ-carboxylation of glutamate (Glu → Gla) on Factors II, VII, IX, X, Proteins C & S.
• Deficiency:
  • ↑PT/INR, bleeding.
  • Hemorrhagic Disease of Newborn (HDN): Routine neonatal prophylaxis.
  • Causes: Malabsorption, antibiotics, liver disease, warfarin.
• ⭐ > Warfarin competitively inhibits Vitamin K epoxide reductase (VKOR), blocking regeneration of active Vitamin K hydroquinone.
• Clinical Use: Reversal of warfarin anticoagulation.

High‑Yield Points - ⚡ Biggest Takeaways

• Vitamin A: Deficiency causes night blindness, Bitot's spots, keratomalacia. Toxicity: pseudotumor cerebri, teratogenic.
• Vitamin D: Deficiency leads to rickets (children) & osteomalacia (adults). Active form: 1,25-(OH)2 D3.
• Vitamin E: Potent lipid-soluble antioxidant. Deficiency: hemolytic anemia, spinocerebellar degeneration.
• Vitamin K: Essential for γ-carboxylation of clotting factors II, VII, IX, X, Protein C & S.
• Warfarin is a Vitamin K antagonist. Deficiency or antagonism causes bleeding disorders.
• All fat-soluble vitamins require bile salts for absorption; deficiencies common in malabsorption syndromes.