Vitamin A D E K😊😍

Vitamin A Deficiency

Conjunctival xerosis β†’ keratinisation of superficial epithelial cells β†’ Eye loses its lustre
Conjunctival xerosis β†’ keratinisation of superficial epithelial cells β†’ Eye loses its lustre
Bitot's spots- Foamy triangular patch on the temporal side of bulbar conjunctiva
Bitot's spots- Foamy triangular patch on the temporal side of bulbar conjunctiva
  • Sources: (in decreasing order ↓↓)
      1. Halibut fish (richest source)
      1. Palm oil.
      1. Dates
      1. Orange/yellow fruits (Pumpkin, papaya, mango).

Xerophthalmia

Grade
Stage (WHO)
Features
XN
Night blindness
1stΒ symptom, non specific feature
Most common presenting symptom
X1A
Conjunctival xerosis
1stΒ clinical sign
X1B
Bitot's spots
β€’ triangular spots
β€’ pearly white
Epidemiological marker
(Prevalence < 0.5%)
Most common indicator
Most common clinical sign for screening
Most specific presentation
X2
Corneal xerosis
Reversible till which stage: X2
X3A
Corneal ulcers/ Keratomalacia
< 1/3rd cornea
Irreversible changes
X3B
Corneal ulcers/ Keratomalacia
> 1/3rd of cornea
Irreversible changes
XS
Corneal scar
γ…€
XF
Xerophthalmic fundus
γ…€
  • Most sensitive screening test: Serum Retinol level
  • Zinc deficiency β†’ ↓ Retinol dehydrogenase β†’ Visual disturbance

Phrynoderma / follicular hyperkeratosis/ Toad Skin

Without 13-cis retinoic acid:

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  • Earliest skin manifestation: Dryness
  • Caused by Vitamin A or essential fatty acid deficiency.
  • Small papillary lesions
    • Dry, rough, hyperkeratotic papules
    • Small keratin plug is at the tip.
    • Near back of elbows, knees, joint areas
  • Pathology: Impaired follicular keratinisation (Vit A essential)

Toxicity

  • Mnemonic: Vitamin A cause everything to overgrow
    • Psedutotumor
    • Exfoliative
    • Bony exostosis
Type
Features
Acute
Pseudotumor cerebri β†’ ↑↑ ICT
Exfoliative dermatitis,
Hepatomegaly
Chronic (>50,000 IU/day)
Bony exostoses,
Cirrhosis
Pregnancy
Teratogenic – Contraindicated
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National Vitamin A prophylaxis program

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  • Dose:
    • 6 monthly doses
      • < 6 months: 50,000 IU
      • 6 months - 1 year or Weight < 8 kg 1,00,000 IU
      • > 1 year or > 8 kg 2 lakh IU
  • Total dose:Β 
    • 17 lac IU (9 megadoses)
    • Starting at 9 months
      • with measles rubella vaccine
      • One dose is given.
    • Then every 6 monthly intervals
  • Storage:Β 
    • Amber coloured bottle (Sensitivity to light > heat)
  • Measurement:
    • 2 mL = 2 lakh IU
    • 1 mL = 1 lakh IU

Rx for documented vit. A deficiency

  • Dose:Β 
    • 3 megadoses on Day 0, 1 & 14

Vitamin A Forms

  • Retinol:
    • Alcohol form
    • Alcohol is ingested and transported β†’ absorbed, transported
    • The form in which vitamin A is absorbed, transported, and stored.
    • Carr & Price reaction (colorimetric assay for retinol)
  • Retinal:
    • Aldehyde form.
    • Mnemonic: RetinaL β†’ Retina
    • Present in the eye as Rhodopsin
    • Without light, Rhodopsin is 11 cis Retinal surrounded by Opsin.
  • Retinoic acid:
    • Acid form.
        1. All Trans Retinoic Acid:
            • Helps in cell growth and differentiation.
        1. 13-Cis Retinoic Acid:
            • Suppresses epithelium keratinization.
            • Stimulates sebaceous gland apoptosis.

Some uses

Compound
Use
Ξ²-carotene
Cutaneous photosensitivity
All-trans retinoic acid
Promyelocytic leukemia (AML 3)(Differentiation therapy)
13-cis-retinoic acid (Isotretinoin)
Severe acne,
Childhood neuroblastoma

Eye Pathology:

  • No 13-cis retinoic acid.
    • No suppression of keratinization.
  • Conjunctiva keratinizes β†’ conjunctival Xerosis (dryness) β†’ Keratin debris β†’ Bitot's spots β†’ Corneal epithelium Keratinization β†’ Softening of the cornea is Keratomalacia β†’ Corneal ulcer β†’ Corneal scar.

Vitamin K Deficiency

Question:

  • Q. A woman with Antidepressants presents with bleeding. She gives a history of bulky stools which stick to the pan. Which of the following vitamin deficiencies can cause bleeding in this condition?
    • A. Vitamin A
    • B. Vitamin D
    • C. Vitamin E
    • D. Vitamin K
        • Explanation:
        • D. Vitamin K
          • Bulky stools that stick to the pan indicate Fat malabsorption.
          • Bleeding with fat malabsorption suggests Vitamin K malabsorption is the cause.

Vitamin K Structure

  • It has an Isoprenoid side chain.
    • The side chain causes lipid solubility.
  • Forms vary by the number of carbon atoms in the side chain.
    • K1 (Phylloquinone): 20 carbons.
      • Dietary form
      • Phyllode β†’ Leaf β†’ Feeding
    • K2 (Menaquinone): 30 carbons.
      • Intestinal flora
      • Newborns (esp. preterm): no gut flora
        • β†’ no endogenous Vit K β†’ Hemorrhagic disease of newborn
      • Depend on exogenous Vit K
      • Vayattil ullath Mena queen
    • Menadione: Has no side chain (R=H).
      • Synthetic form
      • It is water-soluble
      • Can be prescribed for bleeding from fat malabsorption.
      • Dying β†’ Dione
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Vitamin K Function

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  • Acts as a coenzyme for
    • gamma carboxylation /
    • post translational carboxylation.
  • This activates:
    • Clotting Factors 2, 7, 9 & 10.
    • Protein C & S.
    • Osteocalcin.
  • Inactive Epoxide form β†’ Active hydroquinone form of Vitamin K
    • by Epoxide reductase.

Warfarin

  • β›”Epoxide reductase
    • ⇏ Vitamin K active form
    • β›” gamma carboxylase ⇏ Ξ³Β carboxyglutamic acidΒ 
    • Prevent activation of
      • 2, 7, 9, 10
        • Order of decline (fastest β†’ slowest)
        • 7 > 9 > 10 > 2
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      • Protein CΒ &Β protein S
        • Responsible for Prothrombotic action initial days
    • Oral anticoagulant
    • Takes 4-5 days to produce action
    • Mainly used for maintenance purpose
    • Contraindicated in pregnancy β†’
    • Effect of Warfarin is monitored by PT/INR
      • Target INR for Post valve replacement: 2.5 - 3.5

Features of Vitamin K deficiency

  • Newborn
    • Haemorrhagic disease of newborn
  • In older children,
    • Vitamin K deficiency bleeding.

Treatment:

  • By administration of Vitamin K.

In severe bleeding:

  • Four Factor concentrate
  • Fresh frozen plasma.

Drugs Affecting Vitamin K

Category
Examples
Mechanism
Vit. K epoxidase inhibitors
Warfarin,
Dicumarol
β›” Ξ³-carboxylation of II, VII, IX, X
Lipase inhibitors
Orlistat
↓ Fat absorption β†’ ↓ Vit. K absorption
Ammonia-reducing agents
Sodium benzoate,
Phenylbutyrate
Form conjugates with glycine/glutamine
β†’ ↑↑ renal excretion

Ammonia Scavengers

  • Phenyl butyrate (prodrug)
    • Phenyl acetate + Glutamine β†’ Phenyl acetyl glutamine (excreted)
    • Mnemonic: But β†’ Glut
  • Sodium benzoate + Glycine β†’ Benzoyl glycine/hippurate (excreted)
    • (via Glycine synthase)
    • Mnemonic: Benz β†’ Glazing
  • Glycine requires NH₃ + COβ‚‚ + 1 Carbon group

Vitamin E

  • Strongest and most potent antioxidant
  • Most potent lipid-phase chain-breaking antioxidant
  • Forms: Tocopherols & Tocotrienols
    • Most active: Alpha-tocopherol

Therapeutic Uses

  • Retrolental fibroplasia
  • Intermittent claudication
  • Bronchopulmonary dysplasia
  • Intraventricular hemorrhage
  • Delays aging
  • Prevents fatty liver

Deficiency

  • Similar to Vitamin B12 deficiency but:
    • No megaloblastic anemia
    • No hypersegmented neutrophils
    • Normal methylmalonic acid
  • Mimics Friedreich ataxia
  • Hemolytic anemia
  • Neuropathy
    • Axonal degeneration
    • Demyelination of posterior columns β†’ ↓ proprioception, vibration
    • Peripheral neuropathy
    • Spinocerebellar ataxia
  • Eye signs
    • Pigmentary retinopathy,
    • Ophthalmoplegia,
    • Nystagmus

Toxicity

  • Inhibits platelet aggregation
  • Antagonizes Vitamin K
  • Vitamin E to ↑↑ beauty β†’ Bleeding

Use

  • Vitamin E β†’ First line Rx of NASH
  • New drug for NASH: Resmetirom (2024)
    • thyroid hormone receptor-beta (THR-beta) agonist
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  • Not approved, can be given
    • Metformin
    • Liraglutide
    • Pioglitazone β†’ PPAR Ξ³
    • Saroglitazor β†’ PPAR Ξ± + Ξ³
    • Lanifibranor β†’ Pan PPAR (Ξ± + Ξ² + Ξ³)

NOTE

  • Pioglitazone β†’ PPAR Ξ³
  • Saroglitazor β†’ PPAR Ξ± + Ξ³
  • Lanifibranor β†’ Pan PPAR (Ξ± + Ξ² + Ξ³)
  • Telmisartan, Losartan β†’ PPAR-Ξ³
  • PPAR-Ξ³ (Proliferator-activated receptor Ξ³)
    • Nuclear receptor
    • Helps differentiation of mesenchymal preadipocytes to adipose cells in peroxisome
    • Also binds thiazolidinedione
      • Class of insulin-sensitizing drugs
      • Used in treatment of T2DM
  • Mnemonic: PPAR Ξ³
    • ARBS
    • Zones
    • Fibrates β†’ PPAR Ξ±
    • Pappa Pappa movie β†’ Animal (ARBS) β†’ in Zoo (Zones)

Vitamin D

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Form
Source
D2 (Ergocalciferol)
Plants,
D3 (Cholecalciferol)
Animal sources,
synthesized in skin
Storage
25-OH D3
Active (most potent)
1,25-(OH)β‚‚ D3 (Calcitriol)
Β 

Rickets

Deficiency causes:

  • Rickets in children
  • Osteomalacia in adults

Richest source:

  • Cod fish.

Clinical feature in children:

  • Bow legs (Genu varum)

Note:

  • Genu valgum = Knock-knee syndrome

Vitamin D Toxicity β†’ Hypercalcemia

  • d/t intake of 60000 IU tabs
  • Rx:
    • Glucocorticoids
      • β†’ β›” Vitamin D β†’ ↓ intestinal absorption of calcium β†’ ↑ Urinary excretion of calcium β†’ Resulting in negative calcium balance

Richest sources of vitamins and minerals

  • Vitamin A: Halibut fish.
    • A β†’ Alia bhatt β†’ halibut
  • Vitamin C: Amla (Indian gooseberry).
    • Camala (C β†’ Amla)
  • Vitamin B1:
    • Gingelly seeds
    • Organ meat, husk of grains and nuts (Parboiled grains).
  • Vitamin B12:
    • Organ meat (No plant sources).
  • Vitamin D:
    • Cod fish.
      • De (Vit D) code (Cod fish)
  • Iodine: Japanese seaweed.
  • Iron: Heme sources, pumpkin seeds.
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