Functions

• Vision: component of rhodopsin as 11-cis-retinal
• Gene transcription
  • All-trans retinoic acid (ATRA) binds to its nuclear receptors (retinoic acid receptors, RAR; retinoid X receptors, RXR) → receptor dimerization → binding to DNA → uncoiling of chromatin → exposure of promoter regions of genes → binding of transcription factors to promoter → initiation of transcription and cell differentiation
  • Regulation of various genes responsible for cell growth, cell differentiation, apoptosis, reproduction (e.g., spermatogenesis), and embryonic development
• Tissue maintenance and cell differentiation
  • Mainly retinoic acid
  • Promotes differentiation of epithelium into specialized tissue (e.g., pancreatic cells and goblet cells)
  • Prevents metaplasia of squamous cells
• Antioxidant

Vitamin A deficiency

Causes

• Disorders associated with fat malabsorption: inflammatory bowel disease (e.g., Crohn disease), celiac disease, cystic fibrosis, pancreatic insufficiency
  • Exocrine pancreatic insufficiency → lack of digestive enzymes → malabsorption of carbohydrates, proteins, fats, fat-soluble vitamins (A, D, E, K), and vitamin B12

Clinical features

Triad of

• Night blindness
• Dry eyes, Bitot spots
• Hyperkeratosis

• Ocular manifestations
  • Night blindness (nyctalopia)
  • Retinopathy
  • Xerophthalmia
  • Keratomalacia
  • Bitot spots: gray, triangular, dry patches on the bulbar conjunctiva, covered by a layer with a foamy appearance
    • Typical sign of vitamin A deficiency
    • Caused by squamous cell metaplasia and keratinization of the conjunctiva
• Keratinizing squamous metaplasia of the bladder (pearl-like plaques on cystoscopy)
• Xerosis cutis
• Immunosuppression: Vitamin A deficiency increases the risk of a measles infection taking a severe course.

Vitamin A toxicity

• Acute: A single high dose can cause nausea, vomiting, vertigo, and blurred vision.
• Chronic (most common): Long-term ingestion of excessive vitamin A can lead to increased intracranial pressure (ie, benign intracranial hypertension). Other nonspecific symptoms include increased bone resorption (eg, osteoporosis, fractures) as well as alopecia and dry skin and mucous membranes. Because vitamin A is stored in the liver, hypervitaminosis A is hepatotoxic and can cause elevated aminotransferases, hepatomegaly, and liver fibrosis.
• Teratogenic: Excessive first trimester intake can cause neural crest cell toxicity, resulting in fetal microcephaly, craniofacial defects, cardiac anomalies, and death.