As was already discussed, vitamin A is a component of rhodopsin and other visual pigments. Not surprisingly, one of the earliest manifestations of vitamin A deficiency is impaired vision, particularly in reduced light (night blindness).
Other effects of vitamin A deficiency are related to its role in maintaining the differentiation of epithelial cells (
Fig. 8.19 ). Persistent deficiency gives rise to a series of changes involving epithelial metaplasia and keratization. The most devastating changes occur in the eyes and result in the clinical entity referred to as xerophthalmia (dry eye). First, there is dryness of the conjunctiva (xerosis conjunctivae) as the normal lachrymal and
Bitot spots Corneal ulcer Keratomalacia Advanced metaplasia Increased cancer?
Fig. 8.19 Vitamin A deficiency: major consequences in the eye and in the production of keratinizing metaplasia of specialized epithelial surfaces, and its possible role in epithelial metaplasia. Not depicted are night blindness and immune deficiency.
mucus-secreting epithelium are replaced by keratinized epithelium. This is followed by a buildup of keratin debris in small opaque plaques (Bitot spots) and, eventually, the erosion of the roughened corneal surface, leading to softening and destruction of the cornea (keratomalacia) and total blindness.
Vitamin A deficiency also leads to replacement of the epithelium lining the upper respiratory passage and urinary tract by keratinizing squamous cells (squamous metaplasia). Loss of the mucociliary epithelium of the airways predisposes affected patients to pulmonary infections, and desquamation of keratin debris in the urinary tract predisposes to renal and bladder stones. Hyperplasia and hyperkeratinization of the epidermis with plugging of the ducts of the adnexal glands may produce follicular or papular dermatosis.
Another serious consequence of the lack of vitamin A is immune deficiency. This impairment of immunity leads to higher mortality rates from common infections such as measles, pneumonia, and infectious diarrhea. In parts of the world with a high prevalence of vitamin A deficiency, dietary supplements reduce mortality rates for infectious disorders by 20% to 30%.
Vitamin A Toxicity. Both shortand long-term excesses of vitamin A may produce toxic manifestations—a point of concern because of the megadoses being touted by certain sellers of supplements. The consequences of acute hypervitaminosis A were first described in 1597 by Gerrit de Veer, a ship’s carpenter stranded in the Arctic, who recounted in his diary the serious symptoms that he and other crew members developed after eating polar bear liver. With this cautionary tale in mind, the adventurous eater should note that acute vitamin A toxicity also has been described in “hepatoaficionados” who feasted on the livers of whales, sharks, and even tuna!
The signs and symptoms of acute toxicity include headache, dizziness, vomiting, stupor, and blurred vision—all of which may be confused with those of a brain tumor. Chronic toxicity is associated with weight loss, anorexia, nausea, vomiting, and bone and joint pain. Retinoic acid stimulates the production and function of osteoclasts, leading to increased bone resorption and a consequent high risk of fractures. Although synthetic retinoids used for the treatment of acne are not associated with these complications, their use in pregnancy must be avoided because of the well-established teratogenic effect of retinoids.