Vitamin A deficiency can be primary, due to lack of vitamin A in the diet, or secondary, due to impaired absorption or utilization of vitamin A. Clinical signs of deficiency include night blindness and xerophthalmia, initially presenting as dry eyes and progressing to corneal ulceration and keratomalacia if untreated. Laboratory tests of serum retinol and RBP levels can diagnose deficiency, defined as levels less than 0.70 μM. Treatment involves large oral doses of vitamin A supplements to replenish liver stores.

1. Vitamin A deficiency
Domina Petric, MD

2. Introduction
• Hepatic stores are great enough to provide
retinol.
• The plasma retinol level is only minimally
affected by vitamin A deprivation.
• Cellular functions of vitamin A can be expected to
change only after transport of the vitamin is
reduced, after vitamin A stores have dropped to
such levels as to reduce plasma retinol–RBP
concentrations.
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

3. Adequate vitamin A status
Hepatic retinyl ester stores
>20 µg (>0.07 µmol) RE per
gram indicate adequate
vitamin A status.
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

4. Vitamin A deficiency
Primary vitamin A deficiency: lack of
both provitamins A and preformed
vitamin A in diets.
Secondary vitamin A deficiency: failures
in provitamins A and preformed vitamin
A in their physiologic utilization.
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

5. Primary vitamin A deficiency
• Primary vitamin A deficiency can occur
among children and adults who consume
diets composed of few servings of yellow
and green vegetables and fruits and
liver.
• For infants and young children, early
weaning can increase the risk of primary
deficiency.
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

6. Secondary vitamin A deficiency
• Chronically impaired enteric absorption of
lipids, such as in diseases affecting the
exocrine pancreas: pancreatitis, cystic
fibrosis, nutritional selenium deficiency.
• Impaired bile production and release:
biliary atresia.
• Consumption of diets containing very low
amounts of fat.
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

7. Secondary vitamin A deficiency
Chronic exposure to oxidants can also induce vitamin A
depletion: benzo(α)pyrene in cigarette smoke.
Nutritional deficiencies of zinc can also impair the
absorption, transport, and metabolism of vitamin A.
Zinc is essential for the hepatic synthesis of RBP and the
oxidation of retinol to retinal, which is catalyzed by a
zinc-dependent retinol dehydrogenase.
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

8. Secondary vitamin A deficiency
Malnourished populations,
which typically have low intakes
of several essential nutrients
including vitamin A and zinc, are
at risk to vitamin A deficiency.
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

9. Detecting vitamin A deficiency
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

10. Clinical signs
• Clinical signs include impaired dark adaptation,
nyctalopia and ocular lesions.
• Nyctalopia is the first functional sign of vitamin A
deficiency that can be measured.
• The condition can be detected by using the
papillary response to a graduated light stimulus.
• Examination by slit lamp can reveal fundus specs
and disrupted rod outer segments with the
possible involvement of similarly disrupted
cones.
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

11. Clinical signs
Ocular lesions can be diagnosed by direct examination
of the eye:
• conjunctival xerosis with or without
Bitot’s spots
• corneal xerosis
• ulceration
• keratomalacia
• corneal scars
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

12. April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
Bitot´s spot
Flickr.com

13. Bitot´s spot
• Almost always bilateral oval or triangular
structures first appearing temporal to the
limbus and comprising a thickened,
superficial layer of flattened cells usually
with a keratinizing surface,
a prominent granular cell layer, and
acanthotic thickening with a disorganized
basal cell layer, but with no goblet cells.
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

14. Conjunctival impression cytology
Morphological changes in epithelial cells
blotted from the conjunctival surface can
be detected by histologic examination.
The presence of enlarged, flattened
epithelial cells and few or no goblet cells
is indicative of vitamin A deficiency.
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

15. Progression of vitamin A deficiency
• With progressing vitamin A deficiency,
the conjunctival surface takes on a dry,
corrugated, irregular surface,
ultimately developing an overlay of
white, foamy, or “cheesy” material
consisting of desquamated keratin and
a heavy bacterial
growth.
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

16. First sign
Fine, fluorescein-positive, superficial punctuate
keratopathy that usually begins in the inferior
aspect of the cornea, particularly inferonasally.
These lesions can be seen using the slit
lamp microsope.
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

17. April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
Superficial punctate keratopathy
Myalcon.com

18. Progression
• The lesions become more numerous and
concentrated, involving larger portions of
the corneal surface.
• By the time most of the corneal surface is
involved, the lesions are generally apparent
by hand–light examination as a haziness
and diminished wettability on the corneal
surface: corneal xerosis.
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

19. April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
Corneal xerosis
Flickr.com

20. Progression
• Corneas affected at this level of corneal xerosis also
show stromal edema, mostly in the inferior aspect.
• If untreated, the condition progresses to the
point of corneal ulceration, frequently characterized
by the presence of a single (or sometimes two to
three) sharply defined ulcer varying in depth, usually
one-fourth to one-half of corneal thickness.
• Sometimes the ulcer is deep enough to effect stromal
loss.
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

21. April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
Corneal ulcer
Smartypans.com

22. Progression
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

23. Stages of xerophtalmia
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
2
2
1
1
2
Keratomalacia
Ultimate involvement of
iris/lens
Keratomalacia
Secondary infection
Keratomalacia
Softening of cornea
Xerosis
Ultimate extension to cornea
Xerosis
Dryness of conjunctiva
Bitot’s spots

24. Laboratory tests
• The vitamers A can be accurately quantified in
biological specimens using high-performance
liquid–liquid partition chromatography (HPLC).
• Serum retinol is a convenient parameter of
vitamin A status.
• RBP and retinol concentrations less than
0.70 µM (20 µg/dl) are considered indicative of
vitamin A deficiency.
• Almost 20% of night blind children have serum
retinol above this level.
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

25. All signs of vitamin A deficiency
General
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

26. All signs of vitamin A deficiency
Dermatologic
Rough scaly skin and hair
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
Healthh.com

27. All signs of vitamin A deficiency
Muscular
Muscular
weakness
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

28. All signs of vitamin A deficiency
Skeletal
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

29. All signs of vitamin A deficiency
Vital organs
Nephritis
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

30. All signs of vitamin A deficiency
Nervous system
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

31. All signs of vitamin A deficiency
Reproductive
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

32. All signs of vitamin A deficiency
Ocular
Nyctalopia
Xerophthalmia
Keratomalacia
Constriction of optic nerve
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

33. Treatment
• Because vitamin A is stored in appreciable
amounts in the liver, it can be administered in
relatively large, infrequent doses with efficacy.
• In cases of clear or suspected xerophthalmia,
particularly in communities in which the
deficiency is prevalent, vitamin A is
administered orally in large doses, followed by
an additional dose the next day and a third a
few weeks later.
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

34. Treatment
• Oral administration of water miscible or oil
solutions of the vitamin are as effective as
water-miscible preparations administered
parenterally.
• Water-miscible preparations are much more
effective than oil solutions when administered
parentally (intramuscular injection).
• Topical administration on the skin is ineffective.
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.

35. Literature
• Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.
April 8, 2018
Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.