Schematic representations of mammalian retinal rod and cone cells. There are about 500-1500 disks in the outer
segment of each rod cell. The deep membrane invaginations in the plasma membrane of the cone cell outer segment are
thought to be functionally equivalent to the rod cell disks.
a single large dose may last several days. Chronic toxicity
occurs in adults after daily doses of 7500-15,000 retinol
equivalents (25,000-50,000 IU) taken for several months.
Ingestion of carotenes alone does not cause vitamin A
toxicity, probably because of markedly decreased absorp-
tion at high doses and feedback inhibition of carotene con-
version to retinaldehyde, but can cause harmless carotene-
mia with yellowing of the skin, particularly on the palmar
and plantar surfaces. Carotenemia can cause falsely ele-
vated values for the icterus index or for other direct reading
methods for estimating serum bilirubin (Chapter 29).
In cases of toxicity, total serum vitamin A concentration
is elevated two- to eightfold, mostly in the retinyl esters,
which are associated with plasma lipoproteins, while the
RBP level is normal or only slightly increased. Unesteri-
fied retinol is generally increased less than twofold.
Vitamin A is a surfactant, and its toxicity may be due
to labilization and disruption of biological membranes.
Excessive amounts of retinol also increase synthesis and
release of lysosomal hydrolases. In
in v itro
bound to RBP is not toxic, and RBP alone protects against
toxicity of previously added vitamin A. Thus, clinical toxi-
city occurs only when the binding capacity of RBP is ex-
ceeded and retinol and retinyl esters are present either free
or in lipoproteins in the circulation.
Vision and Vitamin A
Photosensitivity in various organisms is based on
photoisomerization of retinaldehyde. In humans, 7/-cis-
complexes with opsin to produce
(visual purple). Absorption of a photon by the
electron system of retinaldehyde changes it to the all-
isomer; this reaction—the only light-catalyzed
step in vision—is transduced to an action potential
transmitted in the optic nerve. The human visual sys-
tem functions over a range of light intensity. If prop-
erly dark adapted, the eye can detect a single photon.
Vitamin A deficiency reduces the amount of rhodopsin
in the retina, thereby increasing the minimum amount of
illumination that can be detected (the visual threshold) and
causing night blindness.