Chapter 030. Disorders of Smell, Taste, and Hearing (Part 1) doc

Chapter 030. Disorders of Smell,
Taste, and Hearing
(Part 1)

Harrison's Internal Medicine > Chapter 30. Disorders of Smell, Taste,
and Hearing
Smell
The sense of smell determines the flavor and palatability of food and drink
and serves, along with the trigeminal system, as a monitor of inhaled chemicals,
including dangerous substances such as natural gas, smoke, and air pollutants.
Olfactory dysfunction affects ~1% of people under age 60 and more than half of
the population beyond this age.
Definitions
Smell is the perception of odor by the nose. Taste is the perception of salty,
sweet, sour, or bitter by the tongue. Related sensations during eating such as
somatic sensations of coolness, warmth, and irritation are mediated through the
trigeminal, glossopharyngeal, and vagal afferents in the nose, oral cavity, tongue,
pharynx, and larynx. Flavor is the complex interaction of taste, smell, and somatic
sensation. Terms relating to disorders of smell include anosmia, an absence of the
ability to smell; hyposmia, a decreased ability to smell; hyperosmia, an increased
sensitivity to an odorant; dysosmia, distortion in the perception of an odor;
phantosmia, perception of an odorant where none is present; and agnosia, inability
to classify, contrast, or identify odor sensations verbally, even though the ability to
distinguish between odorants or to recognize them may be normal. An odor
stimulus is referred to as an odorant. Each category of smell dysfunction can be
further subclassified as total (applying to all odorants) or partial (dysfunction of
only select odorants).
Physiology of Smell
The olfactory epithelium is located in the superior part of the nasal cavities
and is highly variable in its distribution between individuals. Over time the
olfactory epithelium loses its homogeneity, as small areas undergo metaplasia

producing islands of respiratory-like epithelium. This process is thought to be
secondary to insults from environmental toxins, bacteria, and viruses. The primary
sensory neuron in the olfactory epithelium is the bipolar cell. The dendritic
process of the bipolar cell has a bulb-shaped vesicle that projects into the mucous
layer and bears six to eight cilia containing odorant receptors. On average, each
bipolar cell elaborates 56 cm
2
(9 in.
2
) of surface area to receive olfactory stimuli.
These primary sensory neurons are unique among sensory systems in that they are
short-lived, regularly replaced, and regenerate and establish new central
connections after injury. Basal stem cells, located on the basal surface of the
olfactory epithelium, are the progenitors that differentiate into new bipolar cells
(Fig. 30-1).
Figure 30-1

Olfaction. Olfactory sensory neurons (bipolar cells) are embedded in a
small area of specialized epithelium in the dorsal posterior recess of the nasal
cavity. These neurons project axons to the olfactory bulb of the brain, a small
ovoid structure that rests on the cribriform plate of the ethmoid bone. Odorants
bind to specific receptors on olfactory cilia and initiate a cascade of action
potential events that lead to the production of action potentials in the sensory
axons.
Between 50 and 200 unmyelinated axons of receptor cells form the fila of
the olfactory nerve; they pass through the cribriform plate to terminate within
spherical masses of neuropil, termed glomeruli, in the olfactory bulb. Olfactory
ensheathing cells, which have features resembling glia of both the central and
peripheral nervous systems, surround the axons along their course. The glomeruli
are the focus of a high degree of convergence of information, since many more

fibers enter than leave them. The main second-order neurons are mitral cells. The
primary dendrite of each mitral cell extends into a single glomerulus. Axons of the
mitral cells project along with the axons of adjacent tufted cells to the limbic
system, including the anterior olfactory nucleus and the amygdala. Cognitive
awareness of smell requires stimulation of the prepiriform cortex or amygdaloid
nuclei.
A secondary site of olfactory chemosensation is located in the epithelium
of the vomeronasal organ, a tubular structure that opens on the ventral aspect of
the nasal septum. In humans, this structure is rudimentary and nonfunctional,
without central projections. Sensory neurons located in the vomeronasal organ
detect pheromones, nonvolatile chemical signals that in lower mammals trigger
innate and stereotyped reproductive and social behaviors, as well as
neuroendocrine changes.
The sensation of smell begins with introduction of an odorant to the cilia of
the bipolar neuron. Most odorants are hydrophobic; as they move from the air
phase of the nasal cavity to the aqueous phase of the olfactory mucous, they are
transported toward the cilia by small water-soluble proteins called odorant-
binding proteins and reversibly bind to receptors on the cilia surface. Binding
leads to conformational changes in the receptor protein, activation of G protein–
coupled second messengers, and generation of action potentials in the primary
neurons. Intensity appears to be coded by the amount of firing in the afferent
neurons.
Olfactory receptor proteins belong to the large family of G protein–coupled
receptors that also includes rhodopsins; α- and β-adrenergic receptors; muscarinic
acetylcholine receptors; and neurotransmitter receptors for dopamine, serotonin,
and substance P. In humans, there are 300–1000 olfactory receptor genes
belonging to 20 different families located in clusters at >25 different chromosomal
locations. Each olfactory neuron expresses only one or, at most, a few receptor
genes, thus providing the molecular basis of odor discrimination. Bipolar cells that
express similar receptors appear to be scattered across discrete spatial zones.

These similar cells converge on a select few glomeruli in the olfactory bulb. The
result is a potential spatial map of how we receive odor stimuli, much like the
tonotopic organization of how we perceive sound.