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. . 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. 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. 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