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All environmental chemicals necessary for life enter the body by the nose and mouth. The senses of smell (olfaction) and taste (gustation) monitor such chemicals, determine the flavor and palatability of foods and beverages, and warn of dangerous environmental conditions, including fire, air pollution, leaking natural gas, and bacteria-laden foodstuffs. These senses contribute significantly to quality of life and, when dysfunctional, can have untoward physical and psychological consequences. Indeed, a recent longitudinal study of 1162 non-demented elderly persons found, even after controlling for confounders, that those with the lowest baseline olfactory test scores had a 45% mortality rate over a 4-year period, compared to an 18% mortality rate for those with the highest olfactory test scores. A basic understanding of these senses in health and disease is critical for the physician, because thousands of patients present to doctors’ offices each year with complaints of chemosensory dysfunction. Among the more important recent developments in neurology is the discovery that decreased smell function is among the first signs, if not the first sign, of such neurodegenerative diseases as Parkinson’s disease (PD) and Alzheimer’s disease (AD), signifying their “presymptomatic” phase.
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ANATOMY AND PHYSIOLOGY
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Odorous chemicals enter the front of nose during inhalation and active sniffing, as well as the back of the nose (nasopharynx) during deglutition. After reaching the highest recesses of the nasal cavity, they dissolve in the olfactory mucus and diffuse or are actively transported by specialized proteins to receptors located on the cilia of olfactory receptor cells. The cilia, dendrites, cell bodies, and proximal axonal segments of these bipolar cells are located within a unique neuroepithelium covering the cribriform plate, the superior nasal septum, superior turbinate, and sectors of the middle turbinate (Fig. 29-1). Nearly 400 types of G-protein-coupled odor receptors (GPCRs) are expressed on the cilia of the receptor cells, with only one type of GPCR receptor being expressed on a given cell. Other receptors, including trace amine-associated receptors and members of the non-GPCR membrane-spanning 4-domain family, subfamily A (MS4A) protein family, are also present on some receptor cells. Such a plethora of receptor cell types does not exist in any other sensory system. Importantly, when damaged, the receptor cells can be replaced by stem cells near the basement membrane, although such replacement is often incomplete.
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After coalescing into bundles surrounded by glia-like ensheathing cells (termed fila), the receptor cell axons pass through the cribriform plate to the olfactory bulbs, where they synapse with dendrites of other cell types within the glomeruli (Fig. 29-2). These spherical structures, which make up a distinct layer ...