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Year : 2012  |  Volume : 2  |  Issue : 1  |  Page : 2-6

Olfactory function and dysfunction

Department of Surgery, Otorhinolaryngologist, Ahmadu Bello University, Zaria, Nigeria

Date of Web Publication22-Sep-2012

Correspondence Address:
Aminu Bakari
Department of Surgery, Otorhinolaryngologist, Ahmadu Bello University, Zaria
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2278-9596.101251

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Olfaction is phylogenetically the oldest sense, but receives scant attention in contrast to other special senses. Smell is often taken for granted, but it is central to our everyday life and helps to protect us from harmful substances, contributes to the livelihood of many professions as well as to the nutritional status and general quality of life. Olfactory disorders are common, yet remain the least understood. This paper gives an overview of the anatomy, physiology, and management of olfactory disorders with particular emphasis on current clinical measurements of olfactory dysfunction. Literature from relevant textbooks and selected journal articles has been reviewed in this article. Olfactory disorders can be classified as conductive, sensory, and neural. Localization of olfactory centers in the brain by electroencephalography has been described recently. However, quantitative evaluation by threshold measurements and qualitative testing with identification test formats continues to be the most popular type of olfactory test in use. While treatment of olfactory disorders remains disappointing, conductive disorders are amenable to treatment. Full understanding of the olfactory organ and its pathways is essential for the development of any reliable means of testing its function and managing dysfunction. With recent developments in olfactory mapping of the brain, it won't be long before a more robust test for olfaction akin to visual acuity and auditory thresholds is developed.

Keywords: Dysfunction, measurements, olfaction

How to cite this article:
Bakari A, Usman MA. Olfactory function and dysfunction. Arch Int Surg 2012;2:2-6

How to cite this URL:
Bakari A, Usman MA. Olfactory function and dysfunction. Arch Int Surg [serial online] 2012 [cited 2021 May 12];2:2-6. Available from:

  Background History Top

Darwin postulated that loss of olfactory acuity was part of the evolutionary process. [1] Freud and others argued that smell has been left behind and sight had taken priority. [2] These views may underestimate the influence of olfaction on our lives. The olfactory pathway projects to the limbic system and it is not surprising that olfactory perception consists not only of odors, but also the experiences and emotion associated with them. Since antiquity, aromatics have been employed across cultures, for purposes as diverse as seduction, healing, hunting, inducing hallucinations, banqueting, anointing the dead, in amphitheatres, in images of love, in literature, and communication with spirits. Olympian god Aphrodite and his son Eros were fragrant and mount Olympus was itself deemed a place of fragrance. [3]

Egypt's most famous perfume Kyphi was a mixture of 16 ingredients, which reportedly had the power to relieve anxiety, heal the soul, and was burnt in sacrifice to "RE" the Sun God. [4] Olfaction, knowledge, and wisdom were interlinked in the classical world; the origin of the word "sagacious" is from Latin where "sag ax" implies a keen sense of smell. [2]

The association of smell with disease dates back to bin Siena (Avicenna; 1400-1600AD), the Arabian physician. [2] In 19 th century, Europe Chadwick preached "all smell is disease," while his contemporary Hector Garvin, the physician, conducted olfactory tours of London [2]

  Introduction Top

Olfaction is the sensation arising from the nasal cavity following stimulation of the olfactory epithelium by volatile substances. [2] Olfaction is of phylogenic antiquity but receives scant attention in contrast to other special senses. [5] Although it may be crucial for survival in animals, however, it seems less critical for man. [6] Olfaction helps to protect human beings from harmful substances such as environmental contaminants and spoilt food. It also contributes to the livelihood of cooks, wine tasters, fire fighters, chemists, and industrial workers, as well as to the nutritional status and general quality of life. [7] Odor evoked memories have been found to be more emotional than verbally cued memories. [8]

In a study of 750 consecutive patients with anosmia, Nick et al., quoting Deems et al., reported a reduced quality of life and altered daily living among 68% and 56% of the study group, respectively. [2] The greatest pleasure of food is olfactory. [6] Consequently, life has a flat quality for the anosmic patient, distinguishing food by its texture and color (such as the lumpiness of sour milk) and avoiding perfume for fear of over application. [2] A reduced olfactory function is not uncommon; one study showed approximately half of 65-80-year-old people are affected. [9] Age-related olfactory loss appears to begin at 60 years, becoming significantly worse after 70 years. [10] This is 2-10 times higher than for those in their twenties and is exacerbated by illness or multiple medication. [11] Olfactory dysfunction for food odor is believed to contribute significantly to anorexia, malnutrition, and subsequent weight loss in the elderly. [7]

  Anatomy Top

The olfactory system consists of olfactory epithelium, bulbs, and tracts, as well as the olfactory areas in the brain and their communications with other centers. [12] As early as the 24th day of intrauterine life, a pit forms on either side of the anterior end of the neural groove and this becomes the nasal pit. Receptor cells are present by the 7th week and these make connections with the forebrain. The cilia and all other cells in the epithelium have differentiated and are functional at birth. [13] The olfactory neuroepithelium covers an area of 2-10 m², and is located high in the nasal vault including the roof of the nose, the upper part of the superior turbinate, and a corresponding region of the nasal septum. [6]

The receptor cell is a bipolar neuron with a round cell body, whose distal process carries approximately 10- 23 cilia. These cilia are assumed to carry on their surface membrane, receptors sensitive to odoriferous molecules. The proximal process of the neuron, which is long and thin, is invested by the basal cells until it perforates the cribriform plate of the ethmoid and comes into association with the cytoplasm of the Schwann cells. They end in bushy masses called glomeruli in the olfactory bulb, which lie on the intracranial side of the cribriform plate. From the olfactory bulb, fibers of the olfactory nerve project to the amygdala, the pre-pyriform cortex, the anterior olfactory nucleus, and entorhinal cortex, as well as the hippocampus, hypothalamus, and thalamus. [2]

  Physiology Top

The sense of smell is mediated through the stimulation of the olfactory receptor cells by air-borne volatile chemicals that are lipid soluble. [14] Transduction of odorant or chemical information into electrical impulses occurs in the receptors on the olfactory cilia. Odor molecules diffuse to the receptor sites in the cell membrane, opening the ionic channels, and electric current flows across the membrane and sets up a receptor potential that spreads from the cilia to the cell body. Depolarization of the cell body triggers action potentials that begin the transmission of electrical impulse to the olfactory bulb. [12]

Humans can detect more than 10,000 different odors and discriminate between 5000 odors. [2] However, the precise mechanism by which the vast number of smells is recognized and discriminated is unknown. The olfactory mucosa receives efferent projections from the olfactory cortical areas, the basal forebrain, and the midbrain. Within the cortex, the two bulbs are connected by the anterior olfactory nucleus through the anterior commissure; the pyriform cortex projects to the medio-lateral thalamus, which then projects to the orbito-frontal cortex. The right cortex is the suggested olfactory processing area. [15] Adaptation is a characteristic of olfaction and is said to exist when one ceases to be aware of continuous olfactory stimulation. [12]

  Causes of Olfactory Disturbance Top

There are three major classifications of olfactory disorders: transport (conductive), sensory, and neural. [2] Sensorineural is used in practice when differentiation is difficult. Transport disorders interfere with the access of a chemical stimulus to the smell receptors and the commonest examples are inflamed nasal mucosa or nasal polyps. Sensory loses result from damage to the sensory organs. [2] Factors which reduce cell turnover or directly modify cells include toxic chemicals, radiation, medications, neoplasms, and viruses. Neural losses result from interruptions in the peripheral or central nervous olfactory pathways, from head trauma, neoplasm, and surgery. Iatrogenic causes form a small percentage of olfactory disturbances; they include medication, neurosurgery, radiotherapy, and para-nasal sinus surgery. [2]

From the foregoing discussion, it can be appreciated how central olfaction is to our everyday life and how common olfactory disorders are. Indeed, it has been estimated that 1-2% of the American population is anosmic or severely hyposmic and effectively without functional smell. [7],[12] However, few clinical otolaryngologists have the means to carefully evaluate these problems.

  Clinical Measurement of Olfaction Top

A clinical description such as 20/40 with no astigmatism or a 40 dB loss above 4000 Hz is not yet possible for the measurement of olfaction, as there is no simple physical dimension (or dimensions) about which to structure perceptual data in olfaction. [7] Hence, there are no established analogs to acoustic frequency in audition or wavelength in color vision. [7] The evaluation of most olfactory disorders is based on simple measurement of thresholds (acuity) (quantitative) and odor identification (qualitative). [16]

The recognition and identification of test substances still remains the first practical means of assessing the degree of qualitative olfactory sensations. [17] For this assessment, odoriferous substances kept in glass jars or sniff bottles are presented to the patient for identification. Traditionally, nine substances are recommended for use in standard textbooks. These include benzaldehyde (almond), oil of lemon, camphor, coffee, oil of cloves, oil of aniseed, chocolate, oil of peppermint, and tar. [18] The patient is asked to sniff each of the bottles and name the odor. The percentage of positive identification is then noted. [18] Sumner carried out an investigation to determine what substances may be most readily identified and concluded that conventionally the wrong substances are used, and that coffee, benzaldehyde, tar, and oil of lemon are more suitable. He therefore stressed the importance of using fewer and familiar scents. [18]

Doty, Shaman, and Dan developed the University of Pennsylvania Smell Identification Test (UPSIT) kit, using odors microencapsulated in 10-50 mm crystals mounted on a series of cards in booklets. When scratched by a fingernail or pencil, the smell is released and sniffed by the subject, who attempts to identify it with the help of four proffered alternative identifications, one of which must be chosen even if the subject believes that nothing can be smelt. The number of correct responses is then noted. Population studies showed that when presented with a series of 40 different odor impregnated cards, normal subjects gave 32-40 correct responses, hyposmics 20-30, and total anosmics scored 7-14 correct answers (by chance alone). [19] This test is highly reliable (test-re-test reliability = 95) and allows the classification of patients into discrete categories of dysfunction. It also provides a percentile score of patient's performance relative to age- and sex-matched controls and has procedures for detecting malingering. Scores on this test reflect both gross and subtle olfactory problems associated with smoking and numerous neurological diseases (Korsakoff's psychosis, multiple sclerosis, Parkinson's disease) and correlates highly with the levels of certain catecholamine metabolites in the cerebrospinal fluid of some patient group with Korsakoff's psychosis. [19] However, despite the acceptability of the UPSIT in America, it cannot be used in other countries due to cultural differences regarding familiar odors.

The Connecticut chemosensory clinical research odor identification test (CCRC) is a 10-item odor identification test designed to produce almost perfect performance in normal adults. This test employs natural odors commonly encountered in everyday life. The patient sniffs an odor with the eyes closed and then attempts to identify it after familiarizing himself or herself with a cue sheet containing the names of the odor items as well as names of items not presented. [12] Composite score ranges derived from odor identification and butanol threshold subtest are then used to categorize individuals into five distinct levels of olfactory functioning. These categories are: normosmic (normal); mildly, moderately, and severely hyposmic (impaired functioning); and anosmia (no sensation). [20]

"Sniffing sticks" is a test of nasal chemosensory performance that is based on pen-like odor-dispensing devices. It comprises three tests of olfactory function: test for odor threshold (n-butanol), discrimination, and identification (16 pairs of odorants). The results of this test are presented as composite TDI score, i.e. the sum of results obtained for threshold, discrimination, and identification measures. A score of 15 is the cutoff point for functional anosmia. [21] Although detection threshold values typically agree with the results obtained from the smell identification test, in some instances, patients who fail the identification test perform normally on the detection task. [17] Women have been reported to consistently do better than men in odor identification test. [2]

Qualitative assessment of olfactory function is essential for a number of reasons. First, to establish the validity of the patient's complaint; second, to characterize the exact nature of the problem (which is critical for establishing a diagnosis); and third, to monitor objectively the efficacy of any intervention or treatment. [22] Although air dilution olfactometry is the method of choice in presenting stimuli for such assessment, it is not practical in the typical clinical setting. [17] An alternative is to present odorants diluted in a liquid diluents (e.g. odorless mineral oil, distilled water, or propylene glycol) via small vessels held over the nose (i.e. sniff bottles). Odorants employed include butanol, phenyl alcohol, PM-carbinol, pyridine, etc. Serial dilutions of the odorant are then preferably presented in a single staircase procedure in order to avoid adaptation. Doty et al. observed that smelling with both nostrils open is better than unilateral testing since the total nasal resistance across both nasal cavities is relatively constant and free from the effects of the nasal cycle. [17]

Cain et al. developed an odor identification test combined with butanol threshold test and reported five degrees of functioning: normal osmesis; mild, moderate, and severe hyposmia; and anosmia, based on combined scores of the two tests. [23] Robson et al. validated a combined olfactory test consisting of an odor recognition test of nine substances, and a threshold test using serial dilutions of 1-butanol on 133 participants with a normal sense of smell and 94 participants with altered smell. They reported a highly significant difference between the combined olfactory scores in the normal and anosmic groups. This significant difference was the same between the two groups for the threshold and odor identification arms of the test and between the two subgroups of "completely anosmic" and "almost anosmic" participants, indicating that the test could grade the degree of olfactory dysfunction. [24]

  Current Developments in Olfactory Testing Top

Qualitative evaluation of olfactory function by threshold measurements and quantitative testing with identification test formats continues to be the most popular type of olfactory test in use. These parameters are still not widely accepted and variations between different centers are seen for common odorants such as phenyl alcohol.

Recently, topographical comparison of the amplitude of olfactory event related potentials by electroencephalography following monitored release of olfactory stimuli to subjects by an olfactometre has made it possible to localize olfactory centers and to derive an olfactory map of the brain. This technique is able to detect differences between normal and abnormal subjects, but at present it is unable to detect specific defects in the olfactory pathway. [25]

Most recently, Linda Buck and Richard Axel, Nobel laureates in Physiology in 2004, achieved the greatest breakthrough in the understanding of olfaction to date. [25] They discovered a large gene family comprising some 1000 different genes (3% of the human genome), which gives rise to an equivalent number of olfactory receptor types. Each olfactory receptor cell possesses only one type of odorant receptor and each receptor can detect a limited number of odorant substances. This means that each receptor cell is therefore highly specialized. This important piece of the olfaction jigsaw will surely be the first of many more, enabling a greater understanding of this sensory modality. [25]

Full understanding of the olfactory organ and its pathways is essential for the development of any reliable means of testing its function. With the recent developments in olfactory mapping of the brain, it won't be long before a more robust test for olfaction akin to visual acuity and auditory thresholds is developed.

  Therapy of Olfactory Disorders Top

Unfortunately, treatment of olfactory disorders remains disappointing. Management of olfactory disorders depends entirely on the accurate diagnosis of the cause because therapy is dictated by the pathologic condition. [26] Conductive disorders are most amenable to treatment, while sensorineural disorders remain challenging. [26] Therapy has been proven to be effective only for olfactory dysfunction due to sinonasal disease. Specifically, either surgical therapy (e.g. polypectomy, sinusotomy, or ethmoidectomy) or topical or systemic administration of corticosteroids may be helpful. [27] In steroid-dependent anosmia, high doses of steroids will restore the sense of smell. [28] Studies with zinc have produced controversial results. [29] Similarly, results on estrogen replacement therapy are not encouraging in terms of olfactory disturbances. [29] Controlled studies are missing regarding orally administered vitamin A; however, it has been reported to normalize olfactory performance in malabsorption conditions or A-β lipoproteinemia. [29] More recently, α-lipoid acid has been added to the list of potential candidates for the treatment of post-viral olfactory dysfunction. [29]

  References Top

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7.Schiffman SS. Taste and smell in disease. N Engl J Med 1993;308:1337-43.  Back to cited text no. 7
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14.John JB. Clinical anatomy and physiology of the nose and paranasal sinuses. In: Otolaryngology Head and Neck Surgery. Baltimore, MD Williams & Wilkins; 1996. p. 10-3.  Back to cited text no. 14
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17.Doty RL, Kimmelman CP. Smell and taste and their disorders. In: Asbury MM, editors. Diseases of Nervous system1: Clinical neurobiology. London: Heinemann; 1986. p. 466-78.  Back to cited text no. 17
18.Summer D. On testing the sense of smell. Lancet 1962;3:895- 7.  Back to cited text no. 18
19.Doty RL, Shaman P, Kimmelman CP, Dann MS. University of Pennsylvania smell Identification tests. A rapid quantitative olfactory function test for the clinic. Laryngoscope 1984;94:176-8.  Back to cited text no. 19
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21.Hummel T, Sekinger B, Wolf SR, Pauli E, Kobal G. 'Sniffing sticks': Olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold. Chem Senses 1997;22:39-52.  Back to cited text no. 21
22.John EA, Bengt GO. Practical Test Kits for quantitatively evaluating the sense of smell. Rhinology 1983;21:49-54.  Back to cited text no. 22
23.Cain WS, Gent J, Catalan Otto FA. Clinical evaluation of olfaction. Am J Otolaryngol 1983;4:252-6.  Back to cited text no. 23
24.Robson AK. Validation of the combined olfactory test. Clin Otolaryngol 1996;21:512-8.  Back to cited text no. 24
25.Philpott CM, Bennett A, Murty GE. A brief history of olfaction and olfactometry. J Laryngol Otol 2008;122:657-62.  Back to cited text no. 25
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27.Wolfensberger M, Hummel T. Anti - inflammatory and surgical therapy of olfactory disorders related to sino - nasal disease. Chem Senses 2002;27:617-22.  Back to cited text no. 27
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29.Welge-Lussen A. Re - establishment of olfactory and taste functions, an overview of available therapies. GMS Curr Top Otorhinolaryngol Head Neck Surg 2005;4:1-21.  Back to cited text no. 29

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