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Anatomy and etiology of taste and smell disorders

Norman M Mann, MD
Denis Lafreniere, MD
Section Editor
Daniel G Deschler, MD, FACS
Deputy Editor
Janet L Wilterdink, MD


In a survey of American adults, approximately 10 percent reported smell disturbances and 5 percent reported taste disturbances within the prior year [1]. The prevalence of impaired olfaction increases with age; it has been estimated that 50 percent of adults over age 60 have a decreased sense of smell [1-6]. Nevertheless, there has been much less research in these problem areas as compared with disorders of vision and hearing. Patients often do not report the problem and, when they do, frequently get little attention since the complaint is not considered life threatening or important [1]. Often patients, after having seen many physicians, are told to live with their problem or that there is no help for them. Yet their smell and taste disorders are significantly disabling.

The anatomy of taste and olfaction and the etiology of taste and smell disorders are reviewed here. The evaluation of patients with taste and smell complaints and their management is discussed separately. (See "Evaluation and treatment of taste and smell disorders".)


The receptors of smell consist of a small area of neuroepithelial cells (the olfactory mucosa) that are located along the superior and middle turbinates and upper part of the nasal septum [7]. The surface of the epithelium has a mucous layer secreted by submucosal Bowman's glands [8]. Within its secretions are immunoglobulins A and M, secretory component, lactoferrin, and lysozyme; these help prevent pathogens from gaining intracranial entry [9]. Also present are odorant binding proteins that facilitate the transport of odorants to receptors and are thought to remove odorants from the receptor area once activation has occurred [10].

Olfactory chemoreceptor cells are primary neurons that project directly to the brain. New olfactory receptors are formed repeatedly during adulthood [11]. The receptor neurons number approximately 6 to 10 million in each nasal cavity and are flask shaped with a dendritic pole terminating in a dilated knob from which cilia extend into the overlying mucus [9]. The receptors on the cilia bind odorants. The axons of the receptor neurons travel through the cribriform plate of the ethmoid bone and terminate in the glomeruli of the olfactory bulb. These axons constitute the olfactory nerve. Neural pathways subsequently project to the olfactory cortex, orbital frontal cerebral cortex, thalamus, and hypothalamus.

Mammalian olfactory epithelium maintains the ability to replace olfactory neurons lost via injury [12]. Olfactory receptor cells are directly exposed to the external environment and its dangers, including injury from infection, inflammation, and noxious chemical agents. This exposure results in regular turnover of receptor cells via apoptosis, a programmed process in which activation of intrinsic enzymes leads to cell death. Increased levels of Capase3, the dominant enzyme in the apoptotic pathway, have been identified in olfactory epithelial cells in patients with nasal sinus disease and in mouse models of traumatic smell loss, suggesting an increase in apoptosis in these conditions [13].


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Literature review current through: Sep 2016. | This topic last updated: Apr 30, 2015.
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  1. Bhattacharyya N, Kepnes LJ. Contemporary assessment of the prevalence of smell and taste problems in adults. Laryngoscope 2015; 125:1102.
  2. Murphy C, Schubert CR, Cruickshanks KJ, et al. Prevalence of olfactory impairment in older adults. JAMA 2002; 288:2307.
  3. Doty RL. Olfactory capacities in aging and Alzheimer's disease. Psychophysical and anatomic considerations. Ann N Y Acad Sci 1991; 640:20.
  4. Stevens JC, Cruz LA, Hoffman JM, Patterson MQ. Taste sensitivity and aging: high incidence of decline revealed by repeated threshold measures. Chem Senses 1995; 20:451.
  5. Cain WS, Stevens JC. Uniformity of olfactory loss in aging. Ann N Y Acad Sci 1989; 561:29.
  6. Cain WS, Gent J, Catalanotto FA, Goodspeed RB. Clinical evaluation of olfaction. Am J Otolaryngol 1983; 4:252.
  7. Moran DT, Rowley JC 3rd, Jafek BW. Electron microscopy of human olfactory epithelium reveals a new cell type: the microvillar cell. Brain Res 1982; 253:39.
  8. Moran DT, Rowley JC 3rd, Jafek BW, Lovell MA. The fine structure of the olfactory mucosa in man. J Neurocytol 1982; 11:721.
  9. Mellert TK, Getchell ML, Sparks L, Getchell TV. Characterization of the immune barrier in human olfactory mucosa. Otolaryngol Head Neck Surg 1992; 106:181.
  10. Kinammon S, Getchell TV. Sensory transduction in olfactor receptor neurons and gustatory receptor cells. In: Smell and Taste in Health and Disease, Getchell TV, Bartoshuk LM, Doty RL, et al (Eds), Raven Press, New York 1991. p.145.
  11. Morrison EE, Costanzo RM. Morphology of the human olfactory epithelium. J Comp Neurol 1990; 297:1.
  12. Robinson AM, Conley DB, Shinners MJ, Kern RC. Apoptosis in the aging olfactory epithelium. Laryngoscope 2002; 112:1431.
  13. Kern RC, Conley DB, Haines GK 3rd, Robinson AM. Pathology of the olfactory mucosa: implications for the treatment of olfactory dysfunction. Laryngoscope 2004; 114:279.
  14. Mistretta CM. Anatomy and neurophysiology of the taste system in aged animals. Ann N Y Acad Sci 1989; 561:277.
  15. Beidler LM, Smallman RL. Renewal of cells within taste buds. J Cell Biol 1965; 27:263.
  16. Miller IJ Jr. Variation in human fungiform taste bud densities among regions and subjects. Anat Rec 1986; 216:474.
  17. Mistretta CM, Baum BJ. Quantitative study of taste buds in fungiform and circumvallate papillae of young and aged rats. J Anat 1984; 138 ( Pt 2):323.
  18. Mistretta CM. Developmental neurobiology of the taste system. In: Smell and Taste in Health and Disease, Getchell TV, Bartoshuk LM, Doty RL, et al (Eds), Raven Press, New York 1991. p.35.
  19. Farbman AI, Hellekant G. Quantitative analyses of the fiber population in rat chorda tympani nerves and fungiform papillae. Am J Anat 1978; 153:509.
  20. Heckmann JG, Heckmann SM, Lang CJ, Hummel T. Neurological aspects of taste disorders. Arch Neurol 2003; 60:667.
  21. Christensen CM. Role of saliva in human taste perception. In: Clinical Measurement of Taste and Smell, Neiselman HL, Rivlin RS (Eds), Macmillan Publishing Co, New York 1986. p.414.
  22. Bartoshuk LM. The psychophysics of taste. Am J Clin Nutr 1978; 31:1068.
  23. Plata-Salaman CR, Scott TR, Smith-Swintosky VL. Gustatory neural coding in the monkey cortex: L-amino acids. J Neurophysiol 1992; 67:1552.
  24. Mott AE, Leopold DA. Disorders in taste and smell. Med Clin North Am 1991; 75:1321.
  25. Doty RL, Bromley SM. Effects of drugs on olfaction and taste. Otolaryngol Clin North Am 2004; 37:1229.
  26. Kallman FJ, Schoenfield WA, Barrera SE. The Genetic Aspects of Primary Eunuchordism. Am J Mental Deficiency 1944; 47:203.
  27. Costanzo RM, Becker DP. Smell and taste disorders in head injury and neurosurgery patients. In: Clinical Measurement of Taste and Smell, Meiselman HL, Rivlin RS (Eds), Macmillan, New York 1986. p.565.
  28. Graziadei PP, Monti Graziadei AG. Regeneration in the olfactory system of vertebrates. Am J Otolaryngol 1983; 4:228.
  29. Reden J, Mueller A, Mueller C, et al. Recovery of olfactory function following closed head injury or infections of the upper respiratory tract. Arch Otolaryngol Head Neck Surg 2006; 132:265.
  30. Rombaux P, Mouraux A, Bertrand B, et al. Retronasal and orthonasal olfactory function in relation to olfactory bulb volume in patients with posttraumatic loss of smell. Laryngoscope 2006; 116:901.
  31. Doty RL. A review of olfactory dysfunctions in man. Am J Otolaryngol 1979; 1:57.
  32. Jafek BW, Hartman D, Eller PM, et al. Postviral olfactory dysfunction. Am J Rhino 1990; 4:1.
  33. Lee DY, Lee WH, Wee JH, Kim JW. Prognosis of postviral olfactory loss: follow-up study for longer than one year. Am J Rhinol Allergy 2014; 28:419.
  34. Chen Y, Getchell TV, Sparks DL, Getchell ML. Patterns of adrenergic and peptidergic innervation in human olfactory mucosa: age-related trends. J Comp Neurol 1993; 334:104.
  35. Nakashima T, Kimmelman CP, Snow JB Jr. Structure of human fetal and adult olfactory neuroepithelium. Arch Otolaryngol 1984; 110:641.
  36. Bhatnagar KP, Kennedy RC, Baron G, Greenberg RA. Number of mitral cells and the bulb volume in the aging human olfactory bulb: a quantitative morphological study. Anat Rec 1987; 218:73.
  37. Kovács T, Cairns NJ, Lantos PL. beta-amyloid deposition and neurofibrillary tangle formation in the olfactory bulb in ageing and Alzheimer's disease. Neuropathol Appl Neurobiol 1999; 25:481.
  38. Doty RL, Reyes PF, Gregor T. Presence of both odor identification and detection deficits in Alzheimer's disease. Brain Res Bull 1987; 18:597.
  39. Graves AB, Bowen JD, Rajaram L, et al. Impaired olfaction as a marker for cognitive decline: interaction with apolipoprotein E epsilon4 status. Neurology 1999; 53:1480.
  40. Doty RL, Deems DA, Stellar S. Olfactory dysfunction in parkinsonism: a general deficit unrelated to neurologic signs, disease stage, or disease duration. Neurology 1988; 38:1237.
  41. Daniel SE, Hawkes CH. Preliminary diagnosis of Parkinson's disease by olfactory bulb pathology. Lancet 1992; 340:186.
  42. Williams SS, Williams J, Combrinck M, et al. Olfactory impairment is more marked in patients with mild dementia with Lewy bodies than those with mild Alzheimer disease. J Neurol Neurosurg Psychiatry 2009; 80:667.
  43. Ross GW, Petrovitch H, Abbott RD, et al. Association of olfactory dysfunction with risk for future Parkinson's disease. Ann Neurol 2008; 63:167.
  44. Garland EM, Raj SR, Peltier AC, et al. A cross-sectional study contrasting olfactory function in autonomic disorders. Neurology 2011; 76:456.
  45. Kimmelman CP. The risk to olfaction from nasal surgery. Laryngoscope 1994; 104:981.
  46. Nakashima T, Kimmelman CP, Snow JB. Progressive olfactory degeneration due to ischemia. Surg Forum 1983; 34:566.
  48. Talal N. Sjögren's syndrome. Bull Rheum Dis 1966; 16:404.
  49. Baum BJ. Salivary gland fluid secretion during aging. J Am Geriatr Soc 1989; 37:453.
  50. Henkin RI, Talal N, Larson AL, Mattern CF. Abnormalities of taste and smell in Sjogren's syndrome. Ann Intern Med 1972; 76:375.
  51. McConnell RJ, Menendez CE, Smith FR, et al. Defects of taste and smell in patients with hypothyroidism. Am J Med 1975; 59:354.
  52. Green RF. Subclinical pellagra and idiopathic hypogeusia. JAMA 1971; 218:1303.
  53. Amoore JE. Effects of chemical exposure in olfaction in humans. In: Toxicology of Nasal Passages, Barrow CS (Ed), Hemisphere Publishing Co, Washington, DC 1986. p.155.
  54. Antunes MB, Bowler R, Doty RL. San Francisco/Oakland Bay Bridge Welder Study: olfactory function. Neurology 2007; 69:1278.
  55. Nguyen-Khoa BA, Goehring EL Jr, Vendiola RM, et al. Epidemiologic study of smell disturbance in 2 medical insurance claims populations. Arch Otolaryngol Head Neck Surg 2007; 133:748.
  56. Davidson TM, Smith WM. The Bradford Hill criteria and zinc-induced anosmia: a causality analysis. Arch Otolaryngol Head Neck Surg 2010; 136:673.
  57. Bakay L. Olfactory meningiomas. The missed diagnosis. JAMA 1984; 251:53.
  58. Doty RI. Olfactory dysfunction in neurodegenerate disorders. In: Smell and Taste in Health and Disease, Getchell TV, Doty RL, Bartoshuk LM, Snow JB Jr (Eds), Raven Press, New York 1991. p.735.
  59. Greebe P, Rinkel GJ, Algra A. Anosmia after perimesencephalic nonaneurysmal hemorrhage. Stroke 2009; 40:2885.
  60. Wermer MJ, Donswijk M, Greebe P, et al. Anosmia after aneurysmal subarachnoid hemorrhage. Neurosurgery 2007; 61:918.
  61. Kunte H, Schmidt F, Kronenberg G, et al. Olfactory dysfunction in patients with idiopathic intracranial hypertension. Neurology 2013; 81:379.
  62. Schmidt C, Wiener E, Hoffmann J, et al. Structural olfactory nerve changes in patients suffering from idiopathic intracranial hypertension. PLoS One 2012; 7:e35221.
  63. Bershad EM, Urfy MZ, Calvillo E, et al. Marked olfactory impairment in idiopathic intracranial hypertension. J Neurol Neurosurg Psychiatry 2014; 85:959.
  64. Kapoor KG. Do patients with idiopathic intracranial hypertension suffer from hyposmia? Med Hypotheses 2008; 71:816.
  65. Frank ME, Hettinger TP, Mott AE. The sense of taste: neurobiology, aging, and medication effects. Crit Rev Oral Biol Med 1992; 3:371.
  66. Mott AE, Mann NM. Taste. In: Encyclopedia of Occupational Health and Safety, 4th ed, Stellman JM (Ed), 1998. p.1:11.22.
  67. Weiffenbach JM, Baum BJ, Burghauser R. Taste thresholds: quality specific variation with human aging. J Gerontol 1982; 37:372.
  68. Stevens JC, Cain WS. Changes in taste and flavor in aging. Crit Rev Food Sci Nutr 1993; 33:27.
  69. Mistretta CM. Aging effects on anatomy and neurophysiology of taste and smell. Gerodontology 1984; 3:131.
  70. Breslin PA, Beauchamp GK. Suppression of bitterness by sodium: variation among bitter taste stimuli. Chem Senses 1995; 20:609.
  71. Schiffman SS. Taste and smell losses in normal aging and disease. JAMA 1997; 278:1357.
  72. Kinnamon S, Getchell TV. Sensory Transduction in Olfactor Receptor Neurons and Gustatory Receptor Cells. In: Smell and Taste in Health and Disease, Getchell TV, Bartoshuk LM, Doty RL, et al (Eds), Raven, New York 1991. p.145.
  73. Lancet D, Striem BJ, Pace U, et al. Adenylate cyclase and GTP binding protein in rat sweet taste transduction. Soc Neurosci Abstr 1987; 13:361.
  74. Oakley B. Trophic competence in mammalian gestation. In: Taste, Olfaction and the Central Nervous System, Pfaff DW (Ed), Rockefeller University Press, 1985. p.95.
  75. Henkin RI. Drug effects in taste and smell. In: Pharmacology in Medicine: Principles and Practice, Pradham SN, Maickel RP, Dietta SN (Eds), SP Press Int, Bethesda 1986. p.748.
  76. Duffield JE. Side effects of lithium carbonate. Br Med J 1973; 1:491.
  77. Henkin RI, Graziadei PP, Bradley BF. NIH clinical staff conference. The molecular basis of taste and its disorders. Ann Intern Med 1969; 71:791.
  78. Henkin RI. Drug-induced taste and smell disorders. Incidence, mechanisms and management related primarily to treatment of sensory receptor dysfunction. Drug Saf 1994; 11:318.
  79. Koch-Weser J, Goldman P. Drug therapy: metronidazole. N Engl J Med 1980; 303:1212.
  80. Trotti LM, Saini P, Bliwise DL, et al. Clarithromycin in γ-aminobutyric acid-Related hypersomnolence: A randomized, crossover trial. Ann Neurol 2015; 78:454.
  81. Ohdera T, Tokunaga M, Hiroshima S, et al. Arthroscopic management of tibial plateau fractures--comparison with open reduction method. Arch Orthop Trauma Surg 2003; 123:489.
  82. Kachru DN, Tandon SK, Misra UK, Nag D. Occupational lead poisoning among silver jewellery workers. Indian J Med Sci 1989; 43:89.
  83. Gordon T, Fine JM. Metal fume fever. Occup Med 1993; 8:504.
  84. Siblerud RL. The relationship between mercury from dental amalgam and oral cavity health. Ann Dent 1990; 49:6.
  85. Vij S, Kanagasuntheram R. Effect of tri-O-cresyl phosphate (TOCP) poisoning on sensory nerve terminations of slow loris (Nycticebus coucang coucang). Acta Neuropathol 1972; 20:150.
  86. Mossman K, Shatzman A, Chencharick J. Long-term effects of radiotherapy on taste and salivary function in man. Int J Radiat Oncol Biol Phys 1982; 8:991.
  87. Jeppsson PH, Hallén O. The taste after operation for otosclerosis. Pract Otorhinolaryngol (Basel) 1971; 33:215.
  88. Blackburn CW, Bramley PA. Lingual nerve damage associated with the removal of lower third molars. Br Dent J 1989; 167:103.
  89. Mott, A, Shafer, D, Miller, D, et al. Gustatory function after oral maxillofacial surgery: Submitted.
  90. Boenninghaus HG, Denecke U. [Paralysis of the hypoglossal nerve after tonsillectomy? (author's transl)]. Laryngol Rhinol Otol (Stuttg) 1982; 61:189.
  91. Deems DA, Doty RL, Settle RG, et al. Smell and taste disorders, a study of 750 patients from the University of Pennsylvania Smell and Taste Center. Arch Otolaryngol Head Neck Surg 1991; 117:519.
  92. Jääskeläinen SK. Pathophysiology of primary burning mouth syndrome. Clin Neurophysiol 2012; 123:71.