By Dale R. Ehmer Jr. MD
Smell and taste disorders affect over 2 million Americans and present a very common complaint leading patients to seek medical treatment. The importance of intact senses of smell and taste goes beyond enjoying aromas or flavors to the avoidance of life-threatening situations and protection from toxic chemicals or unhealthy foods. Being unable to detect the smell of smoke or the pungent odor from a natural gas leak along with not realizing that milk is spoiled before drinking it can be overlooked by a patient who simply complains of food no longer tasting the way that it used to.
At the roof of the nasal vault along the cribriform plate, superior turbinate, and superior nasal septum sits the olfactory epithelium. This 1cm2 specialized area of mucosa is interspersed with the normal respiratory mucosa but is different in many ways. First, the bipolar olfactory receptor neurons (ORNs) project their dendrites into the mucous layer overlying the mucosa. There are approximately 6 million ORNs in the human nose, each containing ciliated olfactory knobs or vesicles at the mucosal surface. These cilia are in the familiar '9+2' pattern of microtubules, but they lack dynein and are immotile. Second, there are multiple supporting cells in this epithelium, including microvilli, sustentacular, globose, and horizontal cells. The microvilli cells along with the supporting sustentacular cells have microvilli on their surface, and they together form tight junctions with the ORNs at the epithelial surface to effectively seal off the mucosa from chemicals or compounds in the mucus. The sustentacular cells are thought to be involved in regulation of the ionic balance of the olfactory mucus as well as absorbing compounds that have interacted with the olfactory receptors. The basal cells of the epithelium are horizontal and globose (so called light and dark cells), and these cells are the progenitor cells, being able to replace the cells of the epithelium including the ORNs. The globose cells can divide into daughter cells that will become new ORNs, and the horizontal cells can divide into cells that can form all of the remaining supporting cells in addition to forming new ORNs. Separated from the olfactory epithelium in the lamina propria, Bowman's glands secrete the specialized olfactory mucus that travels in the ducts of the Bowman's gland through the lamina propria and out to the surface of the mucosa. Also in the lamina propria are the blood vessels and nerve bundles of ORN axons traveling toward the olfactory bulbs. These ORNs form unmyelinated fascicles in the lamina propria, and once they combine and become myelinated they are called fila olfactoria. It is these 30-40 fila olfactoria that traverse the cribriform plate to enter the olfactory bulb.
At the olfactory bulb, a 6 layered structure at the floor of the anterior cranial fossa, the fila olfactoria enter caudally and synapse with second order neurons at the glomerulus. So named because of the histologic similarity to the renal counterpart, these areas consist of all the input from the ORNs (first order neuron), numbering 6 million, synapsing with mitral and tufted cells (second order neurons) in a total of 8000 glomeruli. Each ORN synapses with only one glomerulus, but the level of convergence is important as there are extensive interneuronal connections between glomeruli and the successively higher levels in the olfactory bulb. The lateral olfactory tract exits the olfactory bulb and bypasses, initially, the thalamus and synapses in the amygdala and hippocampus. Eventually, the olfactory inputs travel to the thalamus for cortical processing, but the strong association of odors and vivid memories stems from this synapse in the memory centers prior to central processing in the thalamus.
The chemical compounds that are inspired in the air will pass through the nasal vault, but only 15% of inspired air passes by the olfactory mucosa with regular breathing. During a sniff, however, a much higher percentage of inspired air is exposed to the neuroepithelium. Along the ciliated ends of the ORNs are the olfactory receptors capable of binding the odorants in the air and signaling the brain of the odor's presence. There are over 1000 genes for the odorant receptors, 3% of our genome, but due to chemical similarity, receptor specificity or unspecificity, concentration, binding affinity, solubility, and exposure time, we are able to process many more than these 1000 odors. The odorants must traverse the mucus overlying the epithelium, and hydrophobic compounds must bind transport proteins to carry them to the olfactory receptors. The binding of the odorant to the olfactory receptor causes activation of the G-protein class olfactory receptor, leading to influx of Ca2+ via c-AMP pathways which results in depolarization of the ORN and neuronal communication. The common chemosensory pathways are separate from those of CN I, as these are mediated by the first and second division of CN V. Reflexes such and sneezing, breath holding in the face of noxious odors, and reaction to ammonia are handled by this pathway.
The primary taste receptor complex is called the taste bud. There are 4 types of taste papillae in the oral cavity and oropharynx: filliform, fungiform, foliate, and circumvallate. The taste bud is a flask-shaped structure with cells arranged concentrically around a central pore. The afferent nerve supplying the taste bud enters from the base and may synapse with multiple taste buds, and each taste bud can have multiple afferent nerves synapsing with it. Filiform papilla are the most numerous papilla in the oral cavity but are heavily keratinized and do not have any functioning taste buds. The fungiform papillae are situated on the anterior 2/3 of the tongue predominately, and these papillae contain 1600 taste buds. Foliate papillae are focused on the lateral aspect of the tongue and contain 1000 taste buds. The circumvallate papillae delineate the anterior 2/3 of the tongue from the posterior 1/3 of the tongue. The 8-12 circular raised lesions in the inverted-V contain 3000 taste buds total. Innervation of the anterior 2/3 of the tongue is provided by the chorda tympani and the greater superficial petrosal nerves (palate taste buds). All fungiform and rostral foliate afferents travel to the geniculate ganglion, and from there to the rostral pole of the solitary nucleus. The CN IX innervates the posterior 1/3 of tongue with afferents traveling via the inferior petrosal ganglion to the caudal pole of the solitary nucleus. CN X via the superior laryngeal nerve innervates taste buds in the oropharynx and larynx and carries afferent neural signal by way of the vagal nodose ganglion to the caudal pole of the solitary nucleus. The neurotransmitter utilized in signal transduction between the taste bud and the afferent nerve has yet to be identified.
There are four basic qualities of taste: salt, sweet, bitter, and sour. The Japanese add a fifth quality called umami, translated "heavenly". This taste quality includes monosodium glutamate (MSG). All four qualities can be perceived in all taste buds, but some of the regions show higher levels of sensitivity to a certain quality. The taste receptor responds quickly to a changing stimulus, but it quickly adapts if the stimulus becomes constant. Saliva plays an important role in the physiology of taste. The low levels of salt ions in the saliva modulate the sensitivity of the receptors to certain tastes, and as the ionic concentration in saliva changes, so does the sensitivities of the taste bud. Saliva also has a trophic influence on the taste buds and limits keratosis that can form a functional barrier blocking binding of chemicals to the taste bud.
Describing the quality or functional defect of the senses of taste and smell is important in diagnosis and management. The nomenclature for smell loss includes anosmia, hyposmia, hyperosmia, and dysosmia to describe complete loss, decreased, increased, or abnormal detection of presented odors. In the category of dysosmias, cacosmia, heterosmia, and agnosia describe the inappropriate description of a normal smell as unpleasant, the inability to detect a difference between two odors, and the inability to classify or contrast odor but with the ability to detect their presence, respectively. The prefixes remain the same for description of isolated taste loss, however the suffix -geusia is exchanged for -osmia, for example anosmia becomes ageusia (absence of the sense of taste).
Objective testing for olfactory loss is now available, and the most accessible and most well studied item for this is called the UPSIT (University of Pennsylvania Smell Identification Test). This is a test bank containing 40 odors; each on an individual stick or paper, and the patient inhales the odor and has to decide which of the 4 choices the correct odor is. The maximum score is 40, and as your level of olfactory loss increases, the score decreases. This test can also be used for malingering or psychogenic olfactory loss, as scores less than 10 indicate possible intentional failure. Normative data has been collected for this test after thousands of patients have been tested. There is a rather flat curve as age increases from teens to fifties, but as age increases into the 60s and 70s, there is a sharp decline in normal test result, indicating an expected level of hyposmia as one reaches the 7th and 8th decades of life.
Seiden et al have extensively studied the etiologies for disorders of taste and smell, and in 2001, they published the results of 428 patients evaluated at their clinic. It is important to realize that although a large number of patients will have the chief complaint as taste loss, isolated taste loss is rare (<3% of all disorders of smell and taste). The most common causes of olfactory loss, in order, are post-URI, post-traumatic, and chronic rhinosinusitis (CRS). When searching for the etiology of the olfactory loss, splitting the causes into 2 categories can help in diagnosis and treatment planning. Similar to hearing loss being conductive, sensorineural, or mixed, one can consider the causes of olfactory loss to be obstructive (conductive), sensorineural, or combined. Examples of an obstructive olfactory loss would be nasal polyposis, tumors, CRS, or allergic rhinitis, as these disease processes hinder airborne transport of odorant molecules to the olfactory mucosa. Sensorineural causes include CRS, post-URI, post-traumatic, toxic, congenital, or neurodegenerative. CRS is listed in both of the groupings and can be considered a combined cause of olfactory loss.
CRS as an inflammatory disease process can result in polypoid mucosal changes, dense cellular inflammatory infiltrate throughout the nasal vault, and recurrent infection and mucociliary stasis due to outflow obstruction. These items independently can alter the olfactory function, and when they are together, can have effects on several vital steps in the olfactory pathway. Mucosal obstruction, as stated before, can limit carriage of odorant molecules to the olfactory cleft, mucociliary stasis due to outflow obstruction also can cause delay or re-routing of airflow away from the olfactory cleft, and the cellular inflammatory mediators can have toxic effects on the ORNs themselves. As would be expected for an inflammatory process, steroids, both topical and systemic, can improve the level of olfactory perception. Unfortunately, complete resolution is not common, with only 5% of anosmics improving to normosmia by UPSIT with maximal and surgical management for CRS. Hyposmics do not fare much better, with only a ¼ of those patients achieving normosmia despite thorough medical and surgical management. The only caveat is that 70% of these patients will have a subjective improvement in their olfactory sense, but this is usually only short lived (< 6-12 months post-surgical). Before performing surgery for olfactory loss due to CRS a pulse dose of oral steroids combined with topical nasal steroids is recommended to evaluate for any functional olfactory neuroepithelium remaining. Those patients that return some of their sense of smell with medical management can be considered for FESS.
Post-URI olfactory loss is an extremely common occurrence, affecting nearly every person multiple times per year. The vast majority of patients, however, recover their sense of smell once the URI clears. Those patients that do not recover their sense of smell after the URI likely sustained permanent damage to the neuroepithelium that may regenerate. During regeneration dysosmia is very common. This cause is more common in older women with most complaining of hyposmia. The pathogenesis is unknown although a viral etiology is the most likely. The prognosis is uncertain and is generally poor for full recovery.
Post-traumatic olfactory loss is expected to occur in 5% of traumatic head injuries, with most of the injuries resulting in anosmia. The shearing effect of the brain with respect to the cribriform plate and fila olfactoria may lead to neuronotmesis of CN I. With the resultant scarring that forms, the ascending bipolar neurons are blocked from making the connection in the olfactory bulb at the correct glomeruli. As a result, dysosmia is very common in the recovery period. The prognosis also is generally poor with few recoveries reported at 5 years.
Toxin induced olfactory loss is due to noxious chemicals inhaled that result in direct damage to the neuroepithelium, alterations in the mucus layer, and ingrowth of respiratory mucosa. There are many toxins that can lead to olfactory loss, so precautionary safety measures should be used to protect against this problem.
Congenital loss is not a common cause of olfactory loss. It will often go undiagnosed until the age of 8 when children are able to comprehend absence of smells noted by their peers. Anosmia to specific odors is the most common, likely due to congenital absence of the olfactory receptor gene needed. Kallman syndrome, hypogonadotropic hypogonadism, is an X-linked disease characterized by anosmia, an absent kidney, bimanual synkinesis, gynecomastia due to absence of gonadotropic neurons in the hypothalamus. Patients with this disorder will suffer some degree of sensorineural olfactory loss.
Neurodegenerative diseases often manifest themselves with olfactory loss. Neurofibrillary tangles and plaques in Alzheimer's disease and neurodegeneration in Parkinson's disease result in olfactory loss in a large majority of patients with these diseases. While it is true that elderly already have expected olfactory loss due to aging, the onset of neurodegenerative diseases can coincide with a more acute loss of olfactory sense in those that may not have manifested the neurologic disease.
Neoplastic processes such as inverting papilloma, sinonasal undifferentiated carcinoma, and esthesioneuroblastoma can also present with olfactory loss. Esthesioneuroblastoma is a malignant tumor of the basal cells of the olfactory neuroepithelium. Approximately 3% of intranasal tumors are esthesioneuroblastomas, and they affect people of all ages with a peak incidence between the 4th and 6th decades. Kadish classified these tumors into 3 stages. Stage A defines disease confined to the nasal cavity. Stage B defines disease that has been confined to the nasal cavity and 1 or more paranasal sinuses. Stage C defines disease that has extended beyond the nasal cavity and paranasal sinuses. Survival is similar for Stages A & B, with treatment consisting of preoperative XRT followed by craniofacial resection 6 weeks later. Stage C also receives preoperative XRT but adds chemotherapy and then followed by craniofacial resection.
Isolated taste loss is uncommon, but it can be due to many treatable causes. Poor dental hygiene is the most common cause of taste loss and also the most treatable (in early stages of disease). Glossitis from vitamin deficiency or infection, GERD, post-nasal drip, pharmacologic treatment, nerve injury, and radiation therapy all can cause gustatory loss. Damage to the chorda tympani nerve during otologic surgery is the most common type of neural loss leading to gustatory dysfunction.
These disorders can have a profound effect on a patient's life, effectively taking the enjoyment out of eating a home-cooked meal, smelling the flowers, or knowing when smoke is in the house. Systematic and thorough history taking, objective testing, and medical and surgical treatment where appropriate are required to appropriately diagnose, counsel, and treat these often dejected patients.
