Olfactory Receptor Neuron (ORN)
• 6 to 10 million ORNs in each nasal cavity; life span of 3 to 7 weeks
• Bipolar neurons with dendrites extending inferiorly to the epithelial surface, and axons extending intracranially to synapse at the OB
• An ORN dendrite has nonmotile cilia at its thickened ending/knob, increasing its overall functional surface area to 22 cm2 for odorant binding.
• Olfactory receptors are expressed on the nonmotile cilia of the ORN dendrites; there are approximately 1000 different human genes encoding different receptor types.
• Unmyelinated axons of ORN join to form myelinated fascicles (fila olfactoria) which travel in bundles of 50 via the foramina of the cribriform plate to synapse in the OB and constitute the olfactory nerve (CN1).
Sustentacular Cell (supporting cells)
• Insulates and protects ORN
• Has high concentration of cytochrome p450
• Maintains cellular homeostasis and regulates mucus composition
• Deactivates odorants
Microvillar Cell (unknown function)
Basal Cells (horizontal and globose)
• Regenerate all cell types in ON into adulthood, including the ORN.
• Regeneration decreases with increasing age of patient or severity of injury.
• Viable neural progenitor cells capable of generating ORN can be cultured from middle turbinate biopsies.
Bowman’s Gland
• Located within lamina propria
• Secretes mucous layer made of IgA/IgM, lactoferrin, lysozyme, and odorant binding proteins
• Assists odorant binding and clearing, and prevents pathogen entry
• Odorant molecule trapped by the mucous layer over the ON and transported by the odorant binding proteins → odorant receptors on ORNs within the olfactory cleft → axons bundle join in myelinated fascicles to become CN1 → passes through cribriform plate → synapse in glomeruli of olfactory bulb → second order neurons (mitral cells) → olfactory tract → olfactory cortex
Olfactory Bulb
• The complex processing center is located at the ventral base of the frontal lobe, on top of the cribriform plate
• Mitral cells within the OB receive axons of the ORN.
• Olfactory nerve bundles synapse with the second order neurons within thousands of glomeruli within the bulb.
• Axons from mitral cells leave the bulb as lateral olfactory tract, which extends to olfactory cortex.
• Anterior commissure is a small commissure that connects the two halves of the olfactory system.
Olfactory Cortex
• Portions of cerebral cortex receiving direct input from the olfactory bulb via mitral cell axons
• Located on the base of the frontal lobe and medial aspect of the temporal lobe
• Temporal lobe of the olfactory cortex covers a portion of the parahippocampal gyrus known as the uncinate gyrus.
• Seizures often arise from the uncinate gyrus and are characterized by hallucinations of smell and taste.
• Olfactory information is relayed via the mediodorsal nucleus of the thalamus to the insular cortex (olfactory and gustatory sensory integration), the orbitofrontal cortex (conscious smell perception), and the amygdala (limbic system, memory).
• The Nobel Prize in Physiology or Medicine in 2004 was awarded jointly to Richard Axel and Linda B. Buck for their discovery of olfactory receptors and elucidation of the molecular basis of olfactory system.
• The human genome contain 1,000 olfactory receptors genes, of which 350 functionally code for unique receptors.
• Each olfactory receptor cell expresses only one type of binding protein.
• This receptor is a transmembrane G-protein-coupled receptor.
• The secondary messenger (cAMP or IP3), generated by the effector enzyme, opens a Ca2+ channel, followed by a Ca2+ gated Cl– channel.
• Cl- leaves the cell and the membrane is depolarized.
• Sufficient depolarization causes an action potential along the ORN axon.
• Most odorants can stimulate multiple receptors and vice versa, allowing for the permutation of thousands of detectable odors.
History
• Quality:
1. Elucidate primary taste vs smell dysfunction
2. Single sided (more likely obstructive etiology) vs bilateral smell loss
3. Classification of dysfunction (see page 44)
4. Perceived degree of smell loss (complete vs partial)
5. Olfactory status prior to loss
• Timing of Onset and Duration:
1. Never had olfaction (ie, congenital)
2. Sudden (ie, trauma, URI) vs gradual (ie, sinonasal disease, tumor, presbyosmia)
3. Persistent vs intermittent (ie, CRS, polyposis)
• Associated Factors:
1. Changes to diet
2. Associated symptoms of URI, sinusitis, allergy, epistaxis, seizure, and psychiatric complaints
3. Mental changes or peripheral nerve difficulties (ie, neurodegenerative disorders)
4. Head trauma (ie, shearing injury of ON)
• Social History
1. Occupational and environmental exposure to toxins
2. Substance abuse (ie, smoking, cocaine, inhalant)
Physical Exam
• Complete ear, nose, throat exam with a focus on the following
• Otoscopy: rule out obvious middle ear pathology affecting the chorda tympani nerve
• Neurological exam: cranial nerve evaluation, optic disc exam
• Mini-mental state exam: perform if dementia or a neurodegenerative disorder are suspected
• Choice of imaging and laboratory tests is largely dependent on history and physical exam (ie, obvious history of URI-related smell loss in an otherwise healthy individual warrants no further imaging).
• CT of paranasal sinuses: indicated if obstructive etiology or sinus disease suspected
• MRI: often first line for idiopathic smell loss, also indicated for intranasal mass to assess intracranial extension, confirmation of agenesis of olfactory bulbs in Kallman syndrome (see page 46), or history of head trauma or neurologic dysfunction
• Idiopathic olfactory loss is often unrevealing on imaging; with only 0.8% of patients found to have a contributing radiographic finding on MRI in retrospective study
• Laboratory studies/tests: targets include CBC, sedimentation rate, plasma creatinine, liver function, antinuclear antibodies, thyroid function, vitamin B12, and other mineral/vitamin deficiencies
• Olfactory testing may establish degree of smell loss; monitor progression/recovery over time, and identify malingering for medicolegal purposes.
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