PHYSIOLOGY OF OLFACTORY SYSTEM & IT’S DISORDERS

Presented byDr. Yousuf F. Choudhury

PGT, ENT Dept.Silchar Medical College

Moderated byDr. Shams Uddin

Prof. & HOD, ENT Dept.Silchar Medical College

INTRODUCTION

• Sense of smell has been recently heavily studied because of it’s importance to human being’s survival.

• It helps to track food , water, mate and even communicate.

• It can alert us to danger like gas leak, fire, rotten food.• It is also linked to brain that process emotion and

memory.• Although not acute as animals, human beings sense

of smell can detect 10,000 different odor molecules

BRIEF ANATOMY OF OLFACTORY SYSTEM

• Olfactory receptors are located high in the nasal vault, within a pseudostratified sensory epithelium lining the cribriform plate and sectors of the superior turbinate, middle turbinate and superior part of the septum.

• In each nostril, the olfactory neuro-epithelium has a surface area of about 2-4 square centimeters with density of 5×104

• The neuro-epithelium is pale yellow in color.• Six general classes of cells are found within neuroeptithelium

structure: *ciliated bipolar sensory receptor cells, *supporting or sustentacular cells , *microvillar cells , *Bowman’s glands and duct cells, *globose basal cells and *horizontal basal cells

OLFACTORY RECEPTOR

• The Receptor cells, which harbor the receptors on their cilia, are derived embryologically from the olfactory placode and hence are of central nervous system origin. The axons of these ~ 6 million cells converge into 50 or so “fila” ensheathed by glia that traverse the cribriform plate to form the outermost layer of the olfactory bulb

• The mucosal end of the olfactory cell forms a knob .• From knob 4 to 25 olfactory hairs (olfactory cilia), project into the

mucus that coats the inner surface of the nasal cavity.

• These projecting olfactory cilia form a dense mat in the mucus.

• These cilia react to odors in the air and stimulate the olfactory cells

SUPPORTING CELLS/SUSTENTACULAR CELLSThe receptor cells in the olfactory epithelium are interspersed among sustentacular cells or supporting cells.

Supporting cells are columnar epithelial cells.

They provide physical support, nourishment and electrical insulation for the olfactory receptors,

They help to detoxify chemicals that come in contact with the olfactory epithelium.

BASAL CELLS• Basal cells are stem cells located between

the bases of the supporting cells.

• They continually undergo cell division to produce new olfactory receptors, which live for only a month or so before being replaced.

• This process is remarkable - olfactory receptors are neurons, and mature neurons are generally not replaced.

• The olfactory renewal process is carefully regulated by bone morphogenic protein (BMP) exerts an inhibitory effect.

**[ BMPs are a large family of growth factors originally described as promoters of bone growth]

Spaced among the olfactory cells in the olfactory membrane are many small BOWMAN’S GLANDS that secrete mucus onto the surface of the olfactory membrane

Mucus is carried to the surface of the epithelium by ducts.

The secretion moistens the surface of the olfactory epithelium and dissolves odorants so that transduction can occur.

Function of MICROVILLAR CELL is still unknown.

The vomeronasal organ is a specialized bilateral membranous structure located in the base of the anterior nasal septum, at the junction of the septal cartilage and the bony septum. It is believed to detect external chemical signals called pheromones. These signals, which are not detected consciously as odors by the olfactory system, mediate human autonomic, psychological, and endocrine responses.

The trigeminal nerve innervates the posterior nasal cavity to detect noxious stimuli like ammoniacal smell.

PHYSIOLOGY OF OLFACTION

THEORIES OF SMELL STIMULATION

• VIBRATION THEORIES• OLFACTORY PIGMENT THEORIES• ENZYME THEORIES• PENETRATION AND PUNCTURING THEORY

(Most acceptable)

Cilium is the portion which respond to the olfactory chemical stimuli.

The odorant substance on coming in contact with olfactory surface first diffuse in to the mucus which covers the cilia.

Then binds with a receptor protein that protrudes through the ciliary membrane.

This receptor is a long molecule, it threads its way through the membrane 7 times, folding inward and outward.

Odorant binds with portion of receptor and coupled to G-PROTEIN.

G-PROTEIN –a combination of heterotrimeric subunits.

MECHANISM OF EXCITATION OF OLFACTORY CELLS

On excitation of receptor, an alpha subunit breaks away from G-PROTEIN and activates adenylcyclase.

Activated cyclase converts many molecules of intracellular adenosine-tri-phosphate into cyclic-adenosine monophosphate(cAMP).

This cAMP activates another near by membrane protein, a gated sodium ion channel.

Allows large number of sodium ions to pour into receptor cell cytoplasm.

Sodium ions helps in exciting the olfactory neuron and transmitting action potential in to the CNS through an olfactory nerve.

OLFACTORY STIMULUS There is a latent phase of 400ms before generating small action

potential which can be measured by ELECTROOLFACTOGRAM by keeping electrodes in olfactory neuroepithelium.

The speed of the rising phase varies with intensity of stimulus. The recovery phase or falling phase is an exponential decay with

a time constant of 0.9–1.45 ms. Olfactory responses show both variations in thresholds and

adaptations. Thresholds of perception is lower than identification i.e. smell is

sensed before recognized. Thresholds depend on levels of inhibitory activity, which are

generated by higher centers. Some animals, particularly dogs, have much lower thresholds.

Odorant + receptor protein

Activation of G protein

Activation of adenylate cyclase

ATP cAMP

Opening of Na+ channels

Na+ influx

depolarization

Mechanism of olfactory cell stimulation

PHYSICAL FACTORS AFFECT THE DEGREE OF STIMULATION

Only volatile substances that can be sniffed into the nostrils can be smelled.

The stimulating substance must be at least slightly water soluble so that it can pass through the mucus to reach the olfactory cilia.

The substance should be at least slightly lipid soluble, because lipid constituents of the cilium itself are a weak barrier to non-lipid-soluble odorants.

THEORIES OF ODOR QUALITY

• VIBRATION THEORY• PENETRATION AND PUNCTURE THEORY• SPECIFIC THEORY

ODOR DISCRIMINATION

• How odors are recognized are exactly not resolved.

• There is theory that receptors are selectively sensitive.

• If two odors are mixed, the resulting intensity is always less than the sum of the two individually perceived intensities and is dominated by the stronger component

• Cribriform plate , part of ethmoid bone separates nasal cavity and cranial cavity.

• Olfactory bulb lies above cribriform plate.

• Small nerves from olfactory membrane in nasal cavity pass through the small perforations in the cribriform plate to enter olfactory bulb in the cranial cavity.

• The olfactory bulb is composed of six concentric layers: *the olfactory nerve layer on the surface, *glomerular layer, *external plexiform layer, *mitral cell layer, *internal plexiform layer and *granule cell layer.

• The unmyelinated axons of the olfactory nerve cells enter the glomerular layer, where they synapse with the second-order neurons, primarily mitral and tufted cells.

• These second-order neurons, in turn, send collaterals that synapse within the periglomerular and external plexiform layers of the bulb, in some cases resulting in self-inhibition of the second-order neurons and in others facilitating or inhibiting the firing of neighboring cells.

• Olfactory nerve fibers leading from olfactory bulb are called Cranial nerve I or olfactory Tract.

OLFACTORY PATHWAYS INTO THE CNS

• The olfactory tract enters the brain at the anterior junction between the mesencephalon and cerebrum;

• there, the tract divides into two pathways, one passing medially into the medial olfactory area of the brain stem, and the other passing laterally into the lateral olfactory area.

• The medial olfactory area represents a very old olfactory system, whereas the lateral olfactory area is the input to (1) A less old olfactory system and (2) a newer system

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Olfactory pathway

Olfactory Tract

Medial Olfactory stria Lateral Olfactory stria

Septal Nuclei

HypothalamusLimbic system(primitive parts)

Prepyriform cortex Pyriform Cortex Entorhinal area Amygdala

Limbic system(hippocampus)

Thalamus

Orbitofrontal Cortex

Olfactory receptor cell Olfactory nerveOlfactory bulb

(Very Old Olfactory System)

(Less Old Olfactory System)

(Newer System)

• Very Old Olfactory SystemMore primitive responses to olfaction

Salivation, licking lips and primitive emotional drives to smell

• Less Old Olfactory System Learned control of food intake

Aversion to food that have caused nausea and vomiting.

• Newer System Conscious perception & analysis of odor

Odor discrimination

OLFACTORY DYSFUNCTION

TYPES OF OLFACTORY DYSFUNCTION

o Anosmia- absence of smello Hyposmiamicrosmia- diminished olfactory sensitivityo Dysosmia- distorted sense of smello Phantosmia- perception of an odorant when none is

presento Agnosia- inability to classify, contrast, or identify odor

sensations verbally, even though the ability to distinguish between odorants may be normal

o Hyperosmia- Abnormally acute smell function ( Rare condition )

CLASSIFICATION & ETIOLOGY

• TRANSPORT OLFACTORY LOSSOlfactory dysfunctions can be caused by conditions that interfere with the access of the odorant to the olfactory neuro-epithelium due to either swollen nasal mucous membrane, structural changes and/or mucus secretion.

Causes- Allergy rhinitis, Bacterial rhinitis and sinusitis, Congenital abnormality like encephalocele, Deviated Nasal Septum, Nasal neoplasms, Nasal polyps, Nasal surgery, Old age, Viral infections.

• SENSORY OLFACTORY LOSSOlfactory dysfunctions can be caused by conditions that damage to the neuroepithelium.

Causes- Drugs that affect cell turn over and inhalations of toxic chemicals, viral infections, neoplasms, radiation therapy.

• NEURAL OLFACTORY LOSSOlfactory dysfunctions can also be caused by conditions that damage the central olfactory pathways.

Causes- AIDS, Alzheimer’s disease, Alcoholism, Chemical Toxins, Cigarette smoke, Diabetes Mellitus, Depression, Drugs, Huntington’s chorea, Hypothyroidism, Kallmann syndrome, Korsakoff psychosis, Malnutrition, Neoplasm, Neurosurgery, Parkinson disease, Trauma, Vitamin B12 def., Zinc deficiency

APPROACH TO OLFACTORY DYSFUNCTIONA. DETAILED MEDICAL HISTORYOnset, course, nature of impairment, their previous illness and the medications taken.

B. PHYSICAL EXAMINATIONThorough ENT, head and neck examinations including nasal endoscopy.A neurological examination emphasizing the cranial nerves, cerebellar and sensorimotor function is essential.Psychological examination like general mood and check for signs of depression should be done.

C. LABORATORY FINDINGSBiopsy of olfactory neuroepithelium can be done in rare cases

D. IMAGINGCoronal CT scan and MRI Brain are useful.

SENSORY EVALUATIONSensory evaluation is necessary to 1)corrobrate the patient’s complaint, 2)evaluate the efficacy of treatment and 3)determine the degree of impairment.Qualitative and quantitative Tests for evaluation of Olfactory sensations-I. ODOR STIX TESTII. TWELVE INCH ALCOHOL TESTIII. SCRATCH AND SNIFF CARDIV. UNIVERSITY OF PENNSYLVANIA SMELL IDENTIFICATION

TEST (UPSIT).V. Threshold Olfactory tests.

UNIVERSITY OF PENNSYLVANIA SMELL IDENTIFICATION TEST (UPSIT)

• Most commonly used & most superior and reliable test.• Self-administered in 10-15 minutes• Scored in < 1 minute by non-med person• Available in various languages• 40 “scratch & sniff “ patches• Pt. chooses from 4 answers & must choose 1• Can detect malingering• Dysfunction classified as Normosmia, anosmia, mild,

moderate or severe microsmia, or probable malingering.

UPSIT

DIFFERENTIAL DIAGNOSIS• At present, no psychophysical methods to differentiate

sensory from neural hearing loss.• History of olfactory loss gives an important clues to the cause.• Leading causes of olfactory dysfunctions are head trauma and

viral infections.• Head trauma are more common cause of anosmia in children

and young adults whereas viral infections are more common cause in older adults.

• Congenital anosmia occurs in Kallmann syndrome and also in albinism.

• Meningioma of inferior frontal region is the most common neoplastic cause of anosmia.

• Dysomia is associated with depression.

TREATMENT

• Transport olfactory lossThe following treatments are effective in restoring sense of smell :i. Allergy managementii. Antibiotic therapyiii. Topical and systemic glucocorticoid therapyiv. Operations for nasal obstruction.

• Sensorineural Olfactory loss.No treatment with demonstrated efficacy for Sensorineural Olfactory loss. Fortunately, spontaneous recovery occurs.Some clinicians advocate zinc and vitamin therapy esp Vitamin A.

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