physiology of olfaction,classification of smell disorders,abnormalities of smell,smell detection tests,upsit

1. MODERATOR:DR SN MUKHERJEE
PRESENTER:DR RAVINDRA DAGGUPATI

2.  A proper functioning sense of smell allows a person to discriminate
between thousands of largely organic, low molecular mass, volatile
compounds and provides information regarding:
(1) the safety of a substance or environment (for example, spoiled
food, leaking natural gas);
(2) the aesthetic properties of everyday objects (for example, rose,
dirty laundry); and
(3) elements of basic communication (for example, mother/infant
interactions).

3.  Loss of smell can result in significant psychological disruption and
even generate feelings of physical and social vulnerability and
victimization.
 most patients who complain of decreased 'taste’ function actually
have an unrecognized impairment of smell.
 Diminished ‘taste’ is typically due to loss of flavour sensations
derived from retro nasal stimulation of the olfactory receptors, rather
than impairment of taste bud mediated sensations, per se.

4.  The olfactory neuroepithelium
exists within a small region of
nasal mucosa (said to be
approximately 2cm2) in the
upper recesses of the nasal
chambers lining the cribriform
plate and sectors of the
superior turbinate, middle
turbinate and septum
 This specialized epithelium is
situated behind the
approximately 1-mm wide
olfactory cleft, making it difficult
to observe even with modern
endoscopic devices.

5.  Most of the airstream coming
into the nose is shunted through
the passages around the
inferior and medial turbinates
and along the septal wall, only
10–15 percent of the air
reaches the olfactoryneuro
epithelium.
 Thus, minor changes in nasal
architecture and airflow can
result in substantial airflow
blockage to olfactory regions
without much impairment in
nasal respiratory ability
 On the other hand, too patent of
an airway, as seen with
excessive turbinate removal,
can improperly shunt air away
from the olfactory cleft, resulting
in a decrement in olfaction

6.  The human nasal passage is intermittently affected, at least in
some individuals, by the ‘nasal cycle’.
 This cycle, an autonomic ultradian rhythm of periodic
alternating side-to-side nasal turbinate engorgement and
disengorgement.
 It is said to occur in 80 percent of the normal population with a
cycle frequency ranging from 40 minutes to four hours.
 The nasal cycle alone does not appear to affect overall
olfactory sensitivity in the normal nose; however, a pre-existing
structural distortion can result in a noticeable changes

7.  Most land mammals have four specialized neural systems within the left
and right sides of the nose:
(1) the main olfactory system (cranial nerve I or CN I);
(2) the accessory olfactory system (i.e. the vomeronasal system);
(3) the trigeminal somatosensory system (CN V); and
(4) the nervus terminalis or terminal nerve (CN 0).
 CN I mediates common odour sensations (for example, vanilla, rose
and chocolate),
 CN V mediates both chemical and nonchemical stimuli in the form of
somatosensory sensations (for example, irritation, burning, cooling,
tickling, touch).
 CN V is also responsible for inducing reflexive responses, such as
secretions of mucus and halting of inhalation, that help to prevent or
minimize chemically or thermally induced damage to the linings of the
nose and lungs.

8.  The vomeronasal system is non-
functional in humans, while a
rudimentary vomeronasal tube is
present on each side of the
septum with an opening into the
human nose, it has no centrally
projecting nerve
 CN 0 was discovered after the
other cranial nerves had been
named and consists of a loose
plexus of ganglionated nerves
that, in most mammals, is in
close proximity to the
vomeronasal organ and nerve.
 It has been suggested by some
that CN 0 may be a vestige of an
ancient nerve whose function
was lost or superseded by other
parts of the nervous system,

9.  Before neural transduction can begin, odorants must:
1. enter the nose during either active (sniffing) or passive
(diffusion) processes;
2. pass through the olfactory cleft;
3. move from the air phase into the largely aqueous phase of
the olfactory mucus.
 From the mucus, odourous chemicals either diffuse or are
transported by specialized proteins (termed ‘odourant-binding
proteins’) to the receptors.

10.  In the adult, at least six distinct
classes of cells –can be identified
within the neuroepithelium :
(1) the bipolar sensory receptor
neuron is derived
embryologically from the
olfactory placode, is of central
nervous system (CNS) origin
and extends odourant receptor-
containing cilia into the mucus;
(2) The supporting or sustentacular
cell insulates the bipolar
receptor cells from one another,
regulates some elements of
mucus production and may aid
in the degradation of odourants;
(3) The duct cell of Bowman’s
glands secretes most of the
mucus within the olfactory
receptor region;

11. (4) The poorly understood
microvillar cell, located at
the surface of the
epithelium, sends tufts of
microvilli into the nasal
mucus;
(5) the horizontal (dark) basal
cells, one of two main
classes of stem cells within
the basement membrane of
the epithelium, and
(6) The globose (light) basal
cells, a multipotent basal
cell that can give rise to
neurons and nonneuronal
cells, including the
horizontal basal cells

12.  Approximately 6 million receptor cell axons ultimately coalesce
into 30–50 fascicles, termed the olfactory fila, which traverse
the cribriform plate and pia matter to synapse with second-order
neurons within the glomeruli of the olfactory bulb.

13.  It is important to recognize that the olfactory nerve cells, as well
as the proximal extra neural spaces, can serve as conduits for
the movement of viruses and exogenous agents from the nasal
cavity into the brain.
 This was recognized many years ago as a major route of
polioviruses into the brain, leading to programmes to cauterize
the olfactory epithelium of school children with zinc sulphate in
Toronto and other major cities to avert contracting polio during
epidemics.
 This ‘olfactory vector’ route has been proposed as a potential
explanation for both the olfactory loss and the aetiology of some
forms of common neurodegenerative diseases, such as
Alzheimer’s disease and idiopathic Parkinson’s disease,

14.  The olfactory bulbs are complex structures located on the
ventral surface of the frontal lobes directly over the cribriform
plate.
 The first synapse of the incoming bipolar olfactory receptor cell
neurons occurs within spherical structures making up a distinct
layer of the bulb – the glomeruli.

15.  A given receptor cell
projects to only one
glomerulus and any given
glomerulus appears to
receive most of its input
from a restricted region of
the epithelium.
 The main afferent second-
order neurons are termed
‘mitral’ and ‘tufted’ cells.
 A considerable amount of
convergence of information
occurs at the level of the
glomeruli.

17. Anosmia refers to an inability to detect qualitative olfactory
sensations (i.e. absence of smell function).
Partial anosmia defines an ability to perceive some, but not all,
odours;
hyposmia or microsmia refers to decreased sensitivity to
odours.
Hyperosmia reflects increased sensitivity to common odours.
 It reflects a patient’s heightened response to an odour, rather
than an increased ability to smell.
 This problem has been reported in some conditions associated
with a change in hormone balance, such as in pregnancy and
Addison’s disease (adrenal-cortical insufficiency), as well as
migraine, drug withdrawal, epilepsy (intericatal period), multiple
chemical sensitivity and psychosis.

18.  Dysosmia (sometimes termed cacosmia or parosmia) is
distorted or perverted smell perception to odour stimulation.
 Phantosmia is a dysosmic sensation perceived in the absence of
an odour stimulus (also known as olfactory hallucination)
 Olfactory agnosia refers to an inability to recognize an odour
sensation, even though olfactory processing, language and
general intellectual functions are essentially intact, as in some
stroke patients.
 Heterosmia – a condition where all odours smell the same;
 Presbyosmia – a decline in smell sense with age and
 Osmophobia – a dislike or fear of certain smells.

19.  Proper assessment of a patient’s smell function requires
(1) a detailed clinical history,
(2) quantitative olfactory testing and
(3) a thorough physical examination emphasizing the head and
neck with appropriate brain and rhinosinus imaging.

20.  Does the patient have a problem with smell, taste or both?
 Mode of onset, duration of impairment and pattern of
occurrence?
 Sudden olfactory loss can be consistent with possible head
trauma, ischaemia, infection or a psychiatric condition.
 Gradual loss may indicate a progressive and obstructive lesion
in or around the naso sinus region, particularly if the loss is
unilateral.
 Intermittent loss may suggest an inflammatory process in
association with nasal and sinus disease.

21.  Any history of precipitating antecedent events, such as head
trauma, viral upper respiratory infections, chemical or toxin
exposures and nasosinus surgeries?
 Does the patient have any nasal discharge that is mucous-
appearing (for example, allergy), purulent (for example, infection),
or clear (CSF rhinorrhoea after trauma)?
 Comorbidities such as renal failure, liver disease, hypothyroidism,
diabetes ?
 Are smells present without an obvious stimulus?
 Given the strong relationship of Alzheimer’s disease and idiopathic
Parkinson’s disease to smell impairment, one should also look for
memory- and parkinsonism related complaints in older patients.

22.  Any signs of trauma such as healing wounds, scarring or
distorted nasal or skull architecture?
 Inspection of the nasal passages to view the peripheral nasal
cavity for signs of polyps, congestion, deviation of septum or
inflammation.
 Nasal endoscopy, employing both flexible and rigid scopes, is
needed to ensure thorough assessment of the olfactory meatal
area.
 The additional presence of polyps, masses and adhesions of
the turbinates to the septum may adequately obstruct airflow.

23.  The presence of mucopus above the Eustachian tube orifice
suggests posterior ethmoid and/or sphenoid sinus disease.
 A pale mucous membrane suggests allergy, usually as a result
of oedema within the lamina propria.
 Atrophy of the lamina propria is suggested by unusual
spaciousness, dryness and crusting, as is seen in atrophic
rhinitis.
 The neurological evaluation should focus on cranial nerve
functions,

24. 40-item University of Pennsylvania Smell Identification Test
(UPSIT).
 The UPSIT is commercially known as the Smell Identification TestTM
 It is the most widely used olfactory test, having been administered
to an estimated 400,000 patients since its development.

25.  The UPSIT can be self
administered in 10–15 minutes by
most patients in the waiting room,
and scored in less than a minute
by nonmedical personnel.
 Each page contains a
microencapsulated odourant that
is released by means of a pencil
tip.
 The reliability of this test is very
high (test– retest, r = 0.94).

26.  This test consists of four booklets containing ten
microencapsulated (‘scratch and sniff ’) odourants apiece.
 Test results are in terms of a percentile score of a patient’s
performance relative to age- and sex-matched controls, and
olfactory function can be classified on an absolute basis into one
of six
 categories:
 1. normosmia,
 2. mild microsmia,
 3. moderate microsmia,
 4. severe microsmia,
 5. anosmia and
 6. probable malingering.

28.  To accurately assess olfaction
unilaterally, the naris
contralateral to the tested side
should be occluded without
distorting the patent nasal
valve region
 An easy way of doing this is to
seal the contralateral naris
using a piece of Microfoam
cut to fit the naris borders.
 The patient is instructed to
sniff the stimulus normally and
to exhale through the mouth.

29. Smell threshold test.
 It can be employed either alone or combined with UPSIT
 A commonly employed test uses phenyl ethyl alcohol as the
odourant and establishes the threshold employing a staircase
procedure.
The recording of olfactory event-related potentials (OREP) is
done for assessing the integrity of the olfactory system.
Brain electroencephalography (EEG) the test consists of
discerning synchronized brain activity recorded from overall
EEG activity following brief presentations of odorants.

30.  Computed tomography (CT), is the most useful and cost-effective
technique to assess sinonasal tract inflammatory disorders,
 MRI is better to evaluate soft tissue and is the technique of choice to
image the olfactory bulbs, tracts and cortical parenchyma
 Positron emission tomography (PET), single-proton emission
computed tomography (SPECT) and functional MRI (fMRI) are other
imaging modes of choice

31.  Loss of olfactory function can be subdivided into two classes:
(1)conductive or transport impairments result from
obstruction of the nasal passages (for example, chronic nasal
inflammation, polyposis, etc.)
(2) sensorineural impairments result from damage to the
olfactory neuroepithelium, central tracts and connections (for
example, viruses, airborne toxins, tumours, seizures, etc.).

32.  The conditions which can decrease the nasal airflow and block
the access of odorants to the olfactory epithelium; however,
patients may still have some retronasal airflow, allowing the ability
to detect the flavor of food.
 Causes of decreased nasal airflow include nasal septal
deformities, nasal polyposis, tracheostomy, or nasal cavity tumors,
post op adhesions.

33.  2.1. Upper Respiratory Infections
 Loss of olfaction after a URI is one of the most common causes
of smell disorders, and occurs more commonly in women and
the elderly.
 Olfactory dysfunction during a URI can initially be conductive,
but persistence of loss of smell after resolution of other
symptoms indicates sensorineural injury to the olfactory
epithelium.
 Most common etiology is viral infection with rhinovirus,
coronavirus, parainfluenza virus, and Epstein-Barr virus
 Other infectious causes that have been reported include
hepatitis, herpes simplex encephalitis, pneumonia and variant
Creutzfeldt–Jacob disease.

34.  Given the ability of the olfactory receptor neurons to regenerate,
spontaneous recovery of some smell function is theoretically
possible over a prolonged period.
 However, complete recovery is less likely, the longer the patient
has the loss, and is inversely related to the degree of dysfunction.

35. 2.2. Head trauma
 Head trauma often results in smell loss, particularly where rapid
acceleration/deceleration of the brain occurs
(i.e.coup/contrecoup injury).
 The prevalence of olfactory loss following head trauma is
around 15 percent and is proportional to the severity of the
injury.
 Blunt trauma to the occiput has been found to produce greater
olfactory loss than trauma to the front of the head.
 Following head trauma, the loss of smell is usually, but not
always, immediate.
 However, it may take a while for the patient to recognize the
presence of the dysfunction.
 Fracturing of the cribriform plate is not a prerequisite for smell
loss.

36.  Common mechanisms include-
 Disruption from shearing forces of
the olfactory fila through the
sinonasal tract,
 Intracranial haemorrhage and
ischaemia can lead to
degeneration of the olfactory
epithelium without transection of
the olfactory nerves.
 Iatrogenic trauma, such as
surgery, can cause smell
impairment and has been seen
with such procedures as sinus
surgery and craniotomy.

37. 2.3. Tumours and mass lesions
 A number of tumours in and around the olfactory bulbs or tracts
can cause olfactory disturbance.
Examples include
 olfactory groove meningiomas,
 frontal lobe gliomas and
 suprasellar ridge meningiomas arising from the dura of the
cribriform plate.
 temporal lobe tumours.
 Structural lesions affecting smell may also affect vision
 Also, olfactory tumours may extend into the frontal lobes
resulting in symptoms of dementia and possibly the release of
primitive reflexes (for example, grasping, snout and glabellar).

38.  Mass lesions around the olfactory region can result in a Foster-
Kennedy syndrome, which consists of:
(1) ipsilateral anosmia;
(2) ipsilateral optic atrophy and
(3) contralateral papilloedema (d/t raised intracranial pressure.)
 Pseudo-Foster-Kennedy syndrome has been reported in
patients with increased intracranial pressure, without any
evidence of mass lesion on MRI.
Fundoscopic findings of papilloedema in one
eye and optic atrophy in the other.

39.  2.4. Congenital Loss
• Accounts for about 3% of anosmia.
• Usually an isolated finding.
• Patients often present during their preteen or teenage years
with an inability to smell, often discovered by family members.
 They may have distinct food preferences due to their inability to
appreciate the flavor of food while retaining the ability to detect
the fundamental taste sensations from the taste buds.

40.  Recent studies have demonstrated that genetic mutations in the
gene SCN9A, which encodes the voltage-gated sodium channel
Nav1.7, cause congenital anosmia.
 Associations exist between congenital anosmia and several
abnormalities including
 Kallmann syndrome,
 de Morsier’s syndrome,
 holoprosencephaly,

41.  Kallmann syndrome consists of anosmia and hypogonadotropic
hypogonadism and has autosomal or X-linked forms.
 Patients usually lack olfactory bulbs and the gonadotropin-
releasing hormone, resulting in hypogonadism.
 The defects are due to a lack of migration of GnRH-releasing
cells from the olfactory placode to the hypothalamus and a lack
of migration of the olfactory neurons to the olfactory bulb and
hypothalamus.

42.  Magnetic resonance
imaging (MRI) findings may
reveal aplasia or hypoplasia
of the olfactory bulb, or
associated encephalocele
or abnormality in the frontal
lobe.

43. Septo-optic dysplasia (SOD), (de Morsier syndrome)
 It is a rare congenital malformation syndrome featuring-
1) optic nerve hypoplasia,
2) pituitary gland dysfunction, and
3) absence of the septum pellucidum (a midline part of the brain).
 Two of these features need to be present for a clinical diagnosis —
only 30% of patients have all three.
 Patients with septo-optic dysplasia (de Morsier’s syndrome) can
have hyposmia, visual symptoms and precocious puberty.

44. Holoprosencephaly (HPE, once known as arhinencephaly)
 It is a cephalic disorder in which the prosencephalon (the
forebrain of the embryo) fails to develop into two hemispheres.
 The condition can be mild or severe.
 According to the National Institute of Neurological Disorders and
Stroke(NINDS), "in most cases of holoprosencephaly, the
malformations are so severe that babies die before birth."

45.  When the embryo's forebrain
does not divide to form
bilateral cerebral hemispheres
(the left and right halves of the
brain), it causes defects in the
development of the face and in
brain structure and function.

46. 2.5. Toxins
 A large number of toxins are associated with olfactory loss.
These include-
 Environmental pollutants.
 Specific metal fumes (Cadmium, Chromium, Nickel, Mercury,
Lead etc).
 Gas exposure from industrial plants (formaldehyde, methyl
bromide).
 Solvents including toluene and paint solvents.
 Tobacco smoke.

47.  Within the supporting cells and Bowman’s glands are high
levels of xenobiotic enzymes, including cytochrome P450
monooxygenases and other biotransformation enzymes.
 These enzymes detoxify inhaled or systemic substances,
presumably to protect the olfactory neurons and CNS, or to
process odorant molecules for receptor activation.
 Byproducts of these enzymes may include toxic metabolites,
which themselves may damage the olfactory epithelium.

48.  Metals, in the form of dust or fumes, can be toxic to the
olfactory system.
 The most well-known is Cadmium, used in the production of
batteries, semiconductors, and electroplating.
 Factory workers exposed to Chromium, which is often used with
nickel in industrial manufacturing and steel production, can have
increased olfactory thresholds.
 Other metals linked to olfactory loss include manganese, mercury,
aluminum, and lead.

49.  Tobacco smoke exposure is associated with hyposmia in active
smokers.
 Studies find increased olfactory receptor neuron apoptosis
with tobacco smoke exposure.
 In one study, the olfactory scores of former smokers were not
significantly different than the scores in lifelong
nonsmokers,suggesting that the olfactory ability can return
with cessation of smoking.

51.  2.6. Age
 Under the age of 65 years, approximately 1% of the population
has major difficulty in smelling.
 Between 65 and 80 years, this increases remarkably, with about
half of the population experiencing a demonstrable decrement
in the ability to smell.
 Over the age of 80, this figure rises to nearly 75%.
 There is accumulation of damage over the years, and a single
event, such as a bad cold, can be the precipitating factor.

52. The age-related changes in smell
function are due to-
1. Damage to the olfactory
receptors.
2. Decreased activity of Basal cell to
regenerate.
3. Replacement of olfactory
epithelium by respiratory
epithelium.
4. Occlusion of the foramina of the
cribiform plate, pinching off the
axons of the olfactory receptor
cells as they enter the brain
cavity.
5. Decreases in number of glomeruli
within the olfactory bulb.
Low magnification of the surface of the
nasal cavity taken from a transition
region.
Patches of respiratory epithelium (R; dark
areas) can be seen within the olfactory
(O) region (×28).

53. 2.7. Neurodegenerative disorders
 In patients with Alzheimer and Parkinson diseases, 90%
exhibit olfactory dysfunction in the early stages of the diseases.
 Olfactory loss may be the first clinical sign of these
neurodegenerative diseases, preceding signs of dementia in
Alzheimer disease (AD) or motor symptoms in Parkinson disease
(PD) by several years.
 Neurofibrillary tangles and neuritic plaques appear in the olfactory
bulb, anterior olfactory nucleus, and olfactory cortex in patients
with AD.
 First degree family members of patients with AD were found to
have significantly reduced smell identification scores, pointing to
genetic predisposition in the development of the disease.

54.  Smell identification is the most accurate predictor of the presence
of PD compared with healthy controls in motor and nonmotor
diagnostic tests for PD.
 Huntington disease is also characterized by olfactory deficits and
findings of degeneration of central olfactory degeneration.
 Multiple Sclerosis: a recent study suggested that hyposmia was
present in almost 50% of patients within a known MS group.

55. 2.8. Epilepsy and migraine
 Olfactory auras, also described as hallucinations, are rare.
 When present, they are often associated with seizures and
headaches.
 Olfactory auras consist of sudden unexplained sensations of
smell that are usually, but not always, unpleasant and are rarely
isolated events.
 In epilepsy, amygdala and hippocampus – have been
implicated as the generators of ictal olfactory sensations
 Common aetiologies include mesial temporal sclerosis and
tumours.

56.  Most of the treatments are available for conductive anosmia.
 Conductive and sensorineural olfactory losses are often
distinguishable using a brief course of systemic steroid therapy
 patients with conductive impairment frequently respond positively
to the treatment, although long-term systemic steroid therapy is
not advised.

57.  Proper allergy management is essential and may require the
use of an antihistamine.
 When a bacterial infection is suspected (for example, infectious
rhinosinusitis), a course of antibiotics should be used.
 Surgery should be considered for:
(1) very large and medically refractory polyps, or
(2) situations where a malignant neoplasm is suspected.

58.  Sensorineural impairment of olfaction is typically more difficult
to manage and the prognosis for patients suffering from long-
standing total loss due to upper respiratory illness or head
trauma is poor.
 The majority of patients who recover smell function subsequent
to trauma do so within 12 weeks of injury.
 Patients who give up smoking typically have dose-related
improvement in olfactory function and flavour sensation over
time.
 Central lesions, such as CNS tumours that impinge on olfactory
bulbs and tracts can often be resected with significant
improvement in olfactory function.

59.  When epilepsy or migraine is suspected, a course of
antiepileptic or antimigraine medications may prove beneficial.
 Medically refractory epilepsy resulting in olfactory disturbance
can be successfully treated with surgery
 In patients with multiple sclerosis, immunomodulatory
therapies, including interferon-beta and occasional steroids, is
the mainstay of treatment.
 When depression or psychosis is suspected, a course of an
antidepressant and appropriate psychiatric referral may be
necessary.

61.  In patients with complete anosmia, supportive measures are
necessary to protect them from further harm.
 1. Smoke and carbon monoxide detectors need to be installed and
properly working.
 2. When possible, electrical appliances should be used instead of
gas appliances.
 3. Expiration dates for food products should be scrutinized and old
food items checked by someone with normal smell function or
discarded.
 4. A balanced diet, particularly in the elderly, must be kept to
prevent weight loss and malnutrition.
 Adding flavour enhancers (for example, monosodium glutamate,
food colouring, chicken or beef stock) to foods can also help with
their appeal.

62. Jai hind