This presentation is a Post graduate level study material compilation of information from standard textbooks.

1. PHYSIOLAOGY
OF OLFACTION
MODERATOR: DR VIKAS
PRESENTER: DR AVINAV

2. Learning Objectives
1) Important aspects of olfactory anatomy and physiology,
2) Describes the common olfactory disorders encountered in clinical practice
3) Provides current practical techniques for the evaluation and management of smell
disturbance.

3. INTRODUCTION
Olfaction or Olfactory perception - the sense of smell mediated by a group of
specialized sensory cells in nasal cavity.
odour - the property of a substance which gives it a particular smell.

4. Importance?
•Safety of a substance or environment
•Flavors of food and aids digestion
•Aesthetic properties
•Elements of basic communication
•Quality of life, Nutrition, longevity
•Profession (cooks, homemakers, firefighters, plumbers, wine merchants, chemical plant
workers, etc)

5. Our role:
•Validate and characterize a patient’s olfactory complaint
•Identify patients who might be malingering
•Quantify and document known presurgical smell impairment
•Longitudinally, follow the course of smell function in the midst of a therapeutic
intervention or during recovery from previous loss.

7. The nose: Structure in relation to
smell
•~2 cm2
•1mm wide, 7 cm deep
•10-15%
•Small polyp
•Too patent airway
•nasal cycle

8. Four neural systems within the
human 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)
4. The nervus terminalis or terminal nerve (CN 0)

11. Medial Olfactory area Lateral Olfactory area
Septal Nuclei
Prepyriform cortex
Pyriform Cortex
Amygdala
Thalamus
Olfactory receptor cell
Hypothalamus
Limbic system
(primitive parts)
Limbic system
(hippocampus)
Orbitofrontal
Cortex
Olfactory nerve
Olfactory bulb
Olfactory Tract
Olfactory pathway

12. OLFACTORY EPITHELIUM
•Olfactory sensory neurons present in
olfactory epithelium.
•Humans Microsmatic
•10 to 20 million bipolar olfactory sensory
neurons
•Supporting cells and basal cells
•Cilia
•Odorant receptors
•The axons of the olfactory sensory
neurons pass through the cribriform plate
of the ethmoid bone and enter the
olfactory bulbs

13. Olfactory Mucus Membrane
• Nervous System closest to external environment
• Secreted from Supporting cells and Bowman`s gland in
lamina propria & respiratory mucosa.
• Moist & protective environment.
• Disperses odourants to olfactory receptors.

14. OLFACTORY BULBS
•Mitral cells and Tufted cells
•Olfactory glomeruli
•Tufted cells are smaller than
the mitral cells and have
thinner axons, but both types
send axons into the olfactory
cortex, and have similar
function

15. • Periglomerular cells and
Granule cells.
The mitral or tufted cell
excites the granule cell by
releasing glutamate, and
the granule cell in turn
inhibits the mitral or tufted
cell by releasing GABA.

16. OLFACTORY CORTEX
•The axons of the mitral and tufted cells pass
posteriorly through the lateral olfactory stria to
terminate on apical dendrites of pyramidal cells in
regions of the olfactory cortex
•Primarily ipsilateral, some contralateral projection via
anterior commissure

17. Higher order brain regions targeted by mitral cells

18. • Anterior olfactory nucleus - Coordination of inputs from contralateral
olfactory cortex transfer of Olfactory memories from one side to
other
• Pyriform Cortex - Olfactory discrimination
• Amygdala - Emotional response to olfactory stimuli
• Entorhinal Cortex - Olfactory Memories
• Orbitofrontal cortex - Conscious discrimination of odors
• The orbitofrontal activation is generally greater on the right side than the
left; thus, cortical representation of olfaction is asymmetric

19. •There is a rich supply of centrifugal fibre projections from sectors of the
olfactory cortex and other central structures to the olfactory bulb which
modify and control olfactory input.
•Third-order projections occur, in a reciprocal fashion, to numerous regions,
including thalamus, hypothalamus, hippocampus, and the orbitofrontal
cortex.
•Areas of the cortex that result in smell perception when stimulated include
the pre-piriform and intermediate piriform cortices.

20. • Lesions of the olfactory
system anterior to the
olfactory trigone (including the
neuroepithelium, fila, bulb,
and tract) can result in total
lack of smell on the affected
side.
• However, lesions within
olfactory structures more
posterior to the olfactory
trigone do not typically cause
complete loss.

21. • Glutamate-Main Neurotransmitter
• Dopamine- modulation of
Olfactory nerve input.
• Olfactory receptors are G protein-
coupled receptors that dissociate
upon binding to the odorant.
• The α-subunit of G proteins
activates adenylate cyclase to
catalyze production of cAMP,
which acts as a second
messenger to open cation
channels.
• Inward diffusion of Na+ And Ca2+
produces depolarization.

22. OLFACTORY THRESHOLDS &
DISCRIMINATION
•Methyl mercaptan 500pg/l air, Ethyl Ether 5mg/l air
•More than 10,000 different odors
•Determination of differences in the intensity of any given odor
is poor

23. SIGNAL TRANSDUCTION
•The genes that code for about 1000 different types of odorant
receptors make up the largest gene family so far described in
mammals
•But all the odorant receptors are coupled to heterotrimeric G protein
•Although there are millions of olfactory sensory neurons, each
expresses only one of the 1000 different odorant receptors.
•Each neuron projects to one or two glomeruli. This provides a distinct
two-dimensional map in the olfactory bulb that is unique to the odorant.
•Lateral inhibition mediated by periglomerular cells and granule cells
sharpens and focuses olfactory signals.

25. VOMERONASAL ORGAN
•The organ is not well developed in humans, but an anatomically separate and
biochemically unique area of olfactory epithelium occurs in a pit in the anterior third of
the nasal septum.
•Relationship between smell and sexual function
•Not advised to disturbed during surgeries unless needed.

26. • SNIFFING: Sniffing is a semireflex response that usually
occurs when a new odor attracts attention.
• ROLE OF PAIN FIBERS : Characteristic “odor” of such
substances as peppermint, menthol, and chlorine.
Activation of these endings by nasal irritants also initiates
sneezing, lacrimation, respiratory inhibition, and other
reflexes.
• ADAPTATION: Mediated by Ca2+ acting via calmodulin on
cyclic nucleotide- gated (CNG) ion channels. When the
CNG A4 subunit is knocked out, adaptation is slowed.

27. Summary: olfactory pathway
• Olfactory receptor neurons detect odorants
in mucosa.
• Signals are sent via olfactory receptor neurons
to bulb structures (glomeruli).
• Mitral and tufted cells carry signals to
orbitofrontal cortex, temporal lobe, and the
limbic system.

28. Molecular structure
Electrochemical Reactions
Stereospatial patterns
Molecular Properties
Olfactory mucus morphology
Theories of olfaction

29. • Moncrieff (1967)
• Molecular structure is important.
Molecular theory
• Briggs and Duncan (1962)
• Some cells contain carotenoids
which give rise to photochemical
reactions.
Electrochemical
reactions
• Mozell (1970)
• Lock and key theory.
Stereospatial
patterns

30. • Laffort, Patte, Etcmeto (1974)
• Molecule has properties of
receptor specificity, proton
affinity and donation, local
polarization.
Molecular
properties
• Holley and Doving (1977)
• The pattern of the stimulus
within the mucosal
configuration of receptor cells
detects the nature of the smell.
Olfactory
mucosa
morphology

31. Anosmia
• Inability to
detect
qualitative
olfactory
sensations
Partial
anosmia
• Ability to
perceive
some, but
not all,
odours
Hyposmia or
microsmia
• Decreased
sensitivity
to odours
Osmophobia
• dislike or
fear of
certain
smells.
Olfactory disorders

32. Hyperosmia
• Increased
sensitivity to
common odours
•Cacosmia/
Dyosmia/Parosmia
• Distorted or
perverted smell
perception
Phantosmia/
Olfactory
hallucination
• Dysosmic
sensation
perceived in the
absence of an
odour stimulus
Olfactory disorders

33. Olfactory agnosia
• Inability to
recognize an odour
sensation, even
though olfactory
processing,
language, and
general intellectual
functions are
essentially intact
Heterosmia
• Condition where all
odours smell the
same
Presbyosmia
• A decline in smell
sense with age
Olfactory disorders

34. Clinical evaluation of smell function
• A detailed clinical history
• Objective quantitative olfactory testing
• A thorough physical examination emphasizing the head and
neck with appropriate brain and rhino sinus imaging

35. History
•Sudden olfactory loss: trauma, ischaemia, infection, or a psychiatric
•Gradual loss: progressive and obstructive lesion in or around the
nasosinus region particularly if the loss is unilateral.
•Intermittent loss: inflammatory process in association with nasal and
sinus disease.
•Seasonal variation: allergic seasonal rhinitis
•Precipitating antecedent events, such as head trauma, viral upper
respiratory infections, chemical or toxin exposures, and nasosinus
surgeries
•Nasal discharge: mucus/ purulent/ clear

36. History
•Drugs of abuse, such as intra-nasal cocaine, ethanol, or tobacco
•Comorbidities: renal failure, liver disease, hypothyroidism, diabetes, or
dementia
•Kallmann’s syndrome - Delayed puberty in association with anosmia (with or
without midline craniofacial abnormalities, deafness, and renal anomalies
•Family history
•Malingering is readily detected in most patients by forced-choice olfactory
testing. Malingerers frequently perform more poorly than expected on the
basis of chance on such tests.

37. Physical examination and evaluation
•Any signs of trauma
•Inspection of the nasal passages with forceps/ endoscopy (polyp or
Forigen body)
•Condition of mucus membrane
•Presence of pus: eustachian tube orifice- above/below
•Atrophy, erosion, exudates and ulcerations
•Other cranial nerves

38. Quantitative Olfactory Testing
1. 3 item Pocket smell test
2. UPSIT
3. OERPs

40. UPSIT
•University of Pennsylvania Smell Identification Test
•40 items test
•Can be self- administered in 10 to 15 minutes by most patients
•This test consists of four booklets containing 10 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
•Olfactory function can be classified on an absolute basis into one of
six categories: normosmia, mild microsmia, moderate microsmia,
severe microsmia, anosmia, and probable malingering.

41. To accurately assess olfaction unilaterally, the naris contralateral to the
tested side should be occluded without distorting the patent nasal valve
region.
Seal the contralateral naris using a piece of Microfoam™ tape (3M
Corporation,Minneapolis, MN) cut to fit the naris borders.
A smell threshold test employs phenyl ethyl alcohol as the odourant and
establishes the threshold employing a staircase procedure.

42. OERPs
Olfactory event-related potentials
Using brain electroencephalography (EEG), the test consists of
discerning synchronized brain activity recorded from overall EEG
activity following brief presentations of odourants.
Can be useful in some cases in detecting malingering

43. Others
•Japan- T and T olfactometer
•Germany- odorant-impregnated felt-tip pens
•Coffee

44. Imaging
CT
• ethmoid,
cribriform
plate,
olfactory
cleft
MRI
• olfactory
bulbs,
tracts, and
cortical
parenchyma
PET/SPECT
• limited
usefulness

45. DISEASES AFFECTING OLFACTION
• Conductive or transport impairment: from
obstruction of the nasal passages (e.g., chronic
nasal inflammation, polyposis, etc.)
• Sensorineural impairment: from damage to the
olfactory neuroepithelium, central tracts, and
connections (e.g., viruses, airborne toxins,
tumours, seizures, etc.).

46. Causes of smell disturbances
Air Pollutants &
Industrial Dusts
• Acetone
• Acids (e.g. sulfuric)
• Benzene
• Cadmium
• Carbon disulphide
• Cement
• Chromium
• Coke/coal
Drugs
• Metronidazole
• Clorfibrate
• Amphotericin B
• Tetracyclin
• Doxorubicin
• PTU, Carbimazole
• Allopurinol
• Amphetamine sulphate
• Fenbutrazate HC
Endocrine/Metabolic
• Addison’s disease
• Congenital adreanl
hyperplasia
• Cushing’s syndrome
• Gigantism
• Hypergonadotropic
• Hypothyroidism
• Kallmann’s syndrome

47. Causes of smell disturbances
Infections –
Viral/Bacterial
• COVID 19
• Acquired
immunodeficiency
syndrome (AIDS)
• Acute viral rhinitis
• Bacterial rhinosinusitis
• Bronchiectasis
• Fungal
• Influenza
• Rickettsial
• Microfilarial
Lesions of the
nose/Airway blockage
• Adenoid hypertrophy
• Allergic rhinitis
• Nasal PolyposisNasal
Polyposis
• Rhinitis medicamentosa
• Deviated septum
• Weakness of alae nasi
• Vasomotor rhinitis
• Chronic inflammatory
rhinitis
Medical Interventions
• Adrenalectomy
• Anaesthesia
• Anterior craniotomy
• Arteriography
• Influenza vaccination
• Laryngectomy
• Oophorectomy
• Haemodialysis
• Hypophysectomy

48. Causes of smell disturbances
Neoplasms – Intra-
cranial
• Frontal lobe gliomas
and other tumours
• Olfactory
groove/cribriform plate
meningiomas
• Osteomas
• Temporal lobe tumours
• Aneurysms
• Craniopharyngioma
• Pituitary tumours
Neoplasms – Intra-nasal
• Neuro-olfactory
tumours
• Adenocarcinoma
• Leukemic infiltration
• Nasopharyngeal
tumours
• Neurofibroma
• Paranasal tumours
• Schwannoma
Neoplasms – Extranasal
and Extracranial
• Breast
• Gastrointestinal tract
• Laryngeal
• Lung
• Ovary
• Testicular

49. Causes of smell disturbances
Neurologic
• Amyotrophic Lateral
Sclerosis
• Alzheimer’s disease
• Cerebral
abscessKorsakoff’s
psychosis
• Migraine
• Meningitis
• Multiple sclerosis
• Head trauma
• Huntington’s disease
• Hydrocephalus
Nutritional/metabolic
• Abetalipoproteinemia
• Chronic alcoholism
• Chronic renal failure
• Cirrhosis of liver
• Gout
• Protein calorie
malnutrition
• Total parenteral nutrition
• Whipple’s disease
• Vitamin deficiency: A B6
B12
Psychiatric
• Anorexia nervosa
• Malingering
• Olfactory reference
syndrome
• Schizophrenia
• Schizotypy
• Seasonal affective
disorder
• Attention deficit disorder
• Depressive disorders
• Hysteria

50. AFTER URI
• Common cold and influenza; COVID 19
• Other infectious causes hepatitis, herpes simplex encephalitis, and variant
Creutzfeldt-Jacob disease
• Reduced number of receptors and abnormal receptors
• Neurons regenerate theoretically however complete recovery less likely
• Necessary to exclude other aetiologies prior to making a diagnosis of post-
viral anosmia.

51. HEAD TRAUMA
• Acceleration/deceleration of the brain occurs (i.e. coup/contrecoup
injury)
• The loss of smell is usually, but not always immediate
• Mechanism: disruption from shearing forces of the olfactory fila
through the sinonasal tract, and direct contusion and ischaemia to the
olfactory bulb and frontal and temporal poles.
• Fracturing of the cribriform plate not necessary

52. Nasal and Sinus disease
While chronic rhinosinusitis can result in nasal airflow blockage,
there is also a component of direct toxicity to olfactory neurons and
impaired ciliary motility resulting in abnormal clearance of mucus
Severity of histopathological change is positively related to the
magnitude of olfactory loss, as measured by the UPSIT
Excessive dryness of the nasal mucosa – as seen in atrophic
rhinitis, Sjögren’s syndrome, and repeated nasal surgery – can
cause olfactory dysfunction, since a moist receptor environment
aids chemoreception and transduction.

53. NEOPLASMS AND MASS LESIONS
• Olfactory groove meningiomas, frontal lobe gliomas, and suprasellar
ridge meningiomas arising from the dura of the cribriform plate.
• Foster-Kennedy syndrome
• Pseudo Foster-Kennedy syndrome has been reported in patients with
increased intra-cranial pressure who had previous unilateral optic
atrophy
• Lymphoma infiltration
• Granulomatous diseases – such as syphilis, sarcoidosis, SLE, and
Wegener’s granulomatosis – often result in anosmia.

54. NEURODEGENERATIVE DISEASE
Olfactory dysfunction may be the first clinical sign of Alzheimer’s
disease (AD) and idiopathic Parkinson’s disease (PD).
In Alzhimer’s disease olfactory dysfunction in the presence of one
or more APOE-e4 alleles was associated with a very high risk of
subsequent cognitive decline
In later life, individuals with Down syndrome show similar clinical
and pathological changes to AD patients and have lower
performance on a modified UPSIT compared to controls matched
on mental age.

55. Epilepsy and Migraine
In epilepsy, mesial temporal lobe structures involved in the
usual processing of odour information – such as the amygdala
and hippocampus – have been implicated as the generators of
ictal olfactory sensations
Candidates for temporal lobe resection, are hyposmic
Osmophobia

56. AG
E
 Decrease in mitral cells with increasing age
 Below 65 yrs: 1%
 65 to 80 yrs: 50%
 Above 80 yrs: 75%
 The age-related changes in smell function are reflected not only in damage
to the olfactory receptors but related decreases in number of glomeruli
within the olfactory bulb

57. CONGENITAL
• Recognisingnear age of 8yrs
• Kallman syndrome/ Hypogonadotrophic
hypogonadism
TOXINS
• Formaline
• Smoking
• Pollutants
• Progressive condition

58. SURGERIES
• Iatrogenic trauma, such as surgery, can cause smell
impairment and has been seen with such
procedures as sinus surgery and laryngectomy.
• Now rare due to FESS
• More common in cranial and skull base surgeries
• Lesswithendoscopicpituitarysureries

59. MANAGEMENT
Conductive and sensorineural olfactory loss are often distinguishable
using a brief course of systemic steroid therapy since patients with
conductive impairment often respond positively to the treatment,
although long-term systemic steroid therapy is not advised.
Increased efficacy presumably occurs when the nasal drops or spray
are administered in the head-down Moffett’s position
Surgery:
(1) very large and medically-refractory polyps; or
(2) situations where a malignant neoplasm is suspected.

60. Rheumatological granulomatous disease is suspected, such as
Wegener’s granulomatosis or sarcoidosis, further
immunomodulation using agents such as cyclophosphamide or
methotrexate may be necessary.
Smoking cessation has dose related improvement over time.
Sensorineural more difficult to manage.

61. The prognosis for patients suffering from long-standing total loss due to
upper respiratory illness or head trauma is poor.
Anti epileptic or anti migraine drugs might prove beneficial.
Seizures, hallucinations and Psychiatric: stereotactic Amygdalotomy
Parkinson's and Psychiatric conditions do not improve with medication.
Medications induced changes often reverts back on stoppage of drugs,

65. Supportive measures in patients with complete
anosmia:
1. Smoke and carbon monoxide detectors need to be installed and properly working
2. When possible, electric 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 (e.g., monosodium glutamate, food
colouring, chicken or beef stock) to foods can also help with their appeal.

66. THANK
YOU