olfaction -- smell. From cummings Otorhinolaryngeology

1. Physiology of Olfaction
Dr. Jinu V Iype
1st year Post Graduate
Department of ENT

2. Reference from Cummings
Otorhinolaryngeology book

3. INTRODUCTION
• Senseof smell has been recently heavily
studied because of it’s importance to
human being’s survival.
• It helps to track food , can alert us
todanger like gasleak, fire, rotten
food.
• It is also linked to brain that
process emotion and memory.

4. Olfaction or Olfactory perception
- the sense of smell mediated by a group
of specialised sensory cells in nasal cavity.
Odour
-the property of a substance which gives it
a particular smell.

5. Anatomy of Olfactory Stimulation
1.Nasal Passageways

6. • Olfactory nerve (cranial nerve I) stimulation,
which is necessary for identification of most
odorants, depends on the odorant molecules’
reaching the olfactory mucosa at the top of the
nasal cavity.

7. • Although molecules can reach the olfactory
cleft by diffusion, essentially olfaction requires
some type of nasal airflow.
• During eating, there is a retro nasal flow of
odorant molecules that stimulate the olfactory
receptors at the top of the nose and contribute
greatly to the flavor of the food.

8. Swallowing and Deglutition
Retronasal Airflow
Production of flavour from swallowed
food Adds Smell to Taste

9. • At physiologic
airflow rates,
approximately 50%
of the total airflow
passes through the
middle meatus,
• ~ 35% flowing
through the inferior
meatus
• About 15% flows
through the olfactory
region

10. • Sniffing is an almost universally performed
maneuver when a person is presented with an
olfactory stimulus.
• It increase the number of olfactory molecules
in the olfactory cleft by means of a transient
change in the airflow pattern of the nose.
• A sniff also may allow the trigeminal nerve to
alert the central olfactory neurons that an
odorant is coming.

12. • For molecules to reach the olfactory area, they
must pass through the tall but narrow nasal
passageways.
• The epithelium lining the walls of these
passageways is wet, has variable thickness.

13. 2. Olfactory Mucus
• After the odorant molecules reach the olfactory
region, they must interact with the mucus
overlying the receptor cells.
• The mucus apparently comes from both
Bowman’s glands deep in the lamina propria
(only of serous type in humans) and the
adjacent respiratory mucosa (goblet cells)

14. • To reach the olfactory
receptors, the odorant
molecules must be
soluble in the mucus.
• Changes in the
thickness or
composition of the
mucus can influence
the diffusion time
required for odorant
molecules to reach the
receptor sites

15. • Once in the olfactory mucus-epithelial system,
the rate at which the odorant is cleared also is
important.
• Studies shows that 79% of a radioactively
labeled odorant (butanol) remained trapped in
the mucus 30 minutes after inspiratory
exposure, whereas radioactively labeled octane
cleared rapidly.

16. 3. Olfactory Epithelium
• Located 7 cm inside the nasal cavity, the
olfactory sensory neurons are protected in a 1-
mm-wide crevice of the postero superior nose.
• At the epithelial surface, these bipolar neurons
are exposed to
the outside world
through their
dendrites
and cilia.

17. • A number of research groups have shown that
there is mixing of olfactory and respiratory
epithelial tissues in adult.
• The number of these clumps of respiratory
epithelium, which are found in the olfactory
area, increases with age, suggesting that a loss
of primary olfactory neurons at least partially
explains the decreased olfactory ability
associated with aging.

18. Low magnification of the surface of the nasal cavity taken from a transition
region.
Patches of respiratory (R) epithelium (dark areas) can be seen within the
olfactory (O) region

19. Low-power three-dimensional scanning view of the olfactory epithelium and lamina
propria. The olfactory epithelium (E) overlies a thick connective tissue lamina propria
that contains olfactory axon fascicles (A x) and blood vessels (V) (×248).
• The human
olfactory
epithelium covers
an area of roughly
1 cm2 on each
side.
• The epithelium is
pseudostratified
columnar, and it
rests on a
vascular lamina
propria with no
submucosa

21. • This portion of mucosa can be readily
identified from the rest of the nasal mucosa by
its unique yellowish color.

22. Embryologically
• Olfactory receptors derive from neuroblasts.
These neuroblasts differentiates to form
olfactory placodes.
• The central part of each placode invagiantes
giving rise to olfactory sac.
• Olfactory sac opens anteriorly

23. • Olfactory organ
is the only part of
the body in which
the cell bodies of
neurons lie at the
surface, directly
in contact with
the external
environment.

24. four main cell types
1. ciliated olfactory receptors
2. microvillar cells
3. supporting (sustentacular) cells
4.basal cells

25. The olfactory receptor neuron
• Bipolar
• Club-shaped peripheral “knob” that bears the
cilia.
• Extends odourant receptor-containing cilia
into mucus.
• olfactory nerve 15 to 20 foramina in the
cribriform plate to synapse in the bulb

26. High-power magnification of an olfactory knob with long cilia
gradually tapering as they extend over the epithelial surface. At
the base of individual cilia, a necklace-like structure (arrow) can
be seen on the surface of the olfactory knob

27. • Allison et al estimate the rabbit to have
approximately 50 million olfactory axons,
whereas Jafek estimates humans to have only
6 million bilaterally.

28. • The olfactory ensheathing cells are unique in that
they share characteristics that are common with
Schwann cells and central glial cells.
• Because olfactory neurons - ability to regenerate
and make functional synapses with the olfactory
bulb.
• possible therapeutic potential for repair of
peripheral neuronal injury.
• potential agents for reversing spinal cord injuries
and demyelinating diseases.

29. The microvillar cell
• one tenth as often as the ciliated olfactory
neurons.
• flask-shaped, is located near the epithelial
surface, and has an apical membrane
containing microvilli that project into the
mucus overlying the epithelium
• The deep end of the cell tapers to a thin, axon-
like cytoplasmic projection that proceeds into
the lamina propria.

30. • Low-power
magnification of
fractured olfactory
epithelium
illustrating the axon-
like processes
(arrows) from
microvillar cells (M),
which extend basally
between supporting
cells

31. SUPPORTING CELLS/SUSTENTACULAR
CELLS
• Tall cells have an apical
membrane that joins
tightly with the surface
of the receptor cells and
the microvillar cells.
• Do not generate action
potentials, nor are they
electrically coupled to
each other

32. • Play a role in ion and
water regulation and,
along with
Bowman’s gland
duct cells, contain
xenobiotic enzymes
such as cytochrome
P-450 that likely
contribute to odorant
metabolism.

33. Cross-sectional view
of the olfactory
epithelium showing
the columnar
supporting cells (S)
that extend the full
length of the
epithelium. An
olfactory neuron (O)
with its dendrite and
basal cell (B) can be
seen among
supporting cells

34. BASAL CELLS
• Sit along the basal lamina.
• Two groups of replicating cells
Horizontal basal cells Globose basal cells
are just above positioned between
the basal lamina the horizontal basal
cells & immature
neurons.

35. •The globose basal cells seem to be responsible
for the continuous replacement of olfactory
receptor neurons

36. • During severe insult
→repopulate the
nonneuronal components
of the epithelium .
• The replication cycle is
between 3 and 7 weeks.
• When the new receptor
cell forms, it also projects
its axon to the olfactory
bulb, where it synapses
with second-order
neurons, thereby ensuring
continual olfactory
function and continual
olfactory neuron
replacement.

37. Vomeronasal Organ
• Many mammals have an identifiable pit or groove
in the anteroinferior part of the nasal septum that
contains chemosensitive cells.
• In most of these animals,
a nerve can be identified
connecting these cells to
the central nervous system,
to an accessory olfactory
bulb.

38. • Biopsy studies of the nasal mucosa in the small
pit often seen along the anteroinferior nasal
septum (Jacobson’s organ) show olfactory-like
histology but no central connection.
• Electrical activity
elicited by certain
compounds directly
delivered to the
vomeronasal area has been
shown to cause changes in
blood pressure, heart rate,
and hormonal levels.

39. • 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
endocrineresponses.

40. Olfactory Bulb
• Located directly over the cribriform plate.
• first relay station in the olfactory pathway
where the primary olfactory neurons synapse
with secondary neurons.

41. Neural components
are arranged in six concentric layers:
the olfactory nerve
 glomerular
External plexiform
 mitral cell
 internal plexiform
granule cell

42. The receptor cell axons
of the olfactory nerve
layer →the glomeruli
→ synapse with the
dendrites of the
mitral and tufted
cells within the
spherical glomeruli.

43. These second order
cells, in turn, send
collaterals that synapse
within the periglomerular
and external plexiform
layers, resulting in
“reverberating” circuits
in which
negative and positive
feedback occur.
mitral cells modulate their
own output by activating
granule cells (which are
inhibitory to them).

44. • The mitral and
tufted cell axons
project
ipsilaterally to the
primary olfactory
cortex via the
olfactory tract

45. Olfactory tract enters brain 2 pathways
Lateral
Olfactory stria
Medial
Olfactory stria

47. MEDIAL OLFACTORY AREA
• consists of a group of nuclei
• located in the mid basal portions of the brain
immediately
• Contain septal nuclei-
feed into the hypothalamus
and other primitive
portions of the brain’s
limbic system

48. Composed of
prepyriform
pyriform cortex
cortical portion of amygdaloid nuclei.
signal pathways- almost all portions of
limbic system , especially hippocampus-
important for learning like or dislike for
food stuffs.

49. An important feature of the lateral olfactory area is
that many signal pathways from this area also feed
directly into an older part of the cerebral cortex
called the paleocortex in the anteromedial
portion of the temporal lobe.
This is the only area of the entire cerebral
cortex where sensory signals pass directly to the
cortex
without passing first through the thalamus.

50. • The mitral and tufted cell axons project
ipsilaterally to the primary olfactory cortex via
the olfactory tract without an intervening
thalamic synapse

51. Primary olfactory cortex is comprised of the
Anterior Olfactory Nucleus - Pyriform Cortex-
Olfactory tubercle - Entorhinal area - Amygdaloid
Cortex - Corticomedial nuclear group of amygdala.

52. Anterior Olfactory Nucleus
Coordination of inputs from
contalateral 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

54. Olfactory pathway
• First order neuron :
olfactory Epithelium to glomerulus
• Second order neuron :It is formed of the cells of
the olfactory bulb (mitral cells & Tufted cell)
Passes centrally as the olfactory tract .
• Third order neuron: Pyriform Cortex(Area 28)
contain primary olfactory cortex, which contain
3rd order neuron

56. Very Old Olfactory System
•More primitive responses to olfaction
salivation, primitive emotional drives to
smell
Less Old Olfactory System
• Learned control of food intake
• Aversion to food that have caused nausea &
vomiting
Newer System
• Odour discrimintation & analysis of odour

57. Olfactory Transduction and Coding
• Once the odorant molecule is dissolved in the
olfactory mucus

58. • Soluble binding proteins, like odorant-binding
protein -> enhance the access of odorants to the
olfactory receptors.
• Same odorant-binding protein molecules act to
remove odorant molecules from the region of
the receptor cell after transduction.

59. • The actual transformation of odorant chemical
information into an electrical action potential
occurs as a result of specific interactions
between odorant molecules and receptor
proteins on the surface of olfactory cilia.
• With the binding of the receptor to an odorant,
adenylate cyclase is activated by G protein–
coupled receptors and converts adenosine
triphosphate (ATP) into cyclic adenosine
monophosphate( cAMP).

60. • The cAMP then binds to a Na, Ca ion channel
to allow influx of these ions.
• As more channels open, the cell depolarizes,
and an action potential is produced

61. • Once the peripheral olfactory receptor cells are
depolarized, there begins a convergence of
electrical information toward the olfactory
bulb → glomeruli and mitral / tufted cells of
the olfactory bulb → Olfactory cortex

62. Molecular structure – Moncrieff 1967
Electrochemical Reactions
Stereospatial patterns
Molecular Properties
Olfactory mucus morphology

63. MOLECULAR STRUCTURE
• By Moncrieff 1967
• Suggested that molecular structure is
important.
• No stereospecific olfactory receptors have
been demonstrated.

64. Odour mol + Receptor  Photochemical reaction 
SIGNALTRANSDUCTION
Receptors containing carotenoids
By Briggs and Duncan,1962

65. By Mozell, 1970
Certain receptors could have a
stereospatial, lock and key form,
and receptor cells fire when the
surface membrane is altered.

66. LOCK KEY
Confirmationalchange
in receptor+mol
complex
SIGNAL
TRANSDUCTION

67. By Laffort et al,1974
Molecular properties depends on
-molecular volume at boiling point
-proton affinity and donation,
-local polarization within the molecule.

68. Holley and Doving,1977
Nature of smell - Pattern of stimulus within
mucosal configuration of receptor cells
This theory is based on
specific receptor sites &
on their position within olfactory mucosa

69.  Vibration Theory
 Olfactory Pigment Theory
 Enzyme Theory
 Penetrating and Puncturing theory

70. Randerbrock 1968
Olfactory perceptors are peptide chains vibrating
in an alpha helix.
Odourant molecules forms a band with peptide
chain modulating the vibration-transmitted to
nerves.
Pigment Theory
Rosenberg 1968
odourant molecule + olfactory pigment- increased
electrical conductivity

71. By Davies
Odourant molecules penetrate membrane
of olfactory receptor cell- diffuse-leaving a
hole.
Leakage of Sodium & pottasium occurs-
nerve impulse

72. OLFACTORY DYSFUNCTION

73. Anosmia
Hyposmia Hyperosmia
Phantosmia
OlfactoryAgnosia
Cacosmia /Parosmia /Troposmia
Presbyosmia Osmophobia

74. TYPESOF OLFACTORY DYSFUNCTION
o Anosmia-absenceof smell
o Hyposmiamicrosmia- diminished olfactorysensitivity
o Dysosmia-distorted senseof smell
o Phantosmia- perception of anodorant when noneis
presentl / Olfactory hallucination.
o Agnosia-inability to classify,contrast, or identify odor
sensationsverbally, eventhough the ability to distinguish
between odorants maybenormal
o Hyperosmia-Abnormally acute smell function (Rare
condition )

75. CLASSIFICATION& ETIOLOGY
• TRANSPORT OLFACTORY LOSS
Olfactory dysfunctions canbe causedby conditions
that interfere with the accessof the odorant to
the olfactory neuro-epithelium due to either
swollen nasalmucous membrane, structural
changesand/or mucussecretion.
Causes-Allergy rhinitis, Bacterial rhinitis and
sinusitis, Congenital abnormality like
encephalocele, Deviated NasalSeptum, Nasal
neoplasms, Nasalpolyps, Nasal surgery,Old age,
Viral infections.

76. • SENSORY OLFACTORY LOSS
Olfactory 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.

77. • NEURAL OLFACTORY LOSS
• Olfactory dysfunctions canalso be causedby
conditions that damagethe 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 B12def., Zinc
deficiency

78. APPROACHTO OLFACTORY DYSFUNCTION
A.DETAILEDMEDICALHISTORY
Onset, course, nature of impairment, their previous illness
andthen medications taken.
B. PHYSICALEXAMINATION
Thorough ENT,head and neck examinations including nasal
endoscopy. Aneurological examination emphasizing the
cranial nerves, cerebellar and sensorimotor function is
essential.
Psychological examination like general mood and check
for signsof depression should bedone.

79. C.LABORATORYFINDINGS
• Biopsy of olfactory neuroepithelium can be done
in rarecases
D.IMAGING
• Coronal CTscanand MRI Brain are useful.

80. sudden olfactory loss suggests
the possibility of head trauma, infection,
ischemia, or a psychogenic condition.
Gradual loss
the development of degenerative processes,
progressive obstructive lesions or tumors
within the olfactory receptor region or more
central neural structures.
Intermittent loss can be indicative
of an intranasal inflammatory process.

81. • A family history of smell dysfunction may
suggest
a genetic basis
Kallmann’s syndrome :
Delayed puberty in associationwith anosmia
(with or without midline craniofacial
abnormalities, deafness, and renal anomalies

82. Quantitative Olfactory Testing
(1)verify the validity of the patient’s complaint,
(2)characterize the exact nature and degree of the
problem,
(3) accurately monitor changes in function over
time
(4) detect malingering,
(5)obtain an objective basis for determining
compensation for disability.

83. UNIVERSITYOFPENNSYLVANIA
SMELLIDENTIFICATIONTEST
(UPSIT)
• Most commonly used & most superiorand reliable
test.
• Self-administered in 10-15minutes
• Scoredin <1 minute by non-med person
• Available in variouslanguages
• 40 “scratch & sniff “ patches
• Pt. choosesfrom 4 answers& must choose1
• Candetect malingering
• Dysfunction classified asNormosmia, anosmia, mild,
moderate or severe microsmia, or probable malingering

84. UPSIT

85. To assess olfaction unilaterally, the naris
contralateral to the tested side should
be occluded without distorting
the nasal valve region. This can be easily
accomplished
by sealing the contralateral naris using a
piece of MicrofoamTM.
The patient is instructed to sniff the
stimulus normally and to exhale through
the mouth.
Such occlusion not only prevents air from
entering the olfactory cleft from the
contralateral naris

86. Olfactory event-related potentials (OERPs)
• synchronized brain electroencephalographic
(EEG) activity induced by repeated pulsatile
presentations of an odorant is isolated from
overall EEG activity
Used as :-
sensitive and useful in detecting malingering

87. ELECTRO-OLFACTOGRAM
(EOG)
• Detected via an electrode placed on the surface
of the olfactory neuroepithelium

88. DIFFERENTIALDIAGNOSIS
• At present, no psychophysical methods to
differentiate sensory from neural hearingloss.
• History of olfactory lossgivesan important clues
tothe cause.
• Leadingcausesof olfactory dysfunctions are
head trauma and viral infections.
• Headtrauma are more common causeof anosmia
in children and young adults whereas viral
infectionsare more common causein older
adults.

89. • Congenital anosmia occurs in Kallmann syndrome
and also in albinism.
• Meningioma of inferior frontal region is the
most common neoplastic causeof anosmia.
• Dysomiais associatedwith depression.

90. TREATMENT
• Transport olfactory loss
Thefollowing treatments are effective
in restoring senseof smell:
i. Allergy management
ii. Antibiotic therapy
iii. Topicaland systemic glucocorticoid
therapy
iv. Operations for nasalobstruction.

91. • Sensorineural Olfactory loss.
No treatment with demonstrated
efficacyfor Sensorineural Olfactory
loss. Fortunately, spontaneous
recovery occurs.
Someclinicians advocate zinc and
vitamin therapy espVitaminA.