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2011

Otolaryngology online

Dr T Balasubramanian

[THE TAMILNADU DR MGR


MEDICAL UNIVERSITY MS
(ENT) BASIC SCIENCES MARCH
2010 QUESTION PAPER WITH
SOLUTION]
This e book contains MS ENT Basic sciences March 2010 question paper with solutions

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March 2010
[KW 225] Sub. Code: 2250
M.S. DEGREE EXAMINATION
Branch IV – E.N.T.
Common to
Paper I - (For candidates admitted from 2004-2005 to 2007-08) and
Part I – (For candidates admitted for 2008-09 onwards)
APPLIED BASIC SCIENCES IN
OTO RHINO LARYNGOLOGY
Q.P. Code : 222250
Time : Three hours Maximum : 100 marks
Answer ALL questions
Draw suitable diagram wherever necessary
I. ANATOMY (4 x 5 = 20)
1. Infratemporal fossa.

Synonyms: Ptreygopalatine fossa, infratemporal fossa.


Definition: Infratemproal fossa is a potential space lying behind the maxilla.

Boundaries of infratemporal fossa:

Lateral: Bounded by Zygoma, the ramus of mandible, parotid gland and masseter
muscle
Medial: Bounded by superior constrictor muscle, Pharyngobasilar
fascia, Pterygoid plates
Anterior: The body of the maxilla lies anteriorly
Superior: Greater wing of sphenoid
Posterior: Auricular tubercle of the temporal bone, glenoid fossa and styloid
process

The floor of the infratemporal fossa is closed by the medial pterygoid muscle.

The infratemporal fossa communicates superiorly with middle cranial fossa by the
neurovascular formaina like carotid canal, jugular foramen, foramen spinosum,
foramen ovale and foramen lacerum. Medially the infratemporal fossa
communicates with pterygopalatine fossa through the pterygomaxillary
fissure. The pterygomaxillary fissure is contiguous with that of the infraorbital
fissure. The roof of the infratemporal fossa is open to the temporal fossa lateral
to the greater wing of sphenoid, deep to the zygomatic arch.

Benign tumors involving the infratemporal fossa always respect these boundaries

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and expand in the direction of soft tissue planes, or follow pre-existent pathways
and foramen described above.
Contents of infratemporal fossa:

1. Lateral pterygoid muscle. This is the largest component of the infratemporal


fossa. This muscle has two heads, upper and lower. The upper head is smaller
and arises from the greater wing of sphenoid, while the larger lower head arises
from the lateral aspect of lateral pterygoid plate. The fibers of both these heads
pass backwards to be inserted into the neck of the mandible. The action of lateral
pterygoid muscle i.e. protrusion of the lower jaw can easily be tested during
clinical examination of the patient.

2. Temporalis muscle: This muscle occupies a wedge shaped space just lateral to
the lateral pterygoid muscle.

3. Pterygoid venous plexus: There is rich plexus of veins seen in this space. It lies
admixed with fatty tissue seen in the infratemporal fossa. These plexus could
cause troublesome bleeding during total maxillectomy surgery.

4. Infratemporal pad of fat: Lies between the temporalis muscle and the
infratemporal surface of maxilla. The pad of fat helps in outlining the posterior
antral tumor spread in CT scans. This infratemporal pad of fat continues with the
cheek pad of fat passing between the posterior wall of maxilla and the zygoma. A
mass present behind the maxilla always betrays itself by displacing this pad of fat
and causing a puffy swelling of cheek (i.e. angiofibroma).
5. Buccal lymph node: Within this infratemporal pad of fat lies the buccal lymph
node. This node links the infratemporal lymphatics to the facial lymphatics. This
node should never be left behind during surgical resection of infratemporal fossa
for malignant tumors as it could commonly cause local recurrence.

6. Mandibular nerve penetrates the roof of the infratemporal fossa through the
foramen ovale. It also gives rise to inferior alveolar and lingual nerve branches.
Tumors involving infratemporal fossa present with a variety of symptoms
depending on the structure involved. It could be a mass effect, eustachean tube
dysfunction, cranial neuropathies, trismus etc. The corner stone of diagnosis of
tumors of this area is imaging which includes a CT scan and MRI.

Surgical approach to infratemporal fossa: It was Barbosa in 1961 who described


an approach to expose this space. He extended the orbital limb of the radical
maxillectomy incision horizontally backwards up to the pretragal region. After
raising the parotid off the masseter, the maxillary artery was ligated. The
temporalis muscle was sectioned at the upper margin of the zygomatic arch and

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the masseter was divided below the arch. The zygomatic arch was freed. The
ramus of the mandible along with the head was detached by a horizontal
mandibular osteotomy at the level of the teeth. The space is entered by
mobilising the block of mandible and its attached muscle forwards.

Pterygopalatine fossa:

This space lies between the posterior wall of the maxilla and the anterior face of
the pterygoid process. This is a small but very important distribution center for
the nasal cavity and the middle 1/3 of the face. Sensory, secretomotor, and
vasoregulatory nerves pass through this niche on their way from the middle
cranial fossa to the face, teeth, palate, turbinates, sinuses, lacrimal glands and
nasopharynx. Entrance to the pterygopalatine fossa from the infratemporal fossa
is through the pterygomaxillary fissure.

Cancers in the pterygopalatine fossa has ready access to the middle cranial
fossa via the foramen rotundum. The lesion here could also reach the orbital
apex through the infraorbital fissure, which is nothing but the open roof of the
pterygopalatine fossa. Lateral spread of tumors from this space could involve the
infratemporal fossa. Nasopharynx could be involved by medial infiltration of the
tumor via the sphenopalatine foramen. Hence involvement of the
pterygopalatine fossa is really ominous in patients with paranasal sinus
neoplasia.

A small parasympathetic ganglion (sphenopalatine ganglion) lies suspended in


this space from the maxillary nerve. The following features are commonly seen
when the pterygopalatine fossa is invaded by a malignant mass:

1. Deep facial pain

2. Hard palate insensitivity

3. Decreased lacrimation

7. Internal maxillary artery and its branches lies on the superficial or deep surface
of the lateral pterygoid muscle.
2. Petrous apex and its approaches.
3. Spaces of posterior mesotympanum.
4. Cavernous sinus.

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2. Petrous apex and its approaches.

Introduction:
Petrous apex is the medial portion of petrous bone that lies between the inner ear
and clivus. Since this is a difficult region anatomically various approaches have
been designed over the ears to access this area.
This portion of the temporal bone is pyramidal in shape wedged in the skull base
between the sphenoid and occipital bones. It is directed medially, forwards and
slightly upwards.
It has an apex, base, three surfaces and three angles.
Base: This portion of the petrous bone is fused with the internal surfaces of the
mastoid and squamous portion of the temporal bone.

Apex: This is rough and uneven and is placed in the interval between the greater
wing of sphenoid and occipital bone. It has the internal orifice of the carotid canal.
It forms the postero lateral boundary of the foramen lacerum.

Anterior surface:

The anterior surface forms the posterior portion of the middle cranial fossa in the
skull base. It continues with the inner surface of the squamous portion of temporal
bone with which it is united by the petro squamous suture line. This suture line is
distinct even in the later phases of life. This surface is marked by the depressions
and convolutions of the brain.

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Features of this surface include:
1. Near its centre lies the arcuate eminence which overlies the projection of
superior semicircular canal.
2. In front and slightly lateral to this eminence lie a depression which indicates
the position of the middle ear cavity. The bone in this area is very thin and
is known as the tegmen plate.

Eagleton’s approach:
This is the superior approach to the petrous apex that involves removal of the
tegmen to the base of the zygoma together with removal of part of the squamous
temporal bone. The dura of the middle cranial fossa can now be elevated to expose
the petrous apex.

Thornvaldt’s operation:
This approach is also along the supra labyrinthine tracts. As the dissection
proceeds it merges with that of Eagleton’s approach.
Almoor’s approach:
This is an inferior approach to the petrous apex through a space bounded by the
cochlea, the carotid artery and the tegmen tympani.
Ramadier’s operation:
This approach is slightly anterior to that of Almoor’s operation that pursues the
peritubal cells to the petrous apex that exists between the cochlea and the carotid
artery.
Frenckner’s operation:
This approach to the petrous apex is through the arch of the superior semicircular
canal. The blood supply to the arch arises from within this arch and some
labyrinthine loss is almost inevitable with this approach. It has to be combined
with an inferior approach.

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Transpetrosal approaches also include a variety of surgical approaches through the
petrous portion of the temporal bone to provide access to:

a. Cerebello pontine angle


b. Petro clival region
c. Basilar artery
d. Brain stem

3. Spaces of posterior mesotympanum.

There are 4 sinuses in the posterior mesotympanum. They can be visualized only
after removing a portion of the annulus and tilting the head of the patient. Two of
them are located above the pyramidal eminence (Suprapyramidal) while the other
two lie below the pyramid (infrapyramidal).
Supra pyramidal recess:
Facial recess - Is defined as an aerated extension posterior superior
portion of the middle ear cavity medial to the tympanic annulus and
lateral to the fallopian canal.
Boundaries:
Medial – Facial nerve
Lateral – Tympanic annulus
Superior – Incus buttress (near the short process of incus)
Running through the wall between these two structures with varying
degrees of obliquity is the chorda tympani nerve. Chorda tympani nerve
always run medial to the tympanic membrane.
Drilling in this area between the facial nerve and annulus in the angle
formed by the chorda tympani nerve leads into the middle ear cavity.
This surgical approach to the middle ear cavity is known as facial recess
approach.

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Posterior tympanic recess - This is a medial sinus. It lies medial to the facial nerve
and the pyramidal eminence. It lies superior to Ponticulus. The Ponticulus divides
the tympanic sinus into smaller posterior tympanic sinus and a larger inferior sinus
also known as the sinus tympani.
Infra pyramidal recess:
Lateral tympanic sinus – Is the most lateral sinus. It lies between the three
eminences of the styloid complex.
Medial – chordal eminence
Inferior – chordal ridge & pyramidal eminence
Superior – styloid eminence

Sinus tympani -
Sinus tympani and facial recess are the two important spaces of posterior
mesotympanum. These spaces are important in deciding the spread of posterior
mesotympanic cholesteatoma. This space was first described by Meckel in 1820.
Sinus tympani:
This is the posterior mesotympanic space of middle ear cavity. Its boundaries
include:
Medially – Annulus of tympanic membrane
Superior – Ponticulus
Inferior – Subiculum
This area is very difficult to visualize as it lies under the pyramidal eminence.
Cholesteatoma is commonly known to be left behind in this area leading to a
recurrence of the disease.

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Diagram showing various posterior mesotympanic sinuses

4. Cavernous sinus.

This is a collection of thin walled venous sinuses lying lateral to the sella
turcica. The sinus is shaped like a boat with its narrow keel located at the superior
orbital fissure and its broader bow (posterior wall) located lateral to the dorsum
sellae above the petrous apex. This sinus has four walls (a roof, lateral, medial
and posterior walls). The roof is formed by the dura lining the lower margin of
anterior clinoid process. It receives blood from the ophthalmic vein through the
superior orbital fissure, and superficial cortical veins. It is connected to the basilar
plexus of veins posteriorly. Vital structures pass through this vascular space. They
include:
a. Internal carotid artery
b. Cranial nerves III, IV, V1, V2 and VI pass through this space.

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This is the only anatomical structure in the whole of the human body where an
artery could be seen travelling within the confines of a vein. If the internal carotid
artery ruptures within the cavernous sinus it creates an arterio venous fistula.
Lesions affecting this sinus also affect the cranial nerves traversing through it.
The pituitary gland lies between the paired cavernous sinuses. Tumours involving
the pituitary can cause compression of this sinus.
It has been stressed that because of its communications with the facial vein via the
superior ophthalmic veins it is possible for infections involving the face to travel
via these connections to involve the cavernous sinus also. Hence the areas of face
supplied by the facial veins have been termed as the dangerous area of the face. In
addition these facial veins don’t have valves and hence it is easy for infected
thrombi to traverse these vessels and reach the cavernous sinus.
II. PHYSIOLOGY (4 x 5 = 20)
1. Physiology of Eustachian tube function.
The following are the functions of the Eustachian tube.
a. Ventilation of middle ear
b. Drainage of middle ear cavity
c. Protection of middle ear cavity from pathogens of nasopharynx
The Eustachian tube connects the middle ear cavity with the nasopharynx.
Normally the pharyngeal end of the Eustachian tube is closed. The middle ear
cavity is slightly negative when compared to that of the atmospheric pressure.
Repeated opening of the Eustachian tube helps in the maintenance of the normal
middle ear pressure. The pharyngeal end of Eustachian tube opens when the
patient attempts to swallow / yawn. This opening of the tube while swallowing
/ yawning is possible due to contraction of tensor veli palatini muscle. The
Eustachian tube function is less efficient in children than adults. In addition to
this inefficiency the incidence of adenoid infection and hypertrophy in children
may cause Eustachian tube block followed by middle ear infections. Normal
Eustachian tube opens frequently maintaining the middle ear pressure between
+50 mm of water and – 50 mm of water. It has been estimated that about 1 ml
of gas from the ear is absorbed per day. This is constantly being replaced by the
repeated opening of the Eustachian tube.
Drainage functions of the Eustachian tube: Secretions from the middle ear
cavity drains via the Eustachian tube due to the Ciliary beat of the middle ear
mucosa, muscular clearance by the Eustachian tube as well as the surface
tension of the lumen.

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The flask model proposed by Bluestone explains the Eustachian tube function
pertaining to its anatomical model. In this model the Eustachian tube and the
middle ear system is likened compared with that of a flask with a long narrow
neck. The mouth of the flask represents the nasopharyngeal end of the
Eustachian tube and the narrow neck represents the isthmus. The middle ear
and mastoid cavities are comparable with that of the body of the flask. Fluid
flow through the neck depends on the pressure at either end, the diameter of the
Eustachian tube and the viscosity of the flowing liquid.
Protective function of the Eustachian tube:
The Eustachian tube is closed at rest; hence loud sounds are dampened before
reaching the middle ear via the nasopharyngeal end of Eustachian tube. It also
prevents the normal commensal microbes of the nasopharynx from entering the
middle ear cavity.
Ostmann pad of fat – is located in the inferolateral aspect of Eustachian tube is
an important factor in Eustachian tube closure. This fat pad contributes in
protecting the middle ear cavity from the nasopharyngeal secretions. This pad
of fat undergoes regression due to rapid loss of weight causing defective closure
of the pharyngeal end of the Eustachian tube orifice. This leads to autophony.
Forceful blowing of nose cause an increase in the nasopharyngeal air pressure
causing reflux of nasopharyngeal secretions into the middle ear cavity.

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2. Physiology of inner ear fluids.
The principal divisions of the fluid spaces in the cochlea are the
perilymphatic space comprising of scala vestibule and scala tympani and the
endolymphatic space consisting of scala media. The walls surrounding the
endolymphatic space have occluding tight junctions between the cells
obstructing the movements of ions into and out of the endolymph. These
endolymphatic and perilymphatic spaces extend right through the whole extent
of the inner ear.

Formation & absorption of endolymph and perilymph: Endolymph is the only


extracellular fluid which has more potassium ions (in concentrations matching
with that of intracellular fluid).
Studies have demonstrated that endolymph of the inner ear is produced by the
stria vascularis. The dark cells of the stria vascularis demonstrate
morphological and biochemical properties of secretory cells. These secretory
cells of the stria are seen as dark staining cells under light microscopy. The
cells of stria vascularis are found to be rich in Na / K ATPase, adenylate cyclase
and carbonic anhydrase which are enzymes associated with active pumping of
ions and transport of fluid into the endolymph. These cells also possess high
levels of oxidative enzymes associated with glucose metabolism.

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Circulation of endolymph:
Endolymph flows along the cochlear duct through the ductus reuniens (which
also communicates with the saccule) to the endolymphatic duct and thence into
the endolymphatic sac. Even though there is a physical connection between the
endolymph of the utricle and semicircular canals, the connection is rather small
and in some cases may be closed by obstructions. It is unlikely for drugs in the
cochlear and saccular division of endolymph to reach the endolymph present in
the rest of the vestibular division of the inner ear. However if the pressures of
endolymphatic fluid are altered due to disease states like Meniere’s disease
some communication could as well occur.
Endolymph is absorbed in the endolymphatic sac. The cells of the sac are
columnar shaped, containing long microvilli on their luminal surface. They also
have many pinocytic vesicles and vacuoles and are hence specialized cells
capable of absorbing endolymph. Phagocytes have also been demonstrated in
the lumen of the sac. These cells perform the important function of removing
cellular debris and foreign materials from the endolymph. Failure in the process
of reabsorption can lead to the formation of endolymphatic hydrops.
The composition of endolymph and electrical potentials of cochlear fluids:
Endolymph is unique among the extracellular fluids of the body with high
potassium ion content and low sodium content. This ionic composition
resembles intracellular fluid.
Even though endolymph has a high concentration of potassium its electrical
potential is strongly positive unlike that seen intracellularly. Electrical potentials
of endolymph have been found to be between +50 - +120 mV. These potentials
are found to be rather high near the stria vascularis. This positive potential is
dependent on ion pumping of stria vascularis.

Perilymph:
The perilymphatic space which contains perilymph is continuous between the
vestibular and cochlear divisions. The site of production of perilymph is
controversial. Some authors consider it to be ultra-filtrate of blood produced by
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perilymphatic capillaries. Some others consider it to originate from CSF. Ionic
concentration of perilymph resembles extracellular fluid composition with high
sodium content and low potassium content. Electrical potential of perilymph
range between +5 - +7 mV.

3. Physiology of balance.

In humans a highly sophisticated mechanism for maintain balance has


developed. This is dependent upon visual, vestibular, proprioceptive and
superficial sensory information. Inputs from these sensors are integrated in the
central nervous system. It is modulated by activity arising in the reticular
formation, the extrapyramidal system, cerebellum and the cortex.

Diagram illustrating the gross physiology of balance maintenance

Vestibular system is not only a primitive sense, but is also paramount


importance in the development and maintenance of balance. It has been
demonstrated that damage to the vestibular apparatus itself or to its multiple
connections may cause severe disabling and distressing symptoms.

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The uniqueness of vestibular system in the human body is that in contrast to
other sense organs which responds to external stimuli it responds to changes
within the human body.
The labyrinth lies within the petrous portion of temporal bone. The peripheral
organ responsible for maintaining equilibrium includes the three semicircular
canals (lateral, superior and posterior) utricle and saccule.

Diagram showing the peripheral vestibular apparatus


The three semicircular canals are small ring like structures each forming two
thirds of a circle with a diameter of 6.5 mm. One end of each canal is dilated
and is known as the ampulla.
The five vestibular receptor organs lie within the membranous labyrinth and
may be divided into two maculae of the otoliths (utricle and saccule). Otolith
organs monitor linear acceleration and the three crista ampullaris present in the
membranous ampullated portion of semicircular canal monitors angular
acceleration.
Each macula is a small area of sensory epithelium measuring less than 1 mm3 is
found on the floor of the utricle in the horizontal plane. This macular layer
supports a statoconial membrane consisting of small calcium carbonate crystals
known as otoconia. Otoconia is found embedded in a mucopolysaccharide gel.
The position of the statoconial membrane relative to the sensory epithelium
varies according to the magnitude and direction of the force acting upon it. The
shearing force between these two structures results in the bending of the hairs of
the hair cells embedded in the statoconial membrane.

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Figure showing otolith organs
The receptor organ of the semicircular canal is the crista ampullaris present in
the dilated ampullary portion of the semicircular canal. This is a crest of
sensory epithelium supported on a mound of connective tissue lying at right
angles to the longitudinal axis of semicircular canal. The crista is surmounted
by a bulbous gelatinous mass the cupula which extends from the surface of the
crista to the ceiling of the ampulla forming a water tight swing door seal. The
specific gravity of the cupula is the same as that of the endolymph and hence
unlike the statoconial membrane of the maculae the cupula does not exert a
resting force on the underlying sensory epithelium

The semicircular canal system is sensitive of angular acceleration of the head.


As the head is rotated, the endolymph within the duct tends to remain stationary
in space because of its inherent inertia. The resultant flow of endolymph with
respect to the duct is resisted by the elasticity of the gelatinous cupola, which
becomes deflected resulting in the bending of hairs of the sensory hair cells.
This causes stimulation of the semicircular canal.

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According to Ewald:
1. Head & eye movements always occur in the plane of the canal being
stimulated and in the direction of the endolymphatic flow
2. In the horizontal canal, ampullopetal endolymph flow causes a greater
response than ampullofugal flow.
3. In the vertical canals ampullofugal endolymph flow causes a greater
response than ampullopetal flow
Vestibular sensory epithelium of the five vestibular receptor organs usually
contains three basic components.
1. Sensory cells with hairs on their free surface
2. Supporting cells which secrete a gelatinous substance
3. The gelatinous substance is composed mainly of mucopolysaccharides.
In to this layer the hair cells are embedded.
The hair projecting from the surface of the sensory cells are of two types. One
which is single, long and thick known as the kinocilium with 50-110 thin
stereocilia. The stereocilia are graded in height with the shortest being at the
most distant point to the kinocilium. When the stereocilia bend towards the
kinocilium it causes stimulation of the vestibular nerve, if they bend away from
the kinocilia it causes inhibition of the vestibular nerve.
Forces of acceleration cause the bending of the hairs of the receptor cells. The
degree of bending is proportional to the degree of force being applied. This
results in transduction of mechanical energy into neural activity. The maximal
stimulus is a force applied parallel to the surface of sensory epithelium which
bisects the bundle of cilia and passes directly through the kinocilium. Whereas
a force perpendicular to the epithelial surface is ineffective in stimulating the
hair cells.
The polarization pattern for each of the sensory organs of the vestibular
apparatus has been described. The kinocilia of the sensory cells are oriented
towards the utricle in the horizontal canal, where as they are directed away from
the utricle in the vertical canals.

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The macula differs from that of cristae in that the kinocilia within each organ
are not uniformly oriented. A curved line the striola divides each macula into a
medial and lateral zone. In each of these halves the kinocilia are oriented in
opposite directions. Displacement of either otolithic membrane in a particular
direction produces an opposite response from the hair cells on either side of the
striola. Signals from movement of otolithic membrane are analysed spatially in
the brain which draws its own conclusions regarding the status of the head in
response to the environment.

4. Physiology of swallowing.
The physiological act of swallowing is known as deglution. During this process
bolus / liquid is transferred from the buccal cavity into the stomach. This
process is a complex, integrated, continuous act which involves somatic and
visceral afferent and efferent nerves together with associated striated and
smooth muscles. For purposes of description the act of deglution has been
divided into three phases:
a. Oral phase
b. Pharyngeal phase
c. Oesophageal phase

The initiation of the first two phases of deglutition is under conscious control
involving the striated muscles which are controlled by a complex of stimulatory
and inhibitory signals from the brain stem. The third phase involves the smooth
muscles of oesophagus depending both on central co-ordination and local
intramural reflex arcs.
The major sphincteric mechanisms protecting the airways are the soft palate
guarding the pharyngeal isthmus and those guarding the laryngeal inlet. Airway
protection mechanisms are activated ahead of the passing bolus. Deglutition

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should be carefully timed in relation to the phases of respiration. Failure of this
timing may lead to difficulties in swallowing.
Timings of swallow:
Oral phase: Once food is of suitable consistency to swallow transit from the
mouth to oropharynx takes one to two seconds, with a further one second delay
for the bolus to traverse up to the cricopharynx.
This stage is split into preparatory phase where the food inside the mouth is
broken down, mixed with saliva and made into bolus form.
Oral phase proper: Bolus is moved to the back of the tongue.
In this stage tongue is involved in squeezing food out of the mouth into the
oropharynx. At the beginning of the oral phase of swallowing the tip of the
tongue is raised to the back of the incisor teeth and is then applied to the palate
from before backwards. This manoeuvre squeezes the contents of the mouth
into the pharynx. As soon as the tail of the bolus has been expelled from the
mouth, the back of the tongue arches posteriorly to meet the soft palate and
pharyngeal wall. The nasopharynx is closed by the elevation of the soft palate
in combination with the contraction of the superior pharyngeal constrictors.
During the oral phase of deglutition the jaws are brought together as the tongue
fills the oral cavity displacing its contents. The hyoid bone is raised towards the
lower border of mandible. Maximum elevation of hyoid bone is reached as the
tail of the bolus is being expelled from the mouth. When the tongue arches
backwards to displace the bolus downwards, the volume of the tongue necessary
to occlude the mouth must be further reduced by rising of the floor of the
mouth. In the event of swallowing a whole mouthful of food it cannot be done
as a single bolus. Subjects may elect to swallow it by means of a series of
boluses. In order to achieve this the subject releases a quantity of the content
into the pharynx by parting the tongue and soft palate and then raising the
tongue in the back of the mouth behind the junction of the hard and soft palates,
thus cutting off the bolus in the pharynx from the rest of the oral cavity’s
contents. It is possible to dissociate the forepart of the tongue from swallowing
and to use it for some other purpose while swallowing is still continuing. The
forepart of the tongue may be lowered in the front of the mouth to create suction
in order to take in liquids. The forepart of the tongue is also used for
manipulation of food in preparation for mastication, in forming consonants of
speech.
Functions of different portions of the tongue:
Anterior portion of tongue:
1. Taking food from a spoon / fork
2. Manipulation of food in the forepart of the mouth, this includes cleaning
the teeth and palate
3. Expressing the contents of nipple and during the initial stages of
swallowing

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Middle portion of the tongue: This region of tongue corresponds to the region
opposite to molars. This region is responsible for:
a. Pressing of food against molars facilitating the process of chewing
b. Passage of food into the upper lateral food channels at the side of the
tongue
c. When elevated this zone cuts off the oral cavity from the pharynx
facilitating break down of large mouth fulls of food into manageable
bolus. By elevating itself against the roof of palate it compensates for
paralysed soft palate reducing nasopharyngeal reflex
Posterior third of tongue:
a. This acts like a wedge of tissue in the pharyngeal phase of swallowing
which, when opposed to the soft palate and pharyngeal constrictors
displaces the bolus downwards and also helps to turn down the epiglottis.
b. When the mouth is closed this area is in apposition with the soft palate
closing off the oral cavity from pharynx at rest.
The whole of the tongue from before backwards is normally involved in the
coordinated peristaltic wave which squeezes the food from the mouth into the
lower pharynx. If the same movement is reversed (from backwards to
forwards) it creates a suction mechanism which is important with continuous
swallowing as in the case of sucking and drinking.
Pharyngeal stage:
When swallowing takes place in the erect position, the first half of the bolus is
passed through the pharynx into the oesophagus by means of tongue thrust and
is assisted by gravity. The peristaltic wave usually commences when the tongue
expressor wave reaches the soft palate. Usually there is no hold up at the level
of cricopharynx because of the preceding wave of relaxation. During
swallowing the bulk of the bolus is usually deflected on either side of the mouth
of larynx and comparatively very little passes down the midline over the
epiglottis. If the bolus is large, the larynx is pulled forwards to accommodate
the extra bulk.
When swallowing occurs in erect position, the bolus is usually directed down
the midline of the tongue up to the level of median glosso epiglottic fold. On
reaching this area it gets deflected into the vallecula on either side. The
epiglottis tilts backwards towards the posterior pharyngeal wall and serves to
arrest the descent of bolus as it descends down wards from the tongue base. As
the bolus accumulates over the epiglottis it spills over the lateral
pharyngoepiglottic folds into the lateral food channels. The bolus thus reaches
the pyriform fossae on either side. As the bulk of the bolus enters the upper
pharynx, the larynx is raised towards the hyoid bone the bolus from the
pyriform fossae is milked into the post cricoid area. The lax cricopharyngeal
sphincter allows the bolus to enter into the oesophagus.
As the tail of the bolus is expressed from the pharynx, the larynx is lowered and
the lateral food channels are cleared from above downwards. Finally the

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cricopharyngeus muscle contracts the expresses the bolus into the upper
oesophagus.
If a person swallows with the head turned fully to one side, the bolus is
deflected down the lower lateral food channel on the side opposite to which the
head is turned.
During this phase of swallowing the epiglottis and the laryngeal sphincteric
mechanism protects the airway from aspiration.

Oesophageal stage of deglution:


This is purely an involuntary reflex governed by oesophageal peristaltic waves.
Oesophagus serves as a conduction tube between the stomach and pharynx.
During the act of swallowing peristaltic waves pass down the oesophagus with
waves of positive pressure reaching 6-13kPa (50-100 mmHg). The form of
these waves varies with the nature of the swallowed food. With liquids and
semisolids there is an initial negative wave resulting from elevation of larynx
drawing on the cervical oesophagus. This is followed by the development of
abrupt positive wave coinciding with the entry of bolus into the oesophagus.
Next comes the slow rise of pressure succeeded by a final large positive
pressure wave which rises and falls rapidly. This is known as the stripping
peristaltic wave.
Tertiary oesophageal contractions are irregular non propulsive movements
involving long segments of oesophagus. This usually occurs during stages of
emotional stress.
At the lower end of oesophagus there is a zone of raised pressure of about 3 cm
length. This zone extends above the below the diaphragm with a mean pressure
of approximately 1kPa higher than that of intragastric pressure.
The consistency of the swallowed food material determines the mechanism
involved in its passage through the oesophagus. When fluid is swallowed, it
may be projected from the pharynx to the oesophagogastric junction in about 1
sec (if the subject is in a standing position) and is ahead of the peristaltic wave.
Due to this rapidity of flow, corrosives when swallowed cause burns which are
localized to the distal end of the oesophagus. If the bolus is solid / semisolid its
movement inside the oesophagus depends on the peristalsis.

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Diagram showing neural control of deglutition

III. BIOCHEMISTRY (3 x 5 = 15)


1. Sialochemistry.
Ninety nine percent of saliva is in the form of water. Sodium content of acinar
fluid is at about the same concentration as interstitial fluid - 140-150mm/l. This
sodium ion is being reabsorbed as the saliva passes through the striated ducts.
In the end saliva has a very low level of sodium concentration. When the flow
rates of saliva increases the concentration of sodium in the saliva approaches
that of plasma levels because the rapidity of flow of saliva via the striated ducts
reduces its ability to reabsorb sodium. Reabsorption of sodium which takes
place in the striated ducts is accompanied by a passive diffusion of chloride in
the same direction. Reabsorption of sodium ions in the striated duct in
conjunction with the movement of potassium in the reverse direction is said to
be under the influence of aldosterone. Reabsorption of water is affected by
antidiuretic hormone.
Potassium levels:
The concentration of extra-cellular potassium is low (4-5mm/l), but in the acinar
and ductal systems the concentration is significantly higher varying between 20-
80 mm/l depending on the flow rates.
As the rate of secretion of saliva increases, bicarbonate which is actively
expelled into the saliva also shows a significant increase. There is a

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simultaneous increase in the rate of reabsorption of chloride ions to adjust the
requisite ionic balance.

Principal constituents of saliva:

Water
Inorganic constituents:
Sodium
Potassium
Chloride
Calcium
Phosphate
Bicarbonate
Thiocyanate
Iodine
Bromide
Fluoride
Copper
Magnesium
Organic constituents:
Mucoproteins
Serum proteins
Enzymes – amylase, lysozyme
Glycoproteins – Fucose, Neuraminic acid, mannose, galactose
Free sugars – glucose
Blood group substances
Lipids
Aminoacids
Urea
The pH of saliva is low when the glands are not actively secreting, but raises
with faster flow rates due to the outpouring of bicarbonate.
The calcium content of saliva is lowest in the parotid and highest in the
accessory salivary glands.
About a third of calcium content of saliva is bound to proteins in the form of
complexes of which amylase comprises a significant proportion.
Salivary secretion of iodine is due to active transport of iodide from the plasma
and is always higher than that of plasma concentration.
Thiocyanate when found in the saliva is of a higher concentration than in
plasma. This is more evident in smokers.
Salivary proteins:

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These are usually a mixture of glycoproteins, mucoproteins, enzymes, blood
group substances and serum proteins. The sum total of these proteins get
elevated with increase in flow rates.
Proteins commonly secreted in the salivary gland are in the form of amylase.
Majority of amylase is secreted from the parotid gland, while the contribution of
amylase by submandibular and sublingual glands is negligible.
Lysozyme is an enzyme which is effective against the carbohydrate components
of the cell wall of certain bacteria. This is mostly secreted by the
submandibular salivary gland while parotid contributes just 10% of its
concentration.
Carbohydrate – protein substances corresponding to the blood group antigens
are secreted by all salivary glands with the exception of parotid. Their
concentration is highest in the accessory glands followed by sublingual and
submandibular salivary glands.
2. Biochemical changes in high altitudes.
In high altitudes the oxygen saturation is very less. Body will have to adapt to
the low oxygen pressures. Hypoxia is chronic at high altitudes. High altitude
hypoxia results from decrease in the barometric pressure with increasing
altitude and hence air flowing into the alveoli of lungs has lower concentration
of oxygen when compared to that of normal sea level.
Hypoxic pulmonary vasoconstriction:
An immediate response to hypoxia in inspired air is pulmonary vasoconstriction
causing narrowing of blood vessels supplying the alveoli of the lung. This is a
local homeostatic mechanism to redistribute blood from temporarily ill
ventilated areas of lung to better ventilated areas. There is also another
explanation for this pulmonary vasoconstriction i.e. it is the deliberate attempt
of the human body to revert back to fetal type of blood flow. This of course has
no physiological beneficial effects. Whatever may be the reason this
vasoconstriction causes an effective reduction in the cardiac output. Exposure
to chronic hypoxia by living at high altitudes for prolonged periods of time
brings about certain changes like muscularization of pulmonary arteries.
Increase in pulmonary ventilation:
This occurs almost within seconds of exposure to hypoxia. This is considered
to be an adaptive mechanism since it ensures more oxygen is delivered to the
alveoli to facilitate better gas exchange. The resting ventilation levels can
increase from the normal 6 L /min to 11 L /min within 8 days of exposure to
chronic hypoxia. This reflex increase in ventilation induced by hypoxia is
known as Hypoxic ventilatory response.
Increase in the concentration of haemoglobin:
This haematological adjustment should be considered as an adaptive response of
the human system to prolonged hypoxia. The increase in haemoglobin
concentration during the first few days of exposure to hypoxia is due to
hemoconcentration. Prolonged stay at these altitudes causes a real time increase

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in the number of red cells there by increasing the oxygen carrying capacity of
blood. The molecular basis of increased haemoglobin concentration is the
increase in the secretion of the hormone erythropoietin. The concentration of
erythropoietin in blood increases many folds.

3. Respiratory control of acid base balance.


There are three primary systems that regulate the hydrogen ion concentration of
the body fluids.
1. The chemical acid base buffer systems of body fluids, which immediately
combine with acid / base to prevent excessive changes in pH
2. The respiratory centre which regulates the removal of carbon dioxide
(bicarbonate) from the extracellular fluid
3. The kidneys which can get rid of excess acid / alkali via urine.
The lungs are responsible for the regulation of the volatile acids in the body
fluids.
Carbon dioxide is a major end product of metabolism. It is being usually
generated on a continuing basis inside the living cells. The carbon dioxide thus
formed diffuses out of the cell and reaches the blood stream through the
interstitial fluid. In the blood stream it is present as carbonic acid. On reaching
the lungs the carbonic acid gets reconverted to carbon dioxide and is breathed
out. In lungs acid is excreted as carbon dioxide, while water produced by the
reaction is dissipated into the general water pool of the body.
Whenever there is an imbalance in the hydrogen ion concentration the
respiratory centre is stimulated. If the body needs to deal with excess hydrogen
ion concentration the lungs respond by increasing the rate of ventilation. This
hyperventilatory response manages to eliminate more acid as carbon dioxide. If
the body needs to retain hydrogen ions to counteract a pH which is too alkaline,
the lungs respond by reducing the ventilatory rate. This hypoventilation
response manages to retain hydrogen ions within the system.

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The respiratory response to changes in hydrogen ion concentration and blood
pH is really rapid. The lungs alone are capable of readjusting the hydrogen ion
concentration within seconds after a sudden change has occurred. Its efficiency
is only about 50-75% hence is not useful in long term maintenance of acid base
balance.
IV. PHARMACOLOGY (3 x 5 = 15)
1. Nonviral vectors in gene therapy.

The transfer of genetic material using non-viral systems preceded the developed
of viral- based vectors. Non-viral vectors, also called physical mechanisms of
gene transfer, can be traced back to the work of Avery, MacLeod, and
McCarthy, in 1944 which showed that genes were transferred by nucleic acids.
Several studies in the early 1960s reported changes in cellular phenotype
following exogenous DNA exposure. The first non-viral technique to gain wide
acceptance was calcium phosphate-mediated transfection. This system has
undergone little change since being well characterized in the early 1970s. It was
not until the advent of cationic liposomes in 1988 that non-viral vectors offered
an efficient means to transfer genes into cells.

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Polycations have been commonly used as non-viral gene carriers because of
their ability to bind to DNA’s in a non-covalent manner forming stable
complexes. Poly (L-lysine) has been commonly used polycation for targeted
gene delivery.
Major advantage of these non-viral vectors in gene therapy is that it does not
have the risk of virus infecting a human cell. All the reactions can be planned at
the lab level itself before injecting the gene.

Non-viral vector therapy can be divided into those that are limited to in vitro
applications and those that can be used for both in vitro and in vivo
applications.

Microinjection:

Microinjection delivers plasmid DNA directly into the cell's nucleus. Using the
light microscope, a glass pipette is guided into the nucleus and a small amount
of DNA or RNA injected. In doing so, both cytoplasmic and lysosomal
degradation of the injected material is avoided and efficient gene expression can
be expected from the surviving cells. Unfortunately, this technique is extremely
labor intensive and requires well isolated cells.

Since safety and efficiency can be closely monitored using microinjection, it


may one day prove useful in germ line gene therapy applications.
Microinjection of a particular gene into a cell at a specific time during
development has the potential to alter the genotype and phenotype of every cell
formed thereafter. Germline modification has already been accomplished in
many mammals, which have been termed transgenic animals, ranging in size
from mice to cattle. Germline modifications in humans for the correction of
specific disorders are far from a present reality and are fraught with ethical
considerations.

Non-viral vectors limited to in vitro applications:

Calcium phosphate transfection:

Calcium phosphate transfection, initially described in the early 1960s, was


refined and systematically improved to result in a standard protocol which has
changed little since the early 1970s. In many cases it remains the system of
choice for transferring plasmid DNA into a variety of cell cultures and
packaging cell lines. It is particularly important in the production of
recombinant viral vectors.

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Microinjection:

Microinjection delivers plasmid DNA directly into the cell's nucleus. Using the
light microscope, a glass pipette is guided into the nucleus and a small amount
of DNA or RNA injected. In doing so, both cytoplasmic and lysosomal
degradation of the injected material is avoided and efficient gene expression can
be expected from the surviving cells. Unfortunately, this technique is extremely
labor intensive and requires well isolated cells.

Since safety and efficiency can be closely monitored using microinjection, it


may one day prove useful in germline gene therapy applications. Microinjection
of a particular gene into a cell at a specific time during development has the
potential to alter the genotype and phenotype of every cell formed thereafter.
Germline modification has already been accomplished in many mammals,
which have been termed transgenic animals, ranging in size from mice to cattle.
Germline modifications in humans for the correction of specific disorders is far
from a present reality and is fraught with ethical considerations.

Electroporation:

Electroporation is the application of high voltage to a mixture of DNA and cells


in suspension. The cell-DNA suspension is placed between two electrodes and
subjected to an electrical pulse. The DNA enters the cells through holes formed
in the cellular membrane during the electrical pulse. The DNA is trapped within
the cytoplasm upon termination of the electrical pulse. For efficient gene
transfer, electroporation depends upon the nature of the electrical pulse, the
distance between the electrodes, the ionic strength of the suspension buffer, and
the nature of the cells. Best results have often been obtained from rapidly
proliferating cells. Electroporation of mammalian cells is an inefficient
technique since many cells do not survive the high voltage nature of this
procedure. Because of its unique characteristics, electroporation has been
difficult to properly design for in vivo applications.

Non-viral techniques used for both in vivo and in vitro applications:

Liposomes:

Liposomes were first described in 1965 as a model of cellular membranes and


quickly were applied to the delivery of substances to cells. Liposomes entrap

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DNA by one of two mechanisms which have resulted in their classification as
either cationic liposomes or pH-sensitive liposomes.

Cationic liposomes: are positively charged liposomes which interact with the
negatively charged DNA molecules to form a stable complex. Cationic
liposomes consist of a positively charged lipid and a co-lipid. Commonly used
co-lipids include dioleoyl phosphatidylethanolamine (DOPE) or dioleoyl
phosphatidylcholine (DOPC). Co-lipids, also called helper lipids, are in most
cases required for stabilization of liposome complex. A variety of positively
charged lipid formulations are commercially available and many other are under
development. One of the most frequently cited cationic lipids is lipofectin.
Lipofectin is a commercially available cationic lipid first reported by Phil
Felgner in 1987 to deliver genes to cells in culture.

pH sensitive (negatively charged liposomes): entrap DNA rather than complex


with it. Since both the DNA and the lipid are similarly charged, repulsion rather
than complex formation occurs. Yet, some DNA does manage to get entrapped
within the aqueous interior of these liposomes. In some cases, these liposomes
are destabilized by low pH and hence the term pH- sensitive. To date, cationic
liposomes have been much more efficient at gene delivery both in vivo and in
vitro than pH-sensitive liposomes. pH-sensitive liposomes have the potential to
be much more efficient at in vivo DNA delivery than their cationic counterparts
and should be able to do so with reduced toxicity and interference from serum
protein.

Liposomes offer several advantages in delivering genes to cells.

• Liposomes can complex both with negatively and positively charged


molecules.
• Liposomes offer a degree of protection to the DNA from degradative
processes.
• Liposomes can carry large pieces of DNA, potentially as large as a
chromosome.
• Liposomes can be targeted to specific cells or tissues.

In addition, liposomes overcome problems inherent with viral vectors -


specifically concerns of immunogenicity and replication competent virus
contamination. The ability to chemically synthesize a wide variety of liposomes
has resulted in a highly adaptable and flexible system capable of gene delivery
both in vitro and in vivo. As liposome technology is better understood, it should
be possible to produce reagents with improved in vivo gene delivery into
specific tissues. Studies involving protein-DNA-liposome complexes are
already showing promise in the ability to target DNA delivery into specific
cells. Current limitations regarding in vivo application of liposomes revolve
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around the low transfection efficiencies and transient gene expression. Also,
liposomes display a small degree of cellular toxicity and appear to be inhibited
by serum components. The ability to overcome these problems should greatly
facilitate their application to a variety of gene delivery mechanisms.

Naked plasma DNA injection:

All gene transfer vector systems rely heavily on plasmid DNA. Surprisingly,
transgene expression has been observed in rodent and primate muscle following
intramuscular injection of plasmid DNA. The simplicity of injecting plasmid
DNA into muscle with a syringe has greatly influenced many aspects of gene
therapy research. Tissues which exhibit transgene expression following plasmid
DNA injection include the thymus, skin, cardiac muscle, and skeletal muscle.
Of these tissues, long-term transgene expression was observed only in striated
muscle. Expression in mouse skeletal muscle has been observed for greater than
19 months following a single intramuscular injection. It has been assumed that
the plasmid DNA must have entered the nucleus in order for gene expression to
occur. Plasmid DNA does not undergo changes in its methylation pattern
suggesting that it has not replicated following its injection into muscle. Also, the
plasmid DNA does not integrate into the host genome following intramuscular
injection.

A variety of factors influence the effectiveness of gene transfer into muscle by


intramuscular plasmid DNA injection. Multiple injections of plasmid DNA
improve the overall expression obtained from a single muscle, but following a
single injection transgene expression is observed in less than 1% of the total
myofibers. A variety of injection solutions have been tested and all those with
physiological osmolarity work similarly. Preinjection of sucrose solutions into
the muscle slightly improves transgene expression levels. Stimulating the
muscle to proliferate prior to the plasmid DNA injection greatly enhances the
levels of transgene expression for at least one month following plasmid DNA
injection. Age and species also appear to influence the effectiveness of this
technique. Younger animals appear to show higher gene transfer efficiencies
than older. Primate muscle appears to be less efficient in its ability to uptake
DNA following its injection than rodent muscle. It has been postulated that both
the age and species related differences are due to variability in the connective
tissue barriers present in muscles of different age or species. Transgene
expression has also been observed following the implantation of pelleted
plasmid DNA into the muscle. Currently, no conclusive evidence has been
provided for the exact mechanism by which plasmid DNA uptake occurs in
muscle or why it appears to be a predominantly muscle- specific phenomenon.
Nuclear entry of the plasmid appears to be regulated by the nuclear pore
complex.

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The greatest advantages of intramuscular plasmid DNA injection are its
simplicity and the fact that plasmids ranging in size from 2-19 kilobases have
been successfully used to transfer genes to muscle. Its greatest limitations are
the low percentage of myofibers which express genes following single injection
and its restriction to skin, thymus and striated muscle.

2. Drug induced sialadenitis.


Drug induced enlargement of salivary gland has certain unique features which
include:
1. Bilateral involvement
2. Painless enlargement
3. Xerostomia is usually common in these patients

Common Drugs which are known to cause sialadenitis include:


Phenylbutazone
Clozapine
Sulphadiazine
Chlorhexidine
Naproxen – sialadenitis caused by ingestion of this drug is considered to be
allergic in nature because of the presence of allergic skin rashes.
Iodide – Radioactive iodine used in the treatment of thyroid malignancy has
been known to cause transient sialadenitis. Clinical features can develop as
early as the first 24 hours after exposure to the drug. Incidence of sialadenitis
due to use of radioactive iodine can be significantly reduced by concomitant use
of sialagogues which could increase the salivary glandular flow.
Other drugs which can cause salivary gland swelling include:
Antithyroid agents
Insulin
Ganglion blockers
Interferons
Cardiac agents like Nifidepine
Drug induced sialadenitis are difficult to diagnose as then tend to become
normal after cessation of medication. High index of suspicion alone will point
towards this diagnosis.

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4. General anesthetics.

Definition:
General anesthetic is a drug which is capable of causing reversible loss of
consciousness.
Categories of general anesthetics:
1. Inhalational: This include gases and vapours which are used to induce
general anesthesia
2. Injections: This category includes drugs used parenterally to induce
general anesthesia. Injections can be used to induce anesthesia / maintain
it.
Inhalational agents:
These agents are either volatile liquids / gases and need special apparatus for
their administration. This apparatus enables mixing of oxygen along with the
anesthetic agent and ambient air and supplies it to the patient. Liquid anesthetic
agents can be vaporised in this machine using special vaporizers.
Commonly used volatiles include:
Desflurane
Isoflurane
Sevoflurane
Halothane
Enflurane
Methoxyflurane

General actions of inhalational agents:


Depresses respiration and responses to carbon dioxide.
Depresses renal blood flow and urine output.
In high concentrations relaxes skeletal muscle.
There is generalized reduction of blood pressure and peripheral vascular
resistance.

Commonly used anesthetic gas:


Nitrous oxide is the most commonly used anesthetic gas. This is usually the
most preferred agent for maintenance anaesthesia.
Commonly used injections as anesthetic agents include:
Propofol
Etomidate
Barbiturates
Benzodiazepines
Ketamine

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Mode of action of general anesthetic agents:
General anesthetic exerts their action by acting on the plasma membrane. For
them to be effective they need to be lipid soluble. These drugs inhibit the
excitatory functions of CNS receptors. Some drugs of this category stimulate
the inhibitory receptors present in the central nervous system. These are all
hypothesis. Mode of action of general anesthetic drugs are largely not known
till date. Various hypotheses have been offered to explain their function. These
include:

1. Lipid theory
2. Protein (receptor) theory
3. Binding theory

Elimination of inhalational anesthetic agents:


Volatile anesthetics are excreted during their terminal phase via the lungs.
Hence it is better for these drugs to have a low blood gas coefficient to enable
rapid elimination via the lungs.
Some of the older anesthetic agents like choloroform were excreted via the liver
and were hence considered to be hepatotoxic agents.

V. PATHOLOGY (3 x 5 = 15)
1. Ameloblastoma - histopathology and subtypes.
This is the most common odontogenic neoplasm with a low malignant
potential.
Types of ameloblastoma:
1. Follicular type
2. Plexiform type
3. Granular cell type
4. Desmoplastic type
5. Vascular type
6. Acanthomatous type
7. Papilliferous – keratotic type
8. Dentinoid induction type
These tumours arise from:
a. Epithelial lining of dentigerous cyst
b. Remnants of dental lamina and enamel organ
c. Basal layer of oral mucosa
A majority of these tumors arise from mandible.

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Histopathology:
Cells in these tumors have a tendency to move the nuclei away from basement
membranes. This is known as reverse polarization.
The follicular type will have outer arrangement of columnar or palisaded
ameloblast like cells and inner zone of triangular shaped cells
resembling stellate reticulum in bell stage. The central cells sometimes
degenerate to form central microcysts. The plexiform type has epithelium that
proliferates in a "Fish Net Pattern". The plexiform ameloblastoma shows
epithelium proliferating in a 'cord like fashion', hence the name 'plexiform'.
There are layers of cells in between the proliferating epithelium with a well-
formed desmosomal junctions, simulating spindle cell layers.

2. Nasopharyngeal carcinoma - etiopathogenesis and histological


Classification.

Etiopathogenesis:

1. Epstein - Barr virus: E.B. virus infections have been postulated to be the
etiological agent responsible for nasopharyngeal carcinoma. The presence of
raised antibody titers, and demonstration of viral genome in tumor cells are
ample proof.

2. Exposure to chemical agents i.e. tobacco, drugs, and plant products.

3. Dietary factors: Ingestion of salted fish, preserved vegetables, fermented food


stuff containing Nitrosamines and nitro precursors.

4. Cooking habits: Household smoke and fumes

5. Religious practices: like incense and joss stick smoke

6. Occupation: Exposure to industrial fumes / chemicals, metal smelting,


Formaldehyde, wood dust

7. Other causes: Socioeconomic status, Nutritional deficiencies, weaning habits

8. Genetic susceptibility: Many HLA haplotypes have been associated with


increased incidence of nasopharyngeal carcinoma. The loci involved are the
HLA-A, B and DR locus situated on the short arm of chromosome 6.

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Histological classification:

WHO classification of nasopharyngeal carcinoma is the most commonly used


method. This classification divides nasopharyngeal carcinoma into three
histological subtypes on the basis of light microscopic examination.

. Type I squamous cell carcinoma (keratinizing):

- well differentiated

- moderately differentiated

- poorly differentiated

. Type II Nonkeratinizing carcinoma

. Type III Undifferentiated carcinoma

4. Nodular fasciitis.

This condition is also known as nodular pseudosarcomatous fasciitis. This


benign lesion is commonly found in the superficial fascia. Etiologically it
should be considered to be similar to that of dermatofiborma. It responds well
to surgical excision and very rarely recurs.
Histology:

 Histologically vast array of patterns.


 Short S-shaped fascicles, inflammation, accelerated mitotic index with
normal mitoses.
 Essentially spindle cell proliferation.
 Stroma is rich in collagen and/or myxoid ground substance.

In adults it is commonly seen in the flexor surface of forearm and trunk. In


infants it is commonly seen in the head and neck region.

V1. MICROBIOLOGY (3 x 5 = 15)


1. Retroviruses in ENT practice.

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These are RNA viruses that are replicated inside the cell with the help of the
enzyme reverse transcriptase. This enzyme produces DNA from the intraviral
RNA. The term retro indicates reversal of RNA genome to DNA genome.
Commonest retrovirus of importance to otolaryngologist is HIV virus.
HIV virus induced conditions of relevance to otolaryngologist:
Oesophageal candidiasis – Candidial infections of upper oesophagus is the
classic feature of HIV infections. These patients have odynophagia. On
examination whitish patches can be seen close to the post cricoid region.
Oral candidiasis: Oral thrush caused due to immunodeficiency. This could
progress to oesophageal candidiasis.
Recurrent serpigenous aphthous ulcer: This is another classic feature of HIV
manifestations of oral cavity.
On infection two things are possible:

1. The virus may remain dormant (latent stage) allowing the cell to perform
its normal functions
2. The virus may begin to proliferate and start to infect other cells
promoting viral transmission

Stages of HIV infection:

Incubation period – This asymptomatic phase could last anywhere between 4-6
weeks.

Second stage – Causes acute symptoms like fever, lymphadenitis, pharyngitis,


myalgia and malaise.

Stage of latency – Asymptomatic phase could last anywhere between 2 weeks


to 20 years.

Final stage – This is brought out by the presence of opportunistic infections


due to suppression of immunity.

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2. Mycology of allergic fungal Rhino-sinusitis.

Pathogenesis of allergic fungal rhinosinusitis is not clearly understood. It has


been postulated that the fungal elements trapped in the nasal mucosa somehow
manages to release antigenic material which could stimulate excessive release
of IgA, IgE, IgG production.
Fungi of Aspergillus species have been implicated. Studies have demonstrated
that viral infections of nasal mucosa increase its susceptibility to fungal
infections.
Fungal mycelium in the sinus cavity can lead to allergic rhinosinusitis by acting
as foreign body within the sinus cavity. The products of metabolism of these
mycelia can also lead to stimulation of immune system causing allergic
reactions.
Allergic rhinosinusitis is common in patients who have undergone dental filling.
This is caused due to diffusion of soluble zinc from the filling into the sinus
mucosa causing excessive growth of Aspergillus species.
The causative fungi belong to the following groups:
1. Bipolaris
2. Curvularia
3. Exserohilum
4. Alternaria
5. Helmintosporium
6. Fusarium
7. Aspergillus

3. Serological tests for syphilis.


Serological tests for syphilis can be sub classified into:
Non treponemal tests
Treponemal tests

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Non treponemal tests: These tests detect nonspecific treponemal
antibodies. Classic examples of this group of tests include the VDRL and
Rapid Plasma Reagin tests (RPR Test).

VDRL: This is also known as Venereal disease research laboratory test.


This is a slide flocculation rapid diagnostic test to diagnose syphilis. The
antigen used in this test is cardiolipin (extracted from beef heart). The
antibodies reacting to cardiolipin has been termed as regain. This test is
based on the principle that patients suffering with syphilis produce the
antibody regain which reacts positively with cardiolipin and hence this
test becomes positive. This test usually becomes positive after the first
week of development of primary chancre. This is a non-specific test and
should always be interpreted with specific tests.
Treponemal tests:
These are highly specific tests for treponemal antigens. These include:
a. TPHA – Treponema pallidum haemagglutination
b. FTA-abs – Fluorescent treponemal antibody absorbed test
c. EIA tests – enzyme immunoassay test

These serogical tests for syphilis are used for:


1. In screening asymptomatic individuals for the presence of syphilis
(especially pregnant women)
2. Screening patients attending genitourinary clinic to rule out syphilis
3. Screening organ / blood donors
4. Excluding syphilis in patients with HIV infections
5. Assessment / staging the stage of disease

Among these tests available FTA-abs is considered to be the gold


standard. Its limitations include its subjective interpretation and difficulties
faced while standardizing it.
TPHA is the most sensitive serological test but has rather high false positive
results. Even though this test can be performed rapidly, but should always be
confirmed by performing other serological tests.
**

Drtbalu’s otolaryngology online Page 37