Dysgeusia

Dysgeusia (/dsu/ or /dsjuzi/) or parageusia is a distortion of the

sense of taste. Dysgeusia is also often associated with ageusia, which is the
complete lack of taste, and hypogeusia, which is the decrease in taste
sensitivity. An alteration in taste or smell may be a secondary process in
various disease states, or it may be the primary symptom. The distortion in
the sense of taste is the only symptom, and diagnosis is usually complicated
since the sense of taste is tied together with other sensory systems.
Common causes of dysgeusia include chemotherapy, asthma treatment with
albuterol, and zinc deficiency. Different drugs could also be responsible for
altering taste and resulting in dysgeusia. Due to the variety of causes of
dysgeusia, there are many possible treatments that are effective in
alleviating or terminating the symptoms of dysgeusia. These include artificial
saliva, pilocarpine, zinc supplementation, alterations in drug therapy, and
alpha lipoic acid.

Background
The sense of taste is based on the detection of chemicals by specialized
taste cells in the mouth. The mouth, throat, larynx, and esophagus all have
taste buds, which are replaced every ten days. Each taste bud contains
receptor cells. Afferent nerves make contact with the receptor cells at the
base of the taste bud.[3] A single taste bud is innervated by several afferent

nerves, while a single efferent fiber innervates several taste buds.Fungiform

papillae are present on the anterior portion of the tongue while circumvallate
papillae and foliate papillae are found on the posterior portion of the tongue.
The salivary glands are responsible for keeping the taste buds moist with
saliva.
A single taste bud is composed of four different types of cells, and each taste
bud has at least 30 to 80 cells. Type I cells are thinly shaped, usually in the
periphery of other cells. They also contain high amounts of chromatin. Type II
cells have prominent nuclei and nucleoli with much less chromatin than Type
I cells. Type III cells have multiple mitochondria and large vesicles. Type I, II,
and III cells also contain synapses. Type IV cells are normally rooted at the
posterior end of the taste bud. Every cell in the taste bud forms microvilli at
the ends.
In humans, the sense of taste is conveyed via three of the twelve cranial
nerves. The chorda tympani is responsible for taste sensations from the
anterior two thirds of the tongue, the glossopharyngeal nerve is responsible
for taste sensations from the posterior one third of the tongue while a branch
of the vagus nerve carries some taste sensations from the back of the oral
cavity.

Diagnosis
In general, gustatory disorders are challenging to diagnose and evaluate.
Because

gustatory

functions

are

tied

to

the

sense

of

smell,

the

somatosensory system, and the perception of pain (such as in tasting spicy

foods), it is difficult to examine sensations mediated through an individual

system. In addition, gustatory dysfunction is rare when compared to
olfactory disorders.
Diagnosis of dysgeusia begins with the patient being questioned about
salivation, swallowing, chewing, oral pain, previous ear infections (possibly
indicated by hearing or balance problems), oral hygiene, and stomach
problems. The initial history assessment also considers the possibility of
accompanying diseases such as diabetes mellitus, hypothyroidism, or cancer.
[10] A clinical examination is conducted and includes an inspection of the
tongue and the oral cavity. Furthermore, the ear canal is inspected, as
lesions of the chorda tympani have a predilection for this site.

Gustatory testing
In order to further classify the extent of dysgeusia and clinically measure the
sense of taste, gustatory testing may be performed. Gustatory testing is
performed either as a whole-mouth procedure or as a regional test. In both
techniques, natural or electrical stimuli can be used. In regional testing, 20 to
50 L of liquid stimulus is presented to the anterior and posterior tongue
using a pipette, soaked filter-paper disks, or cotton swabs. In whole mouth
testing, small quantities (2-10 mL) of solution are administered, and the
patient is asked to swish the solution around in the mouth.

Threshold tests for sucrose (sweet), citric acid (sour), sodium chloride (salty),
and quinine or caffeine (bitter) are frequently performed with natural stimuli.
One of the most frequently used techniques is the "three-drop test."[11] In
this test, three drops of liquid are presented to the subject. One of the drops
is of the taste stimulus, and the other two drops are pure water.[11]
Threshold is defined as the concentration at which the patient identifies the
taste correctly three times in a row.

Suprathreshold tests, which provide intensities of taste stimuli above

threshold levels, are used to assess the patient's ability to differentiate
between different intensities of taste and to estimate the magnitude of
suprathreshold loss of taste. From these tests, ratings of pleasantness can be
obtained using either the direct scaling or magnitude matching method and
may be of value in the diagnosis of dysgeusia. Direct scaling tests show the
ability to discriminate among different intensities of stimuli and whether a
stimulus of one quality (sweet) is stronger or weaker than a stimulus of
another quality (sour). Direct scaling cannot be used to determine if a taste
stimulus is being perceived at abnormal levels. In this case, magnitude
matching is used, in which a patient is asked to rate the intensities of taste
stimuli and stimuli of another sensory system, such as the loudness of a
tone, on a similar scale. For example, the Connecticut Chemosensory Clinical
Research Center asks patients to rate the intensities of NaCl, sucrose, citric
acid and quinine-HCl stimuli, and the loudness of 1000 Hz tones. Assuming
normal hearing, the results of this cross-sensory test show the relative
strength of the sense of taste in relation to the loudness of the auditory
stimulus. Although many of the tests are based on ratings using the direct
scaling method, some tests do use the magnitude-matching procedure.
Other tests include identification or discrimination of common taste
substances. Topical anesthesia of the tongue has been reported to be of use
in the diagnosis of dysgeusia as well, since it has been shown to relieve the
symptoms of dysgeusia temporarily.[9] In addition to techniques based on
the administration of chemicals to the tongue, electrogustometry is
frequently used. It is based on the induction of gustatory sensations by
means of an anodal electrical direct current. Patients usually report sour or
metallic sensations similar to those associated with touching both poles of a
live battery to the tongue.[13] Although electrogustometry is widely used,
there seems to be a poor correlation between electrically and chemically
induced sensations.

Diagnostic tools
Certain diagnostic tools can also be used to help determine the extent of
dysgeusia. Electrophysiological tests and simple reflex tests may be applied
to identify abnormalities in the nerve-to-brainstem pathways. For example,
the blink reflex may be used to evaluate the integrity of the trigeminal
nervepontine brainstemfacial nerve pathway, which may play a role in
gustatory function.
Structural imaging is routinely used to investigate lesions in the taste
pathway. Magnetic resonance imaging allows direct visualization of the
cranial nerves. Furthermore, it provides significant information about the
type and cause of a lesion.Analysis of mucosal blood flow in the oral cavity in
combination with the assessment of autonomous cardiovascular factors
appears to be useful in the diagnosis of autonomic nervous system disorders
in burning mouth syndrome and in patients with inborn disorders, both of
which are associated with gustatory dysfunction. Cell cultures may also be
used when fungal or bacterial infections are suspected.
In addition, the analysis of saliva should be performed, as it constitutes the
environment of taste receptors, including transport of tastes to the receptor
and protection of the taste receptor. Typical clinical investigations involve
sialometry and sialochemistry. Studies have shown that electron micrographs
of taste receptors obtained from saliva samples indicate pathological
changes in the taste buds of patients with dysgeusia and other gustatory
disorders.
Causes
Chemotherapy
A major cause of dysgeusia is chemotherapy for cancer. Chemotherapy often
induces damage to the oral cavity, resulting in oral mucositis, oral infection,
and salivary gland dysfunction. Oral mucositis consists of inflammation of the

mouth, along with sores and ulcers in the tissues. Healthy individuals
normally have a diverse range of microbial organisms residing in their oral
cavities; however, chemotherapy can permit these typically non-pathogenic
agents to cause serious infection, which may result in a decrease in saliva. In
addition, patients who undergo radiation therapy also lose salivary tissues.
Saliva is an important component of the taste mechanism. Saliva both
interacts with and protects the taste receptors in the mouth. Saliva mediates
sour and sweet tastes through bicarbonate ions and glutamate, respectively.
The salt taste is induced when sodium chloride levels surpass the
concentration in the saliva. It has been reported that 50% of chemotherapy
patients have suffered from either dysgeusia or another form of taste
impairment.Examples

of

chemotherapy

treatments

that

can

lead

to

dysgeusia are cyclophosphamide, cisplatin, and etoposide. The exact

mechanism of chemotherapy-induced dysgeusia is unknown.
Taste buds
Distortions in the taste buds may give rise to dysgeusia. In one study
conducted by Masahide Yasuda and Hitoshi Tomita from Nihon University of
Japan, it has been observed that patients suffering from this taste disorder
have fewer microvilli than normal. In addition, the nucleus and cytoplasm of
the taste bud cells have been reduced. Based on their findings, dygeusia
results from loss of microvilli and the reduction of Type III intracellular
vesicles, all of which could potentially interfere with the gustatory pathway.
Zinc deficiency
Another primary cause of dysgeusia is zinc deficiency. While the exact role of
zinc in dysgeusia is unknown, it has been cited that zinc is partly responsible
for the repair and production of taste buds. Zinc somehow directly or
indirectly interacts with carbonic anhydrase VI, influencing the concentration
of gustin, which is linked to the production of taste buds. It has also been
reported that patients treated with zinc experience an elevation in calcium

concentration in the saliva. In order to work properly, taste buds rely on

calcium receptors. Zinc is an important cofactor for alkaline phosphatase,
the most abundant enzyme in taste bud membranes; it is also a component
of a parotid salivary protein important to the development and maintenance
of normal taste buds.
Drugs
There are also a wide variety of drugs that can trigger dysgeusia, including
zopiclone,

H1-antihistamines,

such

as

azelastine

and

emedastine.

Approximately 250 drugs affect taste. The sodium channels linked to taste
receptors can be inhibited by amiloride, and the creation of new taste buds
and saliva can be impeded by antiproliferative drugs. Saliva can have traces
of the drug, giving rise to a metallic flavor in the mouth; examples include
lithium carbonate and tetracyclines. Drugs containing sulfhydryl groups,
including penicillamine and captopril, may react with zinc and cause
deficiency. Metronidazole and chlorhexidine have been found to interact with
metal ions that associate with the cell membrane. Drugs that prevent the
production of angiotensin II by inhibiting angiotensin converting enzyme,
eprosartan for example, have been linked to dysgeusia. There are few case
reports claiming calcium channel blockers like Amlodipine also cause
dysguesia by blocking calcium sensitive taste buds.

Diplopia
What Causes Double Vision?
Opening your eyes and seeing a single, clear image is something you
probably take for granted. But that seemingly automatic process depends on
the orchestration of multiple areas of the vision system. They all need to
work together seamlessly:
The cornea is the clear window into the eye. It does most of the focusing of
incoming light.
The lens is behind the pupil. It also helps focus light onto the retina.
Muscles of the eye -- extraocular muscles -- rotate the eye.
Nerves carry visual information from the eyes to the brain.
The brain is where several areas process visual information from the eyes.
Problems with any part of the vision system can lead to double vision.
Cornea problems. Problems with the cornea often cause double vision in one
eye only. Covering the affected eye makes the double vision go away. The
abnormal surface of the eye distorts incoming light, causing double vision.
Damage can happen in several ways:
Infections of the cornea, such as herpes zoster, or shingles, can distort the
cornea.
Corneal scars can alter the cornea, creating unequal visual images.
Dryness of the cornea can create double vision.
Lens problems. Cataracts are the most common problem with the lens that
causes double vision. If cataracts are present in both eyes, images from both
eyes will be distorted. Cataracts are often correctable with minor surgery.
Muscle problems. If a muscle in one eye is weak, that eye can't move
smoothly with the healthy eye. Gazing in directions controlled by the weak
muscle causes double vision. Muscle problems can result from several
causes:

Myasthenia gravis is an autoimmune illness that blocks the stimulation of

muscles by nerves inside the head. The earliest signs are often double vision
and drooping eyelids, or ptosis.
Graves' disease is a thyroid condition that affects the muscles of the eyes.
Graves' disease commonly causes vertical diplopia. With vertical diplopia,
one image is on top of the other.

Diplopia, commonly known as double vision, is the simultaneous perception

of two images of a single object that may be displaced horizontally,
vertically, diagonally (i.e., both vertically and horizontally), or rotationally in
relation to each other.[1] It is usually the result of impaired function of the
extraocular muscles (EOMs), where both eyes are still functional but they
cannot converge to target the desired object.[1] Problems with EOMs may be
due to mechanical problems, disorders of the neuromuscular junction,
disorders of the cranial nerves (III, IV, and VI) that stimulate the muscles, and
occasionally disorders involving the supranuclear oculomotor pathways or
ingestion of toxins.
Diplopia can be one of the first signs of a systemic disease, particularly to a
muscular or neurological process,[3] and it may disrupt a persons balance,
movement, and/or reading abilities.

Classification
Binocular
Binocular diplopia is double vision arising as a result of strabismus (in
layman's terms cross-eyed), the misalignment of the two eyes relative to
each other either esotropia (inward) or exotropia (outward). In such a case
while the fovea of one eye is directed at the object of regard, the fovea of

the other is directed elsewhere, and the image of the object of regard falls on
an extra-foveal area of the retina.
The brain calculates the 'visual direction' of an object based upon the
position of its image relative to the fovea. Images falling on the fovea are
seen as being directly ahead, while those falling on retina outside the fovea
may be seen as above, below, right or left of straight ahead depending upon
the area of retina stimulated. Thus, when the eyes are misaligned, the brain
will perceive two images of one target object, as the target object
simultaneously stimulates different, non-corresponding, retinal areas in
either eye, thus producing double vision.

This correlation of particular areas of the retina in one eye with the same
areas in the other is known as retinal correspondence. This relationship also
gives rise to an associated phenomenon of binocular diplopia, although one
that is rarely noted by those experiencing diplopia: Because the fovea of one
eye corresponds to the fovea of the other, images falling on the two foveas
are 'projected' to the same point in space. Thus, when the eyes are
misaligned, two different objects will be perceived as superimposed in the
same space. This phenomenon is known as 'visual confusion'.
The brain naturally guards against double vision. In an attempt to avoid
double vision, the brain can sometimes ignore the image from one eye; a
process known as suppression. The ability to suppress is to be found
particularly in childhood when the brain is still developing. Thus, those with
childhood strabismus almost never complain of diplopia while adults who
develop strabismus almost always do. While this ability to suppress might
seem an entirely positive adaptation to strabismus, in the developing child
this can prevent the proper development of vision in the affected eye
resulting in amblyopia. Some adults are also able to suppress their diplopia,
but their suppression is rarely as deep or as effective and takes longer to

establish, and thus they are not at risk of permanently compromising their
vision.

Hence,

in

some

cases

diplopia

disappears

without

medical

intervention, but in other cases the cause of the double vision may still be
present.
Certain persons with diplopia who cannot achieve fusion and yet do not
suppress may display a certain type of spasm-like irregular movement of the
eyes in the vicinity of the fixation point (see: Horror fusionis).

Monocular
More rarely, diplopia can also occur when viewing with only one eye; this is
called monocular diplopia, or, where the patient perceives more than two
images, monocular polyopia. In this case, the differential diagnosis of
multiple image perception includes the consideration of such conditions as
corneal surface keratoconus, subluxation of the lens, a structural defect
within the eye, a lesion in the anterior visual cortex or non-organic
conditions.

Temporary
Temporary diplopia can be caused by alcohol intoxication or head injuries,
such as concussion (if temporary double vision does not resolve quickly, one
should see an optometrist or ophthalmologist immediately). It can also be a

side effect of benzodiazepines or opioids, particularly if used in larger doses

for recreation, the anti-epileptic drugs Phenytoin and Zonisamide, and the
anti-convulsant drug Lamotrigine, as well as the hypnotic drug Zolpidem and
the dissociative drugs Ketamine and Dextromethorphan. Temporary diplopia
can also be caused by tired and/or strained eye muscles or voluntarily. If
diplopia appears with other symptoms such as fatigue and acute or chronic
pain, the patient should see an optometrist immediately.
Voluntary
Some people are able to consciously uncouple their eyes, either by over
focusing closely (i.e. going cross eyed) or unfocusing. Also, while looking at
one object behind another object, the foremost object's image is doubled (for
example, placing one's finger in front of one's face while reading text on a
computer monitor). In this sense double vision is neither dangerous nor
harmful, and may even be enjoyable. It makes viewing stereograms possible.
Causes
Diplopia has a diverse range of ophthalmologic, infectious, autoimmune,
neurological, and neoplastic causes.
Abscess
Anisometropia
Botulism
Brain tumor
Cancer
Damaged

third,

movements.
Diabetes

fourth,

or

sixth

cranial

nerves,

which

control

eye

Drunkenness
Fluoroquinolone antibiotics[6]
Graves disease
Guillain-Barr syndrome
Keratoconus
Lyme Disease
Migraine headaches
Multiple sclerosis
Myasthenia gravis
Opioids
Orbital myositis
Trauma
Salicylism
Sinusitis
Strabismus
Wernicke's syndrome
Treatment
The appropriate treatment for binocular diplopia will depend upon the cause
of the condition producing the symptoms. Efforts must first be made to
identify and treat the underlying cause of the problem. Treatment options
include eye exercises, wearing an eye patch on alternative eyes, prism
correction, and in more extreme situations, surgery or botulinum toxin.

If diplopia turns out to be intractable, it can be managed as last resort by

obscuring part of the patient's field of view. This approach is outlined in the
article on diplopia occurring in association with a condition called horror
fusionis.

Male reproductive system

Scrotum
The scrotum is a sac-like organ made of skin and muscles that houses the
testes. It is located inferior to the penis in the pubic region. The scrotum is
made up of 2 side-by-side pouches with a testis located in each pouch. The
smooth muscles that make up the scrotum allow it to regulate the distance
between the testes and the rest of the body. When the testes become too
warm to support spermatogenesis, the scrotum relaxes to move the testes
away from the bodys heat. Conversely, the scrotum contracts to move the
testes closer to the bodys core heat when temperatures drop below the
ideal range for spermatogenesis.

Testes
The 2 testes, also known as testicles, are the male gonads responsible for
the production of sperm and testosterone. The testes are ellipsoid glandular
organs around 1.5 to 2 inches long and an inch in diameter. Each testis is
found inside its own pouch on one side of the scrotum and is connected to
the abdomen by a spermatic cord and cremaster muscle. The cremaster
muscles contract and relax along with the scrotum to regulate the

temperature of the testes. The inside of the testes is divided into small
compartments known as lobules. Each lobule contains a section of
seminiferous tubule lined with epithelial cells. These epithelial cells contain
many stem cells that divide and form sperm cells through the process of
spermatogenesis.
Epididymis
The epididymis is a sperm storage area that wraps around the superior and
posterior edge of the testes. The epididymis is made up of several feet of
long, thin tubules that are tightly coiled into a small mass. Sperm produced
in the testes moves into the epididymis to mature before being passed on
through the male reproductive organs. The length of the epididymis delays
the release of the sperm and allows them time to mature.

Spermatic Cords and Ductus Deferens

Within the scrotum, a pair of spermatic cords connects the testes to the
abdominal cavity. The spermatic cords contain the ductus deferens along
with nerves, veins, arteries, and lymphatic vessels that support the function
of the testes.

The ductus deferens, also known as the vas deferens, is a muscular tube that
carries sperm superiorly from the epididymis into the abdominal cavity to the
ejaculatory duct. The ductus deferens is wider in diameter than the
epididymis and uses its internal space to store mature sperm. The smooth
muscles of the walls of the ductus deferens are used to move sperm towards
the ejaculatory duct through peristalsis.
Seminal Vesicles
The seminal vesicles are a pair of lumpy exocrine glands that store and
produce some of the liquid portion of semen. The seminal vesicles are about
2 inches in length and located posterior to the urinary bladder and anterior
to the rectum. The liquid produced by the seminal vesicles contains proteins
and mucus and has an alkaline pH to help sperm survive in the acidic
environment of the vagina. The liquid also contains fructose to feed sperm
cells so that they survive long enough to fertilize the oocyte.
Ejaculatory Duct
The ductus deferens passes through the prostate and joins with the urethra
at a structure known as the ejaculatory duct. The ejaculatory duct contains
the ducts from the seminal vesicles as well. During ejaculation, the
ejaculatory duct opens and expels sperm and the secretions from the
seminal vesicles into the urethra.
Urethra
Semen passes from the ejaculatory duct to the exterior of the body via the
urethra, an 8 to 10 inch long muscular tube. The urethra passes through the
prostate and ends at the external urethral orifice located at the tip of the
penis. Urine exiting the body from the urinary bladder also passes through
the urethra.

Prostate
The prostate is a walnut-sized exocrine gland that borders the inferior end of
the urinary bladder and surrounds the urethra. The prostate produces a large
portion of the fluid that makes up semen. This fluid is milky white in color
and contains enzymes, proteins, and other chemicals to support and protect
sperm during ejaculation. The prostate also contains smooth muscle tissue
that can constrict to prevent the flow of urine or semen.
Cowpers Glands
The Cowpers glands, also known as the bulbourethral glands, are a pair of
pea-sized exocrine glands located inferior to the prostate and anterior to the
anus. The Cowpers glands secrete a thin alkaline fluid into the urethra that
lubricates the urethra and neutralizes acid from urine remaining in the
urethra after urination. This fluid enters the urethra during sexual arousal
prior to ejaculation to prepare the urethra for the flow of semen.
Penis
The penis is the male external sexual organ located superior to the scrotum
and inferior to the umbilicus. The penis is roughly cylindrical in shape and
contains the urethra and the external opening of the urethra. Large pockets
of erectile tissue in the penis allow it to fill with blood and become erect. The
erection of the penis causes it to increase in size and become turgid. The
function of the penis is to deliver semen into the vagina during sexual
intercourse. In addition to its reproductive function, the penis also allows for
the excretion of urine through the urethra to the exterior of the body.
Semen
Semen is the fluid produced by males for sexual reproduction and is
ejaculated out of the body during sexual intercourse. Semen contains sperm,
the male reproductive gametes, along with a number of chemicals

suspended in a liquid medium. The chemical composition of semen gives it a

thick, sticky consistency and a slightly alkaline pH. These traits help semen
to support reproduction by helping sperm to remain within the vagina after
intercourse and to neutralize the acidic environment of the vagina. In healthy
adult males, semen contains around 100 million sperm cells per milliliter.
These sperm cells fertilize oocytes inside the female fallopian tubes.
Spermatogenesis
Spermatogenesis is the process of producing sperm and takes place in the
testes and epididymis of adult males. Prior to puberty, there is no
spermatogenesis due to the lack of hormonal triggers. At puberty,
spermatogenesis

begins

when

luteinizing

hormone

(LH)

and

follicle

stimulating hormone (FSH) are produced. LH triggers the production of

testosterone by the testes while FSH triggers the maturation of germ cells.
Testosterone stimulates stem cells in the testes known as spermatogonium
to undergo the process of developing into spermatocytes. Each diploid
spermatocyte goes through the process of meiosis I and splits into 2 haploid
secondary spermatocytes. The secondary spermatocytes go through meiosis
II to form 4 haploid spermatid cells. The spermatid cells then go through a
process known as spermiogenesis where they grow a flagellum and develop
the structures of the sperm head. After spermiogenesis, the cell is finally a
sperm cell, or spermatozoa. The spermatozoa are released into the
epididymis where they complete their maturation and become able to move
on their own.
Fertilization
Fertilization is the process by which a sperm combines with an oocyte, or egg
cell, to produce a fertilized zygote. The sperm released during ejaculation
must first swim through the vagina and uterus and into the fallopian tubes
where they may find an oocyte. After encountering the oocyte, sperm next
have to penetrate the outer corona radiata and zona pellucida layers of the

oocyte. Sperm contain enzymes in the acrosome region of the head that
allow them to penetrate these layers. After penetrating the interior of the
oocyte, the nuclei of these haploid cells fuse to form a diploid cell known as a
zygote. The zygote cell begins cell division to form an embryo.