Ear

Intro to the Ear

The Human Ear: The human ear is comprised of 3 main parts: outer, middle, and inner. The outer ear consists of the pinna, which is the visible part of the ear, and the auditory ear canal to the tympanic membrane(ear drum). The membrane separates the outer ear from the middle ear which is an air-filled space that is connected to the nasopharynx via the eustachian tube. The middle ear consists of the malleus, incus, and stapes. These three tiny bones carry sound from the ear drum to the inner ear. The inner ear (aka the bony labyrinth) is comprised of the membraneous labyrinth which encloses both cochlea and the vestibular apparatus.(5)

Physical Conditions of the Normal Healthy Ear

The conditions of the pinna are similar to that of the skin. Closer to the ear canal the skin develops a thin lining of ear wax. Ear wax is composed mostly of dead skin cells and keratin with a small mixture of cerumen, sweat, and oil. Cerumen is secreted from the ceruminous glands located in the first third outer part of the ear canal and is thought to be composed mainly of cholesterol, squalene, wax esters, ceramides, and triglycerides. The cerumen also has antibacterial/fungal properties which can be attributed to its slight acidic pH of 5 and the presence of lysozyme. In normal circumstances, the ear wax is continuously pushed out of the ear canal by the slow migration of the top layer of skin cells from the tympanic membrane towards the outer ear. The ear wax traps any foreign particles/organisms on its way out. Ear wax type also varies between people. Generally Native American and Southeast Asian's present a dry flaky type of ear wax where as Europeans and Africans produce the "wet type." The dry type falls out easier and is in thinner concentration while the wet type is thicker and stickier, though it should readily fall out as well under normal circumstances. The ear canal is a dark, moist, close to body temperature(~37C), and abundant with nutrients from dead skin cells. Current research on cerumen shows that some of the antimicrobial properties of the cerumen can be attributed to the presence of antimicrobial peptides Human Beta-defensin 1 and Human Beta-defensin 2. Other recent studies have shown that cerumen directly inhibits the growth of Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans, but its effect on the growth of E. coli remains to be determined (2)(3)(13). If not for the cerumen, the ear canal would be a very hospitable place for microbes.

The middle ear, or tympanic cavity, is an air filled space that is connected to the outer ear via the tympanic membrane and the inner ear via the fenestra vestibuli. A mucous membrane lines the middle ear that is continuous with the nasal passageways and nasopharynx via the eustachian tube. This continuity allows the person to equalize the air pressure inside the cavity with that of the outside environment. Mucus has long been known to contain many antimicrobial enzymes and immunoglobulins. In addition to its anti microbial properties, the mucus also serves to trap any foreign particles and microbes that are introduced into the middle ear and ciliary action of the tissue promptly flushes them out to the nasopharynx. This migration of mucus is important to prevent microbes from colonizing as the tympanic cavity would otherwise present a very favorable environment for microbes. It is abundant in nutrients, moist, dark, protected from the external environment, and at body temperature. (4)(14)

The inner ear consists of two labyrinth structures. The bony labyrinth and the membraneous labyrinth. The bony labyrinth is filled with a fluid called perilymph and encloses the membraneous labyrinth. The membraneous labyrinth comprises the vestibular apparatus and the cochlea. It is filled with a seperate fluid that does not mix with the perilymph called endolymph. The both fluids are segregated from but derived from blood plasma implying a high concentration of nutrients and a similar pH (~7.4). In addition to nutrients, small concentrations of immunoglobulins present in blood serum are also found in the perylimph and endolymph, filtered through by the blood-labyrinthe barrier (12). A characteristic of perilymph is that its concentration of sodium is high (about 150 milliequivalents per litre) and its concentration of potassium is low (about 5 milliequivalents per litre), similar to other extracellular fluids. Conversely endolymph has a low concentration of sodium (about 15 milliequivalents per litre) and a high concentration of potassium (about 140 milliequivalents per litre).(5) Since the inner ear is completely membrane enclosed, it should be virtually imperveous to bacterial colonization under normal circumstances.

Microbes in the Healthy Ear

Because it is exposed to the outside environment, despite the best efforts of the ceruminous glands, the normal healthy outer ear still houses a variety of microbes. Some of the most common bacteria are Staphylococcus epidermis, Turicellaotitidis, Alloiococousotitis, Pseudomonas aeruginosa, Corynebacterium, Staphylococcus aureus, and Streptococcus saprophyticum. The most common fungal microbe known to reside in the ear is Candida albicans. (7)(8)

Microbes that are known to inhabit the middle ear are Streptococci, Haemophilus pneumoniae, Moraxella catarrhalis, and less commonly mycobacterium. These bacteria are known to get to the middle ear by mgirating through the nasophraynx and eustachian tube. Recent research shows that the presence of alpha hemolytic streptococci from healthy children (as opposed to children with recurrent acute otitis media) inhibit the growth of pathogenic pneumococci and H. influenzae. As a result of this research, there is now an interest in developing a nasal spray that deposits alpha hemolytic streptococci into the nasopharynx as a means to help prevent rAOM. (9)

The healthy inner ear should be virtually microbe free.

Normal Changes to the Environment of the Ear

Do any of the physical conditions change? How do those changes affect the microbes?

In regards to the ear, the environment of the outer ear is subject to the most variation as it is exposed to the outside environment. One of the biggest effects on the environment of the ear would be those that remove the ear wax. This can occur through excessive showering or swimming as water/soap can wash away the thin protective lining of ear wax. Loss of the cerumen encourages the growth of microbes that are normally kept under control by its antimicrobial properties. Use of cotton swaps or hair pins is also common practice as a means to remove ear wax. In addition to the removal of the ear wax, they can also scratch the surface of the skin which can allow microbes to get in to the unprotected tissue. Use of cotton swabs also can push the ear wax further into the canal, which if allowed to build up can become impacted and damage the inner ear canal and the tympanic membrane. These too provide opportunities for microbes to infect the underlying tissue.

The infectous opportunity of the ear also grows smaller as the person grows older. Young children with immature immune systems are more susceptible to infection by microbes than are adults with developed immune systems.

Blockage of the Eustachian tube can also increase the likelihood of ear infections. This occurs when the mucus in the tube gets too thick or becomes blocked as can occur during infections or allergic reactions of the upper respiratory tract. The opening of the Eustachian tube is also affected by head positioning. A head elevation of 20 degrees above horizontal (as can occur while lying down with a pillow) reduces the flow of air to two thirds of normal while a complete horizontal position reduces it to one third. Blockage of the tube prevents a healthy flow of mucus out of the middle ear and as a result, microbes present inside the middle ear become trapped and are allowed to proliferate.

Infections of the Ear

When do microbes infect the ear, what conditions? Why do those conditions allow the microbes do infect the ear? How do other infections cause a change in the conditions of the ear? How do those change in conditions allow other microbes to infect the ear?

Outer Ear: Even though the human ears are largely exposed to all kinds of material in the environment including water resources, they get rarely infected. [One] can nearly always shower, bathe, swim, and walk in the rain without a problem [because] the ear shape [protects it by] tipping fluid out, and by its lining, which has acidic properties that protect against bacteria and fungi (2). Acute external otitis, also known as Swimmer's Ear, is an infection that takes place in the outer auditory canal. In swimmer’s ear, the infection arises from high concentrations of water causing humidity in the ear. The excess of moisture weakens the ear’s external skin and reduces the concentration of the protective acids. At other times, external otitis can surface when swimming in polluted water, scratching the ear or inside the ear, [or if some kind] of object gets stuck in the ear (1). In all possible cases, bacteria are able to grow and infect the ear canal since they love to live in areas with acidic pH, hot and humid conditions, and skin cuts. Even though the outer ear is not as prone to infection as other parts of the human body it will become infected if for example, swimming pools become unsanitized after the people enter them without prior showering. Therefore, they leave the pool with dirt and their body oils. These oils become nutrients for organisms like Pseudomonas aeruginosa because it has simple nutritional crave. “Pseudomonas aeruginosa is an opportunistic pathogen, meaning that it exploits some break in the host defenses to initiate an infection” (11).

Pseudomonas aeruginosa Scanning electron micrograph. CDC

Pseudomonas aeruginosa is the main bacterium that causes Swimmer’s Ear. It moves fast on the water found in the outer ear by polar flagella. It is commonly found in soil and water environments and is a part of the Gamma Proteobacteria group of bacteria. Pseudomonas aeruginosa use their quorum sensing to sense the density of population nearby which is why they usually form biofilms on inanimate surfaces. This free gram negative rod bacterium likes to live in an aerobic environment; therefore, the outer ear is the perfect habitat for this type of organism. Because this organism is a gram negative and forms biofilms, its outer membrane and the exopolysaccharide coat respectidely protect it from antibacterial compounds. It has also developed resistance mechanisms against many antibiotics and antiseptics. As a result, These bacteria can survive in many environments, including high and low temperature, and “high concentrations of salt and dyes”(11) The only antibiotics that were found to have some effect on Pseudomonas aeruginosa are gentamicin, imipenem, and fluoroquinolones(11). Besides that, the bacterium is so resistant again antibiotics that any available treatments fail on certain patients. Other less common bacterial communities in swimmer’s ear are Staphylococcus aureus, Proteus mirabilis, Streptococci species, and various gram negative Bacilli. Fungi infections caused by Aspergillus niger or Candida albicans are even rarer in the outer ear. The article “Staphylococcus aureus Serves as an Iron Source for Pseudomonas aeruginosa during In Vivo Coculture,” states that pseudomonas aeruginosa uses the lysed staphylococcus aureus to get its required amount of iron(10). However, it is still not known if it is the Pseudonomas aeruginosa that induces the lysing or if Staphylococcus aureus auto lyses.

Middle Ear: The middle ear is the small part of eardrum. It can get infected when microbes from the nose and throat are trapped there. A cold could cause Eustachian tube that connects pharynx to the middle ear swell. When the tube swells enough to become blocked, it can trap fluid inside the ear. This makes it a perfect place for germs to grow and cause an infection. The medical term for middle ear infections is otitis media. Otitis refers to inflammation of the ear, and media means middle. Ear infections usually start with a viral infection, such as a cold. The middle ear becomes inflamed from the infection, and fluid builds up behind the eardrum. Ear infections also can be associated with dysfunction or swelling within the Eustachian tubes - the narrow passageways that connect the middle ear to the nose. Normally these tubes equalize pressure inside and outside the ear. But a child's Eustachian tubes are narrower and shorter than those of an adult. This makes it easier for fluid to get trapped in the middle ear when the Eustachian tubes dysfunction or become blocked during a cold.

Another factor in ear infections is swelling of the adenoids. These are tissues located in the upper throat near the Eustachian tubes. Adenoids contain lymphocytes - cells that normally fight infection. But sometimes the adenoids themselves get infected or enlarged, blocking the Eustachian tubes. Infection in the adenoids can also spread to the Eustachian tubes.

The most common bacteria that grows in the middle ear and causes Otitis media is Haemophilus Influenzae. It is Gram negative bacteria where it has a thin cell walls. “It is generally aerobic but can grow as a facultative anaerobe” (4). According to a current research there is some environment in the middle ear that helps the bacteria grow and survive like histidine “Our results suggest that the ability to make histidine is an important factor in bacterial growth and survival in the middle ear, where nutrients such as histidine may be found in limiamounts”(5). This infection or the microbe mostly effect children under 6 years old. Children at young age can not fight the microbe or a bacterium that enters their body like adults do. For many reasons, children at a young age their bodies start growing and by time they get stronger. Children’s immune system develops and gets stronger when they grow completely. That is one reason why at a young age their body can not fight any microbe they detect as they do when they’re older. Otitis media happens when a child gets a virus that infects the Eustachian tube, “this tube connects between the nose and the middle ear” (2). Children start feeling pain and fluid start draining from ears. “The lack of ventilation may allow fluid from the tissue that lines the middle ear to accumulate. If the eustachian tube remains plugged, the fluid cannot drain and begins to collect in the normally air-filled middle ear” (3).

The second common bacteria that causes the Otitis media infection is Moraxella catarrhalis(aka also known as Branhamella catarrhalis.) It is a bacterium belonging to the Neisseriaceae family. It is considered to cause of middle ear infections and sinusitis in children, and lower respiratory infections in adults. It has also been attributed to pneumonia, bronchitis, meningitis, neonatal ophthalmia, and urinary tract infections. This bacterium is an aerobic, gram negative diplococcus. It is kidney bean shaped and is 0.6 - 1.0 um in diameter and often appears in pairs or tetrads.

How do Moraxella catarrhalis migrate into the middle ear and attach to the human mucosal surface? In general, following by an inflammatory process, the pathogens colonized in the upper respiratory tract such as nose, oral cavity or throat initiates the development of an otitis. These pathogens accumulation trigger the bacteria to migrate into the middle ear via the Eustachian tube (4). Once the bacteria attach to human mucosal surface, they start an infection. On the same hand, Moraxella catarrhalis causes otitis media disease in the middle ear by firstly forming the colonization of bacteria. To be able to initiate the infection, Type IV pili (TFP), filamentous surface appendages, plays a crucial role in initial attachment on human mucosal surface and natural transformation. The biosynthesis of M. catarrhalis TFP is consisted of a single protein named pilin which is encoded by some special genes. In addition, TFP expressed by M. catarrhalis also assists the cells in enhancing the biofilm formation in continous-flow chambers. As a result, TFP is necessary and essential in contributing M. catarrhalis pathogenesis in their early steps of middle ear infection (3).

What is Moraxella catarrhalis? How can they survive in the iron-limited condition in human body, especially in the middle ear? Moraxella catarrhalis is a gram-negative and oxidase-positive diplococcus which lives in an aerobic environment and is found only in humans. Moraxella catarrhalis is a mucosal pathogen which commonly causes of otitis media located in young children’s middle ear and infects lower respiratory tract in adults(2). According to the group study of Campagnari, Shanks and Dyer, they demonstrate that Moraxella catarrhalis’ colonies may often form rough and friable surface with opaque and pinkish-brown color. Its strains can tolerate at lower temperature and can grow well at 28ºC(5). An iron plays an important element in helping most microbes to survive in their living environment. However, most of iron in human body is coupled to carrier proteins such as transferrin (serum) and lactoferrin (mucosal surface). Therefore, in order for this bacterium to grow under the limited-iron conditions or iron starvation, Moraxella catarrhalis can compete for iron by utilizing human carrier proteins without secreting any siderophore production. This mechanism is similar to H. influenzae and Neisseria species which allow these mucosal pathogens to maintain their growth by utilizing directly from their host environment such as the middle ear in this case. In addition, during the infection and the lack of iron nutrient, M.catarrhalis expresses these iron-repressible proteins in its outer membrane which is not induced by other environment stresses to acquire more irons. With this advantageous feature of being able to utilize these serum carrier proteins, iron-limited M.catarrhalis can colonize and survive on human mucosal surfaces, especially in the middle ear where it is mucous and moisture (1).

Inner Ear: There are multiple routes to bacterial infection of the inner ear. They can occur through; the cochlear aqueduct, which connects the subarachnoid space to the scala tympani of the cochlea; the modiolus of the temporal bones; or by hematogenous invasion of bacteria through the stria vascularis of the scala media. Sensorineural hearing loss (SNHL) is an important inner ear condition resulting from acute bacterial meningitis. Streptococcus pneumoniae meningitis and Haemophilus influenzae type B cases play a significant role in the cause of this condition. Hearing lose can also result from lesions of the cochlea, auditory nerve, brainstem, and various auditory pathways.

The micro organisms Pseudomonas aeruginosa: and Staphylococcus are both involved in the cause of sporadic cartilage infections following ear piercing or other trauma. Pseudomonas aeruginosa is a gram-negative, free-living bacterium with an aerobic rod belonging to the bacterial family Pseudomonadaceae. It’s commonly found in water and soil and is known to infect human tissues. Pseudomonas aeruginosa is an opportunistic pathogen. This bacterium almost never infects normal tissues. But if tissue defenses are compromised in some manner, there is hardly any tissue that it cannot infect. Risk for infections increase when newly pierced ears are exposed to Pseudomonas organisms present in lakes or any stagnant water. One way against the activity of these serious infectious organisms is to expose them to the newly discovered fluoroquinoline antibiotic, ciprofloxacin. Ciprofloxacin offers the most antipseudomonal activity against Pseudomonas aeruginosa in vitro. This class of antimicrobial agent also has good activity against staphylococcal species, but resistance can be developed in patients with repeated or prolonged use.

Major research has been focused on the study of auditory sensory cells known as outer hair cells. Located on the cochlea of the inner ear, the outer hair cells play a critical role in hearing and work as a protective layer for inner hair cells. The human cochlea possesses only about 12,000 OHCs, damaging a few of these hair cells results in substantial hearing and balance deficits which affect millions of people.

Viruses have been known to cause most inner ear attacks, but are usually able to resolve on their own. Vestibular neuritis, the technical term for dizziness, is an inner ear disease caused by a virus. The cause for many inner ear conditions are still unknown. However, experiments have shown the certain viruses maybe responsible for infections of specific structures of the inner ear. Herpes simplex virus has been shown to have a link to sudden sensorineural hearing loss. In experiments done these viruses have infected primarily the sensory cells of the labyrinth. Mumps virus have infected principally endolymphatic structures. Influenza virus have shown to infect mesenchymal cells of the perilymphatic channels of the cochlea. These experiments show the possible causality of infections in the inner ear but studies are still being done.

Current Research

To prevent the child ear infection, the study on mice in the lab test by Miranda Hitti indicates that the new and unnamed nasal spray is used effectively to treat mice’s ear infection. The nasal spray contains protein called lysine which is used to attack the common bacterium Streptococcus pneumonia which is grown commonly in children’s ear. As a result, 80% of the mice had developed ear infection without nasal spray. Therefore, even though the new product of nasal spray hasn’t been tested on human, scientists are still working on their way to soon find the best solution for ear infection.

Enter summaries of the most recent research. You may find it more appropriate to include this as a subsection under several of your other sections rather than separately here at the end. You should include at least FOUR topics of research and summarize each in terms of the question being asked, the results so far, and the topics for future study. (more will be expected from larger groups than from smaller groups)

Resources

1)Badshah, Cyrus. "Medical Encyclopedia." Medline plus. 22 June 2007. Http://www.nlm.nih.gov/medlineplus/ency/article/000622.htm. 24 Aug. 2008.

2)By Mayo Clinic Staff. "Swimmer's ear." Mayo clinic.com. 16 Oct. 2006. Http://www.mayoclinic.com/health/swimmers-ear/DS00473. 24 Aug. 2008.

3)^Bortz JT, Wertz PW, Downing DT. "Composition of cerumen lipids." J Am Acad Dermatol. 1990 Nov;23(5 Pt 1):845-9.

4)^James E. Crouch. "Functional Human Anatomy" Lea and Febiger 1978

5)^Encyclopedia Britannica. "Anatomy of the Human Ear" http://www.britannica.com/EBchecked/topic/175622/ear/65043/Endolymph-and-perilymph#tab=active~checked%2Citems~checked&title=human%20ear%20%3A%3A%20Endolymph%20and%20perilymph%20--%20Britannica%20Online%20Encyclopedia

7)^Stroman DW, Roland PS, Dohar J, Burt W. "Microbiology of normal external auditory canal." Laryngoscope. 2001 Nov;111(11 Pt 1):2054-9

8)^Campos A, Arias A, Betancor L, Rodríguez C, Hernández AM, López Aguado D, Sierra A. "Study of common aerobic flora of human cerumen." J Laryngol Otol. 1998 Jul;112(7):613-6

9)^Tano K, Grahn-Håkansson E, Holm SE, Hellström S. "Inhibition of OM pathogens by alpha-hemolytic streptococci from healthy children, children with SOM and children with rAOM." Int J Pediatr Otorhinolaryngol. 2000 Dec 22;56(3):185-90.

http://www.meddean.luc.edu/depts/otolaryn/patient_ed/pdf/ENT%20INNER%20EAR%20FLUID%20IMBALANCE.pdf

http://jama.ama-assn.org/cgi/content/abstract/291/8/981 ( Outbreak of Pseudomonas aeruginosa Infections Caused by Piercing of Upper Ear Cartilage)

a. Ronna Staley, MD, James J. Fitzgibbon, MD, Catherine Anderson, and LSM, MSN. "Auricular Infections Caused by High Ear Piercing in Adolescents." PEDIATRICS. Vol. 99 No. 4 April 1997, pp. 610-611

10)Mashburn, Lauren M., Amy M. Jett, Darrin R. Akins, and Marvin Whiteley."Staphylococcus aureus Serves as an Iron Source for Pseudomonas aeruginosa during In Vivo Coculture." Journal of bacteriology 187 (1994): 554-66.

11)Todar, Kenneth. "Pseudomonas aeruginosa." Todar's Online Textbook of Bacteriology. 2008. University of Wisconsin-Madison Department of Bacteriology. 24 Aug.2008 <http://http://www.textbookofbacteriology.net/pseudomonas.html>.

12)Joel M. Bernstein, Pearay L. Ogra. "Immunology of the Ear" Raven Press New York 1987

13)Yoon YJ, Park JW, Lee EJ. "Presence of hBD-1 and hBD-2 in human cerumen and external auditory canal skin". Acta Otolaryngol. 2008 Mar 10:1-5.

14)Schunknecht, Harold F. "Pathology of the Ear" Lea and Febiger 1993

1)Campagnari, A A, K L Shanks, and D W Dyer. "Growth of Moraxella catarrhalis with human transferrin and lactoferrin: expression of iron-repressible proteins without siderophore production." Infection and Immunity 62 (1994): 4909-914.

2)Constantinescu, Michael. "Excerpt from Moraxella Catarrhalis Infections." Emedicine. 2 July 2008. 26 Aug. 2008 <http://www.emedicine.com/med/topic1500.htm>.

3)Luke, Nicole R., Joseph A. Jurcisek, and Lauren O. Bakaletz. "Contribution of Moraxella catarrhalis Type IV Pili to Nasopharyngeal Colonization and Biofilm Formation." Infection and Immunity 17 (2007): 5559-564.

4)"Moraxella Catarrhalis Antigen, Corresponding Gene and Uses Thereof." WIPO. 23 Aug. 2008 <http://www.wipo.int/pctdb/en/wo.jsp?ia=wo2001019996&display=desc>.

5)"Moraxella catarrhalis." CDC. Centers for Disease Control and Prevention. 27 Aug. 2008 <http://www.cdc.gov/std/gonorrhea/lab/mcat.htm>.