There are a variety of sites within the auditory apparatus that may be affected by multi-systemic diseases. The external and middle ear serve primarily to amplify the sound stimulus. Particularly critical to this function are the tympanic membrane and middle ear bones (ossicles). The inner ear functions to convert the acoustic energy transmitted to the cochlea into an electrical signal that is transmitted to the central nervous system (CNS) via the eighth cranial nerve afferent fibers. This task falls specifically to the sensory receptors within the cochlea known as the inner hair cells. The adjacent outer hair cells participate in this process by maintaining the precise tuning of the cochlea (i.e., the ability of the cochlea to transmit the precise pitch characteristics of the stimulus that ultimately correspond to stimulus clarity). The bipolar cell bodies of the cochlear nerve fibers reside in the spiral ganglion. Axons from these cells form the cochlear nerve and terminate in the ipsilateral cochlear nucleus, from which projections are sent bilaterally to ultimately terminate in the auditory cortex.

Hair-cell function is dependent on the cochlea maintaining precise electrolyte concentrations within its fluid-containing compartments. These fluid compartments, known as the cochlear ducts (scalae), contain either a solution analogous to intracellular (endolymph) or an extracellular (perilymph) fluid. The endolymphatic compartment (scala media), with its high potassium concentrations, is tightly isolated from the sodium-rich perilymphatic compartments (scala vestibuli and scala tympani). The maintenance of these gradients creates an electrochemical gradient of 80 to 100 mV that drives hair-cell depolarization—the key process in auditory stimulus transmission to afferent nerve fibers. These electrolyte concentrations in the scala media are maintained by Na+-K+-ATPase enzyme on the surface of cells in the stria vascularis, a highly vascular and metabolic tissue. Gap junctions are intercellular channels formed by proteins called connexins and are thought to be important in electrolyte metabolism in the stria vascularis and other inner ear supporting cells. Mutations in a gene (GJB2) coding for connexin 26 are an important cause of genetic hearing loss. Blood supply to the cochlea is exclusively from the labyrinthine artery, which is usually a branch of the anterior inferior cerebellar artery.

Sensorineural hearing loss results when one or more components of the inner ear or cochlear nerve are damaged. For example, hearing loss associated with aging (presbycusis) is associated with hair-cell, stria vascularis, and neural pathologies. Noise and most ototoxins primarily affect hair cells, although other cochlear structures may also be involved. The following discussion pertains to systemic diseases that may result in auditory pathology.

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