THE PHYSIOLOGIC BASIS

Gentamicin is toxic to the hair cells of the inner ear, and to certain cells in the kidney. As a result, a person on gentamicin can suffer ototoxicity (damage to the inner ear) and acute renal failure (kidney damage). Occasionally, gentamicin causes more damage to one ear than the other, leaving a person with a unilateral loss rather than bilateral total loss. Vestibulopathy (unilateral or bilateral) is permanent, and acute renal failure, or nephrotoxicity, is usually transient.

The normal vestibular system:

Our ability as human beings to balance and to keep upright when moving is dependent on three sources of information. The first is vision, or the ability to perceive from our environment what is up or down, or when we are in motion. The second is proprioception, or the nerve impulses sent to our brain from our joints and the bottom of our feet that inform the brain where the various parts of our body are positioned and how our weight is distributed over our legs and feet. The third is the vestibular system located within our inner ear. The vestibular system senses gravity and the motion of the head in three dimensional spaces.

The vestibular system is composed of three semicircular, fluid filled canals. These canals are arranged roughly on the three axis of head rotation. Inside each of these canals are specialized cells called "hair cells" that can sense even the slightest movement of the fluid within the semicircular canals. The fluid inside the canals which bathe the hair cells is referred to as "endolymph." The "hair" portion of the cells, or stereocilia, extends from the inner wall of the semicircular canal into the liquid endolymph. These hair cells are connected to nerve cells that transmit this information to the brain. It is in this manner that the brain can perceive even the slightest motion of the head, whether it be up or down like a nod saying "yes", sideways like a headshake saying "no," or sidewise, like tilting the head from side to side.

In addition to the hair cells that detect fluid movement in the semicircular canals, specialized hair cells have crystals of calcium carbonate affixed to the ends of the stereocilia, and are known as otolith cells. These cells detect linear acceleration and gravity. Dr. Timothy Hain, a neurologist at Northwestern University in Chicago has an excellent section on his website devoted to otoliths.

Figure 1 - Anatomy of the inner ear

Figure 2 - Anatomy of the vestibular system

Figure 3 – Schematic representation of hair cells and nerve fibers in fluid filled semicircular canal

Figure 4 - Rotation of a semicircular canal in a counterclockwise manner results in the hairs of the hair cells being bent to the "left" and a corresponding nerve impulse transmitted to the brain. A more complete description of the anatomy of the vestibular system is found in a section of the online Encyclopedia Britannica – Vestibular system

Gentamicin can injure and kill vital hair cells:

Blood capillaries surround the semicircular canals. As gentamicin is introduced into the bloodstream, some of the gentamicin diffuses out of these capillaries and enters the endolymph. The higher the concentration of gentamicin in the blood, and the longer the gentamicin is present, the more gentamicin will diffuse into the endolymph. Since the volume of the endolymph is relatively constant, and since the endolymph is not rapidly replaced, the concentration of gentamicin in the endolymph increases with higher serum gentamicin concentrations and length of gentamicin administration.

Although persons seem to have a varying degree of tolerance for gentamicin, a point may be eventually reached where the gentamicin laced endolymph is too toxic for the hair cells, and they die. Once human hair cells die, there is no demonstrated recovery. With every hair cell killed, there is one less hair cell capable of transmitting balance information to the brain. In cases of severe gentamicin poisoning, virtually all of the hair cells are killed, resulting in no vestibular balance information being transmitted to the brain.