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) which is more precisely referred to as bilateral vestibulopathy, and acute renal failure (kidney damage). The bilateral vestibulopathy is usually permanent, and acute renal failure, or nephrotoxicity, is usually transient. Occasionally, gentamicin causes more damage to one ear than the other, leaving a person with a unilateral rather than bilateral total loss.

 

The Normal Vestibular System.

 

Our ability as human beings to balance and to keep upright when moving is dependent on 3 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 3 dimensional space.

 

The vestibular system is composed of 3 semicircular, fluid filled canals. These canals are arranged roughly on the 3 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, extend 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 cocking 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 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 Calls 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 an Emedicine article by Lee et al

 

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.

 

 

 Figure 5 - Serum Levels Increase with Renal Failure

 

Nephrotoxicity can occur very quickly in patients receiving gentamicin. While the nephrotoxicity or kidney damage is usually reversible, the damage to the vestibular system from high gentamicin serum levels that can occur is not reversible. It is for this reason that careful renal function and gentamicin trough or 6-12 hour post infusion (random) gentamicin levels be obtained during therapy.

 

A more detailed discussion of gentamicin induced nephrotoxicity is found on the nephrotoxicity page. Further discussion can also be found in a paper by Mingeot-Leclercq and Tulkins.

 

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