Biology 202
1998 First Web Reports
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A Brief look at the Physiological Basis and Neurological Effect of Brain Tumors

Zach Hettinger

I've always been interested in medicine, and more specifically, in surgery, but I never really knew which realm of surgery appealed to me the most. So I set out on a quest to find where my future in medicine may lay. I spent time with an orthopedic surgeon and loved the carpentry-like style of the trade, and I spent a week with a general surgeon and watched him fix hernias and cut out moles. But the surgery that struck me the hardest, and the one that I vowed to stay the furthest from, was neurosurgery. The idea of carefully manipulating someone's nervous system in order to give them back the most basic of physical abilities, that of control over one's body, was almost too much to handle. Of all the systems of the body, the nervous system seems to be the most delicate of all. Yet only now, in this class, do I realize the incredible balancing that goes on between so many different components to make the nervous system functional. Furthermore, any alteration to that balance can cause a host of serious problems that could render the nervous system as a whole, or even part of it, completely useless.

Tumors are an excellent example of how the balance can be upset, and are one of the most well known of the afflictions to the brain. There are several different kinds of tumors that effect the brain, each is based on what kind or kinds of cells it developed from in the brain. The four main kinds of cells that are effected are astrocytes, oligodendrocytes, ependymal cells, and microglial. Tumors in each of these cell types are referred to as astrocytomas, oligodendrogliomas, microgliomas or primary nervous system lymphoma, and ependymomas. Although tumors can arise from these nervous system cells and others, approximately 65% of brain tumors are astrocytomas.

The actual cause of any given tumor is difficult if not impossible to determine, but tumors are generally caused by one of or a combination of three things: radiation, chemicals, and viral agents. Tumors can also be caused during mistakes in DNA replication, but this accounts for a smaller incidence of brain tumors. These genetic alterations can often be harmless, resulting in the effected cell dying and being disposed of by the organism. But on occasion, the effected gene is one that is responsible for having a cell lie dormant , oncogenes, or one that is in place to regulate growth, tumor suppresser genes. If either of these types of genes are affected then the cell will undergo unchecked growth and drastically effect the surrounding brain tissue and eventually the entire human being.

Now that the origin of the tumor has been established, the key is to understand how the balance of the nervous system is effected. It is important to remember that much of the nervous system is based on equilibrium and membrane permeability and that for action potentials and other processes to work the proper concentrations must stay constant. When looking at the beginnings of an astroctoma the initial observation is that the new tumor cell relinquishes it's responsibilities of nourishing and disposing of the waste of neurons. This has a very local and passive effect on the site. The neuron may then depend more heavily on other astrocytes and there may be a build up of waste materiel. But more importantly, the astrocytoma begins to grow, use up resources, and produce waste of its own. It is now actively effecting the system. The initial problems that stem from tumors are this build up of waste products. The high concentration of waste in the extracellular fluid results in a osmotic flow of water from inside the cells to outside of the cells, resulting in a swelling of the area, also known as "edema". This is easily seen on CT scanning(computed tomography) and MRI(magnetic resonance imaging) and is one of the first signs of a tumor.

The osmotic changes in concentration lead to a much greater complication than headaches from swelling, they lead to seizures. The precious balance between potassium and sodium that is necessary for action potentials to exist is dependent on the free flow of those ions across the ion specific membrane proteins. When the intercellular water joins the extracellular fluid it grossly effects the ion concentrations inside and outside the neuron. These new and imbalanced levels create erratic and unpredictable signals that manifest themselves as seizures.

As the tumor continues to grow it feeds its destruction of the brain tissue. The larger it gets the more nutrients it needs and the more waste it excretes. To continue its course of action the tumor encourages the growth of new blood supplies which end up taking much needed nutrients from the surrounding brain tissue. This combined with the increased level of waste result in the death of surrounding nerve cells and in turn the increased growth of tumor cells. An additional complication lies in the new blood vessels formed. Although the new blood vessels are formed in order to nourish the dying neurons, astrocytes, oligodendrocytes, and nervous system cells, they are not the same kind of blood vessels that are found in other parts of the brain. Normally, the brain blood vessels work with the astrocytes to allow only certain substances to enter the brain, creating a Blood Brain Barrier. But the new vessels work without the astrocytes and allow all kinds of proteins, white blood cells, and other things that would normally not be present in the brain to flow into the extracellular fluid. This creates an even larger strain on the osmotic pressures and increases the contamination level of the extracellular fluid. Eventually the pressure from swelling and the size of the tumor produce neurological effects and eventually place the subject in a coma and then lead to death.

On first consideration of the effects of brain tumors I find it surprising that the tumors do not have more of a direct effect on the brain. That is to say they do not spread through the brain like a virus or some chemical contaminant. They have the humble beginnings in the mutation of one cell and then effect the rest of the brain through changes in concentrations and mechanical pressure. All that the initial problems, and many of the later problems, are based on is a change in the concentration gradient, proof that without which, neurons can not function properly.

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