Blood Brain Barrier

The movement of substances between the blood and the extracellular fluid surrounding the cells in most tissues of the body occurs very readily. This exchange takes place at the level of the capillaries, the smallest blood vessels in the cardiovascular system whose walls are formed by a single layer of endothelial cells. Lipid-soluble substances are able to move across this layer of endothelial cells at any point because they can move directly through the plasma membrane by passing between the phospholipid molecules of the bilayer. The movement of water-soluble substances is limited to the multiple pores found between the cells; however, it also takes place rapidly and efficiently.

This nonselective exchange of materials, which includes all substances except plasma proteins, does not occur in all vascular beds, however. Many substances found in the blood are potentially harmful to the CNS. Therefore, the brain and spinal cord are protected from these substances by the blood-brain barrier. In the capillaries of the brain and spinal cord, there are no pores between the endothelial cells; instead, tight junctions fuse the cells together. As a result, exchange between blood and the extracellular fluid of the brain is altered. Lipid-soluble substances, such as oxygen; carbon dioxide; steroid hormones; most anesthetics; and alcohol, continue to move directly through the plasma membrane and therefore remain very permeable. Because the blood-brain barrier anatomically prevents movement of materials between the cells, it is impermeable to water-soluble substances such as glucose, amino acids, and ions. These substances are exchanged between the blood and extracellular fluid of the brain by way of highly selective membrane-bound protein carriers.

There are several benefits to the presence of this barrier. It protects the neurons of the CNS from fluctuations in plasma components. For example, a change in the potassium ion concentration could alter neuronal function due to its effect on membrane potential. Second, the barrier minimizes the possibility that harmful blood-borne substances reach the CNS. Finally, it prevents any blood-borne substances that could function as neurotransmit-ters from reaching the brain and causing inappropriate neuronal stimulation.

The blood-brain barrier exists in capillaries in all areas of the brain and spinal cord except the hypothalamus and some regions of the brainstem. The absence of the barrier in a given region coincides with the function of that area. For example, the hypothalamus contributes to homeostasis by monitoring concentration of various blood-borne substances such as glucose and hormones. Glucose and amino acid-derived hormones are hydrophilic and would be unable to come into contact with hypothalamic neurons if the barrier were present. Another instance includes the vomit center of the medulla whose neurons detect the presence of potentially toxic substances in the blood. This center prevents the further absorption of these substances from the gastrointestinal tract by inducing vomiting. Once again, neurons in this region need to be exposed to any hydrophilic toxins in order to carry out this function.

Pharmacy application: antihistamines and the blood-brain barrier

Antihistamine drugs have long been used to treat symptoms of allergy such as sneezing, itching, watery discharge from the eyes and nose, and possibly wheezing. The older or first-generation histamine Hj receptor antagonists such as Benadryl® and Tavist® effectively relieve these peripheral symptoms. However, these medications, of the drug class ethanolamines, are very lipo-philic and readily cross the blood-brain barrier to interact with histamine Hj receptors in the CNS as well. As a result, they also cause central effects such as diminished alertness, slowed reaction times, and sedation. The newer or second-generation histamine Hj receptor antagonists such as Claritin® and Hismanal® have been chemically designed to be less lipophilic and not cross the blood-brain barrier at therapeutic doses. Therefore, these medications which are of the drug class piperidines, eliminate the peripheral symptoms of allergy without this depression of CNS activity.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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