Figure 775

Rapid reaction of the adrenal cortex of a rat to stress caused by fracture of the tibia and fibula at time zero. (In the rat, corticos-terone is secreted in place of cortisol.) (Courtesy Drs. Guillemin, Dear, and Lipscomb.)

dramatically by the experiment shown in Figure 77-5, in which corticosteroid formation and secretion increased sixfold in a rat within 4 to 20 minutes after fracture of two leg bones.

Some of the different types of stress that increase cortisol release are the following:

1. Trauma of almost any type

2. Infection

3. Intense heat or cold

4. Injection of norepinephrine and other sympathomimetic drugs

5. Surgery

6. Injection of necrotizing substances beneath the skin

7. Restraining an animal so that it cannot move

8. Almost any debilitating disease

Even though we know that cortisol secretion often increases greatly in stressful situations, we are not sure why this is of significant benefit to the animal. One possibility is that the glucocorticoids cause rapid mobilization of amino acids and fats from their cellular stores, making them immediately available both for energy and for synthesis of other compounds, including glucose, needed by the different tissues of the body. Indeed, it has been shown in a few instances that damaged tissues that are momentarily depleted of proteins can use the newly available amino acids to form new proteins that are essential to the lives of the cells. Also, the amino acids are perhaps used to synthesize other essential intracellular substances such as purines, pyrimidines, and creatine phosphate, which are necessary for maintenance of cellular life and reproduction of new cells.

But all this is mainly supposition. It is supported only by the fact that cortisol usually does not mobilize the basic functional proteins of the cells, such as the muscle contractile proteins and the proteins of neurons, until almost all other proteins have been released. This preferential effect of cortisol in mobilizing labile proteins could make amino acids available to needy cells to synthesize substances essential to life.

Anti-inflammatory Effects of High Levels of Cortisol

When tissues are damaged by trauma, by infection with bacteria, or in other ways, they almost always become "inflamed." In some conditions, such as in rheumatoid arthritis, the inflammation is more damaging than the trauma or disease itself. The administration of large amounts of cortisol can usually block this inflammation or even reverse many of its effects once it has begun. Before attempting to explain the way in which cortisol functions to block inflammation, let us review the basic steps in the inflammation process, discussed in more detail in Chapter 33.

There are five main stages of inflammation: (1) release from the damaged tissue cells of chemical substances that activate the inflammation process-chemicals such as histamine, bradykinin, proteolytic enzymes, prostaglandins, and leukotrienes; (2) an increase in blood flow in the inflamed area caused by some of the released products from the tissues, an effect called erythema; (3) leakage of large quantities of almost pure plasma out of the capillaries into the damaged areas because of increased capillary permeability, followed by clotting of the tissue fluid, thus causing a nonpitting type of edema; (4) infiltration of the area by leukocytes; and (5) after days or weeks, ingrowth of fibrous tissue that often helps in the healing process.

When large amounts of cortisol are secreted or injected into a person, the cortisol has two basic antiinflammatory effects: (1) it can block the early stages of the inflammation process before inflammation even begins, or (2) if inflammation has already begun, it causes rapid resolution of the inflammation and increased rapidity of healing. These effects are explained further as follows.

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