Porth's Essentials of Pathophysiology, 4e

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Integrative Body Functions

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to increased rates of infection rather than frequency of symptoms after infection. 59 The inflammatory phase of wound repair appears to be disrupted in the presence of chronic stress. 60 Skin blis- ters were induced on the forearms of 36 post-menopausal women. Women with greater stress produced sig- nificantly lower levels of IL-1 α and IL-8, indicating a poorer response to the stressor. Lower cell-mediated immune response to influenza vaccination was observed in elderly participants experiencing chronic stress when compared with counterparts that were not experiencing chronic stress. 61 Chronic stress also has been linked to specific signaling pathways that impact cancer growth and metastasis. 62 Posttraumatic Stress Disorder Posttraumatic stress disorder (PTSD) is an example of chronic activation of the stress response to a traumatic event. 63–66 It was formerly called battle fatigue or shell shock because it was first characterized in men and women returning from combat. Although war is still a significant cause of PTSD, other major catastrophic events, such as weather-related disasters (hurricanes and floods), airplane crashes, terrorist bombings, rape or child abuse, or intimate partner violence also may result in development of the disorder. People who are exposed to such events are also at risk for development of major depression, panic disorder, generalized anxiety disorder, and substance abuse. 66 Frequently, bodily symptoms and physical illnesses such as hypertension, coronary heart disease, asthma, and chronic pain syndromes have been associated with PTSD. Definition. The term posttraumatic stress disorder was originally defined in the third edition (1980) of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-III) as a gross stress reaction that was considered a tempo- rary condition; however it could be changed to a neu- rotic condition if it persisted. 67 In the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) (1994), the diagnosis of acute stress disorder (ASD) was added to distinguish indi- viduals with milder or more transient difficulties from those with PTSD. 68 In the fifth edition (DSM-5-TR) (2013), the traumatic event has been defined as expo- sure to actual or threatened death, serious injury, or sexual experience by directly experiencing, witnessing, learning that it happened to a close family member or friend, or being repeatedly exposed to the averse details of the event (e.g., first responders collecting human remains). 69 According to the DSM-5, the essential features of PTSD include exposure to actual or perceived threat. 69,70 The exposure may not be as narrowly defined as previously thought, and it may include events such as rape, torture, combat, brutal assault, a difficult diagnosis, or sudden death of a loved one. A change in the DSM-5’s criteria for diagnosis of PTSD

production of glucose from non-carbohydrate sources such as amino acids, and an accompanying state of insulin resistance that impairs glucose uptake into skeletal muscle. Clinical data suggest that hypergly- cemia results in worse outcomes and recovery from acute coronary syndromes 51,53 (see Chapter 19), septic shock 52,54 (see Chapter 20), hemorrhagic shock, 49,55 and stroke 56 (see Chapter 36). These findings have led to a goal for strict control of blood glucose in most criti- cally ill patients. This control is often accomplished through the use of low-dose insulin infusions. Insulin itself has been shown to produce anti-inflammatory, antioxidant, antithrombotic, and profibrinolytic effects, separate from those involved in reducing blood glucose levels. 51,53 The optimal level for regulation of blood glucose in the critical care setting, and the expe- diency of initiating insulin therapy, remain current areas of investigation. Effects of Chronic Stress The stress response is designed to be an acute self-lim- ited response in which activation of the ANS and the HPA axis is controlled in a negative feedback manner. As with all negative feedback systems, pathophysi- ologic changes can occur in the stress response system. Function can be altered in several ways, including when a component of the system fails, when the neural and hormonal connections among components of the system are dysfunctional, and when the original stimulus for activation of the system is prolonged or of such mag- nitude that it overwhelms the ability of the system to respond appropriately. In these cases, the system may become overactive or underactive. Chronicity and excessive activation of the stress response can result from chronic illnesses, and it can contribute to development of long-term health problems. It has been linked to a number of health disorders, including diseases of the cardiovascular, gastrointestinal, immune, and neurologic systems, as well as depression, chronic alcoholism and drug abuse, eating disorders, accidents, and suicide. Chronic acti- vation of the stress response is also an important pub- lic health issue from both a health and an economic perspective. The National Institute for Occupational Safety and Health has declared stress as a hazard in the workplace. 57 Occurrence of acute necrotizing gingivitis, an oral disease in which normal bacterial flora of the mouth become invasive, is known by dentists to be associ- ated with acute stress, such as final examinations. 58 Similarly, herpes simplex virus type 1 infection (i.e., cold sores) often develops during periods of inade- quate rest, fever, ultraviolet radiation, and emotional upset. The resident herpes virus is kept in check by body defenses, probably T lymphocytes, until a stress- ful event occurs that causes suppression of the immune system. Psychological stress is associated in a dose– response manner with an increased risk for develop- ment of the common cold, and this risk is attributable