216
U N I T 2
Integrative Body Functions
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
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
