1. Stress
1) Define stress making sure to include both physiologic and psychologic factors
that can play a role (T762, M312)
a) According to Hans Selye: a state or condition of the body produced by “diverse
nocuous agents” and manifested by a syndrome of changes – general adaptation
syndrome (GAS) which produces the stress triad:
i) Enlarged adrenal cortex
ii) Atrophy of thymus gland and other lymphatic organs
iii) Bleeding ulcers in stomach and duodenal lining
b) A person experiences stress, physical or psychological, when a demand exceeds a
person’s coping abilities.
c) Stressors: any agent or stimulus that produces stress
i) Response depends on perception – varies among individuals
ii) Any extreme stimuli: too much or too little of anything
(1) Physical: i.e. extreme temperature – hot or cold
(2) Psychological: i.e. extreme lack of social contact stimuli
iii) Often injurious, unpleasant or painful but not always
(1) Seyle’s quote: a painful blow and a passionate kiss can be equally stressful
iv) Anything a person perceives as a threat – real or imagined
(1) Arouses fear or anxiety
(2) Includes emotion of grief
v) Reactions and stress response varies between individuals and in one individual
at different times
vi) Prenatal stress
(1) Occurs in developing fetus
(2) i.e. fetal alcohol syndrome
2) Describe the structure and function of the autonomic nervous system (M432-441,
T475-485)
a) Structure
i) Considered part of efferent division of the Peripheral Nervous System (PNS)
ii) Carries efferent signals to the autonomic or visceral effectors: cardiac muscle,
smooth muscle, glandular epithelia and adipose and other tissues
iii) Consists of 2 efferent divisions
(1) Sympathetic Nervous System
(a) Preganglionic neurons start in thoracic and lumbar segments of spinal
cord-
(b) Sometimes referred to as thoracolumbar division
(c)

2. (2) Parasympathetic Nervous System
(a) Preganglionic neurons are in the brainstem or sacral cord
(b) Referred to as craniosacral division
b) Function
i) Major functions include: heartbeat regulation, smooth muscle contraction,
glandular secretion, metabolism control to maintain homeostasis.
(1) Sympathetic nervous system functions:
(a) Mobilize energy stores in times of need – fight-or-flight
(b) Increased heart and respiratory rate and strength of cardiac muscle
contraction
(c) Vasodilation of vessels to the heart , skeletal muscles, respiratory
airways
(d) Vasoconstriction of vessels to digestive and other organs, and of spleen
and other blood reservoirs
(e) Increased conversion of glycogen to glucose and breakdown of stored
fats
(f) Increased sweating
(2) Parasympathetic Nervous System functions
(a) Slow heart and respiratory rate
(b) Promote digestion and elimination
(c) Considered the system for “rest and repair.”
3) Describe the three stages of the general adaptation syndrome (GAS) response
and relate to the timing of the development of disease. (M312, T763-764)
a) Alarm stage:
i) Increased activity of sympathetic nervous system
ii) Increased secretion of cortisol by adrenal cortex, and of norepinephrine by
adrenal medulla
iii) Marked reduction of lymphocytes and eosinophils = decreased immune
response and allergic response
iv) Increased mobilization of fats and tissue proteins = hyperglycemia
b) Resistance or adaptation stage
i) Adrenal cortex and medulla return to normal rates of hormone secretion
ii) Sympathetic activity returns to normal
iii) Successful adaptation to stressor
c) Exhaustion stage
i) Occurs when stress is extremely severe or occurs over a long time
ii) First increased cortisol secretion then markedly decreased
iii) Onset stress triad – hypertrophied adrenal cortex, atrophied lymphatic organs,
bleeding ulcers

3. iv) Body can no longer cope with stressor – may lead to death
d) Relationship to development of disease
i) Seyle believed the Stage of Exhaustion marked the onset of disease
ii) He referred to these as “diseases of adaptation”
4) Describe the current contribution of research to our understanding of Seyle’s
GAS response (T766, figure 22-6) (M314, 315, figure 10-2 )
a) Stress is being defined more specifically as any stimulus that directly or indirectly
stimulates neurons of the hypothalamus to release corticotropin-releasing
hormone (CRH) and to send stimulating impulses to sympathetic centers and
posterior pituitary. This activity triggers many responses that together are referred
to as “stress syndrome” or “stress response.”
b) Some effects are immediate(sympathetic activity – fight or flight) and some are
longer term (hormonal effects.)
c) See figure 22-6 on page T767 and compare to figure 22-5 on page T766.
5) Define homeostasis (T19)
a) The relative constancy of the normal body’s internal (fluid) environment
i) Homeo = same or equal
ii) Stasis = standing still
b) The maintenance of relatively constant internal conditions despite changes in
either the internal or the external environment characterize homeostasis
c) The ability of the body to maintain homeostasis serves as a basis for
understanding mechanisms of disease.
d) See figure 1-12 that depicts the the body’s internal environment and systems
involved in maintenance of homeostasis.
6) Describe the role of catecholamines in the neuroendocrine response to stress.
(M314 -316)
a) The catecholamines involved are epinephrine and norepinephrine.
i) Epinephrine is released from the adrenal medulla after stimulation by the
sympathetic nervous system. (80%)
ii) Norepinephrine is released from the locus ceruleus in the brainstem as well as
the adrenal medulla (20%)
b) Catecholamines mimic direct sympathetic stimulation
i) Norepinephrine during stress:
(1) Increases blood pressure via vasoconstrition
(2) Dilates the pupils
(3) Causes pilerection
(4) Increases sweat gland action in armpits and palms

4. ii) Epinephrine during stress:
(1) Greater influence on cardiac action and metabolic regulation
(2) Enhances myocardial contractility,increases heart rate, and increases
venous return to the heart = increases cardiac output and blood pressure.
(3) Dilates skeletal muscle blood vessels = increases oxygenation
(4) Metabolically: causes transient hyperglycemia by:
(a) Promoting gluconeogenesis and glycogenolysis in the liver
(b) Inhibiting glycogen breakdown
(c) Decreasing glucose uptake in the muscles and organs
(d) Decreasing insulin release from pancreas
(5) Mobilizes free fatty acids and cholesterol by:
(a) Stimulating lipolysis and freeing triglycerides and fatty acids from fat
stores
(b) Inhibiting the degradation of circulation cholesterol to bile acids
iii) Catecholamines are immunosuppressive
(1) Increase numbers of NK cells but decreased responsiveness of T and B
lymphocytes
(2) Effect lasts only 2 hours after injection of epinephrine so to be
immunosuppressive levels must be chronically elevated.
7) Describe the role of cortisol in the neuroendocrine response to stress. (M316-317)
a) Stress stimulates hypothalamus  releases CRH  anterior pituitary releases
ACTH ACTH stimulates adrenal cortex to release cortisol.
b) Cortisol effects are widespread and permissive with catecholamines resulting in:
i) Increased blood glucose
ii) Increased blood pressure and cardiac output
iii) Increased blood levels of amino acids via protein catabolism in muscle
iv) Decreased circulating lymphocytes, eosinophils, moncytes/macrophages 
decreased immune and allergic responses
v) Decreased protein synthesis  atrophy of lymphoid tissue and
immunosuppression
c) See table 10-4 page 317 for more detailed outline.
8. Describe the role of endorphins, growth hormone, prolactin, and testosterone
in the stress response.
a. Endorphins are proteins found in the brain that have pain-relieving
capabilities like opiates and they are released into blood as part of the
response to stressful stimuli such as traumatic injury and acute, intense

5. stress situation (i.e. parachute jumping). In inflamed tissue, endorphin
receptors on peripheral sensory nerves get activated to relive pain and in
hemorrhage, b (beta) endorphin levels from the pituitary gland increase to
inhibit blood pressure increase. (325 McCance)
b. Growth hormone (Somatotropin) is synthesized from anterior pituitary
gland and from lymphocytes and mononuclear phagocytic cells. GH
affects protein, lipid, and carbohydrate metabolism and counters effects of
insulin. It is involved in tissue repair and may participate in the growth
and function of the immune system. GH levels increase in the blood in
response to stressful physical and psychological stimuli (i.e. cardiac
catherization, electroshock therapy, gastroscopy, surgery, fever, physical
exercise, taking exam, viewing violent or sexually arousing films, etc).
Prolonged activation of stress response (chronic stress) leads to
suppression of GH. (325 McCance)
c. Prolactin is released from anterior pituitary gland and other extrapituitary
tissue sites including lymphoid cells. Prolactin is necessary for lactation
and breast development and its receptors are present in liver, kidney,
intestine, and adrenals. Prolactin levels in plasma increases as a result of
stressful stimuli (i.e. surgery, pelvic exam, motion sickness, after taking
exam, and after receiving sexual stimulation). Unlike GH, prolactin
shows little change after exercise but similar to GH, prolactin increases
with intense stimuli. Prolactin acts as a second messenger for
interleukin-2 (IL-2) and have a positive influence on B cell activation and
differentiation for immune function. (325 McCance)
d. Testosterone is secreted by Leydig cells and it regulates male secondary
sex characteristics and libido. Its level decreases after physiological and
psychological stressful stimuli (i.e. ether/anestheria, surgery, marathon
running, mountain climbing, respiratory failure, burn, CHF, rigorous
combat training, etc) by cortisol and b (beta) endorphin. Individuals with
acute illnesses, such as respiratory failure, burns, and CHF, show a marked
reduction in testosterone. Estrogen depresses T cell-depended immune
function and enhances B cell function but androgen suppresses both T and
B cells responses leading to greater susceptibility to sepsis and mortality
in males than in females.

6. 9. Diagram the major interactions of the nervous, endocrine, and immune
system in the stress response including all of the major chemical mediators.
See pages 314-315 McCance
Stressor-> limbic system -> SNS (brainstem (locus ceruleus)) -> Adrenal medulla
-> norepienphrine (w/albumin)
norepinephrine: increase sweat gland action, goosebumps, immune effect
(increased blood pressure), increased contraction of arteriole smooth
muscle, pupil dilation
Stressor-> limbic system -> SNS (PVN -> LC) -> norepienphrine
epinephrine: bronchodilation, increase force and rate of cardiac
contraction (increase CO), increase lipolysis (increase circulating free
fatty acids) -> increase circulating free fatty acids, pancreas decrease
insulin-> decreased glucose uptake, increased glycagon-> increased
glucogenesis, liver decreases glycogen synthesis, and increase
glycogenolysis
Stressor -> Hypothalamus-> Anterior Pituitary -> b-endorphins, ACTH,
Prolactin, GH
b (beta) endorphins: decreased pain sensation
prolactin: lactation and breast development
GH: increased protein synthesis, lypolysis, increased gluconeogenesis,
decreased glucose uptake in muscle and adipose, decreased insulin
sensitivity, increased IGH-1
ACTH-> adrenal cortex-> Cortisol-> increase blood glucose (liver),
increase BP and CO, increase catabolism in muscle-> increased amino
acids, increased circulating PMNs, antiimflammatory effects, promotes
lypolysis in extremities, decreased lutenizing hormone (estradiol,
testosterone), promotes lipogenesis in face and trunk, decreased protein
synthesis-> atrophy of lymphoid tissue (immunosuppression, decreased
eosinophils, lymphocytes, and macrophages)
Stressor -> Hypothalamus-> Posterior Pituitary -> Vasopressin, ADH, oxytocin
Vasopressin/ADH: increases water absorption in the kidney
Oxytocin: increase milk let-down and uterine contraction

7. 10. Discuss 3 specific links between the immune system and the neuroendocrine
response to stress.
1) direct effect of CNS neuropeptides on immune cells:
Neuropeptides and neuroendocrine hormones may directly control
biochemical events affecting cell proliferation, differentiation, and fx or may
indirectly control immune cell behavior by affecting the production of
cytokines. (323)
2) stress-induced endocrine products influence immune cell and neurologic
cell fx:
Hypothalamic-pituitary-adrenal (HPA) axis may produce indirect effect on the
CNS that modulate immune response. Increased level of circulating
glucocorticoids (GCSs) may be an important mechanism in stress-related
immune structure alterations and in suppression of immune system. The GCS
level increases are attributable to pituitary ACTH production- a result of
increased hypothalamic CRH then it increases the cortisol secretion. Cortisol
fees bac to inhibit further cytokine release by macrophages and monocytes.
(322)
3) immune cell products (cytokines) affect nervous and endocrine cells fx
through direct and indirect pathways:
Lymphocytes also are known to produce ACTH and endorphins in small
amounts, which probably influence immune response in an autocrine or
paracrine manner in the microenvironment of an ongoing immune response.
The T cell growth factor (IL-2) can up-regulate pituitary ACTH. Immune-
derived cytokines have significan influence on neuroendocrine fx, with
evidence for direct and indirect cytokine effects on nervous and adrenal cell
fxs. (323)
Pathophysiology

8. 1. Identify the physiologic rationale for the following clinical manifestation of
stress: tachycardia, elevated blood pressure, dilated pupils, elevated blood
sugar, pallor.
(314-316 McCance)
a. Tachycardia: stressor activates limbic system, which stimulates SNS
to releases norepinephrine to increase contraction of arteriole smooth
muscle and epinephrine increases force and rate of cardiac contraction.
b. Elevated BP: stressor activates limbic system, SNS stimulated to
release norepinephrine that increases BP by constricting smooth
muscle in all blood vessels. Cortisol stimulates rennin release from
kidneys. Increased renin increases BP by increasing extracellular
volume (increase in blood plasma, lymph, interstitial fluid). Posterior
pituitary releases ADH and adrenal cortex releases aldosterone that
increase water retention that can also contribute to increased BP.
c. Dilated pupils: eye dilation is controlled by parasympatheric and
sympathetic nerve system. Like the mechanism of tachycardia,
norepinephrine from stimulated SNS dilates pupils.
d. Elevated blood sugar: both epinephrine and cortisol can elevate
blood sugar. Epinephrine decreases glycogen sythesis, increase
gluconeogenesis, and increases glycogenolysis in the liver to increase
blood glucose in the system. CRH from hypothalamus stimulates
anterior pituitary to make ACTH, then it stimulates adrenal cortex to
increase the prduction of cortisol. Like epinephrine, cortisol
stimulates liver to increase gluconeogenesis to increase blood glucose
in the blood.
e. Pallor: paleness in skin or mucous membrane is presented by
sympathetic activity. It goes hand-in-hand with clammy and moist
skin and it is affected by the vasoconstricting effect of norepinephrine.
Vasocontriction decreases amount of erythrocytes in the cutanous
system. (http://www.wrongdiagnosis.com/symptom/pallor.htm)
2. Distinguish between effective and ineffective coping for stress

9. a. Effective coping: adaptive coping strategies, especially those that are
problem-focused and those that encourage seeking social support, are
beneficial during stressful experiences.
b. Ineffective coping: cannot manage stress demand and can lead to
change in behavior resulting in potentially adverse health effects (i.e.
increased smoking, change in eating habits), disturbance in sleep-wake
cycle (sleep deprivation and circadian disruption affect respiratory and
immune system function). It may exacerbate the effects of distress on
health, thus augmenting potential for illness.
3. Describe the relationship between stress and disease by analyzing the impact
of stress on the following diseases:
a. Coronary Artery Disease: Stress increases SNS activity, which
releases epinephrine to mobilize free fatty acids and cholesterol by
stimulating lipolysis, freeing triglycerides and fatty acids from fat
stores, and inhibiting the degradation of circulating cholesterol to bile
acids. This causes the increase in circulating free fatty acids,
trigylcerides, and cholesterol and they attach on the walls of coronary
arteries then the plaque accumulates over time.
b. HTN: Stress increases sympathetic activity, which increases
norepinephrine to constrict the vessels in blood reservoirs and dilate
vessels in skeletal muscle, it increase rate and stroke volume of heart
contraction for increased cardiac output, then increases systolic BP.
(see Elevated BP for additional info) The chronic stress can cause
cardiovascular disease, mainly arthrosclerosis due to plaque formation
in the arterial blood vessels (see CAD above for mechanism)
c. Peptic ulcer disease: Stress increases sympathetic activity that
decreases secretion by digestive glands, decreases peristalsis, and
decreased mucosal blood flow. Addionally, cortisol contributes in
gastric ulceration. Stress affects hypothalamus and the anterior
pituitary produces ACTH and it activates the adrenal cortex to secrete
cortisol into the plasma. Among many functions of costisol, it

10. promotes enough gastric secretion to cause unlceration of the gastric
mucous.
4. If given a case study be prepared to identify the clinical manifestation of
stress, discuss the scientific rationale for these findings, and identify
abnormal labs that may be stress related.
Hx:
• Heart palpitation/tachycardia- due to norepinephrine increasing contraction of
arteriole smooth muscle and epinephrine increasing force and rate of cardiac
contraction.
• Dyspnea- epinephrine induces brochodilation
• Indigestion (GERD)- too much gastric secretion
• Constipation- decreases peristalsis by SNS
• Insomnia- pineal gland blocks the production of melatonin
• Diaphoresis- norepinephrine increases sweat gland action
• Alertness- increased glucose arouses CNS
• Unhealing wound/sores and infections - cortisol’s action on
immunosuppresion
• Dark yellow urine- Vasopressin/ADH/aldosterone prevents fluid loss
• Decrease in libido- cortisol and b-endorphins decrease testosterone
• Fatigue- patient reached stage of exhaustion by breaking down the
compensatory mechanisms and homeostasis
Examination:
• Dilated pupil- the SNS produces norepinephrine to dilate pupils
• Elevated blood pressure- see 1b
• Elevated glucose- see 1d
• Elevated GH- by stimulation of anterior pituitary

11. • Elevated CRH- by stimulation of hypothalamus
• Elevated ACTH- by stimulation of anterior pituitary
• Elevated albumin- catacholamines circulate bound to albumin
• Elevated free fatty acids- epinephrine increases lypolysis to circulate free fatty
acids
• Elevated blood level of amino acids (total serum protein (?))- cortisol
increases protein catabolism for amino acid accessibility
• Increased parasites in stool sample- cortisol’s effect on immunosuppression
increases parasite growth in stool
• Decreased WBC (decreased lymphocytes, monocytes, eosinophils)