This document discusses the relationship between stress and disease. It describes how stress triggers the hypothalamic-pituitary-adrenal axis and cortisol release. Elevated cortisol levels over long periods can suppress the immune system and increase risks for diseases like obesity, hypertension, and diabetes. Stress also increases catecholamine and cytokine production, which have pro-inflammatory effects and can further impact immune function and health. The aging process may exacerbate these stress responses through changes in the limbic system, hormones, inflammation, and other physiological factors.

1. Stress and Disease Page 1 of 2
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STRESS AND DISEASE
NURS 242 PATHOPHYSIOLOGY 11/13/2018
STRESS
PERCEIVED OR ANTICIPATED THREAT THAT DISRUPTS A
PERSON’S WELL-BEING OR HOMEOSTASIS
MAY STEM FROM PSYCHOLOGIC/EMOTIONAL (FEAR, SOCIAL
REJECTION), PHYSICAL (DRAMATIC TEMPERATURE CHANGES,
ABUSE), OR PHYSIOLOGIC (INFECTION,INFLAMMATION)STIMULI
THAT TRIGGER THE STRESS RESPONSE
ALLOSTASIS
 “Stability through change”
 Brain continuously monitors for future events and anticipates what is required from
neuroendocrine and autonomic systems
 Allostatic overload
o Overactivation of adaptive systems
o Highly individualized
HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS
 Hypothalamus secretes corticotropin-releasing hormone (CRH)
 Pituitary releases adrenocorticotropic hormone (ACTH)
 Adrenals secrete cortisol and catecholamines
o Cortisol is the link to the immune response
o Too much cortisol over time inhibits the immune system
CORTISOL
 Secreted during stress
 Goes to all tissues
 Reaches all tissues
 Stimulates gluconeogenesis
 Increased Glucose Levels
 Affects protein metabolism
 Powerful anti-inflammatory and immunosuppressive agent
 Abnormal elevations linked to
 obesity,
 sleep deprivation,
 lipid abnormalities,
 hypertension (HTN),
 diabetes,
 atherosclerosis
 loss of bone density
 Secretionduringstress inhibits initial inflammatory effects
 Promotes resolution and repair
 Shown to induce T-cell apoptosis

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CORTISOL EFFECTS
 Used therapeuticallyas powerful anti-inflammatory/immunosuppressive agents
 Influence virtuallyall immune cells
 Elevated levels may decrease innate immunity and increase autoimmune responses
CATECHOLAMINES
 Released from the adrenal medulla
o Epinephrine released
 α-adrenergic receptors
o α1 and α2
 β-adrenergic receptors
o β1 and β2
 Mimic direct sympathetic stimulation
o What happens when Epi / NorEpi are released?
 Bronchodilitation
 Increased HR / BP / Contractility
 Increases proinflammatory cytokine production
HISTAMINE AND OTHER HORMONES
 Peripheral (immune) CRH
o Proinflammatory
o Mast cells are targeted
 Histamine release
 Induces acute inflammation and allergic reaction while suppressing Th1 and
promoting Th2 activity
 Neuropeptide Y (NPY)
o Sympathetic neurotransmitter
o Growth factor
ROLE OF THE IMMUNE SYSTEM
 Stress directly related to proinflammatory cytokines
 Link between stress, immune function, and disease/cancer
 Immune system affected by neuroendocrine factors
 Stress response decreases T-cell cytotoxicityand B-cell function
AGING AND STRESS
 Stress-age syndrome
o Excitability changes in the limbic system and hypothalamus
o Increased catecholamines, ADH, ACTH, and cortisol
o Decreased testosterone, thyroxine, and other hormones
o Alterations of opioid peptides
o Immunosuppression and pattern of chronic inflammation
o Alterations in lipoproteins
o Hypercoagulation of the blood
o Free radical damage of cells