Stress & Disease - CH. 21 Flashcards
Stress is a relationship between…
An individual’s physiologic and psychologic processes and environment
Stress results from situations that…
Require a degree of adaptation
Hans Selye
Came up with the idea of General Adaptation Syndrome
General Adaptation Syndrome (overview)
Internal or external stressors can result in:
-Adrenal gland enlargement
-Immune alterations (reduced lymphocytes from damaged lymphatic structures)
-GI manifestations (bleeding ulcers)
What is needed to respond to stress?
A state of balance
Increased cortisol production
Suppresses the immune response
Stress response is meant to protect against
Acute threats and is normally time limited.
Acute stress
Considered to enhance immunity
Chronic stress
Suppresses immunity
Allostasis
Process by which the body responds to stressors in order to regain homeostasis - stability through change
Allostatic overload
When there is a chronic overactivation of adaptive responses that may in turn increase susceptibility to disease.
General (GAS)
Effect is a general systemic reaction
Adaptation (GAS)
Response was in reaction to a stressor
Syndrome (GAS)
Physical manifestations are coordinated and dependent on each other.
Example of stress and allostatic overload
Sleep alteration and associated damaging effects of elevated evening cortisol, insulin, and glucose.
Three stages of GAS
- Alarm stage (fight or flight)
- Stage of resistance/adaptation
- Allostatic overload or exhaustion
Alarm stage - physiologic activation
SNS -> HPA Axis -> release of catecholamines & cortisol
Alarm Stage - Suppression of certain hormones like GH, thyroid hormone, and reproductive
Necessary to conserve energy that is needed to fend off the stressor
Alarm Stage - ADH secretion
ADH is increased to retain fluid, thereby maintaining the BP needed to perfuse vital tissues.
Alarm Stage - Immune response
Humoral response boosted initially to thwart infection and disease, but with rising cortisol levels the immune response becomes inhibited.
Stage of resistance/adaptation - GAS
Individual attempts to compensate for changes induced by the alarm stage in response to sustained challenge
Persistent stress is followed by
The resistance stage where cortisol decreases through negative feedback
Why is excess cortisol helpful in early stages of stress
Increase metabolism by breaking down proteins, releasing lipids, and increasing circulating glucose
Hypercortisolism - Stage 2 GAS
Leads to exhaustion of inflammatory and immune responses, excessive loss of body proteins and breakdown of tissues, and glucose intolerance
Hormone levels suppressed during the resistance stage
Loss of circulating thyroid, growth, and reproductive hormones
GAS Stage 2 - Persistent increase in ADH
Manifested by excessive fluid retention and subsequent hypertension
Allostatic Overload or Stage of Exhaustion - GAS Stage 3
Can follow if an individual cannot successfully adapt to physiological changes that occur during resistance stage
Stage 3 GAS - Continuous Stress
Causes progressive breakdown of compensatory mechanisms and homeostasis
What specific term occurs during stage 3 of GAS?
Allostatic overload
Stage 3 GAS - Characterization
Characterized by energy depletion and degeneration of cells, tissues, organs, and organ systems
Stage 3 GAS - severe prolonged exposure to stress causes
Contributes to poor health and marks a significant loss to homeostasis
What does the individual lose during stage 3 of GAS?
Loses the capacity to sustain a defense against stress
What can stage 3 of GAS cause (long-term effects)
Organ damage and onset of certain diseases
Stage 3 GAS - Psychological Stressors
Can be anticipatory or reactive
Can cause or worsen several diseases/disorders
Reactive Response
Increased HR and cotton mouth in reaction to taking an exam
Anticipatory Response
Hypothalamus stimulates response from limbic system. Fear/memory generates stress in anticipation of experiencing events.
Brainstem makeup
Locus ceruleus and RAS
What does the brainstem make?
Norepinephrine
What does the brainstem do?
Coordinates performance of the ANS, cortex, limbic system, and HT
Three mechanisms for the physiologic response to stress
HPA axis, SNS, and immune system
What are the HPA and SNS inhibited by
Opioids and GABA
What does the HPA and SNS activate?
Activate the sympathetic response to stress
Four major hormones/groups of hormones involved in the endocrine response to stress
CRH, ACTH, cortisol, and catecholamines
HPA Axis
Hypothalamus releases CRF -> CRF causes anterior pit to release ACTH -> ACTH stimulates release of cortisol from adrenal cortex -> cortisol increases metabolism by breaking down proteins, releasing lipids, and increasing circulating glucose for use in making ATP
Cortisol and CRF
Cortisol acts as a negative feedback loop to restrict release of CRF
Key aspect to HPA axis
Negative feedback loops inhibit further secretion of cortisol, but can be altered by stress
What responses does the hypothalamus trigger
Neural and hormonal responses
ANS
Sympathetic stimulation of the adrenal medulla to secrete catecholamines
Catecholamines
Epinephrine, norepi, and neuropeptide Y
Effect of SNS stimulating release of catecholamines
HR, BP, respiration rate, pupil dilation, and sweating.
Blood flow increases to muscle, heart, lungs.
Gastric function decreased - less oxygen and blood alteration can cause stress ulcers
What do neurons regulate?
Release of norepinephrine to control alertness, arousal, and vigilance
Catecholamines
Prepare the body to act, mimic direct sympathetic stimulation
Person will look pale or ashen and digestion is decreased due to blood being shunted away to important spots
Growth hormone
Released by anterior pit
Affects protein, lipid, and carbohydrate metabolism and counters the effects of insulin
Chronic stress decreases growth hormone secretion in children
Posterior pit releases
Oxytocin and ADH
Oxytocin
Promotes reduced anxiety
ADH
Increased to retain fluid, thereby maintaining the BP needed to perfuse vital tissues
Can cause excessive fluid retention and subsequent hypertension
What does adrenal gland secrete
Cortisol and catecholamines
Cortisol (glucocorticoid)
Reach all tissues, easily penetrate cell membranes, and react with intracellular glucocorticoid receptors
Catecholamines mimic
Direct sympathetic stimulation
Affect of chronic stress on on the parasympathetic/sympathetic systems
During allostatic overload the parasympathetic system is less effective in opposing the sympathetic system
Cortisol’s chief effects involve
Metabolic processes
What is the purpose of cortisol promoting the formation of glucose, AA’s, lipids, and fatty acids
Delivers them to the bloodstream so cells can use them to make ATP.
What does cortisol help with within the CNS?
Regulate memory, cognition, mood, and sleep
Negative aspects of cortisol
Metabolic syndrome, pathogenesis of obesity, can directly cause insulin resistance
Beneficial aspects of cortisol secretion during stress
Inhibiting initial inflammatory effects
-vasodilation, increased capillary permeability, promote resolution and repair by affecting transcription in leukocytes
What can elevated levels of catecholamines and glucocorticoids do?
Decrease innate immunity and increase autoimmune responses
How does cortisol and catecholamines help protect the body from disease
Bind to receptors on immune cells to increase synthesis and release of cytokines, including interleukin-18, interleukin-6, and tumor necrosis factor-a
Adrenal medulla is involved with
Catecholamines, epinephrine, and norepinephrine
Epinephrine
Chief effects on cardiovascular system
Increases CO and blood flow to heart, brain and skeletal muscles
Dilating vessels that supply those organs
Dilates airways to increase oxygen to the bloodstream
Binds with and activates both a and B receptors
Norepinephrine
Constrict blood vessels of viscera and skin, increases mental alertness, directs blood flow to vessels dilated by epi, binds primarily with receptors
Limbic system
Regulates emotional activities, stimulates RAS
Anticipatory response begins in limbic system
Thalamus
Intensifies sensory input related to stressor like vision, hearing, smell
RAS
Increases alertness and muscle tension and contributes to stimulation of the ANS
Prefrontal cortex
Regulates cognitive activities such as intense focus, planning attention, and persistence
B-endorphins
Proteins in brain w/pain-relieving capabilities
Released in response to stressor
Inflamed tissue activates endorphin receptors
Hemorrhage increases levels, which inhibits BP increases and delays compensatory changes
Elevated b-endorphins
Activate endorphin (opiate) receptors on peripheral sensory nerves leading to pain relief or analgesia.
Prolactin
Released from anterior pit
Necessary for lactation/breast development
Levels in plasma increase as a result of stressful stimuli
Oxytocin
Produced by hypothalamus during childbirth and lactation
Produced during orgasm for both sexes
Can promote reduced anxiety
Testosterone
Secreted by leydig cells in testes
Regulates male secondary sex characteristics and libido
Testosterone levels decrease because of stressful stimuli
Exhibits immunosuppressive activity
Estrogen
Calming effect during stressful situations
Release during stressful situations causes depression of T cells and enhancement of B cells
Melatonin
Decreases during stress response
Negative affective states
Depression, anxiety
Reciprocal relationship b/t stress and depression
Individual tries to cope and fails, feelings of helplessness and worthless may occur
Acute stress disorder
Symptoms occur within a month of the event and not expected to last longer than 4 weeks
Three criteria for traumatic event
- Persistent re-experiencing of traumatic event
- Persistent attempts to avoid stimuli associated w/event
- Persistent symptoms of increased arousal
Memory process
- Registration of information from environment
- Information organized by comparison to perceptual maps then forwarded for meaning/interpretation
- Consolidation sets the permanence of the memory trace
Hippocampus and thalamus with explicit memory
Bring together elements of memory trace from neo-cortical areas during retrieval
Unable to distinguish between cues that pose a genuine threat and those that are similar but nonthreatening. Allows for unconscious misinterpretation
Re-experiencing original trauma
Triggers acute response w/activation of SNS -> increased norepi affects coding and retrieval of memory
HPA axis w/ PTSD
Intrusive thoughts increase cortisol levels
Cortisol levels produce reversible alterations of declarative memory
Increased release of dopamine from prefrontal cortex contributes to PTSD
Stress & Respiratory disease
Increased respiratory and heart rates which increases oxygen consumption
Stress & neurologic disease
Alterations in immune function could be related to alterations in cytokine levels
Immune cells can infiltrate brain and secrete inflammatory mediators
Alters brain structure and function
Multiple sclerosis
Have abnormal cytokine profile
Contribute to myelin destruction and death of oligodendrocytes
Decreased anti-inflammatory cytokines
GI disease
Associated with IBD, peptic ulcer disease, and GERD
Slows gastric emptying and increases motility of colon
SNS response might contribute to hypersecretion of gastric acid
Can contribute to localized ischemia and further damage.
Cardiovascular disease
Psych stress can contribute to acute myocardial infarction
Excess hostility and anxiety contribute to coronary artery disease
Chronic inflammation contributes to atherosclerosis
Stress and negative emotions are directly associated with
Production of pro-inflammatory cytokines
Stress response directly influences immune system through HT and PiT peptides, epi and norepi
Immunosenescence
Aging of the immune system
Stress and Natural Killer cells
NKs are first defense against viruses
Reduced killer T cell cytotoxicity associated with higher perceptions of stress
Major mediatory associated with illness & stress
IL-6
