Stress and Adaptation

Week 3

Feedback system

Can be positive (intensifying change) or most commonly, negative (counteracts a change)

Has three essential parts:

1. Sensor – detects change

2. Control center – evaluates the data

3. Effector – takes action

Stress response

Activated by the perception or anticipation of a perceived threat, activates 3 major systems:

1) the HPA (hypothalamic-pituitary-adrenal) axis

2) the SNS

3) the immune system

general adaptation syndrome (GAS)

Hallmark pattern of a nonspecific stress response involving 3 successive stages

alarm stage

Stage of GAS

Emergency reaction that prepares the body to fight or flee from threat. Involves secretion of hormones / catecholamines and boosts the immune system

resistance stage

Stage if GAS

Continued mobilization of the body’s resources, ie cortisol & epi/norepi, to cope and overcome a sustained challenge. Prolonged use of resources causes suppressed immune system

exhaustion stage

Stage of GAS

Body’s resources are depleted and the immune system is no longer able to cope with the stressor. Body is vulnerable to psychosomatic and physical diseases

neuroendocrine response

Coordinated interaction:

Stimulus activates hypothalamus, which triggers the release of hormones which carry out the physiologic response to stress

locus coeruleus

primary location of norepinephrine synthesis, nucleus of the pons.

Role in stress response:

• Triggers cascade of physiologic events that prepare the body for rapid fight or flight response (faster than the HPA axis)

  • HR acceleration

  • Pupillary and bronchial dilation

  • Vasoconstriction

  • Glucose release in the liver

  • Increased blood supply to striated muscles

corticotropin-releasing hormone

Secretion is activated by the hypothalamus, this hormone binds to receptors on the anterior pituitary, to cause production of ACTH

angiotensin ii

Hormone with many systemic effects, in relation to stress response:

• Stimulates the hypothalamus to increase thirst (preparing for potential dehydration)

• Enhances norepinephrine release from sympathetic nerve endings, amplifying the arousal response

• Further activates the HPA axis, encouraging more CRH and ACTH release

• Acts on the amygdala (your brain's threat detection center), enhancing fear and anxiety responses

immune response

System that responds to signals from the HPA hormones and catecholamines from the SNS

• Has an adaptive role as a ginal organ to alter other systems of internally threatening stimuli

• Can trigger a stress response via the release of immune inflammatory mediators after a viral or bacterial infection, cancer, tissue injury, or other stressors

• Increased cytokine production induces CNS and behavior changes during an acute inflammatory infectious episode

catecholamines (CAs)

Rapidly released by activation of the SNS.

• Bind with alpha and beta receptors

• Work with the autonomic nervous system to regulate cv, pulmonary, hepatic, skeletal muscle, and the immune system

Physiologic reserve

The ability of an organ or biological system to endure stressors and return to its original state of function, or to function beyond its baseline level when needed.

Can be “depleted” due to chronic stress or illness

early childhood (_)

Consequence of chronic stress in ______

• Epigenetic modifications that increase the risk of childhood obesity and metabolic disorders

genetics

Play a role in adaptation to stress/disease. ie some may be predisposed to heightened physiologic affects of stress and some may be less so d/t environment

effects of chronic stress

Effects of…

• Obesity

• Metabolic syndrome

• Sleep deprivation

• Lipid abnormalities

• CAD

• DM

• Atherosclerosis

• Decreased bone density

• Cognitive impairments

• Emotional disorders ex depression (leading to shrinkage of the hippocampus and prefrontal cortex)

PTSD

Conditioned fear response that is triggered by sounds, odors, visual images, or other stimuli associated with a traumatic event

Can result in maladaptive behavior and illness

Eustress

“positive stress”

Allostasis

“moves the set-point” for stress. Different parts of the limbic system respond to different types of stress, an adaptive strategy.

b-endorphins (endogenous opiates)

Hormone from the pituitary and hypothalamus

Action r/t stress response:

• activates endorphin receptors on peripheral sensory nerves, providing analgesia

• hemorrhage increases levels of this hormone to inhibit BP elevation

growth hormone (GH or somatotropin)

Hormone from the anterior pituitary

Action r/t stress response:

• affects metabolism

• counters effects of insulin

• involved in tissue repair

• increases after variety of stressful stimuli (cardiac cath, electroshock, gastroscopy, surgery, fever, exercise

• suppressed by chronic stress

prolactin

Hormone from the anterior pituitary

Action r/t stress response:

• increases in response to various stressful stimuli (gastroscopy, proctoscopy, pelvic exams, surgery)

• increased in situ breast cancer

• requires more intense stimuli than catecholamines or cortisol to be elevated

oxytocin

Hormone from the hypothalamus

Action r/t stress response:

• promotes bonding/social attachment

• associated w/ reduced anxiety/HPA axis activation

testosterone

Hormone from the Leydig cells in testes

Action r/t stress response:

• decreases after stressful stimuli

• decreased levels are associated with lowered cortisol responsiveness to stress-induced inflammation

estrogen

Hormone from the ovaries

Action r/t stress response:

• exerts calming effects during stressful situations, works with oxytocin

melatonin

Hormone from the pineal gland

Action r/t stress response:

• increases during stress response

somatostatin (SOM)

Hormone produced by the sensory nerve terminals, released from lymphoid cells and the hypothalamus

Action r/t stress response:

• Decreases natural killer cell function

• Decreases immunoglobulin synthesis

• Decreases growth hormone secretion

vasoactive intestinal peptide (VIP)

Hormone found in neurons of the CNS and peripheral nerves

Action r/t stress response:

• Increases during stress

• Receptors found on both T and B cells

• Influences lymphocyte maturation and cytokine/antibody production

calcitonin gene-related peptide (CGRP)

Hormone found in the spinal cord motor neurons, lymphoid tissues, & sensory neurons

Action r/t stress response:

• Receptors on the T and B lymphocytes

• Vasodilator

• May play a role in inflammation

• Interferes w/ lymphocyte activation

neuropeptide y (NPY)

Hormone found in neurons

Action r/t stress response:

• lymphocytes have receptors

• May be responsible for regional vasoconstriction in response to stress

substance p (SP)

Produced by the neuropeptide tachykinin, found in the brain and some nerves

Action r/t stress response:

• Increases in response to stress

• Receptors are found on membranes of T & B cells, mononuclear phagocytic cells, and mast cells

• Pro-inflammatory activity (release of histamine)

• Causes smooth muscle contraction

• Increases antibody production

Cortisol

Released as a result of the HPA axis, binds with glucocorticoid receptors (GRs).

Effects:

• Promotes gluconeogenesis (increases glucose) and lipolysis

• Inhibits uptake of glucose into cells

• Increases protein synthesis in liver but decreases it in the skeletal muscles

• High levels suppress inflammatory response (treatment)

• May increase local pro-inflammatory effects when released during stress response

• Promotes gastric secretion

• Enhances Ca++ excretion

• Slows connective tissue healing

• Optimizes CV function

• Roles in arousal (not sexual)

Anatomic reserve

The structural redundancy and "extra" physical hardware your body possesses.

Ex: having two kidneys, two lungs, two adrenal glands or having redundant tissue (liver, brain, tissue)

Remains intact in acute stress, gets depleted during chronic stress, in severe chronic stress, the smallest insults can cause failure

adolescence (_)

Consequence of chronic stress in ______

• Reduced gray matter volume in the prefrontal cortex and hippocampus

allostatic overload

Chronic activation of regulatory systems leading to the emergence of diseases and disorders.

Physiologic changes:

• Exaggerated secretion of adrenal cortisol and CAs from the SNS

• Pro-inflammatory cytokines that may initiate gene expression changes

• Structural remodeling of the hippocampus, amygdala and/or prefrontal cortex

• Sleep deprivation

• Elevated evening cortisol secretion

• Height and insulin and body glucose levels

• Increased BP

• Reduced parasympathetic activity

• Increase secretion of ghrelin (promotes appetite)

microbiota-gut-brain axis

This axis regulates immune activity and pro-inflammatory cytokines that stimulate the HPA axis, can also directly impact the CNS immune activity

vagus nerve

Which nerve mediates the effects of the gut-brain axis?

IL-6, TNF (beta), and IFN (interferon)

Immune inflammatory mediators that initiate a stress response through the HPA axis

cytokines

small signaling proteins produced by immune cells to act as chemical messengers, regulating inflammation, immune responses, and cell growth

small large

The adrenal medulla releases a ___ amount of norepi and a ___ amount of epi

epinephrine

Which hormone is responsible for releasing glucose into the bloodstream via beta receptors during the stress response?

hypertrophy

Which cellular adaptation occurs to the adrenal glands due to chronic stress?

atrophy

which cellular adaptation occurs to lymphoid tissue due to chronic stress?

increased

Decreased sleep leads to ____ inflammatory markers

increased TNF (alpha)

Poor glycemic control leads to _____ ___ (inflammatory marker)

th1

which cytokine is suppressed by cortisol

(Innate immunity)

th2

Which cytokine is stimulated by cortisol

(adaptive immunity)

th1 and th2 shift

Describes the relationship between inflammatory markers, th1 and th2, as a result of cortisol

natural killer

Stress causes decreased ____ ___ cells

T B

Stress causes cell cytotoxicity and impaired _ cell function