Stress Flashcards
What is stress?
Any change/event that either disrupts or threatens to disrupt homeostasis to an unusual degree. Any change that threatens a “negative reward”
What are acute stressors?
Physical-extreme heat/cold; blood volume depletion by bleeding; dehydration; hypoglycaemia; pain; surgery; toxins from infection; severe exercise; sleep deprivation and Psychic (anything causing fear reaction).
What are chronic stressors?
Chronic infection; ongoing ‘mental’ stress (complexity of cerebral cortex)
Is the physiological stress response dependent of the stressful stimulus ?
No - any stress will cause the same response
What is the purpose of the stress response?
Prepare the body to meet an emergency situation. It has evolved in order to allow the individual to survive the emergency, and return to normal homeostasis when the stress is no longer present.
What two phases does the stress response consist of?
Short term alarm reaction
Long lasting resistance reaction
What occurs if stress cannot be overcome?
Extreme exhaustion - burnout
What part of the brain controls and coordinates the stress response?
The hypothalamus
What inputs to the hypothalamus about stress?
Brain stem (specific from nucleus tractus solitarius, non-specific from raphé (5-HT), locus coeruleus(NA))
Higher centres (fornix from hippocampus, amygdala, orbito-frontal and septal cortex, dorsomedial and midline thalamic nuclei)
Convey potentially stressful information from the external world, the internal organs, and the ‘psyche’.
What areas of the brainstem input to the hypothalamus about stress?
Specific Nucleus tractus solitarius (NTS)
Non-specific from raphé (5-HT), locus coeruleus(NA)
What does the hypothalamus activate in an alarm reaction?
CNS outputs: neurohormones controlling pituitary; actions on respiratory centre; arousal reaction
Sympathetic nervous system
Adrenal medulla
How does the adrenal medulla respond in stress?
Gives widespread effects via adrenaline (some noradrenaline)
How much Ad/NAd does the adrenal medulla release in stress?
There are large reserves of Ad/NA in the chromaffin cells, stress only releases a small proportion allowing for multiple bouts of stress.
What are do the CNS outputs cause in acute stress? (6)
Increased respiratory rate/depth (via somatic NS)
Increased cardiac output via cardiovascular centre and ANS
Secretion of CRH to activate the pituitary adrenal axis
Secretion of ADH to conserve body water (also increases liver glycogenolysis)
Arouses the cerebral cortex by stimulation of the locus coeruleus and widespread central release of noradrenaline
Blunts pain by release of endorphins and enkephalins - stimulation of descending pain-control circuits
How is arousal stimulated in stress?
By stimulation of the locus coeruleus and widespread central release of noradrenaline
What are the three main actions of the SNS?
Increase circulation and respiration (vasodilation of muscle vascular beds and constriction of visceral beds)
Promote catabolism for energy production
Decrease non-essential activities.
What happens to glycogenolysis in stress?
Increased
What happens to ratio of insulin and glucagon?
Decreased insulin, increased glucagon
What is Phaeochromocytomatumour
Chromaffin cell tumour - uncontrolled secretion of adrenaline and noradrenaline
What is the resistance reaction?
If the stress is more long-lasting, more prolonged effects of the acute response, and more chronic responses occur to produce the resistance reaction
What do the sympathetic nerves stimulate in the resistance reaction?
Juxtaglomerular cells of the kidney
What does juxtaglomerular cell activation in the kidney stimulate?
leads to the release of renin - stimulates RAAS
What happens to RAAS in stress (longer term)?
Upregulated
Describe what happens when there is increased renin?
Converted via a two step process to angiotensin II.
Ang II causes vascular constriction,
Also stimulates mineralocorticoid (aldosterone) release which increases renal Na reabsorption which in turn retains water, maintains a high BP, counteracts fluid loss
Increases elimination (exchange) of H+ ions (which accumulate as a result of the increased catabolism
How does the body remove excess H+ (due to catabolism) in stress?
Increased RAAS/aldosterone
What hypothalamic nucleus releases CRH?
PVN
What happens to hypothalamic CRH release in stress?
Increased release
What does cortisol do to adrenergic receptors?
Increase expression of adrenergic receptors
How are cortisol levels controlled?
Cortisol levels are controlled by negative feedback.
How is cortisol normally released?
Diurnal rhythm of release prepares the body for waking - dysregulated in shift workers which exacerbates the stress response.
What does cortisol do to metabolism?
Accelerates lipid and protein catabolism in liver and peripheral tissues - gluconeogenesis in liver
How does cortisol affect vasoconstriction?
Increases the sensitivity of blood vessels to vasoconstrictors, preventing increased capillary permeability
What does cortisol do to inflammation and immunity?
Glucocorticoids also reduce inflammation to prevent it from becoming disruptive rather than protective
Inhibit the production of fibroblasts (which when injured stimulate the inflammatory reaction)
Inhibit the immune response by an action which damages lymphocytes
What can chronic do to the HPT axis?
Inhibit various elements of the HPT axis
What is the significance of stress affecting HPT at critical periods in development (i.e neglect)?
May program its function.
A history of physical/emotional abuse or neglect has been linked with reduced plasma levels of T3 and low plasma levels of TSH in adult women.
In starvation ‘stress’ what happens to T3/4?
In starvation, stress glucocorticoids reduce T4 conversion to T3, blunting catabolic responses and preserving nutrients.
In starvation, what happens to hypothalamic GHRH, why?
Stimulates the prolonged release of GH (normally it is secreted in short pulses every 4-6h)
Sustained increase of plasma GH has an ‘anti-insulin’ effect which causes
Increased liver breakdown of fats to fatty acids and glycerol
Increased liver conversion of glycogen to glucose.
What is the benefit of the resistance reaction?
Resistance reaction allows the body to continue fighting a stressor long after the effects of the acute alarm reaction.
It produces the energy and circulatory changes required for the performance of strenuous tasks, fighting infection, avoiding fatal haemorrhage.
When the stress is prolonged what happens to GnRH secretion, why?
Reduce GnRH secretion - avoid risk of pregnancy and a further drain on metabolic resources - women may experience amenorrhea
What happens in the hippocampus in chronic stress
In the hippocampus, glucocorticoids act on glucocorticoid receptors to modify emotional reactions - induce mild euphoria, diminishing the psychic effects of the stress.
Prolonged stress kills hippocampal neurons.
What causes the decrease in GnRH in chronic stress?
CRF, glucocorticoids, opioid peptides
What happens due to steroids in stress induced exhaustion?
Prolonged mineralocorticoid activity (high levels of glucocorticoid act on the mineralocorticoid receptors (MR) and swamp the protective 11ßOHSD enzyme) causing continuing loss of K(in exchange for Na), cells become progressively depleted and may die.
What happens to adrenal medulla in stress induced exhaustion?
Adrenal medullary exhaustion occurs (run out of adrenal catecholamines) - this causes a profound fall in blood glucose, loss of vascular tone, hypotension, and death.
Treatment of ‘exhaustion’ is with catecholamines.
Can chronic stress lead to disease?
Yes
