55.3 Physiological Response to Stress

Question 1

Define stress.

Answer 1

• Any change/event that either disrupts orthreatens to disrupt homeostasis to an unusual degree.
• Any change that threatens a “negative reward”

Question 2

Give examples of acute physical stress

Answer 2

Extreme heat/cold
Trauma
Toxins from infection
Surgery
Severe blood loss
Pain
Dehydration
Sleep deprivation

Question 3

Give examples of psychological stressors

Answer 3

Real or percieved threats
Anything causing a fear reaction

Question 4

Give examples of chronic stressors

Answer 4

Chronic infection
Housing problems
Marital problems
Difficulties at work
Financial difficulties
Phobias

Question 5

Where does the hypothalamus receive its inputs for stress?

Answer 5

Brainstem
Amygdala
Hippocampus

Question 6

Which brainstem areas signal to the hypothalamus about stress?

Answer 6

PAG - defensive, fearful and anxiety responses to paraventricular hypothalamus
Raphe nuclei (5-HT) for pain
NTS

Question 7

Which white matter tract connects the hypothalamus to the amygdala? What is conveyed down this tract?

Answer 7

Stria terminalis
Aggression, fear, fight or flight

Question 8

How is the hippocampus affected during stress?

Answer 8

Stress is associated with a decrease in memory formation

Question 9

What type of response is the stress response?

Answer 9

Counter-homeostatic/regulatory response which raises BP, blood sugar, ventilation and cardiac output to prepare for an emergency situation

Question 10

What are the three stages of the stress response?

Answer 10

-Short term alarm reaction
-Long lasting resistance reaction
-Stage of exhaustion if stress cannot be overcome

Question 11

What system governs the acute stress response?

Answer 11

Sympathetic nervous system = adrenergic secretions from SNS and adrenal medulla

Question 12

Describe the acute stress response.

Answer 12

“Fight or flight” response:

• The medulla sympathetic activity increases
• The sympathetic output to organs has organ-specific effects
• Preganglionic sympathetic fibres lead to adrenaline release from the adrenal medulla -> This leads to systemic effects

Question 13

Summarise the different effects of catecholamines on tissues around the body.

Answer 13

Question 14

What are the metabolic effects of the sympathetic NS?

Answer 14

-increased sweat production to eliminate waste products
-increasrd liver glycogenolysis - to mobilise glucose to avoid risk of hypoglycaemia (beta-1)
-lipolysis (beta-1) of adipose to increase FFA

Question 15

How are the actions of the sympathetic nervous system tightly regulated?

Answer 15

Rapid release of catecholamines followed by a very short half life (10s)

Question 16

Summarise how the RAA axis is involved in the acute stress response.

Answer 16

Question 17

How may the CNS also take part in the acute stress response? (5)

Answer 17

-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 2 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
(neurohormones controlling pituitary)

Question 18

What co-ordinates the chronic stress response?

Answer 18

Hypothalamus

Question 19

Which axis is activated during prolonged stress?

Answer 19

Hypothalamo-pituitary-adrenal system

Question 20

Describe the response to prolonged stress.

Answer 20

Activation of the HPA axis:

• Paraventricular nucleus of the hypothalamus is signalled to release CRH (corticotrophin-releasing hormone)
• Portal vessels carry the CRH to the pituitary, where it drives the release of ACTH
• ACTH leads to cortisol release at the adrenal cortex
• Cortisol has metabolic, cardiovascular, immune and CNS effects
• Cortisol also leads to negative feedback on the hypothalamus and pituitary

Question 21

Describe the patterns of cortisol levels throughout the day and what causes this.

Answer 21

• There is a diurnal pattern which is due to the diurnal pattern of ACTH levels.
• This is controlled by the suprachiasmatic nucleus in the hypothalamus, which receives input from the retina about the time of day and influences the secretion of CRH from the paraventricular nucleus.
• This means that there is more altertness during the day.

Question 22

Describe the inputs into the paraventricular nucleus of the hypothalamus that influence the stress response.

Answer 22

• Hippocampus + Amygdala [IMPORTANT] -> Information about cognition, mood, situations, perceptions and phobias
• Brainstem (including PAG, NTS, raphe nuclei and locus coeruleus) [IMPORTANT] -> Information about pain, arousal and stress (via catecholamines)
• Suprachiasmatic nucleus (hypothalamus) -> Information about the light/dark cycle
• Arcuate nucleus -> Information about feeding
• Circumventricular organs can also sample the blood for circulating hormones, osmotic changes and other signals such as cytokines

All of these changes influence the release of CRH from the hypothalamus.

Question 23

Aside from CRH, what is another hormone that can contribute to the stress response by influencing release of ACTH?

Answer 23

ADH

Question 24

What are the effects of cortisol on the body?

Answer 24

SHIFT TO A GLUCOSE SPARING PROFILE TO INCREASE SUGAR FOR BRAIN

-Accelerates lipid and protein catabolism in liver and peripheral tissues; gluconeogenesis in liver
-Increases the sensitivity of blood vessels to vasoconstrictors, prevent increased capillary permeability
-Maintains the contractility of cardiac muscle
-Reduce inflammation - 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
-EPO synthesis to increase O2 capactiy

Question 25

Which hormone does cortisol inhibit the release of? What is the significance of this?

Answer 25

GnRH (Gonadotrophin releasing hormone) from arcuate nucleus Stress is associated with infertility and female amenorrhea = pregnancy is a risk and drain of metabolic resources

Question 26

What are the effects of glucocorticoids in the brain?

Answer 26

* At hypothalamus, glucocorticoids reduce GnRH secretion to avoid risk of pregnancy and a further drain on metabolic resources (Whirledge, 2010) * Have complex effects on appetite (Dallman, 2010) * At hippocampus, glucocorticoids act on GR to modify emotional reactions - induce mild euphoria to diminish psychic effects of the stress. Kills hippocampal neurons

Question 27

What receptors do glucocorticoids act on?

Answer 27

* Intracellular receptors, regulating 10% of genes * This means that cortisol is released quickly during stress but has slow action

Question 28

What occurs when stress is so great that it cannot be sustained by the prolonged response?

Answer 28

Exhaustion

Question 29

What are the two main effects of exhaustion?

Answer 29

Prolonged mineralcorticoid activity = continued loss of K+ = cells depleted and die Adrenal medullary exhaustion (run out of catecholamines) = fall in blood glucose, loss of vascular tone, hypotension and death

Question 30

Name two disorders characterised by abnormal cortisol levels.

Answer 30

* Cushing's disease -\> Cortisol excess * Addison's disease -\> Cortisol insufficiency

Question 31

Why do people with Addison's have hyperpigmentation?

Answer 31

-Lack of cortisol results in lossof negative feedback so high ACTH and MSH -High circulating levels of ACTH/MSH cause hyperpigmentation of skin - stimulates MC1 melanocortin receptors to increase melanin

Question 32

Clinically, what is Cushing's disease and what are the symptoms? [EXTRA]

Answer 32

Cortisol excess, leading to: * Hypertension * Polycythaemia * Bruising * Osteoporosis * Muscle weakness * Poor collagen production * Impaired glucose tolerance * Abnormal fat distribution * Increased response to sympathetic stimulation

Question 33

Clinically, what is Addison's disease and what are the symptoms? [EXTRA]

Answer 33

Cortisol insufficiency, leading to: * Hypotension * Anaemia * Poor bone growth * Muscle weakness * Hypoglycaemia * Decreased adiposity * Decreased response to sympathetic stimulation

Question 34

What is the double-edged sword of stress?

Answer 34

* The function of stress is to prepare the body to meet an emergency situation. * But many of the physical responses are not appropriate to many things that stress humans today. * Stress is a factor in “stress-induced illnesses”, such as heart, peripheral vascular disease, type 2 diabetes, anxiety and depression.

Question 35

For each response to stress, give some examples of modern stress-related conditions where this response becomes unwanted.

Answer 35

Question 36

Why do stress related illnesses come about?

Answer 36

The changes produced by the stress response have been honed by evolution to counter physical stressors. However, humans are often stressed by circumstances in which major physical activity is either inappropriate or counterproductive. Therefore, the rise in BP, plasma glucose and FFA etc are not used by any physical exertion and remain as counter-homeostatic.

Question 37

What are the treatments for stress related illnesses?

Answer 37

Substantial exercise Relaxation techniques Anxiolytics beta adrenergic blockers ACE inhibitors

Question 38

Give examples of in utero stress

Answer 38

Undernourishment Oxygen deprivation Low birth weight

Question 39

Describe how stress in utero can influence the health of the child.

Answer 39

Experience of undernourishment, poor oxygen supply or maternal stress as a foetus can lead to a lower birth weight that is associated with: * Hypertension * Diabetes mellitus * Lower life expectancy (via resetting of HPA axis)