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

What are some examples of stress?

Answer 2

Physical:

• Trauma
• Infection
• Intense heat or cold
• Starvation
• Surgery
• Severe blood loss
• Pain
• Dehydration

Psychological:

• Anxiety
• Depression

Question 3

Describe the acute stress response.

[IMPORTANT]

Answer 3

“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 4

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

Answer 4

Question 5

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

Answer 5

Question 6

Give some clinically relevant conditions related to the acute stress response.

[EXTRA]

Answer 6

Phaeochromocytoma :

• Tumour arising from chromaffin cells
• Uncontrolled secretion of adrenaline and noradrenaline
• Symptoms -> Hypertension and tachycardia

Adrenal medulla exhaustion:

• Plasma adrenaline falls
• Profound fall in blood glucose
• Loss of vascular tone and profound fall in BP
• Renal failure, death

Question 7

What co-ordinates the chronic stress response?

Answer 7

Hypothalamus

Question 8

Describe the response to prolonged stress.

[IMPORTANT]

Answer 8

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 9

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

Answer 9

• 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 10

What is the significance of understanding the diurnal rhythm of cortisol?

[EXTRA]

Answer 10

Understanding the diurnal rhythm of cortisol has enabled improved cortisol-replacement therapies, which involve appropriate infusion of cortisol throughout the day, rather than taking tablets at specific times during the day.

Question 11

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

Answer 11

• 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 12

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

Answer 12

ADH

Question 13

Give some experimental evidence for the place you live influencing stress.

Answer 13

(Lederbogen, 2011):

• Participants took a hard mental arithmetic under time pressure
• The degree of amygdala activation correlated with size of the city the participants lived in

Question 14

What are the functions of glucocorticoids?

[IMPORTANT]

Answer 14

Preserve glucose for the brain:

• Accelerate gluconeogenesis in liver
• Accelerate lipid and protein catabolism in liver and peripheral tissues
• Increased red blood cell production
• Maintenance of circulation

Non-essential functions in stress:

• Infertility
• Reduce inflammation and the immune response

Question 15

What are the effects of glucocorticoids in the brain?

Answer 15

• 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

Question 16

What are some clinical uses of corticosteroids?

[EXTRA]

Answer 16

Treatment for:

• Inflammatory disorders, arthritis, asthma
• Inhibit transplant rejection
• Chemotherapy
• Antenatal to mature the lungs in fetus of women threatening preterm labour

One mechanism for anti-inflammatory actions is the decrease in PLA₂.

Question 17

What receptors do glucocorticoids act on?

Answer 17

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

Question 18

Name two disorders characterised by abnormal cortisol levels.

Answer 18

• Cushing’s disease -> Cortisol excess
• Addison’s disease -> Cortisol insufficiency

Question 19

Clinically, what is Cushing’s disease and what are the symptoms?

[EXTRA]

Answer 19

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 20

Clinically, what is Addison’s disease and what are the symptoms?

[EXTRA]

Answer 20

Cortisol insufficiency, leading to:

• Hypotension
• Anaemia
• Poor bone growth
• Muscle weakness
• Hypoglycaemia
• Decreased adiposity
• Decreased response to sympathetic stimulation

Question 21

What is a distinct diagnostic symptom of Addison’s disease and why does this happen?

[EXTRA]

Answer 21

Question 22

What is the double-edged sword of stress?

Answer 22

• 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 23

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

Answer 23

Question 24

Give some experimental evidence from the WHO about work-related stress.

[EXTRA]

Answer 24

• Stress-related conditions count for more than half of all disability in northern European countries
• Life expectancy has - in one decade - decreased by 10 years in some EU Member States, much due to stress and conditions related to mental ill health
• 10 million days off work in UK in 2011 due to stress-related illnesses e.g. high blood pressure, depression and anxiety, type 2 diabetes
• Over 2/3rd GP visits stress-related

Question 25

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

[IMPORTANT]

Answer 25

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)

Question 26

Give some experimental evidence for stress and fetal programming.

[EXTRA]

Answer 26

Dutch famine study 1944-45 found that fetal stress causes retarded growth. The effects on later life vary depending on the trimester at which the stress was experienced.