Stress Flashcards
Stress
Stress is defined as a non-specific response of the body to any disturbance / demand — triggering the ‘stress response’.
- The demand or ‘stressor’ can be positive (e.g., a new job, new relationship) or negative (e.g., fear, injury)
Causes of stress
- Poor nutrition: Nutritional deficiencies (e.g., highly-processed diets, high intake of alcohol).
- Personal stress: Not feeling happy with oneself; financial problems; problems with family members, friends, at work.
- Poor body functions: Injury or illness e.g., allergy, skin conditions, thyroid disorders, chronic inflammatory disorders. Detoxification — slow or fast detoxification of certain NTs or hormones may result in imbalances in stress hormones (e.g., COMT / MAO).
- Environmental stressors: Radiation e.g., mobile phones, x-rays, microwaves; pesticides, industrial and household chemicals.
The general adaptation syndrome
The general adaptation syndrome — a term coined by the endocrinologist, Hans Selye, that describes the 3 stages of a stress response which are controlled and regulated by the adrenal glands:
- Alarm phase (initial response often referred to as ‘fight or flight’).
- Resistance phase
- Exhaustion phase
- Alarm phase (initial response often referred to as ‘fight or flight’).
- Alarm phase (initial response often referred to as ‘fight or flight’).
- Counteracts danger by mobilising resources for physical activity.
- Stressor hypothalamus sympathetic nervous system adrenal medulla releases adrenaline and noradrenaline.
- Adrenaline activates inflammatory cytokines — ↑ oxidative stress.
- ACTH release (anterior pituitary) cortisol release (adrenal cortex). Cortisol provides additional glucose, ↑ pain threshold and inhibiting immune responses.
- Resistance phase
- Resistance phase:
- Once the stressor has gone the alarm phase abates and the individual returns to a state of equilibrium.
- The first two phases occur repeatedly in life and are part of evolving as human beings.
- Exhaustion phase
- Exhaustion phase:
- If stress is prolonged or severe then equilibrium is not restored and exhaustion results.
- Prolonged release of stress hormones has negative health effects.
- Over time, cortisol levels especially decrease, leading to illness.
If the stressor is perceived as too intense or the duration is too long, maladaptive responses occur, which can lead to disease.
- Glucocorticoid receptors are expressed in most organs and tissues including several brain regions, sympathetic nerves and immune cells.
- Thus, continued stimulus causing hyperactivation of the HPAA can have widespread effects.
- Repeated surges of cortisol can lead to cortisol dysfunction, resulting in unmodulated inflammation, and various sequelae including pain, depression, GI issues and increased risk of cardiovascular disease and cancer
Proposed mechanisms underlying cortisol dysfunction
Proposed mechanisms underlying cortisol dysfunction:
- Prolonged or excessive cortisol secretion leads to desensitisation of glucocorticoid receptors to cortisol (cortisol resistance).
- Impaired binding disrupts negative feedback where cortisol would normally inhibit continued CRH release.
CRH = corticotropinreleasing hormone - CRH ↑ mast cell activation, release of noradrenaline (pro-inflammatory) and upregulates glutamate in the amygdala to promote a fear-based response to stress.
- High surges of cortisol increase its affinity to bind to mineralocorticoid receptors, where it has a pro-inflammatory effect.
Stress and inflammation
Inflammation is a key driver in the physiological effects of stress. Stress in turn increases inflammation. It’s a vicious cycle.
- Stress-induced inflammation is implicated in:
CVD, fibromyalgia, chronic fatigue syndrome, osteoporosis, rheumatoid arthritis, IBD, chronic back pain, TMJ dysfunction and more.
- Inflammation increases oxidative stress and free radical damage, cellular death, ageing and systemic tissue damage.
- The sympathetic response to stress is pro-inflammatory, serving a purpose in the short term (destroys pathogens and foreign bodies).
- In chronic stress situations it contributes to the inflammatory state
Effects of prolonged cortisol secretion
Effects of prolonged cortisol secretion:
Increased risk of insulin resistance and Type 2 diabetes:
Weight gain with central adiposity:
Suppresses reproductive function:
Impaired immune function:
Suppresses thyroid function:
Suppresses gastrointestinal function:
Downregulates the endocannabinoid (eCB) system:
Increased risk of insulin resistance and Type 2 diabetes
Increased risk of insulin resistance and Type 2 diabetes:
- Cortisol increases gluconeogenesis and decreases glycogen synthesis. Prolonged elevations lead to hyperglycaemia.
- Cortisol also inhibits beta cell insulin secretion and impairs insulin-mediated glucose uptake.
Weight gain with central adiposity
Weight gain with central adiposity:
- Cortisol stimulates appetite and intake of highly palatable foods.
- Causes redistribution / accumulation of fat in visceral fat cells.
- Impaired insulin response and consistently high blood glucose sends hunger signals to the brain leading to overeating.
Suppresses reproductive function
Suppresses reproductive function:
- Normal function is inhibited by various components of the HPAA in chronic stress.
- CRH suppresses the secretion of GnRH, disrupting pulsatile release of FSH and LH and in turn, oestrogen, progesterone and androgens.
Impaired immune function
Impaired immune function:
- Increases infection susceptibility.
- Decreases T-cell proliferation and downregulates T-helper cell receptor expression — necessary to induce Th1 immune response
- Inhibits neutrophil, macrophage, NK cell and lymphocyte activity.
Suppresses thyroid function
Suppresses thyroid function:
- HPAA activation with increases in cortisol is associated with reduced TSH production.
- Glucocorticoids inhibit 5-deiodinase activity, which converts thyroxine to triiodothyronine.
- Thyroxine is shunted into the ‘inactive’ rT3.
- In adrenal fatigue, low cortisol ↓ T3 receptor responsiveness.
Suppresses gastrointestinal function
Suppresses gastrointestinal function:
Ongoing stress leads to changes in the ‘gut-brain’ axis (this includes responses from the ANS and HPAA) causing:
- Altered GI motility (impairing digestion and elimination).
- Increased visceral perception.
- Changes in GI secretions — e.g., downregulates HCl production.
- Increased intestinal permeability to large antigenic molecules.
It can lead to mast cell degranulation and colonic mucin depletion.
- Negative effects on microbiota and GI mucosal regenerative.
- Clinical consequences include GORD, peptic ulcers, IBD, SIBO etc.
Downregulates the endocannabinoid (eCB) system
Downregulates the endocannabinoid (eCB) system:
- The eCB system has various homeostatic roles including modulation of neural plasticity, neuroprotection, immunity, inflammation, pain, emotional memory, hunger and metabolism.
- Suboptimal function of the eCB is linked with conditions such as depression, fibromyalgia, migraine and IBS.
- Circulating eCBs are used in the crosstalk between the intestinal microbiome and brain — specifically influencing mood.
Typical symptoms of stress
Insomnia, fatigue, depression, irritability, headache, and digestive disturbances.
Conditions linked to chronic stress include
Anorexia nervosa, asthma, autoimmunity, cancer, CVD, chronic fatigue syndrome, recurrent infections, mood disorders, Type 2 diabetes, IBS, ulcers, headaches, hypertension, menstrual irregularities, PMS and thyroid disorders
- Persistent stress initially leads to hyperactivation of the HPAA and is commonly associated with issues such as depression, anxiety disorders and metabolic syndrome (hyperglycaemia, hypertension, lipid abnormalities and central adiposity).
- Continued stress results in hypo-activation of the HPAA and is linked with fatigue, irritability, pain and associated disorders including chronic fatigue syndrome, fibromyalgia and arthritis.