Stress and Disease

Definition of Stress

A perceived or anticipated threat that activates stress-related systems in the body and brain.

WHO Declaration on Stress

Declared stress as the health epidemic of the 21st century.

Fight-or-Flight Response Origin

Coined by Walter Cannon to describe physiologic responses preparing the body to deal with threat.

General Adaptation Syndrome (GAS)

Global physiologic responses developed by Hans Selye involving adrenal enlargement, immune alterations, and GI manifestations.

Three Stages of GAS

Alarm stage, stage of resistance or adaptation, and stage of exhaustion (allostatic overload).

Psychological vs. Physical Stressors

Psychological stressors are as effective as physical stressors in activating adrenal gland hormone secretion.

Allostasis

Stability through change; dynamic adaptation of the brain to constantly adjust its physiologic operating range.

Sex Differences in Stress Response

Males exhibit 'fight-or-flight' while females exhibit 'tend-and-befriend'.

Allostatic Overload

Chronic overactivation of adaptive regulatory physiologic systems leading to pathophysiology and disease.

Three Major Physiologic Stress Systems

(1) HPA axis, (2) SAM axis, and (3) immune system.

SAM Axis vs. HPA Axis Speed

The SAM axis responds quickly, whereas the HPA axis is slower to respond.

SAM Axis Activation Releases

Norepinephrine from sympathetic nerves and epinephrine from the adrenal medulla.

Parasympathetic Nervous System (PNS) Role

Counters SNS activity and helps maintain overall homeostasis when stress is alleviated.

HPA Axis Regulation

Regulated by pituitary adenylate cyclase-activating polypeptide (PACAP).

HPA Axis Pathway

Hypothalamus secretes CRH -> Anterior pituitary produces ACTH -> Adrenal cortex releases cortisol.

Primary Glucocorticoid Hormone

Cortisol, which mobilizes cellular metabolism and stimulates gluconeogenesis.

Anti-inflammatory Function of Acute Cortisol

Induces an anti-inflammatory state to contain an inflammatory immune response.

Chronic HPA Axis Dysregulation

Linked to obesity, sleep deprivation, hypertension, diabetes, atherosclerosis, and bone density loss.

Sterile Inflammation

Inflammatory responses that occur in the absence of infection, such as those caused by psychological stress.

Immune, Nervous, and Endocrine Communication

Communicate through similar pathways using hormones, neurotransmitters, neuropeptides, and immune cell products.

Adaptive Role of the Immune System

Acts as a signal organ to alert other systems of internally threatening stimuli like infection or tissue damage.

Chronic Stress and Rumination

Prolonged intrusive ruminations lead to persistent immune dysregulation and increased depression and suicide risk.

Chronic Inflammatory Diseases

Cardiovascular disease, osteoporosis, arthritis, type 2 diabetes, and COPD.

Tumor Growth and SNS Activation

Stress-induced SNS release of catecholamines and beta-adrenergic receptors are implicated in primary tumor growth and metastasis.

Burnout Mechanisms

Dysregulation of the HPA axis and ANS accompanied by impaired immune function and inflammation.

Prenatal Stress Effects

Maternal cortisol crossing the placenta increases the risk of low birth weight and later-life diseases like obesity and ADHD.

Adolescent Stress Impact

Associated with smaller prefrontal cortex volumes and poorer executive function.

Early Childhood Adversity

Negatively affects stress and immune systems; lack of parental support leads to long-term HPA axis dysregulation.

Childhood Trauma Link

Associated with psychiatric illnesses (depression, anxiety, PTSD) and health problems (arthritis, cardiovascular disease, cancer).

Telomeres

DNA sequences and proteins at chromosome ends that protect them from fusion and degradation.

Telomere Shortening Causes

Accelerated by aging, inflammation, oxidative stress, smoking, obesity, and type 2 diabetes.

Coping Styles and Resilience

Personality characteristics, optimism, and social support increase stress resilience and improve outcomes.

Maladaptive Coping Responses

Increased smoking, decreased exercise and sleep, and poor diet alter adaptive immune functions and increase disease susceptibility.

Exercise Benefits on Stress

Rebalances neurotransmitters, inhibits proinflammatory cytokines, increases brain metabolism, and reduces obesity.

Mindfulness Therapy

Involves monitoring current experiences with acceptance; modulates HPA-axis cortisol secretion and dampens stress brain regions.

Yoga as Therapy

A mind-body practice used to treat stress and anxiety, promote relaxation, and increase well-being.