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STRESS AND STRESS-RELATED DISEASES. Pathophysiology Department, Tongji Medical College, HUST. Contents. Concepts: general adaptation syndrome , stress , stressor Mechanism-stress response Neuroendocrine: LC-NE/sympathetic, HPA Humoral and cellular: APP, HSP

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STRESS AND STRESS-RELATED DISEASES

Pathophysiology Department, Tongji Medical College, HUST


Contents

  • Concepts: general adaptation syndrome, stress, stressor

  • Mechanism-stress response

    • Neuroendocrine: LC-NE/sympathetic, HPA

    • Humoral and cellular: APP, HSP

  • Functional metabolic alteration

  • Stress-related diseases: stress ulcer

  • Prevention and treatment principle

  • Case discussion


Hans Selye

(1907-1982)


General adaptation syndrome gas
General Adaptation Syndrome (GAS)

Specific symptoms

Different diseases

Non-specific symptoms

A serial of non-specific signs and symptoms caused by various strong stimulus.


General Principle of Stress

Stimulus

Disturbance of homeostasis

Adaptative response

Homeostasis

Diseases or symptoms

A general adaptative response in order to cope with the altered homeostasis.


Stages of GAS

Stimulus

Alarm reaction

Adaptation

Exhaustion

Diseases

Relaxation


Stress Definition

Non-specificresponse of the body to any demand made upon it.


Stressor

Any stimuli that elicit the stress response

External

Internal

Psycho-social

Physical

Psychological

Short-term (acute)

Long-term (chronic)

Stressors: noise, danger, infection

on-going highly pressured work, long-term relationship problems, loneliness, and persistent financial worries.


Importance of Stress

Without stress, there would be no life

Pleasant stress (eustress) wellness

Unpleasant stress (distress) disease


Focus of Stress Mechanism

Stimulus

Disturbance of homeostasis

Alarm reaction

Adaptative response

Diseases or symptoms


Stress Responses

Neuroendocrine

  • Humeral

  • Cellular


Neuroendocrine Response

  • Locus ceruleus-norepinephrine (LC/NE) /sympathetic-adrenal medulla axis

  • Hypothalamic-pituitary-adrenal (HPA) axis


Release of Catecholamines

Dopamine

Norepinephrine

Epinephrine (adrenaline)


Role of Catecholamine

Central: Arousal , vigilance and memory

(Alarm stage)

Peripheral:

Heart

Blood redistribution

Respiratory rate

Gastrointestinal activity

Insulin

Glucagons


CNS Response

amygdala

emotional response

Catecholamines

hippocampus

long-term memory

short-term memory, concentration, and rational thought

the front of the brain



Hormones Released

Corticotrophin-releasing hormone (CRH)

Adrenocorticotropic hormone (ACTH)

Glucocorticoid hormones (cortisol and cortisone)

Others (growth hormones, thyroid hormone, reproductive hormones

(Large surgical operation, long term effect)


Role of Glucocorticoid

Blood glucose↑

Protection

Lysosome

GC

Other hormones

Cardiovascular system

Immune system↓


Interaction of LC and HPA

Amygdala

Hippocampus

Locus ceruleus

Paraventricular nucleus

Spinal cord

Adrenal cortex


Humoral Response

Acute phase protein

C-reactive protein

Serum amyloid A

Ceruloplasmin (chelating protein)

(Severe burn injury)


Complement activation

Superoxide reduction

APP

Bind phosphocholine

Cytokine secretion


Cellular Response

Heat shock protein

e.g., HSP70

Chaperone protein: folding, assembly, translocation, degradation



Electron micrograph of HSP70 in scrapie infected cell

A, Endosome-lysosome related

multivesicular dense body;

B, HSP70 specific glod particles;

C, HSP70 specific particles in

the cytoplasm.



Understanding Stress Mechanism at Cellular and Molecular levels

Stimulus

Intracellular protein

(e.g., HSP)

Release of hormones (e.g., GC)

or neurotransmitters (e.g., NA)

Neuroendocrine response



Memory, Concentration, and Learning levels

Effect of Acute Stress on Memory. Subjects taking cortisone performed significantly worse on memorization tests than those taking the placebo did. Effect of Chronic Stress on Memory. Prolonged exposure to cortisol to shrinkage in the hippocampus, the center of memory.


Heart rate and blood pressure increase; levels

Blood flow may increase 300% to 400%;

Breathing becomes rapid and takes in more oxygen;Dryness and difficulty in talking;

Spasms of the throat muscles, difficult to swallow;

Cool, clammy, sweaty skin;

Scalp tightens, hair stand up;

Digestive activity shuts down (appetite, ulcer, diarrhea);

Genito-urinary system: disturbance of hormone.


Stress levels

Immune system

Neuroendocrine system

CRH

TNF-a

IL-1

IL-6

CRH-R1

b-endorphine ACTH



Stress Ulcer levels

Mucosal damage or lesion of the stomach or duodenum in critical illness or severely stressed situation.

Gastrointestinal mucosal ischemia

Counter-diffusion of gastric hydrogen ion

to mucosa


Psychological Effects of Stress levels

In one study, two-thirds of subjects who experienced a stressful situation had nearly six times the risk of developing depression within that month. Some evidence suggests that repeated release of stress hormone disrupts normal levels of serotoninwhichis critical for feelings of well-being.


Post-Traumatic Stress Disorder Symptoms levels

Posttraumatic Stress Disorder is a psychiatric disorder that can occur following the experience or witnessing of life-threatening events such as military combat, natural disasters, terrorist incidents, serious accidents, or violent personal assaults like rape. People who suffer from PTSD often relive the experience through nightmares and flashbacks, have difficulty sleeping, and feel detached or estranged, and these symptoms can be severe enough and last long enough to significantly impair the person's daily life.


Other levelsGastrointestinal Problems

(Irritable bowel syndrome, Crohn's disease or ulcerative colitis)

Heart Disease

(Essential hypertension, coronary artery disease, arrhythmias)

Immune Disorders

(Rheumatoid arthritis, multiple sclerosis)


Sexual and Reproductive Dysfunction levels

Sexual Function Premenstrual Syndrome Fertility, miscarriage, etc.


Case Presentation levels

A 32-year-old man was severely burned (78% of skin surface, II degree) by gasoline.

On the second day, the patient vomited about 200 ml of coffer-colored bloody juice.

a

Endoscopic examination revealed scattered erosions (2 mm in diameter) throughout the stomach. A bigger ulcer was oozing .

Bleeding was stopped by endoscopic hemostasis.


Principle of Treatment and Prevention levels

Treatingstress is a very important component in a medical regimen.

Some evidence exists that stress management programs may reduce the risk of heart events (eg, heart attack) by up to 75% in people with heart disease.


"Fight for your highest attainable aim; but never put up resistance in vain." 

"Fight for your highest attainable aim; but never put up resistance in vain." 

Hans Selye


General Guidelines resistance in vain." 

Rule One - Find your own purpose in life, that fits

your own personal stress level. 

Rule Two - Control your emotional level by

recognizing situations as being either life-

threatening or non-life-threatening. 

Rule Three - Collect the goodwill and appreciation

of others. 


Thank you resistance in vain." 


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