Transcript General Adaptation Syndrome (GAS)

STRESS AND STRESSRELATED DISEASES
Contents
1. Concepts: general adaptation syndrome,
stress, stressor
2. Mechanism-stress response
• Neuroendocrine: LC-NE/sympathetic, HPA
• Humoral and cellular: APP, HSP
3. Functional metabolic alteration
4. Stress-related diseases: stress ulcer
5. Prevention and treatment principle
6. Case discussion
Hans Selye
(1907-1982)
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
Relaxation
Exhaustion
Diseases
Stress Definition
Non-specific response of the
body to any demand made
upon it.
Stressor
Any stimuli that elicit the stress response
External
Internal
Physical
Short-term (acute)
Psychological Long-term (chronic)
Psycho-social
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)
Unpleasant stress (distress)
wellness
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
the front of the brain
short-term
memory,
concentration,
and rational
thought
Diencephalons
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
Protection
Other hormones
Immune system↓
Blood glucose↑
GC
Lysosome
Cardiovascular 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
Structure of HSP
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.
Regulation of HSP expression
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
Functional and Metabolic Alteration
Memory, Concentration, and Learning
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;
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
Immune system Neuroendocrine system
CRH
TNF-a
IL-1
IL-6
CRH-R1
b-endorphine ACTH
Stress and Disease
Stress Ulcer
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
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 serotonin which
is critical for feelings of well-being.
Post-Traumatic Stress Disorder Symptoms
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 Gastrointestinal 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
Sexual Function
Premenstrual Syndrome
Fertility, miscarriage, etc.
Case Presentation
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
a ml of coffer-colored bloody juice.
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
Treating stress 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
resistance
vain."
"Fight for your
highestup
attainable
aim; but never put upin
resistance
in vain."
Hans Selye
General Guidelines
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 lifethreatening or non-life-threatening.
Rule Three - Collect the goodwill and appreciation
of others.
Thank you