Monday, April 1, 2013

What is Stress and stress related diseases?



Hans Selye (1907-1982) The father of the study of stress 
He developed the idea that there is a direct relationship between stress and excessive wear and tear throughout the body.

1.Definition of  Stress 
 Selye described stress as “ a state manifested by a specific syndrome of the body developed in response to any stimuli that made an intense systemic demand on it.”
Defined as a state of tension that can lead to disharmony or threaten the homeostasis of body.
The current concept of stress is “Non-specific response of the body to any demand made upon it.”

Characters of stress
Non-specific response 
Influenced by some factors 
Double significance of stress
eustress >> increase mental and physical alertness, enhance adaptative abilities  
distress >> disease (peptic ulcers, cardiovascular disease, psychosomatic disease) 

2. Stressor 
Any stimuli ,or demands ,on body that exceeds a threshold and causes stress response are stressors.
Exogenous stressor
Noise, trauma, infection, cold, heat, pollution,   
Endogenous stressor
Alternation of blood compositions, disturbance of homeostasis
Mental-social stressor
Competition, overcrowding, loneliness ,great pressure of work
Acute Stress
 Acute stress is the reaction to an immediate threat, commonly known as the fight or flight response
Common acute stressors include:
noise, crowding, isolation, hunger, danger, infection, and imagining a threat or remembering a dangerous event.
Under most circumstances, once the acute threat has passed, the response becomes inactivated and levels of stress hormones return to normal, a condition called the relaxation response.
Chronic Stress
Frequently, however, modern life poses on-going stressful situations that are not short-lived and the urge to act (to fight or to flee) must be suppressed. Stress, then, becomes chronic. 
Common chronic stressors include: 
on-going highly pressured work, long-term relationship problems, loneliness, and persistent financial worries. 

3.General Adaptation Syndrome

  • General because the effect was a general systemic reaction no matter what stressor is
  • Adaptation because the response was in reaction to a stressor in order to maintain homeostasis 
  • Syndrome because the physical manifestations were coordinated and dependent on each other.



Stages of GAS
The body passes through three universal stages of coping. 
First there is an "alarm reaction," in which the body prepares itself for "fight or flight." No organism can sustain this condition of excitement.
Second stage of adaptation ensues (provided the organism survives the first stage). In the second stage, a resistance to the stress is built.
Finally, if the duration of the stress is sufficiently long, the body eventually enters a stage of exhaustion, a sort of aging "due to wear and tear."





Mechanism-stress response
Neuroendocrine response
1. Locus ceruleus-nor-epinephrine (LC/NE) /sympathetic-adrenal medulla axis
2. Hypothalamic-pituitary-adrenal cortex
(HPA) axis
Humeral response--- Acute  phase response 
Increase of Acute  phase protein in plasma
Cellular response
  Up-expression of heat shock  protein 

1. Neuroendocrine Response

The essential function in stress response

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



The essential function of 
LC/NE- sympathetic/ adrenal medulla axis 




The effects of the increased catecholamines and   sympathetic activity
positive effects
1.Heart function increased: Heart rate↑ ,myocardial contractility ↑
                     cardiac output ↑, blood pressure ↑ →   Blood supply to tissues ↑
2. Blood redistribution →kidney, skin, viscera receive a decreased blood supply >
                    heart, brain, and skeleton muscles receive an increased blood supply
3.Breathing rate↑, bronchodilation →alveolar ventilation ↑,oxygen supply ↑
4.glycogenolysis →blood glucose level ↑
   lipolysis → blood fatty acids level ↑ →energy substrates supply ↑
5.Regulate other hormone level: growth hormones(GH)↑, thyroxine ↑, 
         glucagon ↑, and CRH (corticotropin releasing hormone)↑, insulin↓ 
negative effects: Hypertension, stress ulcer, visceral ischemia

(2)Hypothalamic-pituitary-adrenal cortex (HPA) axis
The essential function of HPA axis 
In central: CRH act as a neurotransmitter within the CNS.It can modulate learning, memory, emotion, etc

  • low doses of CRH promote adaptation →
  • excitation or pleased feeling
  • high doses of CRH cause maladaptation →
  • anxiety, depression, and  inhibition of feeding,growth
  • CRH→ACTH →GC
  • CRH →promote LC-NE neuron →activate LC-NE axis

In peripheral: GC is the final effector of the HPA axis, and plays a key role in the regulation of stress

  • Increased GC will protect the organism against the effects of stressor.
  • Excess GC will exert  detrimental effects on body

The positive effects of the increased GC 
1.GC maintains blood glucose levels by antagonizing the effects of insulin and enhances the glycogenolysis 2. GC provides fundamental supports for many other hormones (CA, GH, glycocargon)----“permission roles” 3. GC can stabilize lysosomal membrane and lessen tissue damage 4. GC also  suppress inflammation and anaphylaxis
All of these functions can protect the organism against the effects of stressor, and focus energy on regaining homeostasis.
The negative effects of the increased GC 
Negative effects

  • alteration of metabolism→negative nitrogen balance
  • Suppress immune response → infection
  • Suppress thyroid axis → delayed growth
  • result in hormonal resistance → delayed growth
  • Suppress gonad axis → delayed development

Note: Person with prolonged stress trend to manifest infection, mental depression, increased incidence of peptic ulcer, delayed growth and development.

Alterations of other hormones in stress

2.Humoral stress response
Acute phase response: is a quick mobilized non-specific immune response against infection, injuries and variety of noxious stimuli, which manifests elevation of WBC count, increase of acute phase protein , etc.
Acute phase protein (APP): are a group of plasma proteins which concentrations in plasma increase quickly upon the acute stress. 
APP represents an important adaptive, protective mechanism in humoral level.

Classification and function of APP
C-reactive protein and complements: raise the eliminating power for infectious agents, necrotic debris,  increase anti-infection and anti-injury capacity of body .
Protease  inhibitors---α1-antichymotrypsin and α1-antitrypsin: protect the tissue from injury by protease 
Coagulating proteins--- fibrinogen: enhance the hemostatic power of body against hemorrhage
Ceruloplasmin: eliminate oxygen free radical, protect body against oxidative stress injury.

3.Cellular stress response
Heat shock protein(HSP): are a family of  stress protein whose synthesis is up-regulated in response to a variety of stressors. 
 Up-expression of HSP during stress represents an important adaptive and protective mechanism in cellular and molecular level.
Classification of HSP
HSPs subfamily:HSP110,HSP90,HSP70,HSP60, HSP40,small HSP20, and ubiquitins 

Function of HSP
■ The primary role of the HSP----- assist protein folding and repairing in vivo, “Molecular chaperone” 
In normal, HSP accelerate proper folding of newly synthesized proteins, guide them translocation and assembly
Under stress conditions, HSP associate with damaged proteins, prevent their abnormal binding with other macromolecules and refold the damaged proteins.
■ Maintain the homeostasis in vivo : degrade and remove  bad-damaged and unreparable protein

Functional and Metabolic Alteration

  1. Central nervous system
  2. Immune system
  3. Cardiovascular system
  4. Digestive system
  5. Genito-urinary system
  6. Metabolic alteration

Central nervous system (CNS)
1-CNS is the regulation center of stress response. 
Without the sensation, recognition, integration, and interpretation by CNS, many stress will not happen, such as social psychology stress . 
2. CNS is effected by stress response. 
The moderate stress response will do profit to memory, concentration, and learning. 
The hypo-arousal or hyper-arousal of CNS are both distress state, which may cause depression, sadness, or anxiety, panic, etc. 

Immune system
1.    Immune system is an internal sensory organ that recognizes non-cognitive stimuli such as bacteria, viruses, and other antigens, and relays information to the neuroendocrine system via hormones secreted by immunocytes. 

The primary Hormones secreted by immunocompetent cells 

2. the stress neurohormones have significant impacts on immune system. 
■ the acute stress enhances the no-specific immune function, the number and activity of phagocytes increases, complements, C-reactive protein levels raise, and there is a brief period of immunopotentiation.
■ But the prolonged stress, variety of distresses are associated with immunosuppression, disturbance of immune system, even autoimmune diseases. 

Cardiovascular system

Digestive system

Genito-urinary system

The reproductive system is inhibited: The signs are typically manifested in ladies upon strong stress, such as menstrual disorder, amenorrhoea, or dysgalactia, galactostasis in breast feeding women, decreased libido, and impotence. 

Metabolic Alteration
The metabolic demands significantly increase upon stress
catabolism increase, anabolism decrease, metabolic rate increase significantly.

Stress and diseases
stress disease
Directly caused by severe noxious stressors. Stress ulcer is a prototype of stress disease. 
stress related disease:
Stress is an involving factor, which may participate or intensify the attack of development of the diseases as a risk factor or precipitating factor. Such as hypertension, post-traumatic stress disorder (PTSD), et al.
    
Stress Ulcer
Mucosal damage or lesion of the stomach or duodenum in critical illness or severely stressed situation, such as severe burning, trauma, hemorrhage, respiratory failure, sepsis, and so on. 
Incidence of stress ulcer in critical patients:75%~100% 
Develop within 72 hours after a great insult
Manifestation: mucosal erosion, 
superficial and multiple ulcer、errhysis. Few ulcer may occur life-threatening hemorrage or perforation. Most of them recovery without any sequela.


Mechanisms of stress ulcer
1.gastrointestinal mucosal ischemia; the basic pathogenic mechanism
 2.counter-diffusion of gastric hydrogen ion to mucosa; the major injurious factor for stress ulcer 

Post-Traumatic Stress Disorder Symptoms 
Post-traumatic 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. 

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 Dysfunction ,Premenstrual Syndrome Fertility, miscarriage, etc.)

Principles of Stress treatment1, remove or diminish the stressor
2, replenish nutrients
3, non-pharmacologic methods:
acupuncture,music etc
4, teaches coping techniques
"Fight for your highest attainable aim; but never put up resistance in vain." 

Some useful techniques 
1.Reduce harmful environmental conditions
2.Teaches techniques by which person can develop  stress tolerance.
3.Helps client maintain a positive self-image.
4.Help maintain emotional equilibrium.
5.Help client maintain or develop satisfying relations with others.

General Guidelines

  1. Rule One - Find your own purpose in life, that fits your own personal stress level. 
  2. Rule Two - Control your emotional level by recognizing situations as being either life-threatening or non-life-threatening.   
  3. Rule Three - Collect the good will and appreciation of others.  


1 comment:

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