Stress And Disease Flashcards
Stress Definition
Stress is commonly defined as a state of real or perceived threat to homeostasis
What is Homeostasis
-Relatively constant internal balance of environment
-Defined as “set points” that keep cells in a normative state
Set points keep cells in normative state by providing:
-Optimal concentrations of gases, nutrients, ions, and water
-Optimal temperature for metabolism
-Optimal intracellular and extracellular fluid volumes
What is homeostasis maintained by
Negative feedback mechanisms designed to prevent significant changes from set post
Which 2 body systems control homeostasis
Nervous
Endocrine
Why is homeostasis important?
Maintains optimum cell structure (morphology) and functions (physiology) to maintain health of entire individual
Hemostasis is integral to
Healthy cellular functioning
Homeostasis must be somewhat ..
Flexible
Since small changes need to occur as cell metabolic activity increases or decreases to meet the body’s needs
Examples of when homeostasis changes
-Exercising
-Eating and digesting good
-Are examples where changes in BP,RR,HR or enzymatic and hormone secretion need to adjust to maintain homeostatic balance
Stressor
Any external or internal stimulus (variable) that causes a change in the internal homeostatic balance
-Thus created detectable homeostatic imbalances
2 Types Of Stressors
Distress
Eustress
Distress
-= bad stress, negative
-etiologies with potential for tissue damage
-e.g genetic, congenital, or acquired causes
Eustress
-=good stress, positive
-energizes, motivates
-Eg. Laughing, exercising, sleeping
Stress is a ___ event designed to..
Normal
-alert the body to potential issues, respond to those issues and then return to normal homeostatic balance
Different individuals and stress
Will be affected by and respond to the same type of stressor to different degrees
-why stress can manifest in many different psychological (behavioural/emotional) or physiological ways
Okay
Dealing with stress
Some suggest that previous life experiences of negative and positive stressors help to condition the individual to new stressors, enabling the individual to cope more efficiently
Categories of stressors affecting homeostasis
Chemical
Physical
Psychological
Chemical Stressors Examples of Internal Stressors
-Blood gases
-Water
-Ions
-pH
-Neurotransmitter
-Hormones
-Blood cell counts
-Hgb
-Nutrients
-Microbes (Infection)
-Drugs
-Inflammation
-Antibodies
Chemical Stressors Examples of External Stressors
-Low 02
-High CO2
-pollutants
-microbes
Physical Stressors Examples of Internal Stressors
-BP
-CO
-Urine
-Ventilation
-Body T
-Mechanical trauma (compression, obstruction, fracture)
-Excess weight gain or loss
-Mobility issues
-Age
Physical Stressors Examples External Stressors
-Air pressure
-Air T
-Mechanical trauma (sports injury, motor vehicle injury)
-Excess noise
-Excess light
-work hazards
Psychological (Emotional Stressors) Examples Internal Stressors
Pain
Fear
Anxiety
Psychological Stressors Examples External Stressed
Relationships
Family
Friends
Work
School
Homeostasis Negative Feedback
-A change from the normal set point of any of these variables would be detected by different body receptors and sent to a control centre (CNS of hypothalamus)
-The control Center would then send signals via effectors to respond to this change and return the variable towards the normal homeostasis state
An abnormal balance of any of these variables could result in
Disease or illness
Changes in internal or external environment variables can
Trigger a stress response
If change becomes permanent
Body cells will try to adapt
Chemical and physical changes are often
Measurable and used in diagnostics
Psychological/ behavioural changes are
Equally important but may be more difficult to measure
What is stressor is long term ?
Ie. chronic
-Then the body will attempt to adapt to the change
-Allostasis
Allostasis
The process of the adaptation to change
-If body cannot adapt, manifestations of chronic stress related disorders may occur
What is Homeostatic Imbalancd
-Normal homeostatic mechanisms are unable to return a physiological process to normal physiological set point
Neuroendocrine Responses
Will try to overcome the physiologic imbalance, reinstablish homeostasis
Moderate Chronic Imbalance
-Physiologic adaptive changes to the normal set point occur
-Includes compensatory mechanisms called Allostasis
-Clinical manifestations subtle/subacute or not observed
Severe and/or Chronic Imbalance
-Body not able to adapt to stress: Allostatic overload
-Clinical manifestations usually present
-Stress related illness, disease, death
How to imagine homeostatic imbalance
The teeter totter is stuck in one potion not adjusting back to normal homeostatic set point
What is Allostasis
-Process of cellular adaptations to chronic/constant change in the homeostatic set point of a variable
What is Allostasis mediated by
Changes (structural/physiological) in neuroendocrine, autonomic, and immune functions (new set point)
-Look for changes in neurotransmitter, hormone, and WBC responses
Allostasis is integral for
Cell survival to chronic homeostatic imbalance
Adaptation
The physiological and psychological (behavioural) processes utilized by the individual to respond to a stressor
Cellular Adaptations May be Used
-Diagnostically, and prognostically
Examples of Cellular Adaptations
-Dysplasia or anaplasia would be examples of cellular adaptations to chronic exposure to a carcinogen
-Development of atherosclerotic plaque in arteries is an example of cellular structural and physiological adaptations to chronic, turbulent, high P blood flow
-Insomnia is an example of psychological adaptations to chronic emotional and/or physiological stress
-Increased blood level of cortisol is an example of a physiological adaptation to chronic stress of any type
Examples of Stressors
-Environmental (work, home, neighborhood)
-Major life events
-Trauma, abuse
Individuals physiological responses to stress are determined by
A number of modifiable and non-modifiable risk factors
-These factors are the allostatic load that stimulates physiologic and/or psychologic responses
A persons ability to adapt to stress is
-Individualized
-Psychological stressors May elicit a physiological stress response and vice versa
Allostasis
Dynamic, adaptive structural, physiological and/or behavioural responses to stressors that can potentially change the homeostatic set point to a new “normal” range
-Often short term issue
Allostatic Load
-Individualized cumulative amounts of stressors that exist in our lives and affect our physiologic responses (genetics, lifestyle, daily or sudden events)
-The physiological and behavioural manifestations of these stressors are determined by our ability to adapt to the stress load, including various coping mechanisms
-May present with subtle clinical manifestations or none at all
Allostatic Overload
-The body is having difficulty managing the cumulative stressors and begins to manifest the effects of a loss of its reserves and its ability to continue to respond to and survive the stress
-Clinical manifestations should be present
-May lead to long term deficits, including stress related diseases
-Corresponds to the exhaustion stage of GAS
When does Allostatic Load become Allostatic Overload Example
-Individual experiencing chronic stress —> causes a prolonged increase in cortisol that the body must adapt to by subtly changing its physiology = minimal is any manifestations may be present for a long time —> Allostatic load —> stress persists —> eventually this increased cortisol manifests as increased BG, HR, BP and decreased immune function —> presence of clinical manifestations of stress related diseases —> Allostatic overload
Neuroendocrine system responds to
All stressors
Neuroendocrine system consists of
-1) neural structures
-2) endocrine structures
Neuroendocrine system neural structures
-Cerebral cortex (cognitive centers)
-Limbic system (survival centers)
-Reticular activating system (alerting centers)
-Hypothalamus (ANS control) d tf
Neuroendocrine System Endocrine Structures
-Hypothalamus (endocrine control Center) which releases hormones that regulate the pituitary gland + other endocrine glands hormone secretion
The body’s ability to elicit a stress response is
-Normal
-Allows the body to respond to and survive acute stressors
-Neurotranmitters and hormones released are quickly removed by enzymes as to not prolong chronic overstimulation that can cause damage
When the body cannot turn off the stress response ..
Problems start to occur
We call those problems stress related diseases
The hypothalamus..
-Controls the body’s physiological responses to stress
-May become aware of a stressor directly or be alerted to the stressor by higher brain centers
-Drives the neuroendocrine response to stress
Cerebral Cortex
-Prefrontal region
-Conscious thought, logic, reasoning, motivation, behaviour, personality
-Stress can create a stage of hyper vigilance, altered cognition, behavioural changes, and focused attention
Limbic System
-Innate survival instinctive behaviours and responses
-Hippocampus and amygdala
Hippocampus
-Medial temporal lobe
-Short and immediate memory and learning
-Stress can impair hippocampal functions making it harder to remember info
Amygdala
-Memory and emotion (fear,anger, excitement) including those related to stressors
-Stress can alter emotional/behavioural responses
Reticular Activating Systems (RAS)
-Collection of CNS areas including Limbic structures and thalamus
-Major sensory input from olfactory receptors, modulates mental alertness, ANS activity and skeletal muscle tone and relays info to the hypothalamus and cerebral cortex via thalamus
-Stress induced over activation stimulates increased skeletal muscle tone (ie muscle tension) and can keep body in state of alertness (trouble relaxing/sleeping)
Hypothalamus
-Both a neural and endocrine organ
-Major regulator of ANS both sympathetic and parasympathetic responses
-Secretes releasing (RH) and inhibiting (IH) hormones that regulate the secretion of other endocrine gland hormones involved in the stress response
Other functions of hypothalamus
-Sensitive to physiological stressors that could affect homeostasis and the health of the body cells
-Detects changes in blood and CSF chemistry, temp and pressures
-Receives input from higher brain centers
-Receives input from central and peripheral receptors
-Regulates ANS (relative balance of sympathetic NE/EPI) and PNS (ACh release)
Stress affects the ability of
-Cerebrum, Limbic system, RAS, and hypothalamus to process information accurately
Chronic activation of ___ stage may lead to
Resistance stage
-Allostasis or even Allostatic overlaid depending on the factors affecting the individual
General Adaptation Syndrome (GAS)
How our body responds to a stressor
Dr Walter B Cannon
-Stress causes physiologic and/or psychological strain on homeostatic balance
-Described the fight or flight response
-Now called the fight, flight or freeze response
Dr Hans Selye
-Stress is a non-specific biological phenomenon resulting from an external or internal environmental change in homeostasis
-Described GAS - the neuroendocrine system response to stress
Cannon and Selye
Considered the modern fathers of the study of the stress response and the effects of stress on homeostasis
Selye proposed
That 2 main factors would determine the nature of the individuals response to a specific stressor
Selye’s 2 main Factors
1) The specific event or environmental stressors (Eg is this an acute or chronic exposure to the stressor)
2) The conditioning of the individual experiencing the stress (Eg internal factors such a genetic predisposition, age, gender, or external factors such as previous exposure, life experience, diet, social supports) = ability for individual to cope with the stressor
GAS describes the
Neuroendocrine response to stress
GAS 3 Stages
1) Alarm Reaction ( fight or flight )
2) Resistance Reaction ( Allostasis/adaptation/Allostatic overload)
3) Exhaustion stage (Allostatic overload)
The Fight or Flight response is initiated by the
Sympathetic nervous system part of autonomic nervous system
Main Neurotransmitter released by F or F
NorEpinephrine
Fight or flight response is also called the
Alarm reaction
The alarm reaction is a __
GAS, survival
The resistance reaction is both
An endocrine and neuro response
GAS: Alarm Reaction
-Fight or flight response
-hypothalamic neural response
-usually only response needed to quickly return to homeostasis
-acute stressor stimulates the hypothalamus to release the neurotransmitter norepinephrine
-small amount of epinephrine is also released
GAS: Resistance Reaction
-During prolonged stress responses
-The alarm stage hypothalamic norepinephrine mediated neural response is reinforced and maintained by the addition of the (^hypothalamic endocrine hormonal response)
-Beginning with release of corticotrophin releasing hormone secretion (CRH)
-CRH initiates the hypothalamic pituitary adrenal axis (HPA)
-HPA response to stress —> ACTH will stimulate increased cortisol secretion from adrenal cortex
-At same time hypothalamus will continue to directly stimulate the adrenal medulla to release epinephrine to reinforce NE effects
-Resistance stage is noted for mobilizing glucose from its reserves leading to hyperglycemia
GAS: Exhaustion stage
-Should the stressor overwhelm the body’s resources = exhaustion stage
-As resources needed to survive a chronic stress are depleted clinical manifestations of a disease process
-Allostatic overload
Exhaustion phase manifestations
-May be physical (Eg muscle fatigue, headache), chemical ( Eg type 2 diabetes/hyperglycaemia, weight gain or loss, amenorrhea) or psychological/behavioural (Eg sleep disturbances, mood changes, habit changes)
Hypothalamic pituitary adrenal (HPA) response
-Negative feedback system
-Physiological effects of the increased release of each hormone should feed back to the initial hormonal regulator (hypothalamus) to decrease its release once the desired physiological effects have achieved the desired homeostatic balance
HPA and cortisol
-During normal everyday body functioning, once the cortisol physiological responses have occurred, the hypothalamus wound decrease its release of CRG and subsequently decrease the levels of ACTH and cortisol back to normal
-But if the individual is in a state of constant real or perceived stress, the hypothalamus keeps the HPA axis active, and cortisol levels and BG levels remain high
Prolonged stress and CRH
During prolonged stress CRH from other peripheral sources (such as immune cells) also stimulates cortisol
Sustained high level of blood cortisol levels are associated with
A variety of stress related disorders
Sympathetic Overdrive
Sometimes HCP refer to individuals with a very pronounced sympathetic fight or flight response
Been used to describe crystal meth users
Alarm Stage Pathway Neuro
-FAST F or F response by SNS —> releases NE
-Hypothalamus —> SNS —> catecholamines —> NE + EPI —> visceral effectors (target cells) —> F or F response
Alarm Stage Hormonal Pathway
Hypothalamus —> NE —> Stimulates adrenal medulla —> Sympathomimetic hormones —> Epi + NE —> visceral effectors (target cells) —> prolong F or F response
NE Stimulates
-Many target organs, including the adrenal medulla which stimulates to secrete hormone Epi to help sustain the acute sympathetic NS responses if necessary
Both NE and EPI are
-Neurotransmitters and adrenal hormones
-Hypothalamus makes lots more NE than EPI (80% NE vs 20% EPI respectively)
-Adrenal medulla makes lots more EPI (80% EPI vs 20% NE)
Physiological Effects of NE and EPI
-Increase perfusion/mobilize resources (Eg glucose) to organs vital to survival
-Those deemed non vital to survival have perfusion decreased
Response Time of Neural and Hormonal Responses
Neural -msec
Hormonal - minutes
-alarm reaction is SNS response evolved for survive thus begins in milliseconds
Resistance reaction pathway
-adaptation/allostasis
-Slower HPA axis response
-Low level alarm stage activity continues, plus additional neuroendocrine adaptation to prolonged stress via HPA axis begins
-Helps to maintain mobilized defenders; keep the stress response going although at a slightly lower level
What is the HPA axis
-The neuroendocrine hypothalamic pituitary adrenal axis (HPA) —> hypothalamic hormones —> pituitary hormones —> target endocrine gland hormones —> body organs respond
Main HPA Pathway
CRH —> ACTH —> cortisol —> physiological stress responses of target tissues
Other Resistance Reaction Pathways
GHRH —> hGH —> IGFs —> physiological stress responses of target tissues
TRH —> TSH —> T3/T4 —> physiological stress responses of target tissues
ACTH and glucose
Adrenal cortex —> cortisol —> gluconeogenesis
hGH and glucose
Liver —> IGF’s —> Glycogenolysis
TSH and glucose
Thyroid gland —> T3/T4 —> increased use of glucose to produce ATP
EPI and glucose
Pancreas —> glucagon —> glycogenolysis, gluconeogenesis
CRH also stimulates
The cerebral cortex and limbic system responses to stress which can keep the F or F stage inundating the adrenal gland
Stress response and BP
-Stress also stimulates hypothalamic posterior pituitary—> ^ antidiuretic hormone (ADH) secretion —> ^ renal water retention + decreased urine output + ^ blood volume —> ^ BP
Resistance response time
-Takes several minutes to begin because all that transport of hormones takes time to travel through the blood stream to its target cells, bind to its receptors, and then stimulate the next endocrine gland or final target cell
-Can last for days, months, even years as long as the body keeps supplying the resources (glucose, energy, protein, lipids) to make the hormones and the resultant body cell responses
Resistance stage also called the
-Adaptation stage
-Can result in a change to the hypothalamic set point ie. allostasis to occur
The adrenal gland is often called the
Stress gland
Why is the adrenal gland often called the stress gland ?
-Cortisol is the major stress hormone made by the adrenal cortex
-The adrenal medulla makes the synpathomimetic hormones EPI and NE
-both mimic SNS responses
Cortisol
-Is a glucocorticoid
-A steroid hormone made by the adrenal cortex that affects blood glucose levels
-When the body is under stress, cellular energy consumption increases in all the cells that are stimulated to respond to stress (those vital organs)
-One if the major metabolic effects of cortisol is to mobilize energy stores to increase blood glucose
Epinephrine
Stimulates the pancreas to secrete hormone glucagon
-Glucagon stimulates the liver to release glucose (from hepatic stores)
Stress increased __ levels
Stress increased cortisol, EPI, and glucagon levels leading to increased blood glucose (hyperglycemic effect)
Normal BG is
4-7 mmol/L
-regulated by glucagon and insulin = 2 pancreatic hormones that work in opposition to eachother
Glucagon _ BG
Increases
Hepatic release via glycogenolysis
Insulin _ BG
Decreases BG
Stimulates glucose uptake by liver hepatocytes, skeletal muscle and adipose cells for storage (glycogenesis) during stress, insulin levels drop
Epinephrine _ BG
Increases BG and decreased insulin
Also stimulates increased glucagon which stimulates increased BG (more hepatic release)
Cortisol _ BG
Increases
Prolonged stress and Diabetes
Prolonged stress from any cause can exacerbate manifestations in a patient with Type 1 or 2 DM because causes hyperglycemia
Stress Related Disorders are Due To
-Dysregulation of the normal stress response
-The SNS and HPA responses are too prolonged and essentially cause wear and tear to many body tissues
-Stress response highly individualized so will manifest different to a specific stressor
Examples of body effects to stressors
-Chronic hyperglycemia: damages endothelial cells lining blood vessels, increases risk of cardiovascular diseases and decreases WBC function
-Norepinephrine stimulates vasoconstriction of dermal and renal arterioles which increases systemic BP and decreases renal perfusion (blood flow)
The release of CRH starts the
Resistance stage HPA axis
-Helps promote the initial SNS response
-Also increases release of more NE
Which Organs are Affected by NE Stimulated Smooth Muscle Contraction
-I.e vasoconstriction
-Kidneys
-A decrease in renal blood flow stimulates renal secretion of renin, triggering activation of the RAAS: ^ renin —> ^ angiotensin + ^ aldosterone system
Angiotensin 2
-Potent vasoconstrictor which can cause systemic vasoconstriction in many organs such as the cerebral or coronary arterioles and the renal arterioles
Aldosterone
Stimulates renal sodium and water retention and potassium excretion, which could affect F and E balance and increase both blood volume and BP
F or F saliva
Flow decreases
F and F skin
Blood vessels constrict, chills and sweating
F and F heart
Beats faster and harder
F and F stomach
Output of digestive enzymes decreases
F and F muscles
Become more tense, trembling can occur
F and F eyes
Pupils dilate
F and F lungs
Quick, deep breathing
F and F bowels
Food movement slows down
F and F blood vessels
Blood pressure increases
Clinical Manifestations to NE mediated SNS Physiological stress response
-Dry mouth
-Pale, shiver, cold hands and feet
-Rapid, bounding pulse
-Stomach upset, indigestion, lack of appetite, constipation
-Lack of bowel sounds
-Twitchy or sore muscles, shakiness, trembling
-Fatigue, altered sleep patterns
-Tunnel vision
-Complaints about bright lights (in ER)
-Rapid almost gasping breathing
-Headaches
-HTN, angina, TIAs, atherosclerosis, CAD, PAD
Blood vessel diameter and stress
If vital = increase blood flow
If non vital = decrease blood flow
PsychoNeuroImmunology
-Researchers have noted strong interrelationships between neural, endocrine and immune function = PNI
-Alterations of one system often affects the normal function of another
-PNI relationship helps to explain why perceived or real stressors can make us sick more often and keep us sick longer
How does PNI = sickness
-By triggering the release of stress chemicals NE, EPI, cortisol and histamine
-Chronic stress causes dysregulation of the neuroendocrine HPA axis leading to abnormal and prolonged elevation of cortisol levels
Cortisol is key …
Mediator of the body’s physiological stress response, including immune defence
2 examples of the PNI in action
- Acute Stress Effects
- Chronic Stress Effects
PNI Acute Stress Response
Individual develops a cold —> HPA activated —> stimulates short term increase in cortisol levels —> cortisols pro inflammatory effects promote acute inflammatory response —> innate WBC destruction of microbes —> individual feels better
PNI Chronic Stress Effects
RRC NS develops a cold + stressful assignment —> sleep deprived—> disrupts the body’s normal circadian rhythm —> HPA chronically activated —> stimulates prolonged increase in cortisol levels —> cortisols anti inflammatory effects suppress acute inflammation response = innate and T cell mediated immune system function decreases —> student can’t shake that cold
Cortisol is both an
Anti inflammatory and pro inflammatory mediators depending on source, location, and duration of its secretions
What is used for treatment of inflammation
Prednisone & hydroxycortisone are used as anti inflammatory drugs
- decrease T cell and innate immune responses
During acute short term stress
Local effects
-proinflammatory activated innate immune responses —> acute inflammatory response —> wound healing —> no deficits
During chronic prolonged stress
Systemic effects
-anti inflammatory: decrease Th1 function —> decreased T cell and innate immune responses —> decreased immune response to viral infections, neoplasms
-proinflammatory: ^ Th2 function —> ^ B cell responses —> ^Ab production & ^ risk of hypersensitivity & autoimmune disorders and ^ mast cell degranulation—> ^ histamine effects —> risk of allergic responses
Th1 helper T cells
Release cytokines that activate cytokines T cells, NK cells and macrophages
Th2 helper T cells
Release cytokines that activate B cells to undergo morphological change, become plasma cells and the begin secreting antibodies
