Stress Physiology
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Transcript of Stress Physiology
Mind/Body HealthRRCC Holistic Health
Spring 2011
Stress ResponseExhaustion stage- hormones don’t get depleted
The stress response becomes more damaging than the stressor- the body spends energy on stress and defense at the expense of growth, reproduction, etc.
HormonesCatecholamines- epi and norepi- act within secondsGlucocorticoids- steroids- cortisol- minutes to hours
HPA axis- CRH (corticotropin releasing hormone) in hypothalamus, ACTH (adrenocorticotropic hormone) in anterior pituitary, glucocorticoids in adrenal
Glucagon- hungry state- mobilizes energy storesProlactin- suppresses reproductionEndorphins and enkephalins- blunt pain perceptionVasopressin (ADH)- holds water in blood Inhibited- reproductive hormones, growth hormones,
insulin
Stress ResponseGlucocorticoids- increase and maintain blood
glucoseGluconeogenesis in liver, amino acid mobilization,
inhibition of glucose uptake, fat breakdownImmune suppression, degradation of wbc’sIncreases blood cholesterol
Why do we need them if natural stressors are acute?Mediate stress response, but also recovery from itAnd prepare for the next one
Stress signatures- each stressor subtly differentSNS and glucocorticoids consistentSpeed and magnitude of both can vary
SNS active in subordinate rat who’s vigilant and trying to cope with a challenge, cortisol more in rat who’s given up
Not all other hormones always activatedTissue sensitivity to hormones also changesPsychological context
Stress and the Heart
Acute stress- HR up, BP up, arteries to mm and vital organs dilate, nonessential arteries constrict, blood flow to kidneys and kidney function downSo why do we pee our pants?Vigilance- HR, blood flow down, vascular
resistance up
Stress and the HeartChronic stress
Hypertension- BP up chronically And small vessels have to work harder to regulate local blood
flow, so they get more muscular, more rigid, raising BP…Left ventricular hypertrophy- blood returns to the
heart with more force, heart muscle thickens Irregular heartbeat more likely Greater demand for blood LV hypertrophy- after age, the best predictor of cardiac risk
Blood vessels- damage at bifurcation points No cell in the body is more than 5 cells away from a blood
vessel, yet the circulatory system is 3% of body mass Inflammatory response, foam cells full of fat Epinephrine increases platelet activity Also mobilizing fat, glucose, LDL cholesterol into bloodstream Vessel damage a better predictor of HD than cholesterol
C-reactive protein (CRP)
Stress and the HeartPlaques
Ischemia- impaired blood flow Angina pectoris- heart, myocardial infarction Claudication- lower body
Thrombus- blood moving with more force more likely to tear the plaque loose Vast majority of MI’s and strokes
Myocardial ischemia- coronary arteries normally dilate in response to stress But in chronic ischemia, they vasoconstrict
The damaged CV system is hypersensitive to acute physical or psychological stressors
Sudden cardiac death- extreme acute stress causing ventricular arrhythmia or fibrillation
Stress and ImmunityThe immune system sorts self from nonselfAcquired immunity
Can target a specific pathogenTakes time to build upNow geared to go after the pathogen, and boosted
with repeated exposureInnate immunity
Saliva, mucosal surfacesCapillary dilation at siteMacrophages, neutrophils, natural killer cells
Cellular StressorsHypoxia- decreased oxygenNutritional imbalance- ex. diabetesPhysical- temperature, radiation, mechanical
trauma, electric shockChemical- poisons, drugs, etc.Infectious- viruses, bacteria, fungi, protozoa,
nematodesGeneticPsychogenic
Local Adaptation SyndromeCellular
immune response
Designed to neutralize, control, or eliminate the offending agent
Inhibited by chronic stress
B and T Cell Formation
B cells- humoral (blood) immunity
T cells- cell-mediated immunity
Both- white blood cells or leukocytes
Both work together in immune response (along with monocytes)
B Cell Activation
B cells make antibodies;some have memory
T Cell Activation
T cells kill infected cells and secrete immune chemicals
Antibody-Mediated Immune Response
B cells secrete antibodies which bind to antigens, enabling Ab-Ag complex to be cleared
B cell antibodies bind to antigens so body can clear them- T cells secrete cytokines which help B cells to mature
Cell-Mediated Immune Response
T cells kill cells with Ag and self Ag
T cells mobilized when they encounter B cells with Ag fragments
Stress and ImmunityThe immune sorting process
Dangerous seen as safe- infectious diseaseSafe seen as dangerous- allergy, autoimmune disease
Multiple sclerosis, juvenile diabetes, rheumatoid arthritis, lupus, etc.
StressSuppresses lymphocyte (wbc) formation and releaseShortens time that wbc’s in circulationInhibits antibody formationDisrupts wbc communicationInhibits innate immunity, suppressing inflammationGlucocorticoids most prominent, but others contribute
Stress and ImmunityAcute stress enhances immunity, particularly
innateMore immune cells in circulation, more at site,
better communication, more Ab’s in salivaGlucocorticoids and SNS both involved
Cortisol (early in a stressor) kills older wbc’s, sculpting stress response, and deploys wbc’s to site of infection
But after about an hour, cortisol and SNS activation starts to dampen the immune response
Why? To bring it back down to baselineThis is part of the recovery from the stress responseAdaptive until chronic stress leads to suppressionPeople with autoimmune diseases (rheumatoid
arthritis, for ex) have glucocorticoid suppression or less tissue sensitivity to cortisol
AutoimmunityOveractivation of the immune system
Steroid treatment- glucocorticoids to suppress immune system
Prolonged major stressors decrease autoimmune Sx in lab rats
But stress is among the most reliable factors in worsening autoimmune diseases
Numerous transient stressors ratchet the system in the direction of autoimmunity
Massive stressors suppress immunity
Stress and MetabolismRapid energy mobilization
Insulin secretion downGlucocorticoids block nutrient transport into fat cellsGC’s, glucagon, epi, norepi
TG’s broken down in fat cells- FFA’s and glycerol in blood Glycogen broken down to glucose Protein to amino acids Gluconeogenesis- glucose made from the amino acids
GC’s block energy uptake into fat cells and muscles Exercising muscles override this blockade
Good for freeing energy in acute stress and normally
Chronic Stress and Metabolism
Inefficient- it costs energy to mobilize energyMuscle wasting- not usually a problem, but
myopathy possible in steroid patientsThe fat and sugar in the blood worsens CVD
And stress increases LDL and lowers HDL
DiabetesThe body’s insulin is insufficient for its
needs, so blood sugar is too high
20.8 million in US have diabetes- 7% of population
Type I- insulin-dependentChildhood onsetLess commonRequires insulin shots
Type II- insulin-resistantAdult (or teen) onsetMore common (90-95%)Diet and lifestyle related- obesityTreated with diet, exercise, meds, insulin shots
Diabetes and the Pancreas
Pancreas makes digestive enzymes, and…Islets of Langerhans in pancreas make insulin
Diabetes and the PancreasInsulin signals “fed
state” and signals body to move glucose from blood to tissues
Underproduction or insensitivity causes blood sugar to remain high
Type I- insulin production genetically impaired
Type II- pancreas wears out and/or insulin resistance
DiabetesRisk Factors
Western dietObesity- largest
factorPhysical inactivity
Early SignsFrequent urinationExcessive thirstCraving for sweets
and starchesWeakness
ComplicationsHeart diseaseStrokeKidney diseaseRetinopathyNeuropathyFoot complicationsSkin complicationsGestational diabetes
2 of 3 with diabetes die of heart disease or stroke
Obesity and DiabetesType 2 DMFat cells distend and respond less to insulinLess glucose and fat taken up- CV damageHormones then trigger fat and muscle to
become more insulin-resistantPancreas secretes more insulinVicious circle, leading to islet cell burnout
and type I DM
Stress and DiabetesMore glucose and fat in the bloodGlucocorticoids make fat cells less sensitive to
insulinStress promotes insulin resistance
Higher rates of major stressors in the three years before onset (of type I)Stress can encourage the immune system to attack
the pancreasStress increases the chances of getting DM,
accelerates its development, and encourages the major complications
Stress and Eating2/3 hyperphagic, 1/3 hypophagicCRH (hypothalamus, HPA axis) suppresses
appetiteGlucocorticoids stimulate appetite
Preferentially for starch, sugar, fatAnd blunt satiation signal of leptin from full fat cells
What’s going on?CRH secreted and cleared faster- seconds
GC’s minutes to hoursAcute stress- high CRH, low GC- low appetiteSustained stress- high CRH, high GC
The CRH overrides the GC- low appetiteRecovery period- low CRH, high GC- high appetite
Stress and EatingSo in acute stress, a few minutes of high CRH,
hours of high GC- appetite stimulatedChronic nonstop stress- high CRH and GC-
appetite suppressionFrequent intermittent stressors
Bursts of CRH, constant GC elevation- munchiesAlso, people secrete GC’s differently- amounts,
and time to return to baselineThe hypersecreters are more likely hyperphagic,
especially for sweetsHyperphagia also more in emotional eaters and in
normally “restrained” eaters
Apples and PearsGC’s stimulate fat storage in presence of high
insulinHigh GC, low insulin = stressorHigh GC, high insulin = recoveryAbdominal fat cells more sensitive
A large WHR (waist to hip ratio) is a better predictor of metabolic trouble than obesityFat released from abdominal fat cells goes to the liver
and is converted to glucose High blood sugar, insulin resistance
Apples, not pears, tend to have prolonged GC responseAnd- the comfort foods and the abdominal fat are
stress-reducers
Metabolic SyndromeAKA “Syndrome X”Cluster of symptoms
HyperinsulinemiaGlucose
intoleranceHyperlipidemiaHypertension
CA not in metabolic syndrome, but patterns of incidence related
These predict each other and major disease outcomes