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