Stress

How is the prefrontal cortex affected by stress and what can this cause?

decreased activity; decreased decision making abilities and behavioral function

___________________________: •Serves to decrease reproductive function, a non-essential function for survival, during times of stress

(ACUTE) Stress Induced Decreases in Reproductive Function

•A PTSD diagnosis requires manifestation of symptoms including: -Intrusive thoughts/memories -Avoidance of trauma related contexts -Cognitive/Mood disturbances/changes -Hyper Arousal/Reactivity •Symptoms must persist ____________

> 1 month

1. The type of events that can cause PTSD: 2. Types of patients that are at risk for developing PTSD:

- Serious road accidents -Violent personal attacks: Sexual assault, mugging, robbery -Natural Disasters -Combat Police officers, rape survivors, military personnel, etc.

The goals of acute stress response are to increase energy by increasing blood glucose levels, decreasing insulin levels, and mobilizing/relocating fat. Which 5 pathologies can be caused in the long term due to chronic stress response, causing metabolic syndrome?

1. visceral obesity 2. insulin resistance 3. hypertension 4. high trigylcerides 5. low LDL-Cholesterol

What are some common comorbid conditions that occur alongside PTSD?

-Alcohol/Substance Use Disorder -Depression and Anxiety -Hypertension -Asthma -Chronic Pain Disorders

What mediators are involved in stress causing increased Heart rate and blood pressure?

-Catecholamines (NE, epi) -Cortisol -RAAS

What are the mediators responsible for stress responses causing metabolic syndrome?

-Cortisol -Catecholamines -Cytokines

Which mediators are involved in the stress response's inhibition of thyroid hormone synthesis and peripheral activation?

-Glucocorticoids (i.e. cortisol) -Somatostatin (STS) -Cytokines

A diagnosis of PTSD requires manifestation of symptoms including:

-Intrusive thoughts/memories -Avoidance of trauma related contexts -Cognitive/Mood disturbances/changes -Hyper Arousal/Reactivity must persist for >1 month

How can chronic stress affect reward system?

-May lead to depression and cravings for food/drug

How can chronic stress affect cognitive and executive function?

-Suboptimal Performance and Planning -Pursuit of wrong decisions

•Pheochromocytoma = adrenal medulla tumor What happens/what are the symptoms?

-catecholamine hypersecretion -sympathetic system hyperactivity -hypertension -sweating -palpitations

•As with all negative feedback systems, pathophysiologic changes can occur in the stress response system when:

-when a component of the system fails -when the neural and hormonal connections are dysfunctional -when the stimulus (stressor) is prolonged or intense and overwhelms the system

Mechanisms by which the stress response affects the cardiovascular system? 1. Heart: _____________ increase HR and Cardiac Output 2. Kidney: ____________ increase renin release 3. Vasculature: _____________ increases vasoconstriction; _______________ increases vascular reactivity by increasing alpha-adrenergic receptors

1. Catecholamines (NE, E) 2. Catecholamines(NE, E) 3. Norepinephrine, Cortisol

Chronic stress can lead to a switch from cellular to humoral immunity. This switch can lead to:

1. Increased vulnerability to pathogens •H. pylori, M. tuberculosis, Common cold virus 2. Increased vulnerability to humoral immunity-driven autoimmune diseases • Graves Disease, Systemic Lupus Erythematosus

How does the neuroendocrine stress response (cortisol) affect: 1. energy availability 2. blood pressure 3. non-essential functions

1. Increases energy substrate availability 2. Maintain blood pressure - enhance vascular reactivity 3. Inhibition of nonessential functions - growth, feeding, reproduction

What is the mechanism by which stress response can lead to metabolic syndrome? 1. ____________ of insulin release 2. ____________ in gluconeogenesis 3. ___________ in proteolysis 4. _____________ in lipolysis

1. Inhibition --> increased blood sugar levels, less sugar to cells/absorption, can lead to insulin resistance 2. Increases --> can lead to visceral adiposity and insulin resistance 3. Increases 4. Increases

What are the negative effects of CHRONIC stress-induced decreases in reproductive function for 1. both genders 2. males 3. females

1. Loss of libido and infertility 2. Low LH, decreased testosterone 3. amenorrhea, loss of protective effects of estrogen

What are the three main issues in the female athlete triad?

1. Menstrual disturbances - Amenorrhea; increased NE and cortisol is inhibiting GnRH/FSH/LH 2. Bone Loss/Osteoporosis: decreased estrogen 3. Low energy availability (due to changes in metabolic rate) and disordered eating

How does chronic stress affect the immune system? 1. Impair _________ lymphoproliferation 2. Suppress secretion of ___________________ 3. Delayed _____________ 4. Decreased response to ____________ 5. Switch from __________ to _________- immunity

1. T cell 2. pro-inflammatory cytokines (TNF, IL-1, IL-8, and IL-1) 3. wound healing 4.vaccines 5.cellular to humoral

Chronic Stress leading to increased Sympathetic Nervous System activation and increased HPA axis activation can lead to: 1. Immune system dysfunction 2. RAAS activation (increased BP) 3. sympathetic overdrive (increased HR and BP) 4. endothelial dysfunction What cardiovascular diseases can chronic stress put people at risk for as a result?

1. atherosclerosis 2. microvasculopathy 3. perfusion deficits 4. impaired tissue function

What structural changes occur in the brain as a result of stress? 1. which areas have decreased activity? 2. which area has increased activity?

1. hippocampus and prefrontal cortex 2. amygdala

PTSD PATHOLOGY - What occurs with: 1. alpha receptors 2. norepinephrine 3. HPA axis 4. Amygdala 5. prefrontal cortex

1. increased 2. increased (**so, increased catecholamines PLUS increased alpha receptors = increased sympathetic response_ 3. decreased cortisol, impaired HPA axis 4. increased amygdala activity 5. decreased prefrontal cortex activity

What do glucocorticoids/cortisol do to inhibit reproductive function?

1. inhibit GnRH via negative feedback 2. Inhibit LH and FSH 3. Inhibit estrogen and testosterone production 4. Increase resistance of target tissues to sex hormones

How do Norepinephrine and cortisol affect the immune system during acute stress?

1. norepinephrine and cortisol: -Influence trafficking and function of leukocytes and accessory immune cells 2. norepinephrine -Increase IL-6 --> Degranulation of mast cells and further increases in stress responses **in acute stress, these anti-inflammatory actions can be helpful, allowing you to manage stress even if ill/injured

Sympathetic Activity causes: 1. Eyes 2. Salivary glands 3. Lungs 4. Heart 5. Vasculature 6. Stomach 7. Liver 8. Adrenal medulla 9. Bladder

1. pupil dilation 2. salivation inhibited 3. bronchi relax/increase respiratory rate 4. increase heart rate 5. vasoconstriction and increased blood pressure 6. inhibit peristalsis & secretion 7. stimulate glucose production/release 8. secrete epinephrine/norepinephrine 9. inhibit bladder contraction

What are the two parts of the stress response?

1. sympathetic nervous system 2. neuroendocrine response

How is the hippocampus affected by stress and what can this cause?

decreased activity; issues with memory formation

•During the acute stress response, the body mobilizes energy stores to prepare for "fight or flight" or to restore homeostasis. This function can become pathological if sustained over prolonged periods or if a patient is critically ill by leading to all of the following EXCEPT _____. A. hypoglycemia B. insulin resistance C. high triglycerides D. high blood pressure

A

________________: the process by which the body responds to stressors in order to regain homeostasis.

Allostasis

______________ is "the wear and tear on the body" which accumulates as an individual is exposed to repeated or chronic stress.

Allostatic load

______________ is defined as the cost of chronic exposure to elevated or fluctuating endocrine or neural responses resulting from chronic or repeated challenges that the individual experiences as stressful.

Allostatic load

Response to Survival Threat: Anticipate Adversaries Selective Advantage: ____________________ Contemporary Disease: ____________________

Arousal and Fear Anxiety Insomnia

Which type of stress can lead to an increased vulnerability to humoral immunity-driven autoimmune diseases • Graves Disease, Systemic Lupus Erythematosus

Chronic stress

Which two components of the stress response lead to inhibition of reproductive function?

Corticotropin releasing hormone inhibits GnRH directly; Cortisol inhibits GnRH and LH, FSH, and therefore estrogen and testosterone via negative feedback. Cortisol also increases resistance of target tissues to sex hormones

•The sympathetic nervous system is involved in the immediate stress response. It engages the "fight or flight" response in multiple organs by causing the release of norepinephrine and epinephrine from _____. A. the hypothalamus B. the anterior pituitary gland C. the adrenal cortex D. nerve terminals and the adrenal medulla

D

Response to Survival Threat: Combat Starvation Selective Advantage: ____________________ Contemporary Disease: ____________________

Energy Conservation Obesity Metabolic syndrome

Response to Survival Threat: Combat Dehydration Selective Advantage: ____________________ Contemporary Disease: ____________________

Fluid and Electrolyte Conservation Hypertension

What does Corticotropin Releasing hormone inhibit to inhibit reproductive function?

GnRH (directly)

Mechanisms by which the stress response affects the cardiovascular system? -Heart: Catecholamines increase _________ and _________ -Kidney: Catecholamines increase ____________- -Vasculature: NE increases ____________ •Cortisol increases vascular reactivity by increasing __________________

HR and Cardiac Output renin release vasoconstriction alpha-adrenergic receptors

Which branch of the stress response causes: Increased blood pressure due to increased blood volume?

Mineralocorticoids/aldosterone from adrenal cortex (neuroendocrine)

Which branch of the stress response causes: retention of sodium ions and water by the kidneys

Mineralocorticoids/aldosterone from adrenal cortex (neuroendocrine)

What can cause increased sympathetic activity, impaired HPA axis functioning, and dysregulated activity in brain areas associated with fear/stress response?

PTSD

•_________________: a mental health condition triggered by experiencing or seeing a terrifying event

PTSD

Response to Survival Threat: Combat Injurious Agents Selective Advantage: ____________________ Contemporary Disease: ____________________

Potent Immune Reaction Autoimmunity Allergy

Response to Survival Threat: Prevent tissue strain and damage Selective Advantage: ____________________ Contemporary Disease: ____________________

Retain tissue integrity Pain syndromes Fatigue syndrome

What might be some ways to help PTSD patients control their symptoms?

Sadly there are not a lot of good treatments out there for now. Therapy, anti-depressants, anti-anxiety medications

Response to Survival Threat: Minimize exposure to danger Selective Advantage: ____________________ Contemporary Disease: ____________________

Social Withdrawal Depression

By what mechanism does stress decrease your basal metabolic rate?

Stress Inhibits Thyroid Hormone Synthesis and Peripheral Activation 1. CRH and NE suppress Thyroid Stimulating Hormone 2. Cortisol suppresses TSH and prevents conversion of T4 to T3

What are the steps of the stress response?

Sympathetic Nervous System Response 1. hypothalamus senses a stressor 2. signal travels down the spinal cord 3. adrenal medulla releases epinephrine and norepinephrine HPA Axis/Neuroendocrine response 1. Hypothalamus senses stressor and releases corticotropin releasing factor (CRF) 2. Anterior pituitary releases Adrenocorticotropic Hormone into the bloodstream 3. ACTH travels in blood to the adrenal cortex 4. Adrenal cortex produces and releases cortisol into the bloodstream where it will reach other organs (also will exert negative feedback on hypothalamus and anterior pituitary)

Which branch of the stress response causes an immediate, short-lived stress response?

The sympathetic nervous system

T/F Some stress is necessary to maintain homeostasis.

True

The ________________ stress response involves the HPA axis or the hypothalamic pituitary axis. Main goal is to get cortisol in the bloodstream to respond to stress

neuroendocrine

What are the main functions of the neuroendocrine stress response?

[increase cortisol] -Increase energy substrate availability -Maintain blood pressure - enhance vascular reactivity -Inhibition of nonessential functions - growth, feeding, reproduction

Which type of stress results in: •Increased arousal •Increased contextual memory formation •Increased concentration

acute (this is a healthy response)

effects of acute vs. chronic stress on brain structural changes?

acute stress: changes are reversible chronic stress: lasting changes

Which part of the adrenal gland release epinephrine and norepinephrine during a stress response?

adrenal medulla

Which branch of the stress response is responsible for: -Increasing energy substrate availability -Maintain blood pressure - enhance vascular reactivity -Inhibition of nonessential functions - growth, feeding, reproduction

neuroendocrine

•Goal of Acute Stress: -Increase energy substrate availability •Effects -Increase in ______________ through increases in hepatic gluconeogenesis -Decrease in _____________ and insulin _____________ in peripheral tissues -Increase in fat ___________ and ______________

blood glucose insulin release, insulin sensitivity mobilization and redistribution

Which type of stress can lead to anorexia or hyperphagia?

chronic

which type of stress can lead to anxiety?

chronic

Which types of events can lead to chronic stress?

chronic illnesses both physical and mental or long term challenges

Which type of stress results in: •Anxiety •Suppression of sleep system -Insomnia, loss of sleep, daytime somnolence •Cognitive and Executive Dysfunction -Suboptimal Performance and Planning -Pursuit of wrong decisions •Anorexia or hyperphagia •Depression of reward system -May lead to depression and cravings for food/drug

chronic stress

Increased metabolic rate can lead to destruction of protein and fat but ____________ can cause deposition of visceral adiposity which can also contribute to insulin resistance.

cortisol

The neuroendocrine response involves the HPA axis or the hypothalamic pituitary axis. Main goal is to get ______________ in the bloodstream to respond to stress

cortisol

Which branch of the stress response has a slower, more prolonged stress response?

neuroendocrine response

Stress Inhibits Thyroid Hormone Synthesis and Inhibits Peripheral Activation. This leads to hypothyroidism and can contribute to _______________, ____________, __________________, and other physical symptoms

fatigue, weight gain, emotional changes

Which branch of the stress response causes: Proteins and fats to be broken down and converted into glucose, leading to increased blood glucose

glucocorticoids/cortisol from adrenal cortex (neuroendocrine)

Which branch of the stress response causes: immune system to be depressed

glucocorticoids/cortisol from adrenal cortex (neuroendocrine)

How does the short-term stress response increase blood glucose?

glycogen --> glucose in the liver

A stressor is a change in ______________ (internal or external environment).

homeostasis

In the sympathetic nervous system stress response, signals from the _____________ cause increased norepinephrine and epinephrine (from nerve terminals and adrenal medulla)

hypothalamus

Stress Inhibits Thyroid Hormone Synthesis and Inhibits Peripheral Activation. This leads to _________________ and can contribute to fatigue, weight gain, emotional changes, and other physical symptoms

hypothyroidism

Why can patients with PTSD have trouble with impulsivity or decision-making?

impaired prefrontal cortex/decreased prefrontal cortex activity

Goal of acute stress = ________________

increase energy substrate availability

What things can lead to insulin resistance as a result of the stress response?

increased blood glucose levels gluconeogenesis visceral adiposity

In the sympathetic nervous system stress response, signals from the hypothalamus cause increased norepinephrine and epinephrine (from _____________ and _________________)

nerve terminals and adrenal medulla

Which stress response system produces negative feedback?

neuroendocrine; cortisol exerts negative feedback on the hypothalamus and anterior pituitary

What are some types of stressors?

injury emotional stress career pressures environmental physical/exercise illness

During ACUTE STRESS: •NE and Cortisol -Influence trafficking and function of ______________ and accessory immune cells •NE -Increase _________ --> Degranulation of mast cells and further increases in stress responses

leukocytes IL-6

In the sympathetic nervous system stress response, signals from the hypothalamus cause increased ___________ and _____________ (from nerve terminals and adrenal medulla)

norepinephrine and epinephrine

•As with all negative feedback systems, pathophysiologic changes can occur in the stress response system: -when a component of the system fails -when the neural and hormonal connections are dysfunctional -when the stimulus (stressor) is prolonged or intense and overwhelms the system Leading to?

overactive or underactive stress response

How can chronic stress affect vaccine response?

person under chronic stress may have delayed/reduced response to vaccines

•____________________ = adrenal medulla tumor

pheochromocytoma

How can PTSD affect a person's response to other stressors?

poor response to other stressors

In the ___________________ stress response, •Signals from hypothalamus cause increased norepinephrine and epinephrine release (from nerve terminals and adrenal medulla)

sympathetic nervous system

Which branch of the stress response causes: Change in blood flow patterns, leading to increased alertness/skeletal muscle flow and decreased digestive and kidney activity?

sympathetic nervous system

Which branch of the stress response causes: Glycogen to be broken down to glucose to increase blood glucose

sympathetic nervous system

Which branch of the stress response causes: Increased blood pressure due to vasoconstriction

sympathetic nervous system

Which branch of the stress response causes: Increased breathing rate

sympathetic nervous system

Which branch of the stress response causes: Increased metabolic rate

sympathetic nervous system

How does the long term stress response cause an increase in blood glucose?

proteins and fats broken down and converted to glucose

The _____________ serves to adapt your body to this environmental change to maintain homeostasis

stress response

What types of events can cause acute stress?

surgery, severe trauma, infection, a short-lived threat or challenge.

Why might someone under chronic stress have increased vulnerability to pathogens, i.e. they may get sick more often or not be able to shake an illness

switch from cellular to humoral immunity

What changes occur in the amygdala in response to stress and what can this cause?

the amygdala has increased activity; people will be more irritable, have form more emotional memories

Stress-induced decreases in thyroid hormone serve (functionally) in acute stress to:

• Conserve energy during times of stress -Decreased basal metabolic rate

Stress-induced decreases in thyroid hormone during chronic stress can cause:

•Decreased reproductive function •Decreased immune function •Decreased basal metabolic rate

How can chronic stress affect sleep?

•Suppression of sleep system -Insomnia, loss of sleep, daytime somnolence