Module 3.4 Stress and Disease Flashcards
What are catecholamines and what type of cell receptors do they stimulate?
Catecholamins are hormones ( epineprhine, norepinephrine) that are produced by the chromaffin cells in the adrenal medulla in response to stress. They timulate 2 major classes of cell receptors: alpha-adrenergic (α-adrenergic) receptors and beta-adrenergic (β-adrenergic) receptors.
Circulation catecholamines essentialy mimic direct sympathetic stimulation.
What are the effects of norepinephrine on your body?
Norepinephrine raises BP by constricting smooth muscle in all blood vessels; it dilates the eyes, causes piloerection, and increases sweatgland action in the armpits and palms.
What effect do catecholamines have on the cardiovascular system during a stress response?
- Increased rate and force of contraction
- Peripheral vasoconstriction
Epinephrine enhances myocardial contractility (inotropic effect), increases hart rate (chronotropic effect), and increases venous return to the heart, all of which increases cardiac output and blood pressure. Noreepinephrine raises blood pressure by constricting peripheral vessels.
What effect do catecholamines have on the immune system?
- Catecholamines can modify the number of immune system cells circulating in the blood. Injection of epinephrine is associated with a transient increase in the number of lymphocytes ( T- cells, NK cells) in the peripheral blood. Qualitatively, lymphocyte responsiveness of T and B lymphocytes is reduced.
- Effects of acute elvation of catecholamine levels on the alteration of lymphockyte function are short lived ( 2 hours).
What are glucocorticoids?
Steroid molecules/hormones released by the adrenal cortex (primarily Cortisol) in response to stress . These steroid molecules reach ALL tissues, including the brain, easily penetrate cell membranes, and react with numerous intracellular glucocorticoid receptors.
What effect does stress have on the hypothalamic-pituitary-adrenal (HPA ) axis?
Stressors triggers the hypothalamic-pituitary-adrenal (HPA) axis.
- Initially one becomes alarmed by a stressor that activates hypothalamus and sympathetic nervous system.
- Hypothalamus secretes coticotropin-releasing hormone (CRH), which binds pituitary receptors
- Pituitary cells produce adrenocorticotropic hormone (ACTH)
- ACTH transported to adrenal glands, where then glucocorticoids hormones (cortisol) are released
- Cortison initialtes metabolic changes.
- Overall, cortisol enhance immunity during acute stress but supress immunity during chronic stress because of prolonged exposure and increased concentration
What effect does stress have on growth hormone?
- Growth hormone (Somatotropin) enhances immune function and is involved in tissue repair. GH regulates phagocytic function and possibly antigen presentation.
- under chronic stress, GH can be suppressed.
- When under stress, chronic glucocorticoid stimulation decreases the release of GH from the pituitary gland. Glucocorticoids antagonize the beneficial actions of GH
What effect does cortisol (glucocorticoids) have on Th1 and Th2 cells?
Cortisol:
- supresses Th1 cells, which leads to decreased innate immunity and to the proinflammatory response
- Stimulates the activity of Th2 cells, which leads to an increase in adaptive immunity and the antiinflammatory response.
- The decreas in Th1 activity and increase in Th2 activity is called a Th1 to Th2 shift
- PPL experiencing a Th1 to Th2 shift are more likely to experience allergic responses, infections, and temporary worsening of autoimmune disordrs such as arthritis.
What effect does Cortisol have on glucose?
Cortisol Increases glucose.
- Cortisol reverses the insulin induced supression of hepatic gluconeogenesis, as well as basal levels of cortisol that stimulate the activity of hepatic enzymes responsible for glycogen and glucose production. The increased amino acid uptake into the liver and the increased levels of glucose producing enzymes favor the production of glucose.
Diseases of excess cortisol, cushings disease, produce characteristics of type 2 diabetes.
Explain the relationship between inflammation, cortisol, obesity and the development of type 2 diabetes
The development of diabetes is secondary to cortisol-induced obesity
- increased glucocortidoids/ Cushings Syndrome –> abdominal fat stores
- Active Cortisol generated locally in abd. fat
- active steroid secreted directly to liver
- In vitro insulin sythesis and secretion from the pancrease are inhibited by glucocorticoids
- Hepatic insulin resistance associate wtih abdominal obesity
- Plasma concentration on inflammatory mediators (TNF-a and IL-6) are increased in the insulin resistant state of obesity and type 2 diabetes
- Increased concentration of TNF-a and IL-6 interfere wtih insulin signal transduction. This interference might promote inflammation
What is the relationship between inflammation and the development of type 2 DM?
Proinflammatory cytokines (such as TNF-alpha and IL-6, CRP) interfere with insulin signaling that leads to insulin resistance. Cytokines can also directly affect dysfunction and destruction of pancreatic beta cells.
What is the relationship between cortisol and type 2 DM?
Increased cortisol levels (from chronic stress, dysregulation of the HPA axis) leads to truncal obesity, thin extremities, etc (Cushingoid presentation). There is also the likelihood of HTN, metabolic syndrome and elevated ratio of intra-abdominal fat to non-abdominal fat from the increase in cortisol combined with increase in insulin action
What is the relationship between obesity and type 2 DM
increased nutrient intake causes obesity, which causes increase in glucose in plasma and increase in free fatty acids, which in turn cause reactive oxygen species which leads to pro-inflammatory cytokine formation interfering in insulin signaling
Discuss the relationship between depression and inflammation
There is building evidence that cytokines; particularly interleukin-, has a strong link to depression - so there is a physiologic basis for depression in chronic illness, it is not only psychosocial factors.
Evidence for connecting depression with the sickness/stress circuitry comes from studies in animals and humans. For example, studies of patients receiving interleukin-1 to fight cancer found that they developed severe depression and, vice versa, people with depression have elevated cytokine levels.
What are the effects of epinephrine on your body?
Epinephrine ( short-acting) causes transit hyperglycemia, decreaes glucose uptake in the muscles and organs, and decreases insulin release from the pancreas.
