Wk 7: Human Anatomy & Physiology

• SNS: fight or flight response, relax lungs, dilate eyes
• PNS: rest and digestion, vagal nerve & vagal tone often considered, slows heartbeat

• Acetylcholine (ACh)
• Epinephrine & Norepinephrine: adrenergic receptors (alpha and beta), alpha adrenergic receptors located in vasculature, GI tract.
• Beta adrenergic receptors located in heat, salivary glands, smooth muscle, and adipose tissues.

• Not: in addition to release from adrenal glands, SNS also triggers release of norepinephrine from nerve terminal with some spill over.
• Wide ranging location of receptors allow wide ranging effects of ANS.

• Blood borne chemical messengers
• Produced by endocrine glands and other organs and cells (eg heart, immune cells)
• Act on target tissues with specific hormone receptors

• Steroid hormones: synthesised from cholesterol. Carried by protein. Long lasting effects. Long half life.
• Adrenal cortex hormones: glucocorticoid (cortisol) and aldosterone
• Gonadal hormones
• Protein hormones: chains of amino acids
• Short= thyrotropin releasing hormone (TRH)
• Long= growth hormone (GH)
• Amines: derivatives of amino acids
• Catecholamines: epinephrine (E), Norepinephrine (NE). High impact but tend to be short lived
• Thyroid hormone

• Circadian rhythms: 24 hour rhythm guided by internal clock and by external cues
• Negative feedback: hormone inhibits release of its releasing factor. Stops release of itself at some point

• Hypothalamus (brain- pituitary (brain)- adrenal gland (torso)
• Activated in response to stress and results in the release of glucocorticoids that serve to regulate the physiological stress response.
• A way of shutting down stress process.
• Hormonally mediated activity, so slower than neurally mediated stress responses.

H secretes releasing and inhibiting factors:-corticotrophin releasing hormone (CRH): produced by neurons in paraventrivular nucleus of hypathalamus. Acts as neurotransmitter and neuropeptide.Luteinizing hormone releasing hormone (LHRH)Thyrotopin releasing hormone (TRH)Growth hormone releasing hormone (GHRH)Growth hormone inhibiting factor (GHIF)Dopamine

• Separated into anterior and posterior
• Posterior pituitary:
• Oxytocin: milk ejection, uterine contractions during labor
• Role in bonding
• Vasopressin: antidiuretic hormone

• Anterior pituitary:
• Connected to hypothalamus via system of blood vessels known as hypothalamic-hypophyseal portal system.
• Adrenocorticotrophic hormone (ACTH): secreted by corticotrophs; derived from POMC, cleaved by CRH into ACTH, beta endorphin and other peptides

CRH turns the other molecules into something else like ACTH

• Adrenal medulla: secretes epinephrine and norepinephrine (catecholamines) (relevant to SNS)
• Adrenal cortex: secretes glucocorticoids, mineralocorticoids, and sex steroids (relevant to HPA)

• Up to 95% of secreted cortisol is bound to large proteins including corticosteroid binding globulin (CBG) and albunim, and carried in the body through the blood. (needs to be unbound for it to work)
• Enters all tissues: passes through parotid gland to saliva; through kidney to urine and through blood-brain barrier.
• Salivary cortisol is unbound (biologically active)
• Adrenal steroids have receptors in every nucleated cell:
• -MR (stronger affinity) compared to GR (low affinity)
• After binding, receptors moves into  nucleus and regulate gene expression

• 1. Metabolic and diurnal functions (sleep, metabolism). Highest wake up then going down, spikes after food
• Driven by signal and hypothalamus
• Highly sensitive to negative  feedback control
• 2. Stress functions: secretion enhanced by input from amygdala
• Negative feedback less effective

• During stress, numerous effects:
• Permissive: GCs present before stressor, prime response
• Stimulating: Increases in GCs enhance effects of first wave hormone response
• Suppressive: increase in GCs rein in stress-induced defense reactions
• Preparative: modulate response to subsequent stressor.
• Enhance SNS effects on cardiovascular stress response
• Increase circulating glucose
• Overall suppress immune response, but permissive on initial activation

Acts as a break

• Hippocampus activates hypothalamus which releases CRF, goes to anterior pituitary to release ACTH, goes to adrenal cortex and releases cortisol. 
• Cortisol in addition to effects on tissues, also has negative impact on anterior pituitary and hypothalamus.
• 

• Wake level and before sleep. (If slope flat, due to constant stress)
• Average 24 sample
• Urine: accumulation of cortisol in urine

• Total daily cortisol
• Overnight/24 hour cortisol
• Diurnal cortisol rhythm
• Morning rise
• Response to acute stress
• Sensitivity tests
• -> dexamethane (synthetic glucocorticoid) give it to them, see what happens when give cortisol
• -> how much less cytokines blood releases when GC is added.

• The immune system generally serves to:
• Discriminate self from non-self
• Destroy and clear foreign substances
• Ignore self, possibly destroy altered self (tumor cells)

• Antigen= any substance that can be identified by the immune system
• Pathogen: microorganisms that can cause disease when they enter the host
• Phagocytosis: ingestion of matter by cells

• Innate: Fast, non specific. Phagocytosis, inflammation
• Adaptive: slow, specific. Recognised by B and T cells

• Also known as leukocytes
• 3 types
• 1. Granulocytes:
• Neutrophils: 50-70% of circulating WBC. Phagocytosis and activation of bacterial mechanisms.
• Eosinophils: 1-3% killing antibody-coated parasites.
• Basophils = <1%% of circulating WBC
• 2. Monocytes 1-6% of circulating WBC
• Early immune response including phagocytosis and antigen presentation.
• Macrophages are mature monocytes in tissue
• Dendritic cell: antigen uptake in peripheral sites. Antigen presentation in lymph nodes
• 3. Lymphocytes:
• 1. Natural killer (NK) cells= 5-10% of lymphocytes: plays role in innate immunity against virally infected cells
• B cells= 10-15% of lymphocytes
• T cells= 75-80% lymphocytes
• Helper T cells (CD4)
• Cytotoxic T cells (CD8) kills the bacteria
• Called t cells because produced in thymus

• Immune cells communicate with each other and with other cells by releasing soluble proteins called cytokines.
• Many different types of cytokines, produced by many different types of cells, with wide variety of biological effects, target cells, receptors, and molecular structures.
• Produced during innate and adaptive immune responses, serve to mediate and regulate immune and inflammatory responses
• Generally, cytokines are produced briefly and locally, in a self limiting manner.

• Cytokines are extremely potent, activity needs to be carefully regulated
• Typically produced rapidly and have short half life, inherently limiting effects
• Activity is modulated by:
• Receptor antagonists
• Cytokine binding serum proteins and/or soluble receptors
• Other cytokines with antagonistic effecrs
• Cytokine receptor expression.