Endocrine System Study Guide PDF

Study Guide Endocrine System (Week 11) A. Briefly describe the basic types of intercellular communication 1. Types of communication i. Endocrine = hormone released from cell into the blood to have a physiologic effect on distant target ce...

Study Guide Endocrine System (Week 11) A. Briefly describe the basic types of intercellular communication 1. Types of communication i. Endocrine = hormone released from cell into the blood to have a physiologic effect on distant target cell(s) ii. Paracrine = hormone released from cell into the interstitial fluid to have an effect on a nearby target cell(s) iii. Autocrine = hormone released from cell into the interstitial fluid to have an effect on itself 2. Components – We’ll go into more detail on each of these separately, so they are just listed here i. The hormone ii. Transport proteins iii. The receptors B. Briefly describe the concept of the hypothalamo-hypophyseal axis (also known as the hypothalamo- pituitary axis) 1. Releasing (or inhibiting) hormone released from hypothalamus i. Hypothalamus receives input from internal and external stimuli ii. Biological clocks influence release from hypothalamus (not discussed, but just recognize things like Circadian rhythm do influence this) iii. Hormones released from hypothalamus have a direct influence on anterior pituitary 2. Tropic hormone released from anterior pituitary i. Stimulates target gland 3. Hormone released from target gland i. Generally inhibits anterior pituitary by negative feedback (a) Decreased tropic hormone release ii. May stimulate or inhibits hypothalamus by positive or negative feedback C. Describe the factors which ultimately determine the biological effect of a hormone 1. Synthesis and release of hormone by endocrine cell results in FREE hormone in the blood i. “Free” just means it is not bound to a protein 2. Free hormone can have three key fates i. Bind to a protein carrier (a) Non-specific (a) Example – albumin (i) Albumin binds to LOTS of different molecules, including various hormones (b) Specific (a) Example – Thyroxine-binding globulin (TBG) (i) Binds to thyroid hormone (c) REMEMBER – Most of these proteins are manufactured in the liver (a) If the liver doesn’t work properly, we will not have these proteins available for transport and “protection.” The consequences of this vary. (i) In some cases, this may mean greater free hormone, thus more biological effects  (ii) In some cases, this may mean faster metabolism of hormone, thus fewer biological effects ii. Be metabolized by various enzymes (a) Degradation in the blood (b) Degradation by other tissues (e.g., in the kidney or liver) (a) This often then leads to elimination from the body (urine or feces) (c) Be transformed into another hormone (a) Example – Angiotensin I is converted to Angiotensin II by ACE iii. Bind to a receptor on the target tissue 3. Upon binding to a receptor, the hormone will have its biological effects i. Biological effects can vary by cell type (i.e., recognize an endocrine hormone has MULTIPLE targets, as opposed to a single tissue type) (a) For example, cortisol has multiple different effects (i) In bone, cortisol turns on osteoclasts (b) In muscle tissue, cortisol (i) Decreases glucose uptake (ii) Increases protein degradation ii. This includes stimulating or inhibiting the cells which produced it (a) Example – Cortisol in the plasma can enter the anterior pituitary, which will then release a different hormone (ACTH), which will have an impact on the adrenal cells which produce cortisol D. Briefly describe how protein binding influences how long a hormone is in the bloodstream 1. Half-life = a measure of how long a hormone (or drug, toxin, etc.) is in the bloodstream i. The time it takes for half of the hormone to be removed from the bloodstream 2. More protein binding means a longer half-life (i.e., a longer duration) i. Example – Thyroid hormone is >99% bound to proteins, and therefore stays in the blood for days after being made 3. Less protein binding means a much shorter half-life (i.e,. a shorter duration) i. Example – Epinephrine and ADH are both minimally protein bound (a) This means they are removed from the blood stream in a matter of minutes (b) This means that the physiologic effects of these hormones will be short lived (a) Think about when you stop exercise – your heart rate will be dramatically reduced in a matter of minutes (sure, it may not go all the way back to resting, but that is because metabolism remains elevated – the main point here is that it does drop quickly once we stop exercising, because we drastically reduce the Epi + NorEpi released, and whatever is in our bloodstream is degraded quickly). E. Describe the concepts of upregulation and downregulation of hormone receptors, and the consequences of this 1. Upregulation – cells produce more receptors i. This allows more sites for a hormone to bind to (a) This increases the physiologic effects ii. Examples – aerobic exercise causes muscle cells to upregulate insulin receptors (a) This allows more insulin to bind to muscle cells, which ultimately allows more blood glucose to enter cells  (a) Insulin triggers the cell to put more glucose transporters on the cell membrane, which allows more glucose to move into the cell (b) This ultimately keeps blood glucose levels lower and reduces the risk of Type II diabetes mellitus 2. Downregulation – cells produce fewer receptors i. This means that there are fewer sites for a hormone to bind to, which lowers the overall physiologic response ii. Example – sedentary behavior causes muscle cells to downregulate insulin receptors (a) This means LESS insulin can bind to muscle cells, which leads to fewer glucose transporter molecules on the cell membrane (b) This ultimately lets less glucose into skeletal muscle cells, which elevates blood glucose levels, and increases the risk for Type II diabetes mellitus F. Selected Endocrine Gland Functions 1. Briefly describe the relationship between the hypothalamus and posterior pituitary i. The hypothalamus produces ADH and oxytocin ii. These then move into the posterior pituitary iii. The posterior pituitary then releases these into the bloodstream iv. This differs from the anterior pituitary (a) Remember, with that system the hypothalamus produces RELEASING (or INHIBITING) hormones, which then go to the anterior pituitary, and then the anterior pituitary produces and secretes TROPIC hormones) 2. Briefly describe the effects of thyroid hormone i. NOTE - we use thyroid hormone as an example of how a hormone is regulated, can have multiple effects on different tissue, and how various types of endocrine dysfunction can occur ii. Bone growth iii. Increased glucose absorption AND breakdown of glycogen iv. Increased metabolic rate v. Increased cardiac output 3. Describe adrenal gland function, including the effects of cortisol i. Two different components, under different control (a) Adrenal cortex (a) Three different zones, each producing different hormones (the three names are listed below, but do NOT worry about remembering the specific names of each zone, just recognize what hormones are produced in the adrenal cortex and what influences them) (i) Zona glomerulosa - makes mineralocorticoids (controls mineral balance) 1. Main hormone produced = aldosterone 2. Controlled by = Angiotensin II (i.e., Angiotensin II causes aldosterone to be released) (ii) Zona fasciculata – makes glucocorticoids (controls glucose balance, amongst other things) 1. Main hormone produced = cortisol 2. Controlled by = ACTH (from the anterior pituitary)  (iii) Zona reticularis – makes androgens (sex hormones) 1. Controlled by = FSH and LH (from the anterior pituitary) (b) Adrenal medulla (a) Controlled by sympathetic nervous system (b) Produces epinephrine and nor-epinephrine ii. Cortisol has MULTIPLE effects (a) Normal physiological function, including (but not limited to) (a) Reduces inflammation (b) Slows down fibrosis (and thus delays healing) (c) Reduces skeletal muscle protein synthesis (d) Redistributes body fat (e) Decreases glucose update (b) Recognize that all of the above are normal, physiological responses (a) So, an abnormally LOW or HIGH levels of cortisol for prolonged periods will have major detrimental physiological effects! (i) Examples 1. Immunosuppression 2. Bone loss (leading to osteoporosis) 3. Skeletal muscle mass loss a. Decreased muscular strength b. Decreased muscular endurance c. Impaired posture 4. Impaired connective tissue strength/function 5. Alteration in body shape 6. High blood glucose (thus, increased type II diabetes mellitus risk) (ii) ALSO recognize that long term immune-suppressive therapy has these same effects!!! 1. So, taking corticosteroid drugs for long-term management of immune- related diseases may be essential to managing the disease, but comes with substantial side effects, as described above G. Describe the endocrine system’s role in calcium homeostasis, including Vitamin D metabolism i. BIG PICTURE (a) Parathyroid gland senses low calcium levels (a) Remember, we need calcium for skeletal and cardiac muscle contraction! (b) Parathyroid gland releases parathyroid hormone (a) Directly increases release of calcium from bone into the bloodstream (b) Directly increases calcium reabsorption from the tubular system in the kidneys (c) Indirectly increases dietary calcium absorption from the small intestine, by activating Vitamin D (c) If calcium levels are high, then thyroid gland (NOT parathyroid gland) releases calcitonin (a) Calcitonin helps create a net calcium deposit into the bones (i) “CalciTONIN TONES the BONES!” (ii) This calcium in the bones does two things: 1. Provides structural support  2. Serves as a storage bank for calcium that can be released into the blood when needed ii. The details (a) Calcium receptors exist in parathyroid gland, thyroid gland, and kidneys (and elsewhere) (b) Our skin has a vitamin D precursor in it (don’t need to know/remember the name, but its 7-dehydrocholesterol) (a) UV light exposure causes this to become VITAMIN D3 (also known as cholecalciferol – but don’t memorize that term) (i) We can get Vitamin D from our diet, but it’s a minimal source – sunlight exposure is more important!!!!! 1. So, limited sun exposure means limited Vitamin D3 – even with a good diet! 2. BUT, there is lots of individual variation! (c) Vitamin D3 then gets metabolized by the LIVER into another form (a) Various names for this metabolite – don’t worry about them… but just so you can follow what is going on, let’s call it 25-hydroxyvitamin D3 (d) 25-hydroxyvitamin D3 then goes to the KIDNEY where it gets made into two forms (a) An inactive form (don’t worry about the name) (b) An active form called CALCITRIOL (i) When blood calcium is low and/or when parathyroid hormone levels are high, more calcitriol is made!!!! (e) Calcitriol then: (a) Increases the amount of calcium absorbed by our intestines (i) So, this raises blood calcium levels 1. Some of this calcium is absorbed by the bones 2. Some of this calcium remains in the blood (b) Increases the amount of osteoclast activity (Remember, parathyroid hormone also does this) (i) This means bone matrix is broken down, and calcium is released from bone (ii) So, this also raises blood calcium levels H. Describe the three main types of endocrine hormones 1. Amine hormones i. Derived from the amino acid tyrosine ii. Includes (a) Catecholamines (b) Thyroid hormone 2. Peptide and protein hormones (may be classified separately or together) i. Structure (a) Peptides = short chains of amino acids (b) Proteins = longer chains of amino acid with a specific folding structure ii. Includes (a) Hypothalamic hormones (b) Pituitary hormones (c) Digestive hormones (d) Hormones involved in calcium homeostasis  3. Steroid hormones i. Require cholesterol for synthesis ii. Generally produced by the (a) Adrenal glands (a) Cortisol (a glucocorticoid) (b) Aldosterone (a mineralocorticoid) (b) Kidney (a) Precursors to vitamin D (c) Gonads (a) Testosterone (b) Estrogen iii. Lipid soluble (a) Can penetrate plasma membranes to work on receptors INSIDE the cell (b) Can be transmitted through skin (a) This means one can put them into a cream and rub them into the skin iv. Since they are all closely related to one another (at the molecular level), this means that a single enzyme can influence the balance between them (a) Example – Aromatase (a) Aromatase can convert (i) androstenedione to estrogen (ii) testosterone to estrogen (b) Aromatase inhibitor drugs can be used to stop this reaction from happening, so the body produces less estrogen (i) This is valuable in stopping estrogen-dependent cancers, like breast cancer I. Describe the two major types of endocrine pathology, and how these develop 1. Types of endocrine pathology i. Hyperfunction – which can result from: (a) Too much hormone produced (b) Too many receptors (upregulation) (c) Overly activate physiological response following hormone-receptor binding (a) ii. Hypofunction – which can result from: (a) Not enough hormone produced (b) Not enough receptors (downregulation) (c) Underactive physiological response following hormone-receptor binding J. Differentiate primary vs. secondary endocrine dysfunction 1. Primary – dysfunction at the level of the endocrine gland, such that it is not producing a normal amount of hormone in the presence of normal physiologic stimulus i. Hyperfunction example – A thyroid tumor is causing the thyroid gland to produce too much thyroid hormone ii. Hypofunction example – Autoimmune disease is destroying the thyroid gland, and not it cannot produce enough thyroid hormone 2. Secondary – dysfunction at the level of the anterior pituitary or hypothalamus, which then causes other glands to have hyperfunction or hypofunction  i. Hyperfunction example – the anterior pituitary is releasing too much TSH (a) This would then cause the thyroid gland to produce too much thyroid hormone (b) In other words, the thyroid gland is only doing what it is told to do by the anterior pituitary, but there is nothing inherently wrong with the thyroid gland ii. Hypofunction example – the anterior pituitary is not releasing enough TSH (a) This would then cause the thyroid gland not to produce enough thyroid hormone (b) So, the thyroid gland is capable of producing sufficient thyroid hormone, but it is not getting the message to do so 3. Clinical notes i. Determining if an endocrine disorder is primary or secondary is usually necessary to clinically manage the condition (ie, get to the “root” of the problem) ii. This can be done through different clinical testing procedures (a) EXAMPLE – ACTH stimulation test (a) Patient has low plasma cortisol levels (b) Synthetic ACTH is provided to patient (i.e. injected into patient) (i) This SHOULD stimulate the adrenal cortex to produce cortisol (c) Plasma cortisol levels measured again (i) If cortisol levels stay low, it means the adrenal cortex is not able to produce cortisol, despite the presence of ACTH (i.e., primary adrenal disease – although there is some nuance behind that) (ii) If cortisol levels increase, it means the adrenal cortex is capable of producing cortisol (so it is healthy), but the anterior pituitary simply is not producing enough ACTH to stimulate the adrenal gland 4. Summarize the different major causes of endocrine dysfunction i. Neoplasia (a) New tissue formation which is able to secrete endocrine hormones, and thus have a physiological effect on the body (a) Key message – tumors can be functional, and the hormones they secrete can cause pathology!!! (b) So, tumors (cancerous or non-cancerous) can cause endocrine dysfunction! (b) Forms of neoplasia (GENERAL – not specific to endocrine system) (a) Malignant (cancer) (i) Invades nearby tissue (ii) Spreads to distant places in the body (where it then invades other tissue) (b) Benign (i) Does not spread and does not invade (ii) HOWEVER, it MAY or MAY NOT cause harm (iii) Examples below are just to show that benign tumors CAN cause harm, but are not specific to the endocrine system dysfunction 1. Example – Non-harmful benign tumor a. Lipoma – a “fatty tumor” beneath the skin which does not affect function b. Mole – a non-cancerous mole on the skin 2. Example – HARMFUL (pathologic) benign tumor a. Meningioma – a benign brain tumor  i. Does not invade other brain tissue or spread elsewhere, BUT… ii. Does compress the brain and cause neurologic signs and symptoms b. Uterine fibroids i. Do not invade other tissues or spread elsewhere, BUT… ii. Causes bleeding, pelvic pain, compresses the bladder (c) Ectopic tissue (i) Tissue develops in an abnormal location in the body (ii) Examples 1. thyroid tissue may form outside the thyroid gland, such as in/near the tongue (and produce thyroid hormone) 2. parathyroid tissue can form in the pharynx (and produce parathyroid hormone) (c) Examples of neoplasia causing endocrine dysfunction (a) Pituitary adenoma – a tumor of the anterior pituitary gland, which produces growth hormone and causes gigantism (i) Fun fact – the world’s tallest man, Robert Wadlow, had this condition and grew to be 8feet, 11 inches tall 1. He died at age 22 (b) Small cell lung cancer – secrets ACTH ii. Autoimmune (a) Immune cells may attack cells to decrease function (a) Example – Hashimoto’s disease (i) A specific type of antibodies attack the thyroid gland (ii) Since the thyroid gland is being destroyed, there is less tissue to make thyroid hormone (b) Immune cells may stimulate cells to increase function (a) Example – Graves disease (i) A specific type of antibodies bind to TSH receptors on thyroid tissue 1. Thyroid gland then starts making thyroid hormone 2. So, it’s not just TSH from the anterior pituitary telling the thyroid gland to make thyroid hormone, but also these antibodies are telling it to make thyroid hormone iii. Iatrogenic (induced by medical care – we don’t have a video on this, but hopefully it makes sense)) (a) Example – providing a patient with excessive corticosteroids or excessive insulin (b) Example – removing or disabling a gland (c) Note – Iatrogenic may be intentional OR accidental (a) Intentional example – putting a patient on immunosuppressive therapy to treat an autoimmune disease, but this does knowingly cause side effects of endocrine dysfunction (which are unavoidable) iv. Infectious / inflammatory (a) Inflammation influences hormone production v. Genetic mutations (a) Hormone mutations  (a) A change in the hormone structure influences its affinity to bind to its receptor, carrier proteins, or be metabolized (b) Receptor mutations (a) Increased affinity between receptors and hormone (b) Decreased affinity between receptors and hormone (c) Mutations may be (a) Hereditary factors (b) Congenital (Random mutations we are born with) (c) Acquired (We develop them with age, potentially due to environmental exposures or just random changes in our DNA) vi. Metabolic / enzymatic alterations (a) Increased cellular responsiveness to binding with receptors (b) Decreased cellular responsiveness to binding with receptors (a) Example – Type II diabetes mellitus (skeletal muscle cells no longer respond as much when insulin binds to its receptor) vii. Nutritional / precursor deficiency (a) If a certain nutrient is needed for hormone production: (a) A lack of it will limit production (i) Example – Iodine is necessary for thyroid hormone production (b) An excess of it MAY cause an overproduction of that hormone (i) Example – Excess iodine leads to excess thyroid hormone production