Physiology (Endocrine) Flashcards

Question

Hormone secreation

Answer 1

1. Basal Secretion - always being secreted at low levels 2. Stimulated secretion (tonic) - stimulated by different things to secrete hormone Secrete hormon from pool of prescuror hrmone into the blood - Secretion can be tonic or basal Example - Insuline secretion is basal and glucose stimulated

Answer 2

Have a chemical sensor that increases or decreases secretion - BUT not electrical = not like nerves

Answer 3

Pulses may have different periodicity - Flucuation of homrone in the blood can be stocahctic (random) OR can be periodic Example: 1. Circa-horal - every hour 2. Cia-dian - Every day (Ex. Ciacadian rhythm - Corisol + testostrone) 3. Ci-Trintan - Every month (Ex. menstral cycle)

Answer 4

Active fraction of hormones for celular action and feed back - Often Amine and Polypeptide hormones because they are water soluble (have a shorter hald life) (EXPPTION is insuline like growth factos bound to IGFBP) In the lab you should measure free hormone but that is not always possible - If you measure total hrmone and there is a carrier protein abnormality the total hormone may not refect the free hormone

Answer 5

Fraction of hormones that are biund to carrier protein largest fraction of hormone) - Hormones that are protein bound are cleared more slol from circulation by the liver and kindeys (have a longer half life) (ex. thyroid + steroid) Bound and free fractions of hormone are in equilibrium

Answer 6

Steroid and thyroid homrones = circulate bound to carrier proteins because they are not water soluble Example - 1. Thyroglobulin bins to T3 and T4 2. SHBG bines to testostrine and E2 3. CBG for cortisol 4. Non-specific Albumin and pre-albumin EXCEPTION - mineracortoid steroids don't have a carrier (Ex. aldostrone)

Answer 7

Hormone ats as ligand on hormone receptor - Only a small fraction of circulating hromone is taken up by the target tissue - Bulk of clearance is dne by the liver and kidneys - Have many kinds of enzymatic reactons (Ex. Hydolysis + Oxidation + Hydroxylation) --> allows hormones to be cleated by the liver? - Smal fraction is extreted intact in urine or feces Have: 1. Agonist 2 Partial Agonist 3. Antagonist ***Can be based on binding seperatley

Answer 8

Most hormones have another hormone that regulates their secretion - Interaction between hormones = Feedback - Most organs secrete hormones AND wil scerete asecond ormoen or a byproduct that will regulate the first hormone Two types: 1. Stimulatpry (Trophic) - Hormones that stimulates the secreation of another hormone 2. Inhibitory - Hormone tha inhibits the secretin of another hormone

Answer 9

A trophic hormone inducdes the secretaion of a second hormone which in turn inhibits the secretionn of that FIRST hormone - Taregt releases a hromone that tells intital cell to stop making the hormone - Increase in Homrone A leads to increase in Hormone B which inhibits production More common

Answer 10

Amplifies abundent signals Target cell makes substance to tell the initial cell to make more hormone - Increase in hormone further increases producton loop Can lead to runaway affect

Answer 11

Pituity - Secretion hormone that regulates other endocrine glands + tissues

Answer 12

ALL regulates by multiple hromones from diffreent places

Answer 13

1. Hypofunction 2. Hyperfunction 3. Hormone release resistce syndromes

Answer 14

Overall - Hormone Deficeincey Primary - the primary (or target) gland itself is defective (Ex ample - primary gland is destroyed by autoreactive lymphocytes such as in Hashimoto or Addison) - Deficney syndome of target - Example - thyroid not making thyroid hormone BUT signal from pititary is fine (occurs in hypothyroidism) Secondary - The trophic hormone in the pituitary us defcetive (pituitary is not sending signal to tissue) Tertiary - The trophic hormone in the hypothalumus is defcetive

Answer 15

Overall - Hormone excess (runaway product of organ) Primary - the primar (target) gland itelf is hyperctive (Ex. Graves) Secondary - The trophic hromone in the pititary is over produced Latrogenic/Fictious - Administartion of synthetic hormones (causes hormone exces) - Intentially (by a physican) - Iatrogenic - Without Physcian knowldge - Ficticous

Answer 16

Hormone is produced in substantial qunatities but is inactve or has reduced activity - Not issue with hormone production but repsponse in target tissue is low Can develope resistnce because: 1. The hormone itself is abnormal 2. The receptor for the hormone is blocked by antibodies 3. The receotor is abnormal 4. Issue downstream of receptor that blocks hormone activity Example - Diabetes --> have the same amount of insulin hormone but it doesn't have enough activity = don't cause glucose uptake (Check clide 24 because cut off at bottome)

Answer 17

Hypothelumus regulates pititary 1. Growth hormoone releaseing homrone 2. Somatostatin 3. Corticotropin releasing hormone 4. Gonadotropin releasing hormine 5. Thryotripin releasing ormone 6. Prolactin Inhibiting Hormone (dopamine)

Answer 18

Pituitary - Sits at the base of the brain - Connected to the hypothalymus - Sits behind the sinus of the nasal passage - Highly vaculirized - When have tumor/englargment of pituitaruy then you have space occupencey issues (have improtant things nearby that pitautray can put pressure on (Example - optic chiasm = lose vision OR pressure on vessels nearby OR have functional loss if press on cranial nerves nearby

Answer 19

Stall (infundibulum) is composed of: 1. Mediam emince of the hypotheluumus 2. Stem that arises from it 3. Pars tueralis of the anterior hypophyis Stalk + Posterior lobe = neurona; in origin Anterior Lobe = secretes most pituitary hormones Overall - pituitary is very small

Answer 20

Each pituitary homrine is made by each type of cell Somatotrophes = Gorwth Secretion Lactotrophes - PRL-secreting Corticotrophes - ACTH-secreting Gonadotrophs - LH-FSH secreting Thyrotropes - TSH-secreting

Answer 21

Pituitary somatatrophes scerete growth hromone --> act on the main tissue (Example - developing oranisms need linear forowth and development) - Function is meidated by acting on liver --> get induction of GH factor 1 = has effect GH = harder to capture on tests --> look at IGF1 levels because they are mre stable and representtative of GH axis

Answer 22

Have Excess of growth hormones before bones are fused = have linear growth Ex. Tallest perosn = gigantism

Answer 23

Too much growth hormone as an adult = get growth of hands and feetor facial featires or internal organs

Answer 24

Polypetide hormone secreted from lactotropes Plasma hhald life of 50 minutes Have several circulating forms of Prolactin --> explains discerpinsies between bioassay and immunoasay - Immunoassays do not always reflect the biologic sitiuation Made by the pititary Growth hormone like (don't 100% know what it is doing) - Most recgnized for effect on lactation but could have effect on other things (affects lactogens and islets in pancreus) Is elevated during seizure

Answer 25

Main function - stimulates milk synthesis in post partum period - Induces the final differentation of milk cells that results in casein synthesis - ALSO has a controceptive effect by inhibiting pulsatile secretion of HnRH = have no midcyle surge = no ovulation (decreased reproduction in women when scereted) Have excess PRL in women causes oligomenorreha/amenorrea/galactorrhea Excessl PRL in men can cause decreased libedo + galactorrhea + erectile dysfunction

Answer 26

SKIPPED SLIDDE

Answer 27

Thyroid is the largest endocrine gland Synthesizes Thyroid homrones (T3 and T4) Thyrod homrones = contain 60% iodine (makes them unique) - used for clincal diognosis and managment Function of thyroid hormones: 1. Promote growth and development 2. Promote Brain development 3. Regulate energy and heat production 4. Regukate metabolism + Body Temperature + Thermogensis 5. Are regulated within tissues of the body by deiodinases

Answer 28

ALL cells have a TH receptor --> Can take up T4 --> converts T4 to T3 in cells

Answer 29

Located at the base of the neck - Highly vacsularized

Answer 30

Big filled circles --> Cells surround the follciles of the stored Thyroid Homrone - When you mobilize TH or have a disease = see loss of the prefomred store = have no bubbles

Answer 31

Thyroid Homrone synthesis requires: 1. Iodine 2. Storage of preformed Thyroid Hormone into colloids --> some TH will be secreyed into the blood and some some are mobilized by thryoglobulin and is released to Thyrocytes

Answer 32

Thyroid = targets the pituitaru Thyroid Stimulating Hormone = stimulates Thyroyd homrone to increase --> Increase T3/T4 --> Homrones go to body --> have negative feedback loop in pititary to decrease TSH - Hypothamuc factir = regulates TSH

Answer 33

1. Normal dveelopment + growth + nueronal differentiarion 2. Metablism regulation + energy regulation 3. Amphibia metamorphisis 4. HR 5. Body temperture 6. GI system speed/function 7. Muscle contraction 8. Skin and bone turnover

Answer 34

Dirven by immune --> immune destoys thryoid cells = get hypothyroidsm - Have fatigure + Weight gane + dry skin Causes Hashimotis (most common cause of Hyothyrodism) - Have autoimmune destruction of thrypod (seen by thrmphocyte infiltration) - Reealse natgen --> get Autoantibodies (anti-TPO) NOT care not casual but evidnece of immune autoreactivity (measure then in clinic)

Answer 35

Overactivation of Thyroid = Graves disase Antibody is made by autoimmune bind to and stimulate Thryoropin (TSH) receotir on the surface of thryoid folicle cels --> thyrocytes to open --> get increase in Thyroid hormone NOT regulated by piuitary - Causes Increased metabolsim --> Get swoellen thyroid + wiht loss + Increase HR + can;t sleep - Have no stored TH in glands on pateints with Graves

Answer 36

Hypothelymas --> sents CRH to Pititary --> Pituitary send ACTN to the Adrenal Gland --> Adrenal cland makes cortisol and androgen

Answer 37

Location - Abive or medial to the upper poles of the kidney ; Retroperitenal Weight - 10g Made up of: 1. Corext (outter) - 90% of weight 2. Medula (inner) - 10% of weight - Medula and cortex secret different hormones Lots of blood goes to the gland

Answer 38

1. Mineralic - saly/water/BP levels 2. Glucocortcoid - stress response 3. Androgen

Answer 39

Main Hormone Prodcuce din teh zoma glamerulosa A signeficant percentage (30-50%) cicuate free onces secreted - remaining majority circulates while bound the albulin and in part to CBG --> short half life (15-20 minutes) Aldostrone = rapidly inactivated in the liver A small amount of free aldostrone filters in the urine and can be eaisliy quantatied

Answer 40

Function - maintain normal Na+ and K+ concentrations and normal extracellular fluid volume Target - Kidneys + Colone + Salivary glands + sweat glands Aldosterone freely crosses the plasma membrane and combines to a specific mineral corticoid receptor in the cytosol --> The steroid-receptor complex moves into the nucleus where it alters the transcription rate of several genes ( Example - affects Na/K ATPase pump gene --> Na+ is taken up into the cell and exchange for K+ or H+ --> Na+ then moves to the other pole of the cell where it is transported into the extracellular fluid, helping maintaining its normal composition and volume)

Answer 41

Uses the renin-angiogenstin system Not Directly regulated by the pituitar BUT regulated by the kidndeys sense of water pressure and volume Kidneys make renin --> Renin goes to the body --> Get increase in angiogenstin 2 in lungs --> stimulates aldostrone production in the adrenal gland Have feedback loop of B and Na/K levels

Answer 42

Synthesized by two pathways (both use 17-alpha hydroxylation_ Main pathay - startes by converting preognenolone to 17-OH pregnenoline --> then converted to 17-OH progestrone --> 21-hydroxylase then converts 17-OH progestrone to 11-deoxycortisol Alternative pathway - converts first pregnenolone to progesterone --> convered to 17-OH progesterone --> 21-hydroxylase then converts 17-OH progestrone to 11-deoxycortisol

Answer 43

Specifc enzymatic diferences that can cause blackages to the pathway --> get defetive cortisol synthesis Enzymes lead to clinical aparent blocks = salt wasting of verilization in kids

Answer 44

Physical stress (ex. surgery + flught + hypoglycemia) AND physological stress quickly stimulates the production of CRH + ACTH and therefore cortisol (within minutes) - Increase the pathway to increase cortisol during stress - Helps body respond to stress IF the stress is prolonged then the circadium rythim is abolished Prior treatmemt with high-dose glucocortorids abolshes the stres responsle of ACTH and cortisol

Answer 45

After release from cortical cells --> majority f cortisol (90) enters the circulaion and binds to corticosteroid-binding globulin (CBG) (75% bind) BUT some will bind to albumin (15%) --> CBG bound goes to cells in the body --> binds to glucocortoird receptors --> Affects stress response - 10% of circulating crtisol is free - Bound hormone is inactive ; free is active Cortical = metabolized in the liverC

Answer 46

Have low levels at midnight (Cortisol (and ACTH) nadir is MN to 2am) --> increase levels in early morning (ncreases to about 7am; half of the total daily cortisol output is produced in this period) --> decrease levels over the course of the day - Cortisol increases in response to eating + exercise + stress Rhythm over the course of the day is disrupted in jet lag or sift workers --> re-establishing to circadium rhthym is important for avoiding issues with cortical excess

Answer 47

Cortisol enters into the cell and binds to a glucocorticoid receotor located in the cytosol --> Hormone reetor complex enters the nuceus --> in nuceus the complex binds to a cysteine rich reginon -- chealtes zinc --> assumes a zine fincer conormation (cis action) - Hormone - reeptor Complex can also interact with other transcription factors (Ex. Nf-Kb) END - have change in gene expression

Answer 48

Overall - Have lots of action on different organs - Cushing - Excess Cortisol - Addison - decrease in Cortisol - Things happen if have decrease of increase in cortisol

Answer 49

HE SKIPED SLIDE

Answer 50

Feedback loop from HPA axis Hypothlymus --> signla to pituitary --> stimulates pituitary to make FSH --> Promotes target gonads to make egg or sperm + to make sex hromone in target cells

Answer 51

Left image - see exersions of glucose and insulin - Normal - Increase glucose after meal = increase nutrients = stimulates islets to increase insulin = puts glucose into target tissue - Diabetes = can't maintain fasting blood glucose --> have excerson of glucose that are pronounced (diabetes have higher glucose) Right - Theoretically shows that Type 2 diabetes pateints can have higehr insulin levels than controls but still have high glucose

Answer 52

Have increase in glucose despite increase in insulin - Example of resistnce to hormone Type 2 = can have higher insulin that conrtols but the glucose level is still high - Depends on when you measure over course of disease - at the late stage = production of insuline is lower relatuve to normal production

Answer 53

NO insulin production

Answer 54

Glucose sensing by Beta-cells leads to physiologic Insulin Secretion Pancreatic beta cell secrete insulin --> beta cells sense glucose level in blood that reflects nutrient state (glucose ___ in beta cell is not regulated) - Intracellularly - glucose is phospholated = traps glucose in the cell = Increase ATP:ADP ratio as glucse increase --> keep increase phosphylation = increase ATP:ADP = get depolarization of the memebrane --> voltage gated Calcium chanel opens --> get insulin exocytosis of preformed insulin - Nueroendocrine cell - stimulated by electrical depolorizatiionn --> release trasniitted -> insulin goes to target tossues

Answer 55

Shows that when you eat = glucose increases = insulin increases in blood - Increase is deteclable within minutes Release of insulin is 1st phase ; ALSO have linger chronic secretion driven by constutive secretion

Answer 56

Insulin is well studied Pre-polypeptide that loades on self ; has intramilecular di-sulfide bonds --> Insulin pre-polypeptide is cleaved = get cypeptis --> have insulin molecule at A chain and B chain and disulfied bonds

Answer 57

Glucose = stiulates a rapid insulin release Diabetes treatment challenge - try to recopitulate insulin pjarmocologially BUT it is hard to do with one molecule Result - they made a mocleule with long acting (bsal avtivating) and shor acting (covers meal time excersions)

Answer 58

Have long acting and short acting insulin Modify insulun with Polypeptide OR adding a fatty acid chain - Rapid = chnage the order of Pysine and proline residues OR add absorbic acid residuce ---> chnages the charge/interactio time - Long acting = tether to interstitial space by adding fatty acid or double lysine residues

Answer 59

Insulin acts on classicy responsive tissues --> binds to classic receptor on insulin respinsive tissues - Example - Liver modultaes fats When fed = increase nutritent = increase insulin = decrease catabolic porcess/increase anabolic process - fed = synthesize glycogen (NOT making glucose) - fed = modify fat stores glycogen and tiglycerides + NOT release substance Decrease insuline = mobilize stored precursors

Answer 60

Insulin binds to insulin receptor --> recetor triggers many downstream chnages to promote Anobolic porcesses and make GLUT 4 go from inracelular pools to the membrane --> get glucose upatje (GLUT 4 takes in glucose)

Answer 61

List = shows diurgs that promote secretion of insulin (used for decades) -- in the last 20/30 years = have diffreent kinds of drugs that can affect glucose metabolism in different ways --> NOW have meds that work on many pathways that regulate glucose metabolsim = have flexibility in treatmmet NOTE - do NOT memorize drugs

Answer 62

Parathyroid regulates phosphate and calcium hmoeostasis Parathyroid makes Parathyroid hormone (PTH) = regulates blood Calcium

Answer 63

Almost all organs have a "non-clasical" endcrine function - organs secrete substances in an endocrine fashion (have endorine aspects to tissues that are not thought to be classical) Example: 1. Gut hormoans --> act as hormones but thought us settled of system they are acting 2. Heart secretings peptides to regulate action 3. Liver regulates body through IGF1 4. Placenta release peptides Endothelial hormone signaling to otehr tissies crosses over to other settings