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89 Cards in this Set
- Front
- Back
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T4 (Thyroxine) |
primary product of thyroid gland add 4 iodine |
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T3 (Triiodothyronine) |
biologically active form 3 idonie cells use this version (converted from T4) |
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Required for thyroid hormone synthesis: |
1. idoine 2. secretion of TG (thyroglobulin) into follicle 3. Reabsorptionof TG bound thyroid hormone from colloid into epithelial cell to be secreted out |
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Steps for thyroid hormone synthesis |
1.Synthesisof thyroglobulin2.Iodineuptake3.Organificationof TG4.Couplingof iodotyrosines5.Secretion |
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how do we bring iodine into epithelial cell? |
secondary active with sodium (co transport) NIS (sodium iodide symporter) brings it in** basal side |
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What are the following steps of making a thyroid hormone? |
Pendrin transporter (fac diffuser) takes iodine and brings it to lumen TG out into follicle add iodine to tyrosine residue couple together and make thyroid hormone |
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MIT/DIT |
tyrosine with one or none iodine no coupled DIT - some more iodine no couples all go through pinocytosis with T4 and T3 chains too |
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pinocytosis |
takes droplets from colloid and pulling them into epithelial cell thyroglobulin merge with lysosomes or proteosomes, where they get cleaved...left with T3 and T4 then gets secreted via exocytosis |
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Organification and couplng |
“trapping”iodine to thyroglobulin, mediated by thyroid peroxidase enzyme |
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T3 |
DIT + MIT |
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thyroid peroxidase |
drives iodination and coupling of tyrosine residues located in membrane of epithelial cell |
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proteolysis |
thyroglobulin in epithelial cell gets cleaved into 2 peptides release of T3 and T4 in the lysosome |
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lysosome |
thyroglobulin protein gets recycled and any extra gets back to ER (any extra iodine) |
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Thyroxinebinding globulin (TBG)** |
transports synthesized by liver hormone has to come off of TBG and be free to bind to cells bound ones still act as a reservoir |
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Thyroid hormone fast or slow? (opposite of ADH) |
slow with long lasting effects latent periods |
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What converts T3 (active) from T4? |
iodinase removes 5' iodnine D1 and D2 produce the active form of T3 D3 degrades wrong iodine and makes T inactive |
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Where is thyroid hormone released? |
hypothalamic pit. axis |
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What decreases TRH/TSH release? |
negative feedback by T3 excitement, anxiety (symp), starvation dopamine and somatostatin |
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What increases thyroid hormone secretion? |
cold low metabolism |
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TSH increases calcium how? |
increases phospoinositol products to increase CALCIUM (extreme cases) |
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TSH is... |
G-protein coupled cAMP mediated PLC mediated (high conc of TSH) increases activity of NIS transporter** TSH is trophic hormone that increases growth of the thyroid gland** |
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T4 binds to what? |
then D2 converts to T3 bind to intracellular nuclear receptors: thyroid hormone receptors and retinoid x receptors are coupled downstream to become thyroid hormone response elements and increase protein expression |
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Thyroid hormone increases... |
basal metabolic rate of cells o2 consumption heat production mitochondrial activit beta adrenergic receptor expression carb and lipid metabolism vitamin utilization |
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also increases oxidative phosphorylation |
heat expression of cytochromes and Na/K ATPase |
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also increases growth of muscles, bone, and fetal brain development |
maturation of nerve cells in fetal brain and inhibits nerve cell replication (without it can lead to mental retardation) stimulates release of GH, synthesis of enzymes/proteins, bone calcification |
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also DECREASES |
plasma cholesterol** so no thyroid hormone = elevated cholesterol |
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Thyroid hormone - Cardio effects |
increases: -heart rate - CO -cardiac muscle strength |
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Thyroid hormone - Respiratory |
increases:
-resting ventilation -minute ventilation |
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Thyroid hormone - nervous system |
regulates:
-development synaptic firing -wakefulness and alertness (think fetal)** *low levels = mental retardation** |
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Thyroid hormone - muskoskeletal |
more activity via even an small rise in TH |
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Hyperthyroidism |
skinny Caused by: 1. Grave's disease -thyroid stimulating immunoglobins (TSI) bind to TSH on thyroid and activates thyroid gland -LOW TSH levels via negative feedback on hypothalamus and ant. pit. because high amounts of t3 and t4 already 2. thyroid adenoma- tumor secreting thyroid hormone -LOW TSH 3. malfunction of hypo-pit axis increasing function -INCREASES TSH -LOW TSH Goiter - enlarged thyroid gland due to hypersecetion of thyroid hormone *CAN'T be used to differentiate between hyper and hypo -TSH elevated has trophic effects (enlarged thyroid) -t3/t4 can stimulate growth of thyroid glands themselves |
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What two hormones would you want to measure with pt with thyroid issues? |
thyroid hormone TSH (thyroid gland overproducing if low; ant. pit. effed up if high) |
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What are the GI effects of TH? |
high- diarrhea low- constipation |
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primary hyperthyroidism |
thyroid gland is location of dysfunction - graves and thyroid adenoma increased release of TSH |
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secondary hyperthyroidism |
something other than gland produces final endocrine hormone malfunction of hypo-pit axis decreased release of TSH |
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hyperthyroidism symptoms: |
1.Heat intolerance● 2.Weight loss●3.High state ofexcitability●4.Muscle weakness (toomuch protein catabolism)●5.Increasecardiovascular stimulation●6.Fatigue with theinability to sleep●7.Exopthalmos –swelling in the eye orbital causing protrusion |
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hyperthyroidism diagnosis: |
basal metabolic rate oxygen consumption assay of t3 circulating TSH levels to zero (primary) immune measurements to TSI levels (Graves) Clinical observation: goiter and ophthalmic signs |
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Treatment of hyperthyroidism |
surgical removal or gland + hormone replacement therapy radioactive iodine destroys secretory cells of gland antithyroid drugs inhibit thyroid -Thiocyanate,perchlorate, and nitrate - inhibits transport of iodine - Propylthiouracil –peroxidase inhibitor |
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Hypothyroidism |
decreased thyroid hormone levels high TSH levels (because no thyroid hormone around so TRH and TSH will keep going) caused by: Hashimoto's disease - autoimmunedestruction of gland leading to fibrosis and decreased secretion (high TRH level) heritable - defective thyroid or pit., decreased hormone synthesis malfunction of hypo-pit axis iodine def. - endemic colloid goiter idiopathic colloid goiter - normal levels of iodine idoine deficiency caused by endemic colloid goiter idiopathic colloid goiter - normal levels of iodine |
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hypothyroidism Sx |
1.Coldintolerance●2.Weightgain●3.Fatigue,excessive sleeping●4.Speechand memory deficiencies●5.Increasecholesterol → atherosclerosis●10.Depressedcardiovascular (↓ HR, ↓CO)●11.Myxedema– bagginess under the eyes and facial swelling due to excess cellular matrixmuco-polysaccharides increasing in interstitial fluid |
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hypothyroidism diagnosis |
assay of T3 TSH levels elevated above normal decreases BMR goiter and swollen face |
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hypothyroidism Tx |
t4 hormone replacement therapy - very effective |
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T3 is produced by the deiodination of T4 where? |
pituitary thyrotrophs |
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tired, fatigue numbness weight gain high TSH t4 is low |
hypothyroidism primary - result of autoimmune disease (not secondary because high levels of TSH) |
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Clinical case: weight gain cold constipated low t4 high tsp t3 uptake decreased |
hypothyroidism primary (high tSH) hashimotos low t4 causes bad negative feedback look at slide 25 |
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Adrenal Cortex anatomy |
adrenal glands sit atop the kidneys |
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medulla: |
inner region that produces EP and NOREP |
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cortex: |
outer region that produced mineralocorticoids (aldosterone), glucocorticoids (cortisol) and androgens (DHEA) () are just examples go find rex make good sex |
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adrenocortical hormones |
steroid hormones derived from cholesterol |
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DHEA |
form of testosterone androgen |
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Adrenocortical Hormone Synthesis |
get cholesterol into adrenal cortex via lipoprotein to enter cortex cell though endocytosis, and stored as lipid droplet (stored by ACAT) cholesterol ester hydrolase (CEH) frees cholesterol from fat droplet and moves then stAR protein mediates movement into mitochondria |
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adrenal cortex hormone synthesis occurs in? |
mitochondria and ER via cytochrome enzymes -mutation or loss of enzymes leads to accumulation of precursors and redirected intermediates |
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what does the first step of hormone synth? |
generate pregnenolone...hormones not stored in adrenal cortex |
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CRF is identical to CRH |
stimulated ant pit to give us ATCH acts on adrenal cortex to make and release glucocorticoids and androgens (cortisol) aldosterone doesn't get stimulated by ACTH |
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main functions of glucocorticoids |
gluconeogenesis** protein mobilization fat mobilization stabilizes lysosomes |
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ACTH acts through cAMP to (5 things)? |
1. increase pregnenolone 2. increase STAR (pulls protein into mito) 3. increase LDL 4. increase HDL 5. increase size of adrenal gland -LDL/HDL helps to replenish fat droplet because using up cholesterol |
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what do mineralocorticoids do? |
zona glomerulosa aldosterone stimulates kidneys to conserve salt and water |
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Release of aldosterone |
-ang 2 synth and release of prenenolone similar actions as ACTH - increased extracellular K activates voltage gated Ca channels (depolarization) -ACTH has minor effect |
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Aldosterone renal actions: |
•Increases K+ secretion• Increases Na+reabsorption• Increases H+ secretion |
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Aldosterone effects on other locations in body: |
•Sweat glands • Intestinal epithelium •Salivary glands |
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glucocorticoids, androgens, and aldosterone |
use transport proteins glucocorticoids bind to CBG, have long half life |
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what happens when GC binds to receptors? |
•Binds tointracellular GC receptors to“activate”•• Receptor complexes translocate to nucleus • Bind to glucocorticoid responseelements• Increasesgene activation or repression |
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glucose fx = |
1.stress, fasting: maintains blood glucose for brain function 2. .Stimulatesgluconeogenesis in the liver 3.Elevation of bloodglucose inhibits uptake to combat stress 4. Increases growth ofthe adrenal medulla also surpresses secretion of sex hormones (androgen pathway) stress increases ACTH and glucocorticoid release |
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what are anti-inflammatory effects of the adrenal cortex? |
stimulatethe production of lipocortins which inhibit phospholipase A2reducing inflammation -seen when exogenous dose given (not normal response) |
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cortisol and gluconeogenesis |
breakdown muscle, fats, shuttle to liver, make new glucose while protecting and keep glucose store stimulates glycogen synth enzymes to increase gluconeogenesis** |
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effects of androgens in male |
androgenscontrol aspects of male development and reproductive physiology, bone growthconverted to testosterone by testes -androgens produced by testes -DHEA- hair, libido -androstenedione converted to testosterone |
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effects of androgens in female |
most androgens from adrenal gland -hair and libido not in postmenopausal women |
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hyperadrenalism |
excess adrenal hormones (Cushing) |
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Etiology of hyperadrenalism |
1.Cushing Disease: too much ACTH (ACTH dep) over stim adrenal gland 2. Cushing Syndrome: Adrenal cortex putting too much out (ACTH ind) 3. Abnormalhypothalamus - ↑ CRH 4. EctopicACTH secreting tumor (elsewhere in the body) 5. Exogenoususe of corticosteroids |
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symptoms of Cushing |
appearance: fat in thoracic and upper abdomen/cheeks, moon face, acne and excess facial hair -HTN due to excess mineralcorticoids (due to excess ACTH) osteoporosis muscular weakness due to breakdown of muscle protein prone to infection due to decreased lymphoid tissue increased skin pigmentation (ACTH Secreting tumor) |
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diagnosis of Cushing |
measure glucocorticoid try to determine etiology (ant pit. or adrenal cortex) via dexamethasone suppression test slide 42 |
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treatment of hypersecretion |
removal of tumor steroidogenesis inhibitors adrenalectormy |
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primary adrenocortical hypo |
all three zones autoimmune infection, cancer, hemmorhage, adenoma ACTH high |
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secondary adrenocorticalhypo |
hypothalamic insufficient CRH pit insufficient ACTH ACTH low |
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inborn errors in corticoid synthesis hypo |
enzyme mutation genetic disorders 21 beta, 11 beta, 17 alpha ** |
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hyposecretion sx |
•Decreasedmineralcorticoids – hyponatremia, hyperkalemia,low blood pressure • Low blood glucose between meals • Sluggish and muscle weakness • Depression of appetite with ↓ GImotility/secretion • Intolerance to “stresses”, even smallones; "kid in the bubble" |
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Addison's hypo primary disease |
elevated ACTH hyper pigmentation of melanin no increase in cortisol |
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Diagnosis of hypo |
ACTH causing rise in cortisol = issue in ant pit ACTH no rise = adrenal (primary) |
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treatment of hyposecretion |
immediate or death adrenocorticoid admin daily avoid stress |
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Congenital adrenal hyperplasia |
too much growth of adrenal glands, but low glucocorticoids so high levels of ACTH lead to hyperplasia of adrenal gland in these cases (excess growth of adrenal gland) low cortisol
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21 beta hydroxylase |
needed for aldosterone and cortisol, everything going to DHEA and because of high ACTH stimulating star and cholesterol losing salt, water, leading to low volume too much testosterone (hypertensive) |
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11 beta hydroxylase |
no cortisol, aldosterone, corticosterone 11-DOC acts as mineralocorticoid and acts similar in function as aldosterone** so makes DHEA, lots of aldosterone low cortisol moderately hypertensive slide 46) |
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functional unit of thyroid gland |
follicle |
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follicle |
contains epithelial layer and colloid epithelial cubodial, tight junctions -apical: facing colloid -basal: facing blood |
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colloid |
gel like solution of aqueous thyroglobulin |
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protein used to make TH |
thyroglobulin |
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parafollicular cells |
secrete calcitonin |
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blood flow volume controlled via |
adrenergic signalling, vasomotors |
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blood supply regulates delivery of what and what? |
iodine and TSH |
