L17 Thyroid Hormones Flashcards
LO2: desc chem struc of thyr horms and mech of prod, stor and sec.
-biosynth thyr horm- iodine uptake Ag conc grad. Iodine from diet only.
Thyr horms cont lot iodine. Follic cells conc diet iodine (20-50x) as colloid store. Iodine activ to reactive form by peroxidases enz. Binds iodine to modif tyrosine, 3 iodine added to T3, 4 to T4. Perox sensit to carbimazole, if not work oblit gl with radioac iodine accum= destruc. Reactive iodine assocs with tyr rich TG. Prot containing iodothyronines then stored as colloid. Oxid of iodine prods iodinating species= iodinating tyr s/c in TG= MIT and DIT. Coupling of DIT with MIT or DIT forms T3 or 4 in the TG. 10x more T4.
-TG- large GP rich in tyr. Synth in ribos- glycosylated on ER cisternae and transloc to Golgi for pack to sec vesics, stored as colloid, a scaff from which thyr horm synth occs. When need rel endoc by pseudopodia to colloid vesic then proteolysis of TG to rel T3/4 which diffuse to circ.
-T3/4- both synth from tyr on TG- tri-iodothyronine and tetra-iodothyronine. At apical surf of follic cells TG iodinated to T3/4. Thyr horms fat sol. Sec determ by TSH. T3/4 stored as part of TG, sev months worth.
-T3 more potent than T4 but shorter t1/2. More T4 prod. When reach periph targ cell, an iodine rem from T4 to make T3. T4 in circ as longer t1/2. Comb with plasma prots mainly TBG, rarely alb and pre alb. Under 1% free. Oestrogen dur preg incr synth TBG= less T3/4 in circ as more bound= more TRH and TSH= more T3/4 prod so free levs return norm but tot amnt in blood incr. Physiol reac act caused by T3. Pass X cell mem, cause resp then brok down.
-tot conc T4 100nM, T3 2nM. T4 binds plasma prots greater affin so protec from breakd. Free conc T4 20pM, T3 8pM. T4 half life 8 days, T3 2 days. Conc changes rel slowly. So check deranged prod over long period.
-inactiv thyr horms- T3/4 deg by em iodine in liver and kidn. T4 used to treat hypoth, easier to maint blood conc.
-T4 conv to T3 by rem 5’ iodide. Rem of 3’ iodide prods inactiv revT3 can bind T3 Rs w/o stim= block eff of T3.
LO3: desc how activ of thyr gl contr.
-hypoth regul of TSH- thyr horm neg feedb regul by hypothalamic pit thyr axis. TRH tripep from dorsomedial nuc of hypoth (stress and low temp incr rel), trans in hypoth pit portal sys and binds Gq/11 Rs on pit. PLC sig= incr Ca causing exoc of TSH From ant pit thyroptropes . TSH rel low amplify pulses diurnal rhyth high overnight. TSH GP trough systemic circ to thyr gl. Binds TSH R on basolat of thyr follic cell. = incr uptake by iodine transporter on basolat= more horm prod and colloid. T3 and lev direc inhib rel of TSH and TRH, when high med feedb short loop to pit, long loop to hypoth. When low no inhib.
TSH R activ of thyr gl= stim all steps in thyr synth and rel. iodine uptake by Na/I transp. Prod and rel TG. Prom of thyr growth as incr vasc, size and no follic cells.
-if low T3 and 4 then persis TSH rel= enlarge. If TSH stim not due to low T3/4 but due to fault then still get enlargem. Enlarge could be overprod T3 and 4 also.
-TSH action- acute effs (min/HR)- sim synth, stor and sec T3 and 4. Chronic (days)- growth and dev follic cells, more colloid, goitre.
-TSH narr norm range, sensit to alt T3/4. 17 yrs onwards: low 0.2, high 3. Approx 1.5mlU/L, range 0.4 to 4 mlU/L in iodine suffic pops. Much above 3 need investig non urgent, hypothyr can be 9/10 urgent.
LO4: desc effs of thyr horm on cells of bod.
-thyr horm range physiological procs. Modulator not all or nothing. Role in growth and dev esp NS. Deranged func in 5% pop. Horm der from tyrosine. Backb- iodinated and modif= thyroxine. Thyroxine R ubiquitous, up reg BMR.
-gen effs thyr horms-
Incr BMR- incr no and size mito, incr O consump and heat prod, incr nutr use.
Stim most metab paths- catab more than anab (lipolysis, glycolysis, glycogenesis, proteolysis). Stim gluc upt and metab, stim mob and oxid FA, stim prot metab.
Prom norm growth and dev of tiss- partic brain in kids. Incr synth specif prots.
Incr responsiveness of tiss to sympathetic NS (Na) and var horms (metab and repro).
-tiss specif effs thyr horms-
NS dev (birth an pub) and functioning (ad)- incr myelinat nerve fibres and neuron dev. Incr speed reflexes. Incr ment activ (alertness, emot tone, mem). Low= cretin. Thyr horm req for dev cellul procs of nerve cells, hyperplasia cortic neurons and myelinat.
CVS- incr cardiac output. Direc eff on heart musc and potentiates eff of Na.
Skin and subcut tiss- incr t/o prot and GP. Low= lax skin.
Direc eff bone mineralisation and incr synth heart musc prot.
-hypoth= cretinism in newborn. Sev ment retard, coarse feats, protruding tongue, short stat, delay sex dev, revers if tx in few wk, screen all newborn assay for TSH and T4.
-Indirec effs as T3/4 stim horm and neurot R synth in eg heart musc and GIT. Incr activ.
-MOA- T3/4 X PM and interac with specif high affin Rs in muc or mito. Have 10x more affin for T3. Bind to horm bind Dom= conf change= unmask DNA bind Dom. So complex binds DNA incr transc cert genes. Incr prot synth stims oxidative energ metab and prods incr specif func prot= incr activ and energ demand.
LO5: desc conseqs of under and over sec thyr horms.
-hyperthyr- incr BMR, excess heat, skin prob, poss heart arrhythmia. Incr sympath and CNS activ (GIT,CNS). Direct eff on CVS.
-hypoth- decr BMR, cold, weight gain, decr GI activ, slow think, slow HR, subcut tiss lack tough. Decr SNS adn CNS activ. Direct eff on CVS and subcut.
-hyperthyr rare in kids adn diffic spot as high BMR anyway. May mature earlier but not more.
-hyperthyr sign adn symp- heat intol, incr sweat, warm moist hands. Weight loss as lip and prot. Tacky often irreg- incr cardiac output. Incr bowel movem, incr appet. Nervous, irrit, emot. Hyper reflexive eg flapp tremor. Exophthalmos as accum adip Ben eye, comp nerve can cause optic neuropathy. Goiter as incr follic and colloid. Init try carbimazole then rem. Physic and ment hyper. Skel adn cardiac myopathy= tired, weak, breathless. Osteoporosis.
-Maj cause hyperthyr- graves dis- 1% pop, 10/1 male to fem. autoimm Ab stim TSH R.
Tx- carbimazole- inhib incorp iodine to TG by inhib peroxidases. Radioac iodine. Surg.
-hypo sign adn symps- sleepy, cold, dry hands, weight gain, decr cardiac output, Brady, constip, mood swings eg anx and dep, poor conc/mem/ init, odema eg myxodema dry firm waxy swell skin adn subcut, dry skin, brittle nails, hair loss. Goitre as low T3/4 incr TSH driving thyr follic but not prod suffic horm. Tired and lethargic. Musc weakness, cramps and ataxia. Dry flaky skin. Deep voice.
-Maj cause hypo- hashimoto dis. 1% pop 10/1 fem to male. Autoimm destr thyr follic and prod Ab blocks TSH R. Treat oral T4 100-200ug/day. Check dose corr by meas TSH.
-tx for hashimoto or idiopathic hypo- T4 dose that causes loss signs hypo, no sign hyper, norm pit prod TSH.
LO1: desc locat and struc of thyr gl.
- thyr gl just under larynx. Ductless alveolar gl base of neck, diffic palate unless enlarged. Wraps rnd trachea below cricoid cartil. 2 lobes connec by isthmus. 20g And 2-3cm across. Abn growth goiter.
- thyr follic. Thyr gl func is format and stor thyr horm. Sec unit is follic- cub epith colloid centre. Epith polarised- transporters and chains basolat diff to apical, specif transp, tight juncs. Colloid= 30% thyr mass, conts TG- imp for thyr horm synth and sec.
- black dark st cell in CT btw follies is C (parafollic) cell sec calcitonin. Follic 0.02-0.3nm.
- blood supp sup and infer thyr arts. 30-60ml per min! Enlarged can reach 1000ml/min. Audib Steth. Sup, mid and infer thyr veins. Rich lymphat sys. S and PNS innerv abund. Sympathetic stim= incr sec thyr horm (minor role in overall regul).
- recurr and super laryngeal nerves inv in speech, careful if rem thyr.
