imissyou419's version from 2017-04-07 02:28


Question Answer
Thyroid glandfound in neck, largest endocrine gland, controls how quickly we use energy, stores iodine, produces T3/T4 and calcitonin
ThyroglobulinHigh MW (660 KD), glycosylated, 2 subunits, ~330 tyrosine residues, harbours carrier protein used to produce T3/T4, found in colloid
IodineNeed ~60 mg per day, Major sources: salt, seafood, dark green vegetables e.g. kelp; important role in production of T3/T4
Iodination and coupling of tyrosine residues in TG takes place atapical microvillus surface of the follicular cell (TPO - thyroid peroxidase iodinates and couples Tg) Iodination (iodinase adds iodines to tyrosine) -> monoiodotyrosine, diiodotyrosine; peroxidase couples mono and di to make T3 or T4
Iodine TrapNIS (sodium-iodide symporter) uses Na+ gradient to transport I- into thyroid cell, 2. Pendrin transports I- into lumen for oxidative coupling to thyroglobulin
Colloidreservoir of material for thyroid hormone production including Tg
How is T3 and T4 brought back into cell?pinocytosis, intracellular enzymes liberate T3 and T4 from thyroglobulin, T3 and T4 come through basolateral side into blood stream (with carrier proteins since it is an a.a derivative that is lipid loving)
TSH action on thyroid cell1. increased activity of NIS (bring more iodine into follicular cells), 2. increased Tg production, 3. increase TPO activity
Thyroid hormone transport, majorityThyroxine binding globulin (TBG), Transthyretin (TTR), Human Serum Albumin (HSA);
majority is TBG;
regulate the bioavailability and half-life of T3/T4, without BPs, thyroid hormones are rapidly cleared from circulation
Explain why 90% of hormone secreted is T4, with 7 day half-life, when T3 is 10x more potentT4 is more stable to circulate, T3 is active form and the conversion of T4 -> T3 is carried out by cell specific deiodinase (D1-D4)
Thyroid hormone action getting into cell1. Serum T4 > T3,
2. T4 -> T3 in cytoplasm by D2. (if it encounters D3 then it is converted to T2 or rT3 which is useless)
3. T3 moves to nucleus and binds to TR (a nuclear receptor) & act as transcription factor, displaces corepressors and recruit coactivators which turn on thyroid targeting genes
Thyroid hormone rolesEARLY GROWTH & DEVELOPMENT - required for GH secretion and action, essential for early neural development (via induction of NGF), maternal lack of T3/T4 -> growth retardation and cretinism
T3/T4 is permissive to GH action and necessary for induction of Prolactin, GH, surfactant and NGF (nerve growth factor) expression

↑ mitochondrial growth, replication and activity therefore ↑ basal metabolic activity (↑ heat production, O2 demand, HR, SV)
Stimulates Na+/K+ ATPase activity & Beta-adrenergic receptors in several tissues incl. heart (↑ metabolic demand e.g. increased glucose)
↑ transcription of energy metabolism enzymes (↑ lipolysis, glycolysis, and gluconeogenesis -> ↑ blood metabolite levels and cellular uptake)

Hypothyroidism extreme leads to goitre(excessive TSH secretion leading to thyroid cell hypertrophy), no physically and mentally growth
HypothyroidismLack of energy, slow heart rate, muscle cramping, lack of concentration poor memory, puffy eyelids, feeling cold
Hashimoto's DiseaseAutoimmune disease - Anti-TPO antibodies -> no ability to iodinate and couple thyroglobulin (lead to hypothyroidism)
HyperthyroidismFeeling hot, increased sweating, fast or irregular heart beat, nervousness, trembling hands
Grave's DiseaseAnti-TSH receptor antibodies - activating -> activate TSH receptor in absense of TSH (too much T3/T4 result in issues with NS)
- hand tremor, insomia, hyperactivity, protrusion of the eye, mood swings, dizzyness
T/F - mutation in any thyroid players give rise to thyroid hormone related pathologymutation in thyroid binding globulin, TR, T3/T4 itself


Question Answer
Ca2+ important b/csignal transduction (secretory vesicle release, transcriptional activation), membrane potential (maintains excitability - neurons and muscle), muscle contraction (necessary for both contraction & relaxation), enzyme co-factor (e.g. troponin-C, calcium-calmodulin)
The human skeleton purposesupport and protection, locomotion, hematopoiesis, Ca2+ regulation
How much Ca2+ is non-skeletal~1% free Ca2+ in blood (protein-bound, complexed, ionized), of the 1% in blood only 50% is ionic and can be used for physiology
How much Ca2+ is in bone99% in form of calcium phosphate, 50% of skeletal weight
What is the net movement of Ca2+ balance0 (average ingestion = fecal & urinary output) - exchange of Ca2+ between kidney, GI, circulating Ca2+, most importantly our bone with ECF critical for bone remodelling
What is the site for calcium absorption?GI tract (CaT1 brings Ca2+ from apical side to basolateral side for absorption), unabsorbed Ca2+ excreted in feces with normal gut secretion of fluid and enzymes NOT kidney b/c that is reabsorption
Ca2+ processing in kidneysprocess ~10 g/day, 98% is reabsorbed through LoH passively, DCT actively - PTH upregulate
What is the most metabolically active region of bone?trabecular bone (provides Ca2+ for rest of body, repairs and strengthens the "scaffold" through bone remodelling on a continous basis)
Parathyroid anatomyposterior to thyroid, average 4 glands
Chief cellsCa2+ sensing receptors, make PTH; When Ca2+ levels get too high, chief cells can shut down PTH production
Parathyroid hormone full biological activity in1-34 fragments from N terminus, (can be secreted in fragments or intact PTH)
PTHRGPCR, PTH circulate freely in blood and when it binds, activate Gsalpha (cAMP -> PKA -> ↑ Ca2+) and Gq11alpha (PLCbeta -> DAG/IP3 -> ↑Ca2+) - increasing intracellular Ca2+; highly expressed in bone & kidney
PTHrPcan bind to PTHR - in prostate cancers which make PTHrP, induce PTHR and lead to high PTH activity (result in HHM - hormone related hypercalcemia)
PTHincrease Ca2+ reabsorption (if low Ca2+ in circulation, PTH released)
Vitamin D3steroid hormone, increase Ca2+ reabsorption
When Ca2+ levels are lowPTH secreted, ↑ bone turnover, ↑ osteoclast activity; ↑DCT Ca2+ reabsorption, ↑ 1 alpha-hydroxylase activity (important for production of vit D3); vitamin D3 "calcitrol" bind to vit D3 in gut to ↑Ca2+ reabsorption
How does PTH affect Ca2+ reabsorption directly/indirectlyPTH directly through bone, kidney, and indirectly through gut (through vit D3 receptor)
Vitamin D metabolismCholcalciferol (precursor) - found in supplemented food, D3 precursor in our skin to cholcalciferal via sunlight (UV) -> cholcalciferol circulate blood, go to liver and 25-hydroxylase convert it to 25-dihyroxycholcalciferol (major circulating form), kidney 1alpha-hydroxylase (upregulated by PTH) convert it to 1,25-dihydroxycholcalciferol (vitamin D3); vitamin D causes ↑ resorption and passive mineralization, and ↑Ca2+ absorption in GI tract
Vitamin D deficiencyrickets - lack of vitamin D/Ca2+, weak bones; pollution/smog - lack of sunlight, decreased vitamin D
Primary Hyperparathyroidismcaused by tumours, causes high plasma Ca2+ result in high BP, pancreatitis, kidney stones, stomach ulcers, osteopenia, osteitis fibrosa cystica, depression and psychosis
Secondary Hyperparathyroidismlow-normal Ca2+, high turnover bone disease, kidney failure, bone deformities, swollen joints
Primary vs. Secondary HPTboth forms affect bone and kidney function, primary involves increase in PTH and Ca, secondary just involves increase in PTH