Thyroid Physiology Flashcards
1
Q
BMR
A
- energy expenditure at rest
- largest proportion of our daily energy usage
- 5% higher in adult males vs females
- increased by several hormones- thyroid in particular
- profoundly increased by strenuous exercise
2
Q
metabolism
A
- encompasses all chemical processes involved in energy release, production, and growth
- can be anabolic or catabolic
- heat, work done on environment, growth
- 70 kg human needs 2100 kcal.day- RMR
3
Q
thyroid gland, growth, development, metabolism
A
- T4 and T3 are biologically active forms
- bilobulated thyroid gland is highly vascularized and contains substantial stores of TH
- gland consists of numerous closed follicles that store TH in their lumens
- each follicle is surrounded by epithelial cells that synthesize and release TH in response to TSH from ant pit
- only endocrine gland easily palpated
- tremendous potential for growth
- follicular epi cells are sites of TH syn/release
- stored form is TG in the colloid
- C cells secrete calcitonin
- fibroblasts, lymphocytes, adipocytes, endothelial cells lining caps provide blood supply
4
Q
thyroid hormones
A
- produced from tyrosine and include iodide from diet
- thyroxine (4) and triiodothyronine (3)
- synthesized from tyrosine residues on TG
- TG is a large protein dimer (660 kDa- gelatinous colloid)
- preferential synthesis of T4
- reverse T3 produced but inactive
- only hormone that requires essential trace element, usually in salt
- lysosomes of follicular cells have enzymes that will cleave the peptide and release T4 from TG
- binds to TBG in blood
5
Q
storage of iodine
A
- most stored in thyroid gland in association with TG
- ingest 300 mcg, excrete 285 in urine and 15 in feces
- must ingest 70-300 micrograms/day
- concentrated in thyroid by 2 Na/I symporter that uses inwardly directed Na electrochemical gradient as a DF, doesn’t use ATP directly
- gland can autoregulate iodide transport- if dietary is low, it will concentrate more)
- chronic iodide def can lead to hypothyroidism that can be fixed with iodine
- mostly in thyroid, remainder is in tissues or circulation as organic and inorganic iodide
- some recycled from organic to inorganic, then trapped back into thyroid, some leaks from thyroid
6
Q
wolff-chaikoff effect
A
- when given high levels of iodide, inhibit gland and makes it firmer, reduces hormone levels
- it will escape at some point
- preparing for surgery
7
Q
TH and TSH
A
- in ER, TG produced and packaged into vesicles by golgi and exocytosed to lumen of cell
- iodide from diet enters the thyrocyte via basolateral Na/I cotransporters, and exits the cell into the lumen via I/CL antiporters
- in the lumen, iodide is oxidized to iodine by thyroid peroxidase and substituted for H on benzene ring of tyrosine residues of TG
- binding of one I forms monoiodotyrosine (MIT), 2 forms DIT-organification. Thyroid peroxidases also catalyze coupling of 2 DITs, forming T4. some will couple to MIT and form T3. products remain attached to TG
- mature TG contains MIT, DIT, T4, 3 (greater to lesser abundance) is endocytosed back into follicle cell and can be stored as colloid until secreted
- colloid proteolysis is stimulated by TSH and constituent molecules released
- MIT and DIT reneter synthetic pool, T3 and 4 exit basolateral membrane into blood
8
Q
thyroid mainly secretes T4
A
- 93% T4 secreted, T3 and reverse other 7%
- majority of circulating T3 is derived from T4 (pro-hormone)
- most circulating boung to thyroid binding globulin (TBG)
- other binding proteins are transthyretin and albumin
- small amt in free form (0.03% of T4 and 0.3% of T3)- free form enters tissues
9
Q
T4 metabolism
A
- by peripheral 5’/3’ deiodinases generates T3 and reverse T3
- deiodization of T3 makes inactive organic compounds
- THs are also deaminated, conjugated, and decarboxylated
- some agent inhibit T4 to T3 provide immediate effects for hyperthyroidism- PTU
10
Q
comparison
A
- T4 half life 7 days, T3 1 day
- T4 has 1 potency, T3 has 4-10 times that
- T4 used to treat because its more stable and longer half life
11
Q
TH entry into cells and transcriptional effects
A
- majority is bound to TBG
- unbound enters target tissues to activate intracellular receptors in the cell nucleus
- mode of entry into cells is under active investigation
- TR (thyroid receptor) heterodimerizes with RXR to regulate genes containing TREs
- TH receptors in virtually all tissues
- regulates metabolism of carbs, proteins, lipids
12
Q
effect of TH
A
- increases Na/K pump
- inc gluconeogenic enzymes
- inc resp enzymes
- inc myosin heavy chain
- inc B adrenergic receptors
- increase metabolic rate and O2 consumption
- promotes bone formation, ossification and fusion of bone plates and bone maturation
- mutiple effects on CNS and essential for development in perinatal period
- increase CO2 output and ventilation
- increase CO, urea and renal function
- increase glu absorption, gluconeogenesis, glycogenolysis, lipolysis, and protein syn/deg (net catabolic)
13
Q
TH timing
A
- slow onset and long duration of action
- if injected at day 0, peak BMR and day 10 and lasts at least 40 days
- if injected T3, curve would shift to the left- faster half life (latency 6-12 hrs and max effect 2-3 days)
14
Q
hyperthyroidism
A
-BMR increases (60-100% with excess secretion) increases: -gluconeo -glycogenolysis -protein syn/degrad -muscle wasting -lipogenesis -lipolysis decreased serum cholesterol -normal serum glucose -increases expression of B-adrenergic receptors- increases sensitivity to catechols
15
Q
hypothyroidism
A
-BMR decreases (40-50% with lack of TH) decreases: -gluconeo -glycogenolysis -protein synthesis -proteolysis -lipogenesis -lipolysis increased serum cholesterol (atherosclerosis, dec LDL receptor?)```` -normal serum glucose -normal levels of catechols
