Thyroid Physiology

Question 1

describe the composition of the thyroid follicle (3)

Answer 1

1. follicular cells (where the magic happens): single layer of cuboidal epithelial cells
2. colloid: jelly inside follicle that stores thyroglobulin (TG)
3. parafollicular (C) cells: release calcitonin

Question 2

explain the thyroid axis and negative feedback loop

Answer 2

the hypothalamus releases thyrotropin-releasing hormone (TRH) that acts on the anterior pituitary and tells it to release thyroid-stimulating hormone (TSH); TSH acts on the thyroid gland and tells it to release T3/T4; then T3/T4 negatively feedback on the hypothalamus to tell it to chill with the TRH

Question 3

list the 4 steps in thyroid hormone synthesis

Answer 3

Step 1: Iodide trapping: iodine from diet is converted to iodide in the GI tract, then travels through the bloodstream to the thyroid gland, where the Na+/K+ ATPase pump sets up an electrical gradient that makes Na+ want to flow back into the cell; it flows back through the NIS (Na+/I- symporter) that moves Na+ and I- into the cell; then I- follows its own electrical gradient from basal to apical membrane of follicular cell

Step 2: Iodide oxidized to iodine by thyroid peroxidase (TPO) and transported into colloid via exchange with Cl-

Step 3: TPO moves I2 to tyrosine residues on thyroglobulin; if one I2 binds, makes MIT; if 2 I2s bind, makes DIT (more DIT is made than MIT)

Step 4: coupling reaction (catalyzed by TPO): if MIT + DIT = T3; if DIT + DIT = T4; since more DIT is made in step 3, more T4 is made

Question 4

list the 3 steps in the secretion of thyroid hormone from colloid to blood

Answer 4

1. pseudopod endocytoses a chunk of colloid-containing thyroglobulin into the follicular cell
2. vesicle containing TG fuses with a lysosome that cleaves T3 and T4 from TG; then another enzyme cleaves I2 from MIT and DIT, allowing for TG recycling in step 3
3. T3 and T4 diffuse out of the cell and TG is recycled

Question 5

describe how the majority of T3/T4 circulates in the blood and name 3 thyroid hormone binding proteins

Answer 5

99% is protein bound!

thyroxine-binding globulin (TBG): major binding protein in dogs; cats DO NOT HAVE; has a higher binding affinity for T4 than for T3

transthyretin/thyroxing-binding prealbumin (TBPA): main binding protein for cats

albumin: lowest binding affinity, but highest quantity so binds a lot of TH

Question 6

name the thyroid hormone that is most biologically active; following receptor binding, how does it increase target cellular activity?

Answer 6

T3 is most biologically active (is the only form that will bind to intranuclear thyroid receptor; then the TH/TR complex binds to the TRE (thyroid hormone response element) to increase or decrease gene transcription to make proteins that will elicit a biological effect

Question 7

list the general effects of thyroid hormones on basal metabolic rate (4)

Answer 7

overall catabolic effects (breakdown)

1. increased heat generation (thermogenesis)
2. increased oxygen consumption
   3.increased energy availability (via glucose and lipid utilization)
3. balanced protein synthesis and breakdown

Question 8

list the general effects of thyroid hormones on nervous system (2)

Answer 8

stimulatory!
1. increases mental alertness
2. shortened nerve reaction times by increasing responsiveness to stimuli

Question 9

list the general effects of thyroid hormones on the GI tract (6)

Answer 9

1. increases appetite
2. increases GI motility
3. increases GI secretion
4. increases glucose absorption
5. on fat: mobilizes free fatty acids, decreases plasma cholesterol, and decreases plasma triglycerides
6. on muscle: maintain normal balanced protein synthesis and breakdown, increase contraction strength and decrease relaxation time, increase energy utilization, increase muscular repair following injury

Question 10

list the general effects of thyroid hormones on the heart (2)

Answer 10

1. sensitized myocytes to catecholamines (epi and norepi) by increasing adrenergic receptor expression
2. increases cardiac output by increasing HR, contractility, and stroke volume

Question 11

list the general effects of thyroid hormones on glomerular filtration rate

Answer 11

RAAS activation to increase blood volume, increasing renal blood flow and GFR (this can mask kidney disease in hyperthyroid cats bc will show a fake normal GFR)

Question 12

list the general effects of thyroid hormones on fetal or juvenile growth and development

Answer 12

1. brain maturation, axonal growth and myelin sheath formation, muscle development, and bone growth
2. stimulates secretion of and works with growth hormone

Question 13

define euythroid sick syndrome

Answer 13

suppression of hormone concentrations due to concurrent illness, stress, trauma, or surgery; TT4 and fT4 will look low, but TSH is typically normal; meaning pituitary and thyroid gland are working normally, but hormones are suppressed; so treat the illness and recheck T4 before diagnosing hypothyroid