Physiology Exam 2- Cheng Lectures

The thyroid gland is a _______ gland

Paired

What sits on top of the thyroid gland?

parathyroid gland

what stimulates thyroid gland secretions?

What inhibits thyroid gland secretons?

Stimulates: TSH & cold

Inhibits: stress

what is the progression of hormones from hypothalamus to thyroid gland to stimulate it to secrete hormones?

Hypothalamus>TRH (thyroid releasing hormone)>Anterior Pituitary> TSH (thyroid stimulating hormone)> Thyroid

causes activation of all steps in T3 & T4 synthesis pathway

thyroid stimulating hormone (TSH)

what are TSH receptors coupled to?

Gs protein signaling

what causes proliferation of follicles & vascularity

proliferation

what in the thyroid gland produces calcitonin?

C cell

where do thyroid hormones come from/what is their precursor?

tyrosine

gives rise to the thyroid hormones

tyrosine

how are thyroid hormones synthesized?

-iodide transported into cell via NIS

-iodide converted to iodine

-at same time, Na has to be pumped out

-cells synthesize thyroglobulin which goes to follicular site

-thyroglobulin converted to T3 & T4 & then secreted

what effects does temperature have on T3 & T4 secretion?

-not significant in adults

-seen in infants/hibernating animals (brown fat oxidation)

-Low body temp = increase TRH = increase TSH = increase T3 & T4 = calorigenesis in brown fat = increase body temp

mimics TSH to increase thyroid hormone secretion; leads to hyperthyroidism

grave's disease (in humans only)

with ____ people feel cold

hypothyroid

with ______ people feel hot

hyperthyroid

thyroid hormones can be what?

free T4

plasma bound

protein bound

what are T4 and T3 mainly bound to?

plasma proteins

increase in T3, found in liver & kidneys

type I deiodinase (5'DI)

increase in T3, found in brain, pituitary, brown fat

type II deiodinase (5'DII)

increase in rT3, found in placenta and brain

type III deiodinase (5DI)

what happens to hypothyroidism & hyperthyroidism when T4 is converted to T3

increase in hypothyroidism

decrease in hyperthyroidism

what would happen to T3 and T4 levels if no food?

after a week of starvation?

decrease= feel bold

after week, rT3 (reserve of T3) would increase bc of depleted T3= don't feel cold anymore

what is the backup T3?

RT3

where do the conjugates/secretions of thyroid hormones enter?

enter the bile & gut & are excreted into stool

where are conjugates of thyroid hormone hydrolyzed?

in the gut

where does most of the iodine go?

to urine

-some goes to produce thyroid hormone

is there more T4 or T3 in the body?

T4 (T4 can be converted to T3)

what do we need thyroid hormone for?

increase heat production and oxygen consumption (calorigenic action)

where is calorigenic action (increase heat production & O2 consumption) from thyroid hormone seen?

heart, skeletal muscle, liver & kidney

what is calorigenic action due in part to?

-increased cellular work (increase Na-K ATPase activity)

-due to metabolism of fatty acids

what is T3 involved in?

temperature regulation

what are secondary action to calorigenesis that thyroid hormone does?

-increase metabolic rate (leads to increased protein breakdown, lipolysis and increased nitrogen excretion)

-increase body temperature > vasodilation > decrease body temperature

-increase milk production

what hormone can increase milk production (besides prolactin)?

thyroid hormone

in what muscle does thyroid hormone synthesize proteins associated with neuromuscular activity?

skeletal muscle

what causes hypothyroidism and hyperthyroidism in skeletal muscle?

hypo: decreased ATP = muscle weakness

hyper: increased protein breakdown

what does thyroid hormone do in the heart?

-increase heart rate & contractibility

-increase oxygen consumption = increase cardiac output

what does thyroid hormone do to catecholamines?

-increase expression of alpha 1 and beta receptors

-increase metabolism, excitability, sweating

where is thyroid hormone found in the nervous system?

gray matter

what is thyroid hormone needed for in the nervous system?

-brain development

-maintains mentation & reflexes

what do high levels of thyroid hormone in the nervous system cause?

excitation

what does thyroid hormone do in cholesterol metabolism?

-decrease plasma cholesterol levels

-increase LDL transport receptors in liver

is thyroid hormone a good approach for controlling high cholesterol levels?

NO

deficiency of thyroid hormone leads to what in children?

cretinism (decrease bone growth)

what is critical for development of neural tissues, especially the brain?

T3

hypothyroidism occurs in what aged dogs?

breeds?

middle aged

-golden retriever, doberman pinscher, irish setter

symptoms of hypothyroidism?

-loss or thinning of fur

-dull hair coat

-excess shedding or scaling

-weight gain

-reduced activity & reduced ability to tolerate the cold

hyperthyroidism is most common in what?

older cats (rare in dogs)

symptoms of hyperthyroidism?

-weight loss, increased appetite & activity

-restlessness

-aggressive or cranky behavior

-poor hair coat

-fast heart rate, increased water intake & urination

-periodic vomiting

-increased stool or diarrhea

what are the treatments of hyperthyroidism?

-surgical thyroidectomy (RARE)

-radioactive iodide (can drink or be a pill) (COMMON METHOD)

-thiourylenes (acts on thyroid gland to inhibit iodine coupling reaction) (COMON METHOD)

what is important for synthesis of thyroid hormones?

where do you get it?

iodide

-in your diet

an enlarged thyroid gland

goiter

a goiter is a result of what?

iodide deficiency

how many people have an iodide deficiency?

20 million

what are the mechanisms for thyroid hormone?

-bind to intracellular T3 receptors causing an increase in mRNA & protein synthesis via gene transcription

-increase ATP production in mitochondria

what are nongenomic actions from thyroid hormones done by?

plasma membrane receptors (increase amino acid transport)

where are receptors for T3?

intracellular (inside cell)

cells only use which form of thyroid hormone?

T3

(more T4 in system but it can be converted to T3)

what does the parathyroid gland secrete?

parathyroid hormone

what stimulus results in a secretion of parathyroid hormone?

decrease in calcium (secretes parathyroid hormone to increase Ca levels back to normal)

The parathyroid gland is located on which side of the thyroid gland?

posterior

what is parathyroid hormone (PTH) synthesized as?

cleaved to form what?

Pre-proPTH

-cleaved to form the biologically active PTH with 34 amino acids

where is parathyroid hormone (PTH) metabolized?

in the liver (kupffer cells)

what stimulates the secretion of parathyroid hormone?

decreases in Ca and Mg levels

what are the Ca sensing receptors on PTH secreting cells activated under?

high Ca and Mg levels

what is the signaling mechanism for parathyroid hormone when Ca and Mg levels are high?

when is this mechanism inhibited so PTH can be released?

Gq > PLC-beta > increase in IP3 > increase Ca2+ release > opens Ca2+ activated K+ channels > hyperpolarization > decrease exocytosis (means decreased PTH secretion)

inhibited when Ca & Mg levels decrease

what are the 3 target organs for PTH?

bone

kidney

intestine

what is Ca in the form of in the body?

calcium phosphate (this is why you see an increase in phosphate in he intestine)

decreased Ca leads to an increase in PTH (parathyroid hormone) which leads to an increase in what?

-increased vitamin D3 activation

-increase intestinal Ca absorption

-increase renal Ca reabsorption

-increase Ca release from bones

what does the kidney convert Vitamin D into?

into active form 1,25- Dihydroxycholecalciferol

where is Vitamin D from?

sun & diet (ex: milk)

what are the forms of calcium from most common to least?

ionized calcium (50%)

protein-bound calcium (41%)

calcium complexed to anions (9%)

how much calcium is in bone?

extracellular fluid?

intracellular fluid?

bone= 99%

extracellular= 1%

intracellular= 0.1%

needed for blood coagulation, secretion, cell function, neural transmission & muscle contraction

calcium

whats the overall action of parathyroid hormone (PTH)?

increase plasma Ca2+ (calcium) & decreased phosphate (PO4^3-)

action of parathyroid hormone (PTH) in bone

increase resorption and Ca2+ mobilization

parathyroid hormone (PTH) has receptors in which: osteoblasts or osteoclasts?

IN osteoblasts (the receptor is RANKL)

NONE in osteoclasts

what does activation of RANKL in pre-osteoclasts lead to?

increase in osteoclasts = increase in bone resorption = increase in Ca2+

when parathyroid hormone begins, what do the levels of calcium & phosphate do?

calcium increases

phosphate decreases

what does parathyroid hormone do in the kidneys?

-increase CA2+ reabsorption in distal tubules

-decrease phosphate (PO4^3-) reabsorption in proximal tubules

-conversion of vitamin D3 to its active form

what does parathyroid hormone do in the intestines?

-with the active form of vitamin D3, it increases Ca2+ & PO4^3- absorption

PTH1R (parathyroid hormone type 1 receptor) binds what?

where is it expressed?

binds PTH and PTHrP

expressed in bones & kidneys

PTH2R (parathyroid hormone type 2 receptor) binds what?

expressed where?

binds PTH ONLY

expressed in brain, placenta, skin, endocrine pancrease (D-cells), myocardial cells

what are the PTH1R and PTH2R receptors coupled to?

Gs & Gq proteins

what causes primary hyperparathyroidism?

-tumors

-familial hypercalcemia

what causes secondary hyperparathyroidism?

chronic renal disease or rickets/osteomalacia

what are the levels of PTH in malignancy-related hypercalcemia (pseudohyperparathyroidism)?

what are the common kinds?

-PTH level is normal or low

-cancers of breast, kidney, ovary, skin, etc. produce PTHrP (80%)

-bone metastases (20%)

what causes hypoparathyroidism?

-traumas

-autoimmune reactions (rare)

-familial hypocalcemia

-pseudo-hypoparathyroidism

what occurs in pseudo-hypoparathyroidism?

-PTH level normal or high

-problem with receptor signaling

-Gs deficiency (mutation)

-PKA deficiency (mutation)

what is eclampsia, puerperal tetany & milk fever due to?

what do these cause?

hypocalcemia (not enough Ca)

cause increase in excitability of nerve & muscle cells= spastic skeletal muscle contractions

what is secreted by ultimobranchial cells incorporated into the thyroid gland called parafollicular or C-cells?

calcitonin

which animal's calcitonin (CT) is >20x more potent than mammal calcitonin?

salmon

calcitonin is the ________ hormone of PTH

What does this mean?

counter-regulatory

-does the opposite

what are the clinical uses of Salmon CT (calcitonin)?

-for Paget's disease (excessive bone remodeling)

-for hypercalcemia of malignancy

-for osteoporosis

how is CT secretion regulated (include increase and decrease)

-Plasma Ca2+ = increase in CT

-increase in Ca2+ sensing recetors > Gq-coupled receptor activation > PLC-beta > increase IP3 + DAG > increase exocytosis

-somatostatin receptors = decrease CT

what does CT inhibit?

-Ca2+ absorption in the intestines

-bone resorption

-inhibits Ca2+ reabsorption in the kidneys

without CT, bone density and plasma Ca2+ are what?

normal

what is the hypothesis about CT protection?

CT protects bone during Ca2+ stress; CT inhibits postprandial hypercalcemia

where are calcitonin receptors?

osteoclasts & real tubule cells

what do the calcitonin receptors do?

-increase Gs > increase cAMP > increase PKA

-increase Gq > increase PLC-beta > increase IP3 + DAG > increase Ca2+ * PKC activation

what is the structure of the adrenal glands?

medulla & cortex (cortex is made up of 3 zones)

-(outside to inside): zona glomerulosa, zona fasciculata, zona reticularis