Physiology: Endocrine # 6, Parathyroid Hormone

Front 1

what's interesting about serum calcium?

Back 1

1% of all body Ca is in the serum - 99% is in the bones.

Only a portion of that 1% is our ionized, Ca++ second messenger.

50% in the plasma is bound to proteins, 45% is ionized and biologically active, 5% is connected to small anions.

So, when we eat Ca++, it binds up proteins to buffer all that new signaling molecule. also serves as a reservoir.

so, we have super-refined controlling of [Ca++]

Front 2

one of our lecture objectives is to learn 7 roles of Ca++ : regurgitate

Back 2

neuronal excitability, release of neurotransmitters.

membrane integrity?

muscle excitation-coupling

endocrine secretion

certain coagulation factors

gene regulation (with calmodulin)

Front 3

plasma pH and binding of ionic, active Ca++ - what's up?

Back 3

raising of pH causes more Ca++ to be bound up by proteins, lowering the amount of active, ionic Ca++ in the plasma.

This means that hyperventilation cases respiratory alkalosis, binds up more Ca++, and causes an effective Ca++ drop in the body.

one way to remember - low pH = lots of protons around, will compete with Ca++ for binding - so low pH kicks off Ca++ from proteins and increases concentration

Front 4

osteoblasts and osteoclasts - which controls which and what factors are released?

Back 4

osteoblasts control osteoclasts by the release of factors.

these include RANKL and MCSF (both turn on osteoclast activity and cause bone resorption).

OPG is also secreted by osteoblasts, this SHUTS DOWN osteoclasts.

Front 5

renal and Ca++ : where is resorption happening, how much, where is there a place for control?

Back 5

98 to 99% is resorbed.

60% in the prox tubule.

distal tubule is where PTH can control more or less Ca++ resorption

Front 6

generally, what are the effects of hyper and hypocalcemia?

Back 6

hypo = excitation threshold lower (easier to get excited or be stimulated)

this means tetany, spasms, LARYNGOSPASM = deadly.

also, get long QT from delayed repolarization


HYPERcalcemia: depression, hard time exciting, coma, weakness. get hypertension and bradycardia (seem opposite?) lower GFR, polyuria, dehydration

Front 7

what can cause hypo and hypercalcemia?

Back 7

hypo can be caused by malabsorption, vitamin D deficiency, hypoPARAthyroidism, or renal disease.


hyper can be caused by hyperPARAthyroidism, too much vitamin D, tumors from the parathyroid gland.

also, osteolytic bone tumors (release all kinds of Ca++)

Front 8

what does PTH do to phosphate resorption in the kidney?

how does eating more phosphate affect the concentration in the body?

Back 8

normally, Ca++ and phosphate go together...but not here.

PTH causes more loss of phosphate from the kidneys by preventing resorption (active form in the proximal tubule).

we absorb phosphate in a linear way with the amount in our diets.

Front 9

what does vitamin D do to phosphate?

Back 9

calcitrol (1,25 OH2-D) increases absorption from the gut. in the presence of calcitonin, the phosphate will be used to make bone.

under the presence of calcitrol, the kidneys will resorb phosphate.

under the presence of PTH or calcitonin, the kidneys will loose phosphate

Front 10

parathyroid - what cells secrete it?

Back 10

in the parathyroid gland, chief cells make it

Front 11

what does PTH receptor look like and what pathways does it induce?

Back 11

parathyroid receptor is a typical 7-pass g-protein, leading to increased cAMP and increased Ca++ uptake by target cells.

Front 12

what regulates PTH secretion?

Back 12

both vitamin D and intracellular Ca++ can inhibit synthesis of PTH.

Vitamin D: the 1, 25 OH2-D feeds back directly on PTH secretion from chief cells.

Ca++ : works through Ca-sensitive receptor (CaSR) to shut off synthesis of PTH in chief cells.

Front 13

what is PTH's big effect in the kidneys?

Back 13

it stimulates 1-alpha hydroxylase to make active form of vitamin D, which in turn will help increase Ca++ plasma concentration...it will also then feed back on PTH, to shut it back down.

It directly increases Ca++ resorption.

OPPOSITE EFFECT - dramatically affects phosphate in an opposite way. High PTH = low phosphate resorption (high phosphate excretion).

Front 14

PTH - what's its halflife and what eats it?

Back 14

halflife is 10 minutes - Kupeffer cells in the liver chew it up.

Front 15

what does PTH do in the bone?

Back 15

in high dose, first reaction is bone resorption.

low dose can be important in MAINTAINING BONE MASS, which is a weird opposite effect. This is why PTH is given in low doses over time. This is through action on osteoblasts.

Front 16

if you have a tumor of the parathyroid gland, making way too much PTH, what happens?

Back 16

bad effects on bone - increased bone resorption and lots of Ca++ floating around in the plasma (so have hypercalcemic effects).

also, you pee out all your phosphate

you'll get lots of vitamin D made due to increased activity of 1-alpha hydroxylase in the kidney tubules

has indirect effects on the intestine (there's no PTH receptor in the intestines) - but vitamin D does act there to get more Ca++ and phosphate out of the diet, attempting to increase the concentration of both in the plasma.

so, the only PTH receptors in the body are in the bones and in the kidney

Front 17

review PTH:

Back 17

too little Ca++ makes cAMP go to work to release PTH. Note that the receptor for both inhibition and secretion is a 7-pass g-protein coupled receptor.

regulation of PTH besides calcium: high phosphate (remember pth gets rid of it), high vitamin D turns OFF SYNTHESIS of PTH.

hypolcalcemia = prolonged QT, hypotension, brady cardia. hard to repolarize.

hypercalcemia = hypertension, bradycardia.