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89 Cards in this Set

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Where is calcium most important functionally?
Intracellularly
What is essential about calcium?
It must be maintained at a BALANCED intake and excretion
What is the normal daily intake of calcium?
1000 mg
How much calcium do we normally absorb from the intestines? What influences this absorption? What is the NET absorption?
350 mg/day; under the influence of Calcitriol; the net absorption is about 100 mg/day
What is the other name for calcitriol?
1,25-dihydroxy Vit D
How much calcium is normally secreted from the ECF via bile and pancreatic juices? Where does it end up?
~250 mg/day
Ends up in feces
So how much calcium do we lose in feces daily?
900 mg/day
Where does the 100 net mg of Ca that we absorb from the intestines go?
To the ECF
How much total calcium is in the ECF normally?
1300 mg
How much calcium in the ECF is free? How much is protein bound?
50% is free, 50% is protein bound
What is the calcium in the ECF in exchange with?
-Cells
-Bone (deposition/resorption)
-the Gut (absorption/secretion)
-the Kidneys (reabsorption/excretion)
How much calcium is filtered by the kidneys daily? What happens to it?
9980 mg of Ca is filtered by the kidneys daily; most is reabsorbed so you don't lose it all.
What is a major cause of hypocalcemia?
Renal failure
So how much calcium daily is:
-Filtered
-Reabsorbed
-Excreted?
Filtered = 9980 mg
Reabsorbed = 9880 mg
Excreted = 100 mg
(daily)
How much calcium is deposited and resorbed from bone daily?
500 mg
What controls bone calcium resorption?
PTH
How much calcium is in the bones normally?
a TON - 1,000,000 mg
What controls calcium reabsorption in the kidneys?
PTH
Does PTH only control calcium reabsorption in the kidneys?
No
3 things controlled by PTH in the kidneys:
-Calcium reabsorption
-Phosphate reabsorption
-Vit D activation
What happens when you deposit and resorb calcium from bone?
You deposit and resorb PHOSPHATE too
Can you ever resorb calcium from the bone without phosphate
NO
So how does the body separate the control of body Calcium and Phosphate?
By the kidney
What protein does calcium circulate bound to?
Albumin
So how do you measure the active amount of calcium (ionized) in the blood?
By measuring Albumin - since 50% of calcium is bound to albumin, the same amount is free.
Where is PTH made and released?
In the parathyroid glands
What does PTH do?
Directly: stimulates bone resorption of Ca/Phosphate
Directly: stimulates Ca reabsorption in kidney
Indirectly: stimulates calcium reabsorption from the gut by activating Vit D in kidney
What stimulates the release of PTH from the PT glands?
Low blood calcium
What inhibits the release of PTH from the PT glands?
High blood calcium
What else does high blood calcium do?
Stimulates Calcitonin release from the Thyroid gland parafollicular cells
What is by far the most important hormone that controls calcium?
PTH
Is calcitonin all that important?
No
If a skilled surgeon does a thyroidectomy will it affect calcium regulation?
Nope
If a skilled surgeon does a parathyroidectomy will it affect calcium regulation?
Yeah - the patient will die
What are the 2 main types of cells in the Parathyroid glands?
-Chief cells
-Oxyphil cells
Which cells secrete PTH?
Chief cells
What is the receptor on the PT glands that senses increased serum calcium levels?
A normal, 7-transmembrane, g-protein coupled receptor.
What is the LIGAND for this receptor?
CALCIUM!!
What happens when calcium binds its receptor on the PT gland?
It inhibits the release of PTH by activating a G-protein coupled cascade
What is the hot new hormone?
Vitamin D
If Vit D is a hormone why do we call it a vitamin?
Because deficiency used to cause rickets
What are the 2 dietary forms of Vit D?
Vit D3 - from animals
Vit D2 - from plants
What is Vit D3 called?
What is Vit D2 called?
D3 = Cholecalciferol
D2 = Ergocalciferol
Which form of Vit D is better? Why?
Vit D3 - it has a longer half life
What is the first step in metabolism of Vit D?
The liver converts it to 25-hydroxycholecalciferol
Is the liver enzyme that hydroxylates vit D regulated?
No - it happens all the time at a constant rate.
What is the best assessment of a person's Vit D levels?
Measurement of 25-hydroxycholecalciferol
What happens to 25-hydroxyVit D?
It goes to the kidney to get hydroxylated at the 1 position
What enzyme is in the kidney to do this?
1-hydroxylase
Primary effect of 1,25-dihydroxy vit D:
Increased intestinal absorption of calcium.
What does the increased serum calcium achieved by Vit D do?
INHIBITS PTH SECRETION
So what is the best index of body Vitamin D stores?
Serum 25-hydroxy Vit D
Why is 25-Hydroxy Vit D the best index of Vit D stores?
Because it won't be affected by changes in 1-hydroxylase enzyme activity
Why won't 1-hydroxylase activity effect the amount of 25-OH Vit D in the body?
Because there is 1000X more 25-hydroxy Vit D than 1,25-dihydroxy vit D; such a tiny amount is ever converted that the overal amt of 25-OH Vit D is constant.
What WILL changes in 1-hydroxylase enzyme activity affect?
Levels of 1,25-dihydroxy vit D
So what is the best index of renal 1-hydroxylase activity?
Measuring serum levels of 1,25-dihydroxy vit D
What type of a hormone is Vit D?
A steroid hormone
Where is the target receptor of Vit D?
In the nuclei of intestinal epithelial cells
What are the results of Vit D binding its nuclear receptor?
-Increased Ca/Na countertransporter
-Phosphate absorption
-Ca absorption
So what are the 3 direct effects of PTH?
1. Stimulates calcium resorption from bone
2. Stimulates Vit D
3. Stimulates Calcium reabsorption in kidney
And what does Vit D do?
Increases calcium and phosphate reabsorption in the gut
What happens if you don't have PTH?
You don't have a normal life
Too low of calcium:
tetany
Too high of calcium:
weakness
What stimulates phosphate reabsorption in the gut?
1,25-dihydroxy vit D
What stimulates phosphate resorption from bone?
PTH
What stimulates phosphate secretion in urine?
PTH
Where is the only place where phosphate and calcium regulation is independent of each other?
In the kidney
3 effects of hypocalcemia ( in order):
1. PTH glands stimulated
2. Decreased blood phosphate due to PTH's phosphaturic effect
3. Increased blood calcium
What causes hypercalcemia?
Increased PTH secretion
What is the usual cause of primary hyperparathyroidism?
Benign tumors in the pt glands
Why do benign tumors secrete so much PTH?
Because they are refractory to the negative feedback effect of high serum calcium
What will hypercalcemia caused by something other than PT tumors result in?
Decreased PTH secretion
What is hypercalcemia that leads to suppressed PTH secretion usually due to?
-Too much Vit D, or -Hypercalcemia of malignancy
What gets released in Hypercalcemia of malignancy?
PTHrp - an analog that is released by tumors
What does PTHrp do?
Binds the same receptor as PTH, so the body thinks it needs to increase serum calcium.
Do patients with hypercalcemia often present with symptoms?
No; they're most often asymptomatic and are discovered by blood workups for other reasons.
What is the cause of hypocalcemia?
Deficiency in PTH secretion
What is the most common cause of hypocalcemia due to low PTH?
A thyroidectomy gone bad.. the surgeon accidently yanked out the PT glands along with it.
What is the result of hypocalcemia?
Tetany
What is the treatment for hypocalcemia due to low PTH?
Recombinant PTH or Vit D
If you give Vit D what does it have to be? Why?
Has to be the already active version because if PTH is low, there's nothing to stimulate Vit D activation in the kidney!
If the PT glands are NORMAL, what does hypocalcemia cause?
Increased PTH secretion
What is it called when hypocalcemia induces increased PTH secretion?
2ndary hyperparathyroidism
In what patients is 2ndary hyperparathyroidism most common? WHY?
Renal failure patients - because they can't activate vit D, so they can't absorb calcium from the gut.
What is another common cause of hypocalcemia and hyperPTH?
Sprue - malabsorption
So 3 causes of hypocalcemia / 2ndary hyperparathyroidism:
-Renal failure
-Sprue
-Low Vit D
What is Vit D Deficiency in
-Children
-Adults
Children = Rickets
Adults = Osteomalacia
If a patient has primary hyperparathyroidism in only one PT gland, will the 3 other glands be big or small?
Small