Pth And Vit D/ca 1-2

Front 1

What are the forms of Calcium in plasma?

Back 1

1) Bound to albumin (40%)
2) Ultrafiltrable
a) Bound to ions (phosphate, sulfate, etc) (10%)
b) free ionic (50%)

Front 2

What 3 hormones control calcium in ECF?

Back 2

PTH, calcitonin, vitamin D

Front 3

What's the typical [Ca] in blood?

Back 3

10.0 mg/dL

Front 4

Biologically active form of Ca

Back 4

Free, ionized

Front 5

What kinds of things alter total [Ca?]?

Back 5

1) Changes in plasma protein concentration.

2) Changes in [complexing ion], like phosphate

3) Acid-base disturbance (Ca2+ competes with H+ for Hb binding sites.)

Front 6

What are symptoms of hypercalcemia?

Back 6

1) Neurologic: lethargy, coma, weakness, hyporeflexia

2) Renal: Polyuria, polydipsia b/c of ADH resistance

3) GI: constipation

Front 7

Sx of hypocalcemia (decrease in plasma [Ca2+])

Back 7

Makes APs more easily elicited/decreases AP threshold.

Spontaneous muscle cramps, tetany, seizures

Front 8

What is the Trousseau sign?

Back 8

Indicates hypocalcemia.

Inflating blood pressure cuff evokes carpopedal spasm.

Front 9

What is Chvostek's sign?

Back 9

tapping finger of supramandibular portion of parotid gland causes spasm is muscles innervated by facial nerve/twitches in upper lip

Front 10

what maintains intracellular [Ca2+]?

Back 10

Cell membrane Ca-pump, Ca-Na exchange, uptake and release of Ca from intracellular organelles

Front 11

What is calcium balance?

Back 11

Net excretion in urine must equal net absorption from GI tract

The Resorption from bone and deposition into bone are the same

Front 12

Bone remodeling is process of

Back 12

Ca leaving bone and entering ECF and vice versa

Front 13

What is positive Ca balance? When does it happen?

Back 13

More Ca is absorbed than is excreted in urine.

Happens in growing child

Front 14

What is negative Ca balance? When does it happen?

Back 14

More Ca is secreted (thru urine or other ways) than is absorbed in GI.

Happens during lactation. Some Ca leaves via milk AND urine.

Front 15

What hormone regulates hypercalcemia?

Back 15

NONE

Front 16

What hormone Increases/Maintains free [Ca2+] in blood?

Back 16

Parathyroid hormone, secreted from chief cells of PT gland

Front 17

What stimulates PTH secretion? Inhibits?

Back 17

Low plasma Ca2+ concentration; Hi plasma [Ca]

Front 18

How does the PT gland know when to secrete PTH?

Back 18

PT cell membranes contain Ca2+-sensing receptors linked to phospholipase C with Gq protein. When extracellular [Ca] increases, more Ca binds, activates PLC, and INHIBITS PTH secretion.

When there is less plasma [Ca], less Ca binds the receptor, PLC is inhibited, levels of IP3/Ca2+ drop, and PTH secretion is stimulated.

Happens within minutes

Front 19

What happens in the PT gland during chronic hypocalcemia (eg., chronic renal failure)?

Back 19

Chronic decrease in blood Ca2+ (Vit D deficiency, chronic renal failure) -> Hyperplasia of PT gland -> ↑ transcription of PTH and ↑PTH stores

Front 20

How do changes in plasma [Mg2+] affect Ca?

Back 20

Low Mg2+ stimulates PTH secretion (Mg2+ mimics Ca2+).

HOWEVER, severe, prolonged low magnesium (hypomagnesemia) inhibits PTH secretion.

Front 21

What are the actions of PTH on
A) Bone
B) Kidney
C) Intestine

Back 21

A) Increases bone resorption

B) Decreases tubular phosphate reabsorption (phosphaturia) --> more phosphate excreted in urine; Increases tubular Ca reabsorption (hypocalciuria)

C) Increases calcium absorption indirectly via VitD

Front 22

How does PTH act on bone?

Back 22

1) Directly, transiently, stimulates osteoblasts (these have PTH receptors) --> transient increase in bone formation

2) PTH binding to receptors on osteoblasts causes them to release cytokines that activate osteoclasts --> causing long-lasting increase in bone resorption.

<b>Overall effect is to promote bone resorption, delivering Ca2+ and phosphate from bone --> ECF.</b>

Front 23

What's hydroxyproline's role in this?

Back 23

As bone is resorbed, hydroxyproline is released from bone matrix and excreted in urine.

Front 24

How does PTH act on kidney to affect phosphate?

Back 24

PTH works thru increasing cAMP production in TWO segments of the nephron: proximal and distal tubules. These have different effects.

1) PTH binds to receptor on blood side of <b>proximal tubule cell</b>, activating Gs --> increase in cAMP --> inhibition of Na-phosphate cotransporter. --> results in phosphaturia because so little phophate is reabsorbed after the prox tubule.

(also inhibits reabsorption of Na, Ca, bicarb and fluid)

Front 25

What is the bioassay for PTH?

Back 25

urinary cAMP

Front 26

How does PTH act on kidney to affect Calcium reabsorption?

Back 26

Two ways.
1) Because it inhibits Na reabsorption and Ca is tightly coupled to Na, it INHIBITS Ca reabsorption in prox tubule, paradoxically

2) <b>Distal tubule Ca reabsorption is increased by PTH</b>. This is the major action.

Front 27

What is PTHrp? and what's the role?

Back 27

PTHrp = PTH related peptide.

It is released from some tumors and causes hypercalcemia.

Front 28

How do loop diuretics affect Ca reabsorption?

Back 28

They inhibit calcium reabsorption passively along with Na in the Loop of Henle because they destroy the luminal gradient that was driving ion movement.

They're use for severe, life-threatening hypercalcemia (would be given along with saline to prevent volume contraction)

Front 29

How do distal diuretics (either potassium sparing or thiazide) affect Ca reabsorption??

Back 29

DIFFERENT from loop. They produce hypocalciurina, lowing urinary Ca excretion.

They do so by increasing distal tubule calcium reabsorption while simultaneously inhibiting distal Na reabsorption.

<b>Increase Calcium reabsorption, inhibit Sodium reabsorption.</b>

Front 30

How does PTH affect intestinal Ca absorption?

Back 30

they increase 1 &alpha;-hydroxylase --> biologically active VitD --> increases Ca absorption from intestine

Front 31

Why wouldn't PTH increase ECF [Ca2+] if it just affected bone?

Back 31

Because both calcium and phosphate would be released, and calcium would complex with phosphate.

MUST BE EXCRETING PHOSPHATE SELECTIVELY.

Front 32

What happens in primary hyperparathyroidism?

Back 32

May be caused by a PTH-secreting tumor (parathyroid adenoma).

High circulating levels of PTH, hypercalcemia, and hypophosphatemia.

Front 33

What happens in secondary hyperparathyroidism?

Back 33

Cause is chronic renal failure or vit D deficiency

See low Calcium in blood, high levels of phosphate

Front 34

What happens in hypoparathyroidism (eg., PT gland removed accidentally during surgery)?

Back 34

Low PTH, low [Ca2+], high phosphate

Front 35

What happens in pseudohypoparathyroidism Type Ia (Albright's osteodystrophy?)

Back 35

Characterized by high levels of PTH but hypocalcemia and hyperphosphatemia.

Other symptoms include short stature, short fingers.


This is because kidneys and bones are resistant to PTH. They're deficient in the Gs protein that couples the PTH receptor to adenylate cyclase.

cAMP and subsequent actions of PTH on kidney and bone are inhibited.

Front 36

What's the main purpose of vitamin D?

Back 36

To increase Ca2+ AND increase phosphate to form new bone.

Front 37

Vitamin D deficiency in A) Children and B) adults

Back 37

A) Rickets
B) osteomalacia

Front 38

What is the principal circulating form of vitamin D?

Back 38

25(OH)cholecalciferol

Front 39

What happens when 25(OH)cholecalciferol gets to the kidney?

Back 39

The proximal tubule cells hydroxylate it to 1,25(OH)cholecalciferol (active form) by 1&alpha;hydroxylase or 24, 25(OH)cholecalciferol (inactive form)

Front 40

What is the active form of vitamin D?

Back 40

1,25(OH)cholecalciferol

Made by 1&alpha;hydroxylase in proximal tubule of kidney

Front 41

When is the active vs. inactive form of vit D made?

Back 41

Active - made by kidney where inadequate amounts of Ca are being absorbed from GI tract.

Inactive - Made when adequate amounts of Ca are being absorbed from GI tract.

Front 42

What regulates whether kidneys make 1, 25(OH)cholecalciferol or 24,25(OH)cholecalciferol?

Back 42

Serum [Ca2+]. If low --> 1,25(OH)cholecalciferol.

If hi, -> 24,25(OH)cholecalciferol

Front 43

What are the 3 mechanisms of regulation on 1 &alpha;-hydroxylase, the enzyme that converts main circulating form of Vit D (25(OH)cholecalciferol) to active form (1,25(OH)cholecalciferol)?

Back 43

1) Decreased plasma [Ca2+] --> increased 1&alpha;-hydroxylase. When plasma [Ca2+] gets too high, it gets turned off.

2) Increased PTH increases 1 &alpha;-hydroxylase

3) Decreased plasma phosphate --> increases 1 &alpha;-hydroxylase.


4) Prolactin, GH, and estrogen also may increase 1&alpha;-hydroxylase activty.

Front 44

What are the actions of 1, 25(OH)cholecalciferol coordinated to do?

Back 44

Increase levels of Ca and phosphate for bone deposition/mineralization

Front 45

T/F no steroid hormone reaction is immediate

Back 45

True.

This is because they work by inducing gene transcription/expression

Front 46

What is the lag time for which cellular actions of 1,25(OH)cholecalciferol are detectable?

Back 46

minimum of 12 hours

Front 47

What is the protein that 1,25(OH)cholecalciferol induces? What does it do?

Back 47

Calbindin in D-28k.

Acts as a shuttle in the small intestine cells for Ca2+ to come in thru lumen and go thru the cell to blood.

Result is increased calcium absorption from diet-->blood

Front 48

How does the intestine respond to a low-Ca diet?

Back 48

It increases the fraction of digested Ca it absorbs.

Does this via vitD

Front 49

What are the actions of 1,25(OH)cholecalciferol on the kidney?

Back 49

Stimulates reabsorption of filtered Ca and phosphate (less impt than its actions on intestine).

Front 50

What are the actions of 1,25(OH)cholecalciferol on the bone?

Back 50

Stimulates bone resorption that requires new protein synthesis. Synergistic with bone-resorbing action of PTH.

(This is because you need Ca and phosphate in ECF to allow bone deposition to proceed)

Front 51

What makes calcitonin?

Back 51

parafollicular cells of thyroid

Front 52

What's the main action of calcitonin?

Back 52

Inhibit bone resorption, bringing plasma Ca2+ down to normal. Debatable relevance, no long-term effect probably.

Front 53

What happens in renal osteodystrophy? How to treat?

Back 53

Pts with advanced renal failure have decreased filtered phosphate and therefore hyperphosphatemia. Also decreased 1,25(OH)cholecalciferol --> hypocalcemia due to lack of good intestinal Ca absorption.

Hypocalcemia causes secondary hyperPTH.

Treat with 1,25(OH)cholecalciferol to bypass renal defect in synthesis.