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Endocrinology > Parathyroid Hormone Metabolism > Flashcards

Parathyroid Hormone Metabolism Flashcards

1
Q

Parathyroid Gland embryology?

A

derived from the 3rd an 4th branchial pouches that migrate

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2
Q 
Parathyroid Hormone (PTH)‏
is the main player in controlling what? 2
A

CA2+ and phosphate homeostasis in the body

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3
Q

What cells comprise the parathyroid glands? 2

A

chief cells- PTH

Oxyphil cells

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4
Q

PTH is packaged in cytoplasmic granules that contain what?

What is the half life once it is released?

A

proteases

Very short half-life (minutes)—once released

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5
Q

PTH feeds back to stimulate conversion of 25-hydroxycholecalciferol in the kidney to 1,25-dihydroxycholecaleciferol. Or in basic terms?

A

Calcitriol

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6
Q

Once PTH released—quickly degraded by what?

Normal calcemic state what is the percentage of circluating PTH?

Hypocalcemia PTH increases to?

Hypercalcemia PTH decreases to?

A

liver and kidney (within 2-4 minutes)

20%

33%

4%

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7
Q

The net effect of PTH on calcium and phophate is what?

A

an increase in the plasma calcium concentraation with no chang or decrease in the plasma phophate concentration

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8
Q

What controls the secretion of PTH?

Parathyroid cells have what kind of receptor?

CaR is also expressed in the kidney and Regulates what?

Hence hypercalcemia directly promotes what?

A

Ca2+

calcium-sensing receptor (CaR)
Ca2+ is the ligand

Regulates Ca2+ handling by the renal tubules

Hence hypercalcemia directly promotes excretion of Ca2+

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9
Q

Adequate/elevated Ca2+ levels block what?

Adequate intake blocks what?

Adequate levels maintain what? 2

A

Adequate/elevated Ca2+ levels block PTH from activating Calcitriol

Adequate intake blocks leaching Ca2+ from bones

Adequate levels maintain balanced renal absorption of Ca2+ and phosphate

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10
Q

PTH-Related Protein (PTHrP)
secreted by what? 2

What does this cause? 2

Less likely to stimulate what?

Does it increase Ca2 absorption from the intestnie?

A

Secreted by nonmetastatic solid tumors and some patients w/ non-Hodgkin lymphoma

Increases bone resorption and distal tubule Ca2+ reabsorption

Less likely to stimulate 1, 25-dihdroxy vitamin D production

Does not increase Ca2+ absorption from the intestines!

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11
Q

Calcitonin is secreted by what?

What is it stimulated by?

How does it decrease plasma Ca2 levels? 2

A

Peptide hormone secreted by the thyroid gland—parafollicular cells

High Ca2 levels

  1. Decreases absorptive activities osteoclasts
  2. Decreases formation of new osteoclasts
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12
Q

Calcium is partially absorbed where?

Filtration where?

Where is 99% of our calcium found?

Where is the rest of it found (active calcium)?

A

Involves partial absorption from the intestines

Filtration in the kidneys with 100-200mg excreted

99% remains in bone as: hydroxyapatite—Ca10(PO4)6(OH)2 (Serves as a reservoir)

1% in extracellular fluid/flows in and out of cells
of which 50% bound to albumin/50% ionized state (nonactve calcium

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13
Q

Where is most of the phosphate in the body found?

A

85% of the body’s phosphate is stored in bone

14-15% in the cells

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14
Q

What helps absorb calcium in intesine?

PTH stimulates calc absoprtion from where and release from where?

If Ca2 is too low what is secreted?

A

Vitamin D

absorption from kidneys and release frrom bones

PTH
more calcium in blood stream

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15
Q

Calcium’s Role in the Body

5

A
  1. Normal bone density
  2. Clotting cascade
  3. Muscle function: smooth, cardiac and skeletal
  4. Transmission of nerve signals
  5. Intracellular signaling of many cellular hormones
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16
Q

Ca2 and PO4 levels tend to be correlated how?

A

Important to note that Ca2+ and PO4- tend to be opposite

When one rises the other falls

Both necessary for normal bone density

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17
Q
  1. How is Vitamin D made in the skin?
  2. How is Vitamin D further metabolized?
  3. Where do we get intestinal absorption from?
  4. Where is Vit D stored and where is excess stored?
    2
A
  1. Photoisomeriztion of provitamin D in the skin to vitamin D3(cholecalciferol)
  2. Binds to vitamin D binding proteins (DBP) and is further metabolized
  3. Intestinal absorption from the diet:
    Fortified milk**
    Fatty fish and cod-liver oil
    Lesser extent eggs

Liver stores Vitamin D, excess stored in adipose tissue

18
Q

Calcitriol causes Ca and phosphate levels do do what in the:
GI?
Bones?
Renal?

A

increased intestinal absorption of calcium

Bone reabsorption

Decreased renal Ca absorption
Increased phosphate absorption

19
Q

Where is Cholecalciferol (vitamin D3)‏ formed?

Where is it converted to 25-hydroxy vit D?

Whats the most active form of Vitamin D?

A

Formed in the skin

Converted to 25-hydroxy Vitamin D in liver, but prevented from over accumulating (vitamin stored in liver-months)‏

1,25-dihydroxycholecalciferol (calcitriol)

20
Q

1,25-dihydroxycholecalciferol (calcitriol) is formed where?

This step of Vit D is stimulated by what?

A

Formed in the proximal tubules (kidney)
Most active form of vitamin D**

This step stimulated by parathyroid hormone (PTH)‏

21
Q

Vitamin D Metabolism is closely coupled with what?

4

A
  1. w/ Ca2+ homeostasis,
  2. serum Ca2+ and
  3. phosphate levels and
  4. parathyroid hormone (PTH)
22
Q

In hypocalcemia increased PTH increases the activity of what?
What does this result in?

(which would result in what?)
3

A

of alpha-1-hydroxylase in the kidney resulting in increased levels of calcitriol

  1. Increased ca bone reabsorption
  2. decreases phohate and calcium excretion in urine
  3. increase intestinal absotption
23
Q

Vitamin D functions? 2

What must it be converted to and where?

What does calcitriol do to Ca2 and the kidneys?

A

1, Increases Ca2+ absorption from GI tract
2. Important in bone deposition & absorption

Must be converted in liver & kidneys to active metabolite (Calcitriol)

Calcitriol increases absorption of Ca2+ in kidneys

24
Q

Calcitriol Concentration depends on what?

2

A
  1. Availability of calcidiol

2. Activity of renal enzyme alpha-1-hydroxylase

25
Q

Activity of renal enzyme alpha-1-hydroxylase: regulated by?

3

A
  1. PTH
  2. Low serum level of phosphate
  3. Plasma calcitriol concentration:
26
Q

Activity of the 24-hydroxylase gene is increased by calcitriol which inactivates it.

PTH reduces the gene activity—Which would do what?

A

increase calcitriol

27
Q

Calcitriol binds to a vitamin D receptor where?

A
  1. In intestine

2. On parathyroid glands

28
Q

Most important action of calcitriol?

Other effects:
3

A

Most important action:

  1. Promote enterocyte differentiation
  2. Promote intestinal absorption of Ca2+**

Other effects:

  1. Stimulate phosphate absorption
  2. Direct suppression of PTH at the level of the parathyroid glands
  3. Allows PTH-induced osteoclast activation
29
Q

Calcitriol Activity on Parathyroids:
Parathyroids contain what kind of receptors?

Calcitriol binds to the receptors inhibiting what?

A

Parathyroids contain vitamin D receptors

Calcitriol binds to the receptors:

  1. Inhibits PTH synthesis
  2. Inhibits parathyroid-cell proliferation
30
Q

Osteoblasts do what?

A
  1. Continually deposit bone even in adults

On the outer surfaces of bone and in bone cavities

31
Q

Osteoclasts do what?

A

Continually absorb bone

Found in the bone matrix

32
Q

In adults deposition and absorption are?

A

equal

33
Q

Describe Bone remodeling.

What is the new matrix like compared to the old?

A

Bone adjusts its strength to stress applied on it

New matrix is tougher and less brittle then old matrix

34
Q

Bone that is “stressed” has greater deposition of bone matrix. Why?

A

Osteoblastic activity is stimulated

The bone is stronger and more dense

35
Q

Describe bone resorption?

What regulates this process?

How long does it take?

A

Osteoclasts remove mineral and matrix on trabecular and cortical bone

High local concentrations of Ca2+ may regulate this process

2 weeks

36
Q

Describe bone reversal. 2 steps

How long does this take?

A
  1. Mononuclear cells appear on the bone surface
  2. They lay down a glycoprotein-rich matrix so the new osteoblasts can adhere

4-5 weeks

37
Q

Describe bone formation
2

How long does this take?

A
  1. Waves of osteoblasts lay down bone until the resorbed bone is completely replaced
  2. When this phase is completed the surface is covered w/ flattened lining cells and there is a prolonged resting period

Up to 4 months

38
Q

PTH effects on kidney?

2

A
  1. ↑ Ca resorption in the renal tubules

2. Kidneys convert Vit D to it’s active form

39
Q

PTH effects on bone?

2

A
  1. ↑ osteoclast activity

2. Release Ca2+ and PO4-

40
Q

PTH effects on GI tract?

1

A
  1. GI tract ↑ absorption of Ca2+, PO4-

Endocrinology (23 decks)

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