Endocrine - Bone, Ca, & Hormones - COX

Question 1

What three forms does plasma calcium exist in? What is the main form? What is the biologically active form?

Answer 1

Complexed with organic compounds
Protein bound - most common
Ionized - biologically active form

Question 2

What symptoms are seen with low Ca levels? High Ca levels?

Answer 2

Low Ca - excitability of cells - titanic convulsions

High Ca - death due to muscle paralysis and coma

Question 3

What three hormones regulate plasma calcium levels? Which two have a major role? Which has a minor role?

Answer 3

PTH & Vit. D - major role

Calcitonin - minor role

Question 4

Where is PTH produced? Is it a protein or steroid hormone?

Answer 4

Produced by chief cells in parathyroid gland

Peptide hormone

Question 5

What portion of PTH contains the biological activity of the hormone? What region is primarily responsible for receptor binding?

Answer 5

N-terminal

Region 25-34

Question 6

What form of PTH is synthesized? Where is it processed? Is it stored?

Answer 6

Synthesized as preproPTH
Processing in ER and golgi
Stored in secretory vesicles

Question 7

What are the three fates of PTH once it is put into secretory vesicles?

Answer 7

Transportation into storage
Degradation
Immediate Secretion

Question 8

How do low plasma Ca+2 levels affect PTH?

Answer 8

Increased PTH synthesis by increasing size and number of chief cells

Question 9

How does Vit D play a role in regulating PTH expression?

Answer 9

PTH gene contains several vit. D response elements (VDRE)

When vit D is bound to there, PTH expression is decreased

Question 10

How do chief cells of the parathyroid gland know where to make PTH or not?

Answer 10

By detecting plasma Ca

Question 11

What type of calcium receptor is on the parathyroid chief cells? How does signaling differ when Ca is bound vs when Ca is not bound?

Answer 11

Ca bound (high plasma Ca) - stimulates phospholipase C which increases IP3, inhibiting adenylate cyclase, decrease cAMP - PTH release REDUCED
Ca not bound (low plasma Ca) - Decreasing IP3 production, which increases CAMP - PTH release INCREASED

Question 12

How is PTH secretion related to calcium concentration?

Answer 12

Inversely proportional

Question 13

Is PTH secretion ever fully suppressed?

Answer 13

No, some PTH is always being released

Question 14

What ionized Ca concentration must be reached to achieve maximal rate of PTH secretion? What is the typical set-point?

Answer 14

1.1 mmol/L

Set-point - 1.3 mmol/L

Question 15

How long can maximal PTH secretion be sustained for? What?

Answer 15

1.5 hours

Parathyroid glands have very fer storage granules

Question 16

What three ways for PTH act on the system to increase Ca+2 concentration? Which is most rapid? Which has largest effect/impact?

Answer 16

Reduce renal excretion - most rapid
Increase intestinal reabsorption
Increase rate of bone dissolution - largest effect

Question 17

In a prolonged dietary deficiency of Ca2+, what gets sacrificed?

Answer 17

Bone (bone density)

Question 18

Besides having a direct effect on production of osteoclasts, what other cell does PTH and vit. D act on to increase osteoclast activity? Through what?

Answer 18

Osteoblasts

They increase OAF (osteoclast activating factors) which stimulates osteoclast activity

Question 19

What is the counter-ion to Ca?

Answer 19

Phosphate

Question 20

How does PTH affect plasma phosphate levels? How?

Answer 20

Increases renal clearance of phosphate

Question 21

What are mild symptoms of hypoparathyroidism? Severe symptoms?

Answer 21

Mild - muscle cramps and tetany

Severe - muscle paralysis, convulsions, and death

Question 22

What are the two usualy, yet rare, causes of hypoparathyroidism?

Answer 22

Autoimmune

Accidental removal during surgery

Question 23

What is pseudohypoparathyroidism? Where does the problem occur? What are 4 phsyical findings seen?

Answer 23

PTH is produced but receptor defect leads to low Ca and high PO4 levels
Short stature, Mental retardation, short metatarsals, short tarsals

Question 24

What is the most common cause of primary hyperparathyroidism? What is seen on blood work? What are symptoms?

Answer 24

Parathyroid ademona
Elevated Ca and PTH, decreased PO4
Kidney stones, nephrocalcinosis, frequent UTIs, decrease renal function

Question 25

What is the most common cause of secondary hyperparthyroidism? Why?

Answer 25

Progressive renal failure | Lack of renal vitamin D synthesis leads to hyperplasia and hypersecretion of PTH

Question 26

In the skin exposed to sunlight, 7-dehydrocholesterol is converted to what?

Answer 26

Vit D3

Question 27

What binds vit. D3, moving it from skin/intestine into blood stream?

Answer 27

Vitamin D-binding proteins

Question 28

What is the major form of vitamin D in the blood? Where is it converted to active form? By what? What else is need?

Answer 28

25(OH)-D3 major form in blood Converted to 1,25(OH)2-D3 in kidney by 1alpha-hydroxylase Require: NADPH, MG2+, oxygen

Question 29

High levels of 1,25(OH)2-D3 inhibit what? Increase activity of what? Producing what?

Answer 29

Inhibit 1 alpha-hydroxylase Increase activity of 24-hydroxylase Produces inactive 24,25(OH)2-D3

Question 30

What hormone receptor family is 1,25(OH)2-D3 receptor a member of?

Answer 30

Steroid receptor family

Question 31

What DNA bind-domain does 1,25(OH)2-D3 have?

Answer 31

Zinc Finger

Question 32

What is seen in Rickets (non-genetic)? Cause?

Answer 32

``` Low plasma calcium and PO4, high bone demineralization due to vit. D deficiency Poor nutrition (low vit D) ```

Question 33

What are the two types of genetic Rickets? Differentiate them

Answer 33

Type I - defect in conversion of 25(Oh)-D3 to 1,25(OH2)-D3 due to mutation of 1 alpha-hydroxylase problem Type II - autosomal recessive due to single amino acid change in zinc finger, creating non-function vit. D receptor

Question 34

What is vit. D deficiency in adults called?

Answer 34

Osteomalacia

Question 35

What are two causes of osteomalacia?

Answer 35

Decreased Vit D intake | Loss of renal parenchyma - leading to increased PTH, increase bone reabsorption

Question 36

What are symptoms of loss of renal parenchyma in osteomalacia known as? What is the treatment?

Answer 36

Renal osteodystrophy | Treat with vit. D

Question 37

What is calcintonin secreted from?

Answer 37

Parafollicular cells of thyroid gland

Question 38

What activity does calcitonin suppress?

Answer 38

Osteoclast activity suppressed, promoting renal excretion of Ca and Phosphate