Endocrine 14 - Calcium Homeostasis And Calcium Regulating Hormones

Front 1

What is the range of plasma Ca concentrations?

Back 1

2.2-2.6 mM (very narrow)

Front 2

What are the results of hypocalcemia?

Back 2

Muscle failure, tetany, convulsions, death.

Front 3

What are the results of hypercalcemia?

Back 3

Renal dysfunction, muscle weakness, coma.

Front 4

What is the level of intracellular Ca concentration?

Back 4

100 μM

Front 5

What will happen if intracellular Ca is increased for prolonged periods?

Back 5

Ca-dependent proteases, nucleases, and lipases will cause cytodegradation.

Front 6

What % of Ca is bound, and to what protein is it bound?

Back 6

50%; albumin.

Front 7

What is measured to estimate free Ca?

Back 7

Albumin.

Front 8

What are the results of severe hypophosphatemia?

Back 8

Muscle weakness, abnormal bone formation.

Front 9

What are the 3 points of regulation for Ca?

Back 9

1) Intestine
2) Kidney
3) Bone

Front 10

What are the 2 points of regulation for phosphate?

Back 10

1) Kidney
2) Bone

Front 11

How is the intestine affected by PTH?

Back 11

No direct effect.

Front 12

How is the intestine affected by Vit D?

Back 12

Increase Ca absorption (primary action of Vit D) via active mechanisms.
*Vit D is the only steroid hormone that regulates Ca at the intestine.

Front 13

How is the intestine affected by Calcitonin?

Back 13

No known effect.

Front 14

How is the kidney affected by PTH?

Back 14

Increase Ca reABsorption
Decrease Phosphate reABsorption (increase Phosphate excretion)
*Remember, PTH wants to keep plasma Ca levels high, but in the case of the kidney, will release phosphate.

Front 15

How is the kidney affected by Vit D?

Back 15

Increase Ca absorption
Increase Phosphate reABsorption

Front 16

How is the kidney affected by Calcitonin?

Back 16

Increase Ca excretion
Increase Phosphate excretion
*Calctinonin wants to keep Ca levels in the plasma low.

Front 17

How is bone affected by PTH?

Back 17

Increase Ca resorption
Increase Phosphate resorption (primary purpose of PTH)

Front 18

How is bone affected by Vit D?

Back 18

Increase Ca resorption
Increase Phosphate resorption
(only during hypocalcemia, when Vit. D levels are extremely high; otherwise it will aid in bone formation.)

Front 19

How is bone affected by Calcitonin?

Back 19

Decreased Ca resorption/Increased Ca absorption (primary purpose).

Front 20

What is ectopic PTH and what are its effects?

Back 20

Cancerous hypersecretion of PTH that promotes bone resorption and hypercalcemia.

Front 21

Why are canaliculi useful in the bone?

Back 21

Canaliculi provide a large interface between mineralized bone and intracellular fluid for efficient bone remodeling to occur.

Front 22

What are osteoclasts?

Back 22

Chew bone for resorption, releasing Ca and phosphate into circulation.

Front 23

What are osteoblasts?

Back 23

Build bones - lay down osteoid to rebuild bone.

Front 24

What 3 hormones will increase bone formation?

Back 24

1) Vit D (mineralization occurs when within normal plasma range)
2) Calcitonin
3) PTH (intermittent, low levels)

Front 25

What 2 hormones will increase bone resorption?

Back 25

1) Vit D - at excessive levels
2) PTH (constant)

Front 26

How will an increase in Ca affect PTH levels?

Back 26

Drastic decrease because no bone resorption necessary.

Front 27

How will a decrease in Ca affect PTH levels?

Back 27

Drastic increase because because bone resorption is necessary to increase plasma Ca.

Front 28

What is the result of PTH binding to bone cell receptors?

Back 28

Bone resorption, releasing Ca and phosphate into the circulation.
*Remember, PTH wants to keep plasma Ca high.

Front 29

What is the result of PTH binding to kidney receptors?

Back 29

Stimulates Ca reabsorption, BUT increases phosphate excretion.

Front 30

What is the general name for Vit D?

Back 30

Calciferol.

Front 31

What is cholecalciferol?

Back 31

Form of Vit D3 found mostly in animals.

Front 32

What is calcidiol?

Back 32

25-OH-Vit D

Front 33

What is calcitriol?

Back 33

1,25-(OH)2-Vit D, active form.

Front 34

Describe the endogenous pathway of 1,25-(OH)2-Vit D synthesis.

Back 34

SLiK pathway - begins with skin Vit D formation by UV light, transport to the liver, and then to the kidney.

Front 35

Describe the exogenous pathway of 1,25-(OH)2-Vit D synthesis.

Back 35

Intestinal absorption of Vit D enters into the liver.

Front 36

What is transcalciferin?

Back 36

Transport globulin that binds Vit D in the plasma.
Also known as DBP.

Front 37

How is Vit D status measured in patients?

Back 37

Assays of 25-OH-Vit D because it is more stable, have high levels in the plasma, longer 1/2 life.

Front 38

What is the inactive, storage form of Vit D?

Back 38

24,25-(OH)2-Vit D

Front 39

What are rickets?

Back 39

Childhood softening of the bone due to Vit D deficiency.

Front 40

How do Vitamin D Receptors (VDR) work?

Back 40

Bind Vit D and then become transcription factors in the nucleus. They heterodimerize with RXR to increase or decrease transcription, depending on the target.

Front 41

How is 1,25-(OH)2-Vit D regulated at the kidney level?

Back 41

Low levels of Ca or Phosphate will produce more 1,25-(OH)2-Vit D.
Production of 1,25-(OH)2-Vit D is negative feedback for PTH because plasma Ca will already be high.
???

Front 42

Describe passive intestinal absorption of Ca.

Back 42

Passive absorption occurs paracellularly and is independent of 1,25-(OH)2-Vit D.

Front 43

Describe active intestinal absorption of Ca.

Back 43

Active absorption occurs transcellularly and is dependent on 1,25-(OH)2-Vit D.
Much more Ca is absorbed by active, transcellular absorption with Vit D.

Front 44

How does Ca get from the intestinal lumen to the blood stream?

Back 44

Via the Ca binding protein, calbindin.

Front 45

What is the result of Vit D binding to VDR on the parathyroid?

Back 45

Suppresses PTH secretion (PTH tries to raise plasma Ca) as negative feedback.

Front 46

What promising benefit does activated VDR seem to have?

Back 46

Anti-proliferative, pro-apoptotic signals to tumor cells.

Front 47

Where is Calcitonin produced?

Back 47

In parafollicular "C" cells of between thyroid follicles.

Front 48

What hormone stimulates the release of Ca postprandially?

Back 48

Gastrin to prevent diet-induced hypercalcemia.

Front 49

What is the effect of calcitonin on the bone?

Back 49

Increases bone formation by absorbing Ca and phosphate, decreasing their levels in the circulation.

Front 50

What is the effect of calcitonin on the kidney?

Back 50

Increase phosphate excretion.

Front 51

What is the relationship between PTH and Calcitonin?

Back 51

Inversely related.

Front 52

Vit D, Calcitonin, PTH: which of these are nonessential for human survival?

Back 52

Calcitonin.

Front 53

What enzyme is responsible for activating Vit D
[25-OH-Vit D3 --> 1,25-(OH)2-Vit D3]?

Back 53

1-α-hydroxylase, which occurs in the kidney.
*Obviously this must be a 1-hydroxylase by looking at the product.

Front 54

What factors cause conversion of 25-OH-Vit D to active 1,25-(OH)2-Vit D3?

Back 54

Any Ca, phosphate, or Vit D deficiency, and an increase in PTH secretion.

Front 55

What factors cause conversion of 25-OH-Vit D to inactive 24,25-(OH)2-Vit D3?

Back 55

Any Ca, phosphate, or Vit D sufficiency or excess.

Front 56

How does Ca homeostasis respond to a state of hypocalcemia?

Back 56

PTH levels will increase, plasma Ca will increase, Vit D will increase, and phosphate will be excreted out through the kidney.
Once levels normalize, PTH and Vit D will decrease to normal levels. Both are regulated by plasma Ca levels.

Front 57

How does phosphate homeostasis respond to hypophosphatemia?

Back 57

Vit D will increase, intestinal absorption of phosphate will increase, bone resorption of phosphate will increase, a subsequent increase in Ca will suppress PTH, which will decrease kidney excretion of phosphate, and plasma phosphate levels will be restored. Vit D will return to normal levels once plasma phosphate normalizes.