Exam #4: Calcium and Bone Physiology

Question 1

List the plasma forms of calcium.

Answer 1

There are three forms of Ca++ in the plasma:

1) Free/ ionized Ca++ (50%)
2) Calcium that is bound to protein i.e. albumin (40%)
3) Ca++ bound to small diffusible anions (10%)

Question 2

In which form is ~ 50% of the total calcium?

Answer 2

Free/ ionized Ca++

*Note that this is the only form of Ca++ that is biologically active & regulated

Question 3

Which forms of Ca++ are filtered in the glomerulus?

Answer 3

Ca++ that is NOT protein bound i.e. 60% of the total Ca++ in plasma is filtered at the glomerulus

Question 4

How does pH effect Ca++ in the plasma?

Answer 4

Alkaline pH= more Ca++ bound to protein

Acidic pH= less Ca++ bound to protein

Question 5

What are the symptoms of hypocalcemia?

Answer 5

Hypocalcemia causes threshold to become CLOSER to membrane potential (more negative), which makes nerves & muscles MORE excitable. Symptoms include:

1) Hypocalcemic tetany
2) Latent tetany revealed by Trousseau or Chvostek sign
3) Paresthesias
4) Laryngospasm
5) Seizures
6) Syncope, CHF, and angina

*Chovstek sign= tapping on the facial nerve that elicits twitching of the facial muscles
Trousseau sign= carpopedal spasm upon inflation of a blood pressure cuff

Question 6

What are the symptoms of hypercalcemia?

Answer 6

Hypercalcemia causes threshold to more FARTHER from resting membrane potential (more positive), making nerves and muscles LESS excitable. Symptoms include:

1) Fatigue
2) Muscle weakness
3) Constipation
4) Polyuria
5) Kidney stones
6) Coma
7) Cardiac arrest

Question 7

Describe the regulation of plasma Ca++.

Answer 7

• Ca++ homeostasis involves the coordinated interaction of the: bone, kidneys, and GI tract
• Balance is attained when renal excretion= GI absorption of Ca++

On a daily basis:

• 1,000mg Ca++ ingested but only 350mg absorbed in the GI tract
• 150 mg secreted into the salivary, pancreatic, and intestinal fluids
• Net 200mg is absorbed, which much be excreted by the kidneys to be in balance

*Note that 1,25-dihydroxycholecaliferol (active Vitamin D) increases GI absorption of Ca++

Question 8

What hormone increased GI absorption of Ca++?

Answer 8

Active form of Vitamin D

Question 9

Describe the regulation of plasma phosphorus.

Answer 9

GI Tract: most of the dietary phosphorus is absorbed
- Vitamin D controls uptake

Bone: phosphorus is part of the major bone crystalline salt, hydroxapatite

Kidney: at low levels all phosphate is reabsorbed but at higher & higher levels some is excreted

• PTH increases phosphate excretion
• Fibroblast growth factor 23 (FGF 23) is a peptide hormone synthesized by osteoblasts and osteocytes that increases renal excretion of phosphate

Question 10

Why does hydroxyapatite precipitate in bone and not in other tissues?

Answer 10

Inhibitors found in other body tissues including plasma prevent precipitation

Question 11

Outline the mechanism of bone growth and calcification.

Answer 11

1) Osteoblasts secrete collagen and ground substance
2) Osteoblasts become trapped in osteoid and become osteocytes
3) Ca++ salts precipitate onto collagen and then hydroxyapatite crystals form

Question 12

What cells are responsible for bone deposition?

Answer 12

Osteoblasts

Question 13

Which cell type is responsible for bone resorption?

Answer 13

Osteoclasts

Question 14

Describe bone remodeling.

Answer 14

Bone remodeling, or the deposition of new bone and reabsorption of old bone, is a continuous process

Question 15

What is the general function of PTH in bone remodeling?

Answer 15

Stimulation of osteoclasts and bone resorption

Question 16

How does PTH stimulate bone resorption?

Answer 16

PTH stimulates bone resorption indirectly:

1) Binds osteoBLASTS and causes them to release cytokines 2) Cytokines, osteoprotegerin ligand (OPLG) activate receptors on preosteoCLAST cells
3) PreosteoCLAST cells differentiate into osteoCLASTS that promote bone resorption

Question 17

What are the roles and alternate names of: OPGL and OPG? Which increases bone resorption?

Answer 17

OPLG= “Osteoprotegerin Ligand” is a cytokine released from osteoBLASTS that induces the differentiation of osteoCLASTS in response to PTH binding to PTH receptors on osteoBLASTS

• OPLG thus increases bone resorption
• OPLG is also called “RANK Ligand”

OPG= “Osteoprotegerin,” is a cytokine produced by osteoBLASTS that INHIBITS bone resorption by acting as a decoy receptor for OPGL

Question 18

What is the name for this most active form of vitamin D?

Answer 18

1,25-dihydroxycholecalciferol

Question 19

Where is vitamin D3 converted (2 steps, 2 organs) into the most active form of vitamin D?

Answer 19

Liver= cholecalciferol–>25-hydroxycholecalciferol

Kidney= PTH converts 25-hydroxycholcalciferol into 1,25-dihydroxycholecalciferol
- Enzyme= 1-alpha hydroxylase & is essential for the formation of ACTIVE Vitamin D

Question 20

What hormone is required for the kidneys to convert Vitamin D into its active form?

Answer 20

PTH

Question 21

What is the function of Vitamin D in the GI tract?

Answer 21

Stimulation of Ca++ & phosphate absorption

Question 22

What is the function of Vitamin D in the Kidney?

Answer 22

Stimulation of Ca++ & phosphate reabsorption

Question 23

What is the function of Vitamin D on the bones?

Answer 23

Promotes PTH activity on osteoclasts i.e. promotes PTH mediated bone resorption

Question 24

What is the dose-dependent effect of Vitamin D on the bones?

Answer 24

Small amounts of Vitamin D promote calcification

Question 25

What is osteomalacia?

Answer 25

Softening of new bone in adulthood due to deficient mineralization–>bending in weight-bearing bones
- Caused by a failure of a damaged kidney to produce the active form of Vitamin D

Question 26

Describe how/why renal disease can cause osteomalacia.

Answer 26

• Kidney is required for the formation of the active form of Vitamin D
• Vitamin D promotes bone calcification
• Without Vitamin D, bones are soft due to deficient calcification/ mineralization

Question 27

What is the primary stimulus for PTH secretion?

Answer 27

Low ECF Ca++

Question 28

What is the general function of PTH?

Answer 28

PTH generally functions to regulate the concentration of Ca++ in the ECF; it increases Ca++ in the ECF BUT DECREASE phosphate

*****Note that a lack of PTH will lead to death from hypocalcemia tetany

Question 29

Why is the action of PTH to decrease phosphate important?

Answer 29

Increase in Ca++ & decrease in phosphate prevents crystallization of calcium phosphate

Question 30

What are the actions of PTH on the kidney?

Answer 30

1) PTH increases the amount of Ca++ reabsorbed in the distal portions of the nephron
2) PTH inhibits phosphate reabsorption from the kidney
3) PTH increases 1a hydroxylase, the enzyme in the kidney that forms active Vitamin D

Question 31

What is the action of PTH in regards to Vitamin D?

Answer 31

1) Increases the enzyme that forms active Vitamin D in the kidney
2) By the action of Vitamin D (indirect), increases uptake of Ca++ & phosphorus from the GI

Question 32

What is the function of Calcitonin (CT)?

Answer 32

Decrease bone resorption & Ca++ release

Question 33

What is the stimulus for CT release?

Answer 33

Elevated plasma Ca++

Question 34

What are the causes and symptoms of primary hyperparathyroidism?

Answer 34

Primary hyperparathyroidism is caused by enlargement of one or more of the parathryoid glands, leading to hypercalcemia and hypophosphatemia. Symptoms include:

• Ca++ kidney stones
• Weak bones & bone fractures from bone resorption
• Constipation & excessive urination

Question 35

What are the causes and symptoms of secondary hyperparathyroidism?

Answer 35

• Secondary hyperparathyroidism occurs in patients with diseases that cause chronically low plasma Ca++
• Low ECF Ca++ leads to COMPENSATORY hyperstimulation of the parathyroid gland, hypertrophy, & HYPERPARATHYROIDISM
• Symptoms are the same as for primary hyperparathyroidism

Question 36

What are the causes and symptoms of hypoparathyroidism?

Answer 36

Hypoparathyroidism is caused by parathyroidectomy i.e. accidental damage during thyroid surgery, and can lead to a steady decline in plasma Ca++. Symptoms include:

• Neuromuscular excitability
• Hypocalcemia tetany

Question 37

What are the causes and symptoms of pseudohypoparathyroidism?

Answer 37

Pseudohypoparathryoidism occurs when patients have signs and symptoms of hypoparathyroidism, but PTH levels are normal or elevated. This is caused by a defect in the PTH receptor, or in the tissue response to PTH. Symptoms include symptoms of hypocalcemia.

Question 38

What is the difference in the effects of PTH and FGF23 on PTH and Calcitriol?

Answer 38

BOTH increase phosphate excretion by the kidneys

Opposite effects on calcitriol

• PTH= increases renal production of calcitriol
• FGF23= decreases renal production of calcitriol

Question 39

What is the role of estrogen in bone remodeling?

Answer 39

Estrogen stimulates OPG production, which is a cytokine that acts as a decoy for OPGL

**Thus, estrogen PREVENTS bone resorption, which is why post-menopausal women are at increased risk for osteoporosis

Question 40

What is the effect of glucocorticoids & PTH on OPG?

Answer 40

Decreased synthesis of OPG i.e. bone resorption