Module 9

Question 1

What is the importance of Calcium (Ca2+)

5 pts

Answer 1

1. Structural component (with phosphate) of bones, teeth
2. Blood clotting
3. Maintain trasnmembrane potential of cells (along with Na+ and K+)
4. Muscle contraction
5. Second messenger in hormonal and neurocrine signal trasnduction

Question 2

What is the body distribution of calcium?

3 pts

Answer 2

1. Intracellular calcium
2. Bllod and extracellular fluid
3. Bone

Question 3

How is calcium distributed intracellularly?

3 pts

Answer 3

• majority of calcium in mitochondria and ER
• concentrations fluctuate greatly (100nM to 1uM)
• integral to calcium’s role in intracellular signaling, enzyme activation and muscle contractions

Question 4

How is calcium distributed in the blood andextracellular fluid?

1 pt

Answer 4

• concentration approximately 1mM, or 10,000x the basal concentration offree calcium within cells

Question 5

How is calcium distributed in the bones?

3 pts

Answer 5

• majority of body calcium is in bone
• 99% of the calcium is tied up in the mineral phase
• 1% is in a pool that can rapidly exchange with EC calcium

Question 6

What are the majorsite of calcium regulation?

3 pts

Answer 6

Regulation of calcium homeostasis occurs via trasnfer of calcium between the blood and 3 major target organs:
* bone
* intestine
* kidney

Question 7

What is the difference between resorption and reabsorption?

2 pts

Answer 7

• Resorption: the process of breaking down and assimilating (Ca2+ mobilization)
• Reabsorption: the process of re-absorbing (absorbing again)

Question 8

How is bone a major site of calcium regulation?

2 pts

Answer 8

• vast reservoir of Ca2+ (immediate source of Ca2+)
• stimulate resorption of bone mineral releases Ca2+ and phosphate into blood

Question 9

How is the small intestine a major site of calcium regulation?

2 pts

Answer 9

• site where dietary Ca2+ is actively transported across mucosa
• dependent on expression of a Ca2+ binding protein in epithelial cells

Question 10

How are kidneys a major site of calcium regulation?

2 pts

Answer 10

• under normal blood (Ca2+), almost all of the Ca2+ that enters glomerular filtrate is reabsorbed from the tubular system back into blood, which preserves blood (Ca2+)
• if tubular reabsorption of Ca2+ decreases, Ca2+ is lost by excretion into urine

Question 11

What hormones regulate calcium homeostasis?

3 pts

Answer 11

1. Parathyroid hormone (PTH)
2. 1,25-DHC or vitamin D3 (active form)
3. Calcitonin (CT)

1 and 2 - increase circulating Ca2+ , 3 - decreases circulating Ca2+

Question 12

What are the parathyroid glands?

4 pts

Answer 12

• Generally two pairs, located behind the thyroid gland
• About 2-5% of the human population has supernumerary parathyroid (usually 6 to 8 glands)
• The parathyroid glands evolved from gills, which also regulate calcium and ionic balance in fishes
• Parathyroidglands are not associated with thyroid in birds, reptiles, amphibians

Question 13

What is the histology of the parathyroid glands?

2 pts

Answer 13

1. Chief cells: source of PTH, most numerous
2. Oxyphil cells: unknown function, appear at puberty, increase in number with age

Question 14

What is a parathyroid hormone (PTH)?

1 pt

Answer 14

• PTH is a single-chain polypeptide hormone of 84 amino acids

Question 15

How is parathyroid hormone secretion controlled?

3 pts

Answer 15

• PTH is released in response to low extracellular concentrations of free calcium
• Calcium concentrations fall below the normal range, there is a steep increase in secretion of prarathyroid hormone
• Low levels of the hormone are secreted even when blood calcium levels are high

Question 16

What are calcium sensing receptors?

4 pts

Answer 16

Chief cell monitors extracellular free (Ca2+) via an integral membrane protein that functions asa calcium-sensing receptor (CaSR)
* seven-spanning membrane G-protein coupled receptor
Expressed in a broad range of cells, including parathyroid cells and C cells in the thyroid gland
* also expressed in several cell types in the kidney, osteoblasts, a variety of hematopoietic cells in bone marrow, and in the gastrointestinal mucosa

Question 17

How does PTH action raise calcium in blood?

4 pts

Answer 17

PTH is a hypercalcemic hormone (action is to increase blood calcium)

Low concentration of calcium in blood -> release of parathyroid hormone -> 1. efflux of calcium from bone or 2. Decreased loss of calcium in urine
2. can possibly lead to -> 3. Enhanced absorption of calcium from intestine
1,2, and 3. lead to -> increased concentration of calcium in blood

Question 18

What is vitamin D/ 1,25-DHC?

6 pts

Answer 18

• Also known as cholecalciferol (Vit D3)
• Acts to increase blood calcium
• Not actually a vitamin!! instead a precursor of a steroid-like hormone
• Generated through the activity of PTH within the kidney
• The most important effect of VitD is to facilitate absorption of Ca2+ from the small intestine
• Together with PTH, VitD also enhances fluxes of calcium out of bone

Study feedback loop for PTH + VitD interaction in slides

Question 19

What is calcitonin (CT)

3 pts

Answer 19

• Considered a hypocalcemic hormone (decrease blood calcium)
• A 32-amino acid polypeptide hormone synthesized by parafollicular “C cells” of the thyroid gland
• Release is stimulated by elevated blood calcium level

Question 20

What is the function of calcitonin?

4 pts

Answer 20

The main function of calcitonin is to inhibit bone resorption by inhibiting osteoclasts (breakdown of bone)
1. Stimulates osteoblasts to form bone taking calcium out of the circulation
2. Inhibits the mobilization of bone (and calcium) by osteoclasts
3. End result is a decrease in the level of calcium in the blood thus helping to maintain proper blood calcium levels
* Increase in blood calcium -> increases secretion of calcitonin , decrease in blood calcium -> increases secretion of parathyroid hormone

Question 21

Give a short summary of each of the hormones that regulate calcium homeostasis.

3 pts

Answer 21

1. Parathyroid hormone (PTH)
   * increase resorption from bone
   * promoting reabsorption of calcium from kidney filtrate
   * increase synthesis of 1,25(OH)2D (a vitamin D metabolite) in the liver
2. 1,25-DHC or vitamin D3 (active form)
   * acceleratescalcium absorption from the intestine
   * increase resorption from bone
3. Calcitonin (CT)
   * inhibits bone resorption

Question 22

What is the pathophysiology of calcium homeostasis?

2 pts

Answer 22

• It is critical to maintain blood calcium concentrations within a tight normal range
• Deviations above or below the normal range frequently lead to serious disease

Question 23

What is hypercalcemia and hypocalcemia?

2 pts

Answer 23

• Hypecalcemia: blood calcium higher than normal
• Hypocalcemia: low blood calcium concentration

Question 24

What is primary hyperparathyroidism?

4 pts

Answer 24

• Also called parathyroid gland disease
• Most commonly due to a parathyroid tumor (adenoma) which secretes PTH without properregulation
• Symptoms: chronic elevations ofblood calcium concentration (hypercalcemia), kidney stones and decalcification of bone
• 3x more common in women than men

Question 25

What is secondary hyperparathyroidism? | 4 pts

Answer 25

* Occurs when a disease outside of the parathyroid gland leads to excessive secretion of PTH * Kidney disease - kidneys are unable to reabsorb calcium, bloodcalcium levelswill fall, stimulating continual secretion ofPTH to maintain calcium levels in blood * Inadequate nutrition - for example, diets that are deficient in calcium or vitamin D * Lead to increase decalcification of bone, leading to pathologicfractures or"rubber bones"

Question 26

What is the pathophysiology of milk fever? | 5 pts

Answer 26

* Milk fever is due to a severe drop in blood calcium - concentration of calcium is 12x higher in milk than in blood - cow must bring >30g of calcium/dayinto the plasma pool - a cow producing10L of colostrum requires about 23 g of calcium ( around 9x the total plasma pool of calcium) - A cow in early lactation milking 40L/day requires 56g of calcium * The earlypostpartum cow may not receive enough dietary calcium due to adepressed diet

Question 27

How to prevent milk fever? | 4 pts

Answer 27

* addition of anionic salts to the diet - anionic salts are minerals with a high proportion of anions. anions are negativelycharged; cations are positively charged * The DCAD (dietary cation-anion difference) method -> lower dietary cations (E.g.) potassium and sodium) and to increase dietary anions(chloride and sulfate)3 wks before parturition -> lowers pH of blood * Feeding a calcium-deficient diet * Higher dietary magnesium

Question 28

What is the treatment for milk fever? | 3 pts

Answer 28

* Supplementing blood calcium levels until the bone and intestinal transportsystems adapt to procide the necessary calcium - Should be implemented asearly aspossible - Must be administered slowly asit can result in cardiac arrest * Most common -> IV injection ofcalcium salts, usually calcium borogluconate * Calcium andphosphorous supplements (oral gels)can also be given around parturition