Calcium Balance

Question 1

What are the effects of hypercalcemia?

Answer 1

-increases in Ca above normal progressive depression of the nervous system
+symptoms appear when the bloof Ca level rises above 12mg/dL
+reflex activities of the nervous system are sluggish
+there is constipation and lack of appetite

Question 2

Decreases in calcium concentration causes the nervous system to become more __________.

Answer 2

Excited

Question 3

What is the distribution of calcium stored in the body?

Answer 3

• 0.1% in extracellular fluid
• 1% in the cells and organelles
• rest is stored in the bones

Question 4

How is phosphate storied in the body?

Answer 4

• 85% in bones
• 14-15% cells
• less than 1% in extracellular fluid
• extracellular phosphate conc is not nearly as well regulated as that of Ca

Question 5

What are the two forms of phosphate in the plasma?

Answer 5

HPO4- and H2PO2-

Question 6

What can hypocalcemia do in the body?

Answer 6

• causes nervous system excitement and tetany
  
  • nervous system is more excitable due to increased neuronal permeability to Na+

-hypocalcemia may also causes seizures
+first signs of tetany typically occurs in the hand, resulting in capopedal spasm

Question 7

When does tetany typically occur?

Answer 7

• when blood conc of Ca falls below normal level of 9.5mg/dL to 6mg/dL (35% below normal Ca conc)
• usually lethal at 4mg/dL

Question 8

How much calcium is typically taken into the body? How is it absorbed?

Answer 8

• 1000mg/day
• usually divalent ions are poorly absorbed but vitamin D promotes Ca absorption by the intestines, so 35% if ingested Ca is absorbed

Question 9

Calcium excretion

Answer 9

-Ca not absorbed is excreted in the feces
+250mg/day enter intestines via secreted GI juices and sloughed mucosal cells
+90% of daily intake is excreted

Question 10

Renal excretion of calcium and phosphate

Answer 10

• about 100mg/day (10%) of the ingested Ca is excreted in the urine
• 41% of plasma Ca bound to plasma proteins is not filtered by glomerular capillaries
• the rest is combined with anions or ionized and filtered through the glomeruli
• renal tubules reabsorb 99% Ca in filtrate

Question 11

What can increase phosphate excretion?

Answer 11

-PTH

Question 12

Hydroxyapatite crystals fail to precipitate in normal tissues except in what? What prevents this precipitation?

Answer 12

• Bones

- pyrophosphate

Question 13

What are the initial calcium salts deposited in the bone?

Answer 13

CaHPO4- * 2H2O + Ca3(PO4)

Question 14

What happens when soluble calcium is injected intravenously?

Answer 14

• Ca+2 conc may increase immediately to high levels

- within 30-60mins, the Ca+2 conc returns to normal

Question 15

How can calcium concs be maintained so well in the body?

Answer 15

• bone contains exchangeable calcium that is always in equilibrium with the Ca+2 in the extracellular fluids
• small amount of exchangeable Ca is found in tissue cells, especially in highly permeable types of cells such as those of the liver and GI tract
• exchangeable Ca provides a rapid buffering system

Question 16

What is the active form of vitamin D?

Answer 16

1,25-dihydroxycholecalciferol

Question 17

What is the importance of vitamin D?

Answer 17

-causes kidneys, intestines, and bones to increases absorption of Ca adn P into the extracellular fluid and contribute to feedback regulation of these substances

Question 18

Where are vitamin D receptors found? What do they do?

Answer 18

-present in most cells in the body and are located mainly in the nuclei of target cells
+hormone and DNA binding domains
+can suppress transcription

Question 19

How does vitamin D promote intestinal absorption of Ca?

Answer 19

-by increasing, over a period of 2 days, formation of calbindin (Ca binding protein) in epithelial intestine cells
+functions in brush border to transport Ca into the cell cytoplasm

• Ca moves through the basolateral membrane of the cell by facilitated diffusion
• calbindin remains in the cell for weeks after the vitamin D has been removed

Question 20

Vitamin D also promotes Ca absorption through the formation of what?

Answer 20

• a Ca stimulated ATPase in the brush border of the epithelial cells
• an alkaline phosphate in the epithelial cells

Question 21

Vitamin D also increases Ca and P reabsorption in the renal tubules

Answer 21

Weak effect

Question 22

What happens when there is an excess of vitamin D?

Answer 22

• causes absorption of bone

- in the absence of vitamin D, the effect of PTH in causing bone formation Iis greatly reduced or prevented

Question 23

How can vitamin D in smaller quantities promote bone calcification?

Answer 23

-increasing Ca and P absorption from the intestines

Question 24

Excess activity of the parathyroid gland causes rapid absorption of ________ from the bones.

Answer 24

• Ca salts -> results in hypercalcemia

- hypo function of parathyroid causes hypocalcemia

Question 25

Outline the synthesis of PTH.

Answer 25

- synthesis occurs in ER and Golgi - hormone is packaged in granules - most of the hormonal activity is caused by 34 aas adjacent to the N terminus of the molecule

Question 26

What effects does the parathyroid hormone have on the bone?

Answer 26

-rapid phase begin in mins and increases for several hours +phase results from activation of the osteocytes to promote calcium and phosphate absorption -slower phase +requires several days of weeks +results from proliferation of osteoclasts, followed by greatly increased osteoclast is reabsorption of the bone not just calcium phosphate salts from the bone

Question 27

How does PTH affect osteoblasts and osteocytes?

Answer 27

- have receptors for PTH | - PTH can activate Ca pumps and cause rapid removal of Ca PO4 salts from amorphous bone crystals that low near the cells

Question 28

How are osteoclasts affected by PTH?

Answer 28

- does not have a receptor for PTH, activated osteoblasts and osteocytes send secondary signals to the osteoclasts - secondary signal is osteoprotegrin ligand which activates receptors on pre osteoclasts cells and transforms them into mature osteoclasts that remove bone over a period of weeks of months

Question 29

What are the 2 stages of osteoclastic activation?

Answer 29

1. Immediate activation of osteoclasts that are already formed 2. Formation of new osteoclasts

Question 30

What are the effects of PTH on renal calcium reabsorption?

Answer 30

- rapid loss of phosphate in the urine - increases renal tubular reabsorption of Ca - diminishes phosphate reabsorption - increases the rate the reabsorption of Mg and H - decreases the reabsorption of Na, K, and aas

Question 31

What happens without the effect of PTH on the kidneys?

Answer 31

-urine would eventually deplete extracellular fluid and bones of calcium

Question 32

Excitable cells, such as neurons, are sensitive to changes in _________ concentrations.

Answer 32

[Ca]

Question 33

What mediates PTH on target organs?

Answer 33

-cAMP

Question 34

What causes the parathyroid gland to increase the rate of secretion?

Answer 34

-slight decrease in Ca ion conc in the extracellular fluid

Question 35

What are some conditions that decrease Ca ion conc?

Answer 35

- Rickets - pregnancy - lactation

Question 36

What conditions increase the Ca+2 conc above normal? What does this result in?

Answer 36

- reduced size of the parathyroid glands - excess quantities of Ca in the diet - increased vitamin D in the diet - bone absorption caused by other factors such as disease

Question 37

What are some characteristics of calcitonin?

Answer 37

- peptide hormone - secreted by the thyroid gland - tends to decrease plasma calcium conc - synthesized in and secreted by parafollicular cells (C cells) - has a weak effect on plasma calcium conc in the adult human - any initial reduction of the calcium in conc caused by calcitonin leads within hours to a powerful stimulation of PTH secretion

Question 38

In certain bone disease, such as Paget's disease, what happens?

Answer 38

-osteoclatic activity is greatly accelerated and calcitonin has a more potent effect of reducing calcium absorption

Question 39

What is hypoparathyroidism?

Answer 39

-parathyroid glands do not secrete sufficient PTH

Question 40

What happens physiologically during hypothyroidism?

Answer 40

- osteoclasts become almost totally inactive - calcium reabsorption from the bones is so depressed that blood calcium levels decrease - when he parathyroid glands are removed suddenly, the calcium level in the blood falls from the normal 9.4 mg/dL to 6-7mg/dL within 2-3 days and the blood phosphate conc may double - signs of tetany begin to develop at this level -> laryngeal muscles sensitive

Question 41

What is the typical cause of death for hypothyroidism?

Answer 41

-spasms of the respiratory muscles obstruct respiration

Question 42

What is primary hyperparathyroidism?

Answer 42

- an abnormality, usually a tumor, of the parathyroid glands that causes excess PTH secretions - this is more prevalent in women bc pregnancy and lactation stimulate the parathyroid glands and predispose to the development of such a tumor

Question 43

What is secondary hyperparathyroidism?

Answer 43

- high levels of PTH occur as a compensation for hypocalcemia - can be caused by vitamin D deficiency, which can lead to osteomalacia