Flashcards in Lecture 23: Calcium Balance Deck (85):
1
In the human body, what type of cells are sensitive to changes in calcium ion concentrations?
Excitable cells, such as neurons.
2
What does an increase in calcium ion levels above normal cause?
Progressive depression of the nervous system.
- symptoms begin to appear when the blood calcium level rises above 12 mg/dl
- reflex activities of the nervous system are sluggish
- there is constipation and lack of appetite
3
What does a decrease in calcium ion levels below normal cause?
The nervous system to become more excited.
4
Is constipation and lack of appetite seen in patients with an increased or decreased calcium ion concentration?
Increased calcium ion concentration above normal - which causes depression of the nervous system.
5
Where is calcium stored in the body?
- 0.1% of total body calcium is in the extracellular fluid.
- 1% is in the cells and organelles.
- The rest is stored in the bones.
6
Where is phosphate stored in the body?
- 85% of total body phosphate stored in bones.
- 14-15% is in the cells.
- Less than 1% is in the extracellular fluid.
7
True or False:
Extracellular phosphate concentration is more regulated that that of calcium concentrations.
False - extracellular phosphate concentration is not nearly as well regulated as that of calcium.
8
Which two forms is inorganic phosphate in the plasma mainly found in?
- HPO4^2-
- H2PO4^-
9
Does large changes in the level of phosphate in the extracellular fluid cause major immediate effects on the body?
No - large changes in the level of phosphate in the extracellular fluid DO NOT cause major immediate effects on the body.
10
Large changes in the level of phosphate in the extracellular fluid do not cause major immediate effects on the body. What about changes in extracellular calcium levels?
Even slight changes in extracellular calcium can cause extreme immediate physiological effects.
11
What does hypocalcemia cause?
Nervous system excitement and tetany.
*hypocalcemia may also cause seizures*
12
How does hypocalcemia cause the nervous system to become progressively more excitable?
Due to increased neuronal membrane permeability to sodium ions.
13
Hypocalcemia causes nervous system excitement and tetany. Where does the fist sign of tetany typically occur in patients with hypocalcemia?
First sign of tetany typically occurs in the hand, resulting in carpopedal spasm.
Tetany ordinarily occurs when the blood concentration of calcium falls from its normal level of 9.5 mg/dl to about 6 mg/dl (35% below normal calcium concentration).
It is usually lethal at about 4 mg/dl.
14
What is the usual rates of intake for calcium and phosphorous each day?
about 1000 mg/day each for calcium and phosphorous
15
Normally, divalent ions are poorly absorbed, but what vitamin promotes calcium absorption by the intestines so that about 35% of ingested calcium is absorbed?
Vitamin D
16
What happens to calcium that is not absorbed in the body?
Excreted in the feces.
**about 250 mg/day of the absorbed calcium enters intestines via secreted GI juices and sloughed mucosal cells.
** Thus, about 90% of the daily intake of calcium is excreted.
17
How many mg/day of calcium is absorbed, which enters the intestines via secreted GI juices and sloughed mucosal cells?
250 mg/day
18
What percentage of daily intake of calcium is excreted?
90%
19
How many mg/day of ingested calcium is excreted in the urine?
100 mg/day (10%) of ingested calcium is excreted in the urine.
20
What percentage of calcium that is bound to plasma proteins is not filtered by glomerular capillaries?
41%
21
True or False:
Renal tubules reabsorb about 99% of the calcium in the filtrate.
True
22
What is the effect of the hormone, PTH, on phosphate excretion?
PTH can greatly increase phosphate excretion.
23
What is the function of pyrophosphate?
Hydroxyapatite crystals fail to precipitate in normal tissues (except in bone).
Inhibitors are present in almost all tissues and plasma, to prevent such precipitation.
Pyrophosphate is once of these inhibitors:
> bone may secrete a pyrophosphate inhibitor to allow hydroxyapatite precipitation.
24
What do osteoblasts secrete in the initial stage of bone production?
Collagen monomers - which polymerize rapidly to form collagen fibers.
*the precipitation of calcium along the collagen fibers eventually forms hydroxyapatite crystals*
25
What does the precipitation of calcium along collagen fibers eventually form?
hydroxyapatite crystals
26
True or False:
Under normal conditions, calcium salts do precipitate in other tissues.
False - under ABNORMAL conditions, calcium salts do precipitate in other tissues.
*This presumably occurs when the inhibitor factors that normally prevent deposition of calcium slats disappear from the tissues.*
27
What happens to the calcium ion concentration after soluble calcium salts are injected intravenously?
> Calcium ion concentration may increase immediately to high levels.
> However, within 30-60 minutes, the calcium ion concentration returns to normal.
28
What happens when large quantities of calcium ions are removed from the circulating body fluids?
[Calcium ion] returns to normal within 30 minutes or so.
29
A small portion of exchangeable calcium is found in all tissue cells, especially in highly permeable types of cells such as those of the liver and GI tract. What does this exchangeable calcium provide?
A rapid buffering mechanism.
**Bone contains exchangeable calcium that is always in equilibrium with the calcium ions in the extracellular fluids.**
30
What are the three hormones that control calcium balance?
- Calcitonin
- PTH
- Vitamin D
31
What is the active form of vitamin D?
1,25-dihydroxycholecalciferol
32
Where are most vitamin D receptors found?
Vitamin D receptors are present in most cells in the body and are located mainly in the nuclei of target cells.
33
What does the active form of vitamin D (1,25-dihydroxycholecalciferol) cause the intestines, kidneys, and bones to do?
Increased absorption of calcium and phosphate into the extracellular fluid and contribute to feedback regulation of these substances.
34
Vitamin D receptors are present in most cells in the body and are located mainly in the nuclei of target cells. What are the characteristics of vitamin D receptors?
> The vitamin D receptor has hormone-binding and DNA-binding domains.
> The vitamin D receptor forms a complex with another intracellular receptor, the retinoid-X receptor, and this complex binds to DNA and activates transcription in most instances.
> Sometimes vitamin D suppresses transcription.
35
How does 1,25-dihydroxycholecalciferol itself promote intestinal absorption of calcium?
> By increasing, over a period of 2 days, formation of calbindin, a calcium-binding protein, in the intestinal epithelial cells.
**this proteins functions in the brush border of the epithelial cells to transport calcium into the cell cytoplasm**
> Then the calcium moves through the basolateral membrane of the cell by facilitated diffusion.
> Calbinding remains in the cell fro weeks after the 1,25-dihydroxycholecalciferol has been removed from the body.
36
Besides 1,25-dihydroxycholecalciferol itself promoting intestinal absorption of calcium by increasing the formation of calbindin, how else does function to promote calcium absorption?
> A calcium-stimulated ATPase in the brush border of the epithelial cells.
> An alkaline phosphatase in the epithelial cells.
> Vitamin D also increases calcium and phosphate reabsorption by the epithelial cells of the renal tubules (this is a weak effect).
37
What happens if extreme quantities of vitamin D are administrated?
- Causes absorption of bone.
- The mechanism of this action of vitamin D is believed to result from the effect of 1,25-dihydroxycholecalciferol to increase calcium transport through cellular membranes.
38
What effect does PTH have on causing bone absorption in the absence of vitamin D?
Effect of PTH in causing bone absorption is greatly reduced or even prevented.
39
What does vitamin D in smaller quantities promote?
Bone Calcification
40
How does vitamin D in smaller quantities promote bone calcification?
By increasing calcium and phosphate absorption from the intestines.
41
What does excess activity of the parathyroid gland cause?
Rapid absorption of calcium salts from the bones.
> results in hypercalcemia in the extracellular fluid
> hypofunction of the parathyroid glands causes hypocalcaemia often with resultant tetany
42
How is PTH first synthesized?
On ribosomes in the form of a preprohormone with 110 amino acids.
**this is cleaved first to a prohormone with 90 amino acids, then to the hormone itself with 84 amino acids by the ER and Golgi.
** The hormone is finally packaged in granules.
** Most of the hormonal activity is caused by 34 amino acids adjacent to the N terminus of the molecule.
43
Where does synthesis of PTH occur?
ER and Golgi
44
Where does most of the hormonal activity of PTH occur in the 84 amino acid hormone form?
Caused by 34 amino acids adjacent to the N terminus of the molecule.
45
What is the effects of PTH?
Causes absorption of calcium and phosphate by bone.
46
What is the rapid phase of calcium and phosphate absorption caused by PTH?
A rapid phase that begins in minutes and increases progressively for several hours.
> This phase results from activation of the already existing bone cells (mainly osteocytes) to promote calcium and phosphate absorption.
47
What is the much slower phase of calcium and phosphate absorption caused by PTH?
> Requires several days or even weeks to become fully developed.
> Results from proliferation of the osteoclasts, followed by greatly increased osteoclastic reabsorption of the bone itself, not merely absorption of the calcium phosphate salts from the bone.
48
Which cell types of bone have receptor proteins for binding PTH on their cell membrane?
- Osteoblasts
- Osteocytes
49
True or False:
PTH can activate the calcium pump and cause rapid removal of calcium phosphate salts from those amorphous bone crystals that lie near the cells.
True
**PTH is believed to stimulate this pump by increasing the calcium permeability of the bone fluid side of the osteocytic membrane, thus allowing calcium ions to diffuse into the membrane cells from the bone fluid.
** Then the calcium pump on the other side of the cell membrane transfers the calcium ions the rest of the way into the extracellular fluid.
50
What are the effects of PTH on osteoclasts?
> The osteoclasts do not have membrane receptor proteins for PTH.
- It is believed that the activated osteoblasts and osteocytes send secondary "signals" to the osteoclasts.
- A major secondary signal is osteoprotegerin ligand, which activates receptors on preosteoclast cells and transforms them into mature osteoclasts that remove bone over a period of weeks or months.
> Activation of the osteoclastic system occurs in two stages:
(1) Immediate activation of the osteoclasts that are already formed.
(2) Formation of new osteoclasts.
51
What are the two stages in which activation of the osteoclastic system occurs?
(1) Immediate activation of the osteoclasts that are already formed.
(2) Formation of new osteoclasts.
52
True or False:
Osteoclasts have membrane receptor proteins for PTH.
False - they DO NOT.
53
Since osteoclasts do not have membrane receptor proteins for PTH, what major secondary signals is sent from activated osteoblasts and osteocytes to activate the osteoclastic system?
Osteoprotegerin Ligand - which activates receptors on preosteoclast cells and transforms them into mature osteoclasts that remove bone over a period of weeks or months.
54
What does osteoprotegerin ligand do?
Activates receptors on preosteoclast cells and transforms them into mature osteoclasts that remove bone over a period of weeks or months.
55
What are the effects of PTH on renal calcium reabsorption?
> Administration of PTH causes rapid loss of phosphate in the urine.
**this is due to the effect of the hormone to diminish proximal tubular reabsorption of phosphate ions**
> PTH also:
- increases renal tubular reabsorption of calcium:
**occurs mainly in the late distal tubules, the collecting tubules, the early collecting ducts, and possibly the ascending loop of Henle to a lesser extent.
- diminishes phosphate reabsorption
- increases the rate of reabsorption of magnesium ions and hydrogen ions
- decreases the reabsorption of sodium, potassium, and amino acid ions
56
How does administration of PTH cause rapid loss of phosphate in the urine?
Due to the effect of the hormone to diminish proximal tubular reabsorption of phosphate ions.
57
PTH also increases renal tubular reabsorption of calcium. Which parts of the kidney does this mainly occur in?
- late distal tubules
- collecting tubules
- early collecting ducts
- possible the ascending loop of Henle to a lesser extent
58
Besides PTH causing calcium and phosphate absorption from bone, what effect does it have on calcium, phosphate, amino acids, and other ions?
> administration of PTH causes rapid loss of phosphate in the urine.
> Increases renal tubular reabsorption of calcium.
> Diminishes phosphate reabsorption.
> Increases the rate of reabsorption of magnesium ions and hydrogen ions.
> Decreases the reabsorption of sodium, potassium, and amino acid ions.
59
What would happen without the effect of PTH on the kidneys to increase calcium reabsorption?
Urine would eventually deplete both the extracellular fluid and the bones of calcium.
60
What is a large share of the effect of PTH on its target organs mediated by?
cAMP
61
What does the slightest decrease in calcium ion concentration in the extracellular fluid cause the parathyroid glands to do?
Increase their rate of secretion of PTH.
62
What are 3 conditions that decrease calcium ion concentration?
- Rickets
- Pregnancy
- Lactation
63
What conditions increase the calcium ion concentration above normal (resulting in a reduced size of the parathyroid glands)?
- Excess quantities of calcium in the diet.
- Increased vitamin D in the diet.
- Bone absorption caused by other factors such as disease.
64
What effect does PTH have on phosphate reabsorption?
Diminishes phosphate reabsorption.
65
What effect does PTH have on the rate or reabsorption of magnesium ions and hydrogen ions?
Increases the rate of reabsorption.
66
What effect does PTH have on the reabsorption of sodium, potassium, and amino acid ions?
Decreases the reabsorption.
67
Look over figure 80-13.
Know well for the EXAM!!
68
What kind of hormone is calcitonin?
Peptide Hormone
69
What gland is calcitonin secreted by?
thyroid gland
70
What effect on plasma calcium concentration does calcitonin have?
Decreases plasma calcium concentrations.
71
What type of cells in the thyroid gland synthesis and secrete calcitonin?
Synthesized in and secreted by parafollicular cells (C cells).
72
True or False:
Calcitonin has a weak effect on plasma calcium concentration in the adult human.
True
**any initial reduction of the calcium ion concentration caused by calcitonin leads within hours to a powerful stimulation of PTH secretion**
73
True or False:
In certain bone diseases, such as Paget disease, osteoclastic activity is greatly accelerated, and calcitonin has a more potent effect of reducing calcium absorption.
True
74
When does hypoparathyroidism occur?
When the parathyroid glands do not secrete sufficient PTH.
75
You know that hypoparathyroidism occurs when parathyroid glands do not secrete sufficient PTH. What happens to osteoclast activity in patients with hypoparathyroidism?
Osteoclasts become almost totally inactive.
*calcium reabsorption from the bones is so depressed that blood calcium levels decrease*
76
What happens to calcium and phosphate levels when the parathyroid gland is suddenly removed?
- Calcium level in the blood falls from the normal 9.4 mg/dl to 6-7 mg/dl within 2 to 3 days.
- Blood phosphate concentration may double.
77
Which muscles in the body are especially sensitive to tetanic spasms?
Laryngeal Muscles
78
What do tetanic spasms in laryngeal muscles cause?
Spasms of these muscles obstruct respiration, which is the usual cause of death.
79
What are the two different types of hyperparathyroidism?
- primary
- secondary
80
What causes primary hyperparathyroidism?
An abnormality (usually a tumor) of the parathyroid glands causes inappropriate, excess PTH secretions.
81
Is primary hyperparathyroidism more prevalent in women or men?
More prevalent in women - because pregnancy and lactation stimulate the parathyroid glands and predispose to the development of such a tumor.
82
What can secondary hyperparathyroidism be caused by?
Vitamin D deficiency
83
What can a deficiency in vitamin D lead to?
Osteomalacia
84
In secondary hyperparathyroidism, what do high levels of PTH occur as a compensation for?
Hypocalcemia
85