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EXCI360 midterm > Calcium and Phosphate ions > Flashcards

Calcium and Phosphate ions Flashcards

1
Q

What quantities of Ca2+ are absorbed from the intestines?

A

1mg/day

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2
Q

How would you qualify the absorption of Ca2+ ions?

A

It is poor, seeing as there is a lot of these ions in our diets but we only absorb 1mg/day

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3
Q

How is most of the daily intake of Ca2+ excreted?

A

90% in feces
10% in urine

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4
Q

What is the normal Ca2+ ion concentration in blood plasma?

A

2.4 mmol/L

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5
Q

What are the three forms that Ca2+ is present in?

A
  1. Most of it, 50% are free Ca2+ ions. They are in their ionized state unbound to anything. In this state, the ions easly diffuse through membrane. It is the most important Ca form for body functions.
  2. Up to 40% of Ca2+ is bound with plasma proteins. In this form it is not able to diffuse through capillary membrane, so it stays in circulation.
  3. Up to 10% of Ca2+ is bound with citrate or phosphate. In these forms, it can diffuse through capillary membranes, so easier for cells to use it.
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6
Q

True or False. The bones are a small reservoir for phosphate and Ca2+ ions.

A

False, they are large reservoirs

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7
Q

How much phosphate is absorbed from the intestines?

A

about 1mg/day

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8
Q

How would you qualify the absorption of phosphate ions compared to Ca2+

A

Much more efficient than Ca2+ since we get less phosphate from our diet.

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9
Q

In what two form is phosphate present in the blood?

A
  1. In the form of HPO4-2, 1.05 mmol/litre.
  2. In the form of H2PO4-1, 0.26 mmol/litre.
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10
Q

What happens when pH of the extracellular fluid is more acidic?

A

concentration of HPO4 2- decreases with relative increase of H2PO4 1-

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11
Q

What happens when there is excess phosphate?

A

phosphate is excreted in urine. The excretion rate is regulated by phosphate concentration in plasma and affected by parathyroid hormone. If above critical value, excretion in urine is proportional to the increase of phosphate concentration.

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12
Q

What happens when phosphate levels are low?

A

If phosphate concentration is below critical value (1mmol/litre), all phosphates are reabsorbed ==> no loss into urine.

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13
Q

Up to 30% of bone tissue has an organic matrix. What is it composed of?

A

o Collagen fibers (majority) that give tensile strength.
o Ground substance (mionority) including extracellular fluid, chondroitin and hyaluronic acid (HA).

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14
Q

The rest of the bone’s chemical structure is inorganic salt crystals. What are they composed of?

A

o Hydroxyapatite which has the chemical structure consistiong of calcium and phosphate Ca10(PO4)6(OH)2. This gives compressional strength to the bone. It makes up the majority of the inorganic salts.
o Many other types of salts of magnesium, sodium, potassium and carbonate ions.

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15
Q

The bone tissue is surrounded by what?

A

bathed in an extracellular fluid that contains exchangeable Ca2+ and PO4- ions

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16
Q

Other than the chemicals composing the bone tissue what else is there?

A

Bone is a living tissue with circulation, gas and nutrient exchange and different types of cells that live inside the bone like osteoblasts and osteoclasts.

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17
Q

What is the chain of events leading to the osteoblasts functions?

A

‘osteoblast’ secretes collagen monomers and ground substance (proteoglycan) ==> the collagen monomers polymerize to form collagen fibers ==> the resultant tissue becomes osteoid ==> osteoblasts become entrapped in the osteoid (called osteocytes or bone cell) ==> the calcium salt deposited on the surface of the collagen fibers to become hydroxyapatite.

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18
Q

What do osteoblasts and osteoclasts do for the bone?

A

Bone is continuously being deposited by osteoblasts and being absorbed by another special type of cells called the osteoclasts.

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19
Q

How does the bone mass stay equal?

A

The bone deposition and absorption rate are normally equal.

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20
Q

What are osteoclast?

A

large phagocytic cell in bone marrow

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21
Q

What happens when the osteoclast is developed?

A

it sends out villus-like projections toward the bone to form a ruffled border adjacent to the bone.

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22
Q

What are the types of substances the villus secrete?

A
  1. Proteolytic enzymes (released from lysosomes of osteoclast) to digest and dissolve organic matrix.
  2. Citric acid and lactic acid (released from mitochondria) to dissolve bone salts.
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23
Q

What do the osteoclasts do?

A

They eat away at the bone to form a tunnel for three weeks and then they disappear.

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24
Q

What happens once the osteoclasts disappear?

A

Osteoblasts replace the osteoclasts => new bone mass begins to develop and to be deposited on the inner surface of the cavity to form layers of concentric circles for several months until the tunnel is filled.

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25
Q

What are new bone depositions called?

A

osteon

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26
Q

What stops the osteoblasts from laying new bone all the time?

A

When bone growth starts to encroach onto blood vessels the depositions stop.

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27
Q

How is the normal toughness of bone maintained?

A

By constantly depositing new bone tissue when the bones before the bones become weak and frail.

28
Q

Bone deposition is proportional to what?

A

Bone deposition is proportional to the compression stress on the bones. Heavy load causes bone thickening.

29
Q

The compressive stress can cause a piezoelectric effect. What is a piezoelectric effect?

A

“piezoelectric effect”, that is, it develops a negative electrical potential in the compressed area and a positive potential elsewhere in the bone. ==> This causes a small amount of electric current flowing in bone, ==> Promotes osteoblastic activity at the negative end of the current flow, ==> Increases the deposition at compression sites.

30
Q

TRUE or FALSE. osteoblasts reshape the bone according to stress pattern to obtain better support of mechanical load.

A

True

31
Q

What effect does a fracture have on osteoblast activity?

A

Fracture of a bone maximally activates osteoblasts ==> immediate great increase of new osteoblasts from osteoprogenitor cells ==> large bulge of osteoblastic tissue and new organic bone matrix develop between the two broken ends of the bone (callus) ==> deposition of calcium salt.

32
Q

The alkaline phosphatase in the blood can be a good indicator of what and why?

A

The alkaline phosphatase in the blood can be an indicator of the rate of bone deposition because when the osteoblasts are depositing bone matrix they secrete large amount of alkaline phosphatase that diffuses into blood.

33
Q

What is vitamin D3?

A

Vitamin D3 (Cholecalciferol) is one of vitamin D family,
o Obtained from daily intake of food; or
o Formed in skin from 7-dehydrocholesterol by ultraviolet rays from the sun.
o Inactive substance that does not cause effects.

34
Q

What are the steps to activate D3?

A
  • Vitamin D3 must be firstly converted to active substance 1, 25-dihydroxycholecalciferol (calcitriol) in liver and kidney as follows.
    o Vitamin D3 is converted to 25-hydroxycholecalciferol in the liver
  • The 25-hydroxycholecalciferol made in the liver has to be further processed to be active.
    o It is converted to calcitriol in the kidney.
    o Parathyroid hormone is required to promote that step, which results in the creation of calcitriol
35
Q

How is the activation of vitamin D3 regulated in the liver?

A

In the liver, a direct negative feedback keeps the process slow, to preserve the vitamin D3 reserves.
o 25-hydroxycholecalciferol inhibits the converstion of vitamin D3 to 25-hydroxycholecalciferol.
o As a result, the concentration of 25-hydroxycholecalciferol in the plasma remains almost constant.
o That negative feedback mechanism prevents excessive action of vitamin D3. It conserves vitamin D3 stored in liver for future use for months.

36
Q

How is the activation of vitamin D3 regulated in the kidney?

A

In the kidney, there is an indirect negative feedback. The formation of calcitriol is inversely affected by the calcium concentration in plasma.

Major effect:
When the Ca2+ ions concentration in blood is too high (above 9-10 mg/dl), it suppress secretion of parathyroid hormone from parathyroid gland.
This means less formation of calcitriol
Instead, the 25-hydroxycholecalciferol is converted to an inactive form called 24, 25-dihydroxycholecalciferol.
When calcitriol is low, the body will excrete Ca2+ ions.

Minor effect:
Ca2+ ions will inhibit the conversion of 25-hydroxycholecalciferol to calcitriol.
that effect does not rely on the parathyroid gland or hormone.
When calcitriol is low, the body will excrete Ca2+ ions.

37
Q

What is the effect of calcitriol on calcium ions?

A

Calcitriol promotes absorption of calcium by intestinal tract by two ways:

  1. By increasing the formation of calcium-binding protein in intestinal epithelial cells  promotes the transport of calcium through cell membrane by facilitated diffusion.
  2. By promoting the formation of calcium stimulated ATPase (enzyme) in the border of the intestinal epithelial cells and increasing alkaline phosphatase in the epithelial cells. This converts calcium into an easy to absorb phosphate form.
38
Q

What is the effect of calcitriol on phosphate ions?

A

It enhance absorption of phosphate ions in gastrointestinal tract. Thus, Ca2+ ions and phosphate ions are co-transported since they interact with each other.

39
Q

What do non-bone effects of calcium and phosphate ions refer to?

A

Their effect on body fluids

40
Q

What is hypocalcemia?

A

low calcium ion concentration in the blood.

41
Q

What happens when CA2+ ion levels are below 50%?

A
  • The membranes of cells become more permeable to sodium (Na+) which allows for easy initiation of membrane action potential.
  • The nerve fibers become very excitable and elicit spontaneous nerve impulses to the peripheral skeletal muscles which causes tetanic muscle contraction (tetany).
42
Q

What is hypercalcemia?

A

It is a high calcium ion concentration in the blood.

43
Q

What can hypercalcemia cause?

A
  • Depress of nervous system.
  • Reflex of CNS becomes sluggish.
  • Decreases QT interval of the heart.
  • Constipation.
  • Lack of appetite.
44
Q

What happens to the body when phosphate levels go really high or get really low?

A

Nothing, phosphate levels can vary without affecting body function

45
Q

What is the parathyroid hormone composed of?

A

Chief cells and oxyphil cells

46
Q

What do chief cells do?

A

Synthesize and secrete parathyroid hormone

47
Q

What do oxyphil cells do?

A

Function is unknown and absent in many animals and young human beings.

48
Q

What are the steps of synthesis of the parathyroid hormone?

A

o Synthesized on ribosomes to preprohormone (polypeptide, chain of 110 amino acids) ==> cleaved to prohormone (90 amino acids) ==> parathyroid hormone (84 amino acids, MW 9500) by endoplasmic reticulum and Golgi apparatus ==> packaged in vesicles in the cytoplasm of cells.

49
Q

What is the effect of PTH on calcium and phosphate ion secretions by the kidney?

A

PTH will decrease the excretion of calcium in the urine by increasing the tubular reabsorption of calcium ( as well as magnesium, hydrogen ) by kidney.

PTH will increase excretion of phosphate in the urine because parathyroid hormone reduces the tubular reabsorption of phosphate ions (and Na+, K+, and amino acids ).

50
Q

In how many phase will PTH increase the absorption of calcium and phosphate ions from bones?

A

2 phases

51
Q

What is the 1st phase of calcium and phosphate absorption from bones?

A
  1. Rapid phase of calcium and phosphate absorption (Osteolysis) begins in minutes and increases progressively for several hours.
    o Parathyroid hormone causes absorption of bone salt from two areas in the bone:
    o in the vicinity of existing osteocytes (bone cell),
    o in the vicinity of osteoblasts along bone surface.
    o The osteocytic membrane system separates the bone from extracellular fluid.
    o The bone fluid exists between the osteocytic membrane and bone and the osteocytic membrane pumps Ca2+ ions from the bone fluid into extracellular fluid,  decrease the Ca2+ ions concentration in the bone fluid,  absorption of Ca2+ ions from bone.
    o The cell membrane of osteoblasts and osteocytes have receptor proteins for binding parathyroid hormone,  parathyroid hormone activates calcium pump ( increase Ca2+ ions permeability of osteocytic membrane ),  causes removal of calcium phosphate salt from bone.
52
Q

What is the second phase of calcium and phosphate absorption from bones?

A
  1. Slow phase of bone absorption and calcium phosphate release
    o Slow absorption for several days to weeks.
    o Parathyroid hormone activates osteoclasts through the activated osteoblasts and osteocytes and promotes the formation of new osteoclasts in a slow developing process ( weeks to months ).
    o The Ca2+ ion absorption of osteoclasts, in turn, stimulates osteoblasts to correct weakened bones ==> cause both osteoblastic and osteoclastic activities.
53
Q

What is the effect of calcium and phosphate concentration on extracellular fluid?

A

Increase of blood calcium concentration caused by
o Increasing the absorption of calcium from bone,
o Decreasing the excretion of Ca2+ ions in urine and increasing reabsorption of Ca by kidney,
o Increasing vitamin D for promoting absorption of Ca2+ ions by intestine.

Decrease of blood phosphate concentration (even though the phosphate absorptions from bone and intestine are increased ) , this is caused by excessive phosphate excretion in urine.

54
Q

What regulates parathyroid hormone secretion?

A
  • Secretion is regulated by Ca2+ ions concentration in the extracellular fluid.
  • Slight decrease of Ca2+ ions concentration causes increase of secretion rate of parathyroid hormone.
  • Parathyroid gland will be enlarged if
    o decrease of Ca2+ ions concentration persists,
    o in pregnancy or lactation ( Ca2+ ions are used for milk production ).
  • Increase of Ca2+ ions concentration above normal causes decreased activity and size of parathyroid glands.
55
Q

What is calcitonin?

A

Calcitonin is a large polypeptide hormone, it is a chain of 32 amino acids.
* synthesized and secreted from C cell in thyroid gland (not parathyroid glands) in human being.

56
Q

True or False. The effect of calcitonin are the same as those of the parathyroid hormone.

A

False, they’re opposite.

57
Q

How does calcitonin reduce blood Ca2+ concentration?

A

Reduce blood Ca2+ ions concentration by:
o Short term effect to decrease absorption of osteoclasts.
o Long term effect to decrease the production of new osteoclasts, ==> in turn, depress the formation of osteoblasts, ==> reduce both osteoclastic and osteoblastic activities.

58
Q

How long does calcitonin has an effect on blood calcium?

A

short effect, lasts a couple of hours.

59
Q

How big of an effect does calcitonin have on blood calcium concentration?

A
  • Has only a weak effect on blood Ca2+ ions in adult human being, because the initial reduction of Ca2+ ions resulted from by calcitonin will cause powerful stimulation of secretion of parathyroid hormone,
  • In adults, the daily absorption and deposition rate of Ca2+ ions are small and has small effect on blood Ca2+ ions concentration.
60
Q

How is calcitonin secretion regulated?

A

Increase of blood calcium concentration (10%) causes increase of secretion rate of calcitonin (twice or more).

Calcitonin is the second hormonal feed-back mechanism for controlling blood Ca2+ ions

61
Q

What is the difference between the calcitonin and parathyroid feedback systems?

A

(1) Calcitonin mechanism operates more rapidly. Time for reaching to peak activity:
o For calcitonin: in < 1 hour.
o For parathyroid hormone: in > 3 to 4 hours.

(2) Calcitonin mechanism acts weakly and as a short-term regulator of Ca2+ ions concentration but parathyroid hormone is more potent and acts over prolonged period of time.

62
Q

What is the first line of defense to prevent uncontrollable calcium levels?

A

The first line of defense is the buffer system of exchangeable salts of bone. A small percent (<1%) of total bone calcium are exchangeable Ca2+ ions. They can go back and forth to blood plasma or bone extremely fast.

63
Q

What does the buffer do if there is a slight increase in calcium concentration?

A

If there is a slight increase of Ca2+ ions in extracellular fluid above normal, it will cause immediate deposition of exchangeable calcium ions into the bone. Now, the Ca2+ ions concentration in extracellular fluid can return to normal.

64
Q

What does the calcium buffer do if there is a decrease in calcium ion concentration?

A

If there is a slight decrease of Ca2+ ions in extracellular fluid below normal the extracellular calcium concentration is too low then the exchangeable calcium can release into the extracellular fluid.

65
Q

When do calcitonin and PTH become important in the hormonal control of Ca2+ ions?

A

When the exchangeable salts of bone can not handle the imbalance.

EXCI360 midterm (9 decks)

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