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Biochem Exam 5 > Calcium and Phosphate Regulation Part 1 > Flashcards

Calcium and Phosphate Regulation Part 1 Flashcards

1
Q

Why are calcium and phosphorus important to study?

A

-essential to many vital physiological processes
-essential for proper mineralization of skeletal/dentition
-disturbances in calcium and phosphorus homeostasis linked to several pathological disorders

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2
Q

What are some of the cellular functions that Ca2+ is important for?

A

-cell division/ cell adhesion
-plasma membrane integrity
-2nd messenger in signal transduction
-muscle contraction
-neuronal excitability
-blood clotting
-skeletal development
-bone, dentin, enamel mineralization
-HARD TO NAME A PROCESS NOT DEPENDENT ON CALCIUM

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3
Q

What are some cellular functions that phosphorus is important for?

A

-membrane composition
-intracellular signaling
-nucleotide structure
-skeletal development
-bone, dentin, enamel mineralization
-chondrocyte differentiation

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4
Q

What are the 3 major pools of calcium in the body?

A

-bone (99%)
-blood and extracellular fluid
-intracellular

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5
Q

How much calcium is in the adult body?

A

around 1 Kg

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6
Q

What is 99% of the calcium in the body stored as?

A

in the mineral phase of bone/teeth as hydroxyapatite crystals

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7
Q

What is HA mineralization of bone important?

A

mechanical and weight bearing properties of bone

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8
Q

What does bone HA serves as?

A

reservoir of calcium to maintain blood ionized calcium within normal range

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9
Q

What is the normal range for total serum calcium?

A

8.5-10.5 mg/dL
(2.1-2.6mM)

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10
Q

What are the three forms of calcium in the serum?

A

-45% ionized (active)
-45% bound to albumin
-10% complexed with citrate or phosphate ions

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11
Q

What is the normal range of ionized calcium?

A

4.4-5.4 mg/dL
(1.1-1.35mM)

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12
Q

How much calcium is ingested by an adult every day?

A

around 1000mg

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13
Q

How much calcium is absorbed by the gut each day?

A

around 200mg

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14
Q

How much calcium is filtered daily through kidney?

A

around 10g

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15
Q

How much calcium is excreted in the urine daily?

A

around 200mg

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16
Q

How much calcium is stored by the skeleton?

A

around 1 Kg

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17
Q

How much calcium is released from the bone daily due to normal bone turnover?

A

around 500 mg

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18
Q

How much calcium is deposited in bone during the day due to bone formation?

A

around 500 mg

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19
Q

Is calcium higher inside or outside the cell?

A

outside

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20
Q

What helps to maintain the steep calcium gradient?

A

Ca2+ pumps in the plasma membrane

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21
Q

Where is the majority of bodies phosphate?

A

85% in the HA mineral phase of tooth

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22
Q

Where else can phosphate be present in the body?

A

tissues and extracellular fluid

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23
Q

How much of dietary phosphorus gets absorbed in the gut?

A

85-90%

24
Q

What is the normal adult phosphorus serum concentration?

A

2.5-4.5 mg/dL

25
Q

Where is most extracellular phosphorus?

A

free in solution
-acts as a buffer to maintain physiological pH

26
Q

Is calcium or phosphate serum levels more tightly regulated?

A

calcium

27
Q

Four organs/organ systems involved with calcium and phosphorus homeostasis?

A

-gut
-parathyroid
-kidney
-skeleton

28
Q

What are the three steps of calcium uptake?

A

-uptake
-transcellular transport of calcium
-extrusion

29
Q

What happens during the uptake stage of calcium uptake?

A

calcium enters the cell from the apical side by ion channels that belong to the TRP superfamily

30
Q

What happens during transcellular transport of calcium?

A

calcium binds to calmodulins

31
Q

What is the extrusion of calcium?

A

calcium leaves the cell from the basal side by membrane transport proteins

32
Q

What is TRPV6?

A

Ca2+ uptake channel on the apical side of the intestinal epithelial cells

33
Q

What does Calbindin D9K do?

A

transcellular transport of Ca2+ to basal side of the cell

34
Q

What does Ca2+ ATPase1b do?

A

pump Ca2+ out of basal side of cell

35
Q

What allows phosphate to enter the cell?

A

phosphate transporter Na+ dependent Pi cotransporter type IIb on brush border of ileum

36
Q

How much of calcium and phosphate filtered by the kidney is reabsorbed?

A

calcium - 99%
phosphate 85-95%

37
Q

Mechanisms of calcium reabsorption in the kidney:

A
  1. uptake by TRPV5
  2. transcellular transport by Calbindin D28K
  3. extrusion by Ca2+ ATPase 1b
38
Q

What cotransporters are responsible for phosphate reabsorption in the kidney?

A

-NaPi-IIa
-NaPi-IIc

39
Q

Main hormones involved with Ca2+ homeostasis?

A

-parathyroid hormone
-1,25 dihydroxyvitamin D3
-calcitonin

40
Q

What are the main hormones involved with phosphate homeostasis?

A

-parathyroid hormone
-1,25 dihydroxyvitamin D3
-fibroblast growth factor-23

41
Q

When serum calcium is high, what happens?

A

-parathyroid stops releasing PTH
-decrease release from bone
-decrease uptake in gut
-decrease reabsorption in kidney

42
Q

When serum calcium is low, what happens?

A

-parathyroid releases PTH
-increase release from bone
-increase uptake in gut
-increase reabsorption in kidney

43
Q

What detects serum calcium concentrations?

A

calcium sensing receptors (CaSR) expressed in parathyroid gland

44
Q

What is PTH?

A

-parathyroid hormone
-84 aa peptide hormone
-calcium regulatory activity
-short half life around 5 mins

45
Q

What receptor does PTH bind to?

A

PTH1R
-class B G-protein coupled receptor
-PTH mediated via activation of adenylate cyclase (cAMP) production

46
Q

What does PTH do to phosphate reabsorption in the kidneys?

A

decreases phosphate reabsorption
-can lead to phosphaturia

47
Q

Where does 25-hydroxyvitamin D3 get converted into 1,25-hydroxyvitamin D3?

A

in the kidneys with the help of PTH

48
Q

What does 1,25-dihydroxyvitamin D3 do?

A

-induced the expression of calbindins
(results in an increase in Ca uptake in gut, reabsorption in kidney, and release from bone)
-induce expression of phosphate transporters
(results in increase in Pi uptake in intestine, reabsorption in kidney, and release from bone)

49
Q

What is calcitonin?

A

hormone released from parathyroid gland in response to elevated serum calcium
-oppose PTH actions
(decrease serum calcium)

50
Q

What is the major effect of calcitonin?

A

inhibit osteoclast resorption in bone by retracted osteoclast ruffled border

51
Q

What is the minor effect of calcitonin?

A

inhibit renal reabsorption of Ca2+ and phosphate allowing them to be excreted in urine

52
Q

What is FGF 23?

A

-fibroblast growth factor
-32 kDa protein important in phosphate regulation
-expression induced when serum phosphate too high

53
Q

What cells are the major source of endocrine FGF23?

A

osteocytes

54
Q

What is the overall function of FGF23?

A

lower serum phosphate

55
Q

What is the main mechanism for rapid regulation of phosphate?

A

kidney reabsorption

Biochem Exam 5 (12 decks)

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