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Physiology- Endocrine > Calcium and Phosphate > Flashcards

Calcium and Phosphate Flashcards

1
Q

Physiological Actions of Calcium (7)

A

(1) Major constituent of bones and teeth
(2) Synaptic Transmission (NT release)
(3) Maintenance of sodium permeability in nerves
(4) E-C coupling in muscle cells
(5) Intracellular signaling molecule
(6) Calcium-dependent enzymes
(7) Blood clotting

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2
Q

Physiological Actions of Phosphate (5)

A

(1) Major constituent of bones and teeth
(2) Intracellular buffering
(3) Constituent of many macromolecules such as phospholipids, phosphoproteins, nucleic acids
(4) Enzyme activation and inactivation via phosphorylation and dephosphorylation
(5) Component of metabolic intermediates (e.g. NADPH)

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3
Q

Plasma Calcium in Blood Plasma

A

45% Ionized Calcium**
45% Protein Bound*
10% Complexed with Citrate/Oxalate/Phosphate**

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4
Q

Plasma Phosphate in Blood Plasma

A

50% Ionized Phosphate**
40% Complexed with calcium/sodium/potassium**
10% Protein bound*

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5
Q

What types of Ca++ and Phosphate can be filtered by glomerulus in kidney and regulated by hormones?

A
  • Ionized Calcium
  • Calcium- complexed with Citrate/Oxalate/Phosphate
  • Ionized Phosphate
  • Phosphate- protein Bound
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6
Q

What are the organs important in Ca and Phosphate regulation?

A

(1) Gut
(2) Kidneys
(3) Bone

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7
Q

What is your daily calcium? How much is secreted?

A

1000 mg/day
825- feces from gut
175- urine

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8
Q

What is your daily phosphate? How much is excreted?

A

1400 mg/day
500- feces from guy
900- urine

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9
Q

Both Calcium and Phosphate are regulated by the same hormones: (3)

A

(1) Parathyroid Hormone (PTH)
(2) 1,25 (OH)2 D3
(3) Calcitonin

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10
Q

Calcium and Phosphate are the principal components of what?

A

Hydroxyapatite crystals; the major component of the mineral phase of bone

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11
Q

Which hormones are calciotropic hormones?

A

(1) Parathyroid Hormone (peptide)

(2) Vitamin D metabolite [1,25 (OH)2 D3]

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12
Q

What does Parathyroid Hormone do in regards to calcium regulation?

A

Increases Plasma Ca2+

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13
Q

What does 1,25 (OH)2 D3 do in regards to calcium regulation?

A

Short term: Supports the actions of PTH to help increase plasma Ca2+
Longer term: Negative feedback over PTH secretion

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14
Q

What does Calcitonin do in regards to calcium regulation?

A

Decreases plasma Ca2+

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15
Q

What cell types do the parathyroid glands contain and what do they do?

A

(1) Chief cells- synthesize PTH

(2) Oxyphil cells- old, non-secreting chief cells

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16
Q

What is Parathyroid Synthesis?

A

From the rough endoplasmic reticulum to the golgi bodies and then are packaged in secretory granules (stored; released by exocytosis)

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17
Q

How is Parathyroid hormone released?

A

Exocytosis

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18
Q

What happens when you have a decrease in plasma calcium? How is it controlled?

A

There will be an increase in Parathyroid Hormone Secretion; Calcium-sensing receptor is the sensor in the chief cell (CaSR is a GPCR)

19
Q

What is the major influence of PTH levels?

A

Plasma Calcium; CaSR regulates PTH output in response to subtle fluctuations on a minute-to-minute basis

20
Q

1,25 (OH)2 D3 does what in regards to PTH? What does that suggest?

A

Decreases synthesis of PTH and increases synthesis of CaSR at the Chief Cell; it provides a long-term negative feedback action by switching off PTH synthesis and increasing CaSR synthesis

21
Q

What does PTH do to restore plasma calcium to the normal range?

A

PTH increases levels of ionized Calcium and decreases Phosphate in the plasma

22
Q

What is the major stimulus for PTH synthesis and secretion?

A

A fall in plasma circulation

23
Q

Major target organ to restore plasma calcium: Kidney (3)

A

(1) Promotes Calcium reabsorption and thus increases plasma calcium
(2) Decreases Phosphate reabsorption and thus reduces plasma phosphate
(3) Increases the production of the Vitamin D metabolite 1,25 (OH)2 D3

24
Q

Major target organ to restore plasma calcium: Bone (1)

A

(1) Promotes bone remodeling with a net loss of calcium and phosphate from bone into the blood

25
Q

What does PTH do in regards to calcium and phosphate in the kidney?

A

Increases Calcium reabsorption and decreases phosphate reabsorption by the kidney

26
Q

Where does PTH increase calcium reabsorption?

A

in the distal tubule and (TAL) loop of henle; this directly increases plasma Ca++ and decreases calcium excretion

27
Q

Where does PTH decrease phosphate reabsorption?

A

the proximal tubules, by down-regulating sodium-dependent phosphate transporter NPT2; this increases urinary phosphate excretion and lowers plasma phosphate.

28
Q

What does PTH do in regards to renal 1-hydroxylase activity? How/Why?

A

It increases it, converting to 1,25 (OH)2 D3; under conditions of low plasma Ca2+, PTH increases synthesis/activity of renal 1-hydroxylase

29
Q

Why does PTH decrease plasma phosphate?

A

With less phosphate in the plasma, the amount of Ca2+ complexed with phosphate is reduced. Therefore, the level of free Ca2+ in the plasma is increased.

30
Q

What does the subsequent low kidney cortical phosphate do?

A

Increases the activity of renal 1-hydroxylase

31
Q

Bone remodeling is a temporal process that involves: (2)

A

(1) Breakdown (resorption) of the bone matrix by cells called osteoclasts. This causes release of Ca2+ and PO4- into the blood
(2) Formation (accretion) of bone by new synthesis of osteoid at the site of bone resorption, and calcification of the osteoid by Ca2+ and PO4- derived from the blood. This causes removal of Ca2+ and PO4- from the blood.

32
Q

T/F PTH exerts only direct actions on the cells that control formation and breakdown (remodeling).

A

FALSE, direct AND indirect

33
Q

What are the factors that induce differentiation of osteoclasts from precursor cells, and then fully activate osteoclast function?

A

(1) M-CSF promotes formation of preosteoclasts
(2) RANKL - stimulates conversation of preosteoclasts to mature osteoclasts.
- directly increases osteoclast activation and secretion hydrolytic enzymes that break up the bone matrix and release Ca2+ and PO4- into the blood

34
Q

What is the role of osteoprotegerin? (OPG)

A

it is secreted from the osteoblasts ~2 weeks after reabsorption begins and inhibits the actions of RANKL

35
Q

Process of Bone Remodeling- Formation (4)

A

(1) Following OPG- osteoblasts migrate into the resorbed area and secrete collagen, IGF-1, and TGFBeta that cause osteoid formation
(2) Ca2+ and PO4- along with OH- and HCO3- are trapped in the new osteoid to form crystalline bone
(3) The osteoblasts eventually become encased in the new bone, become non-secreting and then are known as osteocytes
(4) Osteocytes are thought to transfer Ca+ from the interior of the bone to the surface to assist in bone formation, a process called osteocytic osteolysis

36
Q

PTH receptors are located where on bone?

A

ONLY on osteoblasts!!

37
Q

PTH acts via these receptors on the osteoblast and exerts the following effects (2)

A

(1) Sustained elevated PTH in blood cause bone resorption

(2) Lower levels of plasma PTH or intermittent administration if PTH cause an increase in bone formation

38
Q

Sustained elevated PTH in blood causes bone resorption. This effect of PTH includes: (3)

A

(1) Indirect stimulation of osteoclasts to elicit bone resorption. PTH acts at its receptors on osteoblasts to increase production and secretion of M-CSF and RANKL, stimulating osteoclast activation and bone breakdown
(2) Inhibition of OPG production and secretion by osteoblasts
(3) Direct stimulation of osteoblasts to inhibit collagen production that is important in bone formation

39
Q

Intermittent PTH causes an increase in bone formation that involves 2 different actions:

A

(1) Induction of growth factor secretion from osteoblasts (IGF-1, TGFBeta)
(2) Stimulation of osteocytic osteolysis

40
Q

1,25 (OH)2 D3 has 3 sites of action; where does it come from?

A

(1) Intestine
(2) Bone
(3) Kidney; vitamin D

41
Q

Actions of 1,25 (OH)2 D3 at Intestine- Calcium and Phosphate

A
  • Stimulates reabsorption of calcium into the blood from the intestine (increases plasma Ca levels
  • increases the absorption of PO4 so increases phosphate levels
42
Q

Actions of 1,25 (OH)2 D3 at Bone

A
  • Has direct effects on bone to potentiate PTH induced bone breakdown (High levels of PTH)
  • Has overriding effect on bone is an indirect action to stimulate bone formation (Low PTH)
43
Q

Actions of 1,25 (OH)2 D3 at Kidney

A

Increases calcium reabsorption by the kidney distal tubule, acting synergistically with PTH which increases blood Ca

44
Q

What influences metabolism of 1,25 (OH)2 D3?

A

(1) Vitamin D deficiency
(2) High PTH (Hypocalcemia)
(3) Low Renal Cortex (PO4-)

Physiology- Endocrine (7 decks)

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