Control of Mineral Metabolism Flashcards Preview

My DEMS 4 > Control of Mineral Metabolism > Flashcards

Flashcards in Control of Mineral Metabolism Deck (20):
1

Roles of calcium

1. structural (mineral matrix of bone; reservoir for plasma calcium)
2. biochemical (excitation contraction coupling, stimulus-secretion coupling, blood clotting, memb excitability, cellular permeability)

Hypocalcemia: seizures and tetany (increase excitability)
-increased Ca: sluggishness, muscles dont work well

2

Plasma Calcium and phosphate range

Ca: 8-10 mg/dL
Phosphate: 3-4 mg/dL

-There is a fast exchange of 20g/d b/t ECF and labile bone mediated by osteocytes

3

3 compartments of calcium

1. bone (99% in form of hydroxyapatite)
2. intracellular compartment: 10g. Cytosolic Ca maintained by intracell mobile Ca buffers, compartmentalization into ER Ca stores, ATP linked Ca pump and Na/Ca antiporter
3. Extracellular fluid includes blood and interstitial spaces in equilibrium; 2.5 mM, 1/2 free and filtered by kidney, remainder bound to albumin

Kidney filters 10g Ca/d
98% reabsorbed

4

Phosphate roles

-structural role (mineral matrix of bone)
-intracellular buffer
-phosphorylation reactions
-energy currency
-DNA, RNA
-Regulation

85% in ionized active form (HPO4 2- and H2PO4 2-)

5

Ca forms

50% Albumin bound
10% HCO3-, PO43- (salt forms)

6

Bone formation

-surface osteoblasts
-canals filled with canalicular fluid
-osteocytes
-osteoclasts (phagocytic cells): degradation of matrix
-canalicular:blood 0.6 (normally drive Ca into canalicular fluid down gradient through surface osteoblasts; taken up by surface osteocytes, then back into blood)
-So: net exchange of 10g of Ca per day ("osteocytic process")
-phosphate is NOT part of daily exchange

Osteoclastic process exchanges both Ca, Phosphate

7

Phosphate equilib

-exchange through kidneys
-7g of phosphate/d filtered thru kidneys and 6.1 taken back up
-Blood range: 3-4 mg/d

8

Parathyroid hormone

-produced in parathyroid gland
-from Chief cells
-synth as larger pre-prohormone
PTH leads to increased plasma Ca via:
1. bone:
Rapid: increased efflux of labile bone Ca (not phos)
Slow: increased bone remodeling releases Ca and phosphate

2. Kidney:
increased Ca reabsorption in distal tubule
decreased phosphate reabsorp
increased 1,25 (OH)2 Vit D

3. GI tract:
indirect via Vit D, which enhances Ca absorp

Consequence: increase serum Ca and decrease serum phosphate

But how does a low serum Ca lead to Ca dependent release (increased cytosolic Ca) of PTH?
Chief cells have Ca receptors:
-when bound with Ca: inactive; when you lower serum Ca, GPCR triggered (Gq) (ER releases Ca via IP3 and increases intracell Ca and PTH is released)

PTH receptors: GPCR

9

Calcitonin

-Produced by parafollicular or C cells of thyroid
-secreted when Ca is high
-acts on bone to decrease efflux of labile bone Ca

10

Vitamin D Synthesis and secretion

-7dehydrocholesterol + sunlight leads to Vit D3 (inactive)
-In liver, on hydroxyl group added and second hydroxyl group added in kidney (1 hydroxylase)
-1,25 OH2 Vit transported bound to transcalciferin
(note: 24, 25 (OH)2 Vit D3 is inactive)

11

Actions of Vit D

-GI tract: interacts with nuclear receptor, increases synthesis of mRNAs/prot. 1 of these is Calcium binding protein: promotes absorption of Ca from gut into blood

1,25 OH2 Vit D mobilizes bone similar to PTH

12

Hyperparathyroidism

-tumors of parathyroid
-other tumors

-Ca will exceed set point (high Ca): sluggish, low mental and muscle response

13

Pseudohypoparathyroidism

-receptors don't function normally, but hormones are normal or even elevated

14

Regulation of 1, 25 (OH)2 Vit D synthesis

-1,25 Vit D acts on renal hydroxylase to decrease its action (negative feedback)
-In kidney, increased PTH positively and negatively affect the activities of 1 hydroxylase and 24 hydroxylase respectively.
-high PTH leads to increased levels of 1, 25 (OH)2 Vit D-- acts on GI to increase Ca absorp
-decreased levels of phosphate pos and neg affect activities of 1 hydroxylase and 24 hydroxylase respectively
-so if plasma phosphate falls, 1,25 OH2 Vit D synth is increased, and will act on GI to promote phosphate absorp

15

Minute to minute regulation of blood calcium

-PTH acting to mobilize Ca into plasma
-Calcitonin: help increase rate of storage for acute Ca load

16

Long term regulation of ca balance

-Vit D: regulates intestinal aborp of Ca and phosphate

17

Hyperparathyroidism

-primary: increased PTH increases Ca levels in plasma and urine-- renal stones.
Hypercalcemia:
muscle weakness, depression, GI disorders; severe: bone pain/fractures

Secondary:
any disorder where plasma Ca is low: Rickets, renal failure

18

Hypoparathyroidism

-low PTH leading to low Ca
Sx: neuromuscular excitability, muscle cramps, seizures, mental changes
-Chvostek's sign (facial n.)
-PTH dependent decrease in calcitriol levels, causing decreased serum Ca due to less absorp from intestine/reabs from kidney
-increased phosphate

Tx: Vit D, Ca supp

19

Vit D deficiency

-Kids: Rickets
-Adults: osteomalacia

20

Vit D excess

-large ingestion of Vit D
-can cause hypercalcemia
-can lead ot pathological calcification of soft tissues