2-6: 5/25: Mineral Metabolism

Front 1

___________ contains a labile pool of Ca2+ and allows for ________ exchange.

Back 1

Canaliculi bone fluid = labile pool of Ca2+ and allows for FAST exchange (to central canal plasma)

Front 2

__________ contains a stable pool of Ca2+ and allows for ________ exhange.

Back 2

Mineralized bone = stable pool of calcium and allows for SLOW exchange (to central canal plasma)

Front 3

50% of calcium is _________.

Back 3

Free (Ionized): Ca2+

(40% is bound to protein--90% albumin which is made in liver)
(9% interacts with other anions such as citrate, phosphate)

Front 4

__________ calcium is only 0.1% of total calcium.

Back 4

Extracellular

Excell phosphate is about 1% total P

Front 5

Major crystalline salt of bone is _______

Back 5

Hydroxyapatite

Front 6

How is the matrix of bone formed?

Back 6

Type I collagen fibers organized in triple helix with other proteins to polymerize to form osteroid

Calcium deposition in osteoid converted to hydroxyapatite (calcium phosphate crystals)

Front 7

Osteoblasts vs Osteoclasts

Back 7

Osteoblasts: bone forming cells; receptors for E2, PTH, Vit D; following calcification become OSTEOCYTES

Osteoclasts = bone-remodeling cells that are multinucleated macs

Front 8

Bone mass peaks in ______ and declines with ____.

Back 8

20's and declines with age

Front 9

Bone formation is done by _________.

Back 9

osteoblasts

Front 10

Bone resorption is done by _________.

Back 10

osteoclasts

Front 11

PTH Effects

Back 11

Active osteoclasts indirectly through secretion of soluble factors from osteoblasts

Front 12

Vitamin D effects on bone

Back 12

Activate osteoclasts indirectly through secretion of soluble factors from osteoblasts

Front 13

Estrogen Effects

Back 13

Activates osteoblasts to produce IGF-1 and OSTEOPROTEGRIN
Inhibits osteoclasts indirectly by suppressing IL-6 and increasing OPG

Loss of E2 at menopause increases resorption

Front 14

GH effects

Back 14

Directly and indirectly (via IGF-1) regulates bone turnover and remodeling
Stimulates proliferation of articular chondrocytes, production of matrix

Front 15

Molecular events following PTH binding osteoblast

Back 15

PTH binds receptor on osteoblast
Express Rank Ligand
Rank Ligand binds osteoclast precursor and activates it

Front 16

Function of osteoprotegerin

Back 16

Osteoblasts secrete osteoprotegerin which acts as a decoy receptor for RankL, preventing osteoclast activation

Front 17

PTH is synthesized by _______.

Back 17

Chief Cells of Parathyroid Glands

Front 18

When is PTH released? Describe the effects of PTH.

Back 18

Low Ca2+
Stimulates parathyroid glands (Ca-sensing receptors), release PTH
PTH promotes resorption of Ca2+ from bone and kidney via G-protein coupled receptor, cAMP
Bone: Increased Ca, P resoption via osteocyte (rapid) and osteoclast (slow: indirect)

Kidney: Inc'd Ca absorption, dec'd P absorption (rapid); activates 1alpha hydroxylase to convert 25OH-D to active 1,25 OH-D (vitamin D)

Active form of Vit D (Calcitriol: 1, 25 hydroxy Vit D) stimulates Ca2+ and Phosphorus resorption from gut

Front 19

PTH-rp:
What is it?
Expressed by?

Back 19

homologous to PTH; have common receptor and specific receptors

Expression in placenta, cancer

Front 20

Effects of Mg on PTH.

Back 20

High Mg inhibits PTH
Low Mg stimulates PTH

Front 21

Describe the relation between ionized calcium and PTH secretion.

Back 21

Free Calcium = ionized calcium

Calcium sensing receptor coupled to Gq, when activated (by Ca2+), inhibits PTH release

As Ca2+ falls, PTH is not inhibited and is released

Front 22

Where are calcium receptors located?

Back 22

Brain, skin, bone, stomach

Thyroid C Cells, Renal Distal Tubule

Front 23

____ is required for increased PTH secretion due to low ionized calcium.

Back 23

Mg

Front 24

INACTIVATING mutations in calcium receptors can result in _______.

Back 24

Calcium sensing defects (leads to "benign" hypercalcemia)

Front 25

How is phosphate regulated? Include specific receptors.

Back 25

NPT2a mediates PO4 reabsoprtion in renal tubule

Decreased PTH and FGF23 decrease NPT2a expression to increase PO4 excretion and decrease serum [PO4]

Front 26

FGF23 is synthesized in _____ and acts on ______ to ________.

Back 26

Synthesized in bone
Acts on kidney
To inhibit PO4 absorption AND 1,25-OH Vit D production

(FGF is a phatonin--a protein that makes you excrete PO4)

Front 27

What cofactor is required for FGF23 activation?

Back 27

KLOTHO

Front 28

Vitamin D is derived from ______.

Back 28

Cholesterol

Front 29

What is the precursor of Vitamin D? What is it converted to?
Where is it stored?

Back 29

Cholecalficerol (D3)
Converted to storage form (25OH-D) in liver
Activated by PTH in kidney to active form 1,25(OH)2D

Front 30

Target tissue/Action of Vitamin D?

Back 30

Vitamin D acts on:

Bone (remodeling, mineralization)

Small Intestine: Ca, P, Mg absorption (Ca-binding protein)

Skin: keratinocyte dx/dy

Front 31

Circulating 1,25 OH D is a reflection of ___________.

Back 31

PTH activity

Front 32

What is a non-calcemic effect of vitamin D?

Back 32

Regulation of cell growth (cancer prevention)

Front 33

Calcitonin is made by _____ and is released when _________.

What are its effects?

Back 33

Calcitonin is made in C Cells (neural crest derivs) in thyroid gland

Regulated acutely by elevated Ca levels

Decreases resorption of bone due to inhibition of osteoclasts (DECREASES CA2+ concentration)

Decreases Ca reasborption in kidney at high levels

No consequences on Ca metabolism if athyroidal