Mineral Metabolism

Question 1

Normal Ca conc.

Answer 1

. 10 mg/100mL
. 2.5 moles/L
. Half is ionized and other half is bound to plasma proteins and small anions (90% to albumin, rest to globulins)
. Plasma 5 mg/dl or 1.25 mM

Question 2

T/F total plasma Ca levels provides a good index of free Ca

Answer 2

T

Question 3

Ca in acidosis

Answer 3

. W/ higher H there are fewer Ca binding sites to albumin
. Inc. Ca conc. In plasma and interstitial fluid
. Ca in interstitial fluid association. W/ neg. charges on surface of n. Axons that then dec. frequency of APs in motor n. Axons
. The more Ca bound to membrane surface the harder it is for Na channels to open causing lower excitability
. End cause is mm. Weakness

Question 4

Ca during alkalosis

Answer 4

. More neg. sites available on plasma protein to bind Ca
. Dec. plasma Ca conc. And interstitial fluid
. Ca dissociates from neg. sites on surface of motor n. Axons inc. AP freq. in n.
. Excitability inc. and mm. Contracts more

Question 5

Pathways Ca enters of leave extracellular fluid

Answer 5

. GI tract
. Kidney
. Bone

Question 6

Phosphorous in body

Answer 6

. 15% in plasma bound to plasma proteins
. 85% in plasma corresponds to inorganic phosphate
. Normal plasma level: 4 mg/dl (1.3mM)
. Major intracellular anion
. Acts an intracellular buffer
. Hypophosphatemia:cellular ATP production is impaired
. Vit. D3 regulates phosphorus metabolism

Question 7

Magnesium

Answer 7

. 2/3 total body Mg in exchangeable fraction of skeleton and 1/3 intracellular compartment
. 1/5 bound to albumin, salts, and globulina
. Vit. D3 and PTH modulate Mg exchange in and out of the body

Question 8

Amorphous crystals

Answer 8

. 4.5g of Ca phosphate forming SA all pool size
. Crystals labile and provide fast exchange of Ca in crystals w/ ECF compartment via osteocytic osteolysis (NOT BONE RESORPTION)

Question 9

Hydroxyapatite crystals

Answer 9

. Constitute 1 kg of Ca phosphate forming a large pool size interspersed w/in collagen organic matrix of bone
. Ca pool in hydroxyapatite slowly exchanges (several hrs to days) w/ the ECF
. Process of bone resorption

Question 10

Osteoblasts

Answer 10

. Produce bone collagen (type 1) are involved in complex processes to initiate mineralization of this collagen
. Secrete alkaline phosphatase that elevates the local phosphate conc. Causing Ca phosphate to precipitate forming bone

Question 11

Osteoclasts

Answer 11

. Resorb bone by dissolving hydroxyapatite crystals and secreting collagenase which degrades the collagen matrix

Question 12

Osteocytes

Answer 12

. Conduit for retrieval of Ca from amorphous crystals and delivery of Ca to ECF

Question 13

Bone formation

Answer 13

. Coordination of osteoblasts and osteoclastic activity to bring normal bone growth (modeling)
. Bone shape adapted to mechanical load during growth
. Resorption occurs at endosteal surface while deposition of bone occurs at periosteal surface

Question 14

Quiescence

Answer 14

. Resting state w/ inactive osteoblasts line bone surface

Question 15

Activation

Answer 15

. Bone covered w/ osteoblasts-like precursor cells respond to bone-resorting hormones by secreting enzymes
. Enzymes expose underlying mineralized bone that results in activation of osteoclasts

Question 16

Resorption

Answer 16

. Elevation in bone-resorting hormones foster arrival, replication, and maturation of osteoclasts
. Osteoclasts attach via specific integrin to resorptive site and then form a complex unfolding of plasma membrane ruffled membrane)
. Secrete H through electrogenic proton pump
. Secreted enzymes that degrade the collagen matrix and hydroxyapatite
. Process inc. delivery of Ca and PO4 to ECF

Question 17

Reversal

Answer 17

. Macrophages appear on resorping surface

. Secrete factors required for bone formation

Question 18

Formation

Answer 18

. Osteoblasts secrete collagen on inner surface in certain array and hydroxyapatite crystals slowly mineralized w.in matrix
.

Question 19

Macroscopic states of skeleton

Answer 19

. Cortical bone

. Trabecular bone: has faster remodeling rate and makes greater contribution to extracellular Ca

Question 20

Parathyroid hormone (PTH)

Answer 20

. Peptide synthesized and secreted by chief cells of parathyroid gland
. Actions mediated by cAMP
. Half life is a few minutes

Question 21

PTH secretion

Answer 21

. Main control is ionized Ca
. Inversely related to plasma Ca conc.
. Max secretion when Ca under 3.5
. Even at high Ca conc. There is Ca-independent, non-suppressible component of PTH secretion
. Inverse secretion of PTH w/ Mg (when Mg low, PTH high) except when Mg is extremely low then PTH secretion decreases
. Mg not as potent as Ca

Question 22

Effects of PTH w/ inc. Plasma Ca and dec. plasma phosphate on bone

Answer 22

. PTH stimulates osteocytic osteolysis
. Inc. resorption of hydroxyapatite crystals
. Vit. D permissive for PTH effect on bone
. Estrogen inhibits PTH-mediated bone resorption
. Low dose intermittent PTH administrate stimulates bone FORMATION (we don’t know why)

Question 23

Effect of PTH when there is inc. Ca and dec. plasma phosphate on kidneys

Answer 23

. Dec. Ca excretion by inc. Ca reabsorption in distal tubule
. Inc. phosphate excretion by lowering Tm for reabsorption in prox. Tubule to minimizes inc. in plasma phosphate that results from bone resorption and from gut
. Inc. HCO3 excretion to prevent alkalosis from OH release during bone resorption
. Stimulates 1,25-(OH)2 vit. D synthesis

Question 24

PTH effect on gut when Ca is inc. and phosphate is dec.

Answer 24

. Indirect

. Inc. guy reabsorption of Ca and phosphate via stimulation of vit. D synthesis

Question 25

Relationship between plasma Ca and phosphate

Answer 25

. Reciprocal relationship
. Ant elevation in plasma P that occurs as result of PTH action limits the elevation in plasma Ca
. PTH minimizes elevation in plasma P by selectively inc. excretion of phosphate facilitating return of plasma Ca to normal
. In pathological conditions when Ca and P conc. Exceed 70, Ca phosphate may precipitate in soft tissues that will interfere with organ function

Question 26

Synthesis of vit. D3

Answer 26

. Pre-vitamin D3 is synthesized photochemically in dermis when exposed to wavelengths of 250-310 nm (mid UV)
. Melanin impedes conversion by absorbing wavelength
. Pre-vitamin slowly(days) isomerized to cholecalciferol (vit. D3)
. Vit. D3 transferred into circulation w/ vit. D binding protein

Question 27

Metabolism of vit. D3

Answer 27

. Hydroxylated in liver to 25-OH vit. D
.this form is major circulating form of vit. D bc it has 15 day half-life
. 25-OH vit. D is either hydroxylated again at 1carbon or 24 carbon (1 is active, 24 is inactive)
. Conversion from25 to 1,25 vit. D is stimulated by low Ca,low phosphorus in plasma or kidney, vit. D deficiency, or elevated PTH
. Conversion from 25 to 24,25 is. Stimulated by opposite conditions

Question 28

Vit. D mechanism of action

Answer 28

. Inc. plasma Ca and plasma phosphate
. major effect on GI tract: inc. absorption of Ca phosphate and Mg
. Stimulates bone mineralization (osteoblasts)
. Required for sensitivity of bone to PTH
. Weak effect on kidney: dec. Ca excretion, dec. phosphate excretion

Question 29

Calcitonin

Answer 29

. Small peptide secreted by parafollicular cells
. Inc. as Ca gets above 9 mg/dl
. Dec. bone resorption by inhibiting osteoclasts
. Dec. Ca and phosphate in plasma
. Does NOT participate in minute to minute regulation
. Measurement of calcitonin used to detect presence of medullary carcinoma of thyroid

Question 30

Hypocalcemia

Answer 30

. PTH secretion stimulated to inc. renal reabsorption of Ca, inducing Ca release from bone, and promote 1,25vit. D3 production
. Plasma P has tendency to rise due to enhanced intestinal absorption and bone resorption, the elevated PTH promote renal excretion
. Hypocalcemia seen when PTH/vit.D is inadequate, renal volume due to inc.phopshate accumulation and dec. vit. D synthesis

Question 31

Hypercalcemia

Answer 31

. Develops when Ca input into the plasma exceeds ability of regulating hormones described above to inc. its output
. Primary hyperparathyroidism and malignancy-induced hypercalcemia are most cases
. Dec. PTH secretion and dec. vit. D synthesis in kidneys occur
. Actions dec. Ca reabsorption in gut and inc. Ca excretion in urine
. May also stimulate calcitonin secretion that dec. exit of Ca from bone

Question 32

Hypophosphatemia

Answer 32

. May be cause of hypercalcemia
. Vit. D production inc. to inc. bone resorption and GI reabsorption
. Hypercalcemia inhibits secretion of PTH so phosphate reabsorption inc. and Ca reabsorption dec.

Question 33

Ca and phosphate in aging

Answer 33

. Dec. vit.D synthesis and dec. Ca and phosphate reabsorption from GI tract

Question 34

Ca and PO4 in menopause

Answer 34

. Dec. in plasma estrogen assoc. w/ inc. sensitivity of bone to PTH causes inc. bone resorption and osteoporosis

Question 35

Ca and PO4 and activity

Answer 35

. Pressures generated by gravity are necessary for normal bone cell function

Question 36

Ca and PO4 in immobilization

Answer 36

. Causes inc. bone resorption, dec. bone formation, andCa loss form body

Question 37

Ca and PO4 in exercise

Answer 37

. Causes dec. bone resorption, inc. bone formation, and retention of Ca in the body