Mineral Metabolism Flashcards by Emily Mosher

Normal Ca conc.

. 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

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

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Ca in acidosis

. 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

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Ca during alkalosis

. 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

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Pathways Ca enters of leave extracellular fluid

. GI tract
. Kidney
. Bone

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Phosphorous in body

. 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

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Magnesium

. 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

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Amorphous crystals

. 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)

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Hydroxyapatite crystals

. 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

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Osteoblasts

. 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

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Osteoclasts

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

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Osteocytes

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

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Bone formation

. 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

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Quiescence

. Resting state w/ inactive osteoblasts line bone surface

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Activation

. 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

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Resorption

. 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

Reversal

. Macrophages appear on resorping surface

. Secrete factors required for bone formation

Formation

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

Macroscopic states of skeleton

. Cortical bone

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

Parathyroid hormone (PTH)

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

PTH secretion

. 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

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

. 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)

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

. 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

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

. Indirect

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

Relationship between plasma Ca and phosphate

. 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

Synthesis of vit. D3

. 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

Metabolism of vit. D3

. 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

Vit. D mechanism of action

. 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

Calcitonin

. 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

Hypocalcemia

. 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

Hypercalcemia

. 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

Hypophosphatemia

. 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.

Ca and phosphate in aging

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

Ca and PO4 in menopause

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

Ca and PO4 and activity

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

Ca and PO4 in immobilization

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

Ca and PO4 in exercise

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