Calcium and Phosphate Regulation Part 1 Flashcards by Imgonnatickle yourpickle

Why are calcium and phosphorus important to study?

-essential to many vital physiological processes
-essential for proper mineralization of skeletal/dentition
-disturbances in calcium and phosphorus homeostasis linked to several pathological disorders

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What are some of the cellular functions that Ca2+ is important for?

-cell division/ cell adhesion
-plasma membrane integrity
-2nd messenger in signal transduction
-muscle contraction
-neuronal excitability
-blood clotting
-skeletal development
-bone, dentin, enamel mineralization
-HARD TO NAME A PROCESS NOT DEPENDENT ON CALCIUM

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What are some cellular functions that phosphorus is important for?

-membrane composition
-intracellular signaling
-nucleotide structure
-skeletal development
-bone, dentin, enamel mineralization
-chondrocyte differentiation

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What are the 3 major pools of calcium in the body?

-bone (99%)
-blood and extracellular fluid
-intracellular

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How much calcium is in the adult body?

around 1 Kg

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What is 99% of the calcium in the body stored as?

in the mineral phase of bone/teeth as hydroxyapatite crystals

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What is HA mineralization of bone important?

mechanical and weight bearing properties of bone

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What does bone HA serves as?

reservoir of calcium to maintain blood ionized calcium within normal range

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What is the normal range for total serum calcium?

8.5-10.5 mg/dL
(2.1-2.6mM)

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What are the three forms of calcium in the serum?

-45% ionized (active)
-45% bound to albumin
-10% complexed with citrate or phosphate ions

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What is the normal range of ionized calcium?

4.4-5.4 mg/dL
(1.1-1.35mM)

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How much calcium is ingested by an adult every day?

around 1000mg

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How much calcium is absorbed by the gut each day?

around 200mg

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How much calcium is filtered daily through kidney?

around 10g

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How much calcium is excreted in the urine daily?

around 200mg

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How much calcium is stored by the skeleton?

around 1 Kg

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How much calcium is released from the bone daily due to normal bone turnover?

around 500 mg

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How much calcium is deposited in bone during the day due to bone formation?

around 500 mg

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Is calcium higher inside or outside the cell?

outside

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What helps to maintain the steep calcium gradient?

Ca2+ pumps in the plasma membrane

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Where is the majority of bodies phosphate?

85% in the HA mineral phase of tooth

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Where else can phosphate be present in the body?

tissues and extracellular fluid

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How much of dietary phosphorus gets absorbed in the gut?

85-90%

What is the normal adult phosphorus serum concentration?

2.5-4.5 mg/dL

Where is most extracellular phosphorus?

free in solution -acts as a buffer to maintain physiological pH

Is calcium or phosphate serum levels more tightly regulated?

calcium

Four organs/organ systems involved with calcium and phosphorus homeostasis?

-gut -parathyroid -kidney -skeleton

What are the three steps of calcium uptake?

-uptake -transcellular transport of calcium -extrusion

What happens during the uptake stage of calcium uptake?

calcium enters the cell from the apical side by ion channels that belong to the TRP superfamily

What happens during transcellular transport of calcium?

calcium binds to calmodulins

What is the extrusion of calcium?

calcium leaves the cell from the basal side by membrane transport proteins

What is TRPV6?

Ca2+ uptake channel on the apical side of the intestinal epithelial cells

What does Calbindin D9K do?

transcellular transport of Ca2+ to basal side of the cell

What does Ca2+ ATPase1b do?

pump Ca2+ out of basal side of cell

What allows phosphate to enter the cell?

phosphate transporter Na+ dependent Pi cotransporter type IIb on brush border of ileum

How much of calcium and phosphate filtered by the kidney is reabsorbed?

calcium - 99% phosphate 85-95%

Mechanisms of calcium reabsorption in the kidney:

1. uptake by TRPV5 2. transcellular transport by Calbindin D28K 3. extrusion by Ca2+ ATPase 1b

What cotransporters are responsible for phosphate reabsorption in the kidney?

-NaPi-IIa -NaPi-IIc

Main hormones involved with Ca2+ homeostasis?

-parathyroid hormone -1,25 dihydroxyvitamin D3 -calcitonin

What are the main hormones involved with phosphate homeostasis?

-parathyroid hormone -1,25 dihydroxyvitamin D3 -fibroblast growth factor-23

When serum calcium is high, what happens?

-parathyroid stops releasing PTH -decrease release from bone -decrease uptake in gut -decrease reabsorption in kidney

When serum calcium is low, what happens?

-parathyroid releases PTH -increase release from bone -increase uptake in gut -increase reabsorption in kidney

What detects serum calcium concentrations?

calcium sensing receptors (CaSR) expressed in parathyroid gland

What is PTH?

-parathyroid hormone -84 aa peptide hormone -calcium regulatory activity -short half life around 5 mins

What receptor does PTH bind to?

PTH1R -class B G-protein coupled receptor -PTH mediated via activation of adenylate cyclase (cAMP) production

What does PTH do to phosphate reabsorption in the kidneys?

decreases phosphate reabsorption -can lead to phosphaturia

Where does 25-hydroxyvitamin D3 get converted into 1,25-hydroxyvitamin D3?

in the kidneys with the help of PTH

What does 1,25-dihydroxyvitamin D3 do?

-induced the expression of calbindins (results in an increase in Ca uptake in gut, reabsorption in kidney, and release from bone) -induce expression of phosphate transporters (results in increase in Pi uptake in intestine, reabsorption in kidney, and release from bone)

What is calcitonin?

hormone released from parathyroid gland in response to elevated serum calcium -oppose PTH actions (decrease serum calcium)

What is the major effect of calcitonin?

inhibit osteoclast resorption in bone by retracted osteoclast ruffled border

What is the minor effect of calcitonin?

inhibit renal reabsorption of Ca2+ and phosphate allowing them to be excreted in urine

What is FGF 23?

-fibroblast growth factor -32 kDa protein important in phosphate regulation -expression induced when serum phosphate too high

What cells are the major source of endocrine FGF23?

osteocytes

What is the overall function of FGF23?

lower serum phosphate

What is the main mechanism for rapid regulation of phosphate?

kidney reabsorption