4_4CaPO4 Flashcards
What percentage of the body’s calcium is intracellular?
1%
What percentage of body’s calcium is extracellular?
.01%
How does calcium exist in the blood?
1) 9% complexed to anions, 2) 50% ionized, 3) 41% protein bound
What are the functions of Calcium?
1) neuromuscular excitability, 2) blood coagulation, 3) hormonal secretion, 4) enzymatic regulation, 5) structural integrity of bone
What is the blood concentration of calcium?
9.4 mg/dL = 1.2 mM = 2.4 mEq/L
At what concentration of Calcium is a patient hypocalcemic?
6 mg/dL
What concentration does hypercalcemia occur at?
12 mg/dL
symptoms of hypercalcemia
12 mg/dL = neuromuscular depression; 15 mg/dL = PTH poisoning and CaPO4 precipitates
symptoms of hypocalcemia
6 mg/dL = tetany, spontaneous neural depolarization; 4 mg/dL = death
What percentage reduction in blood [calcium] leads to hypocalcemia?
35
How is calcium excreted?
90% in feces; 10% in urine; regulated by PTH
Describe the absorption of Calcium.
35% bioavailable in the presence of (required) Vitamin D
What is the concentration of HPO4?
1.05 mM
What is the concentration of H2PO4?
0.26 mM
How big of a change in total phosphate can the body tolerate?
2-3 fold
What are the components of bone?
1) organic matrix; 2) bone salts
function of the organic matrix of bone
tensile strength
function of the bone salts
compression strength
Describe the composition of bone’s organic matrix?
90% collagen, 10% ground substance = proteoglycans = chondroitin SO4 + hyaluronate
Describe the composition of bone salts.
hydroxyapatite + Mg/K/Na/CO3 adsorbed to surface
What is the formula of hydroxyapatite?
Ca10.(PO4)6.(OH)2
Describe the ECF of bone.
supersaturated with Ca and PO4
Why doesn’t the ECF of bone precipitate?
pyrophosphate inhibitor
Describe the formation of bone
1) osteoblasts secrete collagen monomers and proteoglycans; 2) collagen polymerizes to form osteoid; 3) osteoblasts are entrapped to become osteocytes; 4) Ca++ precipitates to form hydroxyapatite
What is osteoid
collagen polymers + proteoglycans
Why is bone remodeled?
1) adaptation to loads; 2) replacement of brittle bone
What is an osteon
an area of new bone
How is an osteon formed?
1) osteoclasts eat out tunnel, 2) osteoblasts fill tunnel until vascular impingement
How is osteoclast’s Ca++ absorption stimulated?
PTH and Vit. D stimulate preosteoclasts via osteoBLAST release of OPGL. Differentiation to osteoclasts.
How do osteoclasts resorb bone?
release proteases and acid from ruffled membrane
What is the function of osteoblasts?
bone deposition
How are osteoblasts stimulated?
stress, fractures; increase osteoblasts from osteoprogenitor cells
What is the timeframe for osteoclast tunnel-carving?
3 weeks
What is the timeframe for osteoblast invasion and deposition?
2-3 months
What are the dimensions of the osteoclast-formed tunnel?
0.2-1 mM x 3 mM
Describe Vitamin D synthesis.
1) skin: cholesterol - cholecalciferol; 2) liver: cholecalciferol – 25-OH-D3; 3) kidney: 25-OH-D3 – 1,25-OH-D3
What is the formula of Vitamin D?
1,25-dihydroxycholecalciferol
How does vitamin D stimulate intestinal reabsorption of Ca and PO4?
increases CaBP, Ca-stimulated ATPase, alkaline phosphatase
Describe the feedback inhibition in vitamin d synthesis.
1) 25-OH-D3 inhibits liver conversion; 2) PTH activates kidney conversion, but Ca++ inhibits PTH
What are the functions of Vitamin D?
1) increase Ca/PO4 absorption, 2) regulate bone deposition (low) and reabsorption (high)
What are the functions of PTH?
1) increase Ca/PO4 absorption from bone; 2) increase Ca/PO4 absorption from intestine 3) increase PO4 excretion; 4) decrease Ca excretion; 5) stimulate Vit. D synthesis for Ca absorption in intestine
How many parathyroid glands are there?
4
How is PTH secreted?
as pre-prohormone from chief cells
When is PTH secretion stimulated?
by low Ca++ (rickets, pregnancy and lactation)
When is PTH inhibited?
high Ca++ (diet, lots of Vit. D, excess bone absorption)
Describe PTH’s secretion in acute vs. chronic hypercalcemia.
chronic PTH secretion is more sensitive to low Ca due to PTH hypertrophy
How does PTH exert its effects on bone?
1) Osteocytic osteolysis rapid phase; 2) osteoclast activating slow phase
What is osteocytic osteolysis?
1) PTH acts on osteo cytes to absorb surface Ca and fluid, 2) osteocytes pump to osteoblasts at bone surface; 3) osteoblasts pump out Ca++ to ECF
Describe the osteoclast activating slow phase of PTH on bone
PTH activates existing and generates new osteoCLASTS
Where is calcitonin secreted?
parafollicular cells of the thyroid gland
What stimulates calcitonin release?
increased [calcium]
What is the function of calcitonin?
minor Ca++ homeostasis; promotes bone deposition: 1) decreases osteoclast absorption; 2) prevents formation of new osteoclasts
What are symptoms of hypoparathyroidism?
tetany
What are symptoms of hyperparathyroidism?
erosion of bone (can be completely eroded)
What is the mechanism behind the hypoPTHism Ssx?
1) decreased osteoclast number and activity; 2) decreased bone and intestinal Ca++ absorption
What is the usual cause of hyperparathyroidism?
tumor
What is the mechanism behind hyperPTHism Ssx?
1) increased osteoclast # and activity; 2) increased bone/intestinal Ca++ absorption
What are causes of osteoporosis?
1) lack of physical stress; 2) low estrogen; 3) old age; 4) malnutrition; 5) hyperPTHism
What is the pathophys behind osteoporosis?
decreased bone matrix due to low osteoblast activity
