Physio 5 Flashcards
calcium amounts in the body
Total Ca: 9-10.6 mg/dl
Ionized: 4.5-5.2 mg/dl. tightli regulated.
acidosis/alkalemia
blocks Ca 2+ binding to albumin and increases free ionized Ca. alkalemia is the opposite
High [Ca] (hypercalcemia)
> 12 mg/dl. fatigue, apathy, headache, intercranial pressure, muscle weakness, increased membrane polarization and lower neural responses. bradycardia, polydipsia, polyuria, hypertension, calculi
low [Ca] (hypocalcemia)
<7 mg/dl. learning retardation, apnea, tetany, increased hypersensitivity of neurons, long Q-T interval with reduced cardiac output. Ca/PO4 deficiency leading to weak bone development
calcium economy
maintaining calcium balance in the body involving 3 main organ systems: Digestive system, kidneys, and bone. kidneys filter and recapture all but about 175 mg of Ca. bone acts as repository and buffer with daily turnover of about 280 mg. If low Ca intake, kidneys can increase reabsorption of filtered Ca, but in the log term the bones bear the brunt of Ca donating by bone resorption
Calcitonin
hormone made by thyroid gland and has a strong role in early development. inhibitor of bone resorption.
parathyroid hormone (PTH)
targets kidney where it stimulates reabsorption of calcium. Stimulates excretion of PO4 into urine and increases synth of vitamin D to its active form. affects osteoblastic lineage cells. causes them to secrete RANK-L, causing osteoclastic resorption, releasing more Ca and PO4 into blood
PTH secretion
PTH release by chief cells in parathyroid is caused by a reduction of Ca in the extra cellular fluids and plasma. calcium sensing receptor activates a signal cascade involving intracellular Ca binding/release from the ER that controls release and synth of PTH.
FHH (familial hypercalcemic hypocalcuria)
rare disease. curve is shifted to the right, urine calcium excretion is low, and individuals are otherwise healthy. Ca is stabilized at a very high concentration
Ca transport in kidney
PTH increases Ca reabsorption at distal tubule. Vitamin D aids by increasing calbindin/Ca2+ transport and efflux at the basal side. Active transport occurs in the ascending loop. PTH reduces PO4 reabsorption at proximal tubule
Vitamin D
when plasma Ca drops, active form of vitamin D increases. production is stimulated by increased PTH. increases transport of Ca and PO4 from lumen into the plasma in the small intestine. In bone, activates receptors on osteoblast which cause ccell to make signals that promote maturation and activation of osteoclasts which resorb bone. assists transport of Ca in distal convoluted tubules of the kidney. reduces production of PTH (negative feedback)
Vitamin D synth
precursors are cholesterol derivatives generated in skin, converted to cholicalciferol by UV light. Converted to 25-OH cholicalciferal in liver. Active form formed in kidney (1-25 dihydroxy vitamin D3, or calcitriol) by enzyme 1-alpha-hydroxylase. Activity of this enzyme is enhanced by PTH.
calcitriol
increases active and passive transport of Ca and PO4 into blood in small intestine by increasing synth of the transporter (calbindin)
rickets
chronic deficiency of vitamin D and/or dietary deficiency of calcium or phosphorous during early development. leads to disturbances in developing bone formation. weakened and bowed long bones. in adults, leads to poor quality bone formed during remodeling and is called osteomalacia.
primary hyperparathyroidism vs. secondary hyperparathyroidism
primary = hypercalcemia (too much PTH secretion)
secondary = hypocalcemia (low D, renal failure, diet, etc)
hypoparathyroidism vs. pseudohypoparathyroidism
hypo = hypocalcemia due to genetics or surgical damage to parathyroid.
pseudo = hypocalcemia due to genetic defect in G-protein in PTH receptor in kidney
phosphorus homeostasis
not rigidly maintained. PTH influences reabsorption of PO4 in proximal tubule
collagen matrix synth and mineralization
pre-collagen molecules are synthed by the osteoBlast and then polymerized extracellularly forming fibrils and osteoid matrix that eventually mineralizes.
bone mineralization
microcrystaline HA (hydroxylapatite) mineral deposition in collagen matrix. crystals coalesce and accumulate within and around new collagen fibrils
bone remodeling
one by osteoclast. secrete acidic molecules to dissolve mineral and proteases digest and phagocytize the collagen matrix. RANKL from osteoblasts activates osteoclasts, increasing number and bone resorption and turnover. OPG made by osteoblasts slows down bone resorption by competing with RANKL
regulators of bone remodeling
PTH and vitamin D increase resorption. Estrogen reduces resorption. Calcitonin inhibits osteoclasts. Glucocorticoids inhibit intestinal Ca absorption. Growth hormones stimulate formation. mechanical loading promotes bone accrual and maintenance.
mechanical loading as a means of regulating bone mass
increased loading tends to stimulate bone formation and repair, and vice versa. osteocytes reduce expression of sclerostin, an inhibitor of bone formation, when under stress
osteoporosis
trabecular and cortical sites. related to disease or aging. caused by inappropriate or excessive remodeling. . treat with replacing deficient nutrients, loading exercise, or drugs designed to stop resorption
