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49 Cards in this Set
- Front
- Back
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what regulates osteoclast
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PTH
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what stimulates the expression of Ca transporter
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Vit D
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what is the pathway when there is low Ca
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PTH secreted from parathyroid gland
liver makes 25 hydroxy D3 which goes to the kidney in the kidney PTH activates the 1 hydroxylase which hydroxylizes 25 hydroxy D3 into 1,25 dOH which is the active form of vitamin vit D travels to the gut where it stimulates uptake of Ca since PTH is being secreted it will inhibit the Thyroid C cells from secreting calcitonin therefore there will be an increase in OSTEOCLAST activity in the bone |
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what is the pathway when there is high Ca
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Ca sensors will prevent PTH from being released
since there is no PTH 25 hydroxy D3 becomes 24, 25 diOH instead which is very inactive since there is no PTH Thyroid C cells secrete calcitonin which increases osteoblast activity in the bone therefore more Ca is stored |
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what are some of the causes of hypocalcemia
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malabsorption of Vit D
liver disease or renal disease surgical removal of parathyroid glands |
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what disorders disrupt Ca deposition in the bone
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osteoporosis
pagets disease osteomalacia-rickets cushings syndrom |
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what are some of the causes of hypercalcemia
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hyperparathyroidism
hyperthyroidism(due to increase in bone turnover) addison's disease tumors (some secrete cytokines IL1/IL4 that cause bone resorption) |
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how does addison's disease cause hypercalcemia
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due to adrenal insufficiency in which you don't have enough aldosterone therefore you're not absorbing Na/H2O therefore your blood Ca concentration becomes more concentrated
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what is the most common way hypoparathyroidism occurs
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surgical removal
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what happens ot Ca and Vit D in Primary hypoparathyroidism
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since there is no PTH 1 hydroxylase will not be activated in the kidney resulting in no active Vit D being made
since there is no PTH to inhibit calcitonin secretion from thyroid C cells, calcitonin will go to the bones and activate osteoblast causing more Ca to be stored |
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what are the therapeutics for normal hypocalcemia
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vit D with or without calcium salts
can give ergocalciferol which will get hydroxylated at the 1 position in the kidney into active Vit D3 for people w/o PTH give them calcitriol since it is already active people w/o PTH can also hydroxylate at the 1,25 position of keratinocytes and or macrophages |
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what are the therapeutics for people with severe hypocalcemia
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treat with calcium salts given slowly via IV
calcium regulates all ventricular smooth muscle contraction and relaxation |
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when hypocalcemia is very severe what may occur
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tetany
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what are the therapeutics for tetany
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calcium gluconate
calcium chloride calcium gluceptate |
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how is calcium gluceptate given
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IV and IM
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how is calcium chloride given
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IV only
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how is calcium gluconate given
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IV
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why is calcium chloride never given IM
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may cause renal insufficiency
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what is Doxercalciferol used to treat and how is it given
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PRODRUG (1 alpha cholecalciferol which gets hydroxylated @ the 25 position in the liver)
maintains blood Ca in 2ndary hyperparathyroidism |
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where does ergocalciferol get hydroxylated
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at the 1' position in the kidney
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what is Doxercalciferol used to treat and how is it given
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PRODRUG (1 alpha cholecalciferol which gets hydroxylated @ the 25 position in the liver)
maintains blood Ca in 2ndary hyperparathyroidism |
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where does ergocalciferol get hydroxylated
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at the 1' position in the kidney
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what kind of receptor are the Ca receptors
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GPCR
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what are some of the causes of 2ndary hyperparathyroidism
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renal insufficiency
severe Ca malabsorption |
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what occurs in renal insufficiency and what does it cause
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it causes 2ndary hyperparathyroidism
if there is a renal disease then PTH no longer has control over PO4 secretion and as a result you will have more PO4 in the blood binding up Ca and making the Ca receptors believe there is low Ca thereby secreting more PTH in response |
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what occurs in sever Ca malabsorption and what does it cause
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it causes 2ndary hyperparathyroidism
body sees low Ca b/c its not getting into the blood |
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what are the therapeutics for hypercalcemia
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can treat with loop diuretics, but you often see dehydration and loop diuretics will only intensify this so you must give them fluids. loop diuretics will increase Ca excretion
calcitonin can also be used since it activates osteoblast causing Ca to be stored IV bisphosphonates |
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what is calcitonin escape
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the calcitonin Rc will eventually become desensitized
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how do you treat hypercalcemia if it is due to autoimmunity
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the bone degredation may be due to an inflammatory response and glucocorticoids will be given to treat this BUT glucocorticoids also have the effect of causing hypocalcemia and bone resorption
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what are the properties of loop diuretics
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work in thick ascending limb
increase secretion and excretion of Ca (PREVENT CA REABSORPTION) |
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what occurs in renal osteodystrophy and how does it lead to 2ndary hyperparathyroidism
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since there is a renal problem the kidney will no longer listen to PTH as a result PO4 will be secreted causing HYPERPHOSPHATEMIA which means free Ca drops and the Ca sensors sense this and increase PTH secretions which leads to bone resorption thereby raising Ca in blood
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what does hyperphosphatemia lead to
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2ndary hyperparathyroidism
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what drug can be used to treat 2ndary hyperparathyroidism
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paricalcitrol
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what can be given to treat hypercalcemia
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sevelamer
paricalcitriol cinacelet |
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what does sevelamer do
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absorbs PO4 in the gut
BONUS: lowers cholesterol uptake |
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what does cinacalcet do
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mimics calcium so that it can be sensed by the Ca receptor causing PTH secretions to stop
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what are the therapeutics for osteoporosis
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antiresorptives (estrogen, bisphophonates, SERM, calcitonin)
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how does 1st gen bisphosphonates work
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once inside the osteoclast they form cytotoxic ATP analogs causing the demise of the osteoclast
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what is meant by 2nd and 3rd generation bisphosphonates minimizing "dissolution" activity
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bisphosphonates cause crystal formation of the hydroxy apitite to occur slowly
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what do all bisphosphonates do
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decrease activity of osteoclast by interfering with cholesterol synthesis which causes the cell to undergo apoptosis because cholesterol is needed for membranes
decrease fracture risk increase bone mass taken asfter a fast on an empty stomach and must sit or stand for an hour to prevent oral esophogial irritation |
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what kind of receptor does calcitonin bind to
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GPCR
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what are the properties of Calcitonin
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antiresorptive (used to treat osteoporosis)
protects against fractures but doesn't increase bone mass as well derived from salmon |
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what receptors are expressed by osteoblast and osteoclast
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estrogen and androgen receptors
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what does estrogen do to osteoclast
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estrogen decreases the number and activity of osteoclasts
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what does estrogen do to osteoblasts
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increases : igf1, bone morphogenic protein, TGF-b, osteoprotegrin THESE ARE BONE BUILDING MEDIATORS
decreases: IL-1, IL-6, TNF-alpha ABSORB BONE BY ACTIVATING OSTEOCLAST |
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what all can activate osteoclast
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IL-1
IL-6 TNF-alpha PTH |
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what are examples of SERM
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raloxifene
tamoxifen |
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what are the properties of Raloxifene
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COUNTERS BONE BREAKDOWN
agonist in bone antagonist in breast increases bone density less than bisphosphonates reduce risk for fractures INCREASE IN HOT FLASHES |
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what are the properties of tamoxifen
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competes with estrogen for binding to the estrogen receptor
counters bone break down for post menopausal uteris and bone agonist antagonist in breast increases bone formation |
