parathyroid hormone spadaro Flashcards
Calcium in plasma
normal level is 9-10.5 mg/dl
- the tightly regulated Ca in plasma is ionized Cal. 4.5-5.2 mg/dl
- acidosis blocks Ca binding albumin and increases froo ionized Ca
- 1kg of Ca in body, 99% in bone
high Ca is over 12
low Ca is under 7
- high Ca causes fatigue, apathy, anorexia, coma, delerium. headaches, muscle wakness. INCREASES MEMBRANE POLARIZATION AND REDUCES NEURAL RESPONSES. bradycardia, short QT intervals, calculi Ca stones in urine
- lox Ca: learning retardation, apnea, hypersensitivity spasms, LOW CA REDUCES MEMBRANE POLARIZATION, long QT, reduced CO, weak bone development, rickets
FHH familial hypercalcemia hypocalcuria
Ca normally high w/o any high Ca symptoms. issue with receptors recogizing Ca.
- plasma Ca stabilized at high conc.
- urine calcium secretion is low, but individuals are symptom free
Ca economy
-involves, small intestine, kidney, and bone
-80% of daily ingested Ca is excreted in feces
-kidneys filter 10X the average daily intake of Ca, and only excrete abt 175 mg. (we take in 1000 mg and kidney filters 10,000)
-bone is a repository and a buffer for Ca. daily turnover of 280 mg, but 280 goes in and out
-if dietary intake is low, kidney compensted by excreting less. after this isnt enough though, bone will start using osteoclasts to release Ca. lose bone mass and density and can lead to osteoporosis
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Calcitonin
produced by thyorid and has a stronger role in early development. inhibtor of bone resorption
PTH
PTH secretion is high when Ca is low
- targets the kidneys, increases Ca reabrorption in distal tubules and decreases PO4 reabsorption in the proximal tubules. also increases vitamin D3 synthesis
- target 2 is bone cells, this is a slow target wheras kidney was a rapid target. in bone osteoclasts (which break bone) are activated via receptors that take in the PTH on osteoblasts. increase Ca and PO4 in the ECF and plasma
- you dont want PO4 bc it binds Ca.
- osteoBlasts make bone but they have the receptor for PTH so they are able to signal through RANKL to monocytes to differentiate into multinucleated osteoclasts.
- osteoclast activity breaks bone and releases Ca which is good bc of low Ca level but also releases PO4.
- PO4 issue figures itself out. you just secrete more.
PTH secretion
triggers: low Ca, increase PTH secretion high PO4, increase PTH secretion high vitamin D, decrease PTH secretion -Ca sensing receptor is a gprotein coupled receptor -
Ca kidney transport
- in kidney, PTH increases Ca reabsorption at distal tubules and reduces PO4 reabsortion at proximal
- 60% of kidney Ca reabsortion happens at proximal tubules, only 9% at distal. PTH controls distal though for Ca, not proximal.
- vitamin D aids Ca resorption by increasing calbindin proteins to move Ca from lumenal to basal side.
Vitamin D
major role of vitamin D is Ca and PO4 absorption in intestine. other major role is in bone, stimumlating osteoclast resoprtion via osteoblast receptors
- it decreases PTH for negative feedback
- in kidneys distal tubules, increases Ca and PO4 transport
- vitamin D increases when Ca drops. stimulted by PTH.
synthesis and action of vitamin D
- from cholesterol, in skin to blood, to liver where it becomes 25OHcholecalciferol. active form is 1,25D3 which is made in kidneys.
- Vitamin D increases Ca absorption in intestine by increasing transcription of the gene for calbinidin transporter. increases active transport of Ca and PO4 into the blood. PO4 goes up here ut that ok bc PTH in kidneys will resorp less PO4.
Ricketts
-Rickets is poor mineralization due to lack of sufficent Ca and results in mechanically distorted bowed legs. due to deficiency in Ca, deficnecy in vitaminn D, or PO4 deficiency. lead to poor mineralization of bones.
PTH pathophysiologies
- Primary hyperparathyroidism: hypercalcemia, adenima, unrestrained PTH secretion
- Secondary hyperparathyroidism: hypocalcemia, low D, renal failure, diet, etc
- Hypoparathyroidism: hypocalcemia, surgical damage to parathyroid, or genetic
- pseudohypoparathyroid: hypocalcemia, genetic defect in gprotein in PTH receptor
- humeral hypercalcemia of malignancy: hypercalcemia, PTH-rp mimics PTH
- Familial hypocalciuric hypercalcemia: genetic defect in Ca sensors, increased Ca reabsortion
Prosphorus
not very rigidly maintained
- some is protein bound
- proximal tubule, is not resorped by PTH
Collagen matrix synthesis and mineralization
- osteoblasts make procollagen triple helix molecules. they get polymerized extracellularly forming fibrils and an osteoid matrix that eventually mineralies
- mineralized matrix is dense and dark
- osteoid: uncalcified collagen. size of band tells you abt minerals in the body
- matirx vessicles: release compounds that initiate Ca binding on follicle
- osteoblasts produce collagen that becomes mineralized
bone remodeling
- osteoblasts secrete RANK-Ligand which activates osteoclasts on the RANK receptor
- PTH and vitamin D increase resorption
- estorgen: reduces resorption
- calcitonin: is never the right answer. in childhood is an inhibitor of osteoclasts
- glucocorticoids: inhibit intestinal Ca absorption
- Growth hormones: stimulate formation of bone
- Mechanical loading: promote local bone accrual and maintenance
