L24 - Calcium metabolism and bone physiology Flashcards
(14 cards)
describe calcium (concentrations in plasma, in cells, and what processes its involved in)
- plasma calcium concentration ~2.4mM (half bound to proteins) so free concentration is ~ 1.2mM
- calcium concentration inside cells is ~10^-7 (1000 times less than outside~)
- calcium is involved inL muscle contraction, neurotransmitter and hormone release, enzyme activity, membrane permeability/excitability, coagulation, milk production, bone and tooth formation
describe the regulation of intracellular calcium concentration (diagram on slides)
- calcium flows down its electrochemical gradient when calcium channels open
- some bound to proteins inside cell
- can be stored in (and released from) mitochondria and ER (major intracellular store)
- pumped out by active transport and by using sodium electrochemical gradient
describe calcium homeostasis (calcium balance) - diagram on slides with all the components
Diet = 1000mg/day
Feces = 825mg/day
Urine = 175mg/day
so while we eat 1000 mg/day we also lose that same amount
- resorb: break down and assimilate the components of something
- reabsorb: to take up something previously emitted
we need to keep calcium around a level where if you open the calcium channels it will come into the cell quickly
describe bone structure (two major components)
- cortical (compact bone)
- trabecular (spongy) bone (called alveolar bone in jaw)
describe the cellular composition of bone within the osteon
Cortical bone - osteon
- osteoblast: synthesis and secrete collagen fibres and promote calcium phosphate deposition
- osteoclasts: cause bone to release calcium and phosphate from the non-exchangeable pool (99%)
- osteocytes: exchange calcium phosphate between the exchangeable pool (1%) and extracellular fluid
what are the three hormones involved in the control of calcium balance (graph on slides)
- parathyroid hormone: increases plasma calcium
- calcitriol (1,25-dihydroxyvitamin D): increases plasma calcium
- calcitonin: decreases plasma calcium
free calcium in the mid-range for PTH secretion, below the range for calcitonin secretion
- PTH does main control, calcitonin doesn’t really do anything/much unless PTH stops working. its the backup mechanism
- negative feedback homeostatic control
describe parathyroid hormone (secreted by what cells, what happens if you remove parathyroid glands, what is secretion stimulated other inhibited by)
- peptide secreted by chief cells of the parathyroid glands as a preprohormone (not active form), cleaved in the liver and kidney
- removal of parathyroid glands reduces plasma calcium by 50%
- secretion stimulated by decreased plasma calcium
- secretion inhibited by increased plasma calcium
describe the process of chief cell parathyroid hormone secretion
- plasma calcium activates a Gq protein-couples calcium-sensing receptor
- Gq activates phospholipase C
- PLC increases diacylglycerol (DAG) and inositol triphosphate (IP3)
- DAG activates protein kinase C
- IP3 activates intracellular calcium release from the endoplasmic reticulum
- PKC and intracellular calcium inhibit PTH exocytosis
what are the actions of parathyroid hormone (diagram on slides!! look at it to understand all the loops and effects)
many different negative feedback loops in one, all homeostatically regulated
- think about negative feedback in homeostasis: identify the contributing variable, the sensory, the integrator and the effector(s)
PTH has a major effect on intestinal Ca2+ absorption
PTH also makes calcitriol
describe vitamin D and calcitriol
- calcitriol is a vitamin D derivative made in the body
- calcitriol/vitamin D is a hormone because can be synthesised, but vitamin D is mostly ingested (in cod liver oil or plants)
- steroid hormone that: 1. increases calcium absorption in small intestine: increases plasma calcium. 2. increases bone reabsorption: increases plasma calcium
- vitamin D deficiency leads to softening of bones (rickets in children; osteomalacia in adults)
describe calcitriol synthesis and action (pathway, diagram on slides)
- most vitamin D is from diet
- all steroids are cholesterol derivatives
- go to plasma vitamin D
- in the liver and kidney conversion happens where enzymes are expressed
- calcitriol is involved
- all steroids are secreted as soon as synthesised
steroids can go freely into and around the blood circulation. if the cells that they arrive at in the blood don’t have the correct enzyme then it can diffuse into the cell but wont be converted into vitamin D, so this process is dependent on which cells express the enzyme
describe transcellular intestinal calcium absorption
when calcium levels are low or norma they undergo this process which is similar to what happens in the kidney
- calcium enters through transient receptor potential vanilloid channel (TRPV)
- transported across the cell bond to calbindin
- secreted into blood by plasma membrane calcium ATPase (PMCA)
- calcitriol increases TRPV, calbindin and (possibly) PMCA expression
- getting into the cell by concentration gradient, getting out of cell by active transport
describe calcitonin (what type of hormone, inhibits what to do what, released when)
- peptide hormone from thyroid gland C cells (parafollicular cells)
- inhibits osteoclasts to reduce bone resorption and increases urinary calcium excretion to decrease plasma calcium
- released when calcium levels high, may only be recruited under special conditions
C cell secreted calcitonin
Epithelial cells secrete thyroid hormones
describe the processes involved with bone resorption (diagram on slides)
- process happens in osteoclasts
- Gs activation (by calcitonin) inhibits cell function
- PTH stimulates osteoblast cytokines secretion
- secretes proteins, enzymes and phosphatases into the lacuna
- tight junctions (integrins) seal the cell onto calcified bone forming the lacuna
