Ca metabolism Flashcards
which is produced more, T3 or T4?
T4
true or false: all of T3 and T4 come from the thyroid gland
true for T4, false for T3 (some come from the thyroid gland, some T3 is made from the conversion of T4 elsewhere in the body)
which has greater binding affinity? T3 or T4?
T4
which has a greater half-life? T3 or T4?
T4
which has as a more predominant presence of its free form molecules? T3 or T4?
T3
what organs does PTH stimulate?
- osteoclasts
- kidneys
- small intestine
what does PTH do to the osteoclasts?
encourages resorption of bone tissue (bone calcium is released into the circulation)
what does PTH do to the kidneys?
encourages the retention of Ca and activation vitamin D to calcitrol
what does PTH do to the small intestine?
encourages absorption of calcium
what type of cells produce calcitonin?
C cells (in parafollicular cells)
what does calcitonin do?
decreases blood Ca2+ concentration
what are some remedies for rickets?
original treatments: - fish liver oil - sun exposure - UV-irradiation of certain foods recently: - PTH/calcitonin (20th century)
what are some roles of calcium? (6)
- structure in skeleton (bones contain almost all of the calcium in the body)
- blood clotting (mesh formation)
- regulation of enzymes (cofactor)
- second messenger (GPCR/IP3)
- regulate membrane excitability
- muscle contraction
where is most of the calcium? where’s the rest?
- bones - 99%
- the other 1% is present in the extra-bone space (intracellular)
- 0.1% is present in the extracellular fluid (focus of this lecture)
how do you get tetany?
1) hyperventilation –> increased expulsion of CO2 (decreased CO2 in lungs)
2) CO2 turns into carbonic acid at lesser amounts
3) carbonic acid turns into proton and bicarbonate (less protons in circulation)
4) plasma proteins release protons into circulation, leaving proteins negatively charged
5) proteins look for positive ions and bind Ca++, decreasing free calcium concentration
6) compensated by moving Ca++ from intracellular space into circulation from the sarcoplasm
7) tetany
alternatively: chelating agents bind Ca2+
which cells produce PTH?
chief cells and oxyphil cells
what stimulates release of PTH?
low calcium concentration
function of Calcitonin?
not super clear, and maybe not that important to humans; doesn’t elicit much of a response when injected or when in decreased levels
is PTH stored?
yes, in granules
what gets PTH to release from granules?
calcium sensing receptors (CaR) on chief cells detecting low levels of Ca
what kind of receptor are CaRs?
GPCR
what does high concentration of Ca do to CaRs?
- decreased cAMP, increased IP3
- decreases in PTH synthesis and secretion
what does low concentration of Ca do to CaRs?
- increased cAMP, decreased IP3
- increases in PTH synthesis and secretion
what are the 2 important proteins in bones and what do they do?
- osteocalcin: released by osteoblasts, binds with hydroxyapatite (calcium salt)
- osteonectin: released by osteoblasts, binds with collagen and hydroxyapatite
describe syntehsis of osteoblasts
mesenchymal stem cells –> osteoprogenitor cells –> osteoblasts
describe bone formation
osteoblasts make collagen & proteins (osteoid) –> mineralization –> differentiation of osteoblasts into osteocytes
what cells remove Ca from bones?
osteoclasts
what cells deposit Ca from bones?
osteoblasts
how are osteoclasts attached to bone?
integrins
how do osteoclasts degrade bone?
- proton pumps come to cell membrane where they pump out H+
- dissolves hydroxyapatite
- proteases break down collagen
- transcytosis of degradation product into the interstitial fluid
how does PTH end up stimulating bones?
1) stimulate osteoblasts to release osteoclast activating factors (OAFs)
2) OAF stimulates osteoclasts
3) degrade bone to release Ca
4) stimulates osteoblasts to induce recalcification
5) decreased free calcium
osteoclasts respond to what stimuli?
- OAFs from osteoblasts
- mechanical stress (injury)
what’s PTHrP?
- parathyroid related protein
- produced by other cell types in fetuses and adults (esp women w/placenta)
- regulates proliferation and mineralization of chondrocytes and regulator of placental Ca2+ transport
- acts similar to PTH because it can bind to one of the PTH receptors (PTHR-1)
where is PTHR-1 located?
bone and kidney tissue
what happens to the bones when you have too much Ca?
osteopetrosis (marble bone):
- increased bone density due to defective osteoclasts
- bones are more brittle/prone to fracture
what happens to the bones when you have too little Ca?
oStEoPoRoSiS
- excess osteoclast function
- bones lose strength (too porous) and are more prone to fractures
what’s it called when your bones lose density (reduced calcification) when you age?
involutional osteoporosis
characterization of primary hyperparathroidism?
- too much PTH
- increased parathyroid cell proliferation and PTH secretion INDEPENDENT of calcium levels
what causes hyperparathyroidism?
- radiation exposure
- lithium
- loss of tumor supressor
symptoms of hyperparathyroidism
- stone formation (esp kidney)
- bones undergo abnormal formation (includes weird teeth)
- groans (pain due to weird bones)
- psychosis
what causes hypoparathyroidism?
- insufficient PTH
- nerfed response to PTH
- insufficient vit D
- nerfed response to vit D
surgery, familial causes, autoimmune, idiopathic (spontaneous)
treatment for hypoparathyroidism?
calcium + vit D
what is the only hormone known to reduce hypercalcaemia?
calcitonin
is calcitonin gene significant to humans?
yes, CGRP 1 acts as a potent vasodilator
vitamin D is formed in the skin because of _____ _____ on the molecule _____, to be converted to ______
photochemical reaction; 7-dehydrocholesterol; cholecalciferol (D3)
in what food items is vitamin D being commonly added?
- milk
- butter
what’s vitamin D2?
calcitrol
- found in diet or can be converted from D3 via rxns in liver and kidney
- can be made by irradiation ergosterol from plants
- used to fortify foods
what kind of receptor binds vitamin D?
nuclear
where is vit D degraded?
kidney
how does vit D affect PTH?
inhibits
how is calcium absorbed in the intestines?
- binds to proteins, myosin or calmodulin
- calbindin (regulated by Vit D) binds Ca and brings it to base of intestinal epithelial cell
- Ca is pumped out
treatment of vit D deficiency?
- supplement
- sun
how do you achieve vitamin D toxicity?
too much supplement
symptoms of vitamin D toxicity?
weakness, lethargy, headaches, nausea, polyurea, ectopic calcification
treatments of vit D toxicity
- stop taking supplement
- reduce calcium intake
- cortisol
