Flashcards in Human Endocrinology Deck (109)
what is endocrinology?
study of hormones
where is most (99%) of the total calcium in the body stored?
as calcium phosphate salts in bones.
why is it important that cytoplasmic Ca2+ is very low? (around 0.1μM)
provides steep gradient for calcium entry from organelles or extracellular fluids
features of Ca2+ in extracellular fluid
only about 0.1% of Ca2+, controlled very precisely (within 10% of 2.4mM)
how is Ca2+ present in plasma found ?
40% combined with plasma proteins, 10% is combined with smaller anions (e.g. citrate and phosphate) 50% ionised.
where does extracellular calcium bind?
fixed, negative charges on extracellular surface of plasma membranes, altering profile of potential gradient. across membrane without altering size of membrane potential. (surface charge screening)
what is the use of surface charge screening with calcium?
stabilises the membranes of excitable cells, more difficult to open ion channels.
what is Hypocalcaemia?
extracellular calcium levels drop to around 1.5mM, nervous system becomes progressively more excitable.
- tetanic contraction of muscles.
what can servere hypocalcaemia lead to?
tetany of laryngeal muscles leading to asphyxiation
what happens in hypercalcaemia
depression of nervous and muscular activity. Calcium salts can begin to precipitate out if levels rise higher than 3mM. e.g. calcium oxalate kidney stones
what chemical messengers does calcium homeostasis involve?
parathyroid hormone [1,25(OH)2D] and calcitonin
where does calcitonin and parathyroid hormone target?
- Gut (absorb more or less ca2+)
- Kidney ( modulate our rate of absorption)
- Bone (change balance between erosion and deposition)
what can present challenges to calcium homeostasis?
pregnancy and lactation, egg-laying, poor absorption (vitamin D3 deficiency) and oxalate poisoning
where is parathyroid hormone (PTH) secreted from and where is this located?
parathyroid glands, 4 glands located behind the thyroid.
pattern of PTH release
circadian rhythm, released in pulses.
(innervated by autonomic nerves, helps modulate rhythms)
how many amino acids are in the polypeptides
what is the only significant external stimulus to promote increased PTH release?
decrease in plasma free calcium levels. (low internal calcium levels promotes vesicular release)
what kind of receptors respond to PTH and where are they located?
G(q)-protein linked and located on plasma membrane
what is the response to increased free calcium levels in the plasma?
increase internal calcium levels.
how does PTH work on the bone, kidney and gut to increase Ca2+ levels? (general)
negative feedback system to increase plasma calcium levels.
(gut via Vitamin D3)
what do osteoblasts do?
lay down organic matrix of bone, if they become trapped inside the bone = osteocytes.
both blasts and cytes connect to separate bone fluid (high in calcium and adjacent to bone surface) from ECF.
BOTH HAVE MEMBRANE BOUND PTH RECEPTORS.
What is the matrix of the bone composed of? (and where is calcium involved)
collagen and proteoglycans. Calcium phosphate salts precipitate on collagen fibres, forming hydroxyapatite crystals.
what are osteoclasts?
multinucleate cells that release proteolytic enzymes and acids to help digest and dissolve the bone for bone remodelling.
what takes place in bone remodelling?
bone reabsorption by osteoCLASTS and deposition by osteoBLASTS.
what effects does PTH have on the bone?
osteocytic osteolysis (erosion of bone crystals by osteocytes) where Ca2+ released transfered to ECF.
- osteoblasts inhibited from laying down more bone and produce a paracrine signal stimulating osteoclasts to erode bone (and progenitor cells to differentiate into more osteoclasts)
how does PTH work on the kidney?
increases active reabsorption of calcium by Distal convoluted tubule (DCT)
- inhibits reabsorption of inorganic phosphate ions in PCT, lowering extracellular phosphate levels.
- stimulates synthesis of active vitamin D3 derivative.
why does PTH cause net phosphate loss despite phosphate absorption from gut and bone being increased?
overwhelmed by increased loss of phosphate in urine.
where is Vitamin D3 (cholecalciferol) sythnesised?
keratinocytes (specialised skin cells) from cholesterol. [requires exposure to UVB light]
how can Vitamin D3 be obtained in the diet?
from dairy products and fish liver oils. (or D2 from fungal sterol ergosterol)