19- Parathyroid Gland, Ca2+ And Phosphate Regulation

Question 1

• is there a lot of Ca2+ in the human body? where is most of it held?
• is there a lot of Ca2+ in the plasma? what are the 3 types?
• give 5 uses for Ca2+ in the body.
• why is Ca2+ important in blood clotting?

Answer 1

• yes, around 1000g and most is bones in the form of hydroxyapatite crystals (Ca2+ and phosphate together)
• no it’s v little (2.2-2.6 mM), ionised, protein bound (hard to access) and complexed Ca (easily accessed) forms.
• needed for nerve transmission @ NMJ, maintains bones and teeth, regular heart rhythm, normal kidney function, blood clotting.
• Ca2+ is factor IV in the clotting cascade therefore this is why when blood is collected EDTA or citrate is added (a calcium chelator) to remove Ca2+ so the blood doesn’t clot!

Question 2

• name the 3 hormones involved in regulation of calcium & phosphate.
• what are the 2 interchangeable names for the cells that produce PTH?
• what are oxyphil cells? how do these & chief cells appear in histology?

Answer 2

• PTH (increases plasma Ca2+), calcitriol (aka 1,25(OH)2D or vitamin D/D3- acts as PTH’s assistant), calcitonin (made by parafollicular cells in thyroid gland- not a huge contributor to Ca2+ reg in humans, decreases Ca2+)
• chief/principal cells.
• oxyphil cells=thought to be old chief cells. Chief cells are circles w deep purple nuclei + close together, oxyphils are darker and c,one to adipose cells.

Question 3

• how is PTH synthesised and what regulates its’ synthesis?
• what is PTH’s half life and what does this tell us about it?
• name PTH’s 3 target organs and its physiological effects at each.

Answer 3

• PTH has no serum binding protein, it’s a straight chain pp, pro-prehormone is cleaved. It’s transcription is regulated by Ca2+ levels: High serum Ca2+ down regulates gene transcription & vice versa.
• T1/2= 4 mins telling us it’s a hormone that lasts only a while, acts fast to slight changes and is continually synthesised as little can be stored (chief cells degrade it esp in high Ca2+ levels)
• 1)Bone where it increases resorption of Ca2+ which will stimulate osteolysis via osteoclasts activity, decreases osteoblasts activity to release Ca2+ into plasma, increasing Ca2+ conc. 2)the gut/small intestine(indirectly as its via calcitriol)=activates Vitamin D and hence increases uptake of Ca2+ in GI tract.
  3) kidney=decreases Ca2+ loss to urine, however bc when Ca2+ high it and phosphate can join and form crystals, the kidneys also increase amount of phosphate excreted to prevent them both being high at the same time.

Question 4

• give some sources of vitamin D.
• how does vitD3 and its metabolite compare to hormones?
• describe the 2 steps in which Vitamin D3 is converted to calcitriol & location.

Answer 4

• the sun, cheese, butter, fresh fish, fortified cereals.
• VitD3 is not secreted by an endocrine gland but it’s metabolite acts as a hormone similarly to steroid hormones.
• 1)Vit D3 is the hormone precursor and is from UV. 25(OH)D is the prehormone substrate-it’s produced in the liver from VitD.
  2) 25(OH)D is converted to 1,25(OH)2D ie calcitriol in the kidney and is the active hormone.

Question 5

• give the 3 main effects of calcitriol and what does it act like?
• describe the feedback reg of serum calcium if there’s been an increase.
• give symptoms and causes of hypercalcaemia. Why is this less severe than hypocalcaemia?

Answer 5

• increase Ca2+ reabsorption in gut, kidney and bone. Acts like PTH.
• too much Ca2+=decreases PTH secretion, bone will activate osteoblasts to use calcium, gut will decrease reabsorption, kidney will metabolism less calcitriol from VitD so less gut absorption.
• hypercalcaemia:symptoms=stones (renal stones), moans (depression, fatigue), groans (constipation, dehydration), bones (bone + muscle aches). Causes=primary causes usually either 1)malignant osteolytic bone metastasis from common cancers moving to bone eg breast (not prostate as although it moves to bone, it causes bone building ie osteoblastic activity) OR 2)PTHrP (PTH related peptide) which is a hormone produced by squamous tumours of lung, neck etc that acts at PTH receptors + mimics the effects of PTH so the neg feedback loop is disturbed. Secondary causes= all PT glands undergo hyperplasia after overstimulation to compensate for low VitD eg or in chronic renal failure.
• less severe as hypo affects the NMJ.

Question 6

• what are the most common sites for nine metastases?
• in a patient w malignancy via PTHrP causing hypercalcaemia, why are their VitD levels low?
• what are some symptoms of hypocalcaemia?

Answer 6

• vertebrae, head of femur, pelvis, ribs.
• the PTHrP mimics PTH but cannot increase renal C1-hydroxylase enzyme which normally increases calcitriol levels.
• hypocalcaemia= hyperexcitability of NMJ (less Ca2+ means more Na+ in neurones depolarising them), tetany.

Question 7

• what affects do different Ca2+ levels have on neural activity?
• what sorts of symptoms are seen in hypo and after what procedure?
• give the diff between osteomalacia and osteoporosis & which one comes about fro, a lack of VitD and why?

Answer 7

• hyper causes more Ca2+ in cell and more Na+ needed to AP (less excitable). Hypo means less Ca2+ in cell so need less Na+ to AP (excitable)
• tingling around mouth and fingers due to tetany of muscles, carpopedal spasm of hand. Post thyroid surgery when some PT Gland accidentally removed.
• osteomalacia=lack of VitD causes lack of Ca2+ reabsorption from gut so bones are soft due to lack of mineralisation. Osteoporosis= bone is hard but honeycomb bc oestrogen levels are low, not to do w mineralisation or lack or VitD!!

Question 8

-what is alkaline phosphotase and what is it a marker of?

Answer 8

-it’s an enzyme present in osteoblasts in plasma and a marker of bone turnover. If it’s high, osteoblasts are making lots of bone.