Parathyroid calcium and phosphate

Question 1

What is the role of calcium

Answer 1

• Adult human contains ~1000 g of calcium
• 99% is sequested in bone in the form of hydroxyapatite crystals (Ca10(PO4)6(OH)2)
• Skeleton provides
– structural support
– major reserve of calcium
– Helps to buffer serum levels
– Releasing calcium phosphate into
interstitium
– Up taking calcium phosphate
• ~300-600 mg of calcium is exchanged between bone and ECF each day

Question 2

What are the plasma calculus levels

Answer 2

• Serum calcium 2.2-2.6
mM
• ECF [Ca2+] a very small
fraction of total-body calcium (>1% )
• Distributed among three
interconvertible fractions 
• Biologically active free ionized [Ca2+] closely regulated to 1.0-1.3 mM 
• Most of the calcium in the body is stored in skeleton
See slide

Question 3

What are the fucntions of calcium

Answer 3

Important in intracellular signalling pathways
Appropriate levels of calcium required for nerve transmission at NMJ
Builds and maintains bones and teeth
Regulates heart rhythm
Eases insomnia
Reduces the incidence of colon cancer,
Calcium Ca2+
Reduces blood cholesterol levels
Needed for activity of some enzymes and some hormone receptor binding,
Important to normal kidney function
Lowers blood pressure
Helps maintain proper nerve and muscle function
Helps regulate the passage of nutrients in & out of the cell walls
Assists in normal blood clotting

Question 4

What happens in hypocalcaemia?

Answer 4

Hypocalcaemia
• hyper-excitability of NMJ
– pins and needles
– tetany (muscle spasms)
– paralysis
– convulsions
Lethal

Question 5

What happens in chronic hypercalcaemia?

Answer 5

Chronic hypercalcaemia
– renal calculi
– kidney damage
– constipation
– dehydration
– tiredness
– depression

Question 6

Where are the parathyroid glands located

Answer 6

Stuck to the posterior aspect of the thyroid but are different structures. 4 is the normal amount but there might be more in some people
If thyroid being removed surgeon should not remove parathyroid bc batient cant regulate calcium levels

Question 7

Describe the histology of the parathyroid gland

Answer 7

See slide

Question 8

What are 3 hormones involved in the regulation of calcium and phosphate

Answer 8

Three hormones involved • Parathyroid Hormone (PTH)
• Calcitriol, also called 1,25-dihydroxycholecalciferol, or 1alpha,25-
dihydroxyvitamin D3, 1,25-dihydroxyvitamin D3 and other variants, (need to know the 1,25/1 alpha) is the hormonally active metabolite of vitamin D which has three hydroxyl groups. It
can be abbreviated 1α,25-(OH)2D3 or simply 1,25(OH)2D
Both increase serious calcium ^
• Calcitonin (Thyroid Gland)
– (C cells in the thyroid) - LOWERS serum calcium

Question 9

Describe th control of calcium homeostasis

Answer 9

See slide

Question 10

Describe PTH synthesis

Answer 10

• PTH has no serum binding protein
• Straight chain polypeptide hormone- Pro-pre hormone (115AA long), cleaved to 84AA
• Synthesis is regulated both at transcriptional and post transcriptional levels
• Low serum calcium up-regulates gene transcription
• High serum calcium down-regulate
• low serum calcium prolongs survival of mRNA (mechanism not known)
• T ½ is 4 min and released PTH cleaved in liver
• PTH continually synthesised but little store
– Chief cells degrade hormone as well as synthesis it
– Cleavage of PTH in chief cells accelerated by high serum calcium levels

Question 11

Describe the secretion of parathyroid v ca2+ receptor

Answer 11

Calcium sensitive receptor. Like w/ gq pip2 -> day + ip3
Inhibition of secretion. If calcium binds to receptors - inhibit the release of pth
If there isnt much calcium - removal of inhibitory cascade - release of pth

Question 12

What are the pth target organs and what are the physiological effects

Answer 12

• Kidney
– Decreases loss to urine 
• Gut
– Activates Vitamin D and hence
increases transcellular uptake from GI tract
• Bone
– Increase resorption

Question 13

Describe teh reabsorption of ca2+

Answer 13

Ionised calcium
Bound calcoium calcium is too big to get filtered
Ionised calcium is freely filtered at teh glomerulus
Normally 60-70% reabsorbed calcium in PCT
In AL DCT and CD, varying amount of calcium reabsorption
Some excreted in urine
But most of ionised ca2+ reabsorbed

Question 14

Describe teh effect of pth on the kidney

Answer 14

Elevated pth, increase of uptake in LOH, -> increase serum calcium levels - i creating reabsorption in ascending limb

Question 15

What is the PTh actio on gut

Answer 15

• Dietary intake of calcium is typically 1000 mg/d
– Only 30% of which is absorbed by a paracellular uptake effective when
[Ca2+] is not limited – Absorption is significantly increase by Vitamin D via a transcellular uptake
• PTH stimulates conversion of vitamin D to its active form which
↑uptake of Ca2+ from gut.

Question 16

Describe calcium balance and bone

Answer 16

• Skeleton has two primary functions
conc. and vice versa
• structural support and maintaining serum Ca2+ conc. – maintenance of serum Ca2+ conc. is priority
• Diseases in bone that affect structural integrity have consequences for serum calcium – Calcium phosphate crystals found within collagen fibrils
• Ca2+ + Pi = hydroxyapatite crystals

Question 17

What are teh actions of pth on bone

Answer 17

• 1-2 hrs PTH stimulates osteolysis
– PTH induces osteoblastic cells to synthesis and secrete cytokines on cell surface
– Cytokines stimulate differentiation and activity in Osteoclasts and protect them from apoptosis
– PTH decreases Osteoblasts activity exposing bony surface to Osteoclasts
– Reabsorption of mineralized bone and release of Pi and Ca2+ into
extracellular fluid

Question 18

Describe teh synthesis on vitamin d

Answer 18

Make vitamin d in skin. Need sunlight. Made from cholesterol. Makes cholecalciferol - vit d3. Cholecalciferol sis similar to dietary vit 3 (early calciferol)
Either one - liver hydroxylates it on carbon 25 (add OH)
His tertiary form of vitamin d is not the active form
It can hand aground in this form for a few weeks (long half life)
In the. Kidney under influence of pth, second hydrokylation
25-hydroxyvitamin d3 becomes 1,25-dihydroxy vitamin d3 - aka calcitriol

Question 19

How does vitamin d compare to hormones

Answer 19

• Each of the forms of Vitamin D is hydrophobic
• transported in circulation bound to carrier proteins: acts through a nuclear receptor
• 25-hydroxyvitamin D in the liver t ½ life ~2 weeks: Active form t ½ of 5 hrs
• Pre-vitamin bound to carrier small enough to be filtered by the glomerulus and enter PCT where the conversion to active form takes place by enzyme 1a hydroxylase
• The active form of the hormone is released from the kidney
• C-1 hydroxylation is under negative feedback to serum calcium levels, elevated calcium prevents C-1 hydroxylation
• Elevated PTH stimulates C-1 hydroxylation to form Calcitriol, 1,25-dihydroxycholecalciferol

Question 20

Where is calcitonin produced ad what is its role?

Answer 20

Made in thyroid from c calls 
C cells are sparsely distributed
Action is somewhat unsure
In animals - lower serum calcium
In humans - if u remove thyroid (and tf c cells) - patients to not have dysregulation on calcium levels - appears not to have an effect - this hormone doesnt have much of an effect n human s

Question 21

What is the role of calcium in blood clotting

Answer 21

It is factor IV in the clotting cascade
EDTA is a calcium chelation
Citrate chelates calcium ions. Need to give recipients of massive blood transfusions intravenous calcium!

Question 22

Describe hospital setting aetiology of hypercalcaemia

Answer 22

• Malignant osteolytic bone metastases
• Multiple myeloma
Common cancers that metastasise to bone causing lytic lesions and hypercalcemia 
• Breast 
• Lung 
• Renal 
• Thyroid
Prostate cancer is a common cause of bone metastases. However, it causes osteoblastic metastases that do not cause hypercalcemia