Parathyroid gland and calcium Flashcards
What are the cells of the parathyroid gland?
- Chief cells
* Oxyphilic cells
What is the primary action of the parathyroid gland?
Maintenance of plasma Ca2+
What increases plasma Ca2+?
- PTH
* Vitamin D3
what decreases plasma Ca2+?
Calcitonin
Describe the distribution of Ca2+ in the body
- 99% in the bone and teeth
- 0.1% in the plasma - 1/2 is free, 45% bound to proteins, 5% chelated to di-carboxylic acids
- Rest intracellular
What are the physiological functions of Ca2+?
- Prosthetic group for many enzymes and structural proteins
- Structure of the plasma membrane - needed for the structure of the Na+ channel
- Excitation coupling in the muscle
- Excitation-secretion coupling at axonal terminals and in endocrine and exocrine glands
- Blood coagulation
- Major intracellular second messenger
What are the symptoms of hypocalcaemia?
- Muscle cramps/twitches
- Numbness in fingers/toes
- Brittle nails
- Irritability
- Reduced mental capacity
Levels of calcium - hypocalcemia
- Ca<8mg/dl in the plasma
* Less than 1.6mmol/l are lethal
What are the causes of hypocalcemia?
no/low PTH:
• Post surgical hypoparathyroidism
• Inherited hypoparathyroidism
Signalling mechanism of PTH disrupted:
• Pseudo-hypoparathyroidism
• Pseudo-pseudo-hypoparathyroidism
• Vitamin D related
Calcium levels - hypercalcemia
- Total plasma calcium >10.6mg/dl
* Lethal if >3.8mmol/l
What are the symptoms of hypercalcemia?
- Anorexia
- Various GI tract disturbances
- Lethargy
- Depression
- Confusion
- Aches/pains
What are the causes of hypercalcemia?
- Hyperparathyroidism/ adenoma in the parathyroid gland or ectopic tumour raising PTH/PTHrP levels
- High vitamin D intake
- Familial hypocalciuric hypercalcemia
- Sarcoidosis/granuloma
Which cell is responsible for PTH release?
Chief cells
Describe the release of PTH
- G protein coupled receptor in the chief cell binds calcium
- This binds to Gq, activates phospholipase C which hydrolyses PIP2-> IP3 + DAG
- IP3 binds to IP3 receptors which opens calcium channels and calcium then leaves the ER
- DAG activates protein kinase C which phosphorylates a number of proteins
- The rise of calcium inhibits the exocytosis of PTH
- When calcium drops you get constitutive release of PTH
Describe the processing of PTH
- Pre-pro PTH
- Signal sequence gets cleaved making pro-PTH
- Then the pro-sequence gets cleaved making PTH which gets secreted
Describe the processing of calcitonin
- In the parafollicular C cells within the thyroid or brain neurones
- CCP = calcitonin C terminal peptide
- CGRP= calcitonin gene related peptide - potent neurotransmitter in the brain
- In the thyroid CCP and calcitonin are synthesised
- In the brain CGRP is synthesised
In which part of the bone does most calcium turnover take place?
Trabecular bone on the outside
Osteoblasts
- Lay down new bone
- Secrete osteoid (range of bone proteins - 90% type 1 collagen)
- Some proteins in osteoid bind calcium and phosphate and promote the development of hydroxyapatite crystal
- When they are surrounded by bone they become osteoclasts
How are osteocytes connected to each other?
Canaliculi
Describe the action of osteoblasts when the levels of PTH are low
- Osteoblasts (in the presence of vitamin D) secrete osteoid and release calcium and phosphate in high concentrations
- Hydroxyapatite - collagen fibres and proteins stimulate bone growth
Describe the action of osteoblasts when the levels of PTH are high
- Osteoblasts release cytokines e.g. Il-6, RANK ligand, M-CSF
- Binds to circulating stem cells and causes them to differentiate in to osteoclast precursors and cause osteoclasts-> mononuclear osteoclasts -> RANK)
- Stimulates bone reabsorption
Describe bone resorption by osteoclasts
- Integrins bind to vitronectins on the bone sealing apical surface
- Bone reabsorption is promoted
- Increased carbonic anhydrase acid is secreted into the apical surface (HCO3- is exchanged for chloride)
- Exocytosis of proteolytic enzymes from the cytosol via lysosomes fusing with the apical surface - stimulated by cytokines
- Collagen is broken down into amino acids
- Hydroxyapatite is broken down into calcium and phosphate which is taken up into the cell on the apical surface and is released on the basolateral surface into circulation
Where do we get vitamin D from?
Mainly from the diet, some as a byproduct of cholesterol biosynthesis (in the presence of UV light in the skin)
Where do we get vitamin D3 from?
- Milk
- Eggs
- Some fish
Where do we get vitamin D2 from?
- Mainly plants
* Ergocalciferol
What are the enzymes involved in vitamin D metabolism?
- In the liver: a-25 hydroxylase
* In the kidney 1 hydroxylase
Describe the intestinal absorption of Ca2+
- In the intestine, the uptake of calcium is dependent on vitamin D3/D2- it stimulates the synthesis of proteins needed for calcium uptake and calbindin
- Ca2+ is accumulated in the cytosol by binding to calbindin which transmits the calcium to two places- an ATPase and a calcium exchanger
- Because of calbindin, free intracellular Ca2+ remains very low
- Ca2+ is exchanged for 3 Na+ at the calcium exchanger and for a H+ (and ATP-> ADP) at the ATPase
Describe the intestinal absorption of phosphate
- Co-transporter: 2Na+ and HPO4 2-
* unknown ion channel transports HPO42- or H2PO4- out of the cell into the interstitial fluid
