parathyroid function Flashcards
1
Q
Describe the distribution of calcium throughout the body
A
- Calcium and phosphate are the main minerals in teeth.
- Changes in calcium concentrations ultimately effect tooth health.
- Vit. D deficiency (Rickets) remains a health problem and can be suspected in dental chair.
- Most of this exists as hydroxyapatite crystals within the bones (99%) and teeth.
○ Hydroxyapatite are crystal made of Ca2+ and PO42- - Intracellular calcium concentration is normally held at about 0.1 mol/L (i.e. very low).
- Extracellular (Plasma) calcium concentration is 2.20-2.60 mmol/L.
○ 50% is bound to plasma proteins or in inorganic complexes.
○ The concentration of free calcium ions (ionised) is around 1.4 mmol/L. Responsible for physiological effects and under hormonal control
2
Q
List the important roles of calcium in the body and its sources
A
- Major component of bones, teeth and connective tissue
- Calcification of bone occurs with formation if hydroxyapatite (Ca10(PO4)6(OH)2) crystals
- Has a central role in blood clotting
- Is a second messenger
- Used to contract muscles
○ Unblocks binding site my moving tropomyosin out the way
○ Require for nerve transmission (release of neurotransmitter) at the neuromuscular junction - Can either get from diet or from the storage in the bone
- Will sacrifice the bone to collect Ca2+ if deficient
- If low Ca2+ (ionised) in the body you will die
3
Q
Describe the roles of calcitonin, parathyroid hormone (PTH) and vitamin D in calcium homeostasis
A
- As your blood ionising Ca2+ falls the PTH is released
- When Ca2+ is low PTH is high
- Want Ca2+ to remain in the window 1.2-1.4 mmolL
- Ca2+ is very reactive so if too much then will react with things like proteins.
○ Can cause kidney stones - Parathyroid has 4 glands (sometimes 3 or 5) embedded in the posterior surface of the thyroid tissue
- Parathyroidectomy results in hypocalcaemic tetany and death due to asphyxia if untreated
○ Therefore, parathyroids are essential for life
○ If all the parathyroids are removed then PTH won’t be produced and you will die
○ If thyroid is removed then parathyroids are stitched back into body - Regulate calcium and phosphate levels
- Secrete parathyroid hormone (PTH) in response to:
○ Low ionised calcium
○ High phosphate - PTH is a single chain of 84 amino acids but biological activity is in first 34 amino acids1-34aa,
- PTH is synthesized as a large precursor molecule and has a short half-life of 5 mins.
- Chief cells of the parathyroid gland responds directly to changes in plasma calcium level and secrete PTH
○ decreased calcium= increased PTH so Ca2+ increace
○ increased calcium = decreased PTH so Ca2+ decrease
○ Short term regulation of calcium - Synthetic machinery & storage vesicles are in chief cell.
- PTH pre-stored for rapid release.
- If chronic hypocalcemia then CaR stimulate PTH synthesis.
1. When Ca2+ drops the rectors activate
2. Sends impulse the chief cell
3. PTH is released
4
Q
Describe the whole body handling of calcium in the maintenance of calcium balance
A
- Calcium regulation:
○ Endocrine control of calcium homeostasis: Parathyroid hormones, vitamin d and Calcitonin (some people don’t have calcitonin but remain fine)
○ Acts on: one, kidney and intestine
○ Parathyroid is controlled by a negative feed-back loop- The action of chief cells when the calcium level is too high
- Ca2+ binds to the G protein CaR on the surface of the chief cells
- This leads to the production of phosphoinositide
- The activation of phosphoinositide stops PTH secretion so Ca2+ is deposited back into the bones
▪ Since PHT also increases the vitamin D activation, less PTH means that there will be less active vitamin D in the body so less CA2+ will be absorbed
○ Is Ca2+ levels are too low the opposite effect occurs and more PTS is released
- Vitamin D synthesis and action
○ PTH increases the activation of vitamin d in the kidneys so more Ca2+ can be absorbed
○ PTH increases vitamin D activation in the kidneys
○ PTH increases the activation of Vitamin D so indirectly increases the Absorbtion of Ca2+ in the small intestine
○ Vitamins D acts like a hormone as it comes from cholesterol
○ Synthesised by the skin and activated at the kidneys then will have an effect at the target tissue
○ >90% of the vitamin D (D3) comes from sunlight- cholesterol in the skin is converted to 7-dehydrocholesterol to cholecalciferol
○ Can also be obtained from foods and supplements (D£ from diary, oily fish and liver- D2 from yeast fungi and margarines)
○ Vitamin D3 (cholecalciferol) is Activated to calcitriol (1,25-dihydroxyvitamin D3) after 2
successive hydroxylations in the liver and kidney
▪ It is bound by a specific globulin and transported to the liver where it is converted to 25(OH)2D3
▪ In the kidney proximal tubule this is converted to 1,25(OH)2D3 by the enzyme 1alpha-hydroxylase
▪ Transcription of 1alpha-hydroxylase is increased by PTH
▪
▪
▪ Long-term regulation of calcium (cf PTH)
Acts on nuclear receptors (VDR) in intestinal mucosa
▪ increases synthesis of calcium binding protein (calbindin) in intestinal cells
▪ Increases calcium (and phosphate) absorption
▪ Facilitates remodelling of bone
▪ Negative feedback on PTH
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- The action and role of osteoclast and how they are stimulated
○ PTH binds to the receptors on the osteoblast
▪ This causes the release of RANK-L from the osteoblast which stimulates the activity of the osteoclast
▪ Osteoclast break down bone to release Ca2+]
▪ Osteoblasts form bone
▪ Osteocytes regulate the health of the bone
▪ Break the bone down if chronically low on Ca2+
▪ Release calcium phosphate
▪ Osteoblasts will reform the lost bone
▪ If you have too much Ca2+ lost the osteoclasts activity is higher than the osteoblasts
○ PTH binds to the cells surface receptor in bone and kidney
○ Causes a direct increace of Ca2+ release from the bones (stimulates bone reabsorption)
○ Ca2+ is bound to phosphates in the bone and interstitial fluid
○ interstitial fluid has lots of calcium phosphate
○ Bone is remodelling and uses calcium phosphate to do this (fix the minor fractures that happen every day) - PTH action on the nephron
○ Proximal convoluted tubal-phosphate reabsorption
▪ PTH blocks the sodium phosphate co-transporter in the proximal convoluted tubal
▪ PTH inhibits the cotransporter so decreased blood phosphate level and increased phosphate level in the urine
▪ Decreased phosphate reabsorbing means that less hydroxyapatite crystals can form and trap the Ca2+
○ Distal convoluted tubule- calcium reabsorption
▪ PHT causes the synthesis of more Ca2+ ATPase activity so more CA2+ can be reabsorbed
▪ Increases the Na2+/Ca2+ exchange - Calcitonin action
○ There are two cell types in the thyroid gland:
▪ Follicular cells release and store thyroid hormone.
▪ Parafollicular cells - also called C cells, secrete calcitonin (role in Ca2+ metabolism – not related to major thyroid hormones)
○ Produced by Parafollicular Cells in thyroid, 32 amino acids long
○ Release stimulated by raised plasma calcium levels
○ Binds to receptors in bone
○ Acts to inhibit bone resorption - returns plasma calcium level to normal
○ Not essential to life (post thyroidectomy no calcium problems) Physiological relevance?? - *
- The action of chief cells when the calcium level is too high
5
Q
State the consequences of hypocalcaemia
A
- hypercalcaemia is when blood Ca2+ levels are too low
- Causes:
- Hyperparathyroidism (over secretion of PTH).
- Malignancy
- Others – less common
- Results in kidney stones, constipation, dehydration, kidney damage, tiredness and depression
- Primary hyperparathyroidism
○ Parathyroid adenoma (noncancerous tumour in the parathyroid gland that causes the gland to produce too much parathyroid hormone (PTH))
○ Treatment – parathyroidectomy (surgical procedure to remove one or more of the parathyroid glands)
○ restore CFV after excessive urine loss.
*
- Causes:
6
Q
State the consequences of hypocalcaemia
A
- Most of the blood Ca2+ if from the diet. If Ca2+ is not being absorbed then body will have to break down the bones to use the serum Ca2+ in the bones
- Physiological response to hypocalcaemia:
Increase PTH
Breakdown of bone to release calcium - Causes: Vitamin D deficiency, PTH deficiency, renal disease. PTH resistance, vitamin D resistance (rare)
- Hypoparathyroidism rare. Can be caused by removal of parathyroids
- Causes life threatening hypocalcaemia (death when respiratory muscles affected) also hyperphosphataemia
- Vitamin D deficiency
○ caused by
§ Poor diet
§ Lack of sunlight
§ Chronic renal failure (kidney cannot activate vitamin D)
○ Can cause
§ Bone is sacrificed to maintain plasma calcium levels
□ Rickets in children
® Rickets show curly legs as they are sacrificing bone to get Ca2+. Get weakened bones so when they start standing the bones will curve out.
□ Osteomalacia ‘soft bones’ in adults
○ Treated with vitamin D supplements
§ Not advised to go into the sun due to skin cancer - Hypocalcaemia can result in hyperexcitability if the neuromuscular junction (pins and needles) tetany-paralysis-convulsion
○ Low Ca2+ means Na+ takes over and produce action potentials
§ This could lead to diaphragm spasming which is fatal
○ PCa <1.5mmol -carpopedal spasms/convulsions
○ PCa <1.0mmol -fatal laryngospasm – asphyxiation - DEATH
○
- Physiological response to hypocalcaemia:
