Calcium and phosphate metabolism Flashcards
What and where are the body stores of calcium?
1.3kg, 99% skeleton, 1% intracellular, 0.1% ECF.
What is the standard dietary intake and absorption of calcium?
Approx 25 mmol, with net absorption 3mmol
Describe the turnover of calcium stores.
Bone turnover of 500mmol, with cell mediated bone turnover of 7mmol. GF (what is this????) 250mmol, reabsorbed 247mmol, 3mmol excreted.
Where is calcium absorbed? What is active absorption dependant on?
There is active absorption in the duodenum and upper jejunum. This is dependant on calcitriol. A small amount of passive absorption occurs downstream.
What inhibits calcium absorption?
Phosphates, oxalates, FA -> (??) form insoluble Ca2+ compounds.
How is calcium found in the plasma?
45% is protein bound to albumin, 45% is ionised (active fraction and regulated (??), 10% is in various complexes.
What is calcium binding to albumin dependant on?
pH. Acidosis causes decreased binding and therefore more free calcium. Alkalosis increases binding, makes less free calcium and increases risk of tetany.
What is the effect of PTH on the kidney?
PTH stimulates reabsorption in the distal tubule.
What occurs to calcium in the kidney?
Ionised and complexed calcium is filtered, with 99% reabsorbed. 60% in the proximal tubule, and 40% in the ascending limb of the loop of hence and the distal tubule.
Describe the body stores of phosphate.
Total body stores of phosphate are 700g, with 85% in the skeleton and a significant amount in cellular molecules.
What is the plasma concentration of phosphate?
1.2mmol/L but this varies.
What is phosphate absorption dependant on?
Dietary intake, but calcitriol stimulates absorption.
Describe urinary excretion of phosphate. What inhibits this?
85-90% of filtered phosphate is reabsorbed in the proximal tubule. This is inhibited by PTH.
Describe the parathyroid glands.
Each parathyroid gland is a richly vascularised disk 3x6x2mm containing two types of cells; chief cells (majority) and oxyphil cells(minority).
What is the role of chief cells?
Chief cells contain a prominent golgi apparatus, endoplasmic reticulum and secretory granules, and secrete PTH
What is the role of oxyphil cells?
Oxyphil cells are larger than chief cells and have an unknown function.
Where is PTH synthesised?
In the chief cells.
Describe the synthesis and molecular makeup of PTH
Liner polypeptide with a molecular weight of 9500; 84AA. PreproPTH->EF->proPTH->PTH secretory granules.
What is the normal plasma level and half life of PTH?
10-55pg/mL, t1/2 10mins, cleared by the kidneys.
What stimulates increased secretion of PTH?
Low calcium low magnesium, high phosphate.
What inhibits secretion of PTH?
High calcium, high magnesium, calcitriol.
What are the actions of PTH?
PTH increases plasma Ca2+
Decreases plasma phosphate
??can cause a mild acidosis
Long term, PTH stimulates osteoblasts and osteoclasts
How does PTH increase plasma calcium levels?
PTH acts directly on bone to increase bone resorption and mobilise calcium.
PTH also increases the reabsorption of calcium in the renal tubules, although if ??Ca2+ concentration is too high this system may be overwhelmed and renal secretion may increase.
PTH also increases the formation of 1,25 DHCC which increases GI Ca2+ reabsorption
How does PTH decrease plasma phosphate?
PTH increases urinary phosphate excretion due to a decreased reabsorption of phosphate in the proximal tubules.
What is the mechanism of action of PTH?
Probably via 3 different receptors: G2 coupled -> adenlylxxx? cyclase -> this increases intracellular cAMP
What regulates secretion of PTH?
Circulating ionised calcium acts directly on the PTH glands in a negative feedback fashion. The key is a cell membrane Ca2+ receptor which when bound inhibits PTH secretion.
If Ca2+ is high, …… secretion is …… and calcium is deposited in ……. . If Ca2+ is low, ……. is secreted, and …… is mobilised.
PTH, inhibited, bones. PTH, calcium
What is the effect of 1,25 DHCC on PTH secretion?
1,25 DHCC decreases preproPTH mRNA
What effect does plasma phosphate have on PTH secretion?
Increased plasma phosphate stimulates PTH secretion.
What other electrolyte is necessary?
Mg2+ is required. (How???)
How is is calcitriol known?
vitamin D
Describe the formation of calcitriol
Cholesterols ->UV light->vitamin D3 -> liver -> 25HC (T1/2 12 days) -> 1,25HC
What stimulates the last step of calcitriol formation?
PTH, decreased plasma calcium, prolactin, GH, calcitonin, and ??decreased by opposites including acidosis
What is the mechanism of action of calcitriol?
Calcitriol binds to nuclear receptors and modifies DNA/RNA
What are the effects of calcitriol?
??Calcitriol increases GUT uptake of calcium, increases calcium reabsorption, increases osteocyte change, and provides negative feedback to PTH.
Where is calcitonin synthesised?
In the parafollicular cells of the thyroid
What stimulates calcitonin secretion?
increased calcium (??et al??)
What is the caction of calcitonin? How?
Calcitonin decreases calcium and decreases phosphate, by inhibiting bone reabsorption and increasing urinary excretion.
What other hormones affect calcium homeostasis?
Glucocorticoids, GH, thyroid hormones.
How do glucocorticoids affect calcium homeostasis?
They inhibit bone formation and gut absorption (??through bit D)
How does growth hormone affect calcium homeostasis?
Growth hormone stimulates Vit D formation leading to increased Ca2+ and increased phosphate.
How do thyroid hormones affect calcium homeostasis?
Thyroid hormones can increase calcium levels and cause hypercalcuria and osteoporosis.
What are the clinical features of hypercalcaemia
-Weakness and and constipation due to decreased muscular excitability
-Polyuria due to inhibition of ADH, and dehydration (??)
-Renal calculi, hypertension, caridac arrythmias, psychological disturbance
Peptic ulceration from increased gastric acid secretion secondary to increased calcium.
Describe the symptoms of primary hyperparathyroidism
stones (renal), bones, (GI) groans and (psychiatric) moans
What are the clinical features of hypocalcaemia?
Tetany (from increased excitability), numbness, stridor, cataracts, psychological disturbances
What are the causes of hypocalcaemia?
Transient post-op, pancreatitis, prolonged hypoparathyroidism, malabsorption and CRF
What are the causes of hypercalcaemia?
Hyperparathyroidism, malignancy (PTHrP, multiple myeloma, bone metastasis), sarcoidosis (increased bit D), thiazide diuretics (stimulate calcium reabsorption), thyrotoxicosis, Paget’s disease
How does chronic renal failure affect calcium homeostasis
Chronic renal failure results in increased plasma phosphate, decreased vitamin d production, leading to a significant decrease in calcium. This causes secondary hyperparathyroidism, leading to increased bone reabsorption with increased ALP and ectopic calcification.
What are the effects of a parathyroidectomy? What eponymous clinical signs are associated with this?
PTH is essential for life. Following a parathyroidectomy there is a steady decline in plasma calcium. Low plasma calcium causes neuromuscular hyper excitability and hypocalcaemic tetany. Symptoms usually develop 2-3 days postoperatively but may be delayed. Chvostek and Trousseau’s signs.
Describe Chvostek and Trousseau’s signs
Chvostek: nerve hyperexcitability - tap facial nerve at angle of jaw and facial muscles on that side contract momentarily
Trousseau: Inflate BP cuff to occlude brachial artery for 3 minutes. Without blood flow, hypocalcemia and subsequent neuromuscular irritability will induce spasm of the muscles of the hand and forearm. The wrist and metacarpophalangeal joints flex, the DIP and PIP joints extend, and the fingers adduct.
What causes PTH excess?
PTH injections, parathyroid adenomas.
What characterises parathyroid excess (is this just primary hyperparathyroidism??)
Hypercalcaemia and hypophosphatemia
PTHrP is produced by .. ….. of ……. and is necessary for ……
a number of tissues, survival
Why is hypercalcaemia common in malignancy?
20% due to bone metastasis, or 80% due to high levels of PTHrP - breast, kidney, ovary, skin.
