8 - calcium balance

what are the main functions of calcium in the body

signalling - essential for the exocytosis of synaptic vesicles (releasing neurotransmitters and hormones), muscle fibre contraction, and altering enzyme function. 

blood clotting

apoptosis

skeletal strength - 99% of body calcium in the bone

nerve and muscle excitability - Ca2+ decreases Na+ permeability

what can hypocalcaemia lead to

increases neuronal Na+ permeability leading to overexcitability of neurones

what are the extreme symptoms of hypocalcaemia

tetany - spread to larynx and respiratory system causing aphyxiation

why can hypercalcaemia cause cardiac arrhythmia and death

decreases Na+ permeability which reduces excitability and depresses neuromuscular activity

why does hypocalcaemia cause tetany

increases neuronal Na+ permeability leading to hyperexcitability of neurones

where is majority of calcium found

bones and teeth

where is intracellular calcium found

mitochondria and smooth ER

where is calcium found in ECF

bound to protein

where in bone is calcium stored

calcified extracellular matrix stored as hydroxyapatite

when is binding capacity of calcium increased?

alkaline conditions

pH and hyperventilation - calcium effect

hyperventilation increases plasma pH

plasma proteins bind more calcium causing plasma Ca2+ concentration to fall and therefore may precipitate hypocalcaemic tetany

pH decreases - calcium

acidotic conditions reduce binding capacity and free Ca2+ rises

calcium in - calcium out =

total body calcium

what are osteoblasts

bone forming cells

why are osteoblasts important in calcium storage in bone

they are highly active and lay down a collagen matrix which they calcify

what do osteoblasts differentiate into

osteocytes

what is the function of osteocytes

maintain bone matrix

why are osteoclasts important

they mobilise bone

- secrete H+ ions to dissolve salts and provide proteolytic enzymes to digest ECM

what are the 2 endocrine hormones involved in control of calcium homeostasis

parathyroid hormone

calcitriol

what is parathyroid hormone (PTH)

polypeptide hormone produced by parathyroid glands

what is calcitriol

active form of vitamin D - a steroid hormone produced by vitamin D by liver and kidneys

what is calcitonin and its function

peptide hormone released from parafollicular (clear) cells of thyroid

- acts to decreased plasma calcium

where are parathyroid glands found

posterior surface of the thyroid gland

when is PTH released

decreased free plasma calcium

how does PTH increase plasma calcium

on plasma Ca2+: stimulate osteoclasts to increase bone resorption - releases calcium from bone and increasing renal Ca2+ reabsorption

on phosphate: Decreases plasma phosphate concentration by reducing renal reabsorption of phosphate, causing more to be excreted in the urine. This prevents the formation of calcium-phosphate crystals in soft tissues. 

what are the effects of PTH on renal formation of 1a,25-dihydroxycholecalciferol

PTH stimulates the final activation step of Vitamin D in the kidney, converting calcidiol into calcitriol (1,25-dihydroxycholecalciferol) by activating the 1-alpha-hydroxylase enzyme. 

how does calcitriol work

complements action of PTH which increases plasma Ca2+

what are the 2 areas for calcitriol production

liver

kidneys

what is calcitriol formed from

cholecalciferol (vitamin D inactive) from diet or skin via UV

what is formation of calcitriol enhanced by

prolactin

what is the action of calcitriol

increases absorption of Ca2+ from gut

facilitates renal absorption of Ca2+

mobilises calcium stores in bone by stimulating osteoclast activity

why does calcitriol increase Ca2+ absorption in gut

calcium passes straight through and excreted in faeces

- active transport of Ca2+ moves from intestinal lumen to blood via calcitriol

- low plasma Ca2+ - increases PTH which increases calcitriol and intestinal absorption of Ca2+

- also increased plasma Ca2+ causes inhibition of PTH causing a shift in greater osteoblast deposition and less osteoclast resorption

when is someone classed as vitamin D deficient

<20mg/ml

how does vitamin D3 have an effect on calcium concentration

releases Ca2+ from bone - increased mineralisation of bone

- increases Ca2+ absorption from gut and reabsorption at kidneys

how does PTH have a role in vitamin D3 deficiency

maintains plasma Ca2+ and removes Ca2+ in bones that are soft

what does calcium removal result in in vitamin D deficiency

osteomalacia in adults

rickets in children

what does vitamin D3 deficiency lead to

calcium and phosphate deficiency

- results from intestinal malabsorption

- decreases Ca2+ plasma and increased PTH

- promoted phosphate deficiency by stimulating Ca2+ loss from bone

what conditions are a result of vitamin D deficiency

MS

cancer

arthritis

CVD

does PTH increase or decrease the following: -

- osteoblast activity

- osteoclast activity

- renal PO4 excretion

- renal Ca2+ excretion

- Ca2+ absorption from gut

- decreases

- increases

- increases

- decreases

- indirectly through calcitriol formation in kidney

does calcitriol increase or decrease the following: -

- osteoblast activity

- osteoclast activity

- renal PO4 excretion

- renal Ca2+ excretion

- Ca2+ absorption from gut

- indirectly

- increase

- indirectly

- decreased

- increased

how does calcitriol help keep PTH levels low

by increased plasma Ca2+ through increased gut uptake of Ca2+

- reduces PTH mediated osteoblast inhibition and PO4 excretion therefore promoting new bone formation

how is calcium decreased

calcitonin release

- stimulated by increased Ca2+ plasma

what is calcitonin main action

binds to osteoclasts to inhibit bone resorption ass well ass increased renal excretion so preventing further increase in Ca2+

how does cortisol play a role in calcium homeostasis

inhibits osteoblasts

increases renal excretion of Ca2+ and phosphate

reduces intestinal absorption

- decreased plasma Ca2+ but increases PTH so increased bone resorption

what condition can cortisol and calcium cause

osteoporosis

how does insulin play a role in calcium balance

increases bone formation and antagonises action of cortisol

what may be seen in diabetes in terms of calcium

significant bone loss

how does oestrogen/testosterone have a role in calcium homeostasis

promotes bone formation via receptors on osteoblasts

what is a common problem seen post menopause as a result of oestrogens role in calcium homeostasis

post-menopausal osteoporosis

how do growth hormone and prolactin play a role in calcium homeostasis

growth hormone

- role in bone formation

prolactin

- stimulates calcium absorption from gut by stimulating synthesis of calcitriol

Describe the effect of 1, 25 - dihydroxycholecalciferol on Calcium absorption from the gut 

Calcitriol is the only hormone that significantly increases calcium absorption from the small intestine. It does this by stimulating the synthesis of calcium-binding proteins in the intestinal cells. 

Outline the effect of 1, 25 - dihydroxycholecalciferol on parathyroid gland function.

Calcitriol exerts negative feedback on the parathyroid glands to inhibit the synthesis and secretion of PTH. 

what investigations are used to detect abnormalities of calcium control especially Hypercalcaemia. 

Measuring total and ionized plasma Ca2+, plasma PTH, and phosphate levels. 

most common causes, symptoms and signs of hypercalcaemia

causes: primary hyperparathyroidism, malignancy

symptoms/signs: lethargy, muscle weakness (Decreased neuromuscular excitability), constipation, kidney stones (stones, moans and groans), cardiac arrhythmias

most common causes, symptoms and signs of hypocalcaemia

hypoparathyroidism, vitamin D deficiency, renal failure

signs/symptoms: tingling, numbness (increased neuromuscular excitability), muscle cramps, tetany

clinical tests: s: Trousseau’s sign (wrist/finger spasm when a BP cuff is inflated) and Chvostek’s sign (facial twitching when the facial nerve is tapped).