Hormonal control of plasma calcium

Hormonal control of plasma calcium

Dr Joy Hinson

Calcium in plasma Sources of calcium Vitamin D3 Parathyroid hormone (calcitonin) Disorders of calcium metabolism

Calcium in plasma
Total plasma [Ca++] = 2.5mmol/l Range is 2.0 to 2.5 mmol/l (varies between populations) Very tightly controlled

Calcium in plasma
~ 45% bound to plasma proteins ~10% complexed (with glucose, citrate etc) ~ 45% Free ionised (physiologically active)

Sources of plasma calcium

1. Uptake from diet 2. Resorption of bone 3. Inhibition of loss in urine

Bone: a dynamic tissue

Balance between two cell types OsteoBlasts: Builders of bone OsteoCLAsts: CLAw back bone Cell activity partly regulated by hormones which maintain plasma calcium

Bone cells

Parathyroid hormone (PTH)

A peptide hormone from the parathyroid glands. There are usually 4 of these, associated with thyroid gland.

PTH secretion:
Stimulated directly by low plasma calcium Inhibited by high plasma calcium

PTH increases plasma calcium

It does this by acting on kidney and bone

Actions of PTH
2. Bone effects -stimulates bone resorption PTH receptors on osteoblasts causes a) Inhibition of osteoblasts b) Release of osteoclast activating factor So PTH increases resorption and slows building

Renal effects: -stimulates calcium resorption - causes increased phosphate excretion - increases production of an enzyme **

Disorders of parathyroid hormone

1. Hypoparathyroidism Uncommon but very serious. Leads rapidly to hypocalcaemia, tetany and death

2. Hyperparathyroidism
Primary: tumour of parathyroid Secondary: hypersecretion to compensate for chronically low serum calcium - Hypercalcaemia - Renal calculi (kidney stones) - Bone disease

Vitamin D3

Sources of Vitamin D3
SKIN Action of sunlight (ultraviolet light) converts 7-dehydrocholesterol to vitamin D3 DIET Vitamin D3 is found in fish and eggs. In UK it is added to margarine

A tasty breakfast..?

Or maybe

How is this regulated?

There seems to be no control of Vitamin D3 production. Surely all hormones have regulated production?

Vitamin D3 is inactive
It has to be converted by two hydroxylation reactions to 1,25 dihydroxy-vitamin D3 The first reaction is in the liver: not regulated The second reaction is a 1alphahydroxylation. It is the 1 alpha hydroxylase enzyme that is regulated by PTH**

Activated vitamin D3: calcitriol

Actions of calcitriol
Increases levels of calcium binding protein in gut so increased absorbance of dietary calcium In bone increases number of osteoclasts Raises plasma calcium

Vitamin D3 deficiency
In children leads to rickets. In adults causes osteomalacia These diseases are both failure of bone mineralisation

Both PTH and active D3 raise plasma calcium

But ONLY the actions of Vitamin D3 allow an increase in total body Ca++. In the absence of enough active D3, bone is sacrificed to maintain plasma calcium. What happens when plasma calcium is too high?

Calcitonin
Made in parafollicular cells of thyroid

Excess calcium is just lost in urine.

But. There is another hormone that appears to act to lower plasma calcium

Stimulated by high plasma calcium Acts to lower plasma calcium by inhibiting osteoclasts and increasing calcium excretion in urine.

BUT:
Patients with XS calcitonin have normal plasma calcium and normal bone structure Patients with no calcitonin also have no symptoms May have role in protecting the skeleton in pregnancy, definitely needed in birds and fish, otherwise not important.

A use for calcitonin

Pagets Disease of Bone
A condition in older people where osteoclast activity is abnormally high and bone remodelling becomes disorganised. Associated with pain and fractures.

The first widely available treatment for this disorder was salmon calcitonin.

Summary 1
If plasma calcium is high

Summary 2
If plasma calcium is low:

PTH secretion decreases so: i) Less activation of vitamin D3 and less uptake of calcium from gut ii) Bone resorption inhibited so more bone building happens iii) Less Ca++ resorption in kidney so XS calcium is lost in urine.

PTH increases so: i) Less Ca++ lost in urine ii) More D3 activated so more Ca++ absorbed in gut iii) Bone resorption stimulated

And finallyphosphorous
90% of total body phosphate is in skeleton Plasma phosphorous is 120mg/l 65% of this is in organic compounds Remainder is Pi (inorganic phosphorous) Pi is filtered and 90% resorbed in kidney PTH inhibits Pi resorption Pi comes from diet: uptake stimulated by active D3

THE END