Hormonal Calcium06
Content
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
1
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 **
2
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………
3
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?
4
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
5
And finally…phosphorous
• • • • • • • 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
6
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
1
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 **
2
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………
3
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?
4
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
5
And finally…phosphorous
• • • • • • • 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
6
