13 Calcium Metabolism Flashcards
What is calcium vital for?
- Nerve and muscle function - neuromuscular junction
- Bone formation
Three organs important in calcium metabolism
Bone
Kidney
Gut
Where is the parathyroid gland?
Behind the thyroid
Completely different to thyroid gland
4 of them
Relationship between main organs and calcium.
Gut - vitamin D activation absorption
Bone- resorption
Kidney- retention
Explain the role of PTH in regulating serum calcium levels
- Increase bone resorption + Ca release into circulation
- Increase kidney Ca retention + excretion of phosphate
- Stimulation to make active vitamin D - calcitriol > indirectly acts on GI tract
- decreases plasma phosphate
- increases plasma calcium
What does calcium cause in relation to phosphate?
Phosphate loss
What molecule causes phosphate loss?
FGF23
What is needed to vitamin D synthesis?
Sunlight
Present in diet too
Vitamin D synthesis
Vitamin D3 + sunlight
25-hydroxylation
1-hydroxylation
Active form of vitamin D
Where do you get vitamin D2 and D3 from?
D2 - mushrooms
D3 - oily fish e.g. salmon
Action of vitamin D
- Kidney - increased Ca reabsorption
- Parathyroid- decreased PTH production + parathyroid growth
- Bone- promotes formation and growth
- Gut - increased absorption of Ca2+ and PO4 3-
- increases plasma calcium and phosphate
What is hypercalcaemia?
High calcium
>2.51mmol/L
>3mmol/L severe
Symptoms of hypercalcaemia
Polydipsia
Polyuria
Moans - tried, depressed
Groans - constipation, pancreatitis
Stones - kidney stones, polyuria
Bones - bone and muscle aches
Causes of hypercalcaemia
PTH independent - PTH low
PTH dependent - PTH high
Outline the negative feedback regulation of serum calcium when there is an increase in plasma calcium
Decreased PTH secretion
Less calcitriol made
Less Ca2+ reabsorption in kidneys
Less bone breakdown, more bone building
Less Ca2+ absorbed in gut
Plasma Ca2+ levels decreases
Outline the negative feedback regulation of serum calcium levels when plasma calcium decreases
Increased PTH secretion
More calcitriol made
More Ca2+ reabsorption in kidneys
More bone breakdown, less bone building
More Ca2+ absorbed in gut
Plasma Ca2+ levels increases
Explanation of high Ca and low PTH
High calcium form somewhere else
Most likely cancer
Cancer produced PTH-like peptide
Cancers with high calcium
- Myeloma-cancer of blood cells
- Bone metastases -typical tumours that go to the bone: bronchus, thyroid, breast, kidney
NOT prostate
Causes of high Ca, low PTH that’s not cancer
Tuberculosis
Sarcoidosis
Granulomas
Produce vit D
What is sarcoidosis?
Condition which causes small patches of swollen tissues (granulomas) to develop in organs
No necrosis
What are granulomas?
Small patches of swollen tissue
Epithelial histiocyte with surrounding lymphocytes
Primary hyperparathyroidism
High Ca due to high PTH levels
Due to benign parathyroid adenoma
Effects of primary hyperparathyroidism
Causes hypercalcaemia:
Moans - tried, depressed
Groans - constipation, pancreatitis
Stones - kidney stones, polyuria
Bones - bone and muscle aches
What do you need to do in acute severe hypercalcaemia?
Medical emergency
Severe dehydration
Fluid into vein quickly
Treat underlying cause
Hypocalcaemia
Low calcium levels
<1.9mmol/L
Symptoms of hypocalcaemia
Numbness
Muscle cramps
Palpitations
Seizures
Severe symptoms if sudden drop
Signs of hypocalcaemia
Convulsions
Prolonged Q-T interval on ECG
Hyperreflexia- over responsive reflexes
Trousseau’s sign
Chvostek’s sign
Swelling of optic disk
What is trousseau’s sign?
Involuntary contraction of muscle in hand and wrist
What is chvotek’s sign?
Contraction of ipsilateral face muscles after percussion over facial nerve
Causes of hypocalcaemia
Vitamin D deficiency
Hypoparathyroidism
Biochemistry of vitamin D deficiency
Low vit D
Low Ca
High PTH
Low phosphate
Causes of vitamin D deficiency
Lack of sunlight
Pigmented or covered skin
Dietary deficiency
GI disease
Kidney disease
What can severe vitamin D deficiency cause?
Rickets in children
Osteomalacia in adults
What is osteomalacia/rickets?
Demineralisation of bones
Soft and weak bones
Bend and break more easily
Bowed kegs
Biochemistry of hypoparathyroidism
Low Ca
Low PTH levels
High phosphate
Causes of hypoparathyroidism
Surgical damage or removal
Pathology of parathyroid gland
Failure of 3rd or 4th branchial arch
Look for scar in neck from surgery
What is needed in acute severe hypocalcaemia?
Medical emergency
Assess airway and conscious level
ECG monitor to check heart
Intravenous calcium and monitor
What is osteoporosis?
Demineralised bone
Brittle, fragile bones
Break easily
Looks like an areo bar
Risk factors for osteoporosis
- Post menopausal women
- Family history
- Smoking
- Immobility
- Endocrine diseases- hyperparathyroidism, hyperthyroidism, low testosterone in men, premature ovarian failure
Classic places for osteoporotic fractures
Vertebra
Hip
Wrist
Symptoms of osteoporosis
No symptoms
Not painful until break
How is calcium transported in the blood?
Free ionised Ca2+
Bound to plasma protein
Complexed with citrate
Explain the role of calcitonin in regulating serum calcium levels
- Released from thyroid gland from parafollicular cells
- Opposes PTH action
- Decreases plasma calcium levels
What cells are found in the parathyroid gland?
Chief cells - synthesis PTH
Oxyphil cells
How does calcium regulate PTH synthesis?
Low serum calcium up-regulates gene transcription of PTH
High serum calcium down-regulates gene transcription of PTH
Outline the action of PTH on the bone
1- PTH induces osteoblasts to secrete cytokines
2- cytokines stimulate differentiation + activity of osteoclasts
3- PTH decreases osteoblast activity
4- reabsorption of mineralised bone > releases Pi and Ca2+
How is vitamin D3 transported?
Found to transcalciferin
What is the half life of calcitriol
6hours
How much calcium is present in the adult human body in kg?
1kg
How do parathyroid glands sense plasma calcium conc.
By GPCR that are activated by calcium
Storage of calcium
In bones as hydroxyapatite crystals
What hormones are involved in calcium regulation?
Parathyroid hormone
Calcitriol
Calcitonin
What is released if calcium levels are high vs low?
- high: calcitonin to decreased plasma [Ca2+]
- low: PTH to increased plasma [Ca2+]
Action of calcitriol on serum calcium
Raises calcium levels where there has been prolonged reduction
