Calcium Dysregulation Flashcards
What increases calcium?
- Vitamin D
2. PTH secreted by parathyroid glands
How do you get vitamin D?
Synthesised in skin or intake via diet
What decreases calcium?
Calcitonin
What is calcitonin secretion by?
thyroid parafollicular cells
What is a good indicator of body vitamin D?
Serum 25-OH vitamin D
What is another name for 1,25(OH)2 vitamin D?
Calcitrol
What makes Vitamin D3?
- UVB on skin or diet Vit D2
- 7-dehydrocholesterol
- Pre vitamin D3
- Vitamin D3
What forms Vitamin D3 into 25(OH) cholecalciferol?
25 hydroxylase in the liver
What turns 25(OH) cholecalciferol into 1.25(OH)2 cholecalciferol?
1 alpha hydroxylase in the kidney
What is the active form of vitamin D?
- Calcitriol
- Once. calicotriol made negative feedback to 1 alpha hydroxlase
What are the effects of calcitriol?
- Increased osteoblast activity
- Increase Ca2+ absorption from gut + in kidney
- Increase PO4 3- absorption from gut + in kidney
What does PTH do?
- Increase Ca2+ reabsorption from bone
- Increase Ca2+ absorption in gut
- Increase PO4 3- absorption gut
- Increase Ca2+ absorption in kidney
- Increase PO4 3- excretion in kidney
- Increase 1 alpha hydroxylase action in kidney so more calcitrol synthesised
What happens in hypocalcaemia?
Sensitises excitable tissues; muscle cramps, tetany, tingling
What are the symptoms in hypocalcaemia?
- Paraesthesia (hands, mouth, feet , lips)
- Convulsions
- Arrhythmias
- Tetany
- Chvosteks’ sign – facial paresthesia
- Trousseau’s sign – carpopedal spasm
What are causes of hypocalcaemia?
- Low PTH levels: hypoparathyroidism
2. Low vitamin D levels
Why might you have low PTH levels?
- Surgical – neck surgery
- Auto-immune (every endocrine gland)
- Magnesium deficiency
- Congenital (agenesis, rare)
What are reasons for low Vitamin D levels?
Deficiency – diet, UV light, malabsorption, impaired production (renal failure)
What are the renal effects of hypercalcaemia?
Nephrocalcinosis – kidney stones, renal colic
What are the GI effects of hypercalcaemia?
- Anorexia
- nausea
- dyspepsia
- constipation
- pancreatitis
What are CNS effects of hypercalcaemia?
- Reduced neuronal excitability – atonal muscle
- Fatigue
- depression
- impaired concentration
- Altered mentation
- coma (usually >3mmol/L)
What are the causes of hypercalcaemia?
- Primary hyperparathyroidism
- Malignancy
- Vitamin D excess (rare)
What primary hyperparathyroidism would cause hypercalcaemia?
- Too much PTH
- Due to a parathyroid gland adenoma
- No negative feedback - high PTH, but high calcium
What malignancy would cause hypercalcaemia?
- Bony metastases produce local factors to activate osteoclasts (release calcium)
- Certain cancers (eg squamous cell carcinomas) secrete PTH-related peptide that acts at PTH receptors
What happens in parathyroid adenoma?
- Produce too much PTH
- Calcium increases, but no negative feedback to PTH due to autonomous PTH secretion from parathyroid adenoma (primary hyperparathryoidism)
What is the relationship between PTH and calcium?
- When Low Ca2+ feedback to parathyroid glands so high PTH
2. When High Ca2+ feedback to parathyroid glands low PTH
What is the biochemistry of primary hyperparathyroidism?
- High calcium
- Low phosphate – increased renal phosphate excretion (inhibition of Na+/PO43- transporter in kidney)
- High PTH (not suppressed by hypercalcaemia)
What is the treatment of primary hyperparathyroidism?
Parathyroidectomy
Untreated hyperparathyroidism has risks of
What does untreated hyperparathyroidism have a risk of?
- Osteoporosis
- Renal calculi (stones)
- Psychological impact of hypercalcaemia – mental function, mood
What is secondary hyperparathyroidism?
normal physiological response to hypocalcaemia
What are the causes of secondary hyperparathyroidism?
vitamin D deficiency
What are the common cause of vitamin D deficiency?
diet, reduced sunlight
What are the less common causes of vitamin D deficiency?
renal failure – can’t make calcitriol in renal failure
What is the biochemistry in secondary hyperparathyroidism?
- Calcium will be low or low/normal
- PTH will be high (hyperparathyroidism) secondary to the low calcium
- diff from primary hyperparathyroidism where calcium is high
How do you treat secondary hyperparathyroidism with people with normal renal function? What are the two forms?
- Give 25 hydroxy vitamin D
- Patient converts this to 1,25 dihydroxy vitamin D via 1a hydroxylase
- Ergocalciferol 25 hydroxy vitamin D2
- Cholecalciferol 25 hydroxy vitamin D3
How do you treat secondary hyperparathyroidism with people with not normal renal function?
- inadequate 1a hydroxylation, so can’t activate 25 hydroxy vitamin D preparations
- Give Alfacalcidol - 1a hydroxycholecalciferol
What is the general treatment of secondary hyperparathyroidism?
Vitamin D replacement
When does tertiary hyperparathyroidism happen?
Rare, chronic renal failure
What happens in tertiary hyperparathyroidism?
- Occurs in chronic renal failure
1. Can’t make calcitriol
2. PTH increases (hyperparathyroidism)
3. Parathyroid glands enlarge (hyperplasia)
4. Autonomous PTH secretion causes hypercalcaemia
What is the treatment for tertiary hyperparathyroidism?
parathyroidectomy
What do you look at for patients with hypercalaemia?
PTH
What is the diagnosis if patient with hypercalcaemia has raised PTH?
- Hyperparathyroidism
- PTH should fall normal
How do you diagnose vitamin D deficiency?
- Calcium will be low or low/normal
2. PTH will be high (hyperparathyroidism) secondary to the low calcium
How is vitamin D measured?
- as 25 (OH) vitamin D
- Calcitriol (1,25 dihydroxy vitamin D) is very difficult to measure
What are the main regulators of calcium. and phosphate?
Homeostasis actions on kidney bone and gut
What happens if parafollicular cells are removed?
There is no negative effect if parafollicular cells (make calcitonin) are removed e.g. thyroidectomy
What is the overall effect of PTH?
- Increase activity of 1 alpha hydroxylase so more calciferol made so more Ca2+ and PO43- absorbed in gut to increase plasma Ca2+
- Acts on osteoclasts in bone to increase plasma Ca2+
- Increase Ca2+ reabsorption and PO43- excretion in kidney
How is phosphate secreted in kidney?
- By Na+/PO43- co-transporter and PTH inhibits this channel and stops phosphate from being absorbed and also by FGF23
- If low PTH sometimes high phosphate
What is FGF23?
- Inhibits Na+ and PO43- transporter
- Inhibits calcitrol so less phosphate reabsorption form gut as well
- Secreted by bones
What happens in hyperparathyroidism e.g. with adenoma?
- Parathyroid adenoma producing too much PTH
- Calcium increases, but no negative feedback to PTH due to autonomous PTH secretion from parathyroid adenoma
- Primary hyperparathyroidism
What happens in tertiary hyperparathyroidism?
- Chronic renal failure and chronic vitamin D deficiency so low calcium
- PTH increases a lot
- Overtime this PTH all 4 glands v busy and calcium goes up
What are the levels like in hypercalcaemia?
- High calcium (hypercalcaemia)
- Low/suppressed PTH
What is hypercalcaemia due to sometimes?
malignancy
What is the diagnosis if patient with hypercalcaemia has raised PTH?
hyperparathyroidism
