Calcium Dysregulation Flashcards
1
Q
What hormones increase serum calcium and phosphate?
A
- Vitamin D
2. Parathyroid hormone
2
Q
What hormone decreases serum calcium and phosphate?
A
Calcitonin
3
Q
What are the sources of Vitamin D?
A
- Synthesised in skin
2. Intake via diet
4
Q
Where is PTH secreted from?
A
Parathyroid glands
5
Q
Where do the main regulators of calcium and phosphate have actions?
A
- Kidney
- Bone
- Gut
6
Q
What is calcitonin secreted by?
A
Thyroid parafollicular cells
7
Q
What is an indicator of body vitamin D status?
A
Serum 25-OH vitamin D
8
Q
How does calcitriol regulate its own synthesis?
A
Decreasing transcription of 1 alpha hydroxylase
9
Q
What is calcitriol?
A
1,25(OH)2 cholecalciferol/vitamin D
10
Q
Which Vitamin D is from sunshine?
A
D3
11
Q
Which Vitamin D is from the diet?
A
D2
12
Q
How is active vitamin D formed?
A
UVB
7-dehydrocholestrol
Pre-vitamin D
Vitamin D3
25-hydroxylase
25(OH)cholecalciferol
1 alpha-hydroxylase
1,25(OH)2 cholecalciferol
13
Q
Where is 25-hydroxylase located?
A
Liver
14
Q
Where is 1 alpha-hydroxylase located?
A
Kidney
15
Q
What is active Vitamin D called?
A
Calcitriol
1,25(OH)2 cholecalciferol
16
Q
What are the effects of calcitriol?
A
- Increased osteoblast activity
- Increased calcium and phosphate absorption in the kidney
- Increased calcium and phosphate absorption in the gut
17
Q
What are the actions of PTH?
A
- Increased calcium resorption from bone
- Increased calcium reabsorption, and phosphate excretion in the kidney
- Increased 1 alpha-hydroxylase activity in the kidney
=> Increased 1,25(OH)2D3 synthesis
=> Increased calcium and phosphate absorption in the gut
18
Q
What inhibits the sodium/phosphate co-transporter?
A
- PTH
2. FGF23
19
Q
What does FGF23 do?
A
- Inhibits sodium/phosphate co-transporter
=> Phosphate lost in urine, not reasbsorbed - Inhibits calcitriol formation
=> Less phosphate reabsorption from gut
20
Q
What are the symptoms of hypocalcaemia?
A
- Paraesthesia (hands, mouth, feet , lips)
- Convulsions
- Arrhythmias
- Tetany
21
Q
What are the signsof hypocalcaemia?
A
- Chvostek’s sign
2. Trousseau’s sign
22
Q
What is Chvostek’s sign?
A
Facial paresthesia
23
Q
What sign is facial paresthesia?
A
Chvostek’s sign
24
Q
What is Trousseau’s sign?
A
Carpopedal spasm
25
What sign is a carpopedal spasm?
Trousseau's sign
26
What are the causes of hypocalaemia?
1. Low PTH levels - hypoparathyroidism
| 2. Low vitamin D levels
27
What are causes of hypocalaemia relating to hypoparathyroidism?
1. Surgical – neck surgery
2. Auto-immune
3. Magnesium deficiency
4. Congenital (agenesis, rare)
28
What are causes of hypocalaemia relating to low Vit D levels?
Deficiency:
- Diet
- UV light
- Malabsorption
- Impaired production (renal failure)
29
What are the symptoms of hypercalcaemia?
1. Stones – renal effects
2. Abdominal moans - GI effects
3. Psychic groans - CNS effects
30
What are the renal symptoms of hypercalcaemia?
1. Nephrocalcinosis
2. Kidney stones
3. Renal colic
31
What are the GI symptoms of hypercalcaemia?
1. Anorexia
2. Nausea
3. Dyspepsia
4. Constipation
5. Pancreatitis
32
What are the CNS symptoms of hypercalcaemia?
1. Fatigue
2. Depression
3. Impaired concentration
4. Altered mentation
5. Coma (usually >3mmol/L)
33
What are the causes of hypercalcaemia?
1. Primary hyperparathyroidism
2. Malignancy
3. Vitamin D excess (rare)
34
How does primary hyperparathyroidism cause hypercalcaemia?
Too much PTH
Usually due to a parathyroid gland adenoma
No negative feedback - high PTH, but high calcium
35
How does malignancy cause hypercalcaemia?
```
Bony metastases produce local factors to activate osteoclasts
Certain cancers (eg squamous cell carcinomas) secrete PTH-related peptide that acts at PTH receptors
```
36
What is the relationship between PTH and calcium?
Inversely proportional
37
What is primary hyperparathyroidism caused by?
Parathyroid adenoma producing too much PTH
38
What happens in primary hyperparathyroidism?
Calcium increases, but no negative feedback to PTH due to autonomous PTH secretion from parathyroid adenoma
39
What is the biochemistry of primary hyperparathyroidism?
1. High calcium
2. Low phosphate – increased renal phosphate excretion (inhibition of Na+/PO43-transporter in kidney)
3. High PTH (not suppressed by hypercalcaemia)
40
What is the treatment of primary hyperparathyroidism?
Parathyroidectomy
41
What are the risks of untreated hyperparathyroidism?
1. Osteoporosis
2. Renal calculi (stones)
3. Psychological impact of hypercalcaemia – mental function, mood
42
Is secondary hyperparathyroidism pathological or physiological?
Normal physiological response to hypocalaemia
43
What is the biochemistry of seconday hyperparathyroidism?
1. Calcium will be low or low/normal
| 2. PTH will be high (hyperparathyroidism) secondary to the low calcium
44
What are the causes of secondary hyperparathyroidism?
-Most common cause of secondary hyperparathyroidism is vitamin D deficiency
- Commonly - diet, reduced sunlight
- Less common, but important = renal failure – can’t make calcitriol in renal failure
45
What does PTH stimulate?
Renal 1-alpha-hydroxylase
46
What is the treatment of secondary hyperparathyroidism in patients with normal renal function?
- 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
47
What is the treatment of secondary hyperparathyroidism in patients with renal failure?
Give Alfacalcidol - 1a hydroxycholecalciferol
48
Why cannot you give 25 hydroxy vitamin D to treat secondary hyperparathyroidism in patients with renal failure?
Inadequate 1a hydroxylation, so can’t activate 25 hydroxy vitamin D preparations
49
When does tertiary hyperparathyroidism occur?
- Chronic renal failure
| - Chronic vit D (calcitriol) failure
50
What happens in tertiary hyperparathyroidism?
- Can’t make calcitriol
- PTH increases (hyperparathyroidism)
- Parathyroid glands enlarge (hyperplasia)
- Autonomous PTH secretion causes hypercalcaemia
51
What is the treatment for tertiary hyperparathryoidism?
Parathyroidectomy
52
What is the diagnostic approach to hypercalaemia?
Always look at the PTH
53
What is the normal PTH response to hypercalaemia?
PTH falls
54
What will you see in hypercalaemia due to malignancy?
Hypercalaemia
| Low/supressed PTH
55
What is the diagnosis if a patient with hypercalaemia has raised PTH?
Hyperparathyroidism
56
When is it primary hyperparathyroidism?
If renal function is normal
| e.g. parathyroid adenoma
57
When is it tertiary hyperparathyroidism?
If chronic renal failure
58
What is it called if all 4 glands are enlarged in tertiary hyperparathyroidism?
Hyperplastic
59
What is vitamin D measured as?
25 (OH) vitamin D
