Regulation of Calcium and Phosphate Flashcards
1
Q
Describe some features of calcium
A
- Most abundant metal in the body
- Diet should meet all requirements
- Recommended adult intake ~1000 mg/day
2
Q
What is the calcium distribution in the body like?
A
- 99% resides in skeleton and teeth as calcium hydroxyapatite crystals
- Extracellular calcium (tiny amount of total body calcium) is tightly regulated
3
Q
Why is calcium important?
A
Neuromuscular excitability •Muscle contraction •Bone strength •Intracellular 2nd messenger •Intracellular co-enzyme •Hormone/neurotransmitter stimulus-secretion coupling •Blood coagulation (factor IV)
4
Q
What is the function of calcium?
A
Essential component of:
• High energy compounds e.g. ATP
• 2nd messengers
• Fundamental molecules eg DNA, RNA, phospholipids
5
Q
What is the relationship between extracellular phosphate and extracellular calcium?
A
Extracellular phosphate is inversely proportional to extracellular calcium – so both regulated by same hormones
6
Q
What is serum calcium measurement like?
A
- 50% ‘unbound’ free (ionised) around 1.25 mM
- 45% bound to plasma proteins around 1.13mM
- 5% associated with inorganic inions e.g. phosphate, lactate, bicarbonate) around 0.13 mM
7
Q
What hormones increase calcium?
A
- Parathyroid hormone (PTH) (secreted by parathyroid glands)
- Vitamin D
- Synthesised in skin or intake via diet
- Main regulators of calcium & phosphate homeostasis via actions on kidney, bone and gut
8
Q
What hormones decrease calcium?
A
- Calcitonin (secreted by thyroid parafollicular cells)
* Can reduce calcium acutely, but no negative effect if parafollicular cells are removed eg thyroidectomy
9
Q
What are sources of vitamin D?
A
- Vitamin D2 (diet) ergocalciferol
2. Vitamin D3 (sunshine) cholecalciferol
10
Q
How is Vitamin D made?
A
- UVB light shines of skin
- 7 dehydrocholesterol
- Converted to Pre-vitamin D3
- Then converted to Vitamin D3 in skin
- Vitamin D2 from diet
- Vitamin D2 and D3 then go to liver then gets hydroxylated at 25 position by 25 hydroxylase to form 25(OH)cholecalciferol (NOT ACTIVE)
- Then goes to kidney and get hydroxlayed again by enzyme which is made in kidney - 1 alpha hydroxylase to form 1,25(OH)2 cholecalciferol (ACTIVE form of Vitamin D)
11
Q
What is the name for active Vitamin D?
A
Calcitrol
12
Q
How do you measure vitamin D?
A
- Serum 25-OH vitamin D = good indicator of body vitamin D status
- 1,25(OH)2 vitamin D (calcitriol) regulates its own synthesis by decreasing transcription of 1 alpha hydroxylase
- Negtaive feedback
- Also hard to measure calciferol
13
Q
What does vitamin D (calcitrol) do?
A
- Acts on kidney increase Ca2+ and PO4 3- reabsorption (increases calcium)
- Works on SI stimulates absorption of calcium and phosphate (Ca2+ and PO4 3-)
- Increased osteoblast activity
14
Q
What is parathyroid hormone (PTH)?
A
- Chief cells in parathyroid glands
- Secreted as a large precursor (pre-pro-PTH) & cleaved to PTH - peptide hormone
- G-protein coupled calcium sensing receptor on chief cells detects change in circulating calcium concentration
- PTH secretion inversely proportional to serum calcium
15
Q
What are chief cells?
A
Contain PTH
16
Q
What happens if Ca2+ ECF is high?
A
- Ca2+ binds to receptors on parathyroid cells
- PTH secretion inhibited
17
Q
What happens if Ca2+ ECF is low?
A
- Less Ca2+ binding to receptors on parathyroid cells
- PTH secreted
18
Q
How does PTH increase calcium?
A
- Increase Ca2+ reabsorption and PO4 3- excretion in kidney and increased activity of 1-alpha hydroxylase activity in kidney
- This causes more calcitrol production
- In gut indirectly works on SI stimulates absorption of calcium and phosphate (Ca2+ and PO4 3-)
- Increase calcium reabsorption from bone increase osteoclast activity
19
Q
What is an osteoblast?
A
(B=build bone)
20
Q
What is osteoclast?
A
(C=consume bone)
21
Q
How does PTH act in bone?
A
- PTH binds to PTH receptor on osteoblast and convert them into osteoclast
- causes osteoclast activating factors (OAFs (e.g, RANKL; receptor activator of nuclear factor kappa-B ligand) - Bone reabsorption so release calcium
22
Q
How is PTH regulated?
A
- Negative feedback
- If extracellular calcium falls, less calcium bind to PTH receptor so more PTH secreted
- Increase Ca2+ by stimulating osteclast activity in bone,, stimulates calcium reabsorption from kidney and indirectly on gut as 1 alpha hydroxylase to form calcitrol
- SO if too much Ca2+ less PTH and PTH also has calcitiol receptors so too much so negative feedback by calcium and calcitriol
23
Q
Where is calcitonin secreted from?
A
parafollicular (C) cells of the thyroid gland
24
Q
What does calcitonin do?
A
- Reduces serum calcium
- Physiological role in calcium homeostasis in humans unclear
- Removal of thyroid gland does not affect serum calcium
25
How does calcitonin act?
- Increase in calcium which is detected by parafollicular cells of thyroid
- Release calcitonin
1. Increase Ca2+ excretion in kidney
2. Decrease osteoclast activity
- Therefore decreased plasma Ca2+
26
How is serum phosphate regulated?
1. Normally phosphate secreted in urine
2. Or Sodium and Phosphate can be reabsorbed by Na+/PO4 3- transporter
3. PTH inhibits phosphate reabsorption and more phosphate excretion (Inuits sodium phosphate co transporter)
4. FGF23 inhibits phosphate reabsorption, inhibits sodium phosphate co transporter and inhibits calcitriol (so less phosphate reabsorption from the gut)
27
What is it called when it is high serum calcium?
Hypercalcaemia
28
What is it when there is low serum calcium?
Hypocalcaemia
29
What happens if hypercalcaemia?
- Action potential generation in nerves/skeletal muscle requires Na+ influx across cell membrane
1. HIGH extracellular calcium (HYPERcalcaemia)
2. Ca2+ blocks Na+ influx, so LESS membrane excitability
30
What happens if hypocalcaemia?
1. LOW extracellular calcium (HYPOcalcaemia)
| 2. enables GREATER Na+ influx, so MORE membrane excitability
31
What are the signs and symptoms of hypocalcaemia?
-Sensitises excitable tissues; muscle cramps, tetany, tingling
-Signs & symptoms:
•Paraesthesia (hands, mouth, feet , lips)
•Convulsions
•Arrhythmias
•Tetany
Mnemonic - [CATs go numb]
32
What is chvosteks signs? (hypo)
- Tap facial nerve just below zygomatic arch
- Positive response = twitching of facial muscles
- Indicates neuromuscular irritability due to hypocalcaemia
33
What is Trousseau's sign? (hypo)
Inflation of BP cuff for several minutes induces carpopedal spasm = neuromuscular irritability due to hypocalcaemia
34
What are causes of hypocalcaemia?
```
1. Low PTH levels = hypoparathyroidism
•Surgical – neck surgery
•Auto-immune
•Magnesium deficiency
•Congenital (agenesis, rare)
2. Vitamin D deficiency
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35
What are the causes for Vitamin D deficiency?
1. Malabsorption or dietary insufficiency
2. Inadequate sun exposure
3. Liver disease
4. Renal disease
5. Vitamin D receptor defects (rare)
36
What are the consequences of Vitamin D deficiency?
1. Lack of bone mineralisation = ‘soft’ bones
2. In children – rickets (bowing of bones)
3. In adults – osteomalacia (fractures, proximal myopathy)
37
What are the signs and symptoms of hypercalcaemia?
‘Stones, abdominal moans and psychic groans’
Reduced neuronal excitability – atonal muscles
1. Stones – renal effects
•Nephrocalcinosis – kidney stones, renal colic
2. Abdominal moans - GI effects
•Anorexia, nausea, dyspepsia, constipation, pancreatitis
3. Psychic groans - CNS effects
•Fatigue, depression, impaired concentration, altered mentation, coma (usually >3mmol/L)
38
What are the causes of hypercalcaemia?
1. Primary hyperparathyroidism
•Too much PTH
•Usually due to a parathyroid gland adenoma
•No negative feedback - high PTH, but high calcium
2. Malignancy
•Bony metastases produce local factors to activate osteoclasts
•Certain cancers (eg squamous cell carcinomas) secrete PTH-related peptide that acts at PTH receptors
3. Vitamin D excess (rare)
