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Endocrinology > Regulation of calcium and phosphate > Flashcards

Regulation of calcium and phosphate Flashcards

1
Q

What is the most abundant metal in the body?

A

Calcium

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2
Q

How is calcium distributed in the body?

A 
99% in skeleton and teeth as calcium hydroxyapatite crystals
1% Intracellular
0.1% Extracellular
- Plasma (Ionised Ca2+ and Bound Ca2+)
- Bound to plasma proteins 45% and
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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)
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4
Q

Why is phosphate important?

A

Essential component of:
High energy compounds e.g. ATP 2nd messengers
Fundamental molecules eg DNA,
RNA, phospholipids
Extracellular phosphate is inversely proportional to extracellular calcium – so both regulated by same hormones

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5
Q

Which hormone decreases calcium?

A

Calcitonin secreted thyroid parafollicular cells

Can reduce calcium acutely but lack of hormone does not cause any negative effects

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6
Q

What are the two form of Vitamin D?

A

Ergocalciferol- Diet

Cholecalciferol- Sunshine

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7
Q

How is Vitamin D made?

A 
UVB light from the sun shines on skin cells
Triggers a series of reactions 
Precursor- 7-dehydrocholesterol
CONVerted to pre-vitamin D3
Converted to Vitamin D3
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8
Q

Where is the first step of Vitamin D synthesis?

A

Liver
D3 or D2 from diet is hydroxylates to form 25 hydroxycholecalciferol
(not active)

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9
Q

Where does the second step of Vitamin D synthesis take place?

A

Kidney
Second hydroxylation using 1 alpha hydroxylase producing
1,25 dihydroxycholecalciferol

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10
Q

Where is the first step of Vitamin D synthesis?

A

Liver
D3 from skin or D2 from diet is hydroxylates to form 25 hydroxycholecalciferol
(not active)

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11
Q

Where does the second step of Vitamin D synthesis take place?

A 
Kidney
Second hydroxylation using 1 alpha hydroxylase producing
1,25 dihydroxycholecalciferol
Active form 
AKA Calcitrol
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12
Q

How is vitamin D production regulated?

A

Negative feedback from calciferol on 1 alpha hyroxylase

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13
Q

What are the effect of calcitorol?

A

Works on kidney to increase calcium and phosphate reabsorption
Works on the small intestine to stimulate the absorption of Ca2+ from the gut
Increases reabsorption from bone and stimulates osteoblasts

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14
Q

How is parathyroid hormone produced?

A

Chief cells in parathyroid glands secrete a large precursor (pre-pro-PTH) and cleaved to PTH
G-protein couples calcium sensing receptor on chief cells detect change
G-protein coupled calcium sensing receptor on chief cells detects change in circulating calcium concentration
PTH is directly proportional to serum calcium

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15
Q

Why is it called parathyroid hormone?

A

Parathyroid glands sit at the back of the thyroid gland

Nothing to do with the production of thyroid hormone

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16
Q

How is calcium regulated by PTH?

A

Increase in extracellular calcium
Ca binds to G protein coupled receptors on chief cells
Inhibits PTH secretion

Decrease in extracellular calcium
Less CA2+ binding to receptors on parathyroid cells
More PTH secreted

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17
Q

How does PTH increase calcium in kidney?

A

Works on kidney by increasing calcium reabsorption in the kidney
Increase phosphate secretion
Stimulates 1-alpha hydroxylase activity
Increase in production of active Vitamin D

18
Q

How does PTH increase calcium in bones?

A

Works on the bones by increasing osteoclast activity, reabsorbing more calcium
Converts osteoblast to osteoclasts
PTH stimulates activating factors for conversion

19
Q

How does PTH increase calcium in gut?

A

Indirectly- increased cacitrol production

Increased calcium reabsorption in the gut

20
Q

What are osteoblasts?

A

OsteoBlasts- build bones

21
Q

What are osteoclasts?

A

OsteoClasts- consume bones and release calcium

22
Q

How is PTH regulated?

A

Negative feedback loop

As extracellular Ca falls, less binding, more PTH produced
Action on kidney, gut and bone
Indirect action by stimulating enzyme producing calciferol

Increase in calcium decreased PTH secretion
Chief cells have calcitriol receptors negatively feedbacks on parathyroid cells

23
Q

How many parathyroid glands are there?

A

4

24
Q

What are the main features of calcitonin?

A

Secreted from parafollicular cells of the thyroid gland
Reduces serum calcium
Physiological role in calcium homeostasis in humans unclear
Removal of thyroid gland does not affect serum calcium
Unclear how critical it is

25
Q

What are the actions of calcitonin?

A

As Ca2+ rises
Increasing Ca2+ excretion from kidney
Reduces action of osteoclasts

26
Q

How is serum phosphate regulated?

A

PTH inhibits phosphate reabsorption in kidney

Inhibits sodium/phosphate co-transporter

27
Q

How is serum phosphate regulated by FGF23?

A

Fibroblast growth factor
Inhibits phosphate reabsorption

  1. Inhibits sodium/phosphate co-transporter
  2. Inhibits caclitriol production, less phosphate reabsorption in the gut
28
Q

What is high serum calcium?

A

Hypercalcaemia

29
Q

What is low serum calcium?

A

Hypocalcaemia

30
Q

What are the effects of hypercalcaemia?

A

Ca2+ blocks Na+ influx, so less membrane excitability

31
Q

What are the effects of hypocalcaemia?

A

Enables greater Na+ influx, so more membrane excitability

32
Q

What are the symptoms of hypocalcaemia?

A 
Paraesthesia (pins and needles) hands, mouth, feet, lips
Convulsions
Arrhythmais 
Tetany
CATs go numb
33
Q

What is Chvostek’s sign?

A

Tap facial nerviest just below zygomatic arch
Postive response- twitching of facial muscles
Indicates neuromuscular irritability due to hypocalcaemia

34
Q

What is Trousseau’s sign?

A

Inflation of BP cuff for several minutes induces carpopedal spasm
Indicates neuromuscular irritability due to hypocalcaemia

35
Q

What are the causes if hypocalcaemia?

A 
Hypoparathyroidism
Surgical- neck surgery 
Auto-immune
Magnesium deficiency 
Congenital (agenesis, rare) 
Vitamin D deficiency
36
Q

What are the causes of Vitamin D deficiency?

A 
Malabsorption or dietary insufficiency  
Inadequate sun exposure
Liver disease
Renal disease
Vit D receptor defects (rare)
37
Q

What is the consequence of vitamin D deficiency?

A

Lack of non mineralisation= soft bones
In children - rickets
In adults - osteomalacia (fractures, proximal myopathy)

38
Q

What are the signs of hypercalcaemia?

A

Stones, abdominal moans and psychic groans

Reduced neuronal excitability- atonal muscles

39
Q

Explain the symptoms of hypercalcaemia?

A

Stones – renal effects
• Nephrocalcinosis – kidney stones, renal colic
Abdominal moans - GI effects
• Anorexia, nausea, dyspepsia, constipation, pancreatitis
Psychic groans - CNS effects
• Fatigue, depression, impaired concentration, altered mentation, coma (usually >3mmol/L)

40
Q

What are the causes of hypercalcaemia?

A

Primary hyperparathyroidism
• Too much PTH
• Usually due to a parathyroid gland adenoma
• No negative feedback - high PTH, but high calcium
Malignancy
• Bony metastases produce local factors to activate osteoclasts
• Certain cancers (eg squamous cell carcinomas) secrete PTH-related peptide that acts at PTH receptors
Vitamin D excess (rare)

Endocrinology (9 decks)

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