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Calcium & phosphate Flashcards

1
Q

What are the 5 functions of calcium?

A 
Neuromuscular excitability and muscle contraction
Bone strength (calcium hydroxyapatite crystals)

Intracellular 2nd messenger system and co enzymes

Hormone/neurotransmitter stimulus secretion coupling

Blood coagulation (Factor IV)

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2
Q

Where is the majority of calcium stored?

A

99% stored within skeletons as calcium hydroxyapatite crystals

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3
Q

How is extracellular calcium regulated?

A

Parathyroid hormone and calcitriol (vitamin D)

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4
Q

What are the three main functions of phosphate?

A

Inorganic phosphate is essential for cellular metabolism and skeletal mineralisation.

Component of nucleic acids (RNA and DNA), as well as fundamental for phospholipids

Mediator of intracellular signalling (2nd messengers, and regulates protein activity)

Component of high energy ATP molecules

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5
Q

Describe the relationship between extracellular phosphate and extracellular calcium?

A

Inversely proportional relationship

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6
Q

Which cells synthesis vitamin D3?

A

Keratinocytes within epidermis

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7
Q

Which source of Vitamin d is synthesised by the body or obtained from dietary sources?

A

Cholecalciferol (D3)

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8
Q

What is vitamin d2?

A

Ergocalciferol

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9
Q

Which precursor molecule is converted into previtamin-d3 in the skin?

A

7-dehydrocholesterol

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10
Q

How is pre-vitamin D3 converted into Vitamin-D3?

A

UV radiation

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11
Q

Where does the initial hydroxylation of vitamin d3 occur?

A

Liver

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12
Q

Which enzyme catalyses the hydroxylation of Vitamin D3?

A

25-hydroxylase

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13
Q

What is the fate of vitamin-d3 in the liver?

A

Initiation hydroxylation of vitamin d3 into 25-hydroxy-cholecalciferol.

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14
Q

Where the second hydroxylation for vitamin d occur?

A

Proximal convoluted tubule (Kidney)

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15
Q

Which enzyme catalyses the second hydroxylation of vitamin d?

A

1-alpha-hydroxylase

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16
Q

Which molecule is formed from the second hydroxylation of vitamin d?

A

1,25-dihydroxycholecalciferol

Calcitriol

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17
Q

What is active vitamin D?

A

Calcitriol

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18
Q

What is the function of calcitriol?

A

Autoregulates synthesis by decreasing transcription of 1-alpha-hydroxylase, negative feedback.
Increased osteoblast activity
Increased calcium absorption
Increases phosphate and calcium reabsorption

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19
Q

Which receptors does vitamin D bind to?

A

vitamin D receptors (VDR), causes VDREs activation

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20
Q

How does vitamin d increases calcium absorption?

A

Increased production of calcium transport proteins (Calbindin-D proteins) in gut so increases uptake of calcium.

increases plasma calcium maintaining PTH secretion at low levels

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21
Q

What effect does calitriol have on PTH?

A

Exerts negative feedback ,inhibits release

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22
Q

How does vitamin D increases calcium and phosphate reabsorption?

A

Decreases urinary loss of calcium, and phosphate, to filtrate by stimulating reabsorption within the proximal convoluted tubule

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23
Q

Where are parathyroid hormones secreted from?

A

Parathyroid glands

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24
Q

Which cells secrete and synthesise parathyroid hormone?

A

Chief cells

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25
What is the precursor of PTH?
pre-pro-PTH
26
Where does pre-pro-PTH cleavage occur?
Cleaved by proteases into smaller peptides, by endoplasmic reticulum and Golgi body
27
What are the two target sites for PTH?
Kidney and bone
28
What are the effects of PTH?
PTH increases the reabsorption of calcium from filtrate with the proximal convoluted tubule, and increases the expression of 1-alpha-hydroxylase, activating Vitamin-D This increases the formation of calcitriol. Increases phosphate and calcium absorption from gut Increases phosphate excretion from kidney
29
Which types of receptors does parathyroid hormone bind onto on osteoblasts?
PTH receptors
30
Which factors are released from osteoblasts that stimulates osteoclastogenesis?
RANK ligand | Osteoclast activating factor (OAF)
31
Which nuclear factor is stimulated upon RANK L receptor activation?
Kappa b ligand
32
What are the functions of osteoclasts?
Cause déminéralisation of hydroxyapatite, thus releasing calcium and phosphate ions into the blood Forms ruffled border, attaches the osteoclast to the bone
33
Which binding proteins attach osteoclasts to surface of bone?
Sialoprotein | Osteopontin
34
Which enzyme is the rate limiting step of vitamin D synthesis?
1-alpha-hydroxylase
35
Which enzyme is potentiated by parathyroid hormone?
1-alpha-hydroxylase
36
What happens to a PTH secretion during hypocalacaemic conditions?
Increases
37
What effect does PTH have on osteoclast activity?
Stimulates osteoclast activity
38
Which hormone is responsible during elevated calcium serum levels?
Calcitonin
39
Which cells secrete calcitonin?
Parafollicular cells
40
What suggests that calcitonin does not play a significant role in calcium homeostasis?
Removal of thyroid gland does not affect serum calcium
41
Where does phosphate reabsorption occur in the body?
Proximal convoluted tubule and gastrointestinal tract
42
Which transporters reabsorb phosphate?
Sodium phosphate co transporters
43
What effect does parathyroid hormone have on renal phosphate reabsorption?
Inhibits these transporters- therefore there is increased phosphate loss in the urine, reducing serum phosphate levels
44
What condition causes increased phosphate loss in urine?
Hyperparathyroidism (serum phosphate is low due to increased phosphate excretion)
45
Which cells produce FGF23?
Osteocytes
46
What is FGF23?
Fibroblast growth factor-23
47
Why is FGF23 secreted?
Due to elevated calcitriol levels
48
What effects do FGF23 exert?
Less phosphate reabsorption from gut due to decreased expression of co-transport NPT2 in proximal tubule cells Inhibitory effects towards the synthesis of calcitriol
49
What is hypercalcaemia?
High serum calcium
50
What are the main effects of hypercalcaemia?
Action potential generation in neuroskeletal muscle requires sodium influx for depolarisation of the cell membrane at the nods of ranvier in order to stimulate the threshold voltage, and conduct an electrical impulse High extracellular calcium reduces the membrane excitability
51
What is hypocalcaemia?
Low serum calcium
52
What are the effects of hypocalcaemia?
Reduction in calcium ions increases the ability of sodium ion influx, thus the membrane is more excitable
53
What are the clinical effects of hypocalcaemia?
Sensitises excitable tissues, resulting in increased stimulation of muscles , causing muscle fatigue, tetany & tingling Convulsions, arrythmnias, paraesthesisa
54
What is Chvostek's sign?
Tap the zygomatic branch of the facial nerve, examine positive response = twitching of the facial muscles - this indicates neuromuscular irritability due to hypocalcaemia
55
What is Trousseau's sign?
Inflation of BP cuff for several minutes induces carpopedal spasm = neuromuscular irritability due to hypocalcaemia
56
What are the five main causes of hypocalcaemia?
Surgical neck injury: Autoimmune disease Magnesium deficiency Congenital Vitamin-D deficiency
57
Which congenital disorder contributes to cause of hypocalcaemia?
Hypoparathyroidism is a sporadic or inherited condition whereby the parathyroid glands are absent or atrophied
58
Why does a magnesium deficiency cause hypocalcaemia?
Magnesium is required for PTH synthesis
59
What are the 4 causes of vitamin-d deficiency?
Renal disorder for the second hydroxylation of 25-hydroxycholecalciferol into calcitriol (Insufficient synthesis of 1-alpha-hydroxylase) Insufficient consumption or UV exposure Liver disease: Reduction in the synthesis of 25-hydroxylase reducing the conversion of vitamin D into 25-hydroxy-D3
60
What are the consequences of a vitamin-d deficiency?
Lack of bone mineralisation (reduction of hydroxyapatite) = causing soft bones Rickets in children *Bowing of bones cannot support growing weight) In adults; Osteomalacia (fractures proemial myopathy)
61
What effect does parathyroid hormone related peptide exert?
Behaves as an agonist to PTH, thus is attributed to hypercalcaemia
62
What are the clinical signs of hypercalcaemia?
STONES MOANS GROANS Kidney stones: Increased calcium serum concentrations within the filtrate result in accumulation and kidney stone formation Nephrocalcinosis (deposition of calcium salts) Abdominal moans: Dyspepsia, anorexia,constipation Psychic groans: CNS effects, depression, impaired concentration,fatigue
63
What is primary hyperparathyroidism?
Results in increased secretion of parathyroid hormone. | Unresponsive from negative feedback system due to elevated calcium serum concentrations
64
How does malignancy cause hypercalcaemia?
Bony metastases produce local factors to activate osteoclasts (increased bone retortion)
65
What are squamous cell carcinomas?
Secrete PTH related peptides that act on PTH receptors

Y1 BRS (39 decks)

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