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Chemical pathology - L > Calcium metabolism > Flashcards

Calcium metabolism Flashcards

(51 cards)

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1
Q

Three forms of serum Calcium

A

Free (“ionised”) ~50% - biologically active; Protein-bound ~40% - albumin; Complexed ~10% - citrate / phosphate

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2
Q

Normal range of total calcium serum

A

2.2 - 2.6 mmol/L

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3
Q

Corrected Calcium calculation

A

serum calcium + 0.02 * (40 - serum albumin in g/L)

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4
Q

Effect of low albumin on calcium

A

Bound calcium will be low, but free calcium will be normal. Low overall calcium reading.

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5
Q

Calcium homeostasis response to decreased Calcium

A

Hypocalcaemia is detected by parathyroid gland. Parathyroid gland releases PTH. PTH “obtains” Calcium from 3 sources: Bone, Gut (absorption), Kidney (resorption and renal 1 alpha hydroxylase activation)

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6
Q

Main roles of PTH

A

Stimulate osteoclasts to release Ca from bone; Stimulate renal Ca resorption; Stimulates 1,25 (OH)2 Vit D synthesis (1alpha-hydroxylation); Stimulates renal phosphate wasting (Phosphate trashing hormone)

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7
Q

Enzyme activated by PTH in the kidney

A

1alpha-hydroxylase

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8
Q

Vitamin D synthesis process

A

7-dehydrocholesterol is converted into cholecalciferol (D3) by UV light. Cholecalciferol (D3) is converted into 25-hydroxycholecalciferol (25-OH D3) by 25-hydroxylase in the liver. 25-hydroxycholecalciferol (25-OH D3) is converted by 1,25-dihydroxycholecalciferol (1,25-(OH)2 D3) by 1alpha-hydroxylase in the kidney. 1,25(OH)2 D3 is the physiologically active form of Vitamin D.

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9
Q

Inactive form of Vitamin D stored in the body

A

25-hydroxycholecalciferol

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10
Q

Physiologically active form of Vitamin D

A

1,25-dihydroxycholecalciferol

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11
Q

Plant product form of Vitamin D

A

Ergocalciferol (D2)

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12
Q

Enzyme in the liver that hydroxylates Vitamin D at the 25 position

A

25-hydroxylase

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13
Q

Rate limiting step in Vitamin D activation

A

1-alpha hydroxylase in the kidney. This enzyme is activated by PTH only when calcium is needed.

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14
Q

Pathological expression of 1-alpha hydroxylase

A

Can be expressed in lung cells of sarcoid tissue.

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15
Q

Effect of PTH on bone

A

PTH activates osteoclasts to release calcium and phosphate from the bone.

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16
Q

What enzyme does osteoblast activation release?

A

ALP

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17
Q

Vitamin D deficiency effects

A

Osteomalacia in adults and Rickets in children.

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18
Q

Risk factors for vitamin D deficiency

A

Lack of sunlight exposure, dark skin, dietary, malabsorption.

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19
Q

Chappati consumption and vitamin D deficiency

A

Phytic acid binds to vitamin D in gut and prevents absorption, contributing to the vitamin D deficiency.

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20
Q

Lifestyle treatments for osteoporosis

A

Weight-bearing exercise, stop smoking, reduce EtOH.

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21
Q

Bone structure in osteomalacia

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A

Abnormal. Vitamin D deficiency causes defective bone mineralisation.

22
Q

Clinical features of Osteomalacia

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A

Bone and muscle pain, increased fracture risk, Looser’s Zones (pseudofractures).

23
Q

Clinical features of Rickets

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A

Bowed legs, costochondral swelling, widened epiphyses at the wrists, myopathy.

24
Q

Biochemistry of Osteomalacia

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A

Low Calcium, low Phosphate, raised ALP (due to osteoblasts trying to build up the bone).

25
Drugs inducing breakdown of Vitamin D
Anticonvulsants.
26
Hormone from placenta for calcium metabolism
PTHrp.
27
Calcium levels in secondary hyperparathyroidism
Calcium must be low to stimulate PTH.
28
Bone structure in osteoporosis
Normal.
29
Characteristics of osteoporosis
Osteoporosis has bone loss but with normal calcium. It is due to a reduction in bone density with normal mineralisation.
30
Major causes of Osteoporosis
Old age, lack of oestrogen, immobilisation, too many steroids (Cushing's), hyperthyroidism.
31
Biochemistry of osteoporosis
Normal.
32
T score definitions
Osteoporosis: T-score < -2.5; Osteopaenia: T-score -1 to -2.5.
33
Typical fractures in osteoporosis
Neck of femur, vertebral (kyphosis), wrist - Colle's fracture.
34
Investigation used in diagnosis of osteoporosis
DEXA scan (dual energy X-ray absorptiometry) with T-score and Z-score.
35
Causes of Osteoporosis
Lifestyle: sedentary, EtOH, smoking, low BMI/nutritional; Endocrine: hyperprolactinaemia, thyrotoxicosis, Cushings; Drugs: steroids; Others: genetic, prolonged intercurrent illness.
36
Drug treatments for osteoporosis
Vitamin D/Ca, Bisphosphonates (eg alendronate) -↓ bone resorption, Teriparatide (PTH derivative) - anabolic, Strontium - anabolic + anti-resorptive, SERMs eg raloxifene.
37
Calcium level in Paget's disease
Normal because even though turnover is high the balance of calcium is normal; ALP will be high.
38
Symptoms of Paget's disease
PAIN, warmth, deformity, fracture, increased risk of high output cardiac failure.
39
Bones affected by Paget's disease
Pelvis, femur, skull and tibia.
40
Gold standard investigation for Paget's disease
IV radiolabelled bisphosphonates. osteoblasts building bone will take it up.
41
Pain treatment in Paget's disease
Bisphosphonates.
42
Secondary hyperparathyroidism mechanism
Calcium levels fall, PTH levels rise, this activates osteoclasts that release calcium into the circulation, restoring plasm calcium. (tiny bit of bone sacrificed)
43
Commonest cause of osteoporosis
Taking steroids
44
What areas do you do the DEXA scan of?
hip (femoral neck etc) and lumbar spine
45
What is the T score?
standard deviation from mean of young healthy population - useful to determine fracture risk
46
What is the Z score?
standard deviation from mean of age matched control - useful to identify accelerated bone loss in younger patients
47
How do bisphosphonates work?
contain phosphate and nitrogen, osteoblasts don't recognise the bisphosphonates as being different to phosphate and so make bone using the bisphosphonates. The osteoclasts are then unable to break it down as it isn't biodegradable. This bone is much stronger than normal bone and so decreases bone resorption.
48
How must you take bisphosphonates?
Cannot take any other tablets or food as it will form calcium phosphonate in the gut which won't be absorbed. And then can't lie down as it is irritant and can cause problems such as ulcers. (Intravenously is much better but expensive)
49
What enzyme is raised in Paget's disease?
ALP
50
Bone disorder that can be caused by longstanding primary hyperparathyroidism
osteitis fibrosa
51
Bone disorder caused by secondary hyperparathyroidsim due to renal failure
renal osteodystrophy

Chemical pathology - L (7 decks)

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