Calcium Metabolism Flashcards
(106 cards)
1
Q
What are the roles of calcium in the body? (2)
A
Skeleton strength.
Metabolic actions.
2
Q
What are the metabolic actions of calcium? (2)
A
Action potentials.
Intracellular signalling.
3
Q
What percentage of the body’s calcium is stored in bone?
A
99%
4
Q
What three organ systems are involved in calcium uptake/excretion in the body?
A
Digestive system.
Bone.
Kidneys.
5
Q
What percentage of the body’s calcium is present in serum?
A
1%
6
Q
What three forms is serum calcium present in? (3)
A
Free (ionised) - approximately 50%
Protein-bound - approximately 40%
Complexed - approximately 10%
7
Q
What form of plasma calcium is the biologically active form?
A
Free (ionised calcium)
8
Q
What protein is calcium bound to in the serum?
A
Albumin.
9
Q
What is serum calcium complexed with?
A
Citrate/phosphate.
10
Q
What is the normal range of serum calcium?
A
2.2-2.6mmol/L
11
Q
What is normally reported when looking at calcium levels in the body?
A
‘Corrected’ Calcium
12
Q
How is the correct calcium calculated?
A
serum calcium + 0.02 x (40-serum albumin in g/L)
13
Q
What other form of calcium is measured in the blood (Apart from corrected)
A
Ionised calcium.
14
Q
Why is it important to measure the corrected calcium in the blood?
A
If you have low albumin, the bound calcium will be low, but the free calcium will be normal.
The corrected calcium allows you to see where the problem lies.
15
Q
Why is it important to maintain a normal level of circulating calcium? (2)
A
Important for normal nerve and muscle function.
16
Q
What happens to circulating calcium levels in calcium and vitamin D deficiency?
A
Plasma concentration must be maintained despite calcium and vitamin D deficiency.
Chronic calcium deficiency thus results in loss of calcium from bones in order to maintain circulating calcium.
17
Q
What is the homeostatic response to low calcium? (2)
A
Hypocalcaemia is detected by the parathyroid gland.
The parathyroid gland releases PTH.
18
Q
Where does PTH obtain calcium from? (3)
A
Bone.
Gut (absorption - increased 1,25(OH) vitamin D).
Kidney (resorption and renal 1 alpha hydroxylase activation)
19
Q
How does PTH obtain calcium from the gut?
A
Through vitamin D.
20
Q
How does PTH obtain calcium from the kidneys? (2)
A
Actions of PTH direction.
Vitamin D actions.
21
Q
How does PTH obtain calcium from bone?
A
Direct action of PTH.
22
Q
What type of hormone is vitamin D?
A
Steroid hormone.
23
Q
Where is PTH released from?
A
Parathyroids.
24
Q
How many amino acids make up PTH?
A
84 amino acid protein.
25
What are the roles of PTH? (3)
Bone and renal calcium resorption.
Stimulates 1,25(OH)2 vitamin D synthesis (through 1-alpha-hydroxylation)
Also stimulates renal phosphate wasting.
26
What is the pathway for vitamin D synthesis? (4)
7-dehydrocholesterol --> cholecalciferol (D3) ((sun))
cholecalciferol (D3) --> 25-hydroxycholecalciferol (25-OH D3) ((liver))
25-hydroxycholecalciferon (25-OH D3) --> 1,25-dihydroxycholecalciferol (1,25(OH)2 D3) ((kidneys))
27
What is the physiological active form of vitamin D?
1,25(OH)2 D3 (1,25-dihydroxycholecalciferol)
28
What is ergocalciferol?
Vitamin D2 - a plant vitamin.
| Active form.
29
What is cholecalciferol?
Vitamin D3 - synthesised in the skin.
| Active form.
30
What enzyme in the liver hydroxylates cholecalciferol --> 25- hydroxycholecalciferol
25-hydroxylase.
31
Is 25-hydroxycholecalciferol active or inactive?
Inactive - this is the stored and measured form of vitamin D.
32
Where does activation of vitamin D occur?
Kidney.
33
What enzyme in the kidney activates vitamin D?
1-alpha-hydroxylase.
34
From where can 1-alpha-hydroxylase be secreted from? (2)
Kidney.
| Rarely from lung cells of sarcoid tissue.
35
What is the mechanism of action of 1,25-dihydroxycholecalciferol? (4)
Intestinal calcium absorption.
Intestinal phosphate absorption.
Critical for bone formation.
Vitamin D receptor controls many genes (e.g. for cell proliferation, immune system, etc...)
36
What is vitamin D deficiency associated with? (3)
Cancer.
Autoimmune disease.
Metabolic syndrome.
37
What is the rate limiting step in vitamin D synthesis?
Activation of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol.
Rate limiting in the kidney under PTH control.
38
What is the role of the skeleton? (8)
Metabolic role in calcium homeostasis.
Main reservoir of calcium, phosphate and magnesium.
```
Structural framework.
Strong.
Relatively lightweight.
Mobile.
Protects vital organs.
Capabel of orderly growth and remodelling.
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39
What are the main types of metabolic bone disease? (5)
Osteoporosis.
Osteomalacia.
Paget's disease.
Parathyroid bone disease.
Renal osteodystrophy.
40
How does vitamin D deficiency affect the bone?
Defective bone mineralisation.
41
What does vitamin D deficiency lead to? (2)
Childhood --> Rickets.
| Adulthood --> Osteomalacia.
42
What percentage of UK adults have vitamin D deficiency? (2)
50% of adults have insufficient vitamin D.
16% have severe deficiency during winter and spring.
43
What are some risk factors for vitamin D deficiency? (7)
Lack of sunlight exposure.
Dark skin.
Dietary.
Malabsorption.
Renal failure.
Anticonvulsants induce breakdown of vitamin D.
Chappatis (phytic acid)
44
What are the clinical features of osteomalacia? (4)
Bone and muscle pain.
Increased risk of fracture.
Looser's zones on x-ray (pseudofractures).
Biochemical abnormalities - low calcium, low phosphate, raised ALP.
45
What are the biochemical abnormalities in osteomalacia? (3)
Low calcium.
Low phosphate.
Raised ALP.
46
What are the clinical features of rickets? (4)
Bowed legs.
Costochondral swelling.
Widened epiphyses at the wrists.
Myopathy.
47
What is the underlying pathology of osteomalacia?
Demineralisation of bone.
48
What is osteomalacia caused by?
Vitamin D deficiency.
49
What is the underlying pathology of osteoporosis?
Loss of bone mass, leading to pathological fractures.
50
Is the bone abnormal in osteoporosis?
No, residual bone is normal in structure.
51
What age does bone density decrease from?
20.
52
What is the strongest risk factor for osteoporosis?
Increasing age.
53
How is calcium level affected in osteoporosis?
It isn't - normal calcium.
54
What is the biochemistry in osteoporosis? (3)
Normal calcium.
Normal phosphate.
Normal ALP.
55
How does osteoporosis normally first present?
Asymptomatic until a fracture occurs.
56
What are the most common areas for osteoporotic fractures to occur? (3)
NOF.
Vertebral.
Wrist (Colle's)
57
How is osteoporosis diagnosed?
DEXA scan (Dual energy X-ray absorptiometry)
58
What areas of the body are scanned using a DEXA scan? (2)
Hip (femoral neck)
| Lumbar spine.
59
What is the T-score in a DEXA scan?
SD from mean of young healthy population
60
What is the T-score used for in DEXA scanning?
Useful to determine fracture risk.
61
What is the Z-score in DEXA scanning?
SD from mean of age-matched controls.
62
What is the Z-score used for in DEXA scanning?
Useful to identify accelerated bone loss in younger patients.
63
What T score indicates osteoporosis?
64
What T score indicates osteomalacia?
Between -1 and -2.5.
65
What are the causes of osteoporosis? (4)
Age-related decline in bone mass (e.g. menopause).
Failure to attain peak bone mass (e.g. childhood illness).
Early menopause.
More rapid bone loss during adulthood (e.g. lifestyle: sedentary, alcohol, smoking, low BMI/nutritional; endocrine: hyperprolactinaemia, thyrotoxicosis, Cushing's; Drugs: steroids; other: genetic, prolonged intercurrent illness).
66
What are the lifestyle treatments for osteoporosis? (3)
Weight-bearing exercise.
Stop smoking.
Reduce alcohol.
67
What are the drug treatments for osteoporosis? (6)
Vitamin D/calcium.
Bisphosphonates (e.g. alendronate) - reduced bone resportion.
Teriparatide (PTH derivative) - anabolic actions.
Strontium - anabolic and anti-resorptive actions.
Oestrogens (HRT)
SERMs (e.g. reloxifene)
68
What are the symptoms of hypercalcaemia? (3)
Polyuria/polydipsia.
Constipation.
Neurological - confusion/seizures/coma.
69
What calcium level is required for symptoms of hypercalcaemia to develop?
>3mmol/L
70
What is the normal physiological response to hypercalcaemia?
Suppression of PTH.
71
What are the two most important questions to ask when faced with a patient with hypercalcaemia?
Is it a genuine result (repeat).
| What is the PTH?
72
What are the causes of hypercalcaemia without PTH suppression (2)
Inappropriate PTH response to hypercalcaemia = primary problem with PTH regulation.
1. primary hyperparathryoidism (most common).
2. Familial hypocalciuric hypercalcaemia (rare)
73
What are the causes of hypercalcaemia with PTH suppression? (2)
Appropriate PTH response to hypercalcaemia = seek other causes.
1. Malignancy (most common)
2. Others (rare) - sarcoid, vitamin D excess, thyrotoxicosis, milk alakali syndrome.
74
What is the most common cause of hypercalcaemia?
Primary hyperparathyroidism.
75
What are the causes of primary hyperparathyroidism? (3)
Parathyroid adenoma, hyperplasia, carcinoma.
76
What syndrome is parathyroid hyperplasia associated with?
MEN1.
77
Who is more often affected by primary hyperparathyroidism?
Women more often affected than man.
78
What is the biochemistry of primary hyperparathroidism? (4)
Raised serum calcium.
Raised or inappropriately normal PTH.
Low serum phosphate.
Raised urine calcium (due to hypercalcaemia)
79
What is the best way to remember to symptoms of primary hyperparathyroidism?
Bones (PTH bone disease).
Stones (renal calculi).
Abdominal Moans (constipation, pancreatitis).
Psychic Groans (confusion).
80
Where is the calcium sensing receptor present? (CaSR)
Parathyroids - regulates PTH release.
| Renal - influences calcium resorption (PTH independent)
81
What is the defect in familial hypocalciuric hypercalcaemia (FHH/FBH).
CaSR mutation.
Higher set point for PTH release --> mild hypercalcaemia
Reduces urine calcium.
82
What are the most common malignancies that cause hypercalcaemia? (3)
```
Hymoural hypercalcaemia of malignancy (e.g. small cell lung carcinoma)
Bone metastases (e.g. breast carcinoma causing local one osteolysis).
Haematological malignancy (e.g. myeloma - cytokines).
```
83
What are some other causes of non-PTH driven hypercalcaemia (apart form malignancy) (5)
Sarcoidosis (non-remal 1-alpha hydroxylation).
Thyrotoxicosis (thyroxine --> boen resportion)
Hypoadrenalism (renal calcium transport).
Thiazide diuretics (renal calcium transport)
Excess vitamin D (e.g. sunbeds).
84
What is the acute treatment for hypercalcaemia? (3)
FLUIDS
FLUIDS
Bisphosphonates (if cause is known to be cancer) - OTHERWISE AVOID.
85
What is the long-term management of hypercalcaemia?
Treat the underlying cause.
86
What are the clinical signs of hypocalcaemia? (4)
Neuro-muscular excitability (e.g. trousseau's sign, hyperreflexia, chvostek's sign, convulsions).
Laryngeal spasm (stridor)
ECG - prolonged QT interval.
Choked optic disc.
87
What is the treatment for hypocalcaemia? (2)
Calcium and vitamin D
| usually activated - i.e. 1-alpha forms, except simple vitamin D deficiency
88
What are the two questions you have to ask when faced with a result showing hypocalcaemia (2)
Is it a genuine result - repeat and adjust for albumin.
| What is the PTH?
89
What are the two broad causes of hypocalcaemia?
Non-PTH driven
| Due to low PTH
90
What are some non-PTH driven causes of hypocalcaemia? (3)
```
Vitamin D deficiency (dietary, malabsorption, lack of sunlight).
Chronic kindney disease (1-alpha hydroxylation)
PTH resistance (pseudohypoparathyroidism - PTH will be raised)
```
91
What are some causes of hypocalcaemia due to low PTH? (4)
Surgical (including post thyroidectomy)
Auto-immune hypoparathyroidism.
Congenital absence of parathyroids (e.g. DiGeorge syndrome).
Magnesium deficiency (PTH regulation)
92
What is Paget's disease of the bones.
Focal disorder of bone remodelling.
93
What are the clinical signs of Paget's disease of the bones.
Focal pain, warmth, deformity, fractures, SC compression
94
What are some causes of Paget's disease of the bones (2)
Malignancy.
| Cardiac failure.
95
What bones are most often affected in Paget's disease of the bones? (4)
Pelvis.
Femur.
Skull.
Tibia.
96
What is the biochemical sign of Paget's disease of the bones?
Elevated ALP.
97
How is Paget's diagnosed on imaging? (2)
Nuclear medical scan.
| X-ray.
98
What is the treatment for Paget's disease of the bone?
Bisphosphonates for the pain.
99
Which has the lowest calcium?
```
Primary hyperparathyroidism
Secondary hyperparathyroidism
Osteoporosis
Paget's disease of the bone
Breast Cancer
```
Secondary hyperparathyroidism
100
What is a cause of primary hyperparathyroidism?
Osteitis fibrosa.
101
What is the cause of renal osteodystrophy?
Due to secondary hyperparathyroidism and retention of aluminium from dialysis fluid.
102
What is the biochemistry in osteoporosis?
```
Normal calcium.
Normal phosphate.
Normal PTH.
Normal vitamin D.
Normal ALP.
```
103
What is the biochemistry in osteomalacia/rickets?
```
Low calcium.
Low phosphate.
Raised PTH.
Low vitamin D.
Raised ALP.
```
104
What is biochemistry of Paget's?
```
Normal calcium.
Normal phosphate.
Normal PTH.
Normal vitamin D.
Raised ALP.
```
105
What is the biochemistry in parathyroid bone disease?
```
Raised calcium.
Low phosphate.
Raised PTH.
Normal vitamin D.
Raised/normal ALP.
```
106
What is the biochemistry in renal bone disease?
```
Normal/low calcium.
Raised phosphate.
Raised PTH.
Normal vitamin D.
Normal/raised ALP.
```
