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Chemical Pathology 10 - Calcium metabolism Flashcards

1
Q

Around what percentage of the body’s calcium is in the skeleton?

A

99%

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2
Q

What % of serum calcium is free/ionised?

A

50%

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3
Q

Which form of serum calcium is biologically active?

A

Ionised

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4
Q

Recall the 3 forms of serum calcium?

A

Free/ionised
Bound to albumin
Complexed with citrate/phosphate

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5
Q

What is “corrected calcium”?

A

Calcium corrected for albumin level

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6
Q

How can ionised calcium be measured?

A

Blood gas

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7
Q

What is the key role of circulating calcium?

A

Nerve and muscle function

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8
Q

Where in the body is calcium level detected for calcium homeostasis?

A

Parathyroid gland

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9
Q

Which cells are involved in releasing calcium from bone?

A

Osteoclasts

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10
Q

Recall the 3 ways in which PTH can act to increase serum calcium

A
  1. Increase bone Ca resorption
  2. Increase renal Ca resorption
  3. Indirectly: increase 1-alpha hydroxylase action in kidneys - this increased vit D activation, and vit D increases gut absorption of vit D
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11
Q

What type of hormone is PTH?

A

Peptide hormone

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12
Q

What type of hormone is vitamin D?

A

Steroid hormone (derived from cholesterol)

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13
Q

What are the actions of PTH?

A
  1. Increased resorption of calcium from bone and kidney
  2. Renal phosphate wasting
  3. Increase renal 1 alpha hydroxylase, which activates vit D
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14
Q

Recall the pathway of vit D synthesis

A
  1. Cholecalciferol obtained from diet or converted by sunlight exposure from 7-dehydrocholesterol
  2. 100% of absorbed cholecalciferol is converted to storage form (vit D3) in liver conversion by 25 hydroxylase
  3. Activated by renal 1-alpha-hydroxylase - an enzyme under control of PTH - to the active form (1,25-(OH)2 D3)
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15
Q

Which hormone stimulates 1-alpha-hydroxylase production by the kidney?

A

PTH

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16
Q

In which disease can 1 alpha hydroxylase be produced outside the kidney, and where?

A

Sarcoidosis - in sarcoid lung tissue

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17
Q

Does sarcoidosis cause hypo or hypercalcaemia?

A

Hypercalcaemia

Sacroid tissue releases 1 alpha hydroxylase –>
Vit D activated outside the kidney –> calcium increased

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18
Q

Where is 1-alpha-hydroxylase produced in sarcoidosis?

A

Lung sarcoid tissue

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19
Q

What is calcitriol another name for?

A

1,25-dihydroxycholecalciferol

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20
Q

Where is 25 hydroxylase found?

A

Liver

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21
Q

What effect does 1,25(OH)2 vit D (active form) have on calcium and phosphate?

A

Increases calcium and phosphate absorption from intestines

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22
Q

Why is bone-specific ALP high when there is increased bone turnover?

A

Alkaline phosphatase pushes calcium and phosphate into bone

When it does this, some Alk phos is leaked into blood

Therefore, when you have increased bone turnover, you can measure the bone-specific AlkPhos in the blood and it will be high

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23
Q

Which electrolyte is necessary for PTH synthesis?

A

Magnesium

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24
Q

What is the difference between osteoporosis and osteomalacia in terms of bone structure and mass?

A 
Osteoporosis = less bone of normal structure
Ostemalacia = normal amount of bone of wacky structure
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25
What type of bone disease is caused by renal failure?
Renal osteodystrophy 1. Can't make 1 alpha hydroxylase --> lack of calcium absorption into bone 2. Can't excrete phosphate in kidney failure
26
Which conditions are caused by vit D deficiency in children and adults?
Children: Ricketts Adults: osteomalacia
27
Recall 4 risk factors for vit D deficiency
Lack of sunlight exposure Dark skin Dietary Malabsorption (eg coeliac)
28
Recall 4 clinical features of osteomalacia, including the biochemistry
Bone and muscle pain Increased fracture risk Looser's zone fractures Biochem: low Ca and Pi, raised ALP
29
Recall 4 clinical features of Rickets
Bowed legs Costochondral swelling Widened epiphyses at the wrists Myopathy
30
Why does chappati consumption increase vit D deficiency?
``` Phytic acid (This chelates vit D in gut, adding to the vit D deficiency) ```
31
What is the biochemsistry of low calcium, low phosphate and high Alk Phos indicative of?
Vit D deficiency
32
What is the expected calcium and phosphate level in osteoporosis?
Normal
33
Recall 3 endocrine causes of osteoporosis
Cushings's Hyperthyroidism Acidosis (less common)
34
What are the 3 typical fragility fractures seen in osteoporosis
#NOF Colle's (wrist) Vertebral
35
What scan is used to diagnose osteoporosis?
DEXA scan
36
Recall the symptoms of Paget's disease
PAIN, warmth, deformity, fracture, increased risk of cardiac failure
37
Which bones are most commonly affected by Paget's?
Pelvis, femur, skull and tibia
38
What is the gold standard investigation for diagnosing Paget's disease?
IV radiolabelled bisphosphonates
39
How is pain treated in Paget's disease?
Bisphosphonates
40
What is the expected ALP level in Paget's disease?
High
41
What are the symptoms of hypercalcaemia?
Polyuria and polydipsia (increased solute --> increased urine volume) Constipation (calcium causes muscle movement to slow down) Neurological - seizures, confusion, coma (but only if Ca >3.0)
42
Recall how hypercalcaemia should be investigated to determine a cause - and some differentials for your diagnostic approach
1. Question whether it is a genuine result - send back to lab 2. What is the PTH? 3a. If PTH is LOW this is an *appropriate* response so could be due to malignancy, or more rarely - sarcoid/ thyrotoxicosis 3b. If PTH is HIGH (suppressed) = *inappropriate* response to hypercalcaemia therefore = a problem with PTH regulation (mostly primary hyperparathyroidism, rarely, familial hypocalcuric hypercalcaemia)
43
Which 3 types of malignancy might cause hypercalcaemia?
1. Small Cell Lung Cancer (produces PTHrP) 2. Bony metastases - causes local osetolysis 3. Haematological malignancy (eg myeloma and CRAB)
44
Recall some causes of primary hyperparathyroidism, and which of these is most common
``` Parathyroid adenoma (most common) Parathyroid hyperplasia (rare) Parathyroid carcinoma (eg in Men1) ```
45
What is the pathophysiology of familial hypocalcuric hypercalcaemia?
Calcium Sensing Receptor (CaSR) is mutated PTH glands can't detect Ca so well Causes a MILD hypercalcaemia which is *asymptomatic* There will be low urinary calcium (in name)
46
How does thyrotoxicosis affect calcium?
Causes hypercalcaemia via increased bone resorption
47
How do thiazide diuretics affect calcium?
Cause hypercalcaemia - due to reduced calcium transport in the renal tubules
48
How should hypercalcaemia be treated?
FLUIDS, fluids, fluids! 0.9% saline - 1L over 1 hour Treat underlying cause
49
When can bisphosphonates be used to treat hypercalcaemia?
Only if the cause is known to be malignant
50
Recall 2 signs of hypocalcaemia
Chovstek's (C = cheek) | Trousseau's (T = Tighten BP cuff)
51
Which calcium imbalance may cause stridor, and why?
Hypocalcaemia - due to laryngeal spasm
52
How should hypocalcaemia be treated?
Calcium + activated vit D Nb: If cause is vit D deficiency (rare in UK) then give regular (not activated) vit D
53
Recall some differentials for hypocalcaemia when the PTH is low
This is an inappropriate response (low calcium should cause high PTH) Could be due to: 1. Surgical mishap during thyroidectomy 2. Autoimmune hypoparathyroidism (rare) 3. Di George syndrome (even rarer! Agenesis of parathyroids) 4. Magnesium deficiency - can be caused by OMEPRAZOLE
54
Recall some differentials for hypocalcaemia when the PTH is high
This is an appropriate response to low calcium - SECONDARY HYERPARATHYROIDISM Could be due to: 1. Vit D deficiency (common) 2. CKD (as low renal alpha-1-hydroxylase) 3. Pseudohypoparathyroidism (gene deficit --> PTH resistance)
55
What is the difference between the Z score and the T score in osteoporosis?
Z score = compared to someone of same age | T score = copared to healthy, young female
56
Recall 3 lifestyle modifications that can treat osteoporosis
Weight-bearing exercise Stop smoking Reduce EtOH
57
Give an example of a bisphosphonate drug
Alendronate
58
How do SERM drugs work in osteoporosis treatment?
Antagonist of oestrogen at the breast but an agonist in the bone - so it reduces risk of breast Ca but increases bone density
59
What plasma Ca level will you get in a patient with osteoporosis?
2.40 mmol/L | It will be normal because in osteoporosis, Ca is normal
60
What is the first thing to measure in a hypercalcaemic patient?
PTH
61
What are the 4 main symptoms of primary hyperPTH?
Bones Stones Psychic roans Abdominal moans
62
How does hypoadrenalism (Addisson's) affect calcium?
Hypercalcaemia | Renal calcium transport decreased
63
Is neuromuscular excitability a sign of hypocalcaemia or hypercalcaemia?
Hypocalcaemia
64
What is the most common cause of secondary hyperPTH?
Vit D deficiency
65
What is the calcium level in Paget's disease?
Normal because even though turnover is high the balance of calcium is normal
66
How does Paget's disease affect the heart?
Causes high output cardiac failure

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