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YEAR 5: Pathology 2 FW > Chemical Pathology 10 - Calcium metabolism > Flashcards

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

Recall the 3 forms of serum calcium?

A

Free/ionised (50%)
Bound to albumin (40%)
Complexed with citrate/phosphate (10%)

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3
Q

What is “corrected calcium”?

What is the equation for calculating it?

A

Calcium corrected for albumin level

Serum calcium + 0.02(40 - serum albumin)

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4
Q

How can ionised calcium be measured?

A

Blood gas

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5
Q

What is the key role of circulating calcium?

A

Nerve and muscle function

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6
Q

What are the actions of PTH?

A
  1. Increase bone Ca and phosphate resorption
  2. Increase renal Ca reabsorption and phosphate wasting
  3. Increase 1-alpha hydroxylase action in kidneys - this increases vit D activation, and vit D increases gut absorption of vit D
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7
Q

What type of hormone is PTH?

A

Peptide hormone

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8
Q

What type of hormone is vitamin D?

A

Steroid hormone (derived from cholesterol)

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9
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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10
Q

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

A

Sarcoidosis - in sarcoid lung tissue. This is why sarcoidosis causes hypercalcaemia.

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11
Q

Where is 25 hydroxylase found?

A

Liver

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12
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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13
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 ALP is leaked into blood

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

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14
Q

Which electrolyte is necessary for PTH synthesis?

A

Magnesium

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15
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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16
Q

What type of bone disease is caused by renal failure?

A

Renal osteodystrophy

  1. Can’t make 1 alpha hydroxylase –> lack of calcium absorption into bone
  2. Can’t excrete phosphate in kidney failure
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17
Q

Which conditions are caused by vit D deficiency in children and adults?

A

Children: Rickets
Adults: osteomalacia

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18
Q

Recall 5 risk factors for vit D deficiency

A 
Lack of sunlight exposure + dark skin
Renal disease or failure
Anti-convulsants -> cause Vit D breakdown
Dietary (chapatis)
Malabsorption (eg coeliac)
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19
Q

Recall 4 clinical features of osteomalacia, including the biochemistry

A

Bone and muscle pain
Increased fracture risk
Looser’s zone fractures
Biochem: low Ca and Pi, raised ALP

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20
Q

Recall 4 clinical features of Rickets

A

Bowed legs
Costochondral swelling
Widened epiphyses at the wrists
Myopathy

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21
Q

Why does chappati consumption increase vit D deficiency?

A 
Phytic acid
(This chelates vit D in gut, adding to the vit D deficiency)
22
Q

What is the biochemsistry of low calcium, low phosphate and high Alk Phos indicative of?

A

Vit D deficiency

23
Q

What is the expected calcium and phosphate level in osteoporosis?

24
Q

Recall 3 endocrine causes of osteoporosis

A

Cushings’s
Hyperthyroidism
Acidosis (less common)

25
What are the 3 typical fragility fractures seen in osteoporosis
#NOF Colle's (wrist) Vertebral
26
Recall the symptoms of Paget's disease
PAIN, warmth, deformity, fracture, increased risk of cardiac failure
27
Which bones are most commonly affected by Paget's?
Pelvis, femur, skull and tibia
28
What is the gold standard investigation for diagnosing Paget's disease?
IV radiolabelled bisphosphonates
29
How is pain treated in Paget's disease?
Bisphosphonates
30
What is the expected ALP level in Paget's disease?
High
31
What are the symptoms of hypercalcaemia?
Bones, stones, abdominal moans, psychic groans 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)
32
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 = *inappropriate* response to hypercalcaemia therefore = a problem with PTH regulation (mostly primary hyperparathyroidism, rarely, familial hypocalcuric hypercalcaemia)
33
Which 3 types of malignancy might cause hypercalcaemia?
1. Lung Cancer (squamous cell can produce PTHrP) 2. Bony metastases - causes local osteolysis 3. Haematological malignancy (eg myeloma and CRAB)
34
Recall some causes of primary hyperparathyroidism, and which of these is most common
``` Parathyroid adenoma (most common) Parathyroid hyperplasia (rare) Parathyroid carcinoma (eg in Men-1) ```
35
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)
36
How does thyrotoxicosis affect calcium?
Causes hypercalcaemia via increased bone resorption
37
How do thiazide diuretics affect calcium?
Cause hypercalcaemia - due to reduced calcium transport in the renal tubules
38
How should hypercalcaemia be treated?
FLUIDS, fluids, fluids! 0.9% saline - 1L over 1 hour Treat underlying cause
39
When can bisphosphonates be used to treat hypercalcaemia?
Only if the cause is known to be malignant
40
Recall 2 signs of hypocalcaemia
Chovstek's (C = cheek) | Trousseau's (T = Tighten BP cuff)
41
Which calcium imbalance may cause stridor, and why?
Hypocalcaemia - due to laryngeal spasm
42
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
43
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
44
Recall some differentials for hypocalcaemia when the PTH is high
This is an appropriate response to low calcium - SECONDARY HYPERPARATHYROIDISM Could be due to: 1. Vit D deficiency (most common cause) 2. CKD (as low renal alpha-1-hydroxylase) 3. Pseudohypoparathyroidism (gene deficit --> PTH resistance)
45
What is the difference between the Z score and the T score in osteoporosis?
Z score = compared to someone of same age and gender T score = compared to healthy, young adult
46
Recall 3 lifestyle modifications that can treat osteoporosis
Weight-bearing exercise Stop smoking Reduce EtOH
47
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
48
How does hypoadrenalism (Addisson's) affect calcium?
Hypercalcaemia | Renal calcium transport decreased
49
Is neuromuscular excitability a sign of hypocalcaemia or hypercalcaemia?
Hypocalcaemia
50
What is the calcium level in Paget's disease?
Normal because even though turnover is high the balance of calcium is normal
51
How does Paget's disease affect the heart?
Causes high output cardiac failure

YEAR 5: Pathology 2 FW (87 decks)

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