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Year 5 - Pathology > CHEMPATH: Calcium Handling > Flashcards

CHEMPATH: Calcium Handling Flashcards

1
Q

What are the 3 forms of calcium in serum?

What is the total serum calcium?

What is corrected calcium?

A
  • Corrected - correcting for albumin.
    • Equation is (serum Ca + 0.02 * [40 - serum albumin]).
  • If Ca falls then epilepsy can result.
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2
Q

How do you know if low albumin state is the cause of abnormal calcium?

A

Use corrected Ca and compare to total Ca

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3
Q

What is the function of Ca in the body?

A
  1. Nerve and muscle function
  2. Bone maintenance
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4
Q

What is the response to low Ca?

A
  1. Osteoclast activation
  2. Increased gut absorption
  3. Kidney retains calcium - 1 -alpha hydroxylase is activated in the kidney
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5
Q

What 2 hormones invovled in calcium homeostasis?

A
  1. PTH
  2. Vitamin D (steroid hormone)
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6
Q

What is the function of PTH?

A

84 aa protein, only released from parathyroids

Roles

  1. Bone & renal Ca2+ resorption
  2. Stimulates 1,25 (OH)2 vit D synthesis (1α hydroxylation)
  3. Also stimulates renal Pi wasting

“phosphate trashing hormone”

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7
Q

Cholecalciferol or ergocalciferol is a plant product?

A

Ergocalciferol - D2 - plant product

Cholecalciferol - D3 - comes from mammals; this is an inactive form, made in the skin under the influense of sunlight

No differences in activity but slightly different molecular shape

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8
Q

What is the influence of sunlight on vitamin D?

A
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9
Q

How is Vitamin D activated? What happens in sarcoid?

A
  1. In the kidney by 1-alpha-hydroxylase
  2. 1-alpha hydroxylase is overactivated in the lung in sarcoid so you get dysregulation of calcium. They should not take vit D.
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10
Q

What is the activated form of vitamin D called?

A

Calcitriol = activated vit D with OH in position 1 and 25.

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11
Q

Where is 25 hydroxylase found?

A

Liver

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12
Q

What is the role of 1,25 dihydroxy vitamin D?

A
  1. Intestinal Ca absorption
  2. Intestinal P absorption
  3. Critical for bone formation

(opposite of PTH)

Other:

  • Controls many genes e.g. for cell proliferation, immune system
  • Vit D deficiency is associated with cancer, AI and metabolic syndrome (does not mean causation)
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13
Q

Where is phosphate excreted?

A

In the kidney - activated by PTH

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14
Q

What is phoshate absorbed alongside and how?

A

In the intestine alongside Ca with the help of vitamin D

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15
Q

What is the role of the skeleton?

A
  • Metabolic role in calcium homeostasis
  • Reservoir of Ca, P and Mg
  • Structural framework
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16
Q

Name 3 metabolic bone diseases.

A
  • Osteoporosis
  • Osteomalacia
  • Paget’s disease
  • Parathyroid bone disease
  • Renal osteodystrophy
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17
Q

What is the difference between osteomalacia vs osteoporosis?

A

Osteoporosis - normal ageing process with normal ratios, normal Ca with bone loss e.g. in Cushing’s, hyperthyroidism, menopause. The bone is just weak so the ALP is normal.

Osteomalacia - bone disease caused by vitamin D deficiency

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18
Q

What are the effects of vit D deficiency in children vs adults?

A

Rickets vs osteomalacia

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19
Q

What are the features of vit D deficiency clinically?

A

Pseudofractures

Low Ca, low P, raised ALP

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20
Q

Name 3 risk factors for osteomalacia.

A
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21
Q

What is the calcium in 2o hyperparathyroidism?

A

In secondary hyperparathyroidism the calcium is always low

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22
Q

What is PTHrP important for?

A
  • Made in placenta and goes into mother’s blood to make your own skeleton and steal her calcium
  • Found in breast milk

Also found in many cancers and usually kills people within 6 months. Bisphosphonates are therefore used a lot in oncology. If Ca is high and PTH is low it is usually the result of PTHrP.

23
Q

What happens to Ca if you have high dietary phosphate intake?

A

High diet phosphate causes low calcium because it binds calcium in the kidneys and they are both lost

24
Q

What are the presenting symptoms of osteoporosis? What is the biochemistry in osteoporosis?

A
25
Q

What is the diagnostic test for osteoporosis?

A

DEXA scan - much less than CXR radiation so relatively safe

26
Q

How is the DEXA scan done? What does DEXA stand for? What results does DEXA produce?

A

T score is low in all old people because you are comparing to a population of age ~ 20years

27
Q

What is the difference between the T score and Z score?

A
28
Q

How does anorexia affect bone health?

A

Failure to attain peak bone mass so risk of fracture earlier will be higher. Furthermore early menopasue (before age 45) can make this even earlier.

29
Q

Name some lifestyle/endocrine/drug causes of osteoporosis.

A
30
Q

How is osteoporosis managed conservatively/medically?

A
31
Q

What is the effect of tamoxifen on bone? What is the risk of using it?

A

Increases the bone density and reduces risk of breast cancer (but increases risk of endometrial cancer). Raloxifene does not cause endometrial cancer.

32
Q

What is the range for normal Ca levels in plasma?

A

2.2-2.6mmol/L

33
Q

What are the effects of hypercalcaemia? How high must Ca be for these symptoms to occur?

A
  • Polyuria/polydipsia
  • Constipation
  • Neuro - confusion/seizures/coma

Unlikely unless Ca is >3.0mmol/L.

34
Q

What is one of the most common causes of hypercalcaemia?

A

primary hyperparathyroidism

35
Q

What is the first question to ask if you find Ca on a blood test?

A
  1. Is it real?
  2. What is the PTH?
  3. Is the PTH suppressed?
    • If suppressed then probably malignancy because they have PTHrP
    • If not then probably (1) primary hyperparathyroidism as there is a clear problem with PTH regulation (or (2) familial hypocalcuric hypercalcaemia)
36
Q

Which blood tube is used for PTH measurement in blood?

A

Purple top

37
Q

What is a genetic cause of hypercalcaemia?

A

Familial hypocalcuric hypercalcaemia (rare)

38
Q

What are the most common causes of primary hyperparathyroidism?

A
  • Parathyroid adenoma
  • Hyperplasia
  • Carcinoma
  • Hyperplasia associated with MEN1 (dominant inheritance)
39
Q

What sex is 1o hyperparathyroid more common in ?

A

Females > males

40
Q

What is the biochemistry in 1o hyperparathyroidism?

A
  • High serum Ca or
  • high inappropriately normal PTH
  • Hypercalcuria
  • Low serum phosphate
41
Q

What is the sensor for calcium and where is it found? What is its effect on the kidneys? Which genetic condition affects this receptor?

A

CaSR - calcium sensing receptor in the parathyroid glands which regulate PTH release.

Its effect in the kidneys is PTH dependent

42
Q

What are the types of hypercalcaemia in malignancy?

A
43
Q

Name 5 causes of non-PTH/non-malignancy driven hypercalcaemia.

A
  • Thiazides - block the release of calcium into the urine so they can decrease stone risks but increase serum Ca
  • Vitamin D would have to be very high for it to cause hypercalcaemia
44
Q

What is the acute management of hypercalcaemia?

A
  1. FLUIDS - 1L over 1 hour
  2. If that fails, give bisphosphonates (especially if the cause is known to be calcium, otherwise avoid).
  3. Treat underlying cause - to know the diagnosis measure the PTH before you give bisphosphonates.
45
Q

What is the clinical effect of hypocalcaemia (on examination)?

A
  • Neuromuscular excitability
  • Trousseau’s sign - when you take BP then you have more albumin. This binds the already low Ca and causes carpal spasm (flexion of the fingers).
  • Chvostek’s sign
  • Convulsions

NB: these signs will only be seen if Ca falls rapidly; not if chronically low Ca

46
Q

What are the non-PTH driven causes of hypocalcaemia?

A
47
Q

Wha are the PTH related causes of hypocalcaemia?

A
48
Q

Which type of hyperparathyroidism is related to hypocalcaemia in CKD?

A

secondary hyperparathyroidism - Ca is always low

This can PROGRESS to tertiary hyperparathyroidism (large parathyroid glands)

49
Q

What happens in CKD patients with long term hypocalcaemia followed by kidney transplant?

A

Secondary hyperparathyroidism - low Ca eventually leads to..

Tertiary hyperparathyroidism - after transplant this acts like primary hyperparathyroidism due to overactive parathyroids in relation to kidney function

50
Q

What bone scan is used for Paget’s disease?

A

Technetium radionucleotide bone scan - also used in cancer

51
Q

What is the biochemistry of Paget’s disease?

A

normal Ca, normal P, with very high ALP

52
Q

What is the cause of renal osteodystrophy?

A

Due to secondary hyperparathyroidism and aluminium retention from dialysis fluid

53
Q

What is osteitis fibrosa?

A

Long standing hyperparathyroidism causes cortical bone loss

54
Q
A

Year 5 - Pathology (89 decks)

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