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Clinical Biochemistry > Calcium and Phosphate Metabolism > Flashcards

Calcium and Phosphate Metabolism Flashcards

1
Q

Which mechanisms aid Calcium and phosphate balance?

A

Homeostasis of serum calcium and phosphate maintained via:

  • Bone turnover
  • Parathyroid hormone (PTH)
  • Vitamin D (1,25-dihydroxy D3)
  • Calcitonin
  • FGF-23
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2
Q

How are calcium stores maintained in the short term?

A

Bone remodelling releases minerals esp. calcium into circulation, therefore can be controlled in short-term in
calcium homeostasis

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3
Q

Where is Ca found in the body?

A

99% of body calcium is in bone

Remaining 1% is mainly intracellular

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4
Q

Describe the significance of the hormonal control of calcium

A

Hormonal control of the tiny (<0.1%) extracellular fraction is what maintains Ca balance

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5
Q

Outline the normal extracellular calcium level

A

Extracellular: plasma Ca 2.2-2.6 mmol L-1

About half is free [Ca2+] (physiologically active), half protein bound (mainly albumin)

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6
Q

Where is phosphate found in the body?

A

85% of body phosphorus is in bone

Remainder is mainly intracellular

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7
Q

What are the normal extracellular phosphate levels?

A

Extracellular H2PO4-, HPO42-

  1. 5-4.5 mg dL-1
    (0. 75-1.45 mmol L-1)

May fluctuate more than Ca

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8
Q

What is hypercalcaemia?

A

Excessive Ca2+

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9
Q

Outline the clinical features of hypercalcaemia

A
  • Depression, fatigue, anorexia, nausea, vomiting,
  • Abdominal pain, constipation
  • Renal calcification (kidney stones)
  • Bone pain: “painful bones, renal stones, abdominal
    groans, and psychic moans,”

Severe: cardiac arrhythmias, cardiac arrest

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10
Q

What are the most common causes of hypercalcaemia?

A

In ambulatory patients
- primary hyperparathyroidism

In hospitalized patients
- malignancy

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11
Q

What are the less common hypercalcaemia causes?

A

Hyperthyroidism

Excessive intake of vitamin D

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12
Q

Where is PTH found in the body?

A

PTH synthesized and secreted by parathyroid glands (4 small glands located behind the thyroid)

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13
Q

What is hyperparathyroidism?

A

Hyperparathyroidism is typically a benign tumour of one (or more) of the 4 glands, causing increased PTH levels ⇒ increased serum Ca2+

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14
Q

How is the serum biochemistry altered in hypercalcaemia?

A

Calcium - modest / marked increase
Phosphate - low / low normal
Alkaline phosphatase raised in ~ 20% of cases

Creatinine may be elevated in long standing disease (kidney damage)

[PTH] should be interpreted in relation to calcium - inverse relationship

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15
Q

What is alkaline phosphatase?

A

Enzyme found in the liver, bone and many other tissues

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16
Q

What causes increased levels of alkaline phosphatase?

A

In presence of bone disease may be elevated due to increased bone turnover

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17
Q

What is hypercalcaemia of malignancy?

A

(HCM) - condition in cancer patients defined when serum calcium level (corrected for albumin) is > 2.6 mmol/L

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18
Q

Describe humoral hypercalcaemia of malignancy

A

Humoral
e.g., lung carcinoma secreting PTHrP

PTHrP secreted by tumor cells and binds to PTHr ⇒ hyperparathyroidism

Can cause bone lesions in hospitalised patients

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19
Q

How does metastatic hypercalcaemia of malignancy occur?

A

Tumour cells release cytokines promoting osteoclast differentiation = bone resorption

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20
Q

What causes haematological hypercalcaemia of malignancy?

A

Myeloma of plasma cells secreting osteoclastogenic cytokines e,g, RANKL

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21
Q

What are the most common causes of hypocalcaemia?

A

Vitamin D deficiency

Renal failure

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22
Q

What are the less common causes of hypocalcaemia?

A

Hypoparathyroidism

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23
Q

What are rickets / osteomalacia?

A

Bone disease associated with vitamin D deficiency

24
Q

What is rickets?

A

Rickets - in children, failure of bone mineralisation and disordered cartilage formation

25
Q

What is osteomalacia?

A

Osteomalacia - in adults, impaired bone mineralisation that lead to bone lesions

loss of bone mineralization - thinning of trabecular mesh and cortical bone

26
Q

Describe the features of osteomalacia

A

Diffuse bone pain
Waddling gait, muscle weakness
On X-ray, stress fractures

27
Q

Describe the serum biochemistry of osteomalacia patients

A
  • Low/normal calcium
  • Hypophosphatemia
  • Raised alkaline phosphatase
  • Secondary hyperparathyroidism: -ve feedback from low Ca2+ causes inc. PTH release
28
Q

What is osteoporosis?

A

Metabolic bone disease causing loss of bone mass - asymptomatic

29
Q

What are the causes of osteoporosis?

A 
Endocrine 
Malignancy 
Drug-induced
Renal disease
Nutritional
30
Q

What are the signs of osteoporosis?

A

common presentation of fragility fractures (wrist /hip)

31
Q

How is osteoporosis diagnosed?

A

Measurement of bone mineral density (BMD)

Dual-energy X-ray absorptiometry (DEXA or DXA scan)

32
Q

What does a T score tell us?

A

Number of SDs below average for young adult at peak bone density

33
Q

What does a Z score tell us?

A

Matched to age and/or group

34
Q

Outline the different T scores for varying stages of bone disorders

A

Normal
- T score of > -1

Osteopenia
- T score of > 2.5 and < -1

Osteoporosis
- T score of < -2.5

Severe osteoporosis

  • T score of < -2.5
  • presence of a fragility fracture
35
Q

What increases the natural risk of developing bone disorders?

A

Likelihood of developing osteopenia and later osteoporosis increases with age

36
Q

What are the endocrine causes of osteoporosis?

A

Hypogonadism – notably any cause of oestrogen deficiency

Excess glucocorticoids – endogenous or exogenous

Hyperparathyroidism
Hyperthyroidism

37
Q

What is the effect of oestrogen on bones?

A

Oestrogen inhibits bone resorption

osteoblasts > osteoclasts
favours formation

38
Q

What is the effect of oestrogen deficiency on bone remodelling?

A

Osteoclast apoptosis is regulated by oestrogens

With deficiency osteoclasts live longer and able to resorb more bone

39
Q

How does oestrogen levels change in women at different stages?

A

Growing follicles are the source of oestrogen

Menopause:
No more follicles; no more oestrogens

Remaining oestrogen levels in women is dependent on peripheral aromatase conversion

40
Q

What is a common postmenopausal osteoporosis treatment?

A

HRT – effects well established but safety of long term treatment has been questioned

41
Q

Give examples of osteoporosis treatments

A
  • HRT
  • Bisphosphates
  • PTH analogues
  • Denosumab
  • Romosozumab
  • Exercise, VIt. D and Ca
42
Q

How do bisphosphates work in osteoporosis treatment?

A

Inhibit osteoclasts function

e.g. risedronate, alendronate

43
Q

How are PTH analogues administered to counteract osteoporosis?

A

Intermittent doses at modest level promote ‘good’ bone remodeling (not excess osteoclast > osteoblast)

44
Q

What is denosumab?

A

Human monoclonal antibody against RANK ligand

45
Q

What is Romosozumab?

A

Antibody against sclerostin protein promoting osteoblast differentiation

46
Q

How does exercise reduce osteoporosis effects?

A

Exercise (walking) creates stresses on the skeletal structure detected by osteocytes which regulate bone remodelling (more exercise = osteoblast > osteoclast)

47
Q

Outline the HRT guidelines

A

Short-term therapy (3-5 years) for treating vasomotor symptoms

Lowest effective dose to be used

Long term use not recommended

48
Q

What is the role of osteoblasts in bone remodelling?

A

Osteoblasts lay down new bone (osteoids) where old bone has been dissolved by osteoclasts

49
Q

What is RANK?

A

RANK (receptor activator of nuclear factor kappa-B): surface receptor on pre-osteoclasts, stimulates osteoclast differentiation

50
Q

Where is RANK-L produced?

A

RANK-ligand: produced by pre-osteoblasts, osteoblasts and osteocytes

51
Q

What is the role of RANK-L?

A

Binds to RANK and stimulates osteoclast differentiation

52
Q

What is OPG?

A

Osteoprotegerin is a decoy receptor produced by osteocytes

53
Q

What is the role of OPG?

A

Binds to RANK-L, preventing activation of RANK

- commonly used against osteoporosis etc.

54
Q

Which pathway regulates osteoblast differentiation?

A

Wnt Signalling Pathway

55
Q

How is the Wnt signalling pathway mediated?

A

Negatively regulated by DKK (dickkopf) and sclerostin (SOST)

56
Q

What is Wrt?

A

Wnt is a family of protein signalling molecules important in development throughout the animal kingdom

57
Q

What is the Wrt receptor?

A

The receptor is called frizzled, which requires a co-receptor, Low-density lipoprotein receptor-related protein 5 (LRP5)

Clinical Biochemistry (7 decks)

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