Clincal Biochemistry: Calcium and phosphate metabolism Flashcards
What things help control serum calcium and phopshate levels?
- Bone turnover
- Parathyroid hormone (PTH)
- Vitamin D (1,25-dihydroxy D3)
- Calcitonin
- FGF-23
What is bone turnover?
- Bone turnover is the process of resorption followed by replacement by new bone.
How is calcium distributed within the body?
- 99% of body calcium is in bone
- Most of remaining 1% is intracellular
- <0.1% extracellular

Very briefly describe how calcium balance is maintained
- Hormonal control of the tiny extracellular fraction is what maintains Calcium balance
What % of extracellular calcium is free and what % is potein-bound?
- 50% is free [Ca2+] (physiologically active)
- 50% protein bound (mainly to albumin)
How is phosphate distributed within the body?
- 85% of body phosphorus is in bone
- Remainder is mainly intracellular
- <0.1% extracellular

What forms of phosphate mainly make up extracellular portion of it in the body?
- Dihydrogen phsophate (H2PO4-)
- Hydrogen phosphate (HPO42-)
What are the clinical features of hypercalcemia (high blood calcium)?
- Depression, fatigue, anorexia, nausea, vomiting
- Abdominal pain, constipation
- Renal calcification (kidney stones)
- Bone pain
- Severe symptoms: cardiac arrhythmias, cardiac arrest
What saying can be used to help remeber the symptoms of hpercalcemia?
- “Painful bones, renal stones, abdominal groans, and psychic moans”
What are some of the causes of hypercalcaemia?
- Most common causes:
- Primary hyperparathyroidism
- In hospitalized patients: malignancy
- Less common causes:
- Hyperthyroidism
- Excessive intake of vitamin D
Describe the serum biochemistry of someone suffering from hypercalcaemia
- Serum calcium: Modest to large increase
- Serum phosphate: Low or low normal - PTH increases renal reabsorption of calcium but also increases phosphate excretion
- Serum alkaline phosphatase: Raised in 20% of cases
- Serum creatinine: May be elevated in longstanding disease (kidney damage)
-
Serum PTH: Concentration should be interpreted in relation to calcium as PTH causes increase in serum calcium.
- This means if calcium is high PTH should be low (inverse relationship)
Use the following information to provide a diagnosis to the patient
A 52 year old woman was investigated for
suspected kidney stones.
Serum investigations:
reference range
Total calcium: 2.82 mmol/L (2.20 - 2.52)
Phosphate: 0.69 mmol/L (0.75 - 1.50)
Albumin: 42 g/L (35 - 48)
Alkaline phosphatase: 135 U/L (30 - 100)
PTH: 7.3 pmol/L (1 - 6.9)
Creatinine: 118 mmol/L (60 - 110)
- Serum investigations show patient has the following:
- High total calcium level
- Low phosphate level
- High alkaline phosphate level
- Slightly high PTH
- High creatinine level
- This all suggests that the patient has hyperparathyroidism as they have raised PTH and calcium
Use the following serum investigations to explain whether hyperparathyroidism should be investigated
reference range
Total calcium: 2.82 mmol/L (2.20 - 2.52)
PTH: 6.8 pmol/L (1 - 6.9)
- Hyperparathyroidism should still be investigated in this case even though PTH levels are within normal range
- This is because PTH levels are on high end of normal and total calcium is way above normal level
- This suggests something is wrong as in a normal situation high PTH = low calcium and high calcium = low PTH
What are the different types of malignancy that can cause hypercalcaemia?
-
Humoral: E.g. lung carcinoma secreting parathyroid hormone-related peptide (PTHrP)
- PTHrP will bind to the PTH receptor and cause over-secretion of PTH from parathyroid glands (hyperparathyroidism)
- This results in hypercalcaemia and can lead to bone lesions in cancer patients
- Metastatic: Tumour cells grow and release cytokines which promote osteoclast differentiation and therefore bone reabsorption which leads to bone lesions and associated hypercalcaemia
- Haematological: Tumour originating in haematopoietic cell line, e.g. multiple myeloma, expands and may secrete various cytokines that activate osteoclastogenic factors such as RANK-L which results in bone lesions (in cancer patients) and associated hypercalcaemia
What are some causes of hypocalcaemia?
- Most common causes:
- Vitamin D deficiency
- Renal failure
- Less common causes include:
- Hypoparathyroidism
What deficiency is assciated with Rickets and osteomalacia?
- Vitamin D
What is Ricktes and who does it mainly affect?
- Condition that results in failure of bone mineralisation and disordered cartilage formation
- Mainly affects children
What is osteomalacia and who does it mainly affect?
- Condition that results in impaired bone mineralisation
- Mainly affects adults
What are some of the clincial features of Osteomalacia?
- Diffuse bone pain
- Waddling gait
- Muscle weakness
- May see stress fractures on an X-ray
Describe the serum biochemistry of osteomalacia
- Low/normal calcium
- Low phosphate (Hypophosphataemia)
- Raised alkaline phosphatase
- Secondary hyperparathyroidism - due to low calcium levels leading to lack of negative feedback on PTH release
What is the difference between Osteoporosis and Osteomalacia?
- Osteoporosis: Loss of bone mass
- Osteomalacia: Loss of bone mineralization

Osteoporosis itself is asymptomatic (no pain associated with loss of bone mass) so what’s the first sign of osteoporosis that someone would notice?
- Fragility fracture - Fracture caused by incident that wouldn’t damage healthy bone
- Intervertebral fracture - Get a compression fracture of the vertebrae (vertebrae may be more triangular)
What things may contribute to the development of osteoporosis?
- Endocrine causes
- Malignancy
- Drugs
- Renal disease
- Nutritional causes (lack of calcium in diet)
How can osteoporosis be diagnosed?
- Measurement of bone mineral density (BMD)
- Dual-energy X-ray absorptiometry (DEXA or DXA scan) - 2 X-ray beams with different energy levels aimed at patients bone with one measuring bone density and the other measuring bone thickness
-
Bone densites given either a T or Z score:
- T score - Number of SDs below average for young adult at peak bone density
- Z score - Matched to age and/or group



