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Clinical Pathology > Theme 5: Calcium, Phosphate and Magnesium homeostasis > Flashcards

Theme 5: Calcium, Phosphate and Magnesium homeostasis Flashcards

1
Q

What is calcium physiologically important for?

A
  • blood clotting
  • muscle contraction
  • neuronal excitation
  • enzyme activity
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2
Q

What is calcium structurally important for?

A

hydroxyapatite - Ca₁₀(PO₄)₆(OH)₂ - is the predominant mineral in bone

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3
Q

Total plasma calcium (circulating calcium) is in 3 forms, what are they?

A
  1. ionised “free” ca2+ (50%) –> biologically active
  2. bound to plasma proteins (41%) –> predominantly bound to albumin
  3. Complexed to anions (9%) e.g phosphate, bicarbonate
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4
Q

How much of total body calcium is in bone?

A

99%

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5
Q

What is the relationship between total calcium and albumin?

A

as albumin increases, total calcium increases

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6
Q

What is adjusted calcium?

A

as total calcium concentration depends on albumin concentration, we report adjusted calcium, where calcium is corrected for changes in albumin

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7
Q

How do we calculate adjusted calcium?

A

Adjusted Ca = total Ca + [(40-Alb]) x 0.025

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8
Q

What is the reference range for adjusted calcium/ total plasma Ca

A

2.2-2.6 mmol/L

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9
Q

What is the physiological importance of phosphate?

A
  • the P in ATP - our fuel!
  • intracellular signalling
  • cellular metabolic processes e.g glycolysis
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10
Q

What is the structural importance of phosphate?

A
  • backbone of DNA
  • component of hydroxyapatite
  • membrane phospholipids
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11
Q

How much of total body phosphorous is in bone?

A

85% (rest is intracellular)

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12
Q

What two forms can phosphorous be found in the blood?

A
  • organic form (covalently bound) - 70%

- inorganic form as phosphate - 30%

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13
Q

What are the two key controlling factors of calcium homeostasis?

A
  • parathyroid hormone

- vitD and metabolites

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14
Q

When is PTH secreted?

A

when calcium is low (magnesium is also required for secretion of PTH)

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15
Q

What are actions of PTH?

A
  1. PTH acts on bone to drive resorption of Ca and PO4
  2. PTH acts on kidneys to increase reabsorption of Ca but increase excretion of PO4
  3. AND acts on kidneys to increase conversion of VitD to active vitD which increases Ca and PO4 absorption from the gut
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16
Q

What is the net effect of PTH is to?

A
  • increase serum calcium

- decrease serum phosphate

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17
Q

How do we obtain VitD?

A
  • from diet (esp oily fish)

- from cholesterol from action of UV-B sunlight on skin

18
Q

What is the main circulating form of Vitd?

A

25-hydroxy vit D - this is what we measure

19
Q

For bone health, how much 25-OH VitD is sufficient?

A

50-99 nmol/L

20
Q

What factors affect your VitD level?

A
  • season
  • latitude/climate
  • clothing
  • use of sunscreen
  • time spent indoors/outdoors
  • skin tone
  • age
  • diet
  • body fat & BMI
  • malabsorption
21
Q

What are the other regulators of calcium and phosphate homeostasis (other than PTH and VitD)

A
  • FGF23 (fibroblast growth factor 23) - increases renal phosphate excretion
  • calcitonin - opposes the effect of PTH by acting on osteoclasts to inhibit bone resoroption
  • oestrogen - inhibits bone resorption
22
Q

Give 6 causes of hypocalcaemia

A
  1. VitD deficiency
  2. Inadequate dietary calcium intake
  3. Hypoalbuminaemia
  4. High phosphate
  5. Hypoparathyroidism
  6. Spurious cases e.g EDTA contamination
23
Q

What are the signs and symptoms of hypocalcaemia?

A
  • tetany (muscle spasms)
  • paraesthesia in the extremities
  • cramps
  • convulsions
  • psychosis
24
Q

How might tetany (muscle spasms) as a result of hypocalcaemia be demonstrated?

A
  • chvostek’s sign = tapping on the facial nerve causes twitching of facial muscles
  • trousseaus sign = compression of forearm causes painful spasm of wrist and hand
25
Q

In a patient with VitD deficiency, what would the calcium and PTH levels be?

A

PTH will be increased in response to low calcium

26
Q

What are 6 causes of hypercalcaemia?

A
  1. Hyperparathyroidism (most common)
  2. Malignancy (most common)
    - tumours secreting PTH
  3. Medications
  4. VitD excess
  5. hyperthyroidism
  6. bone disease / immobilisation
27
Q

What are the signs and symptoms of Hypercalcaemia (stones, bones, moans and groans)

A

Stones:
-renal stones due to hypercalciuria, causing renal colic

Bones:
-bone pain and osteoporosis

Moans:
-lethargy, fatigue, depression

Groans:
-abdominal pain, constipation, nausea, vomiting

28
Q

What are the first line biochemical investigations for hypo/hypercalaemia

A
  • Ca & PTH
  • adjusted Ca
  • bone profile (adjusted calcium, phosphate, ALP)
  • VitD
  • magnesium
29
Q

What are the causes of phosphate deficiency?

A
  • low intake - malnutrition, malabsorption, alcoholism
  • excess losses - hyperparathyroidism, renal tubular damage, diarrhoea
  • ECF/ICG redistribution
30
Q

What are the signs and symptoms of phosphate deficiency?

A
  • haemolysis, thrombocytopenia and poor granulocyte function
  • severe muscle weakness, respiratory muscle failure and rhabdomyolysis
  • convulsions, coma, death
  • chronic phosphate deficiency will cause rickets/osteomalacia
31
Q

What are the common causes of hyperphosphataemia?

A
  • renal failure: AKI and CKD

- hypoparathyroidism

32
Q

What is the physiological importance of magnesium?

A
  • cofactor for ATP - our fuel
  • neuromuscular excitability
  • enzymatic function
  • regulates ion channels
33
Q

How is total magnesium distributed in the body?

A
  • bone (54%)
  • intracellular (45%)
  • extracellular (1%)
34
Q

What are the 3 forms of magneisum found in the blood?

A
  • ionised “free” Mg2+
  • bound to plasma protein (mostly albumin)
  • complexed to anions e.g phosphate, bicarbonate
35
Q

Where does homeostasis of magneisum occur?

A

predominatly in the kidneys

36
Q

How would severe hypomagnesaemia cause hypocalcaemia?

A

PTH release is magnesium-dependent, so severe hypomagnesaemia will inhibit PTH release and cause hypocalcaemia

37
Q

What are the causes of hypomagneaemia?

A

inadequate intake:

  • malnutrition
  • malabsorption

renal loss:
-drugs e.g antibiotics, chemotherapy, diuretics

GI loss:

  • diarrhoea
  • PPIs

refeeding syndrome and EDTA contamination also could cause hypomagnesia

38
Q

What are the signs and symptoms of magnesium depletion?

A
  • neuromuscular hyperexcitability (tremor, tetany, convulsions), muscle weakness
  • CNS - depression/psychosis
  • cardiovascular - ECG changes, reduced contractility, arrythmias
  • GI - nausea and anorexia
39
Q

Why is hypermagneseamia rare?

A

kidneys have a large capacity to excrete excess

40
Q

What levels of calcium is thought of as a medical emergency, requiring immediate treatment?

A

calcium > 3.5 or < 1.6

Clinical Pathology (57 decks)

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