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10. CP - Endocrine System and Disease > (52) Disorders of calcium metabolism > Flashcards

(52) Disorders of calcium metabolism Flashcards

1
Q

What type of ion is calcium?

A

Divalent cation (Ca2+)

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2
Q

In which processes is calcium physiologically important?

A
  • muscle contraction
  • neuronal excitation
  • enzyme activity (Na/K ATPase, hexokinase etc)
  • blood clotting
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3
Q

In what way is calcium structurally important?

A

Key component of hydroxyapatite Ca10(PO4)6(OH)2 - the predominant mineral in bone

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4
Q

What type of ion is phosphate?

A

Monovalent anion (PO4-)

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5
Q

Why is phosphate physiologically important?

A
  • the P in ATP
  • intracellular signalling
  • cellular metabolic processes eg. glycolysis
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6
Q

Why is phosphate structurally important?

A
  • backbone of DNA
  • component of hydroxyapatite
  • membrane phospholipids
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7
Q

Is phosphate predominantly intracellular or extracellular?

A

Predominantly intracellular

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8
Q

When these electrolytes are out of balance, it can be attributed to what…

A
  • increased or reduced intake
  • increased or reduced excretion/loss
  • increased or reduced storage
  • tissue redistribution
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9
Q

Calcium is normally tightly regulated at what levels?

A

2.20-2.60mmol/L

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10
Q

The two key controlling factors for calcium are..

A
  • PTH

- vitamin D and metabolites

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11
Q

There are complex but well-characterised relations between calcium and what?

A
  • GI uptake
  • renal clearance
  • bone
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12
Q

Total Ca = ..

A

ionised Ca + bound Ca + complexed Ca

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13
Q

Which form of calcium is the physiologically active fraction?

A

Ionised calcium

  • calcium sensing receptor
  • cellular effects
  • regulation of PTH
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14
Q

Is bound calcium active?

A

Physiologically INACTIVE

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15
Q

What is the main binding protein in bound calcium?

A

Albumin (around 50%)

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16
Q

What are complexed calcium compounds?

A

Salts - calcium phosphate and calcium citrate

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17
Q

Calcium values can be corrected for what? (adjusted calcium)

A

Corrected for changes in albumin

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18
Q

What is adjusted calcium?

A

Total calcium + (40-Alb) x 0.025

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19
Q

What is the reference range for adjusted calcium?

A

Same as normal

2.20-2.60mmol/L

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20
Q

Describe the calcium distribution in the plasma

A

ionised calcium = 1.3mmol/L

bound calcium = 0.95mmol/L

complexed calcium = 0.05mmol/L

roughly

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21
Q

Total calcium doesn’t necessarily reflect ionised calcium; why?

A
  • total calcium affected by albumin

- pH influences ionised Ca

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22
Q

Describe the ways that pH influences ionised/bound calcium

A

acidosis = reduced Ca-albumin

alkalosis = increases Ca-albumin

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23
Q

Why does acidosis reduce Ca-albumin so reduce the amount of bound calcium?

A

Calcium and H+ ions compete for the albumin binding sites

  • this means less bound calcium and more ionised calcium
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24
Q

How does the distribution of calcium change in alkalosis?

A

Increased bound calcium and decreased ionised calcium

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25
Q

Alkalosis (eg. hyperventilation) can precipitate which condition?

A

Tetany

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26
Q

What is tetany?

A

Intermittent muscular spasms, caused by deficiency of calcium

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27
Q

What would cause an acidotic patient to not develop symptoms?

A

Being hypocalcaemic

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28
Q

How does a reduction in binding protein change calcium distribution?

A
  • decrease in bound calcium
  • ionised calcium and complexed calcium stay the same
  • overall decrease in total calcium
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29
Q

Calcium levels tend to increase as levels of which protein increase?

A

Albumin

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30
Q

What are the albumin levels reference range?

A

35-55g/L

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31
Q

What 4 things can cause pathophysiology of calcium?

A
  • disorders of homeostatic regulators
  • disorders of the skeleton
  • disorders of effector organs
  • diet
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32
Q

Disorders of homeostatic regulators can cause pathophysiology of calcium. Give examples

A
  • PTH

- vitamin D

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33
Q

Disorders of the skeleton can cause pathophysiology of calcium. Give an example

A

Bone metastases

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34
Q

Disorders of effector organs can cause pathophysiology of calcium. Give examples

A
  • gastro-intestinal tract (malabsorption)

- kidney

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35
Q

Describe calcium metabolism

A

slide 20 and 21 of lecture

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36
Q

Describe vitamin D physiology

A

slide 22 and 23 of lecture

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37
Q

What are the endogenous environmental factors that affect vitamin D?

A
  • skin colour

- ageing

38
Q

What are the exogenous environmental factors that affect vitamin D?

A
  • ozone
  • sunscreens and clothing
  • latitude and season
  • time of day
  • diet and supplements
39
Q

Vitamin D falls with which 3 factors?

A
  • age
  • body fat
  • BMI
40
Q

What are the stages in the parathyroid hormone loop

A
  • parathyroid glands
  • PTH
  • positive feedback to bone, GI, kidney
  • calcium
  • negative feedback to parathyroid glands
41
Q

Magnesium plays a key role in which stage of the parathyroid hormone loop?

A

Parathyroid glands producing PTH

42
Q

What does PTH do?

A
  • increases Ca turnover in bones with net resorption
  • decreases Ca clearance at kidneys but increase phosphate excretion
    = both of these increase plasma Ca
43
Q

What does vitamin D do in turns of calcium levels?

A

Increases calcium absorption in gut

44
Q

What effect does increased plasma calcium have on PTH?

A

Negative feedback

45
Q

Name 6 main causes of hypocalcaemia

A
  • hypoproteinaemia
  • vitamin D deficiency
  • hypoparathyroidism
  • inadequate intake of calcium
  • pseudohypoparathyroidism
  • artefactual causes
46
Q

Vitamin D deficiency causes hypocalcaemia but what are the causes of vitamin D deficiency?

A
  • dietary/malabsorption
  • hepatic disease
  • renal disease
  • end-organ vitamin D resistance
47
Q

Name 2 types of hypoparathyroidism (causes hypocalcaemia)

A
  • primary

- secondary to Mg depletion

48
Q

What is psuedohypoparathyroidism?

A

End-organ PTH resistance

49
Q

Give examples of artifactual causes of hypocalcaemia

A
  • EDTA contamination (chelates calcium ions)

- venestasis will cause low adjusted calcium (total calcium is unaffected)

50
Q

How would you distinguish between hypoparathyroidism and vitamin D deficiency?

A

Hypoparathyroidism = low PTH with slightly low calcium

vitamin D deficiency = very high PTH with low calcium

51
Q

What are the 5 main causes of hypercalcaemia?

A
  • hyperparathyroidism
  • malignancy
  • drugs
  • vitamin D excess
  • bone disease and immobilisation
52
Q

What types of malignancy might cause hypercalcaemia?

A
  • lytic lesions

- humoral eg. PTHrp

53
Q

What should be done during differential diagnosis of hypercalcaemia?

A
  • consider adjusted calcium (look at the albumin)
  • check drug history
  • exclude excess vitamin D intake
  • check for renal failure
  • simultaneous measurement of Ca and PTH

Consider rarer causes and more complex investigations

54
Q

How would you differentiate between hyperthyroidism and bone metastases?

A

Calcium high in both but in hyperparathyroidism, the PTH is high, whereas in bone metastases, the PTH is slightly low

55
Q

Which calcium disorder involves low serum ionised calcium and low plasma PTH?

A

Primary hypoparathyroidism

56
Q

Which calcium disorder involves low-normal serum ionised calcium but high plasma PTH?

A

Secondary hyperparathyroidism (usually renal or nutritional)

57
Q

Which calcium disorder involves high serum ionised calcium and but low plasma PTH?

A

PTH independent hypercalcaemia (eg. malignancy, vitamin D toxicity)

58
Q

Which calcium disorder involves high serum ionised calcium and high plasma PTH?

A

Primary hyperparathyroidism

59
Q

Where is phosphate found?

A

Major intracellular ion, small proportion in the plasma

similar to phosphate

60
Q

Phosphate is involved in which reactions?

A

Involved in high energy reactions eg. those involving ATP eg. Na/K pumps, Hexokinase

61
Q

Deficiency of phosphate can cause what?

A
  • weakness and dysfunction

- severe depletion can be fatal

62
Q

Describe phosphorus homeostasis

A

slide 38 of lecture

63
Q

What are the 4 main causes of phosphate deficiency?

A
  • hyperparathyroidism
  • excess losses
  • poor intake (malnutrition/inadequate IVN)
  • ECF/ICF redistribution (like potassium)
64
Q

What are the causes of excess losses of phosphate leading to phosphate deficiency?

A
  • renal tubular damage
  • gastro-intestinal
  • diabetes (diuresis)
65
Q

Name the factors that increase phosphate absorption in the intestine?

A
  • reduced dietary intake of phosphate

- elevated serum 1,25-dihydroxyvitamin D

66
Q

Name the factors that reduce phosphate (Pi) absorption in the intestine?

A
  • reduced serum 1,25-dihydroxyvitamin D
  • elevated concentrations of calcium salts in intestinal lumen
  • MEPE
67
Q

Name the factors that increase phosphate reabsorption in the kidney?

A
  • phosphate depletion
  • parathyroidectomy
  • 1,25(OH)2D
  • volume contraction
  • hypocalcaemia
  • hypocapnia
68
Q

Name the factors that decrease phosphate reabsorption in the kidney?

A
  • phosphate loading
  • parathyroid hormone and cyclic AMP
  • volume expansion
  • hypercalcaemia
  • carbonic anhydrase inhibitors
  • dopamine
  • glucose and alanine
  • acid-base disturbances
  • increased bicarbonate
  • hypercapnia
  • metabolic inhibitors
  • arsenate
  • FGF-23
69
Q

What are the symptoms of phosphate deficiency?

A
  • haemolysis, thrombocytopenia, poor granulocyte function
  • severe muscle weakness, respiratory muscle failure and rhabdomyolysis
  • confusion, irritability and coma may be due to a metabolic encephalopathy due to phosphate deficiency
  • renal dysfunction
70
Q

If phosphate deficiency is confirmed, treatment is essential; what might be necessary?

A

Changes to IV fluid regimens including TPN formulations (total parenteral nutrition)

71
Q

Magnesium has a close relationship with which other disorders?

A

Calcium and potassium (K) disorders

Similar problem with disorders of phosphate metabolism

72
Q

Describe the physiology of renal magnesium handling

A

slide 43 of lecture

73
Q

Describe magnesium metabolism

A

slide 44 of lecture

74
Q

Describe the proteins implicated in the molecular control of Mg2+ homeostasis

A

slide 45 of lecture

75
Q

Describe the effectors of Mg2+ homeostasis?

A

slide 46 of lecture

76
Q

Hypomagnesaemia is associated with which other conditions

A
  • hypokalaemia (40%)
  • hyponatraemia (23%)
  • hypophosphataemia (29% )
  • hypocalcaemia (25%)
77
Q

How common is hypomagnesaemia?

A

Prevalence in hospitalised patients - alone on routine estimation 6-11%

78
Q

What are the renal causes of magnesium depletion?

A
  • diuretic phase of acute tubular necrosis
  • hypercalcaemia states
  • drugs
79
Q

Which drugs can cause renal magnesium depletion?

A
  • antibiotics eg. gentamicin, carbenicillin
  • chemotherapy e.g. cisplatin
  • diuretics
  • FK506
80
Q

What are the GI causes of magnesium depletion?

A
  • malnutrition
  • intravenous nutrition
  • diarrhoea
  • malabsorption
81
Q

What are the cellular effects of magnesium depletion?

A
  • reduced mitochondrial respiration and impaired phosphorylation
  • defective Na-K ATPase activity
  • impaired DNA synthesis
82
Q

What are the biochemical effects of magnesium depletion?

A
  • hypocalcaemia
  • hypophosphataemia
  • hypokalaemia
83
Q

What are the endocrine effects of magnesium depletion?

A
  • impaired PTH release

- PTH resistance in bone

84
Q

What are the CVS effects of magnesium depletion?

A
  • cardiac irritability

- reduced contractility

85
Q

What are the CNS effects of magnesium depletion?

A
  • hyper-reflexia
  • tetany
  • ataxia/vertigo
  • psychosis/depression
86
Q

What are the muscle effects of magnesium depiction?

A
  • weakness
  • muscle fibrillation
  • myopathic EMG
87
Q

What types of tissue magnesium levels can be measured?

A
  • serum magnesium
  • erythrocyte magnesium
  • leucocyte magnesium
  • muscle magnesium (20% body Mg)
88
Q

Erythrocyte magnesium is affected by what?

A

High reticulocyte count

89
Q

What is required to take muscle Mg levels?

A

Biopsy

90
Q

Mg deficiency should always be considered with combined..

A

hypokalaemia and hypocalcaemia

91
Q

Screening for Mg deficiency is advocated because of high prevalence but…

A
  • most patients are asymptomatic
  • most patients recover spontaneously
  • hypomagnesaemia usually manifests itself alongside obvious causative disease eg. chemotherapic side effects
92
Q

Calcium at what levels is a medical emergency requiring immediate treatment?

A

Over 3.5mmol/L or under 1.6mmol/L

10. CP - Endocrine System and Disease (5 decks)

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