(52) Disorders of calcium metabolism Flashcards
1
Q
What type of ion is calcium?
A
Divalent cation (Ca2+)
2
Q
In which processes is calcium physiologically important?
A
- muscle contraction
- neuronal excitation
- enzyme activity (Na/K ATPase, hexokinase etc)
- blood clotting
3
Q
In what way is calcium structurally important?
A
Key component of hydroxyapatite Ca10(PO4)6(OH)2 - the predominant mineral in bone
4
Q
What type of ion is phosphate?
A
Monovalent anion (PO4-)
5
Q
Why is phosphate physiologically important?
A
- the P in ATP
- intracellular signalling
- cellular metabolic processes eg. glycolysis
6
Q
Why is phosphate structurally important?
A
- backbone of DNA
- component of hydroxyapatite
- membrane phospholipids
7
Q
Is phosphate predominantly intracellular or extracellular?
A
Predominantly intracellular
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
9
Q
Calcium is normally tightly regulated at what levels?
A
2.20-2.60mmol/L
10
Q
The two key controlling factors for calcium are..
A
- PTH
- vitamin D and metabolites
11
Q
There are complex but well-characterised relations between calcium and what?
A
- GI uptake
- renal clearance
- bone
12
Q
Total Ca = ..
A
ionised Ca + bound Ca + complexed Ca
13
Q
Which form of calcium is the physiologically active fraction?
A
Ionised calcium
- calcium sensing receptor
- cellular effects
- regulation of PTH
14
Q
Is bound calcium active?
A
Physiologically INACTIVE
15
Q
What is the main binding protein in bound calcium?
A
Albumin (around 50%)
16
Q
What are complexed calcium compounds?
A
Salts - calcium phosphate and calcium citrate
17
Q
Calcium values can be corrected for what? (adjusted calcium)
A
Corrected for changes in albumin
18
Q
What is adjusted calcium?
A
Total calcium + (40-Alb) x 0.025
19
Q
What is the reference range for adjusted calcium?
A
Same as normal
2.20-2.60mmol/L
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
21
Q
Total calcium doesn’t necessarily reflect ionised calcium; why?
A
- total calcium affected by albumin
- pH influences ionised Ca
22
Q
Describe the ways that pH influences ionised/bound calcium
A
acidosis = reduced Ca-albumin
alkalosis = increases Ca-albumin
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
24
Q
How does the distribution of calcium change in alkalosis?
A
Increased bound calcium and decreased ionised calcium
25
Alkalosis (eg. hyperventilation) can precipitate which condition?
Tetany
26
What is tetany?
Intermittent muscular spasms, caused by deficiency of calcium
27
What would cause an acidotic patient to not develop symptoms?
Being hypocalcaemic
28
How does a reduction in binding protein change calcium distribution?
- decrease in bound calcium
- ionised calcium and complexed calcium stay the same
- overall decrease in total calcium
29
Calcium levels tend to increase as levels of which protein increase?
Albumin
30
What are the albumin levels reference range?
35-55g/L
31
What 4 things can cause pathophysiology of calcium?
- disorders of homeostatic regulators
- disorders of the skeleton
- disorders of effector organs
- diet
32
Disorders of homeostatic regulators can cause pathophysiology of calcium. Give examples
- PTH
| - vitamin D
33
Disorders of the skeleton can cause pathophysiology of calcium. Give an example
Bone metastases
34
Disorders of effector organs can cause pathophysiology of calcium. Give examples
- gastro-intestinal tract (malabsorption)
| - kidney
35
Describe calcium metabolism
slide 20 and 21 of lecture
36
Describe vitamin D physiology
slide 22 and 23 of lecture
37
What are the endogenous environmental factors that affect vitamin D?
- skin colour
| - ageing
38
What are the exogenous environmental factors that affect vitamin D?
- ozone
- sunscreens and clothing
- latitude and season
- time of day
- diet and supplements
39
Vitamin D falls with which 3 factors?
- age
- body fat
- BMI
40
What are the stages in the parathyroid hormone loop
- parathyroid glands
- PTH
- positive feedback to bone, GI, kidney
- calcium
- negative feedback to parathyroid glands
41
Magnesium plays a key role in which stage of the parathyroid hormone loop?
Parathyroid glands producing PTH
42
What does PTH do?
- increases Ca turnover in bones with net resorption
- decreases Ca clearance at kidneys but increase phosphate excretion
= both of these increase plasma Ca
43
What does vitamin D do in turns of calcium levels?
Increases calcium absorption in gut
44
What effect does increased plasma calcium have on PTH?
Negative feedback
45
Name 6 main causes of hypocalcaemia
- hypoproteinaemia
- vitamin D deficiency
- hypoparathyroidism
- inadequate intake of calcium
- pseudohypoparathyroidism
- artefactual causes
46
Vitamin D deficiency causes hypocalcaemia but what are the causes of vitamin D deficiency?
- dietary/malabsorption
- hepatic disease
- renal disease
- end-organ vitamin D resistance
47
Name 2 types of hypoparathyroidism (causes hypocalcaemia)
- primary
| - secondary to Mg depletion
48
What is psuedohypoparathyroidism?
End-organ PTH resistance
49
Give examples of artifactual causes of hypocalcaemia
- EDTA contamination (chelates calcium ions)
| - venestasis will cause low adjusted calcium (total calcium is unaffected)
50
How would you distinguish between hypoparathyroidism and vitamin D deficiency?
Hypoparathyroidism = low PTH with slightly low calcium
vitamin D deficiency = very high PTH with low calcium
51
What are the 5 main causes of hypercalcaemia?
- hyperparathyroidism
- malignancy
- drugs
- vitamin D excess
- bone disease and immobilisation
52
What types of malignancy might cause hypercalcaemia?
- lytic lesions
| - humoral eg. PTHrp
53
What should be done during differential diagnosis of hypercalcaemia?
- 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
How would you differentiate between hyperthyroidism and bone metastases?
Calcium high in both but in hyperparathyroidism, the PTH is high, whereas in bone metastases, the PTH is slightly low
55
Which calcium disorder involves low serum ionised calcium and low plasma PTH?
Primary hypoparathyroidism
56
Which calcium disorder involves low-normal serum ionised calcium but high plasma PTH?
Secondary hyperparathyroidism (usually renal or nutritional)
57
Which calcium disorder involves high serum ionised calcium and but low plasma PTH?
PTH independent hypercalcaemia (eg. malignancy, vitamin D toxicity)
58
Which calcium disorder involves high serum ionised calcium and high plasma PTH?
Primary hyperparathyroidism
59
Where is phosphate found?
Major intracellular ion, small proportion in the plasma
| similar to phosphate
60
Phosphate is involved in which reactions?
Involved in high energy reactions eg. those involving ATP eg. Na/K pumps, Hexokinase
61
Deficiency of phosphate can cause what?
- weakness and dysfunction
| - severe depletion can be fatal
62
Describe phosphorus homeostasis
slide 38 of lecture
63
What are the 4 main causes of phosphate deficiency?
- hyperparathyroidism
- excess losses
- poor intake (malnutrition/inadequate IVN)
- ECF/ICF redistribution (like potassium)
64
What are the causes of excess losses of phosphate leading to phosphate deficiency?
- renal tubular damage
- gastro-intestinal
- diabetes (diuresis)
65
Name the factors that increase phosphate absorption in the intestine?
- reduced dietary intake of phosphate
| - elevated serum 1,25-dihydroxyvitamin D
66
Name the factors that reduce phosphate (Pi) absorption in the intestine?
- reduced serum 1,25-dihydroxyvitamin D
- elevated concentrations of calcium salts in intestinal lumen
- MEPE
67
Name the factors that increase phosphate reabsorption in the kidney?
- phosphate depletion
- parathyroidectomy
- 1,25(OH)2D
- volume contraction
- hypocalcaemia
- hypocapnia
68
Name the factors that decrease phosphate reabsorption in the kidney?
- 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
What are the symptoms of phosphate deficiency?
- 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
If phosphate deficiency is confirmed, treatment is essential; what might be necessary?
Changes to IV fluid regimens including TPN formulations (total parenteral nutrition)
71
Magnesium has a close relationship with which other disorders?
Calcium and potassium (K) disorders
Similar problem with disorders of phosphate metabolism
72
Describe the physiology of renal magnesium handling
slide 43 of lecture
73
Describe magnesium metabolism
slide 44 of lecture
74
Describe the proteins implicated in the molecular control of Mg2+ homeostasis
slide 45 of lecture
75
Describe the effectors of Mg2+ homeostasis?
slide 46 of lecture
76
Hypomagnesaemia is associated with which other conditions
- hypokalaemia (40%)
- hyponatraemia (23%)
- hypophosphataemia (29% )
- hypocalcaemia (25%)
77
How common is hypomagnesaemia?
Prevalence in hospitalised patients - alone on routine estimation 6-11%
78
What are the renal causes of magnesium depletion?
- diuretic phase of acute tubular necrosis
- hypercalcaemia states
- drugs
79
Which drugs can cause renal magnesium depletion?
- antibiotics eg. gentamicin, carbenicillin
- chemotherapy e.g. cisplatin
- diuretics
- FK506
80
What are the GI causes of magnesium depletion?
- malnutrition
- intravenous nutrition
- diarrhoea
- malabsorption
81
What are the cellular effects of magnesium depletion?
- reduced mitochondrial respiration and impaired phosphorylation
- defective Na-K ATPase activity
- impaired DNA synthesis
82
What are the biochemical effects of magnesium depletion?
- hypocalcaemia
- hypophosphataemia
- hypokalaemia
83
What are the endocrine effects of magnesium depletion?
- impaired PTH release
| - PTH resistance in bone
84
What are the CVS effects of magnesium depletion?
- cardiac irritability
| - reduced contractility
85
What are the CNS effects of magnesium depletion?
- hyper-reflexia
- tetany
- ataxia/vertigo
- psychosis/depression
86
What are the muscle effects of magnesium depiction?
- weakness
- muscle fibrillation
- myopathic EMG
87
What types of tissue magnesium levels can be measured?
- serum magnesium
- erythrocyte magnesium
- leucocyte magnesium
- muscle magnesium (20% body Mg)
88
Erythrocyte magnesium is affected by what?
High reticulocyte count
89
What is required to take muscle Mg levels?
Biopsy
90
Mg deficiency should always be considered with combined..
hypokalaemia and hypocalcaemia
91
Screening for Mg deficiency is advocated because of high prevalence but...
- most patients are asymptomatic
- most patients recover spontaneously
- hypomagnesaemia usually manifests itself alongside obvious causative disease eg. chemotherapic side effects
92
Calcium at what levels is a medical emergency requiring immediate treatment?
Over 3.5mmol/L or under 1.6mmol/L
