Disorders of Calcium, magnesium and phosphate Flashcards
What blood test tube should never be used for or before serum calcium?
EDTA - it gets rid of the calcium
What are the 4 main roles of calcium physiologically?
1) Muscle contraction
2) Neuronal excitation
3) Enzyme activity (Na/K ATPase, hexokinase)
4) Blood clotting
What is the structural role of calcium in the body?
Key component of hydroxyapatite which is the predominant mineral in bone
What kind of chemical is phosphate?
Monovalent anion PO4-
What are the 3 physiological roles of phosphate?
1) The P in ATP
2) Intracellular signalling
3) Cellular metabolic processes eg. glycolysis
What are the 3 structural roles of phosphate in the body?
1) Backbone of DNA
2) Component of hydroxyapatite - predominant mineral in bone
3) Membrane phospholipids
Is phosphate predominantly extracellular or intracellular?
Intracellular
What kind of ion is magnesium?
Divalent cation
What are the 4 physiological roles of magnesium?
1) Cofactor of ATP - our fuel
2) Neuromuscular excitability
3) Enzymatic function
4) Regulates ion channels
What is the structural role of magnesium?
Comprises 0.5-1% of bone
Is magnesium an intracellular or extracellular ion?
Predominantly intracellular
If you receive serum calcium serum results which are very unusual what is the likely problem?
EDTA contamination
In terms of homeostasis, when something goes wrong one of what 4 things is normally the cause of the abnormality?
1) Intake
2) Tissue redistribution
3) Storage
4) Excretion/loss
What is the normal range of calcium?
2.20-2.60mmol/L
What are the 2 key controlling factors in regulating calcium?
1) PTH
2) Vit D and metabolites
What 3 organs have a role in calcium levels?
1) GI uptake
2) Renal clearance
3) Bone
What 3 types of calcium make up total calcium?
Total Ca = Ionised Ca + Bound Ca + Complexed Ca
What is the physiologically active fraction of total calcium?
Ionised calcium
What are the 3 roles of ionised calcium?
1) Acts on calcium sensing receptor
2) Regulates PTH
3) Cellular effects
Which is the main binding protein for bound calcium?
Albumin
Is bound calcium physiologically active?
No
In what 2 forms is complexed calcium found?
1) Calcium phosphate
2) Calcium citrate
What is meant by adjusted calcium?
Calcium values which are corrected for changes in albumin:
Adjusted Ca = Total Ca + (40-Alb) x 0.025
Are the reference values for adjusted calcium different to those for total calcium?
No
What are the relative proportions of the 3 forms of calcium in the plasma?
About 50% is ionised - 1.3mmol/L
Bound = 0.95mmol/L
Complexed = 0.05mmol/L
What is the routine lab measurement for calcium, give 2 reasons why this is used?
Total calcium - cost and convenience
For what 2 reasons does total calcium not necessarily reflect ionised calcium?
1) Total Ca is affected by [albumin]
2) pH influences ionised Ca
What is the reference range for total calcium?
2.20-2.60mmol/L
Why does pH affect the proportions of ionised calcium?
H+ and Ca2+ compete for albumin binding sights
Decreased pH = more H+ competing with Ca so more ionised Ca
How does alkalosis affect ionised calcium?
Increases the amount of Ca-albumin complexes so reduces the amount of ionised Ca
How does acidosis affect ionised calcium?
Decreases the amount of Ca-Albumin complexes so increases the amount of ionised Ca
Does pH affect the amount of complexed calcium?
No
Why can alkalosis precipitate tetany?
Because is reduces the amount of ionised calcium so less available to bind to receptors
What implication does acidosis have for hypoclacaemic patients?
Don’t develop symptoms because the acidosis increases ionised calcium
Disorders of which 4 systems affects calcium levels?
1) Disorders of homeostatic mechanisms eg. PTH and Vit D
2) Disorders of the skeleton eg. bone mets
3) Disorders of effector organs eg. GI tract (malabsorption) and kidney
4) Diet
Which 3 substances are involved in calcium regulation?
1) PTH
2) Vit D
3) Klotho
By what 2 organs is calcium excreted, roughly how much from each?
1) Kidney - 10mmol/day
2) GI tract - 15 mmol/ day
What organ stores 99% of the bodies calcium?
Bones
What is the average dietary intake of calcium?
25mmol/day
How is vitamin D produced?
Precursors are ingested through diet
UVB light converts the precursors into further pre cursors in the skin
Kidneys convert Vit D precursors to the final active product (regulated by PTH)
What are the 4 site of action of active Vit D?
1) Intestine - increases absorption
2) Bone - increases bone mineralisation
3) Immune cells - induces differentiation
4) Tumour microenvironment - inhibits proliferation and angiogenesis and induces differentiation
Vit D acts as negative feedback to which hormone?
PTH
Give 2 endogenous and 5 exogenous factors which affect the amount of Vit D people get?
Endogenous: 1) Skin colour 2) Aging Exogenous: 1) Ozone 2) Suncreens and clothing 3) Latitude and season 4) Time of day 5) Diet and supplements
What 3 biological factors lead to reduction in Vit D?
1) Age
2) BMI
3) Body fat (Vit D gets sequestered in adipose tissue)
What are the steps in the PTH loop?
PTH glands release PTH
By positive feedback this acts on the bone, GI and kidneys
Leads to increase in serum calcium
Calcium acts as negative feedback of PTH glands so they stop releasing PTH
What is the role of magnesium in the PTH loop?
PTH stored in zymogens in the PTH gland
Need magnesium to release PTH as it stimulates zymogens binding to the phospholipid membrane and releasing PTH
What are the 4 actions of PTH?
1) Decreases Ca clearance from kidneys in exchange for phosphate
2) So increases phosphate excretion
3) Causes activation of Vit D by the kidneys which increases Ca gut absorption
4) Increases Ca turnover with net resorption from bone
What are the 6 causes of hypocalcaemia?
1) Hypoproteinaemia
2) Vit D deficiency (dietary, hepatic/renal disease, end organ Vit D resistance)
3) Hypoparathyroidism
4) Inadequate calcium intake
5) Pseudohypoparathyroidism (end organ PTH resistance)
6) Artefactural causes (EDTA contamination, venestasis)
What levels of calcium and PTH suggest Vit D deficiency?
Low calcium
High PTH
Suggests Vit D deficiency
What levels of calcium and PTH suggest hypoparathyroidism?
Low calcium
Low PTH
Give the 5 causes of hypercalcaemia?
1) Hyperparathyroidism
2) Malignancy - lytic lesions, humoral eg. PTHrp
3) Drugs
4) Vit D excess (1alpha cholecalciferol, sarcoidosis)
5) Bone disease and immobilisation
Which drug can lead to hypercalcaemia?
Lithium
What 5 steps can help you achieve a differential diagnosis for hypercalcaemia?
1) Consider adjusted Ca - look at albumin
2) Check drug history
3) Exclude excess Vit D intake
4) Check for renal failure
5) Simultaneous measurement of Ca and PTH
How can you distinguish between hyperparathyroidism and metastases as a cause of hypercalcemia using the PTH and calcium levels?
High calcium and low PTH = metastases
High calcium and high PTH = hyperparathyroidisim
What is the role of phosphate physiologically?
Involved in high energy reactions eg. those involving ATP - Na/K pumps, hexokinase
What does deficiency of phosphate cause?
Deficiency of phosphate causes weakness and dysfunction - severe depletion can be fatal
What 2 organs are involved in phosphate excretion?
1) Kidney
2) GI tract
Which organ is a store of phosphate?
Bone
What is the average daily intake of phosphate per kilo?
20mg
What are the 4 causes of phosphate deficiency?
1) Hyperparathyroidism
2) Excess losses
3) Poor intake
4) ECF/ICF redistribution
Why does hyperPTH lead to phosphate deficiency?
PTH leads to decreased renal excretion of calcium in exchange for phosphate thus PTH increases renal excretion of phosphate
What 3 things can lead to excess losses of phosphate?
1) Renal tubular damage
2) gastrointestinal
3) diabetes (diuresis)
What are the 4 groups of symptoms of phosphate deficiency?
1) Haemolysis, thrombocytopenia and poor granulocyte function
2) Severe muscle weakness, respiratory muscle failure and rhabdomyolysis
3) Confusion, irritability and coma may be due to metabolic encephalopathy due to phosphate deficiency
4) Renal dysfunction
What is the treatment for phosphate deficiency?
Changes to IV fluid regimes including TPN formations
What percentage of hospital admissions have phosphate/magnesium disorders?
Around 10%
Magnesium and phosphate disorders are closely related to disorders of what other 2 minerals?
Ca and K
What are the 2 methods of absorption of Mg in the kidneys?
1) Between cells (thick ascending loop)
2) Via receptor (distal convoluted tubule)
What 2 organs are the main stores of magnesium?
1) Bone - 60%
2) Muscle intracellular space - 39%
What is the bodies store of magnesium?
1.9 Mol
Which 2 organs are involved in excretion of magnesium?
GI tract and kidneys
What is the normal range of Mg in the plasma?
0.7 -1.0 mmol/L (about 12mmol)
Hypomagnesaemia is associated with what 4 conditions?
1) Hypokalaemia
2) Hyponatraemia
3) Hypophosphataemia
4) Hypocalcemia
What is thought to be the prevelance of hypomagnesaemia in hospitalised patients?
6-11%
What are the 3 renal and 4 GI causes of magnesium depletion?
Renal: 1) Diuretic phase of acute tubular necrosis 2) Hypercalcaemic states 3) Drugs - Abx, chemo, diuretics, FK506 GI: 1) Malnutrition 2) IV nutrition 3) Diarrhoea 4) Malabsorption
What are the 3 cellular effects of magnesium depletion?
1) Reduced mitochondrial respiration and impaired phosphorylation
2) Defective Na-K ATPase activity
3) Impaired DNA synthesis
What are the 3 biochemical effects of magnesium depletion?
1) Hypocalcemia
2) Hyponatremia
3) Hypokalaemia
What are the 2 endocrine effects of magnesium depletion?
1) Impaired PTH release
2) PTH resistance in bone
What are the 2 CVS effects of magnesium depletion?
1) Cardiac irritability
2) Reduced contractility
What are the 4 CNS effects of magnesium depletion?
1) Hyper reflexia
2) Tetany
3) Ataxia/ vertigo
4) Psychosis / depression
What are the 3 muscular effects of magnesium depletion?
1) Weakness
2) Muscle fibrillation
3) Myopathic EMG
Out of serum Mg, erythrocyte Mg, leucocyte Mg and muscle Mg, how does each correlate with tissue magnesium status?
Serum Mg - poor correlation but only one likely to use
Erythrocyte Mg - poor correlation and affected by high reticulocyte count
Leucocyte Mg - good correlation and good predictive value
Muscle Mg - 20% body mg, important physiologically but requires biopsy
Which lab measurement of Mg most accurately reflects tissue Mg status?
Leucocyte Mg
In what situation should Mg deficiency always be considered?
Combined hypokalaemia and hypocalcaemia
For what 3 reasons is screening for Mg deficiency advocated?
1) Most patients asymptomatic
2) Many patients recover spontaneously
3) HypoMg usually manifests itself alongside obvious causative disease eg. chemo side effects
What levels of calcium is a medical emergency requiring immediate treatment?
Calcium >3.5mmol/L
Calcium
