calcium phosphate and magnesium Flashcards
what is the biochemistry of calcium?
it is a divalent cation Ca2+ unless in EDTA that is physiologically important and structurally important. A patient who has low albumin will have the same ionised and complexed calcium but low protein bound calcium
why is calcium structurally important?
it is a component of hydroxyapatite - Ca10(PO4)6(OH)2 which is the main mineral in bones
why is calcium physiologically important?
neuronal excitation, muscle contraction, enzymatic activity such as the Na/K ATPase and hexokinase and for blood clotting
what are the three areas that calcium is distributed?
99% of it is in the bone, 1% intracellular and 0.1% extracellular
what is a normal range of plasma calcium and how is this comprised?
2.2-2.6mmol/L
it is arranged into complexed anions for 9%, 41% bound to plasma proteins and 50% ionised free calcium ions
the ionised free calcium ions can be made by the bound and complexed and in turn can make these
what is considered a medical emergency with calcium?
when the calcium is <1.6 or >3.5mmol/L and requires treatment
what is the total calcium?
ionised calcium+complexed calcium+ bound calcium
what is the adjusted calcium?
calcium values can be adjusted and corrected for changes in albumin - the adjusted calcium is the total calcium + ((40-alb)x0.025)
the reference range is 2.2-2.6mmol/L
and the equation is not valid if the albumin is less than 20g/L
what is the recommended measure of calcium?
a point of care blood gas analyser to measure the calcium ions
what will happen if the albumin or other protein binders drop?
the protein bound calcium will drop but the ionised or complexed will remain the same and therefore the total calcium will drop
total calcium increases as albumin increases
what is the biochemistry of phosphate?
it is PO43- and is physiologically and structurally important. A deficiency can be fatal. It is predominantly intracellular
why is phosphate physiologically important?
ATP fuel, intracellular signalling and cellular metabolic processes such as glycolysis
why is phosphate structurally important?
for membrane phospholipids, component of hydroxyapatite and forms the backbone of DNA
what is the structure of phosphate?
it is a central P with a double bond to one O, and three single bonds
what is the distribution of phosphate in the body?
the total body phosphorus is 23mol or around 700g and this is distributed in 85% bone, 14% intracellular and 1% extracellular
what do the distributed forms of phosphorus make?
they make phosphorus in the blood of which 70% in organic and covalently bound such as in phospholipids and 30% in in the inorganic form as phosphate with a ratio of 4:1 of HPO4 2-: H2PO4-
what is the reference range for phosphate?
0.8-1.5mmol/L
in terms of these ions, what is homeostasis?
it is balancing the internal environment and responding to changes in stimuli - this involves intake, excretion and loss and tissue redistribution and storage
how is calcium levels maintained?
it is tightly regulated in the reference range and there are two key controlling factors - these are parathyroid hormones and Vit D and metabolites. The calcium homeostasis is a direct result of the balance of GI uptake, bone storage and renal clearance
what is the main function of PTH?
to increase serum calcium and to decrease serum phosphate
how does the role of PTH relate to the process?
high calcium will inhibit PTH released by negative feedback via the CaSR and high phosphate to a lesser ectent will stimulate PTH along with low calcium
how does PTH work?
parathyroid glands (where magnesium also works) secretes PTH in states of low calcium. This PTH acts on the bone and drives resorption of Ca and PO4. It also acts on the kidneys to increase resabsorption of Ca from the filtrate but increase excretion of PO4. It also acts on the kidney to increase the conversion of Vit D to its active form which increases Ca and PO4 absorption from the gut
what is vitamin D for?
it is for providing enough energy. It is for bone health and therefore recently there has been a recent resurgence in rickets due to around 30% of children in the UK being insufficient in Vit D
what are the reference ranges for vit D?
25-OH Vit D :
<75nmol/L is insufficient
>75nmol/L is normal
>500nmol/L is toxicity
what factors affect vitamin D levels?
age - younger have more BMI and body fat - lower has higher level malabsorption clothing sunscreen climate, latitude and season time spent in or outdoors skin tone diet
what is the Vitamin D cycle?
there is a dietary source of vitamin D which goes into the intestine, then circulation. Or therer is a UV source of vitamin D which makes the D3 eventually and goes into circulation. From the circulation it goes to the liver where it is excreted or goes to the kidney. The PTH also acts directly on the kidney. From the kidney it acts on tumour microenvironment, intestine, bone and immune cells
what does vit D do in the intestine, immune cells, bone and tumour micorenvironment?
in the intestine it increases absorption of calcium and phosphate
in the bone it increases bone mineralisation
in the immune cells it induces differentiation
in the tumour microenvironment it inhibits proliferation, induces differentiation and inhibits angiogenesis
what are other regulators of calcium and phosphate homeostasis?
PTH, calcitonin, Vit D, oestrogen, FGF 23
how does FGF23 work?
increases renal phosphate excretion
how does calcitonin work?
it opposes the effects of PTH by acting on osteoclasts to reduce bone resorption and is usually insignificant in function of normal homeostasis of calcium
what are the causes of hypocalcaemia?
lack of dietary calcium intake, high phosphate intake, hypoparathyroidism, hypoalbuminaemia, vitamin D deficiency and spuruious causes such as EDTA contamination and cirtation contamination
what are the main causes of vitamin D deficiency?
dietary, lack of sunlight, malabsorption and liver or renal disease
what are the results of hypoalbuminaemia?
there is a reduction in the total calcium but this is adjusted for in adjusted calcium
what can hypoparathyroidism be causes by?
primary, hypomagnaesaemia or pseudo-hypoparathyroidism where there is end organ resistance to PTH
what is latent tetany demonstrated by?
Chvosteks or Trousseaus sign
what are the signs and symptoms of hypocalcaemia?
convulsions, psychosis, cramps, tetany, latent tetany, paraestheia in the extremities
what are the clinical signs of K+ EDTA and hypoparathyroisim?
K+ EDTA = low adjusted calcium, alkaline phosphate, magnesium and high potassium
hypoparathyroisism - low calcium and PTH but high phosphate
what are the clinical signs of vit D deficiency (particularly in vegans) and low 1,25(OH)2 Vit D?
in low 1,25(OH)2 - there will be low adjusted calcium but high phosphate, ALP, creatinine and urea
in low vit D in vegans there will be high PTH and low calcium
what is low calcium and low PTH and low calcium but high PTH?
if both are low then hypoparathyroism, if low calcium but high PTH then there is vit D deficiency
as calcium increases then how does PTH change?
the PTH will decrease - inversley correlated
what are the causes of hypercalcaemia?
hyperparathyroidism, malignancy, medications, vitamin D excess,, bone disease, immobility, hyperthyroidism
what are some causes of hyperparathyroidism?
parathyroid adenomas
what are the malignancy causes of hypercalcaemia?
tumours secreting PTHrp, tumours secreting osteoclast activating cytokines that are with or without bone mets and cells that have 1a hydroxylase activity with activation of Vit D such as in lymphoma
what are the medications that can cause hypercalcaemia?
thiazides and lithium
what are the vitamin D excess causes?
over supplementation or sarcoidosis - 1a hydroxylase activity
what are the signs and symptoms of hypercalcaemia?
stones, bones, moans and groans
dehydration via renal resistance to ADH
describe stones, bones, moans and groans?
stones - renal stones due to hypercalciuria, causing renal colic
bones - pain and osteoporosis due to inappropriately high PTH
moans - lethargy fatigue and depression
groans - abdo pain, constipation, nausea and vomiting
what are the signs in hypercalcamia due to malignancy and hyperparathyroidism?
hyperparathyroidism will have high calcium and PTH, if due to malignancy then high calcium but low PTH
what are the first line investigations for derrangement of calcium?
simultaneous measurement of Ca and PTH, consider the adjusted calcium equation - look at albumin concentration and measure the ionised calcium on blood gas analyser, vit D, magnesium, bone profile with adjusted calcium, ALP and phosphate and consider the rare causes and more complex investigations
what are the issues with phosphate deficiency and what are the three main causes?
it is often overlooked or disregarded, and the three main causes are low intake, excess losses or ECF ICF redistribution
what are the main causes of low intake?
malnutrition, malabsorption, alcoholism
what are the main causes of excess loses of phosphate?
hyperparathyroidism, renal tubular damage in fanconi syndrome and diarrhoea
what are the causes of ICF and ECF redistribution?
refeeding syndrome and alkalosis
what are the signs and symptoms of low phosphate?
rhabdomyolysis, respiratory muscle failure and muscle weakness, convulsions, coma, death, haemolysis, thrombocytopaenia and poor granulocyte function, chronic phosphate deficiency, rickets
what are the treatments of low phosphate?
if acute then is essential to confirm and treat - oral or IV phosphate
what does chronic phosphate deficiency cause?
rickets in children and osteomalacia in adults
what are the three main causes of hyperphosphataemia?
hypoparathyroidism, spurious or renal failure
what are the signs and symptoms of hyperphosphataemia?
they are due to hypocalcaemia usually
what are the causes of renal failure?
AKI or CKD
what are the causes of spurious hyperphosphataemia?
haemolysis, delayed separation of sample and assay interference
what is the biochemistry of magnesium?
divalent cation Mg2+ and is physiologically and structurally important
what are the physiological roles of magnesium?
cafactor for ATP, neuromuscular excitability, enzymatic function and regulates ion channels
what is the structural importance of magnesium?
comprises 0.5-1% of bone matrix
what is the distribution of body magnesium?
total body magnesium around 1.1mol that is separated into bone (54%), intracellular (45%) and extracellular (1%)
what is the reference range of magnesium?
0.7-1.0mmol/L
what happens to magnesium in the blood?
60% is ionised free
25% is bound to plasma protein - predominately albumin and 15% is complexed to anions such as phosphate, citrate and bicarbonate
what is the homeostasis of magnesium?
it is predominantly done by the kidneys but the mechanism is not completely understood. PTH is released by a decreased in magnesium and inhibited bu an increase but calcium is a much more potent stimulus. Having said this, the PTH release is magnesium dependent and therefore severe hypocalcaemia
how does severe hypomagnesaemia cause hypocalcaemia?
it interferes with the parathyroid gland CaSR mediated release of PTH and blunts end organ response. Profound hypomagnasaemia then decreases the release of PTH and results in hypocalcaemia
how do the kidneys regulate magnesium?
coming up to the proximal tubule and ascending limb there is paracellular absorption but in the DCT there is transcellular absorption. There is urinary excretion in the collecting duct and this all uses the NaK ATPases
where is hypomagnesaemia prevalent and why?
in hospitalised patients as it is a forgotten cation
what is hypomagnesaemia associated with?
hyponatraemia, hypokalaemia, hypocalcaemia and hypophosphataemia
what are the main causes of hypomagnesaemia?
spurious cases, redistribution into cells, renal and GI loss and inadequate intake
what are the reasons for inadequate intake of magnesium?
malnutrition especially in alcoholics, malabsorption, and total parenteral nutrition through IV
what are the reasons of renal loss of magnesium?
drugs - diuretics, chemo such as cisplatin, ABs such as gentamicin and carbenicillin and FK506 tacromilus
rare inherited disorders
what are the reasons behind magnesium insufficiency in GI loss?
PPIs and diarrhoea
what does redistribution of magnesium into cells cause?
refeeding syndrome
what are spurious cases of hypomagnesaemia?
EDTA contamination
what is EDTA?
it is a widely used anticoagulant that may cause pseudothrombocytopaenia and platelet clumping
what are the signs and symptoms of hypomagnesaemia?
can affect various symptoms such as neuromuscular hyperexcitability (tremor, tetany, convulsions and muscle weakness), CNS - depression and psychosis, cardiovascular - ECG changes, arrhythmia, reduced contractility, GI - nausea and anorexia and biochemical consequences such as hypocalcaemia, hypokalaemia, associated signs and symptoms
why is hypermagnesaemia rare?
the kidneys have a large capacity to excrete magnesium
what is the main cause of hypermagesaemia?
usually iatrogenic in cardiac surgery or pre-eclampsia and you need to rule out a drip-arm sample issue
