Calcium, phosphate and magnesium homeostasis

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  • Created by: hadar
  • Created on: 23-02-18 10:21
Why is the biochemistry of calcium important physiologically? (4)
1)Muscle contraction 2)Neuronal excitation 3)Enzyme activity (Na/K ATPase, hexokinase etc.) 4) Blood clotting
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Why is the biochemistry of calcium structurally important?
Key component of hydroxyapatite Ca₁₀(PO₄)₆(OH)₂ - the predominant mineral in bone
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What is thedastribution of calcium in the body?
bone 99% intracellular 1% extracellular 0.1%
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What is the normal total plasma calcium level? (reference range)
2.2 – 2.6 mmol/L
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What are the 3 forms of calcium in the blood?
1)bound to plasma proteins 41% 2)complexed to anions 9% 3)ionised 'free' ca2+ 50%
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What is the equation for total calcium?
ionised calcium + bound calcium + complexed calcium
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Which form of calcium is biologically active?
Only free ionised calcium is biologically active
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What is the effect of changes in binding proteins on calcium?
Changes to levels of binding proteins will impact how much calcium can be bound and is free
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what is the relationship between bound calcium and total calcium levels?
The more bound calcium the more total calcium whereas if there is less bound calcium/ less binding proteins there is less total calcium
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What does adjusted calcium take into account?
Corrected for changes in albumin
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What would blood results look like if they were contaminated with EDTA?
high levels of potassium and low levels of adjusted calcium, calcium, alk phos, magnesium (low levels due to collation)
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What is the distribution of phosphorus in the body?
bone 85% intracellular 14% extracellular 1%
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What are the 2 forms of phosphorus in the blood?
organic form which is covalently bound 70% and inorganic form as phosphate 30%
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What is the reference range for phosphate?
0.8 – 1.5 mmol/L
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What levels of calcium are a medical emergency and require immediate treatement?
Calcium < 1.6 or > 3.5 mmol/L
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What it the total body calcium amount?
1kg
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What is the total body phosphorus amount?
700g/ 23 mol
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Why is the biochemistry of phosphate physiologically importnat?(3)
1)The P in ATP – our fuel! 2)Intracellular signalling 3)Cellular metabolic processes e.g. glycolysis
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Where is phosphate predominantly found?
Intracellular
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Why is the biochemistry of phosphate structurally important? (3)
1)Backbone of DNA 2)Component of hydroxyapatite Ca₁₀(PO₄)₆(OH)₂ 3)Membrane phospholipids
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What can deficiency in phosphate cause?
Weakness and dysfunction - severe deplete can be fatal
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What are the 3 causes to homeostasis unbalance?
1)intake 2)excretion/loss 3)tissue redistribution/ storage
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What are the 2 key controlling factors of calcium homeostasis?
1) parathyroid hormone (PTH) 2)vitamin D and metabolites
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Describe the homeostasis of calcium
highly regulated at 2.2-2.6mmo/L- complex relationship between GI uptake, renal clearance, bone storage
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What does PTH act on? (4)
1) acts on bone to drive resorption of ca+ PO4 2)acts on kidney to increase reabsorption of ca and increase excretion of PO4 3)act on kidney increase conversion vitamin D to active form--> increases Ca + PO4 absorption from gut
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What mineral is required to release PTH?
magnesium
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What is the release of PTH stimulated by?
Low calcium but also high phosphate
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What is the net effect of PTH?
Increase serum calcium and decrease serum phosphate
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Wat are the levels of vitamin D?
25-OH Vitamin D < 75 nmol/L is deficient or depleted 25-OH Vitamin D >75 nmol/L is sufficient 25-OH Vitamin D > 500 nmol/L suggests toxicity
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What factors affect vitamin D levels?(10)
1)season 2)latitude/climate 3)clothing 4)use of sunscreen 5)time spent indoors/outdoors 6)skin tone 7)age 8)diet 9)body fat and BMI 10)malabsorption
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What regulate calcium and phosphate homeostasis? (6)
1)PTH 2)vitamin D 3)FGF23 4)calcitonin 5)oestrogen 6)klotho
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What is FGF23 secreted by and for what response?
Secreted by osteocytes in response to an increase in the active form of vitamin D Suppresses 1α hydroxylation of vitamin D by the kidneys (negative feedback) Increases renal phosphate excretion
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What is calcitonin secreted by and whats its response?
Secreted by the C-cells of the thyroid gland in response to increased calcium concentration Opposes the effect of PTH by acting on osteoclasts to inhibit bone resorption Function is usually insignificant in regulation of normal calcium homeostasis
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What are the signs and symptoms of HYPOcalcaemia? (5)
1)tetany 2)paraesthesia in extremities 3)cramps 4)convulsions 5)psychosis
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What 2 signs are observed in tetany with regards to hypocalcarmia?
Latent tetany may be demonstrated by Chvostek’s sign (tapping over the facial nerve causes twitching of facial muscles) or Trousseau’s sign (compression of the forearm produces spasms of the wrist and hand)
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What are the causes of HYPOcalcaemia? (8)
1)vitamin D deficiency 2)inadequate dietary calcium intake 3)hypoproteinaemia 4)hypoparathyroidism 5)pseudo-hypoparathyroidism 6)high phosphate 7)high citrate 8)spurious causes
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What blood results would you see in hypoparathyroidism?
low PTH, low calcium, high phosphate
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What blood results would you see in vitamin D deficiency?
high PTH and low calcium
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What is the difference in hypoparathyroidism and vitamin D deficiency with relation to PTH and calcium?
Hypoparathyroidism is where there is an inappropriate response so would have a low PTH and low calcium Vitamin D deficiency the patient will have an appropriate response so a high PTH for a low calcium
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What are the signs and symptoms of HYPERcalcaemia? (6)
1)stones-renal 2)bones- pain and osteoporosis 3)moans- lethargy, fatigue, depression 4) groans(GIT)- abdominal pain, constipation, nausea, vomiting 6)dehydration via renal resistance to ADH
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What are the causes of HYPERcalcaemia?
1)hyperparathyroidism 2)malignancy 3)medication-thiazides, lithium 4)vitamin D excess 5)hyperthyroidism 6)bone disease/immobilisation
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What is the difference in hyperparathyroidism and bone metastases with relation to PTH and calcium?
Hyperparathyroidism inappropriate response with a high PTH and calcium Metastasis appropriate response with a low PTH with a high calcium
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What is the first line biochemical investigations for for hypo/hypercalcaemia?
Consider the adjusted calcium equation - look at the albumin concentration Could measure ionised calcium on blood gas analyser Bone profile (adjusted calcium, phosphate, ALP) Vitamin D Magnesium Simultaneous measurement of Ca & PTH
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What are the symptoms of phosphate deficiency?
Haemolysis, thrombocytopenia and poor granulocyte function Severe muscle weakness, respiratory muscle failure and rhabdomyolysis Convulsions, coma, death Chronic phosphate deficiency will cause rickets (children) / osteomalacia (adults)
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What is the treatment for acute phosphate deficiency?
Often necessitates changes to IV fluid regimens including TPN formulations
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What are the causes of phosphate deficiency? (3)
1)poor intake-malabsorption/malnutrition/alcoholism 2)excess losses-hyperparathyroidism/diarrhoea/renal tubular damage/diabetes 3)ECF/ICF redistribution-refeeding syndrome/alkolosis
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What the the symptoms of HYPERphosphataemia usually due to?
HYPOcalcaemia
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What are the causes of HYPERphosphataemia? (4)
1)renal failure 2)hypoparathyroidism 3)vitamin D toxicity 4)spurious
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Why is the biochemistry of magnesium physiologically important? (4)
1)Cofactor for ATP – our fuel! 2)Neuromuscular excitability 3)Enzymatic function 4)Regulates ion channels
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Why is the biochemistry of magnesium structurally important?
Comprises 0.5 – 1% of bone matrix
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What is the total magnesium body amount?
1.1mol
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What is the distribution of magnesium?
Bone 54% Intracellular 45% Extracellular 1%
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What are the forms of magnesium in the blood?
ionised 'free' 60% bound to plasma proteins 25% complexed to anions 15%
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What is the reference range for magnesium?
0.7 – 1.0 mmol/L
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What is the relationship between magnesium and PTH?
PTH release stimulated by decrease in magnesium and inhibited by increase in magnesium (but calcium is a much more potent stimulus) HOWEVER, PTH release is magnesium-dependent, so severe hypomagnasaemia will inhibit PTH release causing hypocalcaemia
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How is magnesium controlled?
Predominantly by the kidneys Mg is freely filtered at the glomerulus then reabsorbed at the proximal tubule and the thick ascending loop. The distal convuluted tubule provides fine-tuning of magnesium levels.
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What is HYPOmagnesaemia associated with?
Hypokalaemia 40% Hyponatraemia 23% Hypophosataemia 29% Hypocalcaemia 25%
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What are the signs and symptoms of magnesium depletion?
CNS - neuromuscular hyperexcitability (tremor, tetany, convulsions), muscle weakness, depression, psychosis Cardiovascular – ECG changes, reduced contractility, arrythmia GI – nausea and anorexia Biochemical consequences: hypokalaemia, hypocalcaemia
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What are the causes of magnesium depletion?
1)inadequate intake-malnutrition/maabsorption/total parenteral nutrition 2)renal loss 3)GI loss-diarrhoea 4)redistribution into cells-reseeding syndrome 5)spurious causes
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What drugs can cause a depletion in magnesium?
Antibiotics - gentamicin / carbenicillin Chemotherapy - cisplatin Diuretics FK506 (Tacrolimus)
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What are the causes of HYPERmagnesaemia?
Rare since kidneys have a large capacity to excrete excess Usually iatrogenic Cardiac surgery Pre-eclampsia
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Why is the biochemistry of calcium structurally important?

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

Card 3

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What is thedastribution of calcium in the body?

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Card 4

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What is the normal total plasma calcium level? (reference range)

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Card 5

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What are the 3 forms of calcium in the blood?

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