Calcium, Phosphate and Magnesium Flashcards
What are functions of Calcium?
- Bone growth and remodeling
- Secretion (exocytosis)
- Excitation-contraction coupling
- Stabilization of membrane potentials
- Enzyme co-factor (e.g. in blood coagulation)
- Second messenger – intracellular signalling
What are the different forms of calcium?
- Calcium is in the skeleton (reservoir)
- Serum Calcium 2.20 – 2.60 mmol/L
- Ionised calcium 1.1-1.3 mmol/L: 45% exists in ionised form (physiologically active form), 45% bound to proteins (predominantly albumin), 10% complexed with anions (citrate, sulphate, phosphate)
Why is calicum reported as adjusted calcium and calcium?
Ionised calcium difficult to measure
- ABG machine
- Calcium electrode
- Not readily available
- Dependent on pH
What are benefits and limitations of reporting adjusted Calcium?
Benefits
- Accounts for changes in albumin. This is useful when a decrease in albumin may mask hypercalcaemia.
Limitations
- Interpret with caution in extremes of pH. Acidosis decreases binding. Alkalosis increases binding
- Conversely not useful in very low albumin states <20g/L. The body regulates unbound calcium and in low protein states ACa may be inaccurate
What are common mechanisms of Hypercalcaemia?
Increased GI absorption
- Elevated Vitamin D: Excess exogenous (therapeutic), Excess endogenous (e.g. sarcoidosis), Elevated PTH, Hypophosphataemia
- Milk-alkali syndrome
Increased bone resorption
- Increased net bone resorption (Elevated PTH, Malignancy)
- Increased bone turnover (Paget’s disease, Hyperthyroidism)
Decreased bone mineralisation
- Elevated PTH
- Aluminium toxicity
Decreased urinary excretion
- Elevated Vitamin D
- Elevated PTH
- Elevated PTH
What are common mechanisms of Hypocalcaemia?
Decreased GI absorption
- Poor dietary intake
- Vitamin D deficiency (Poor dietary intake of Vit DMalabsorption) leading to low absorption of calcium
- Decreased conversion of Vitamin D (Liver failure, Renal failure, Low PTH, Hyperphosphataemia) leading to low absorption of calcium
Decreased bone resorption/Increased bone mineralisation
- Hypoparathyroidism
- PTH resistance (pseudohypoparathyroidism)
- Vitamin D deficiency
- Hungry bone syndrome
- Osteoblastic metastases
Increased urinary excretion
- Low PTH (Thyroidectomy, I-131 treatment, Autoimmune hypoparathyroidism
- PTH resistance
- Vitamin D deficiency
What are aetiologies of Hypercalcaemia?
- Primary hyperparathyroidism (99% ambulant patients): Single adenoma (80%), Hyperplasia (15%), Double adenoma (2%), Carcinoma (<1%)
- Malignant disease (99% of ill patients): Metastases and myeloma, PTHrp secreting, Lymphoma, PTH secreting (v. rare)
- Vitamin D excess
- Tertiary hyperparathyroidism
- Hyperthyroidism
- Familial hypocaliuric hypercalcaemia
What are the signs and symtpoms of Hypercalcaemia?
- Nausea
- Depression
- Mental Disturbances
- Constipation
- Renal Failure
- Renal Stones
- Polyuria
- Soft Tissue Calcification
- Peptic Ulcers
What are the Parathyroid related aetiologies of Hypocalcaemia?
- Parathyroid agenesis (Isolated, Part of complex developmental anomaly eg DiGeorge Syndrome)
- Parathyroid destruction (Surgery, Radiation, Infiltration eg Haemochromatosis, Wilson’s)
- Autoimmune (Isolated, Polyglandular)
- Reduced parathyroid function (PTH gene defects, Hypomagnesaemia, Neonatal hypocalcaemia, Hungry bone disease)
What are the aetiologies of non-parathyroid causes of Hypocalcaemia?
- Vitamin D deficiency
- Vitamin D resistance
- Altered vitamin D metabolism eg phenytoin, ketoconazole
- PTH resistance (Pseudohypoparathyroidism, Magnesium deficiency)
- Bisphosphonates
- Acute pancreatitis
- Acute rhabdomyolysis
What are signs and symptoms of Acute Hypocalcaemia?
- Tetany
- Carpopedal spasm
- Muscles cramps
- Seizures – all types
- Prolonged QT interval on ECG
- Bronchospasm
- Laryngospasm
What are signs and symptoms of Chronic Hypocalcaemia?
- Ectopic calcification eg in basal ganglia causing extrapyramidal neurological symptoms
- Cataract
- Papilloedema
- Abnormal dentition
What are functions of Phosphate?
- Formation of high energy compounds e.g. ATP, creatinine phosphate
- Formation of second messengers e.g. cAMP, inositol phosphates
- Component of: DNA/RNA, Phospholipid membranes, Bone
- Phosphorylation (activation/inactivation) of enzymes
- Intracellular anion
What is the Distribution of Phosphate?
- 85% is within the skeleton and teeth
- 14% is located within the cells
- Only 1% is present in the extracellular fluids
Present as organic (phosphoproteins, phospholipids) and inorganic (phosphate)
What are causes of Hyperphosphataemia?
Pseudohyperphosphataemia
- Haemolysed specimen
- Myeloma
- Delayed separation / Old sample
Increased Phosphate Input
- IV PO4
- Rectal PO4
- Cell death (Tumour lysis syndrome, Rhadbomyolysis, Malignant hyperpyrexia, Heat stroke)
Reduced phosphate excretion
- Reduced eGFR (Acute renal failure, Chronic renal failure)
Increased renal tubule reabsorption
- Physiological (Recovery from Vit D def, Lactation)
- Pathological (Reduced PTH or PTH resistance, Vitamin D toxicity, Thyrotoxicosis, Acromegaly)
What is required to exclude Hypocalcaemia?
- EDTA contamination
- Multiple transfusions with citrated blood products
What is the causes of Hypophosphataemia?
Inadequate phosphate absorption
- Low dietary intake (very rare)
- Phosphate binders (dialysis patients)
- Phosphate binding antacids (rare due to new therapies for peptic ulcers)
Abnormal urinary phosphate loss
- Primary and secondary hyperparathyroidism
- Osmotic diuresis e.g. hyperosmolar hyperglycameic state
- Diuretics
- Fanconi syndrome
- Genetic conditions e.g.X-linked hypophosphataemia
Shifts of phosphate from extracellular fluid into cells
What can causes shifts of phosphate from extracellular fluid into cells?
<1% in extracellular space
Recovery from DKA
- Treatment with insulin causes phosphate to move back into cells
Refeeding syndrome
- Starving or chronically malnourished are refed or given IV glucose
- Carbohydrates stimulate insulin which drives phosphate and glucose intracellularly
- Cells switch to anabolic state resulting in further depletion
Respiratory alkalosis
- Activating phosphofructokinase which stimulates intracellular glycolysis
Increased muscle intake
Hepatic encephalopathy
Salicylate toxicity
Acute leukaemia
- Rapid growing malignancies may consume phosphate preferentially
What is FGF23?
What are the functions of Magnesium?
- Cofactor for 300+ enzymes
- Mg-ATP complex is substrate for many ATP requiring enzymes
- Critical role for DNA replication, transcription and translation
- Maintenance of structure of ribosomes, nucleic acids and some proteins
- Interacts with calcium
- Affects permeability of excitable membranes and their electrical properties (ECF depletion of Mg causes hyperexcitability)
What are symptoms of Hypomagnesaemia?
- Loss of appetite
- Nausea and vomitting
- Fatigue
- Weakness & numbness
- Tingling
- Muscle cramps
- Seizures
- Personality changes
- Hypokalaemia
- Hypocalcaemia
What are symptoms of Hypermagnesaemia?
- Non-specific symptoms include nausea, vomiting and flushing
- Neuromuscular symptoms - Blockage of neuromuscular transmission
- Conduction system symptoms (Mild decrease in blood pressure, Higher concentrations lead to symptomatic hypotension, Heart block >7mmol/L)
- Hypocalcaemia
What are causes of Hypomagnesaemia?
Decreased intake +/- absorption
- Starvation (protein calorie malnutrition), Malabsorption syndrome, Prolonged gastric suction, Inadequate parenteral nutrition,
Loss from body
- Extra renal, Diarrhoea, Laxative abuse, Gut fistula, Excessive lactation (rare)
Miscellaneous
- Acute pancreatitis, Multiple transfusions, Insulin therapy, Hungry bone syndrome
Renal
- Alcoholism, Interstitial nephropathy, Diuresis (e.g. DKA, post ATN), Drugs e.g. loop diuretics, cis-platinum (65-75% reabsorbed in Loop of Henle), Hypercalcaemia, RTA, Bartter’s syndrome, Gitelman’s, Endocrine (e.g. hypoparathyroidism, primary hyperaldosteronism, hyperthyroidism), K depletion, PO4 depletion, Post renal Tx, Primary renal Mg wasting
What are causes of Hypermagnesaemia?
- Impaired renal function
- Large Mg load: IV Contamination, Post cardiac surgery, Pre-eclampsia (used to decrease neuromuscular excitability), Enema/laxative abuse
- Excessive tissue breakdown
- Lithium therapy (decrease renal excretion)
- Hypothyroidism
- Addison’s disease
- Familial hypocalciuric hypercalcaemia
What are the effects of hypermagnesaemia?
- Cardiac conduction is affected at concentration >2.5-5.0 mmol/L
- Very high concentrations >7.5 mmol/L cause respiratory paralysis and cardiac arrest
Significant hypermagnesaemia is uncommon as readily excreted in urine
