Published on May 8, 2008
Sodium and Water: What Laboratory Scientists Need to Know: Sodium and Water: What Laboratory Scientists Need to Know Graham Jones Staff Specialist in Chemical Pathology St Vincent’s Hospital, Sydney Presented RCPA/AACB Chemical Pathology training Course, February 2004, Adelaide Objectives: Objectives Measurement Physiology Pathology Lab-based knowledge Sodium Measurement: Sodium Measurement Most Australian Laboratories use Ion Sensitive Electrodes (ISE) May be direct or indirect Indirect Dilution of the sample Most automated analysers Affected by lipid and protein concentrations Direct No dilution of the sample Blood gas machines Vitros analysers What we measure: What we measure Analyte: Sodium Measurand: activity of sodium ions per volume of sample (indirect) Activity of sodium ions per mass of water* (concentration) * expressed per volume of plasma Sodium Measurement: Interferences: Sodium Measurement: Interferences Analytical Electrodes are very specific In the presence of increased amounts of non-aqueous components we get reduced values with indirect methods (pseudohyponatraemia) Pre-analytical Drip-arm Wrong patient Gross haemolysis (dilution with intracellular fluid) Drip arm contamination: Drip arm contamination Common diluents: Normal saline: 154 mmol/L Na and Cl 5% dextrose: 278 mmol/L glucose 4% & 1/5th saline: 222 mmol/L gluc, 31 Na & Cl Results tend to values in diluent eg Na of 170 unlikely to be drip-arm Osmolality tends to be normal Measuring glucose, albumin and protein helpful Artefacts: examples: Artefacts: examples Questions: Could it be pathology? Could it be artefact? * * * * * * * * * * How good are we: How good are we Average analytical CV about 1% Gives SD of about 1.4 mmol/L for normal result 95% of results in a 5.6 mmol/L range (+/- 2SD) Biological variation Within person 0.6 % Between person variation 0.6% Acceptable CV is <0.75 x within person CV Not acceptable!! Water Measurement: Water Measurement Clinical Weight (change in weight) Physical examination: pulse, blood pressure, JVP, lung auscultation, oedema Concentration of blood components High albumin#, high sodium may mean low water content of samples. # or prolonged tourniquet for albumin Low albumin or low sodium may mean high water concentration of samples 5% dehydration highly significant Water and electrolytes: Other Tests: Water and electrolytes: Other Tests Serum Urea, Creatinine Glucose Osmolality (and osmolar gap) Albumin, Total Protein Lipids Urea Sodium Osmolality Creatinine Physiology: Physiology Body Sodium : Body Sodium Sodium: major extracellular cation Approx 10 mmol/L intracellularly 140 mmol/L extracellularly Intake: 100 - 200 mmol/day Excretion: Faecal: 10 mmol/d Sweat: 10-20 mmol/d Renal: the rest (ie matches intake) Equally distributed in extracellular fluid ie drain fluid except urine and gastro-intestinal fluid! Sodium and Water: Sodium and Water Sodium and Water homeostasis are inextricably linked “where sodium goes, water follows” Measure sodium concentration Affected by changes in water and sodium Clinical effects due to movement of water in and out of cells Salt and Water regulation: Salt and Water regulation Water Thirst (regulates input) Vasopressin (ADH) (regulates output) Sodium Renin-Angiotensin-Aldosterone (RAA) Natriuretic peptides Both regulate output Vasopressin (ADH): Vasopressin (ADH) Hormone from Posterior pituitary Released in response to high osmolality Released in response to low volume Low volume over-rides low osmolality Increases permeability of kidney distal tubule Controls renal WATER excretion Low ADH -> high urine volume, low urine osmo High ADH -> low urine volume, high urine osmo Also potent vasocontrictor Vasopressin (ADH): Vasopressin (ADH) Dehydration Hypernatraemia (Increased osmolality) ADH Release Reduced renal water loss Reduced BP Vasocontriction Euvolaemia Concentrated Urine Renin-angiotensin-aldosterone (RAA): Renin-angiotensin-aldosterone (RAA) Low renal perfusion -> renin release eg hypovolaemia, heart failure, shock. Renin converts Angiotensinogen to Angiotensin I ACE converts AI to AII AII releases Aldosterone from adrenal gland Aldosterone acts in proximal tubule resorbs sodium, excretes potassium Controls urine SODIUM excretion RAA Response to Dehydration: RAA Response to Dehydration Dehydration Reduced Renal Perfusion Vasocontriction Renal Sodium resorption Renin release Euvolaemia Angiotensin I Production Aldosterone release Angiotensin II Production Incr Plasma osmolality, ADH, thirst ACEI Low urine sodium Renal Water & Sodium Handling: Renal Water & Sodium Handling Active sodium Passive water Sodium only (no water) Makes dilute urine Water: ADH-sensitive Sodium: 25 mol/d Water: 150 L/d Sodium: 100-200 mmol/d Water: 1-2 L/d Sodium: Aldosterone-sensitive Additional Mechanisms: Additional Mechanisms Thirst Responds to high osmolality and low volume Powerful but slow regulator Natrurietic Peptides Atrial (ANP, atrium); Brain (BNP, ventricle) Respond to stretch (over filling) Causes renal sodium and water loss Blocks RAA, causes vasodilation Markers of heart failure, HT Pathology: Pathology Sodium and Water balance: Sodium and Water balance In normals: Sodium in = sodium out Water in = water out With changes: Systems try to correct changes eg dehydration -> water retention With defects in systems: other mechanisms try and correct defect eg DI, thirst can correct body interior Clinical Derangements: Clinical Derangements Water Too much, too little, just right Sodium Too much, too little just right Combination leads to sodium concentration Sodium - Clinical Effects: Sodium - Clinical Effects Hypernatraemia - draws water out of cells Hyponatraemia - water drawn into cells Main effects on brain!! >160 twitching, siezures, coma >150 weakness, lethargy <130 nausea, drowsiness <120 vomiting, confusion <110 convulsions, coma Depends on rate of change and other factors Hyponatraemia: Hyponatraemia Hyponatraemia: Important Diagnoses: Hyponatraemia: Important Diagnoses Diuretics Renal Failure Addison’s disease Hypothyroidism Liver failure Heart Failure SIADH Artefacts Hyponatraemia diagnosis: Hyponatraemia diagnosis Hyponatraemia Measure plasma osmolality Normal Drip-arm Pseudohyponatraemia: - Hyperlipidaemia - Hyperproteinaemia Decreased True Hyponatraemia Increased Hypertonic Hyponatraemia: - Hyperglycaemia - Hyperglycinaemia (post TURP) Measure Urine Sodium and osmolality, state of hydration Urine sodium >20 mmol/L Urine sodium <20 mmol/L Exclude common drugs, eg diuretics Hyponatraemia diagnosis: Hyponatraemia diagnosis Hyponatraemia Measure plasma osmolality Normal Drip-arm Pseudohyponatraemia: - Hyperlipidaemia - Hyperproteinaemia Decreased True Hyponatraemia Increased Hypertonic Hyponatraemia: - Hyperglycaemia - Hyperglycinaemia (post TURP) Measure Urine Sodium and osmolality, state of hydration Urine sodium >20 mmol/L Urine sodium <20 mmol/L Exclude common drugs, eg diuretics Drugs and Hyponatraemia: Drugs and Hyponatraemia Diuretics (sodium loss) Eg thiazides, frusemide, indapamide Potentiate ADH secretion (water retention) barbiturates; narcotics; oral hypoglycaemics; antineoplastics; anticonvulsants, antidepressants miscellaneous (clofibrate, isoprenaline, nicotine derivatives) Potentiate ADH action (water retention) Chlorpropamide, paracetamol, indomethacin Hyponatraemia diagnosis: Hyponatraemia diagnosis Hyponatraemia Measure plasma osmolality Normal Drip-arm Pseudohyponatraemia: - Hyperlipidaemia - Hyperproteinaemia Decreased True Hyponatraemia Increased Hypertonic Hyponatraemia: - Hyperglycaemia - Hyperglycinaemia (post TURP) Measure Urine Sodium and osmolality, state of hydration Urine sodium >20 mmol/L Urine sodium <20 mmol/L Exclude common drugs, eg diuretics Low Sodium and Normal Osmolality: Low Sodium and Normal Osmolality Normal Osmolar gap Drip Arm Glucose high, included in osmolar gap calculation High Osmolar Gap Pseudohyponatraemia High total protein (>100 g/L) High Lipids Triglycerides Lipoprotein X Pseudohyponatraemia: Pseudohyponatraemia Reduced measured sodium (and other analytes) in indirect measurements Caused by increase in non-aqueous components Triglycerides > 30 mmol/L Protein > 100 g/L Sodium molality is normal Sodium molarity is low Normal measured osmolality (high osmolar gap) Normal result in blood gas analyser BODY THINKS SODIUM IS NORMAL Hyperosmolar Hyponatraemia(dilutional hyponatraemia): Hyperosmolar Hyponatraemia (dilutional hyponatraemia) High extracellular osmolality Glucose (normal osmolar gap) Glycine (raised osmolar gap) Occurs after TURP Draws water out of cells With treatment glucose returns into cells Water follows glucose into cells Sodium level increases Sodium rise = glucose(mmol/L)/4 Eg Sodium 125 mmol/L Glucose 40 mmol/L * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * True Hyponatraemia: True Hyponatraemia Low osmolality Normal osmolar gap Further investigation indicated Clinical evaluation of state of hydration Spot urine sample sodium Osmolality Hyponatraemia: further investigation: Hyponatraemia: further investigation Measure Urine sodium and osmolality, determine state of hydration Urine sodium > 20 mmol/L Urine sodium < 20 mmol/L Patient Hypovolaemic Renal losses (UPO>1) - Diuretic therapy - Addisons Disease - Salt-losing nephritis - Proximal RTA Osmotic diuresis (UPO1) - glucose, urea Patient Euvolaemic Chronic water overload - SIADH (U osmo>200) - Hypothyroidism - Cortisol deficiency (UPO>1) Acute Water Overload - Stress, post surgery - Psychogenic polydipsia (UPO<1) Patient Overloaded Renal failure - acute, chronic Hyponatremia: low Urine sodium: Hyponatremia: low Urine sodium Patient Hypovolaemic Extra-renal losses (UPO>1) - vomiting, diarrhoea - skin loss, pancreatitis Patient Oedematous Renal sodium retent’n - cirrhosis, CCF - nephrotic synd. Patient Euvolaemic Fluid depletion and hypotonic replacement SIADH with fluid restriction Measure Urine sodium and osmolality, determine state of hydration Urine sodium > 20 mmol/L Urine sodium < 20 mmol/L Sodium in urine: Sodium in urine Vital investigation for sodium abnormalities Spot urine most useful Normal range: NOT USEFUL Decision point: 20 mmol/L Only when patient has true hyponatraemia Consider effects of salt (RAA) and water (ADH) 24 hour urine In normals reflects daily intake Can be useful for assessing replacement Hyponatraemia: Important Diagnoses: Hyponatraemia: Important Diagnoses Diuretics - History Renal Failure - creatinine Addison’s disease - Cortisol, Synacthen test Hypothyroidism - TFTs Liver failure - LFTs Heart Failure – History, BNP SIADH SIADH: SIADH True Hyponatramia Euvolaemic (slight overload) Urine sodium > 20 mmol/L (RAAS not on) Urine osmolality > 200 (ADH present) No renal, cardiac, liver or adrenal problems Response to water restriction CNS lesions, lung lesions, cancer SIADH: SIADH Increased ADH Water retention in Kidney Urine osmolality high (>200 mosm/kg) Hypervolaemia (not dehydrated) Inhibition of RAAS Hyponatraemia Urine sodium > 20 mmol/L Hypernatraemia: Hypernatraemia Hypernatraemia diagnosis: Hypernatraemia diagnosis “Dehydration until proven otherwise” 1. Exclude artefact (drip arm) 2. Not enough water Not enough in too sick, old, young, restrained; thirst center lesion Too much out DI, GIT, renal 3. Too much salt Iatrogenic, sea water drowning, Conn’s Hypernatraemia: Hypernatraemia Patient Dehydrated U Na > 20 mmol/L Salt ingestion (tablets, sea water, iv hypertonic saline or Na Bicarbonate) Mineralocorticoid excess syndromes (only with inadequate fluid intake) Determine state of hydration and measure urine sodium and osmolality. U Na < 10 mmol/L Inadequate intake (U osmo > 800) - too young, too old, too sick, prevented, oesophageal stricture, thirst centre damage Non-renal water loss (Uosmo > 800) - GI loss, skin loss Diabetes insipidus with inadequate fluid intake (U osmo < 300) U Na > 20 mmol/L Renal Sodium loss - osmotic diuresis (UPO 1) - diuretics with decreased water intake - renal disease Patient Hypervolaemic Patient Euvolaemic U osmo < 800 Diabetes insipidus - central - nephrogenic U osmo > 800 Insensible water losses - lung - skin Polyuria: Polyuria Polyuria: Polyuria Distinguish from urinary frequency Timed collection can be useful High Urine osmo makes polyuria unlikely 2. Consider causes Diabetes mellitus (osmotic) Drugs: Diuretics, lithium Diabetes insipidus (insufficient ADH) Psychogenic polydipsia (depressed ADH) Renal failure (polyuria) Polyuria investigation: Polyuria investigation Urine osmolality >400: not present at time of testing Approx 300: osmotic, eg diabetes, renal <200: Diabetes Insipidus, Psychogenic polydipsia Biochemically indistinguishable Needs water deprivation test Laboratory Knowledge: Laboratory Knowledge Laboratory Type of assay Alternatives (blood gas, osmolality) What drip-arm sample look like Hyponatraemia Interpretation of serum osmolality Pseudohyponatraemia, dilutional hyponatraemia Importance of drugs Requires spot urine Na and osmo “Reference intervals” are not required for urine sodium Hypernatraemia usually dehydration Polyuria Spot urine Cannot separate DI and polydipsia Closing thoughts: Closing thoughts Sodium measurements very common Sodium and water must be considered together Diagnosis of disorders requires both clinical and laboratory investigation Drug history and urine samples are vital www.sydpath.com.au
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Hyponatraemia Hyponatraemia . Addison’s disease; Compulsive water drinking; Treatment with diuretics; Syndrome of inappropriate antidiuresis . A
Title: Electrolytes - A Romp! Author. Last modified by: gjones Created Date: 1/29/1999 2:33:53 AM Document presentation format: On-screen Show Other titles