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
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