Objectives
Major
Electrolytes
• Discuss the physiologic functions of the major
electrolytes: Na+, K+, Cl- and HCO3• Discuss the role of plasma protein in exerting
oncotic pressure related to tissue edema
Ricki Otten, MT(ASCP)SC
uotten@unmc.edu
• Describe the relative distribution of water and
electrolytes in intracellular and extracellular body
fluids
2
Objectives
Objectives
• Discuss the kidney’s role in maintaining
electrolyte and water balance: RAAS, ADH
• Discuss specimen collection and handling
requirements for plasma electrolytes
• Correlate abnormal plasma electrolyte results to
possible clinical conditions
• Discuss the cause of the apparent difference
seen between plasma and serum potassium
levels
• Determine the anion gap and assess its clinical
usefulness
• Correlate abnormal anion gap values to possible
clinical conditions
• Discuss sources of error in electrolyte
measurement
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4
Major Electrolytes
Major Electrolytes
• Na+, K+, Cl- and HCO3-
• Anions:
– Negatively charged ions
– Migrate towards the anode (positive electrode)
• Exist as ‘free ions’ in solution, capable of
carrying an electrical charge
• Cations:
– Positively charged ions
– Migrate towards the cathode (negative electrode)
• Often classified as
– Major intracellular anion or cation
– Major extracellular anion or cation
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CLS 500 Application and Interpretation of Clinical Laboratory Data
Electrolytes
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Major Electrolytes
Major Electrolytes
• Virtually every metabolic process depends
on the presence of electrolytes
• Body has complex systems for monitoring
and maintaining electrolyte concentrations
in a narrow normal range
• Electrolytes create an ‘electric potential’
• Abnormal electrolytes may be the cause or
consequence of a disorder or disease
process
• Electric potential is needed to do ‘cellular
work’
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Physiologic Functions
Importance of Body Water
• Maintenance of osmotic pressure and
water distribution (water homeostasis)
• Conduction of neuromuscular impulses
• Acid-base maintenance
• Enzyme activation
• Electron transfer
• Water is the solvent for all body processes
– Transports nutrients to cells
– Determines cell volume
– Removes waste products
– Acts as the body’s coolant system
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Total Body Water
Water Homeostasis
• Intracellular (ICF) ~ 2/3 total body water
• Maintenance of normal protein and electrolyte
concentrations controls water distribution in
these compartments
• Extracellular (ECF)
Intravascular ECF (plasma)
Interstitial cell fluid
• Water passes freely
across cell membranes
• Ions and proteins
cannot freely diffuse
across most cell membranes
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CLS 500 Application and Interpretation of Clinical Laboratory Data
Electrolytes
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Osmotic Pressure
Regulation of Osmolarity
• The concentration of proteins and
ions on one side of a membrane
or the other will influence the flow
of water across that membrane
• Osmolarity of ECF is controlled by the
– Kidney
– Renin-angiotensin-aldosterone system
– Hypothalamus (thirst and ADH)
– Atrial natriuretic factor
• Sodium and its related anions
account for ~90% of the osmotic
activity in plasma
(major osmo-regulator)
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Regulation of Osmolarity
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Regulation of Osmolarity
• Thirst sensation
Increases water
content of ECF
(and decreases Na+)
• Antidiuretic hormone
Acts on DCT and
collecting ducts in
kidney to reabsorb
water
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Sodium (Na+)
Regulation of Osmolality
• Aldosterone:
Stimulates sodium
(and H2O) retention
by kidney
(at expense of K+)
• Major cation in ECF (plasma)
• Responsible for
almost ½ the
osmotic strength
of plasma
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CLS 500 Application and Interpretation of Clinical Laboratory Data
Electrolytes
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Sodium (Na+) Regulation
Hyponatremia – Decreased Na+
• Kidneys are the primary regulators of body sodium
and water
• Sodium is freely
filtered by
glomerulus, 70-80%
actively reabsorbed
by PCT
• Increased sodium loss by kidney:
–
–
–
–
Decreased aldosterone production
Diuretics (thiazides)
Ketonuria (sodium is lost with ketones)
Potassium deficiency (Na+ into urine to conserve K+)
• Increased sodium loss by GI tract:
– Prolonged vomiting
– Prolonged diarrhea
• In times of deficit all sodium is reabsorbed by kidney
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Hyponatremia – Decreased Na+
Hyponatremia – Decreased Na+
• Increased water retention (causes dilution of
plasma sodium)
• Water imbalance: excess water intake resulting
in sodium dilution
–
–
–
–
Nephrotic syndrome
Hepatic cirrhosis
Acute and chronic renal failure
Congestive heart failure (CHF)
– Increased ADH production (SIADH) resulting in
body water intoxication
– Defect in ADH regulation: pulmonary disease,
malignancies, CNS disorders, infections, trauma
Loss of protein Æ decreased osmotic pressure Æ edema
Æ low plasma volume Æ ADH Æ fluid retention Æ dilution
• Hyperglycemia - increased glucose forces water
out of the cell into the plasma resulting in a
dilution of sodium
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Hypernatremia – Increased Na+
Hypernatremia – Increased Na+
• Excess loss of water compared to sodium
loss (loss of hypotonic fluid)
• Decreased water intake (dehydration)
– Elderly
– Infants
– Adults with impaired mental status
– Profuse sweating, fever, exposure to heat
– Prolonged diarrhea, vomiting
– Severe burns
• Increased sodium intake or retention
– Diet
– IV infusion
– Increased aldosterone secretion
– Diabetes insipidus with impaired thirst
mechanism (neurogenic or nephrogenic)
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CLS 500 Application and Interpretation of Clinical Laboratory Data
Electrolytes
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Potassium (K+)
Potassium (K+) Regulation
• Major intracellular cation
• Neuromuscular
excitability, heart
contractions, maintain
ICF volume, maintain
H+ concentration
• Na+-K+-ATP-ase pump continually transports K+ into
cells against
concentration gradient
• High intracellular ‘stores’
aid to maintain nearnormal extracellular K+
levels in times of deficit
K+
• 23x higher in RBC
compared to plasma;
higher in tissue cells
K+
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Potassium (K+) Regulation
26
Hypokalemia – Decreased K+
• Kidney response to conserve K+ is not as
immediate and thorough as its response to
conserve Na+
• Decreased dietary intake
• Aldosterone:
when sodium is
retained, K+ (or H+)
is excreted into
urine
• Renal loss
• Increased cellular uptake
– Excess insulin, alkalosis, catecholamines
– Hyperaldosteronism, RTA, magnesium deficiency,
diuretics (thiazides)
• GI loss
– Vomiting, diarrhea, laxative abuse, malabsorption
27
Hyperkalemia – Increased K+
Hyperkalemia – Increased K+
• Intracellular to extracellular shift
• Increased intake
– Dietary
– IV infusion (most common cause in hospitalized patients)
• Increased cellular release
–
–
–
–
–
28
– Metabolic acidosis
– Diabetes mellitus - insulin deficiency, hyperglycemia
• Impaired renal excretion
Tissue damage from crushing injury, trauma
Chemotherapy, massive blood transfusion
Exercise (transient)
Phlebotomy (fist clenching, prolonged use of tourniquet)
Hemolysis
– Acute or chronic renal failure
– Hypoaldosteronism (Na+ lost into urine, K+ retained)
– Addison’s disease
• Some medications – impair K+ entry into cell
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CLS 500 Application and Interpretation of Clinical Laboratory Data
Electrolytes
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Chloride (Cl-)
Chloride (Cl-) Regulation
• Filtered by glomerulus, passively reabsorbed by the
proximal tubules and actively reabsorbed by the
ascending Loop of Henle
• Major anion in ECF
• Most often Cl- ions
shift with Na+
(passive association)
and HCO3- to maintain
electrical neutrality,
osmolality and blood
volume
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Chloride (Cl-) Regulation
32
Chloride (Cl-) Disorders
• Chloride disorders often parallel the causes of
sodium disorders due to passive association
with sodium
• Chloride shift: maintains anion-cation balance
during buffering process in response to cellular
metabolism
• Hypochloremia: associated with high
bicarbonate levels seen in metabolic alkalosis or
compensated respiratory acidosis
• Hyperchloremia: associated with metabolic
acidosis due to excess loss of bicarbonate
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Bicarbonate – HCO3-
Bicarbonate (HCO3-) Regulation
• Filtered by the glomerulus and reabsorbed in the
proximal and distal tubules
• 2nd most abundant
anion in ECF
• Maintenance of
acid/base balance
as the major buffer
ion in the
carbonic acid/bicarbonate
buffer system; major
component (>95%) of
total CO2 (tCO2)
34
• Kidney has the
capacity to reabsorb
all or none of
the filtered HCO3as needed to
maintain acid/base
balance in body
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CLS 500 Application and Interpretation of Clinical Laboratory Data
Electrolytes
85% HCO3-
15% HCO3-
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Decreased Bicarbonate (HCO3-, tCO2)
Increased Bicarbonate (HCO3-, tCO2)
• Metabolic acidosis
• Metabolic alkalosis
– Renal failure
– Renal tubular acidosis (RTA)
– Ketoacidosis
– Lactic acidosis
– Severe vomiting
– Excess ingestion of antacids (alkali)
– Hypokalemia
• Renal compensation for respiratory
acidosis
• Diarrhea
• Renal compensation for respiratory
alkalosis
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Anion Gap
Anion Gap
• Calculated parameter:
Na+ – (Cl- + tCO2)
• Normal anion gap = 7 - 16
• An estimate of the concentration of anions
not normally measured in plasma
• Assessment made on every set of
electrolytes
• Used clinically to detect the presence of
metabolic disorders affecting electrolyte
balance
• Normal anion gap = 7 - 16
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Anion Gap
Cation and Anion Balance
• Cations and anions are always in balance
to maintain electrical neutrality
Measured:
Na+ - (Cl- + tCO2)
142 – (103 + 28) = 11
Unmeasured cations
5
Ca2+
2
Mg2+
+
4
K
Total
11
• The sum of all anions = sum of all cations
Unmeasured anions
Protein
17
Phosphate
1
Sulfate
1
Organic acids 3
Total
22
Anion gap estimates amount of anions
not normally measured = 22 – 11 = 11
Normal = 7 - 16
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CLS 500 Application and Interpretation of Clinical Laboratory Data
Electrolytes
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Low Anion Gap
High Anion Gap
• Decreased unmeasured anions
• Decreased unmeasured cations (results in lower
levels of anions in plasma)
– Hypocalcemia
– Hypomagnesemia
– Hypokalemia
– Hypoalbuminemia
– Hypophosphatemia
AG = Na+ - (Cl- + HCO3-)
• Increased unmeasured anions
–
–
–
–
–
–
Uremia of renal failure (H2PO4-2 and SO4-2)
Ketoacidosis: diabetes mellitus, starvation (organic acids)
Salicylate toxicity (salicylic acid)
Methanol toxicity (formic acid)
Ethylene glycol toxicity (glycolic and oxalic acids)
Lactic acidosis (lactic acid)
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Specimen Requirements
• Increased unmeasured cations
–
–
–
–
Hypercalcemia
Hypermagnesemia
Paraproteins
Drugs (lithium)
• Over estimation of Cl- (presence of bromides)
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Serum or Plasma?
• Serum or plasma collected by venipuncture
• Capillary blood collected by fingerstick
• Arterial blood collected for blood gases
• Values differ slightly between these two
fluids
• Difference is most significant with
potassium
• Anticoagulant:
lithium heparin or ammonium heparin
• Serum K+ > plasma K+
Dependent upon platelet count: platelets
rupture during clotting process
• Plasma or whole blood analysis decreases
turnaround time ~ POCT
45
HCO3- versus
Reference Ranges
Serum Normal
mmol/L
•
•
•
•
(adults)
Sodium
Potassium
Chloride
tCO2
136 – 145
3.4 – 5.0
98 – 107
22 – 29
46
Serum Critical
mmol/L
<115
<2.5
<70
<10
or
or
or
or
>160
>6.5
>120
>40
47
tCO2
• tCO2
– Directly measured on serum/heparinized plasma
– Part of ‘electrolyte’ panel: Na+, K+, Cl-, tCO2
– All forms of CO2 in plasma are measured
• HCO3– Predominant form of CO2 in plasma (>95%)
– Often used interchangeably with tCO2
– Calculated using pH and pCO2 obtained from
arterial blood gas sample
pH = 6.1 + log HCO3pCO2 x 0.03
CLS 500 Application and Interpretation of Clinical Laboratory Data
Electrolytes
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Sources of error
Sources of error
• Micro clot formation due to poor mixing
of sample with heparin at point of blood draw
• Hemolysis: falsely increases K+
• Alcohol on skin surface not dry when blood
draw performed causes hemolysis
• Exposure of sample to room air (loss of CO2)
• Drawing from a line that was not properly
flushed
• Not analyzing sample immediately after
collection (cellular respirations continue,
potential of bicarbonate-chloride shift)
• Drawing from line and first 5cc blood not
discarded
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Sources of error
50
Good Practice
• Drawing above a line
• Good venipuncture technique
• Drawing below a line but from the same vein
as the line
• Always note fluids being infused
• Obtain sample from the opposite arm if
patient has a line
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Laboratory Results: venous
Consider the following:
• 15 year old female, comatose in ER
• Type 1 diabetic for 7 years
• Several episodes of hypoglycemia and
ketoacidosis
• “too busy to take insulin”
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Sodium
Potassium
Chloride
tCO2
Glucose
BUN
Creatinine
TSP
Albumin
AST
LD
Lactate
Osmolality
CLS 500 Application and Interpretation of Clinical Laboratory Data
Electrolytes
134 mmol/L (136-145)
6.0 mmol/L (3.5-5.0)
96 mmol/L (98-107)
11 mmol/L (22-29)
1050 mg/dl (FPG <100)
35 mg/dl
(5-20)
1.8 mg/dl
(<1.1)
6.8 g/dl
(6.5-8.3)
3.3 g/dl
(3.5-5.5)
45 U/L
(0-50)
650 U/L
(100-200)
5 mmol/L
(<2.2)
385 mOsm/L (275-295)
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Laboratory Results: arterial
pH
pO2
pCO2
7.21
85 mmHg
25 mmHg
(7.35-7.45)
(75-100)
(35-45)
HCO3-
??? mmol/L
(22-26)
Laboratory Results: urine
Color
Appearance
Sp gravity
pH
Protein
Bilirubin
Urobilinogen
Glucose
Ketones
Blood
Nitrite
Leuk.esterase
Specimen:
pH = 6.1 + log HCO3
pCO2 x 0.03
amber
hazy
1.030
6.0
1+
negative
1.0 mg/dl
4+
4+
1+
positive
2+
catheterized
5-10 RBC/hpf
25-50 WBC/hpf
5-10 squamous epi/lpf
2-5 transitional epi/hpf
50-100 bacteria/hpf
0-2 hyaline casts/lpf
Budding yeast present
Mucus threads present
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Laboratory Results: venous
• Assess the abnormal test results for
possible causes:
Chemistry panel (venous)
Arterial Blood Gas
Urinalysis
57
Laboratory Results: venous
Sodium
Potassium
Chloride
tCO2
134 mmol/L
6.0 mmol/L
96 mmol/L
11 mmol/L
Sodium
Potassium
Chloride
tCO2
Glucose
BUN
Creatinine
TSP
Albumin
AST
LD
Lactate
Osmolality
134 mmol/L (136-145)
6.0 mmol/L (3.5-5.0)
96 mmol/L (98-107)
11 mmol/L (22-29)
1050 mg/dl (FPG <100)
35 mg/dl
(5-20)
1.8 mg/dl
(<1.1)
6.8 g/dl
(6.5-8.3)
3.3 g/dl
(3.5-5.5)
45 U/L
(0-50)
650 U/L
(100-200)
5 mmol/L
(<2.2)
385 mOsm/L (275-295)
58
Laboratory Results: arterial
(136-145)
(3.5-5.0)
(98-107)
(22-29)
pH
pO2
pCO2
7.21
85 mmHg
25 mmHg
(7.35-7.45)
(75-100)
(35-45)
HCO3-
??? mmol/L
(22-26)
pH = 6.1 + log HCO3
pCO2 x 0.03
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CLS 500 Application and Interpretation of Clinical Laboratory Data
Electrolytes
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Laboratory Results: urine
Color
Appearance
Sp gravity
pH
Protein
Bilirubin
Urobilinogen
Glucose
Ketones
Blood
Nitrite
Leuk.esterase
Specimen:
amber
hazy
1.030
6.0
1+
negative
1.0 mg/dl
4+
4+
1+
positive
2+
catheterized
Diagnosis:
5-10 RBC/hpf
25-50 WBC/hpf
5-10 squamous epi/lpf
2-5 transitional epi/hpf
50-100 bacteria/hpf
0-2 hyaline casts/lpf
Budding yeast present
Mucus threads present
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CLS 500 Application and Interpretation of Clinical Laboratory Data
Electrolytes
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