ELECTROLYTES

FUNCTIONS Neuropsychiatric (Less than 125, <120)

 Nausea
 Volume and osmotic regulation (Na, CI, K)  Vomiting
 Myocardial rhythm and contractility (K, Mg, Ca)  Lethargy
 Cofactors in enzyme activation (Mg, Ca, Zn)  Seizure
 Regulation of ATPase ion pumps (Mg)  Coma
 Acid-base balance (HCO3, K, CI)  Respiratory depression
 Blood coagulation (Ca, Mg)  Muscular weakness
 Neuromuscular excitability (K, Ca, Mg)  Headache
 Production and use of ATP from glucose (Mg, PO4)  Ataxia
HYPERNATREMIA
SODIUM (Na+)  >142 or >145 mEq/L
SODIUM ION  Less common
 Monovalent cation  Probable cause
 Most abundant cation in the ECF  Excess water loss
 Accounts 90% of all the ECF cations  Decrease water intake
 Large determinant of plasma osmolality  Inc sodium intake or retention
REGULATION Inc water loss
 Intake of water in response to thirst  Profuse sweating
 Excretion of water  Diarrhea
 Blood volume status
↑ sodium intake/ retention
 Primary active transport
 Na-K ATPase pump  Hyperaldosteronism
 Normally, 60-75% of filtered NA is reabsorbed in the Decrease water intake
PCT  Geriatric patients
 Sites of reabsorption: Altered mental status (above 160)
 loop of Henle  Lethargy
 DCT  Irritability
 connecting segment and cortical collecting  Restlessness
tubule: exchanged for K  Seizures
CLINICAL SIGNIFICANCE  Muscle twitching
HYPONATREMIA  Hyper Reflexes
 <136 mEq/L  Difficult respiration
 1 of the most common electrolyte disorders  Increased thirst
 Probable cause  Nausea
 Inc sodium loss
 Inc water retention DETERMINATION OF SODIUM
 Water imbalance 1. Chemical methods
Inc water retention  Albanese Lein Method
 Renal failure - Na+ Zinc uranyl acetate + polyvinyl
 Nephrotic syndrome alcohol = sodium uranyl acetate
 Hepatic cirrhosis  Protein precipitant: TCA
 CHF - Protein precipitant: Uranyl acetate and
Water imbalance mg acetate
 Excess water intake  Magnesium-Uranyl Method
 SIADH 2. FES
 Pseudohyponatremia 3. AAS
↑ sodium loss 4. ISE
 Hypoadrenalism
 K+ deficiency REFERENCE RANGES
 Diuretic use Serum 136-145 mmol/L
 Ketonuria
 Salt-losing nephropathy Urine (24-hour) 40-220 mmol/day, varies with diet
 Prolonged vomiting CSF 136-150 mmol/L
 Diarrhea
 Severe burns
 POTASSIUM (K+)
 Things to note about potassium? 1. Renal Loss
 How does our body regulate them? -Diuretics
 Clinical significance (diseases)  Which do not promote the secretion of K+
 Laboratory diagnosis (principles & methods) (e.g. spironolactone – competitive
antagonist of aldosterone)
POTASSIUM ION - Nephritis
 Major intracellular cation in the body - Renal Tubular Acidosis
 concentration 20 times greater inside the cells  Due to increase accumulation of acid in
than outside the body, more bicarbonate ions will be
 "Housed" within the cell excreted together with K+
REGULATION  Hyperaldosteronism
 Primary active transport  More Na ions will be retained in
 Na-K ATPase pump exchange of K ions
 Cushing Syndrome
 PCT reabsorb nearly all the potassium
 High levels of cortisol by the adrenal
 Secreted into the urine in exchange for sodium cortex
in both the DCT and the collecting ducts  Hypomagnesemia
 Under the influence of aldosterone  Potassium channels are inhibited by
FUNCTIONS magnesium
 Regulation of neuromuscular excitability  Results in increased efflux of intracellular
 Contraction of the heart K
 ICF volume  Cell loses potassium which then is
 Hydrogen ion concentration excreted by the kidneys
 Regulation of neuromuscular excitability 2. Cellular Shift
 Contraction of the heart  Alkalosis
- Elevated K+ decreases the resting  causes a shift of potassium from the
membrane potential of the cell, which plasma and interstitial fluids; perhaps
decreases the net difference between mediated by stimulation of Na+-H
the cell's resting potential and action exchange and a subsequent activation
potential of Na+/K+-ATPase activity
 Insulin Dose
Hydrogen lon Concentration  Decreased Intake
 Low serum K - sodium and H ions move into the  K-rich food: banana, beans, fish,
cell peanut, potatoes, tomatoes, meats, milk
Factors that influence the distribution of potassium Symptoms
between cells and ECF  Can lead to muscle weakness or paralysis,
- Insulin promotes acute entry of K ions which can interfere with breathing
into skeletal muscle and liver by Treatment
increasing Na-K ATPase activity  Oral KCI replacement
 Exercise  V Fluid
- K is released from cells during exercise  Diet
- Increases K by 0.3 - 1.2 mmol/L
- Reversed after several minutes of rest HYPERKALEMIA
1. Decreased Renal Excretion
- Forearm exercise during venipuncture can
 Renal Failure
cause erroneous high plasma K
 Hypoaldosteronism
concentrations
 Addison's disease
 Cellular Breakdown
 Low cortisol and even aldosterone
- Releases K into the ECF
 Adrenal cortex insufficiency
- Severe trauma, tumor lysis syndrome, and
 Diuretics
massive blood transfusions
2. Cellular Shift
 Acidosis
CLINICAL SIGNIFICANCE
 Cellular injury
HYPOKALEMIA
 Chemotherapy
 Can occur with Gl or urinary loss of potassium or
 Leukemia
with increased cellular uptake of potassium
 Hemolysis
 GI Loss
3. Increase Intake
 Vomiting
 Oral or IV potassium replacement
 Diarrhea
4. Artifactual
 Gastric Suction
 Sample Hemolysis
 Intestinal Tumor
 Thrombocytosis
 Malabsorption
 Prolonged tourniquet or excessive fist
 Cancer Therapy
clenching
 Large doses of laxativeS
Collection of specimens & Specimen handling Cardiac irregularities Gl:
 Collection of specimens & Specimen handling  Arrythmia  constipation,
- Use heparin  Heart block nausea,
 Prolonged tourniquet application or fist clenching vomiting,
= increases K+ shift anorexia, peptic
- Proper patient care ulcer disease
 In vitro hemolysis Renal:
 Whole blood samples should be stored at ROOM  Nephrolithiasis
TEMP. and analyzed ASAP  Nephrocalcinosis

Colorimetric Methods
 Lockhead and Purcell Method CHLORIDE (CI)
 Potassium is reacted with sodium cobaltinitrite to CHLORIDE ION
produce sodium potassium cobaltinitrite  major extracellular anion
 With the addition of phenol (color developer), a
blue color is produced and determined PATHOPGYSIOLOGY & REGULATION
spectrophotometrically
 Main source: DIET
 GI absorption
ISE
 Uses valinomycin membrane and KCI as inner
 Kidney filtration and reabsorption in PCT
electrolyte solution  Excess chloride is excreted in the urine and sweat
CALCIUM Ca2+  Excessive sweating stimulate
REGULATION aldosterone secretion → sweat glands
(conserve sodium and chloride)
3 hormones which regulate Ca++ secretion:
 PTH
Electrical Neutrality
 Vitamin D
 Calcitonin  Act as rate-limiting component
 Limits the amount of Na+ reabsorbed in
the kidney by the amount of Cl-
DISTRIBUTION
available
 99% bone
 Chloride shift
 1% circulation (blood) + ECF
 Cl- diffuses into the red blood cell in
 15% → bound to anions
 40% → bound to protein (albumin) exchange of bicarbonate ions and
 45% Free → ionized Ca++ sodium ions
CLINICAL SIGNIFICANCE Hypochloremia Hyperchloremia
Hypocalcemia Hypercalcemia Excess loss of HCO3- as a Excess loss of Cl- as a
result of: result of:
Primary Primary
hypoparathyroidism hyperparathyroidism
 Gl losses  Prolonged
Hypomagnesemia & Hyperthyroidism
 RTA or vomiting
Metabolic  Diabetic
hypermagnesemia
acidosis ketoacidosis
Hypoalbuminemia Benign familial
 Aldosterone
hypocalciuria
deficiency
Acute pancreatitis Malignancy
 Salt-losing
Renal disease Multiple myeloma
nephropathy
Rhabdomyolysis Increase vitamin D (pyelonephritis)
Psedohypoparathyroidism Thiazide diuretics
Prolonged
immobilization Determination
 Specimen: Serum or plasma
Signs and Symptoms  Anticoagulant of choice: lithium heparin
Hypocalcemia Hypercalcemia  Hemolysis does not cause a significant
Neuromuscular Neurologic: change in serum or plasma values
irritability:  Mild drowsiness/  However, with marked hemolysis, levels
 Parasethesia weakness may be decreased as a result of a
 Muscle  Depression dilutional effect
cramps  Lethargy DETERMINATION METHODS
 Tetany  Coma  ISE (ion-exchange membrane to selectively bind
 Seizures Cl-)
 Amperometric-coulometric titration
 Silver ions + chloride = AgCl2
 Excess Ag → endpt. of titration
 Mercurimetric titration
 Colorimetry
Mercurimetric Titration (Schales and Schales Method)
 PFF preparation using tungstic acid as
precipitating agent of protein
 PFF is titrated with standard solution of
mercuric ions (mercuric nitrate) to form a
soluble compound of mercuric chloride which
does not dissociate to mercuric ions
 Excess mercuric ions combine with s-
diphenylcarbazone to form a blue-violet
colored complex
Colorimetric Methods
 Mercuric Thiocyanate (Whitehorn Titration)
Method Specimen is mixed with a solution of
mercuric thiocyanate
 Mercuric chloride - final product
 Free thiocyanate reacts with ferric ions present in
ferric nitrate to form a reddish brown complex of
ferric thiocyanate
REFERENCE RANGES
 Plasma, serum: 98-107 mmol/L
 24-hour urine: 110-250 mmol/24-hour
MAGNESIUM (Mg2+)
 Fourth most abundant cation in the body and
second most abundant intracellular ion
 53% - bone
 46% - muscle and other organs and
soft tissue
 less than 1% - serum and erythrocytes
 Protein-bound (primarily albumin)
 Free or ionized form
 ln complexed with other ions
REGULATION
 Richest source
 Raw nuts, dry cereal, and "hard"
drinking water
 Vegetables, meats, fish, and fruis
 Small intestine may absorb 20-65% of the dietary
magnesium
 Controlled largely by the kidney
 Controlled largely by the kidney
 Nonprotein-bound are filtered by the
glomerulus
 25-30% is reabsorbed by the PCT
 50-60% is reabsorbed in ascending
loop of Henle
 2-5% is reabsorbed in DCT
 Renal threshold: 0.60 -0.85 mmol/L
 Only about 6% of filtered Mg is excreted in the
urine per day
 PTH
 increases the renal reabsorption and
intestinal absorption
 Aldosterone and Thyroxine
 increases the renal excretion of
magnesium
SPECIMENS
 Non hemolyzed serum
 Lithium Heparin Plasma
 Oxalate, EDTA, and citrate will bind with
magnesium
 24-hour urine
 Preferred for analysis because of a
diurnal variation in excretion
 Must be acidified with HCI to avoid
precipitation
Colorimetric Methods
 Calmagite Method
 Formazan Dye Method
 Methylthymol Blue Method
 Atomic Absorption Spectrophotometry
- Reference method
BICARBONATE ION
 Second most abundant anion in the ECF
 Total CO2 HCO3- + H2CO3+ dC02
 More than 90% HCO3- at pH 7.35-7.45
 Thus, total CO2 measurement is
indicative of HCO3-measurement
 Major component of the buffering system in the
blood
In alkalosis
- With a relative increase in bicarbonate ion
compared to carbon dioxide
- Kidneys increase excretion of bicarbonate into
the urine, carrying along a cation (Na+)
- Loss of this ion from the body helps correct pH
In acidosis
- With a relative increase carbon dioxide
- Kidneys increase excretion of hydrogen ion into
the urine
- Bicarbonate ion reabsorption is virtually
complete (90%) in the PCT and the remainder in
the DC
DETERMINATION OF CARBON DIOXIDE
Specimen
 Venous serum or heparinized plasma
 Anaerobic collection
 If the sample is left uncapped before
analysis, CO2 escapes (decrease by 6
mmol/L per hour)
Methods
 ISE
 Uses an acid to convert all the forms of
CO2 to C02 gas and is measured by a
pCO2 electrode
 Enzymatic Method
 Alkalinizes the sample to convert all forms
of CO2 to HC03-
 HCO3- is used to carboxylate PEP in the
presence of PEP carboxylase, which
catalyzes the formation oxaloacetate
 Coupled with NADH and is consumed as
a result of the action of MDH
  The rate of change in absorbance of
NADH is proportional to the
concentration of HCO3-
PHOSPHATE
 Found everywhere in living cells
 Participate in many of the most important
biochemical processes
 Reservoirs of biochemical energy
 ATP, creatine phosphate, and PEP
 2,3-DPG in red blood cells
REGULATION
 Phosphate may be absorbed in the intestine from
dietary sources
 Released from cells into blood and lost from bone
 Hormones/conditions affecting PO4 levels:
 Vitamin D
 Calcitonin
 GH
 acid-base status
 PTH- which overall lowers blood
concentration by increasing renal
excretion
 Vitamin D acts to increase phosphate in the
blood
 Increases both phosphate absorption in the
intestine and phosphate reabsorption in the
kidney
GH
 ↑ secretion or administration, phosphate
concentrations in the blood may increase
because of decreased renal excretion of
phosphate
DISTRIBUTION
 Total Phosphorus
 About 12 mg/dL (3.9 mmol/L)
 3-4 mg/dL inorganic phosphate
 Predominant intracellular anion
 80% is in the bone
 20% in soft tissues
 Less than 1% is active in serum/plasma
DETEREMINATION OF INORGANIC PHOSPHATE
Specimen
 Serum
 Lithium heparin plasma
 Oxalate, citrate, or EDTA can interfere
with the analysis
 Hemolysis should be avoided
 Circulating phosphate levels are
subject
 Highest in late morning and lowest in
the evening
 24-Hour Urine
Method
 Involve the formation of an ammonium
phosphomolybdate complex
 Measured by UV at 340 nm
 Or can be reduced to molybdenum blue, which
is read between 600 and 700 nm
LACTATE
 Is a by-product of an emergency mechanism
that produces a small amount of ATP when
oxygen delivery is severely diminished
 Pyruvate is the normal end product of glucose
metabolism (glycolysis)
 Conversion to lactate is activated when
a deficiency of oxygen leads to an
accumulation of excess NADH
REGULATION
 lactate is a by-product of anaerobic metabolism,
it is not specifically regulated
 As oxygen delivery decreases below a critical
level, blood lactate concentrations rise rapidly
and indicate tissue hypoxia earlier than pH
 Liver is the major for removing lactate by
converting lactate back to glucose by
gluconeogenesis
CLINICAL SIGNIFICANCE
 For metabolic monitoring in critically ill patients,
for indicating the severity of illness, and for
objectively determining patient prognosis
 Type A lactic acidosis
 Associated with hypoxic conditions, such
as shock, MI, severe CHF, pulmonary
edema, or severe blood loss
 Type B lactic acidosis
 Metabolic origin
 Diabetes mellitus
 Severe infection
 Leukemia
 Liver or renal disease
 Toxins (ethanol, methanol, or salicylate
poisoning)
DETERMINATION OF LACTATE
Specimen Handling
 Tourniquet should not be used
 After sample collection, anaerobic glycolysis will
occur
 Heparinized plasma but must be
delivered on ice and the plasma must be
separated quickly
 Fluoride inhibits glycolysis but the specific
method directions must be consulted
 Enzymatic Method
 Uses lactate oxidase to produce
pyruvate and hydrogen peroxide
 Addition of chromogen and catalyzed
by peroxidase to form a colored complex
ANION GAP
 Concentration difference between commonly
measured cations (Na + K) and commonly
measured anions (CI+ HCO3)
 AG=Na+-(CI + HCO3-)
 AG (Na++K+)-(CI- + HCO3-)
 Useful in indicating an increase in one or more of
the unmeasured anions in the serum
 As a form of quality control for the analyzer used
to measure electrolytes
 Consistently abnormal AG in serum from healthy
persons may indicate an instrument problem