chem - electrolytes

electrolytes are essential - what processes do they partake in?

• volume & osmotic regulations → Na, Cl, K

• myocardial rhythm and contractility → K, Mg, Ca

• co-factors in enzyme activation → Mg, Ca, Zn

• regulation of ATPase ion pumps → Mg

• acid-base balance → HCO3, K, Cl

• blood coagulation → Ca, Mg

• neuromuscular excitability → K, Ca, Mg

• production and use of ATP from glucose → Mg, PO4

water

• avg water content varies from 40-75% of total body weight

  • values decline w age and especially obesity

  • women have lower average as a result of higher fat content

• water distribution

  • 67% intracellular fluid

  • 33% extracellular fluid

    • 25% interstitial

    • 8% plasma

• normal plasma - 93% water

  • remaining occupied by lipids and proteins

water and ions

• concentrations of ions within cells and in plasma are maintained by:

  • active transport

    • requires energy to move ions across cellular membranes

    • intracellular K+ and plasma Na+ requires energy from breakdown of ATP by ATP-ase dependent ion pumps

  • diffusion

    • passive movement of ions across a membrane

    • depends on size and charge od ion and nature of membrane through which it is passing

    • rate of diffusion may be altered by physiological and hormonal processes

H2O gain vs loss sources

• H2O gain

  • drink: 1200 ml

  • food: 1100 ml

  • O2: 300 ml

• H2O loss

  • lungs: 700 ml

  • persp.: 300 ml

  • sweat: 100 ml

  • feces: 100 ml

  • urine: 1400 ml

• normally GAINS = LOSSES

electrolytes

• electrolytes are ions capable of carrying an electrical charge

  • anions: negatively (=) charged

  • cations: positively (+) charged

• intracellular ions

  • potassium (K+)

  • magnesium (Mg 2+)

  • phosphate (PO4 -)

• extracellular ions

  • sodium (Na+)

  • chloride (Cl -)

  • bicarbonate (HCO3 -)

electrolyte distribution of extracellular fluid (ECF)

• extracellular cations

  • Mg 2+ → 2 mEq/L

  • Ca 2+ → 5 mEq/L

  • K+ → 5 mEq/L

  • Na+ → 140 mEq/L

• extracellular anions

  • SO4-

  • HPO4-

  • org. acid → 6 mEq/L

  • protein → 15 mEq/L

  • HCO3- → 25 mEq/L

  • Cl- → 105 mEq/L

electrolyte distribution of intracellular fluid (ICF)

• intracellular cations

  • Na+ → 10 mEq/L

  • Mg 2+ → 35 mEq/L

  • K+ → 160 mEq/L

• intracellular anions

  • Cl-

  • HCO3-

  • proteins → 55 mEq/L

  • PO4 -

osmolality

• total solute concentration per kilogram of water

• major osmotic substances in plasma

  • Na+, Cl-, glucose, urea

• regulation: thirst and antidiuretic hormone

  • both stimulated by hypothalamus when increased osmolality

  • dilutes elevated solutes (Na+) and decrease osmolality

  • ADH released from anterior pituitary to increase water reabsorption

osmolality clinical significance

• regulation of osmolality also affects Na+

• 1-2% increase of osmolality causes 4x increase of ADH

  • bloated → due to increase of salt consumption

• water load:

  • excess intake of water → lowers plasma osmolality

    • ADH and thirst is suppressed

    • absence of ADH will increase urine production

    • hypoosmolality and hyponatremia occurs in patient with impaired renal excretion

• water deficit

  • ADH and thirst activated

  • concern for infants, elderly, anyone unable to drink or ask for water

determination of osmolality

• specimen

  • serum or urine (NOT plasma)

  • Na+, Cl-, HCO3-, are major contributors to osmolality

  • turbid samples need to be centrifuged to remove other particles

• methods

  • changes in freezing point and vapor pressure

  • increase in osmolality decreases freezing point temperature and vapor pressure

osmolality - freezing point depression

• osmometers for measured osmolality

  • sample is supercooled to -7C and “seeded” to initiate freezing process

  • when temperature equilibrium is reached → freezing point is measured (mOsm/kg)

• measured osmolality - calculated osmolality = osmol gap

  • can indicate presence of osmotically active substances such as ethanol, methanol, ethylene glycol, isopropanol, lactate or B-hydroxybutyrate

  • confirm/rule out suspected PSEUDOhyponatremia

  • osmol gap: < 10 mOsm/kg (> 15 mOsm/kg - CRITICAL)

calculated osmolality

• because the major contributors to serum osmolality are tightly regulated, the osmolality of serum can be calculated

• calculated osmolality (mOsm/kg H2O) = 1.86 [Na+] + ([glucose]/18) + ([BUN]/2.8)

  • 1.86 is used bcs each sodium ion is balanced by an anion but there is not a perfect dissociation

  • 18 is used bcs the molecular weight of glucose is approx. 180

  • the factor 18 converts mg/dL to mM/L

  • the molecular weight of blood urea nitrogen (BUN) is approx 28; thus, 2.8 is used

sodium regulation

• Aldosterone (increases sodium)

• ADH (water retention; decreases sodium)

• renal absorption and excretion

potassium regulation

• intestinal absorption

• aldosterone (decreases potassium)

• renal absorption

calcium regulation

• parathyroid hormone (increases calcium)

• calcitonin (decreases calcium)

• renal absorption

magnesium regulation

• internal absorption

• renal absorption

chloride regulation

• intestinal absorption

• renal resabsorption

ADH (antidiuretic hormone)

• the higher the osmolality, the more ADH is secreted

  • thirst center stimulated

  • kidneys conserve water

aldosterone

• secreted by adrenal cortex

• causes kidney to retain sodium (water follows salt)

• stimulated by:

  • increased potassium

  • decreased sodium

  • RAS (Renin-Angiotensin System)

atrial natriuretic peptide

• released by distended atrial walls of the heart

• secretion caused by increased pressure/volume

• antagonist to aldosterone

ion selective electrode (ISE)

• a sensor which converts the activity of a specific ion into a voltage which can be measured using a pH meter

• the transport of specific ion from a high concentration to a low concentration through a selective binding within a membrane creates a potential difference

• the potential is measured against a stable reference electrode of constant potential

• ion selective electrode with a membrane allows ion of interest to pass, but excludes the passage of other ions

• internal reference electrode

  • the solution also contains the same ions to the one that is being measured

• electrodes are made of silver wire coated w/ solid silver chloride

sodium (Na+)

• most abundant EXTRACELLULAR cation

  • reference range: 135-145 mmol/L

  • representing 90% of all extracellular cations

• responsible for almost half of osmotic strength in plasma

  • central role in maintaining normal distribution of water and osmotic pressure in extracellular fluid

• also has a role in the maintenance of acid-base balance

  • by the Na+ H+ exchange mechanism in the nephron

• and the excitation of nerve and muscle

control mechanisms o regulating sodium

• intake of water in relationship to plasma osmolality (stimulated or suppressed) and response to thirst

• excretion of water in relationship to blood volume and osmolality → largely affected by release of ADH

• kidneys conserve or excrete sodium depending on aldosterone; increased Na reabsorption and K excretion

sodium - clinical significance

• hyponatremia: < 135 mmol/L

• one of the most common electrolyte disorders in hospitalized patients

• symptoms

  • 125-130: mostly GI

  • <125: more severe neuropsychiatric (muscular weakness, headache, lethargy, ataxia, seizures, coma and respiratory distress)

  • < 120: medical emergency

• treatment is directed at correction of the condition that caused either water loss or sodium loss in excess of water loss. fluid administration and monitoring are required while the underlying cause is treated

hyponatremia causes

• increased sodium loss

  • hypoadrenalism

  • potassium deficiency

  • diuretic use

  • ketonuria

  • salt losing nephropathy

  • prolonged vomiting or diarrhea

• increased water retention dilutional

  • renal failure

  • nephrotic syndrome

  • congestive heart failure (CFH)

• water imbalance

  • excess water intake

  • SIADH (syndrome of inappropriate arginine vasopressin hormone secretion)

  • pseudohyponatremia (ion levels falsely decreased due to high proteins/lipids)

hypernatremia

• defined as a plasma level >145 mmol/L

• symptoms most commonly involve the CNS due to hyperosmolar state:

  • altered mental status, lethargy, irritability, restlessness, seizures, muscle twitching, hyper reflexes, fever, nausea or vomiting, difficult respiration, and increased thirst

• >160 mmol/L is associated w a mortality rate of 60-75%

• treatment is directed at the condition that either caused the water depletion or the sodium retention

• hypernatremia must be corrected gradually either by oral or intravenous infusion of fluids

  • otherwise cerebral edema and death can be induced

causes of hypernatremia

• excess water loss

  • diabetes insipidus (AVP) → kidney not responding to AVP/AVP secretion is impaired

  • renal tubular disorder

  • prolonged diarrhea

  • profuse sweating

• decreased water intake or retention

  • older persons

  • infants and mental impairment - cant drink water on their own nor ask for water

• increased intake or retention

  • hyperaldosteronism

  • sodium bicarb excess

sodium methods

• specimen: serum or plasma

• ISE (ion selective electrode) is the most routinely used method in clinical labs

  • electrode w glass membrane more sensitive to sodium

• ISE uses a semipermeable membrane to develop a potential produced by having different ion concentrations on either side of the membrane

• in this type of system 2 electrodes are used:

  • reference electrode (constant potential)

  • measuring electrode

• the activity of the ion is measured and related to concentration

sodium - caution

• pseudohyponatremia:

  • can occur when Na+ is measured using indirect ISE methods ONLY

  • hyperproteinemia/hyperlipidemia

  • increase of plasma water displacement where ion levels are falsely decreased (Sample is diluted)

  • falsely decreased ionic activity Na - within vitro hemolysis (Na+ released from RBCs)

potassium (K+) reference ranges

• normal: 3.5 - 5.0 mmol/L

• critical values:

  • < 3.0 mmol/L

  • > 6.0 mmol/L

potassium (K+)

• major functions: regulation of neuromuscular excitability, contraction of the heart, ICF volume, and hydrogen ion concentration

• regulation:

  • kidneys

  • PCT reabsorbs nearly all the K+

  • DCT and collecting ducts - K+ excreted in exchange for NA (effects of aldosterone)

• cellular uptake — important when plasma concentration increases

  • Na/K pump inhibition — K+ loss occurs

  • insulin — increases Na/K ATPase activity — promotes acute entry of K+ ions

  • epinephrine — promotes cellular entry of K

potassium (K+) regulation

• exercise

  • K+ is released from the cells during exercise

  • mild to moderate exercise may increase plasma K+ (usually 1 point or less increase)

  • exhaustive exercise may increase plasma K+ by as much as 2-3 mmol/L

  • reversed after several minutes of rest

• more K+ = more vasodilation

  • equals more O2

• forearm exercise during venipuncture can cause erroneously high plasma K concentrations

potassium (K+) - clinical significance

• K+ helps establish the resting membrane potential of cardiac cells

  • lower levels

    • inside cardiac cells becomes hyperpolarized → harder to depolarize (generate electrical impulse)

    • leads to abnormal repolarization and arrhythmias

  • increased levels

    • lack of muscle excitability, slower conduction, decreased excitability → bradycardia, paralysis, risk of cardiac arrest

hypokalemia

• symptoms often become apparent as plasma K decreases below 3 mmol/L

• symptoms:

  • weakness

  • fatigue

  • constipation

• severe symptoms:

  • muscle weakness/paralysis can interfere w/ breathing

  • arrythmia

hypokalemia major causes

• gastrointestinal loss

  • ex: vomiting, diarrhea, excessive laxative use

  • why: K+ is lost directly or through secondary renal loss

• renal loss

  • ex: diuretics, hyperaldosteronism, Cushing syndrome

  • why: increased potassium excretion through urine

• cellular shift

  • ex: alkalosis, excessive insulin

  • why: potassium moves from blood into cells

hyperkalemia

• symptoms of hyperkalemia generally start when levels rise above 5.0

  • muscular effects

    • muscle weakness (above 6/6.5 mmol/L)

    • tingling or numbness

    • decreased neuromuscular function (7-8 mmol/L)

    • severe cases → flaccid paralysis

  • cardiac effects

    • slowed cardiac conduction (above 6/6.5 mmol/L

    • bradycardia

    • ventricular arrythmias

    • cardiac arrest

hyperkalemia major causes

• decreased renal excretion

  • ex: acute or chronic kidney failure

  • why: kidneys cannot adequately eliminate potassium (dialysis needed)

• decreased aldosterone

  • hypoaldosteronism

  • why: less potassium is secreted into the urine

• cellular shift

  • ex: acidosis, insulin deficiency

  • why: potassium may move out of cells

• cellular injury

  • ex: rhabdomyolysis, extensive tissue injury

  • why: intracellular potassium is released

• preanalytical error

  • ex: hemolysis

  • why: falsely increases measured potassium

potassium specimens

• serum, plasma, urine are all acceptable

• avoid HEMOLYSIS

• avoid “pumping” during phlebotomy

• heparin = anticoagulant of choice

• ICE can interfere → promotes release of K form RBCs

• delay of testing:

  • separate serum and cells quickly — RBCs lyse over time (falsely increases)

  • urine samples: collect over 24 hrs to avoid influences of diurnal variation

potassium methods

• ion selective electrode (ISE) is the method of choice

  • VALINOMYCIN MEMBRANE selectively binds K, causing an impedance change that can be correlated to K concentration

  • KCl (potassium chloride) - is the inner electrolyte solution

chloride

• reference range: 98-108 mmol/L

• involved in maintaining osmolality, blood volume, and electric neutrality during gas exchange

  • Na reabsorbed w chloride in PCT

  • chloride ions shift secondarily to a movement of sodium or bicarbonate'

• testing methodology

  • ion selective electrode (ISE) — most common

chloride electroneutrality

• Na+ is reabsorbed along w Cl- in the proximal tubules

• chloride shift

  • occurs during cellular metabolism in the RBC

  • carbon dioxide generated by cellular metabolism within the tissue diffuses out into the RBC

  • within RBC, CO2 forms carbonic acid → readily splits into H+ and bicarb

    • bicarb diffuses out into the plasma

    • Cl- diffuses into the RBC to maintain the electric balance of the cell

chloride disorders

• chloride disorders are often a result of the same causes that disturb Na+

• decreased

  • diabetic ketoacidosis

  • excessive loss of Cl-

    • prolonged vomiting, aldosterone deficiency, or salt-losing renal diseases such as pyelonephritis

  • high bicarb concentrations (Cl- and HCO3- have an inverse relationship)

• increased

  • dehydration, renal tubular acidosis

  • metabolic acidosis — prolonged diarrhea, salicylate intoxication (aspirin)

  • excessive loss of HCO3 ion (inverse relationship) — GI loss, renal tubular acidosis, or metabolic acidosis

• INVERSE RELATIONSHIP WITH HCO3-

chloride specimens

• serum, plasma, urine, whole blood (some analyzers), sweat are all acceptable

  • lithium heparin anticoagulant

• hemolysis does not cause a significant change

• urine should be a 24 hour specimen (due to diurnal variation)

chloride methods

• amperometric-coulometric titration

  • coulometric generation of silver ions generated at a constant rate

  • Cl ions combine w Ag+ (silver ions)

  • when all Cl ions are bound to Ag+; excess or free silver ions are present

  • as Ag+ increases, current stops timer

  • TIME IS PROPRTIONAL TO CL- CONCENTRATION (what is measured)

    • higher Cl- means more time is needed to bind to silver

sweat chloride

• increased chloride concentration in sweat to confirm diagnosis of cystic fibrosis

  • inherited disorder

  • defect in the cystic fibrosis transmembrane conductance regulator protein

    • normally regulates electrolyte transport across epithelial membranes

  • values often seen up to 160 mmol/L, usually diagnosed in childhood w shortened survival

• clinical presentation

  • affects lungs and digestive system

  • chronic obstructive pulmonary disease

  • pancreatic insufficiency

sweat chloride methodology

• gibson & cooke QPIT

  • iontophoresis → collects sweat

    • positive electrode: pilocarpine (cholinergic drug to induce sweat)

    • neg electrode: NaCl-

    • gauze pad on site, seal, and collect sweat for 20-30 minutes

  • remove gauze and titrate Cl in collected sweat

    • need minimum of 100 mg for accuracy

  • alternative to gauze - macroduct collector uses small amt hydraulic pressure

sweat chloride reference intervals

• infants:

  • < 29 mmol/L = CF unlikely

  • 30-59 mmol/L = intermediate (might wanna order other tests to have a definitive answer)

  • > 60 mmol/L = indicative of CF

• beyond infancy:

  • < 39 mmol/L = CF unlikely

  • 40-59 mmol/L = intermediate chance of CF

  • > 60 mmol/L = indicative of CF

bicarbonate (HCO3-)

• reference range: 23-31 mmol/L

• critical values: <10 or >40

• second most abundant extracellular ion

• total CO2 comprises the bicarbonate ion (HCO3-) and dissolved CO2

  • ratio of bicarb to dCO2 is 20:1

• because HCO3- composes the largest fraction (90%), TOTAL CO2 measurement is indicative of bicarb

• major component in the buffering system in the blood (less acidic)

bicarbonate - clinical significance

• increased in metabolic alkalosis

• decreased in renal failure and respiratory acidosis

• specimen = serum or heparinized plasma

  • best if anaerobic

  • often calculated rather than measured

  • ESTIMATED FROM TOTAL CO2

bicarbonate (total CO2)

• in alkalosis, with relative increase in bicarbonate compared to CO2

  • the kidneys increase increase excretion of bicarbonate into the urine, carrying along a cation such as sodium

  • the loss of bicarb helps correct pH

• responses of the body to acidosis

  • increased in the excretion of H+ into the urine

  • bicarbonate reabsorption is virtually complete with 90% reabsorbed in the proximal tubule and the remainder in the distal tubule

magnesium

• second most abundant intracellular ion

• overall regulation is controlled largely by kidney

• reference range: 1.7 - 2.4 mg/dL

  • hypomagnesemia

    • most common in hospitalized patients w diuretic therapy or digoxin therapy + GI disorders

    • associated w glycosuria and tetany

  • hypermagnesemia

    • less frequent

    • due to renal failure or increased Mg in diet

calcium

• specimen - heparin anticoagulant

  • NEVR USE EDTA; it binds all the calcium due to calcium oxalate

• total calcium reference range: 8.6 - 10.6 mg/dL

• hypocalcemia

  • common in critically ill patients - cardiopulmonary insufficiency

• hypercalcemia

  • main cause: hyperparathyroidism (PTH/parathyroid hormone = increased Ca)

• methodology

  • total calcium: arsenzo III dye to form complex w Ca2+

    • free + bound calcium

  • ionized: ISE

ionized Ca

• AKA FREE calcium (more active/ biologically potent)

  • not attached to protein

• concentration proportional to amplitude of heart contraction

  • decreased concentration impairs myocardial function

phosphate

• predominant intracellular ion

• reference range: 2.5 - 5.0 mg/dL

• hypophosphatemia

  • common in hospitalized patients

  • diabetic acidosis

  • total parenteral nutrition

• hyperphosphatemia

  • greatest risk are those w acute/chronic renal failure

• methods

  • formation of ammonium phosphomolybdate complex and reduced to form molybdenum blue which is read between 600-700 nm

lactate

• by product of anaerobic metabolism

• produces small amount of ATP when oxygen delivery is diminished

• increased levels seen indicate tissue hypoxia earlier than pH

• liver is major organ for removing lactate → converts lactate back into glucose (gluconeogenesis)

• clinical application:

  • useful for metabolic monitoring in critically ill patients

  • indicate severity of illness and determine prognosis

electrolytes in urine

• limited diagnostic value

• reference ranges for 24 hr urines

  • sodium: 40 - 220 mmol/24 hr

  • potassium: 25 - 150 mmol/ 24 hrs

  • Na:K ratio: 2:1

• spot or random measurements

  • many variables

• urine Cl- evaluate persistent metabolic acidosis

  • < 10 mmol/L gastric or diuretic

  • > 10 mmol/L renal