2IntroductionThis chapter is largely about the water and electrolytes ( salts )in your plasma and how the body manages to keep you from drying up and blowing away even if you are in the hot Texas sun and without liquid drink.
4General ObjectivesDefine the key termsDiscuss the factors that regulate each of the electrolytesDiscuss the physiological functions and clinical significance of each of the electrolytesDiscuss ISE and Osmometers
5Electrolytes Electrolytes Substances whose molecules dissociate into ions when they are placed in water.CATIONS (+) ANIONS (-)Medically significant / routinely ordered electrolytes include:sodium (Na)potassium (K)chloride (Cl)and CO2 (in its ion form = HCO3- )
6Electrolyte Functions Volume and osmotic regulationMyocardial rhythm and contractilityCofactors in enzyme activationRegulation of ATPase ion pumpsAcid-base balanceBlood coagulationNeuromuscular excitabilityProduction of ATP from glucose
7Electrolytes General dietary requirements Most need to be consumed only in small amounts as utilizedExcessive intake leads to increased excretion via kidneysExcessive loss may result in need for corrective therapyloss due to vomiting / diarrhea; therapy required - IV replacement, Pedilyte, etc.
8ElectrolytesWater (the diluent for all electrolytes) constitutes 40-70% of total body and is distributed:Intracellular – inside cells2/3 of body water (ICW)Extracellular – outside cells1/3 of body waterIntravascular – plasma 93% waterIntrastitial -surrounds the cells in tissue (ISF)
10ElectrolytesIons exist in all of these fluids, but the concentration varies depending on individual ion and compartmentThe body uses active and passive transport principles to keep water and ion concentration in place
11Electrolytes Sodium has a pulling effect on water Na affects extracellular fluids (plasma & interstitial) equally.However, because there is considerably more Na outside cells than inside, the water is pulled out of cells into the extracellular fluid.Na determines osmotic pressure of extracellular fluid.
12ElectrolytesProteins (especially albumin) inside the capillaries strongly pulls/keeps water inside the vascular systemAlbumin provides oncotic pressure.By keeping Na & albumin in their place, the body is able to regulate its hydration.When there is a disturbance in osmolality,the body responds by regulating water intake,not by changing electrolyte balance
13ElectrolytesLaboratory assessment of body hydration is often by determination of osmolality and specific gravity of urine
14Electrolytes Osmolality - Physical property of a solution based on solute concentrationWater concentration is regulated by thirst and urine outputThirst and urine production are regulated by plasma osmolality
15Electrolytes Osmolality - osmolality stimulates two responses that regulate waterHypothalamus stimulates the sensation of thirstPosterior pituitary secrets ADH( ADH increases H2O re-absorption by renal collection ducts )In both cases, plasma water increases
16Electrolytes Osmolality another term: concentration of solute / kg reported as mOsm / kganother term:Osmolarity - mOsm / L - not often used
17Electrolytes Determination 2 methods or principles to determine osmolalityFreezing point depression(the preferred method)Vapor pressure depressionAlso called ‘dewpoint’
18Specimen Collection Serum Urine Plasma not recommended due to osmotically active substances that can be introduced into sampleSamples should be free of particulate matter..no turbid samples, must centrifuge
19Electrolytes Calculated osmolality uses glucose, BUN, & Na values (Plasma Sodium accounts for 90 % of plasma osmolality)Formula:1.86 (Na) + glucose∕18 + BUN∕2.8 = calculated osmolalityOsmolal gap = difference between calculated and determined osmolatityShould be less than units difference(measured – calculated = 10 to 15)
20ElectrolytesIncrease in the difference between measured and calculatedwould indicate presence of osmo active substances such as possibly alcohol - ethanol, methanol, or ethylene glycol or other substance. Osmolality are concerns forInfantsUnconscious patientsElderly
21Electrolytes Decreased osmolality Diabetes insipidus ADH deficiency Because they have little / no water re-absorption, produce 10 – 20 liters of urine per day
22Electrolytes Osmolality normal values Serum – 275-295 mOsm/Kgm 24 hour urine – mOsm/Kgmurine/serum ratio –Osmolal gap < mOsm (depending on author)
23Electrolytes Classifications of ions - by their charge Cations – have a positive charge - in an electrical field, (move toward the cathode)Na+ = most abundant extracellular cationK+ = most abundant intracellular cation
24Electrolytes Anions – have a negative charge - move toward the anode Cl– (1st) most abundant extracellular anionHCO–3 – (bicarbonate) second most abundant extracellular anion
25ElectrolytesPhosphate is sometimes discussed as an electrolyte, sometimes as a mineral.HPO / H2PO-4when body pH is normal, HPO-24 is the usual form 80 % of time)
26Electrolyte Summary cations (+) anions (-) Na 142 K 5 Ca 5 Mg 2 154 mEq/Lanions (-)Cl 105HCOHPO4-2 2SO4-2 1organic acids 6proteins 16154 mEq/L
27Routinely measured electrolytes Sodium –the major cation of extracellular fluid outside cellsMost abundant (90 %) extracellular cationFunctions - recall influence on regulation of body waterOsmotic activity - sodium determines osmotic activity (Main contributor to plasma osmolality)Neuromuscular excitability - extremes in concentration can result in neuromuscular symptoms
28Routinely measured electrolytes Diet - sodium is easily absorbedNa-K ATP-ase Pumppumps Na out and K into cellsWithout this active transport pump, the cells would fill with Na and subsequent osmotic pressure would rupture the cells
29Regulation of Sodium Concentration depends on: intake of water in response to thirstexcretion of water due to blood volume or osmolality changesRenal regulation of sodiumKidneys can conserve or excrete Na+ depending on ECF and blood volumeby aldosteroneand the renin-angiotensin systemthis system will stimulate the adrenal cortex to secrete aldosterone.
30Sodium (Na) Aldosterone From the (adrenal cortex) Functions promote excretion of Kin exchange for reabsorption of Na
32Sodium (Na) Urine testing & calculation: 1st. Because levels are often increased, a dilution of the urine specimen is usually required.Then the result from the instrument (mEq/L or mmol/L) X # L in 24 hr.
33Clinical Features: Sodium Hyponatremia: < 135 mmol/LIncreased Na+ lossAldosterone deficiencyAddison’s disease (hypo-adrenalism, result in ➷ aldosterone)Diabetes mellitusIn acidosis of diabetes, Na is excreted with ketonesPotassium depletionK normally excreted , if none, then NaLoss of gastric contents
34Hyponatremia Increased water retention Dilution of serum/plasma Na+ excretion of > 20 mmol /mEq urine sodium)Renal failureNephrotic syndromeWater imbalanceExcess water intakeChronic condition
35HypernatremiaExcess water loss resulting in dehydration (relative increase)SweatingDiarrheaBurnsDehydration from inadequate water intake, including thirst mechanism problemsDiabetes insipidus(ADH deficiency … H2O loss )
36Hypernatremia Excessive IV therapy comatose diabetics following treatment with insulin. Some Na in the cells is kicked out as it is replaced with potassium.Cushing's syndrome - opposite of Addison’s
37Specimen Collection: Sodium (Na) serum (sl hemolysis is OK, but not gross)heparinized plasmatimed urinesweatGI fluidsliquid feces (would be only time of excessive loss)
38Sodium (Na)Note:Increased lipids or proteins may cause false decrease in results. artifactual/pseudo-hyponatremia
39Sodium (Na) Sodium determination direct measurement Ion-selective (specific) electrodeMembrane composition = lithium aluminum silicate glassSemi-permeable membrane allows sodium ions to cross 300X faster than potassium and is insensitive to hydrogen ions.direct measurementwhere specimen is not dilutedgives the truest resultssystems that dilute the sample give lower results (called dilutional effect)
40Sodium (Na) Flame emission spectrophotometry (flame photometer) Na emits λ 589 nm (yellow)Use internal standard of lithium or cesiumPossible for a dilutional error to occur in some flame photometer systems, but literature does not dwell on it.
41Routinely measured electrolytes Potassium (K)the major cation of intracellular fluidOnly 2 % of potassium is in the plasmaPotassium concentration inside cells is 20 X greater than it is outside.This is maintained by the Na pump, (exchanges 3 Na for 1 K)
42Potassium (K)Function – critically important to the functions of neuromuscular cellsCritical for the control of heart muscle contraction!↑ potassium promotes muscular excitability↓ potassium decreases excitability (paralysis and arrhythmias)
43Potassium (K) Regulation Diet Kidneys easily consumed (bananas etc.) Kidneys - responsible for regulation. Potassium is readily excreted, but gets reabsorbed in the proximal tubule - under the control of ALDOSTERONE
45Hypokalemia Effects Decrease in K concentration neuromuscular weakness & cardiac arrhythmia
46Causes of hypokalemiaExcessive fluid loss ( diarrhea, vomiting, diuretics )↑ Aldosterone promote Na reabsorption … K is excreted in its place (Cushing’s syndrome = hyper aldosterone)Insulin IVs promote rapid cellular potassium uptake
47Causes of hypokalemia Increased plasma pH ( decreased Hydrogen ion ) RBCH+K+K+ moves into RBCs to preserve electrical balance,causing plasma potassium to decrease.( Sodium also shows a slight decrease )
48Hyperkalemia Increased K concentration Causes IV’S or other increased intakeRenal disease – impaired excretionAcidosis (Diabetes mellitus )H+ competes with K+ to get into cells & to be excreted by kidneysDecreased insulin promotes cellular K lossHyperosomolar plasma (from ↑ glucose) pulls H2O and potassium into the plasma
51Potassium (K) Determination Ion-selective electrode (valinomycin membrane)insensitive to H+, & prefers K X over Na+Flame photometry- K λ 766 nm
52Chloride ( Cl - ) Chloride - the major anion of extracellular fluid Chloride moves passively with Na+ or against HCO3- to maintain neutral electrical chargeChloride usually follows Na (if one is abnormal, so is the other)Function - not completely knownbody hydrationosmotic pressureelectrical neutrality & other functions
53Chloride ( Cl - ) Regulation via diet and kidneys In the kidney, Cl is reabsorbed in the renal proximal tubules, along with sodium.Deficiencies of either one limits the reabsorption of the other.
59Chloride ( Cl - ) Mercurimetric titration of Schales and Schales Precipitate protein out - 1 st stepTitrate using solution of mercuryHg Cl- = HgCl2When all chloride is removed, next drop of mercury will complex with diphenylcarbazone indicator to produce violet color = endpointa calculation required to determine amt of Cl present by the amt of Hg used
60Chloride ( Cl - ) Colorimetric Procedure suitable for automation Chloride complexes with mercuric thiocyanateforms a reddish color proportional to amt of Cl in the specimen.
61Chloride ( Cl - ) Sweat chloride – Remember, need fresh sweat to accurately measure true Cl concentration.Testing purpose - to ID cystic fibrosis patients by the increased salt concentration in their sweat.Pilocarpine iontophoresisPilocarpine = the chemical used to stimulate the sweat productionIontophoresis = mild electrical current that simulates sweat production
62Chloride ( Cl - ) CSF chloride NV = mEq/L (higher than serum)Often CSF Cl is decreased when CSF protein is increased, as often occurs in bacterial meningitis.
63bicarbonate ion (HCO3- ) Carbon dioxide/bicarbonate –* the major anion of intracellular fluid2nd most important anion (2nd to Cl)Note: most abundant intra-cellular anion2nd most abundant extra-cellular anion
64bicarbonate ion (HCO3- ) Total plasma CO2 =HCO H2CO3- + CO2HCO3- (carbonate ion) accounts for 90% of total plasma CO2H2CO3- carbonic acid (bicarbonate)
65bicarbonate ion (HCO3- ) Regulation:Bicarbonate is regulated by secretion / reabsorption of the renal tubulesAcidosis : ↓ renal excretionAlkalosis : ↑ renal excretion
66bicarbonate ion (HCO3- ) Kidney regulation requires the enzyme carbonic anhydrase - which is present in renal tubular cells & RBCscarbonic anhydrase carbonic anhydraseReaction: CO2 + H2O ⇋ H2CO3 → H+ + HCO–3
67bicarbonate ion (HCO3- ) CO2 Transport forms8% dissolved in plasmadissolved CO227% carbamino compoundsC02 bound to hemoglobin65% bicarbonate ionHCO carbonate ion
68bicarbonate ion (HCO3- ) Normal valuesTotal Carbon dioxide (venous) mmol/Lincludes bicarb, dissolved & undissociated H2CO3 - carbonic acid (bicarbonate)Bicarbonate ion (HCO3–) – mEq/L
69bicarbonate ion (HCO3- ) Function –CO2 is a waste productcontinuously produced as a result of cell metabolism,the ability of the bicarbonate ion to accept a hydrogen ion makes it an efficient and effective means of buffering body pHdominant buffering system of plasmamakes 95% of the buffering capacity of plasma
70bicarbonate ion (HCO3- ) SignificanceThe bicarbonate ion (HCO–3) is the body's major base substanceDetermining its concentration provides information concerning metabolic acid/base
71bicarbonate ion (HCO3- ) CO2 /bicarb DeterminationSpecimen can be heparinized plasma, arterial whole blood or fresh serum. Anaerobic collection preferred.methodsIon selective electrodesColorimetricCalculated from pH and PCO2 valuesMeasurement of liberated gas
72Electrolyte balanceAnion gap – an estimate of the unmeasured anion concentrations such as sulfate, phosphate, and various organic acids.
73Electrolyte balance Calculations 1. Na - (Cl + CO2 or HCO3-) =NV 8-12 mEq/LOr2. (Na + K) - (Cl + CO2 or HCO3-) NV 7-14 mEq/Lwhich one to use may depend on whether K value is available. Some authors feel that K value is so small and usually varies little, that it is not worth including into the formula.
74Electrolyte balance Causes in normal patients Increased AG – what causes the anion gap?2/3 plasma proteins & 1/3 phosphate& sulfate ions, along with organic acidsIncreased AG –uncontrolled diabetes (due to lactic & keto acids)severe renal disordersDecreased AG -a decrease AG is rare, more often it occurs when one test/instrument error
76ELECTROYTE TOP 10 Osmolality is detected by the Hypothalamus Gland Thirst sensation and secretion of ADH by Posterior Pituitary Gland. ADH increases renal reabsorption of water Blood Volume stimulates Renin - Angiotensin - Aldosterone system. Aldosterone secretion by the Adrenal Cortex stimulates increased renal absorption of sodiumSodium is the main extracellular cation and contributor to plasma osmolalityPotassium is the main intracellular cationPlasma “CO2” = Dissolved CO2 + H2 CO3 + HCO3-Chloride is usually a passive follower of Sodium to maintain electrical chargeSodium and Potassium usually move opposite each otherParathyroid Hormone ( PTH ) secretion increases plasma calcium , increases plasma magnesium and decreases phosphateAcidosis is associated with Potassium ( Alkalosis with Potassium )Most electrolytes are measured by Ion Selective Electrodes ( ISE )