CHAPTER 15: ELECTROLYTES

Electrolytes- ions capable of carrying an electric charge Classification: 1. Anions- negative charge and move toward the anode 2. Cations- positive charge, migrate toward the cathode Functions: volume and osmotic regulation (sodium, chloride, potassium) myocardial rhythm and contractility (potassium, magnesium,calcium) cofactors in enzyme activation (magnesium, calcium, zinc) regulation of ATPase ion pumps (magnesium) acid-base balance (bicarbonate, potassium, chloride) blood coagulation (calcium, magnesium) neuromuscular excitability (potassium, calcium, magnesium) production and use of ATP from glucose (magnesium, phosphate) WATER 40% to 75% of total body weight values declining with age and obesity women have lower water content than men as a result of higher fat content solvent for all processes in the human body transports nutrients to cells determines cell volume by its transport into and out of cells removes waste products by way of urine bodys coolant by sweating Intracellular Fluid- fluid inside the cells, 2/3 of body water Extracellular Fluid- 1/3 of total body water, subdivided into the intravascular extracellular fluid (plasma) and the interstitial cell fluid that surrounds the cells in the tissue Normal plasma- 93% water, the rest is composed of lipids and proteins Active transport- requires energy to move ions across cellular membranes Diffusion- passive movement of ions across membrane, depends on size, charge of ion and nature of membrane

OSMOLALITY physical property of a solution based on the concentration of solutes (mmoles per kg of solvent, w/w) Freezing point depression & Vapor pressure decrease- basis for routine measurement of Osmolality Osmolarity- reported as milliosmoles per liter parameter to which hypothalamus responds thirst and arginine vasopressin hormone (AVP) secretion- stimulated by the hypothalamus in response to an increased osmolality of blood Thirst- important in mediating fluid intake AVP- secreted by posterior pituitary gland water conserved, osmolality , turns off AVP secretion Clinical Signifance of Osmolality Na+, and its associated anions account for approx. 90% of osmotic activity in plasma osmolality (Na+) regulated by changes in water balance volume- regulated by changes in Na+ balance Normal plasma osmolality: (275295 mOsm/kg of plasma H2O) 1%2% osmolality, fourfold in circulating concentration of AVP 1%2% osmolality, shuts off AVP production AVP- increases reabsorption of water in the Cortical and medullary collecting tubules; has half life of 15-20 mins. Renal water excretion- controls water excess Thirst- controls water deficit/ dehydration Water Load plasma osmolality, AVP and thirst are suppressed, vol. of dilute urine excreted (10-20 L daily) Water Deficit plasma osmolality, AVP & thirst are activated Thirst- major defense against hyperosmolality and hypernatremia

Hypernatremia- common in infants, unconscious patients or anyone who is unable to either drink or ask for water Regulation of Blood Volume Essential to maintain blood pressure & ensure good perfusion to all tissue and organs 1. Renin is secreted due to renal blood flow 2. Renin converts angiotensin I to angiotensin II 3. Angiotensin II causes vasoconstriction 4. Blood pressure and aldosterone 5. Retention of Na+ & water that accompanies Na+ Factors affecting blood vol.: 1. Atrial natriuretic peptide (ANP) 2. Volume receptors independent of osmolality 3. Glomerular filtration rate 4. Increased plasma Na+ Polydipsia- excessive H2O intake Determination of Osmolality Specimen Serum or urine Discussion Osmolality, freezing pt temp and vapor pressure Turbid serum and urine samples should be centrifuged before analysis Osmometers- that operate by freezing point depression are standardized using NaCl ref. solns. Osmolal gap- difference bet. the measured and calculated osmolality Indirectly indicates presence of osmotically active substances other than Na+, urea, glucose, ethanol, methanol, ethylene glycol, lactate, or Bhydroxybutyrate THE ELECTROLYTES SODIUM Most abundant cation in ECF (90%) Normal plasma osmolality is 295mmol/L, w/ 270mmol/L being the result of Na+ and anions Much larger conc. Inside the cells ATPase ion pumps- prevent equilibrium from occurring; moves 3 Na+ ions out and 2 K+ ions into the cell K+ - major intracellular cation Regulation 3 processes:

1. Intake of H2O in response to thirst 2. Excretion of H2O 3. Blood vol. status 60% to 75% of filtered Na+ is reabsorbed in the proximal tubule, some in the loop and distal tubule Clinical Applications Hyponatremia- serum/plasma level <135mmol/L; one of the most common electrolyte disorders May be caused by Na+ loss, water retention, water imbalance Urine Na+ > 20mmol/day acute/ chronic renal failure Urine Na+ <20mmol/day- nephritic syndrome, hepatic cirrhosis Defect in AVP assoc. w/ pulmonary disease, malignancies, CNS disorders, infections or trauma Pseudohyponatremia- Na+ is measured using indirect ion-selective electrodes (ISEs) in a patient who is hyperproteinemic or hyperlipidemic, seen w/ in vitro analysis Indirect ISE- dilutes the sample prior to analysis, result of plasma/serum water displacement Symptoms of Hyponatremia: 125 and 7130 mmol/L- gastrointestinal Below 125 mmol/L- neuropsychiatric symptoms including nausea and vomiting, muscular weakness, headache, lethargy, and ataxia Below 120 mmol/L for 48 hours or less (acute hyponatremia)- medical emergency Treatment of Hyponatremia: fluid restriction and providing hypertonic saline and/or other pharmacologic agents correcting it too rapidly- cerbral myelinolysis correcting it too slowly- cerebral edema Conivaptan- blocks the action of AVP in the collecting ducts of nephron, not effective for hypovolemic hyponatremia Euvolemic hypernatremia- assoc. w/ SIADH, hypothyroidism, adrenal insufficiency Hypervolemic hyponatremia- assoc. w/ liver cirrhosis w/ ascites, CHF, overhydrated postoperative patients

Hypernatremia- excess loss of H2O relative to Na+ loss, decreased water intake, or increased Na intake or retention; less commonly seen in hospitalize patients Loss of hypotonic fluid may occur either by the kidney or through profuse sweating, diarrhea, or severe burns Chronic hypernatremia in alert patientsindicative of hypothalamic disease, w/ defect in the osmoreceptors Symptoms of Hypernatremia: altered mental status, lethargy, irritability, restlessness, seizures, muscle twitching, hyperreflexes, fever, nausea/vomiting, difficult respiration, and increased thirst Serum Na >160mmol/L assoc. w/ 60-75% mortality rate Treatment of Hypernatremia: should be corrected gradually rapid correction- induce cerebral edema and death, maximal rate should be 0.5 mmol/L per hr Determination of Sodium Specimen Serum, urine, plasma (w/ lithium heparin, ammonium heparin, lithium oxalate), whole blood w/ analyzers, sweat hemolysis- not significant 24 hr collection- specimen of choice for urine Na analyses Method flame emission spectrophotometry (FES), atomic absorption spectrophotometry (AAS) Chemical methods- outdated due to large sample vol., lack of precision ISE- most routinely done, uses 2 electrodes: reference electrode (constant potential), measuring electrode Types of ISE: 1. Direct- undiluted sample react w/ ISE, measures plasma water only, more accurate 2. Indirect- diluted sample Source of error in ISE- protein buildup POTASSIUM Major intracellular cation, 20x greater inside than outside of cell Only 2% of total K circulates in plasma Major effect on contraction of skeleteal and cardiac muscles

Plasma K resting membrane potential, net difference Lower than normal difference increases cell excitability, muscle weakness Excess K is secreted in urine Funtions: 1. Regulation of neuromuscular excitability 2. Contraction of heart 3. ICF volume 4. H+ concentration Hyperkalemia- lack of muscle excitability, paralysis, fatal cardiac, arrhythmia, Hypokalemia- decreases cell excitability,arrhythmia, paralysis Regulation Kidneys are important in K balance Distal nephron- principal determinant of urinary K excretion Factors affecting K Distribution: 1. K loss- hypoxia, hypomagnesemia, digoxin overdoes 2. Insulin promotes acute entry of K into skeletal muscle & liver 3. Catecholamines: Epinephrine- promote cellular entry Propranolol- impairs cellular entry ECF Exercise K is released from cells Cellular breakdown- releases K into the

Clinical Applications Hypokalemia- plasma K conc. Thiazide diuretics- most common cause Symptoms of Hypokalemia: Weakness, fatigue, constipation, paralysis, increased risk of arrhythmia Treatment of hypokalemia: Oral KCl replacement of K Intravenous replacement Food high in K content (nuts, cereals, bananas) Hyperkalemia- usually have an underlying disorder, impairment of urinary K excretion Therapeutic K admin.- most common cause Symptoms of hyperkalemia:

 Muscle weakness, tingling, numbness, mental confusion, cardiac arrhythmia Treatment of hyperkalemia: Ca 2+ provides immediate but short-lived protection to the myocardium sodium bicarbonate, glucose, or insulin, may also be administered hemodialysis Collection of Samples Causes of Artifactual Hyperkalemia: 1. coagulation 2. long tourniquet application 3. storage in ice 4. hemolysis- most common Specimen Serum, plasma, urine heparin- anticoagulant of choice Method ISE- uses valinomycin membrane CHLORIDE major extracellular anion maintains osmolality, blood vol., electric neutrality completely absorbed in the GI tract excess is secreted in urine, sweat excessive sweating- stimulates aldosterone secretion Chloride shift- maintains electroneutrality Hyperchloremia- excess loss of HCO3 as a result of GI losses, RTA, or metabolic acidosis Hypochloremia- excessive loss of Cl from prolonged vomiting, diabetic ketoacidosis, aldosterone deficiency, or salt losing renal diseases such as pyelonephritis Specimen Serum, Plasma (lithium heparinanticoagulant of choice), whole blood w/ analyzers, 24hr urine, sweat Methods ISE most common, uses ion-exchange membrane amperometric-coulometric titration- uses silver ions mercurimetric titration, and colorimetry BICARBONATE

2nd most abundant anion in ECF Composes the largest fraction of total CO2 Major component of the buffering system in the blood Regulation 85% is reabsorbed in proximal tubules 15% in distal tubules Clinical Application Acid-base imbalances cause changes in HCO3 and CO2 levels HCO3 metabolic acidosis Metabolic alkalosis- severe vomiting, hypokalemia, excessive alkali intake Determination of Carbon Dioxide Specimen Venous serum, plasma (sample is capped until examination to prevent CO2 escapes) Method ISE- uses acid reagent enzymatic method MAGNESIUM 4th most abundant cation 2nd most abundant intracellular ion Average human body contains 1 mole of Mg 53% of Mg2 is found in bone, 46% in muscle and other organs and soft tissue, and >1% in serum and red blood cells Essential cofactor of more than 300 enzymes Regulation Sources- raw nuts, dry cereal, and hard drinking water,etc. Henles loop is the major renal regulatory site Parathyroid hormone- increases renal reabsorption of Mg Aldosterone, thyroxine- increases renal excretion of Mg Hypomagnesemia- mostly observed in ICU or those receiving diuretic therapy/ digitalis therapy Symptoms of Hypomagnesemia: cardiovascular, neuromuscular, psychiatric, and metabolic abnormalities Treatment of Hypomagnesemia:

 oral intake using magnesium lactate, magnesium oxide, or magnesium chloride or an antacid w/ Mg2 severely ill patients, an MgSO4 solution is given parenterally Hypermagnesemia- less frequently than hypomagnesemia renal failure- most common cause dehydration- causes pseudohypermagnesemia Symptoms of hypermagnesemia: most frequent- cardiovascular, dermatologic, GI, neurologic, neuromuscular, metabolic, and hemostatic abnormalities moderate- hypotension, bradycardia, skin flushing, increased skin temperature, nausea, vomiting, and lethargy life-threatening- electrocardiogram changes, heart block, asystole, sedation, coma, respiratory depression or arrest, and paralysis treatment of hypermagnesemia: discontinue the source of Mg2 hemodialysis diuretic, IV fluid Specimen Nonhemolyzed serum, lithium heparin plasma, 24 hr urine acidified w/ HCl oxalate, citrate, EDTA-not acceptable Methods Colorimetric: Calmagite method- reddish-violet complex Formazen dye- colored complex Methylthymol blue- colored complex AAS- reference method for measuring Mg CALCIUM Essential for myocardial contraction Decreased ionized Ca impairs mycordial function, may cause neuromuscular irritability (tetany-irregular muscle spasm) Regulation PTH, vit. D, calcitonin- regulates serum Ca PTH secretion stimulated- ionized Ca PTH- activates bone resorption, increases tubular reabsorption of Ca, stimulates renal prod. Of vitamin D 25-hydroxycholecalciferol- inactive form of vitamin D

1,25-dihydroxycholecalciferol- active form of Vit. D Calcitonin- from the medullary cells of thyroid gland, secreted when Ca conc. Distribution 99% is part of bone, 1% in blood & ECF Hypocalcemia- frequent cause is hypomagnesemia- for it inhibits glandular secretion of PTH, impairs PTH action, causes vit.D resistance Pseudohypoparathyroidism- rare hereditary disorder in w/c PTH target tissue response is decreased blood-ionized Ca concentrations in neonates are high at birth and then decline Symptoms of hypocalcemia: Neuromuscular irritability- parasethesia, muscle cramps, tetany, seizures cardiac irregularities- arrhythmia, heart block Treatment of hypocalcemia: Oral or parenteral Ca Vitamin D Hypercalcemia- main cause is primary hyperparathyroidism (excess secretion of PTH) 2nd cause- malignancy Thiazide diuretics Symptoms of hypercalcemia: Neurologic- mild drowsiness/weakness, depression, lethargy, coma GI- constipation, nausea, vomiting, anorexia, peptic ulcer renal symptoms- nephrolithiasis and nephrocalcinosis Treatment of hypercalcemia: estrogen replacement therapy Parathyroidectomy may be necessary in some hyperparathyroidic patients Salt and water intake Biphosphanates- main drug Specimen Serum, lithium heparin plasma w/o venous stasis, urine acidified w/ 6mol/L of HCl No liquid heparin should be used Methods ortho-cresolphthalein complexone (CPC)uses 8-hydroxyquinoline to prevent Mg interference

arsenzo III dye

can be reduced to molybdenym blue-stable blue chromophore LACTATE by-product of an emergency mechanism that produces a small amount of ATP when oxygen delivery is severely diminished pyruvate-normal end product of glucose metabolism conversion of pyruvate to lactate is activated when a deficiency of oxygen leads to an accumulation of excess NADH citric acid cycle- produces 38 moles of ATP accumulation of excess lactate- indicator of oxygen deprivation Regulation oxygen delivery lactate conc. Liver- major organ in lactate removal Gluconeogenesis- lactate to glucose Clinical applications Lactic acidosis: 1. Type A- assoc. w/ hypoxic conditions (shock, myocardial infarction, severe congestive heart failure, pulmonary edema, or severe blood loss) 2. Type 2- metabolic origin (DM, severe infection, leukemia, liver or renal disease, toxins (ethanol, methanol, salicylate poisoning) Specimen Tourniquet- causes venous stasis, increases lactate levels Heparinized blood on ice, plasma must be quickly separated Iodoacetate, fluoride- satisfactory additives Methods Lactate-sensitive indicator of inadequate tissue oxygenation indwelling catheters that measure blood flow, pulse oximeters, base-excess determinations, and measurements of oxygen consumption enzymatic method- uses lactate oxidase, peroxidase *Kindly check the tables found in the book (very useful). Also, Anion Gap is not included here (sorry). This is just a summary. Feel free to read the book for more elaborate explanations. Goodluck! MERRY CHRISTMAS!

PHOSPHATE predominant intracellular anion Important in biochemical processes ATP, creatine phostphate, phosphoenolpyruvate- most impt. Reservoirs of biochemical energy Transcellular shift- major cause of hypophosphatemia, increased shift of phosphate into the cell Regulation Absorbed in the intestine from dietary sources, released from cells into blood, lost from bone PTH- most important factor, lowers blood conc by increasing renal excretion Vitamin D- increases phosphate absorption in intestine, reabsorption in kidney Growth hormone- increases phosphate Distribution Mostly organic phosphate 80% in bone, 20% in soft tissue, 1% serum/plasma Hypophosphatemia- increased incidence in patients w/: diabetic ketoacidosis, chronic obstructive pulmonary disease (COPD), asthma, malignancy, longterm treatment with total parenteral nutrition, inflammatory bowel disease, anorexia nervosa, and alcoholism, sepsis Other causes- hyperparathyroidism, vitamin D deficiency or antacid use Hyperphosphatemia- high risk w/ acute or chronic renal failure Neonates are susceptible- from cows milk, laxative severe infections, intensive exercise, neoplastic disorders, or intravascular hemolysis, lymphoblastic leukemia Specimen Serum, lithium heparin plasma,urine 24 hr hemolysis- should be avoided phosphate levels- high in morning, low in evening Methods mostly involves formation of ammonium phosphomolybdate complex read at 340nm