WATER, SODIUM AND POTASSIUM Attila Miseta Tamás Kőszegi Department of Laboratory Medicine, 2016 1
Average daily water intake and output of a normal adult 2
Approximate contributions to plasma osmolality 3
Distribution of water in the body
The Volume and Distribution of Total Body Water (TBW) TBW = ~60% total body mass Extracellular Fluid (ECF) ~2/3 TBW or 40% body mass Interstitial Fluid (~3/4 ECF) 10.5 L H 2 0 capillary endothelium cell membrane Intracellular Fluid (ICF) ~1/3 TBW or 20% body mass 28 L H 2 0 Intravascular Fluid (~1/4 ECF) Plasma = ~3.5 L H 2 0 Adapted from C.A. Burtis, ed., et. al. Tietz Textbook of Clinical Chemistry. 3 rd ed. Philadelphia: WB Saunders Company, 1999, pg 1096. 5
The Clinical Significance of Electrolytes Volume and osmotic regulation Maintaining Acid/Base balance Enzyme cofactors and ATP production Conduction of nerve impulses Second messengers Maintain cardiac contractility and rhythm Plus many others. 6
Electrolytes Electrical Neutrality Component (Cations) Plasma (mmol/l) Component (Anions) Plasma (mmol/l) Na + 142 Cl - 103 K + 5 HCO 3-24 Ca 2+ 2 Protein - 15 Mg 2+ 1 Organic acids - 3 HPO 4 --- 2 SO 4 -- 1 Total Anions 1 Total cations 149 149 Adapted from C.A. Burtis, ed., et. al. Tietz Fundamentals of Clinical Chemistry. 5 th ed. Philadelphia: WB Saunders Company, 2001, pg 725. 7
Change in [Electrolyte] Can Occur By 1.) Increase/Decrease in amount of electrolyte 2.) Increase/Decrease in amount of water Remember Concentration = amount of solute volume of solution 8
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Sodium (Na + ) Key role (s): Regulation: Clinical: plasma osmolality and water balance Thirst Kidney Na + /K + ATPase pumps Na + /H + pumps Blood volume status ADH (saves water) when blood volume or plasma osmolality renin when arteriolar pressure or Na + aldosterone (saves salt) when Na + ( renin) Na disorders = water disorders Hyponatremia Hypernatremia 10
Hyponatremia Sodium and/or Water Symptoms nausea/vomiting generalized weakness mental confusion headache lethargy possible coma if too low Possible causes excessive renal loss of salt (aldosterone deficiency, kidney disease, diuretics) excessive ADH secretion water overload (congestive heart failure, cirrhosis, renal disease) 11
Hyponatraemia Water retention Total sodium normal Serum/urine osmolality Sodium loss, insufficient intake (rare) (gastrointestinal, kidney)
Hypernatremia Sodium and/or Water Symptoms dehydration increased thirst fever tremors altered mental status lethargy seizures coma Possible causes extrarenal loss (diarrhea, skin losses) renal losses (diuretics therapy and water intake) impaired secretion or ability to respond to ADH (diabetes insipidus) excessive water loss hyperaldosteronism 13
Hypernatraemia Loss of water (dehydration) Diabetes insipidus Serum/urine osmolality Excess sodium intake Hyperaldosteronism
Potassium (K+) Key role (s): Regulation: Clinical: Regulate cardiac contraction and rhythm, muscle contraction Kidneys Na + /K + -ATPase pump Acid/Base balance (i.e., K + /H + pumps) Aldosterone results in K + excretion and shift extracellular to intracellular. Hypokalemia Hyperkalemia 15
Potassium balance Major intracellular cation Easily released and reuptaken again (acidosis, catabolism, insulin dependence) 3,7-5,2 mmol/l Not well regulated Daily intake is important! Hyper- hypokalaemia may be lethal! Measurement of whole body potassium
Hypokalemia Potassium and/or Water Symptom weakness fatigue anorexia nausea arrhythmia possible cardiac arrest Possible Causes extra -> intracellular shifts (alkalosis, diuretics) extrarenal losses (excessive diarrhea, vomiting) renal losses (renal disease, polyuria) hyperaldosteronism 17
Hyperkalemia Potassium and/or Water Symptoms muscular weakness tingling numbness confusion cardiac arrhythmias possible cardiac arrest Remember: About 98% K + is intracellular leaving only 2% extracellular. Hence, a K + shift from the ICF to the ECF of only 2% can double the [plasma]. Possible Causes intra -> extracellular shifts (acidosis) renal failure (K + secretion deficiency) adrenal failure (hypoaldosteronism) leukemia pseudohyperkalemia (hemolysis of sample, leukocytosis) 18
Functional K + test Intravenous load test 4h slow infusion, known amount of K Urine collection: excreted K/4h Calculation: balance, deficit, excess
Characteristic ECG changes in hyper- and hypokalaemia. Each sinus discharge produces atrial depolarization (P wave) followed by ventricular depolarization (QRS complex) and ventricular repolarization (T wave). A shallow U wave, of unknown cause, is present in many normal ECGs. 20
Calcium (Ca 2+ ) Key role (s): Regulation: Clinical: primarily resides in bone, muscular contraction, neurotransmission, membrane transport, enzymes, and blood coagulation Kidney (reabsorbed in the proximal tubules) Parathyroid hormone (PTH) Vitamin D active form controls homeostasis Calcitonin exact mechanism not known Hypocalcemia hypoparathyroidism, malabsorption of calcium or Vit. D, renal failure Hypercalcemia hyperparathyroidism, excess Vit. D, tumors Serum Calcium = Ca 2+ ionized (45%) + Ca protein-bound (45%) + Ca complexed to anions (10%) 21
Magnesium (Mg 2+ ) Key role (s): Regulation: Clinical: enzyme cofactor; calcium and bone homeostasis Kidney PTH, serum Mg 2+ aldosterone hypomagnesemia decreased intake (malabsorption, malnutrition), increased loss (renal disease, hyperaldosteronism, hyperparathyroidism) hypermagnesemia usually increased intake of magnesium or renal disease 22
Chloride (Cl - ) Key role (s): Regulation: Clinical: Maintains osmolality, blood volume, electric neutrality kidneys (reabsorbed /w Na + in the proximal tubules), aldosterone Hypochloremia similar causes as hyponatremia, prolonged vomiting, high [bicarbonate] associated metabolic alkalosis Hyperchloremia similar causes as hypernatremia, dehydration, low [bicarbonate] associated with prolonged diarrhea or metabolic acidosis 23
Bicarbonate (HCO 3- ) Key role (s): Regulation: Clinical: determines ph (along with H + ); buffering the blood and maintaining acid/base equilibrium kidneys (reabsorption in the tubules) lungs Acid/Base disorders (another lecture for another time) CO 2 + H 2 O H 2 CO 3 HCO 3- + H + 24
The Importance of the Anion Gap Anion Gap = Na + - (Cl - + HCO 3- ) Normal range = 8-12 mm Anion Gap = unmeasured anions in the sample Clinical significance: diseases relating to increased anions like lactate, acetoacetate, ß-hydroxybutyrate, phosphates, sulfates, etc. 25
Measuring Electrolytes in Human Samples Flame Spectrophotometry Ion-Selective Electrodes (ISE) Other: colorimetric 26
Summary Some of the most important electrolytes measured in a clinical lab include Na +, K +, Cl -, HCO 3-, Mg 2+, and Ca 2+. Electrolytes can give many clues to the causes of patient illness and are measured frequently within the chemistry labs. Ion-selective electrodes are a powerful tools for measuring many different ions. 27
Related exam questions 1. The principles of flame and atomic absorption spectrophotometry and applications in lab diagnostics. 2. Disorders of water and sodium homeostasis. Different disease states due to water and/or sodium deficit or excess. Laboratory tests useful in these disorders. 3. Disorders of potassium balance of the organism. Potassium deficiencies due to administration of diuretics (determination of serum and urinary K levels and/or excretion, renal functional tests) 28