Chemistry General and Basic Panels: The Laboratory Diagnosis of Fluid and Electrolyte Disorders Sally E. Self, MD Objectives: I. To understand the biochemistry and physiology of water and electrolyte homeostasis. To understand the four major syndromes of electrolyte abnormalities: hypernatremia; hyponatremia; hyperkalemia; hypokalemia. To understand the use of serum/plasma vs whole blood to optimize turnaround time (TAT) for electrolytes. To understand the use of chemistry panels to optimize test ordering and reduce patient costs. To understand the artifactual changes in electrolytes. Biochemistry, pathophysiology and laboratory diagnosis of fluid and electrolyte disorders. A. B. Definition of electrolytes: small molecular weight cations and anions of body fluids and tissues Na+, K+, Cl-, HCO3-, Ca2+, HPO42-, SO42Concentration in blood (Figure 1): 1. Sodium: 137 145 mMol/L 2. Potassium: 3.6 5.0 mMol/L 3. Chloride: 98 107 mMol/L 4. Carbon dioxide (HCO3-): 22 30 mMol/L Sodium (Na+) 1. Major cation of blood; responsible for approximately one-half osmolality of plasma. 2. Daily intake greatly exceeds daily requirements. 3. Excess lost thru kidney, gut, and skin. 4. Central role in maintaining osmotic pressure in extracellular fluid compartment; Figure 1 sodium regulates, along with anti-diuretic hormone and the colloid oncotic pressure, the distribution of water.
C.
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General Chemistry Regulation of sodium homeostasis in blood: a. Adrenal and kidney (Figure 2): 1) Aldosterone secreted by the adrenal cortex: reabsorbs Na+ in distal tubule and increases serum sodium; cortisol (adrenal cortex) has a mild aldosteronelike effect. b. Cardiovascular dynamics: affect sodium concentration thru excretion or retention of water; mediated by glomerular filtration rate Figure 2 (GFR). c. Water balance: 1) Refer to section F. Fluid Balance Hypernatremia a. Na+ > 145 mMol/L b. Serum osmolality >290 mOsm/Kg c. Causes: 1) Profuse sweating with heat-exhaustion; dehydration. 2) Water loss due to vomiting, diarrhea, diuresis. 3) Excess mineralocorticoids: distal nephron retention of sodium; excretion of potassium. a) Conns Syndrome aldosteronoma of adrenal. b) Cushings Syndrome (excess cortisol production); cortisol has a low-grade aldosterone effect . c) Congenital adrenal hyperplasia: 11-B hydroxylase deficiency with elevated 11-deoxycorticosterone (DOC), a potent mineralocorticoid giving salt retention and hypertension. d. Diabetes insipidus: AVP insufficiency after brain injury or posterior pituitary damage central type; renal tubular insensitivity to AVPnephrogenic type. e. Hypertonic saline therapy. f. Clinical: hypernatremia leads to intracerebral dehydration with confusion, coma, death.
6.
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General Chemistry Hyponatremia a. Na+ < 137 mMol/L b. Serum osmolality < 280 mOsm/Kg c. Types / Causes: 1) Depletional hyponatremia a) Osmotic diuresis secondary to diabetes mellitus, hypercalcuria, diuretic drugs b) Renal loss due to: o Chronic renal disease. Decreased nephrons receive an increased solute load resulting in osmotic diuresis. o Renal tubular damage aminoglycoside damage and distal nephron damage. o Addisons Disease decreased aldosterone leads to increased urinary excretion of sodium and decreased serum sodium. 2) Dilutional hyponatremia a) Cardiac failure decreased cardiac output leads to decreased renal perfusion and increased water retention (proportionally greater than sodium retention). b) Hypoalbuminemia secondary to liver disease, malnutrition, nephrotic syndrome, etc., leads to decreased oncotic pressure and edema and, in turn, to decreased effective circulating plasma volume. This activates thirst and AVP secretion, which leads to excessive water intake/retention, and finally to hyponatremia. c) Excess hypotonic fluid intake, especially in chronic renal disease. 3) Syndrome inappropriate ADH secretion (SIADH) a) Hyponatremia with hypertonic urine. b) Causes include malignancy (ectopic ADH production), CNS disorders and drugs. 4) Congenital adrenal hyperplasia: 21-hydroxylase deficiency Salt-Losers. a) Decreased cortisol, DOC, aldosterone. b) Na+ < 137 mMol/L; K+ > 5.0 mMol/L c) Vomiting, dehydration, weight loss, shock, death if untreated 1st weeks of life. d. Clinical: hyponatremia leads to intracerebral edema, nausea, malaise, headache, lethargy, seizures, coma, death.
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General Chemistry
Potassium (K+) (Figure 3) 1. Major intracellular cation; high concentration in red blood cells. 2. Excess excreted in urine; GI fluids have high concentration of K+. 3. Central role in neuromuscular function thru participation in membrane electrochemical gradients. Figure 3 4. Regulation of potassium homeostasis in blood: a. Adrenal and kidney: Mineralocorticosteroids (Aldosterone): secrete K+ in distal tubule; lower serum potassium. Cortisol has a lesser effect. b. Pancreas: Insulin causes intracellular K+ shift as glucose enters cells; lowers serum K+. c. Acid-base balance acidosis causes extracellular potassium shift, raising serum K+ to maintain electroneutrality, as H+ ions move into the cell. 5. Hyperkalemia a. K+ >5.0 mMol/L b. Etiology: 1) Renal failure decreased renal excretion 2) Addisons Disease hypoaldosteronism and hypocortisolism lead to increased serum K+ and decreased Na+. 3) Acidosis shift of K+ to extra-cellular space as H+ moves into cells. 4) Hemolysis; rhabdomyolosis. 5) Excess IV fluid treatment c. Clinical cardio-toxicity, muscle weakness and paralysis. 6. Hypokalemia a. K+ <3.5mMol/L Etiology: b. 1) Mineralocorticoid or glucocorticoid excess: a) Conns Syndrome (aldosteronoma):elevated serum aldosterone causes decreased serum K+ due to increased urinary secretion of K+; increased serum Na+. b) Cushings Syndrome: elevated serum cortisol gives an aldosterone-like effect with mild hypokalemia. 2) Diuretics - impaired renal reabsorption of filtered K+ (i.e., thiazides). 3) GI loss especially diarrhea. 4) Hyperglycemia osmotic diuresis. 5) Starvation - dietary requirement up to 150 mMol/day; mechanism: uncertain. 6) Insulin therapy potassium enters cells. 7) IV treatment with potassium poor fluids. page 117
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c. E.
General Chemistry 8) Alkalosis extracellular shift of H to compensate; intracellular shift of K+. Mechanisms: partially to maintain electroneutrality; other factors. Clinical: muscle weakness and irritability, tachycardia and conduction defects.
+
F.
Chloride (Cl-) 1. Major anion of blood 2. Homeostasis: Chloride follows sodium and water; chloride / bicarbonate exchange occurs in the intestines and kidneys. 3. Blood concentration of Cl- usually goes in opposite direction of HCO3- in acid-base disorders. 4. Important in calculation of anion gap and in fluid/electrolyte therapy protocols. Fluid balance (Figure 4) 1. Water intake a. Controlled by hypothalamic osmoreceptor which stimulates thirst mechanism. 2. Water excretion a. Arginine vasopressin (AVP) = anti-diuretic hormone (ADH); synthesized in hypothalamus; secreted by posterior pituitary; AVP secretion controlled by hypothalamic osmostat in response to serum osmolality. b. AVP acts on renal collecting Figure 4 ducts to reabsorb water. c. Regulation of water reabsorption and excretion, serum osmolality, and serum sodium concentration are interconnected by the hypothalamic osmostat and AVP secretion. d. Disturbed water homeostasis often results in major changes in serum sodium concentration. 3. Fluid excess a. Most common cause in hospitalized patient is iatrogenic: excess H2O given in IV solutions. 4. Fluid depletion a. Most common causes include diarrhea; vomiting; dehydration (i.e., excess sweating in summer); burns; etc.
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Sally E. Self, MD II. The use of Chemistry Panels 1.
General Chemistry
2. 3. 4. 5. 6. III.
Chemistry panels are multiple chemistry tests grouped as a single panel or profile and include the following: a. Basic metabolic profile (BMP) 1) Na+ 2) K+ 3) Cl4) HCO35) Glu (Glucose) 6) UN (Urea Nitrogen) 7) Creat (Creatinine) 8) Ca2+ (Ionized Calcium) b. Comprehensive metabolic profile (CMP) 1) Na+ 2) K+ 3) Cl4) Glu (Glucose) 5) UN (Urea Nitrogen) 6) Creat (Creatinine) 7) Ca2+ (Ionized Calcium) 8) T Prot (Total Protein) 9) Alb (Albumin) 10) T Bili (Total Bilirubin) 11) AST (Aspartate Aminotransferase) 12) ALP (Alkaline Phosphatase) Both the BMP and CMP include electrolytes. The BMP includes tests of organ function (kidney) and related disorders which may lead to electrolyte imbalance. The CMP provides for a more comprehensive laboratory evaluation of organ dysfunction. The use of panels eliminates the need to check off individual tests on a test request card. The patient charge for panels is less than the same tests ordered individually.
Measurement in blood fluids A. B. C. Serum (red top tube) or plasma (green top tube heparinized) or whole blood (green top tube). Serum (30 min: centrifuge to result in Fast Flow Lab for STAT; ~ 15 min. for plasma). Whole blood (3 min. on blood gas analyzers in OR and NNICU lab); all electrolytes performed on surgery patients and many performed on intensive care patients use arterial whole blood; in an emergency, can use venous whole blood for electrolytes and simple chemistries. Disadvantages of whole blood: arterial sample, unless venous whole blood sample is used (not to be used for blood gases).
D. IV.
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Sally E. Self, MD General Chemistry A. Hyperkalemia 1. Caused by traumatic venipuncture. 2. Caused by tissue fluid contamination during heel and finger sticks. 3. Caused by thrombocytosis. B. Pseudohyponatremia 1. A laboratory phenomena caused by markedly elevated triglycerides and/or chylomicrons. 2. No longer a problem with microultracentrifuging of lipemic specimen, the use of ion selective electrodes and serum dilution prior to Na+ analysis. V. Questions: A. B. C. D. E. F. References: Harrisons Textbook of Medicine: 15th Edition. Fauci et al (Eds). McGraw-Hill, New York Chapter 49; Fluid and Electrolyte Disturbances, [The Gold Standard]. Niederhuber, Fundamentals of Surgery. Appleton and Lange, Stanford CT 1998. Chapter 19; Fluids, Electrolytes and Acid-Base Balance. pp 201 210 [Outstanding & Short; Seen Thru Surgical Eyes]. 4th Edition. Griffin and Ojeda (Eds). Textbook of Endocrine Physiology: Oxford University Press, New York 2000. [General Reference; Paperback; short; readable] Brenner and Rectors, The Kidney: 6th Edition. Brenner (Ed.), W.B. Saunders, Philadelphia 2000. Chapter 10; Control of Renal Potassium Excretion, pp 417 454. Chapter 20; Pathophysiology of Water Metabolism, pp 866 924. Chapter 22; Disorders of Potassium Balance, pp 998 1035. [Definitive; Unsurpassed; Unique illustrations] How is fluid hemostasis normally regulated? What are electrolytes? What are the major regulators of Na+ and K+ concentration in blood? What are the major electrolyte syndromes in terms of laboratory values, etiology, pathogenesis and clinical effects? What is a Strategy for effective use of test profiles? What are the advantages / disadvantages of plasma or serum vs whole blood for electrolyte assays?
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