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Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist
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Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist

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The objective of this manuscript is to provide a concise introduction to the application of physicochemical acid-base analysis in critical illness. …

The objective of this manuscript is to provide a concise introduction to the application of physicochemical acid-base analysis in critical illness.

Edward Omron MD

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  • 1. 1 Acid-Base Assessment by Physicochemical Analysis: A Primer for the Intensivist Edward M. Omron MD, MPH, FCCP Pulmonary Critical Care Medicine 18525 Sutter Blvd, Suite 180 Morgan Hill, CA 95037 Email:pulmonarydiseases@gmail.com Disclosures: The author of this manuscript has no personal or financial conflicts of interest to disclose with regards to this publication and received no funding from institutional organizations public or private.
  • 2. 2 Abstract The objective of this manuscript is to provide a concise introduction to the application of physicochemical acid-base analysis in critical illness. The hydrogen ion concentration [H+ ] is regulated to approximately 40 nanoEq/liter (pH 7.40) in health but in disease wide fluctuations from this standard physiological state occur. The magnitude and direction of these changes constitute an exquisitely sensitive index of human physiologic stress. The arterial PCO2-plasma bicarbonate system with anion gap calculation is the dominant paradigm for understanding changes in [H+ ]. In complicated critically ill patients with multi-organ dysfunction, the system is unable to explain the pH altering effects of hyperchloremia, hypochloremia, dehydration, water intoxication, hypoalbuminemia, unmeasured anions and crystalloid resuscitation. The anion gap calculation is rendered unreliable by critical illness related hypoalbuminemia and pH changes. Physicochemical analysis integrates the power of the both the Henderson–Hasselbalch equation and anion gap calculation but further expands the dimensions of clinical acid-base assessment from a diagnostic tool to a therapeutic instrument. A complex systems view of acid-base status allows the clinician to appreciate the elegant complexity of acid-base disorders but also to manipulate pH for clinical benefit. An easily grasped, mechanistic physicochemical explanation follows for the common acid-base disorders seen in critical illness with rational treatment approaches. Key Words: acid-base status; strong ion difference; metabolic acidosis; metabolic alkalosis; physicochemical analysis; strong ion gap
  • 3. 3 Introduction The objective of this manuscript is a review of metabolic acid-base disorders by physicochemical analysis after trauma, major surgery, or acute illness. The hydrogen ion (H+ ), tiny though it is, remains unsurpassed in its ability to influence human physiology or to confound the clinician. Why is the assessment of acid-base status so important in the acutely ill and can we, as intensivists, do better? Precise measurement of the change in hydrogen ion concentration [H+ ] and the mechanism of disturbance has been the focus of clinical medicine for the past century (1). The [H+ ] is regulated to approximately 40 nanoEq/liter (pH 7.40) in health but in disease wide fluctuations from this standard physiological state occur. The magnitude and direction of these changes constitute an exquisitely sensitive index of human physiologic stress. Once diagnosed, acid-base abnormalities remain a marker for severity of illness, and correction to standard physiological state remains a strategic endpoint in the acute resuscitation phase of shock, and a cornerstone of treatment in critical illness (2,3). The arterial PCO2-plasma bicarbonate system with anion gap calculation is the dominant paradigm for understanding changes in hydrogen ion concentration [H+ ]. The Henderson–Hasselbalch (HH) equation relates plasma bicarbonate concentration [HCO3] and partial pressure of arterial carbon dioxide (PaCO2) to pH. The anion gap calculation assesses for a discrepancy between measured plasma cations and anions. If this discrepancy exceeds a threshold value, an anion gap metabolic acidosis is present independent of measured pH (4,5). From a diagnostic standpoint in uncomplicated acute illness, the PaCO2-plasma bicarbonate system with anion gap calculation is adequate to diagnose and treat simple
  • 4. 4 acid-base disorders. In complicated critically ill patients with multi-organ dysfunction, the system is unable to explain the pH altering effects of hyperchloremia, hypochloremia, dehydration, water intoxication, hypoalbuminemia, unmeasured anions and crystalloid resuscitation (6-8). The anion gap calculation is rendered unreliable by critical illness related hypoalbuminemia and pH changes (9,10). Physicochemical analysis integrates the power of the both the HH equation and anion gap calculation but further expands the dimensions of clinical acid-base assessment from a diagnostic tool to a therapeutic instrument (11). This analysis allows the clinician to appreciate the elegant complexity of acid-base status but also manipulate pH for clinical benefit. An easily grasped, mechanistic physicochemical explanation follows for the common acid-base disorders seen in critical illness with rational treatment approaches. Plasma pH as a Physicochemical System Analyses of complex physicochemical systems have found wide application in the natural sciences (12,13). The goal of acid-base complex systems analysis is to predict, repair, and control plasma pH. Henderson (14) first introduced blood as a physicochemical system in 1921, which was extended further, by Singer and Hastings (15) in 1948, Stewart (16) in 1978, and more recently by Figge, Rossing, and Fencl (17,18) in 1991. Arterial blood plasma is an open, complex non-linear physicochemical system that determines plasma [H+ ]. Within the plasma compartment, the system is physically and chemically constrained by the laws of conservation of mass, electrical neutrality, and dissociation equilibrium constants. The system is complex because it describes a set of chemical reactions that must me examined and solved simultaneously
  • 5. 5 and not extracted and analyzed separately. For example, the PaCO2-plasma bicarbonate subsystem is a component within the plasma acid-base physicochemical system. The system is open because PaCO2 is in equilibrium with alveolar air and can be manipulated external to the system by changes in minute ventilation. The system is non-linear because the exact solution for [H+ ], a dependent variable in plasma, is a fourth order polynomial equation uniquely determined by three independent variables: strong ion difference (SID), PaCO2, and total concentration of plasma nonvolatile weak acids (AT). In the words of Stewart, “ Independent variable values are imposed on a system from the outside, and are not affected by the equations which govern the system… Dependent variables are internal to the system; their values are determined by the system equations and by the values of the independent variables (19).” Law of Electrical Neutrality in Acid-Base Status A Gamblegram is presented in Figure 1 demonstrating the ionic constituents of human plasma expressed in milliequivalents per liter (mEq/L). Plasma cations and anions are grouped into two main divisions and are equal. The law of electrical neutrality requires that charge balance always be maintained or more precisely: the sum of the cation concentrations equal the sum of the anion concentrations within the plasma compartment. The majority of the ionic constituents of plasma are strong ions because they are fully dissociated, exert no buffering effect, and their concentrations are unaffected by pH changes. The most important plasma strong ions are Na+ , K+ , Ca++ , Mg++ , Cl- , and lactate where Na+ is sodium, K+ is potassium, Ca++ is ionized calcium, Mg++ is magnesium, and Cl- is chloride. The strong ion difference (SID) is a collective unit of charge defined as
  • 6. 6 the net electrical charge difference of the plasma strong cations minus the plasma strong anions in mEq/L ([Na+ ] + [K+ ] + [Ca++ ] + [Mg++ ] – [Cl- ] – [Lactate- ] – [unmeasured strong anions]). The SID at standard physiological state (pH 7.40, PCO2 = 40 mm Hg, and [HCO3] = 24.6 mEq/L) demonstrates a combined positive electrical effect of 39 mEq/L. Electrical neutrality requires that the positive SID (+39 mEq/L) is balanced by an equivalent negative charge from the plasma buffer anions (-39 mEq/L) or the buffer base. The buffer base consists of both the volatile bicarbonate ([HCO3] = - 24.6 mEq/L) and the dissociated components (A- ) of the total nonvolatile weak acid buffers (AT) grouped together ([albumin] + [inorganic phosphate] + [total citrate] = -14.4 mEq/L) within the plasma compartment. The concentrations of the cation H+ and the anion OH- are too low to be illustrated. The total concentration of plasma nonvolatile weak acid buffers (AT) is composed of disassociated (A– ) and undisassociated (HA) components. Normal baseline in plasma is set to [albumin] = 4.4 g/dL, inorganic phosphate (Pi) = 1.15 mmol/L, and citrate = 0.135 mmol/L. The disassociated component (A- ) reflects the net charge (mEq/L) of albumin, inorganic phosphate, and citrate and is derived from the Figge-Fencl quantitative physicochemical model (17,18). Solutions to all clinical examples in this manuscript unless otherwise stated utilize the Figge-Fencl model and were solved by an iterative computer program adapted to Microsoft Excel Visual Basic for Applications 2008. The model can be used to calculate the pH of plasma for any set of values for PaCO2, SID, and AT. The program is available online at http:// www.figge-fencl.org/ (20,21).
  • 7. 7 The SID is central to understanding and treating many of the metabolic acid-base disturbances seen in critical illness. The SID is an independent determinant of plasma pH and the plasma buffer anions. Conversely, the plasma buffer anions are dependent variables and cannot independently change the SID. This simple principle allows both qualitative and quantitative mechanistic exploration of the common metabolic acid-base derangements seen in acute illness. Hyperchloremic Metabolic Acidosis Hyperchloremic metabolic acidosis is a common acid-base disorder seen in critical illness (22,23). High volume normal saline resuscitation, resolution phase of diabetic ketoacidosis, profuse diarrhea, renal tubular acidosis, and acute kidney injury are common causes. In Figure 2 plasma chloride is hypothetically raised 10 mEq/L from standard state to 115 mEq/L over the course of several hours but not long enough for renal compensation. Consequently, the SID is now reduced from 39 to 29 mEq/L. The buffer base in response to the lowered SID and hyperchloremia must contract to -29 mEq/L to maintain charge balance reducing [HCO3] to 15.8 mEq/L resulting in a metabolic acidosis. The SID constrains the charge boundary the buffer base must conform to revealing one of the more controversial aspects of physicochemical analysis: bicarbonate concentration is dependent upon the charge boundary set by the SID. Further, the reduction in bicarbonate only approximates the change in SID because of decrease in the net negative charge of the non-bicarbonate buffer anions (A- ) during acidosis (17). These emergent system effects could not have been deduced otherwise. Bicarbonate remains
  • 8. 8 correlated with PaCO2 and [H+ ] by the Henderson–Hasselbalch equation but the mechanistic change in [HCO3] can only be elucidated by physicochemical analysis. The standard base deficit (-11 mEq/L) closely approximates the increment in plasma chloride concentration. The mechanism of acid generation, loss of positive charge or excess gain in negative charge is readily apparent. All of the organic metabolic acidoses: ketoacidosis (-hydroxybutyrate), lactate, salicylate, methanol (formate), ethylene glycol (glycolate and oxalate)… can be similarly represented as an excess of negatively charged plasma strong organic acid anions. Treatments of the organic acidoses are outside the scope of this discussion (24). The treatment of hyperchloremic metabolic acidosis primarily consists of reducing [Cl- ] and restoring SID to standard state ([Cl- ] = 105 mEq/L, SID = 39 mEq/L), which would restore normal charge balance and acid-base status. If kidney function remains intact, after several hours to days, secondary renal compensation would occur by diminished chloride reabsorption and enhanced excretion. The plasma SID would begin to increase with a concordant increase in pH. Acute kidney injury is the more common scenario in critical illness however, with rapidly evolving coexisting organic and hyperchloremic acid-base emergencies. The ventilatory response to an acute metabolic acidosis is a secondary respiratory alkalosis with increased work of breathing necessitating acute intervention. Acute Interventions for hyperchloremic metabolic acidosis include removing chloride altogether from intravenous fluids (isotonic sodium bicarbonate for both resuscitation and maintenance fluids and sodium acetate for parenteral nutrition), prudent electrolyte replacement (calcium gluconate instead of the chloride, magnesium sulfate instead of
  • 9. 9 chloride, and potassium phosphate instead of the chloride); replacing intravenous piggybacks with D5W instead of normal saline; and hemofiltration with sodium bicarbonate buffers (25,26). An alternative treatment approach would be to increase total plasma strong cation relative to strong anion concentration. The weak base Tris- hydroxymethyl aminomethane (THAM) is a strong cation and administration during acute metabolic acidosis increases strong ion difference and pH (27). Hypochloremic Metabolic Alkalosis Hypochloremic metabolic alkalosis is also commonly seen in critical illness. Common pathologic causes include protracted nausea and vomiting, nasogastric aspiration, and aggressive diuresis with loop diuretics. In Figure 3 plasma chloride is hypothetically decreased by 10 mEq/L from standard state to 95 mEq/L over the course of several hours but not long enough for renal compensation. Consequently, the SID is increased from 39 mEq/L to 49 mEq/L. The buffer base in response to the higher SID and hypochloremia must expand to -49 mEq/L to maintain charge balance increasing [HCO3] to 33.8 mEq/L resulting in a metabolic alkalosis. The increment in [HCO3] only approximates the change in SID because of the increase in the net negative charge of the non-bicarbonate buffer anions (A- ) during alkalosis (17). The standard base excess of +11 mEq/L closely approximates the decrement in [Cl- ]. The mechanism of alkali generation is the excess gain in strong cations or a loss of strong anions relative to standard state. Another mechanism by which a metabolic alkalosis can be generated is by the addition of unmeasured or known strong cations to the plasma compartment (THAM, cationic drugs, magnesium hydroxide, calcium carbonate) (28,29).
  • 10. 10 The differential of metabolic alkalosis is extensive and outside the scope of this manuscript (30). The correction of the acid-base disorder however is straightforward and collapses to restoration of [Cl- ] to standard state under most circumstances in critical illness (31,32). If kidney function remains intact, over the course of hours to days, secondary renal compensation would occur by increased chloride reabsorption and diminished excretion. The plasma SID would begin to decrease with a concordant decrease in pH. In hypovolemic hypochloremic metabolic alkalosis; however, glomerular filtration rate is reduced and renal conservation of sodium takes precedence over chloride reabsorption perpetuating the alkalosis. Fluid loading with normal saline will restore ECF chloride content and correct the volume deficit. Hypochloremic metabolic alkalosis is sometimes misdiagnosed as a “contraction alkalosis” leading to inappropriate fluid loading (9,31,33). Metabolic alkalosis is often associated with hypovolemia, excessive diuretic use, and or dehydration; but can also be seen in euvolemic (mineralocorticoid excess) and hypervolemic states (congestive heart failure). Contraction of the extracellular fluid compartment volume (ECF) or absolute hypovolemia has no significant effects on the independent determinants of plasma acid- base status. ECF volume status should not be diagnosed by electrolyte abnormalities but by prudent physiologic assessment of the cardiac output venous return curve, macrocirculatory impairment (blood pressure, heart rate, orthostatics), and or microcirculatory impairment (lactic acidosis, low SvO2 or ScvO2). In intubated patients with severe chronic obstructive pulmonary disease and chronic hypercapnea, the hypochloremic metabolic alkalosis seen is appropriate compensation for chronic primary respiratory acidosis when arterial pH approximates
  • 11. 11 7.40 and should not be initially corrected. Over ventilation will unmask the alkalosis and exuberant correction may potentially prolong ventilator support (34). In contrast, the ventilatory response to a primary metabolic alkalosis is hypoventilation and hypercapnea, which can potential interfere with spontaneous breathing trials and prolong mechanical ventilatory support (35,36). Replacement of plasma chloride content can be accomplished by providing intravenous 0.9% saline, 0.1 N hydrochloric acid infusion, or supplemental chloride content in electrolyte replacement and parenteral/enteral nutrition. Historically intravenous ammonium chloride and arginine monohydrochloride have been used but potential toxicity precludes routine clinical use (37). Judicious use of acetazolamide is also a useful therapeutic adjunct by increasing renal excretion of serum sodium relative to chloride resulting in a decrease in the SID and increase in plasma chloride (38). Dehydration and Water Intoxication Effects on Acid-Base Status Strong ion difference is affected by changes in plasma free water content with acid- base consequences (9). Water loss from the intracellular compartment defines dehydration and is recognized clinically as euvolaemic hypernatremia. Extracellular fluid volume depletion defines hypovolemia, which has been erroneously associated with dehydration (39). Contraction of the extracellular fluid volume, as stated earlier, has no significant effects on the independent determinants of plasma acid-base status but both conditions may simultaneously occur as in hypovolemic hypernatremia. An absolute free water deficit to the intracellular compartment is quantitatively described as the volume of water that must be added to restore [Na+ ] to standard state
  • 12. 12 conditions (Deficit = 0.6 x Weight (kg) x [(Current Na+ /142) – 1] (40). Dehydration concentrates the plasma sodium and chloride in equal proportions; thus, increasing the plasma SID. The hyperchloremia of dehydration, however, should not be construed as a hyperchloremic acidosis. To prevent misinterpretation of acid-base status, the plasma [Cl- ] should be corrected for the degree of concentration and the chloride excess or deficit calculated. Figure 4 demonstrates the plasma [Na+ ] and [Cl- ] changes with a 3-liter free water deficiency from standard state (40). The hyperchloremia of a 3-liter free water deficiency when corrected for concentration normalizes to standard state [Cl- ] and consequently does not affect the SID or pH ([Cl- ] corrected = [Cl- ] observed x ([Na+ ] normal/[Na+ ] observed) or [Cl- ] corrected = 105 mEq/L = 112 x (142/152)). The chloride excess = 0 mEq/L ([Cl- ] normal – [Cl- ] corrected) objectively quantitates the chloride contribution to the change in SID. The increased SID from dehydration results in a progressive albeit mild concentrational metabolic alkalosis and should not be confused with a “contraction alkalosis”. A “contraction alkalosis” refers to the supposed acid-base effects of extracellular compartment volume depletion (hypovolemia). The treatment of dehydration consists of intravenous water expansion usually 5% dextrose to correct the intracellular fluid deficit. Water gain to the intracellular compartment defines water intoxication and is recognized clinically as euvolemic hyponatremia (41). Water intoxication is quantitatively described as the volume of water that must be removed to restore [Na+ ] to standard state conditions (Excess = 0.6 x Weight (kg) x [(Current Na+ /142) – 1]). The plasma [Na+ ] and [Cl- ] are diluted in equal proportions; thus, decreasing the plasma SID. The hypochloremia of free water excess, however, should not be construed as a
  • 13. 13 hypochloremic metabolic alkalosis. To prevent misinterpretation of acid-base status, the plasma [Cl- ] should be corrected for the degree of dilution and the chloride excess or deficit calculated. The dilutional effects of severe hyperglycemia, nonketotic hyperosmolar state, and mannitol on plasma electrolytes are excluded from this example (42). Figure 5 demonstrates the [Na+ ] and [Cl- ] changes with a 3-liter free water excess from standard state (41). The hypochloremia of water intoxication when corrected for dilution normalizes to standard state [Cl- ] and thus does not affect SID or pH ([Cl- ] corrected = [Cl- ] observed x ([Na+ ] normal/[Na+ ] observed) or [Cl- ] corrected = 105 mEq/L = 98 x (142/132)). The chloride deficit = 0 mEq/L ([Cl- ] normal – [Cl- ] corrected) objectively quantitates the chloride contribution to the change in SID. The decreased SID from water intoxication results in a progressive albeit mild dilutional acidosis (9). Dilutional acidosis should not be confused with the term “dilution acidosis” which refers to the supposed acid-base effects of extracellular compartment volume excess (hypervolemia). Hyperchloremia or hypochloremia do not result in an acidosis or alkalosis unless the corrected chloride is concomitantly increased or decreased relative to standard state (43). The diagnosis and treatment of water intoxication is beyond the scope of this discussion but common ICU interventions include hypertonic saline, water restriction, hyperosmolar enteral feedings, loop diuretics, and vasopressin antagonists. (44). Plasma Non-volatile Weak Acid Effects Total plasma nonvolatile weak acid concentration (AT) is an independent determinant of plasma pH. Albumin and inorganic phosphate are the principal plasma weak acids.
  • 14. 14 Albumin normal concentration ranges from 4 to 4.4 g/dL. Major surgery, trauma, and acute illness result in large fluctuations in albumin concentration and hypoalbuminemia is an independent risk factor for poor outcome (45,46). In the example of hyperchloremic metabolic acidosis with serum albumin = 4.4 g/dL, pH and SBE equals 7.210 and -11 mEq/dL respectively. At serum albumin = 2 g/dL, pH and SBE are improved to 7.338 and -4 mEq/dL respectively, Figure 5. A decrease in plasma albumin by 1 g/dL increases base excess by approximately 3 mEq/L (47). Hypoalbuminemia corrects pH towards standard state in acute illness and appears to be an adaptive, short-term response to metabolic acidosis in critical illness. Mechanistically this is best appreciated by examining the charge balance in Figure 6. The buffer base is delimited by the charge space of the plasma strong ion difference and is equal to the algebraic sum of the individual charged species of serum bicarbonate, albumin, inorganic phosphorus, and citrate concentrations. With the loss of negative charge space from hypoalbuminemia, the serum bicarbonate must expand to maintain charge balance resulting in a mitigating hypoalbuminemic metabolic alkalosis during concurrent metabolic acidosis (48). In other words, the decrease in plasma nonvolatile weak acid concentration is equivalent to gain in serum bicarbonate. Hypoalbuminemia is pervasive in acute illness and major surgery and hypoalbuminemic alkalosis exists to some extent in all critically ill and post-operative patients (43). The mechanism of hypoalbuminemia is likely multifactorial: impaired hepatic synthesis, acute phase protein down-regulation, increased capillary permeability, exudative losses, and expansion of the intravascular volume by crystalloid/colloid
  • 15. 15 resuscitation are all potential mechanisms. Hyperalbuminemia is infrequently encountered in severe dehydration and may present as an increased gap acidosis (49). Hyperphosphatemia may be seen in acute, chronic kidney injury, rhabdomyolysis, tumor lysis syndrome, excessive intake or administration (50). The increased negative charge space forces bicarbonate to contract and generates a metabolic acidosis (51). Treatment options include oral phosphate binders, hemodialysis, and parenteral calcium replacement. Normal concentration of serum inorganic phosphate is 1.15 mmol/L and consequently hypophosphatemia is unable to generate a metabolic alkalosis. Standard Base Excess Dr Sigaard Anderson developed the base excess and deficit concepts in the 1960’s and standard base excess (SBE) remains a powerful quantitative tool in the assessment of critical illness acid-base status (52). It is easily calculated by an arterial blood gas measurement and reduces metabolic acid-base disturbances to a simple, quantitative numerical scale. Standard base excess provides no insight into mechanism but provides the magnitude and direction of a metabolic acid-base disturbance. A positive value indicates an excess of base, whereas a negative value indicates an excess of fixed acid in vivo with respect to the extracellular fluid compartment (ECF). SBE and SID are conceptually related by sharing similar volumes of distribution. The plasma strong ions distribute throughout the entire extracellular fluid compartment and strong ions added to the plasma compartment are diluted by the interstitial fluid strong ions. The distribution, however, of strong ions between the plasma and interstitial fluid compartments is dictated by Gibbs-Donnan Equilibria. Conceptually, standard base
  • 16. 16 excess represents an excess of strong cations in mEq/L and standard base deficit represents an excess of strong anions in mEq/L relative to standard state conditions when AT is normal. Historically, the BE nomograms were determined by in vitro titrations of strong acids and bases to standard state conditions. Total plasma nonvolatile weak acids were assumed to be normal (43,53). Consequently, hypoalbuminemia is registered as a SBE and hyperphosphatemia is registered as a standard base deficit. The problem with SBE is that it does not discriminate between changes in SID or AT. Fortuitously, SBE is a summation function of the changes in both plasma SID and A- or SBE = ΔSID + ΔA- (48). The partitioning of SBE into physicochemical components allows quick recognition of the mitigating effects of hypoalbuminemia in strong ion acidosis and the aggravation of base excess in strong ion alkalosis. The change in SID from standard state conditions is calculated as ΔSID (mEq/L) = SID (measured) – 39. A positive value indicates an excess of base or plasma strong cations, whereas a negative value indicates an excess of fixed acid or plasma strong anions. The nonvolatile plasma weak acid buffer deficit (ΔA- ) reflects alterations in the concentrations of albumin, inorganic phosphate, and citrate from normal baseline consequent to surgery or acute illness. Note that ΔA- is expressed as a positive quantity because a decrement in plasma nonvolatile weak acid content is equal to a gain in base. The calculation of ΔA- is complex and can be found in reference 48. In practice, the ΔA- calculation is unnecessary because this value can be deduced from the difference between ΔSID and SBE. For example, Figure 6 reveals a hyperchloremic strong ion acidosis mitigated by a hypoalbuminemic alkalosis. The SBE = -4 mEq/L, the SID = -10 mEq/L, and the A- =
  • 17. 17 +6 mEq/L (calculated from the Figge-Fencl Model). The SID reflects the magnitude and direction of the strong ion imbalance: 10 mEq/L of excess strong anions. The A- reflects the magnitude of the hypoalbuminemic alkalosis: 6 mEq/L. The algebraic sum of ΔSID + ΔA- equals the SBE which reflects the overall magnitude of the metabolic acid- base disorder relative to the ECF compartment. Classification of Primary Metabolic Acid-Base Disorders In summary, in vivo plasma pH is a function of 3 independent determinants: (1) SID; (2) AT; and (3) PaCO2. Disorders of any of the independent determinants may coexist simultaneously in acute illness. Table 1 reviews the primary classification of metabolic acid-base disturbances. The pH is a function of SID and the difference from 39 mEq/L is a measure of ionic imbalance from standard state (Figure 7). If the SID < 39 mEq/L, an excess of strong anions (i.e. hyperchloremia), organic acids, or free water (water intoxication) is present resulting in a metabolic acidosis. If the SID > 39 mEq/L, a deficiency of strong anions (i.e. hypochloremia), free water (dehydration), or excess of strong cations are present resulting in a metabolic alkalosis. The loss of strong cations in relation to strong anions is associated with an acidosis and the loss of strong anions in relation to strong cations is associated with an alkalosis. Thus, “according to the law of electrical neutrality it is impossible to change the [H+ ] in a solution without simultaneously changing the amount of some anion, or exchanging the [H+ ] with some cation (54). “ Albumin and inorganic phosphate are the principal nonvolatile plasma weak acids. A decreased AT (Hypoalbuminemia) is pervasive in critical illness and generates a
  • 18. 18 metabolic alkalosis. An increased AT (Hyperphosphatemia) is most commonly seen in acute and chronic kidney injury and generates a metabolic acidosis. The Effects of Crystalloid Infusion on Acid-Base Status The intravenous administration of acidic or alkaline crystalloid solutions to correct severe metabolic alkalosis and acidosis respectively is routinely performed in the acutely ill. Physicochemical analysis provides a rational basis for understanding the effects of crystalloid administration on acid-base status (8, 55-57). Theoretically, selective crystalloid infusion can manipulate the SBE in a predictable and quantitative manner. The crystalloid SID is the net electrical charge difference of the infusate strong cations minus the anions. Normal saline, for example, contains 154 mEq/L of sodium and 154 mEq/L of chloride and thus the SID is equal to zero. Isotonic sodium bicarbonate, in contrast, contains 150 mEq/L of sodium and 150 mEq/L of bicarbonate and thus the SID is equal to 150 mEq/L. Infusion of an isotonic crystalloid solution modifies plasma pH by simultaneously altering both SID and AT. For example, normal plasma SID equals 39 mEq/L and when combined with a low SID crystalloid (normal saline SID = 0 mEq/L), the admixture will reduce plasma SID resulting in a strong ion acidosis. In contrast, the SID of sodium bicarbonate (SID = 150 mEq/L) is higher than plasma SID; the admixture will increase plasma SID and result in a strong ion alkalosis. Crystalloid solutions are devoid of AT (albumin, inorganic phosphate, and total citrate) and intravenous administration will reduce plasma weak acids by simple dilution, resulting in a mitigating dilution alkalosis.
  • 19. 19 Plasma metabolic acid-base status will be determined after equilibration and Gibbs- Donnan effect by the plasma SID admixture and diluted AT. If the induced crystalloid strong ion acidosis is exactly balanced by a dilution AT metabolic alkalosis, no significant change in SBE occurs. The crystalloid SID necessary to achieve this ‘‘balance point’’ is equal to standard state actual bicarbonate (24.6 mEq/L). In other words, crystalloid solutions with an ionic composition similar to plasma and SID close to standard state bicarbonate are referred to as balanced solutions (lactated Ringer’s and Hartmann’s solution) and clinically minimize acid-base disturbances when infused. The ‘‘balance point’’ is also useful when using crystalloid solutions to achieve a particular acid-base endpoint. If the infused crystalloid SID is greater than 24.6 mEq/L, metabolic alkalosis will result; if less than 24.6 mEq/L, metabolic acidosis will result. If the crystalloid SID equals 24.6, no change in SBE is observed. Figure 7 demonstrates the potency of various crystalloid solutions as a function of crystalloid SID to induce an acidosis or alkalosis, respectively, from standard state conditions under ideal conditions. These projections are reasonably accurate in surgical patient populations during perioperative fluid replacement with normal saline, lactated Ringer’s, and plasmalyte solutions. High-quality clinical data sets are unfortunately lacking in critically ill populations and more research is needed to define the optimal fluid resuscitation strategy. Anion Gap and Strong Ion Gap In critical illness, unmeasured strong anions may appear (ketone acids, anions of renal failure, and lactate) resulting in a metabolic acidosis and an increased anion gap (ANG).
  • 20. 20 The ANG is a screening tool for unmeasured strong anions and is derived from an abreviated form of the law of electrical neutrality in plasma (Figure 9): Na+ - Cl- – HCO3 = Unmeasured Anions – Unmeasured Cations + A- ≅ 12 ± 4 mEq/L (57). The value of the ANG includes the unmeasured plasma strong cations and anions, and the disassociated component of AT. The simplified charge balance equation ignores potassium, calcium, and magnesium, which become unmeasured cations. During standard state conditions, the entirety of the ANG can be accounted for by the negative charge component of AT (17, 18). An increase in unmeasured strong anions will titrate plasma bicarbonate, generate a metabolic acidosis, and increase the ANG to maintain charge balance. An increased ANG historically has been quite helpful in the differential diagnosis of metabolic acidosis; however, the validity of the calculation is questionable in critical illness. Inspection of the ANG calculation reveals several major sources of error (58-60). Hypoalbuminemia is pervasive in critical illness resulting in a low to normal ANG in the organic acidoses (61). A decrease in albumin by 1 g/dL reduces the ANG by 2.5 mEq/L secondary to the loss of negative charge from the albumin moiety. The disassociated component of AT is reduced in acidemia and increased in alkalemia decreasing and increasing the ANG respectively by titration of the negative charges on the albumin moiety. Figure 2 demonstrates the reduction in the ANG during acidemia from 12 to 11 mEq/L; Figure 3 demonstrates the increase in the ANG during alkalemia from 12 to 13 mEq/L. Figure 6 demonstrates the combined effects of acidemia and hypoalbuminemia on ANG. The ANG is reduced from 12 mEq/L at standard state to 6 mEq/L secondary to loss of charge from both hypoalbuminemia and acidosis with no change in unmeasured
  • 21. 21 anions or cations. A proposed adjusted ANG for hypoalbuminemia (adjusted ANG = observed ANG + 2.5 x ([Normal Albumin] – [Observed Albumin]) has improved sensitivity to detect occult organic acidoses and is in common use (61). In Figure 6, the adjusted ANG corrects to normal (adjusted ANG = 12 mEq/L (6 + 2.5 x (4.4 – 2)). Low ANG can also be seen with an excess of strong cations (hypercalcemia, hypermagnesemia, hyperkalemia, lithium, and THAM) and laboratory error. In physicochemical analysis the appearance of unmeasured strong anions or cations are collectively termed the strong ion gap (SIG) and are codeterminants of the SID (Figure 10). The SIG is similar to the ANG in that both are derived from the law of electrical neutrality but unlike the ANG, the SIG is resistant to changes in pH, PaCO2, and albumin concentration (62). Figures 2, 3, and 6 demonstrate the robustness of the SIG measurement is acidemia, alkalemia and hypoalbuminemia. The SIG is thus a more reliable parameter of unmeasured strong anions than ANG in critical illness. The SIG in health is normally less than 6 mEq/L but the range of abnormal values in critical illness remains undefined in the literature (63). Recent literature has focused on the utility of the SIG as a marker of tissue damage and predictor of mortality in severe sepsis, trauma, and cardiac arrest (64-67). The SIG is calculated as the difference between the SID apparent and effective. The SID apparent (SIDa) is the net electrical charge difference between the commonly measured strong cations minus the strong anions in the plasma: SIDa = Na+ + K+ + Ca++ + Mg++ - Cl- - lactate. The SIDa is normally 42 – 44 mEq/L. For bedside calculations the combined expression (Ca++ + Mg++ ) is replaced by 3 mEq/L. The strong ion difference effective (SIDe) is the net electrical charge difference of the plasma strong cations minus
  • 22. 22 the strong anions including the SIG: Na+ + K+ + Ca++ + Mg++ - Cl- + [SIG]. The SIDe is normally 39 mEq/L. The calculation of the SIG combines both equations: SIG = SIDa – SIDe. For bedside calculations the SIDe is closely approximated by its negatively charged reflection, the plasma buffer base: SIDe ≈ [HCO3] + 2.8 x [albumin g/dL] + 0.6 x [Pi mg/dL] (43). The full Figge-Fencl quantitative physicochemical model can be applied at the bedside with a programmable calculator (20, 21). Illustrative Examples A 50-year-old male presents with end stage liver disease in septic shock. His admission pH = 7.263, PaCO2 = 20.2 mm Hg, [HCO3] HH = 9 mEq/L, SBE = -16 mEq/L, Na+ = 139 mEq/L, K+ = 3.7 mEq/L, Cl- = 117 mEq/L, lactate = 2.9 mEq/L, [albumin] = 2.4 g/dL, Pi = 4.3 mg/dL, the ANG = 13 mEq/L, adjusted ANG = 18 mEq/L, SIDa = 26 mEq/L, SIDe = 18 mEq/L, and the SIG = 8 mEq/L. Conventional analysis reveals a severe metabolic acidosis with respiratory compensation and a normal ANG but elevated adjusted ANG. Physicochemical analysis suggests a marked excess of strong anions within the ECF compartment (Δ SID = -21 mEq/L) with a mitigating hypoalbuminemic alkalosis (ΔA- ) of 5 mEq/L. The SBE = -16 mEq/L or (Δ SID + ΔA- ). The source of the strong anion acidosis is hyperchloremia, unmeasured anions from the SIG, and to a lesser extent lactate. The nature of the SIG and unmeasured anions in acute illness remains elusive although Krebs cycle strong anions have been implicated (68). Therapeutic intervention would require removing chloride altogether from resuscitation and maintenance fluids, initiation of isotonic sodium bicarbonate (SID =
  • 23. 23 150 mEq/L) infusion, changing all IV drips to D5W with acute, early goal directed resuscitation to both macro and microcirculatory endpoints. A physicochemical resuscitation refers to the application of physicochemical analysis to correct acid-base status with early goal directed resuscitation endpoints (8). A physicochemical resuscitation in acute illness is physiologically appealing but remains untested in the literature. A 69 year-old male with acute myelogenous leukemia and acute respiratory distress syndrome day 14 on pressure regulated volume control. His pH = 7.530, PaCO2 = 40 mm Hg, [HCO3] = 33 mEq/L, SBE = 9.8 mEq/L, [Na+ ] = 140 mEq/L, [K+ ] = 2.8 mEq/L, [Cl- ] = 105 mEq/L, [albumin] = 1.1 g/dL, [Pi] = 3.3 mg/dL, ANG = 2 mEq/L, adj ANG = 10.3 mEq/L, SIDe = 38.6 mEq/L, SIDa = 40.8 mEq/L, SIG = 2.2 mEq/L. Conventional analysis reveals a primary metabolic alkalosis. The SIDe is normal and thus ΔSID = 0 mEq/L, the ΔA- = 9.8 mEq/L secondary to the profound hypoalbuminemia, and the SBE (SBE = ΔSID + ΔA- ) can be entirely accounted for by the hypoalbuminemia of critical illness. The patient is euvolemic based on bedside echocardiography. The metabolic alkalosis would have to be corrected to initiate spontaneous breathing trials. Confusion with a “contraction alkalosis” might lead to inappropriate fluid loading and prolongation of mechanical ventilation. The patient received intravenous acetazolamide with normalization of pH the next morning. A 22 year-old male presents with an altered mental status, nausea and vomiting, increased thirst, frequent urination and admission glucose of 241 mg/dL. Serum acetone and urine ketones were positive. His admission pH = 6.985, PaCO2 = 20.5 mm Hg, [HCO3] = 4.8 mEq/L, SBE = -23.9 mEq/L, [Na+ ] = 154 mEq/L, [K+ ] = 4.4 mEq/L, [Cl- ]
  • 24. 24 = 101 mEq/L, lactate = 0.8 mEq/L, Pi = 6.7 mg/dL, [albumin] = 6.1 g/dL, SIDa = 61.1 mEq/L, SIDe = 22.1 mEq/L, SIG = 39 mEq/L, ΔSID = -16.9 mEq/L, ΔA- = -7.0 mEq/L, and ANG = 48 mEq/L. The corrected [Cl- ] for dehydration = 142/154 x 101 = 93 mEq/L. The chloride deficit = 105 – 93 ≈ 12 mEq/L. Conventional analysis reveals a high anion gap metabolic acidosis with a compensatory respiratory alkalosis. Electrolyte profile supports dehydration and bedside echocardiography reveals hypovolemia with preload dependency. Physicochemical analysis reveals a severe strong anion acidosis with a high SIG presumably secondary to ketone bodies from diabetic ketoacidosis (ΔSID = -16.9 mEq/L of excess strong anions). Secondary acidoses emerge from the hyperalbuminemia of dehydration with a smaller component from hyperphosphatemia (ΔA- = -7.0 mEq/L). A chloride deficit of 12 mEq/L reveals a moderate hypochloremic metabolic alkalosis. Fluid resuscitation in diabetic ketoacidosis (DKA) remains contentious in the medical literature and current guidelines continue to recommend 0.9% saline (69,70). Physicochemical analysis clearly reveals that 0.9% saline infusion aggravates a preexisting metabolic acidosis and induces a coexisting hyperchloremic strong ion acidosis (8, 48). Unfortunately, randomized, placebo controlled studies of crystalloid fluid resuscitation in DKA have not been performed and recommendations fall to dogma and practice preference. The author strongly advocates the use of physiologically balanced fluids (lactated Ringer’s and Hartmann’s solution) both during the acute resuscitation and maintenance phases of DKA in adults. Lactated Ringer’s infusion, for example, would correct the ECF volume deficit, minimize crystalloid-induced acid-base changes, provide free water replacement (osmolarity = 275 mOsmol/liter) for
  • 25. 25 dehydration, minimize hyperchloremia, and supplement total body potassium stores slightly. Theoretical Advantage of Physicochemical Acid-Base Analysis The binary separation of acid-base status into pure respiratory and metabolic components forms the foundation of acid-base lore. The Henderson Equation ([H+ ] = 24 x PaCO2/[HCO3]) illustrates the concept. Classical teaching states that the PaCO2 represents the respiratory component and [HCO3] the metabolic component of an acid- base disturbance and both are independent determinants of [H+ ] (71). It was Schwartz and Relman that initially questioned the validity of this concept and began “The Great Trans-Atlantic Acid-Base Debate (72).” “ …it must be recognized that a certain quantity of “metabolic acidosis” normally complicates primary respiratory alkalosis and that a certain quantity of “metabolic alkalosis” normally complicates primary respiratory acidosis, it is apparent that the recognition of abnormal metabolic complications of primary respiratory disturbances becomes extremely difficult (73).” Physicochemical acid-base analysis moves the clinician away from the simplistic binary classification scheme to a systems view of acid-base status. Le Chatelier’s Principle states that if a physicochemical system is exposed to a stress, the system will shift to minimize that stress. For example, hyperchloremia is a recognized as an excess of ECF strong anions resulting in a strong ion metabolic acidosis. Primary repair of the system requires removal of the excess strong anions from the ECF compartment. The physiologic response is to restore standard state conditions: a secondary respiratory
  • 26. 26 alkalosis, intracellular buffering of the ECF compartment acidosis, and diminished chloride reabsorption with enhanced excretion by the kidneys till all excess chloride is removed. The Intensivist can facilitate the restorative process by prudent use of fluids, electrolyte replacement, enteral nutrition, mechanical ventilation, and diuretics. The essence of acid-base systems analysis is to predict, repair, and control plasma pH. Conclusion This manuscript was written exclusively for the critical care physician. Intensivists are broadly trained to diagnose and treat multi-organ dysfunction and I would argue a more appropriate appellation of their skill set is complex systems clinician. Physicochemical analysis and the diagnosis, treatment, and control of acid-base disorders are a natural extension of this skill set. Plasma pH is a subsystem of whole body acid- base balance. ““Whole body acid-base balance,” refers to the set of mechanisms by which the parts of the body, notably the lungs, kidneys, and gastrointestinal tract, control the composition of the circulating blood plasma, so as to keep its [H+ ] generally within the range from 2 x 10-8 to 1 x 10-7 Eq/liter or pH 7.7 to 7.0 (74).” The ultimate therapeutic goal of critical care medicine is restoration of multi-organ standard state conditions after multi-organ dysfunction. Physicochemical analysis with manipulation of fluids, electrolytes, and plasma pH in the acute resuscitative phase of critical illness is a necessary component of this endeavor.
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  • 34. 34 70. Dhatariya KK. Diabetic Ketoacidosis: Saline should be used for fluid replacement rather than Hartmann’s solution. BMJ 2007; 334: 1284-1285. 71. Rose BD. Clinical Physiology of Acid-Base and Electrolyte Disorders (Fifth Edition). New York: McGraw-Hill; 2001: 325-326. 72. Bunker JP. The Great Trans-Atlantic Acid-Base Debate. Anesthesiology 1965; 26: 591- 594. 73. Schwartz WB, Relman AS. A Critique of the Parameters Used in the Evaluation Acid-Base Disorders. “Whole-blood Buffer Base” and “ Standard Bicarbonate” Compared with Blood pH and Plasma Bicarbonate Concentration. N Engl J Med 1963; 268: 1382-1388 74. Stewart PA. How to Understand Acid-Base. A Quantitative Acid-Base Primer for Biology and Medicine. New York, NY: Elsevier; 1981. Chapter 9; p 161.
  • 35. 35 Figure 1: Charge balance at standard physiologic state SID = strong ion difference; SBE = standard base excess; ANG = anion gap; SIG = strong ion gap; A- = dissociated component of AT 20 40 60 80 100 120 140 160 mEq/L Cations Anions Na+ = 142 K+ Ca++ Mg++ Cl- = -105 HCO3 = -24.6 A- = -14.4 0 Buffer Base = -39SID = +39 pH = 7.40 PaCO2 = 40 mm Hg SBE = 0 mEq/L ANG = 12 mEq/L SIG = 5 mEq/L
  • 36. 36 Figure 2: Hyperchloremic strong ion acidosis SID = strong ion difference; SBE = standard base excess; ANG = anion gap; SIG = strong ion gap; A- = dissociated component of AT 20 40 60 80 100 120 140 160 mEq/L Cations Anions Na+ = 142 K+ Ca++ Mg++ Cl- = -115 HCO3 = -15.8 A- = -13.2 0 Buffer Base = -29SID = +29 ( 10) pH = 7.209 PCO2 = 40 mm Hg SBE = -11 mEq/L ANG = 11 mEq/L SIG = 5 mEq/L
  • 37. 37 Figure 3: Hypochloremic strong ion alkalosis SID = strong ion difference; SBE = standard base excess; ANG = anion gap; SIG = strong ion gap; A- = dissociated component of AT 20 40 60 80 100 120 140 160 mEq/L Cations Anions Na+ = 142 K+ Ca++ Mg++ Cl- = -95 HCO3 = -33.8 A- = -15.2 0 Buffer Base = - 49SID = +49 ( 10) pH = 7.54 PCO2 = 40 mm Hg SBE = 11 mEq/L ANG = 13 SIG = 5 mEq/L
  • 38. 38 Figure 4: A concentration strong ion alkalosis: three-liter free water deficit from standard physiologic state (weight = 70 kg and total body water = 0.60). SID = strong ion difference; SBE = standard base excess; ANG = anion gap; SIG = strong ion gap; A- = dissociated component of AT 20 40 60 80 100 120 140 160 mEq/L Cations Anions Na+ = 152 ( 10) K+ Ca++ Mg++ Cl- = 112 ( 7) HCO3 = -27.3 A- = -14.7 0 Buffer Base = -42SID = +42 pH = 7.447 PCO2 = 40 mm Hg SBE = 3 mEq/L ANG = 13 mEq/L SIG = 5 mEq/L
  • 39. 39 Figure 5: A dilution strong ion acidosis: three-liter free water excess from standard physiologic state (weight = 70 kg and total body water = 0.60). SID = strong ion difference; SBE = standard base excess; ANG = anion gap; SIG = strong ion gap; A- = dissociated component of AT 20 40 60 80 100 120 140 160 mEq/L Cations Anions Na+ = 132 K+ Ca++ Mg++ Cl- = 98 HCO3 = -21.9 A- = -14.1 0 Buffer Base = -36SID = +36 ( 10) pH = 7.351 PCO2 = 40 mm Hg SBE = -3 mEq/L ANG = 12 SIG = 5 ( 7 )
  • 40. 40 Figure 6: Hyperchloremic strong ion acidosis with concurrent hypoalbuminemic alkalosis ([albumin] = 2g/dL) SID = strong ion difference; SBE = standard base excess; ANG = anion gap; SIG = strong ion gap; A- = dissociated component of AT 20 40 60 80 100 120 140 160 mEq/L Cations Anions Na+ = 142 K+ Ca++ Mg++ Cl- = -115 HCO3 = - 21.2 A- = - 7.8 0 Buffer Base = -29SID = +29 ( 10) pH = 7.338 PCO2 = 40 mm Hg SBE = - 4 mEq/L ANG = 6 mEq/L Adj. ANG = 12 mEq/L SIG = 5 mEq/L
  • 41. 41 Table 1: Classification of primary metabolic acid-base disorders Acidosis Alkalosis 1.Strong Ion Difference a. Decreased Hyperchloremia Organic Acid Anions Water intoxication b. Increased Hypochloremia Dehydration Strong Cations (THAM) 2. Nonvolatile Weak Acids a. Increased Hyperphosphatemia Hyperalbuminemia b. Decreased Hypoalbuminemia
  • 42. 42 Figure 7. pH as a function of strong ion difference (SID) AT = plasma nonvolatile weak acid total 6.8 6.9 7 7.1 7.2 7.3 7.4 7.5 7.6 15 20 25 30 35 40 45 50 55 pH SID (mEq/L) pH = 7.4 PaCO2 = 40 mm Hg SID = 39 mEq/L AT = Standard State +-
  • 43. 43 Figure 8. Standard base excess (SBE) as a function of crystalloid infusion volume in liters -15 -10 -5 0 5 10 15 20 25 30 35 40 0 1 2 3 4 5 6 7 8 9 10 SBEmEq/L Crystalloid Infusion Volume (Liters) Normal Saline (SID = 0) Crystalloid SID = 24.5 mEq/L Ringer's Lactate (SID = 28) Plasmalyte 148 (SID = 50) 1/2 NS + 75 mEq/L NaHCO3 (SID = 75) 0.15 M NaHCO3 (SID = 150)
  • 44. 44 Figure 9. The Anion Gap (ANG) SBE = standard base excess; ANG = anion gap; SIG = strong ion gap; A- = disassociated component of of AT 20 40 60 80 100 120 140 160 mEq/L Cations Anions Na+ = 142 K+ = 4 Cl- = -105 HCO3 = -24.6 A- = -14.4 0 pH = 7.40 PCO2 = 40 mm Hg SBE = 0 mEq/L ANG = 12 mEq/L SIG = 5 mEq/L XA- XA- = Unmeasured Anions: Cyanide Glycols Iron Isoniazid Ketoacids Krebs Cycle Lactate Methanol Paraldehyde Toluene Salicylate Uremia ANG
  • 45. 45 Figure 10. The Strong Ion Gap (SIG) SIDa = apparent strong ion difference; SIDe = effective strong ion difference; SBE = standard base excess; ANG = anion gap; SIG = strong ion gap; A- = disassociated component of AT 20 40 60 80 100 120 140 160 mEq/L Cations Anions Na+ = 142 K+ = 4 Cl- = -105 HCO3 A- 0 pH = 7.40 PCO2 = 40 mm Hg SBE = 0 mEq/L ANG = 12 mEq/L SIG = 5 mEq/L XA- SIDa Strong Ion Gap SIDe or Buffer Base

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