887CHAPTER 72 Acid Base Disorders Clinical Approach to Disorders of Acid Base Balance Is Abnormal pH Dangerous? In critical care medicine, the fear of abnormal pH, particularly acidemia, is widespread[.]
CHAPTER 72 Acid-Base Disorders Clinical Approach to Disorders of Acid-Base Balance Is Abnormal pH Dangerous? In critical care medicine, the fear of abnormal pH, particularly acidemia, is widespread This is secondary to the concern that cellular proteins are exquisitely sensitive to the H1 concentration of their environment and that a pH change may have detrimental effects on a host of bodily functions.6,13,23 In the critically ill patient, disorders of acid-base balance are more important for what they reveal about the patient’s condition than for any direct damage Studies have repeatedly showed that mortality is more closely related to the nature of acid-base disorders than to the magnitude of metabolic acidosis.21 Despite these data, the fear remains that acid-base derangement itself may cause harm, particularly in extreme circumstances (pH ,7.0 or 7.7).29,51 Clinically, it is important to consider how fast the acid-base derangement occurred, along with the specific expected consequences of the derangement The physiologic effects of acidemia and alkalemia on the human body are complex Acidemia causes an initial sympathetic and adrenal stimulation, an effect that is counterbalanced by a depressed responsiveness of adrenergic receptors to catecholamines as the acid-base disturbance becomes more severe.64 The impact of acidemia appears to differ depending on the type, degree, and timing In some studies, children are able to tolerate a pH less than 7.2, including those undergoing permissive hypercapnia,65 those with diabetic ketoacidosis,66 and those with grand mal seizures.67 Severe acidemia (pH ,7.1–7.2) is associated with decreased cardiac performance that provokes a drop in cardiac output, along with decreased vascular reactivity This manifests as arterial vasodilation and venous constriction.1,24,29,64 Other potential effects of acidemia include endogenous catecholamine and aldosterone secretion, insulin resistance, increased free radical formation, increased protein degradation, gut barrier dysfunction, further respiratory depression, and decreased sensorium.21 In severe alkalemia (pH 7.6) from both metabolic and respiratory alkalosis, blood pressure and cardiac output decline In an acute setting, this may be associated with the left shift of the oxyhemoglobin dissociation curve In chronic alkalemia, this effect is counterbalanced by an increase in the 2,3-diphosphoglyceric acid concentration in red cells.29 Cerebral circulation then responds with vasoconstriction Acute hyperventilation to Pco2 of 20 mm Hg may drop cerebral blood flow to 50% of the basal flow While this can be used to manage increased intracranial pressure emergently, it may also decrease blood flow to areas of the brain, increasing the risk of ischemia and cerebral infarction.68 Additionally, alkalemia facilitates transcellular shifts of potassium and calcium, leading to neuromuscular, seizures, and cardiac arrhythmias if pH exceeds 7.7.68 Despite this evidence, whether acidemia and alkalemia themselves result in harm continues to be debated While potential mechanisms of harm exist, damage depends on multiple interlocking factors, including the clinical context, type of derangement (metabolic vs respiratory), timing, and magnitude Blood Gases: Arterial, Central Venous, or Capillary Samples? There is good correlation in pH, Pco2, partial pressure of oxygen (Po2), and HCO32 among arterial, central venous, and capillary blood gases in healthy volunteers and stable patients In the presence 887 of critical illness (notably, shock and hypotension), there is very poor correlation.69 In some clinical situations, capillary and central venous blood gas measurements may serve as alternatives to arterial samples for acid-base evaluation.70 However, in the setting of severe circulatory failure, such as in cardiac arrest or septic shock, widening of the arteriovenous differences in pH, Pco2, and lactate commonly occurs In the presence of tissue hypoperfusion, hypercapnia and acidemia are best detected in central venous blood.71 Notably, in acute respiratory distress syndrome (ARDS), the lungs themselves may produce lactate, leading to higher levels of lactate in the arterial blood gases than in the venous blood gases Considering the variety of tissue metabolism throughout the body, the value of a single sample to assess blood pH is limited, particularly as most functional proteins are intracellular.3 Thus, in critical illness, both arterial and central venous blood samples are helpful in the assessment of acid-base status There is now growing evidence that peripheral blood samples may provide useful and sufficient data in pediatric patients.72 Evaluation of Acid-Base Disorders Despite differences in approach to acid-base physiology, most clinicians accept a bimodal categorization of acid-base disorders as either respiratory or metabolic There is, however, no agreed upon method of defining and quantifying the metabolic component This is not surprising given the conceptual differences reviewed earlier and ongoing controversy in approach.13,15,39 All available methods (bicarbonate, SBE, AG, and Stewart’s) have simultaneously been criticized and extolled as the gold standard.13,32,73 To simplify acid-base evaluation and make these tools more applicable at the bedside, there are now surrogates of some of the complex physicochemical equations With Pco2 analysis and the Henderson-Hasselbalch equation, clinicians can more easily describe and quantify the respiratory component of the acid-base balance Evaluation of the metabolic side component requires more complex analysis The traditional tools for approaching the metabolic side (e.g., AG and SBE) have been enhanced by Stewart’s physical-chemical concepts.48,74 Prompt identification of unmeasured anions is essential in any acid-base analysis in the critical care setting because mortality associated with strong ion acidosis, both lactic and nonlactic, is significantly higher than that associated with hyperchloremic acidosis.1,48 Three methods are currently applied to evaluate and describe acid-base disorders: the bicarbonate/CO2 physiologic approach, base excess approach, and physicochemical approach The first two are the most widely used methods to evaluate the metabolic component of acid-base disturbance They rely on the plasma concentration of bicarbonate and SBE and use the plasma AG These two methods are clinically useful, as they are easy to understand and apply in clinical situations However, as the SBE is a calculated figure, reliance on a calculated value to quantify metabolic disturbances has a number of pitfalls SBE cannot identify whether an acidosis is due to increased tissue acids, hyperchloremia, or a combination of both Additionally, SBE assumes normal plasma protein, limiting its utility in critically ill patients and resulting in the underestimation of AG in the setting of hypoalbuminemia.18,58 Given these limitations, a third method is founded on physiochemical principles described by Stewart and modified by Figge.22,43 This approach quantifies individual components of acid-base abnormalities and evaluates the pathogenesis of each component in turn.18 Many studies have shown that Stewart’s approach works best to identify acid-base disorders in critically ill 888 S E C T I O N V I I Pediatric Critical Care: Renal patients However, it is a time-consuming method and unsuitable at the bedside (see eTable 72.2).75 Based on these underlying principles, we suggest a four-step approach to categorizing acid-base disorders First, using the available data usually from blood gas and electrolyte evaluation, the primary disorder should be determined (see eTable 72.2) With the exception of chronic respiratory alkalosis and rarely in respiratory acidosis, compensatory responses not return the pH to normal range Therefore, a normal pH in the presence of both changes to HCO3– and Pco2 is suggestive of a mixed acidbase disorder Second, assess the degree of compensation for the individual disorders (see eTable 72.1) The compensatory response must be correlated with the history Third, determine whether there is an elevation in the AG This step is most essential in metabolic acidosis (as will be reviewed later) If the AG is increased, the ratio between the AG and change in bicarbonate should be calculated as well Finally, the information should be used to establish the acid-base derangement and clinical diagnosis Once this has been identified, the underlying cause or causes of each disorder can be addressed Metabolic Acidosis Metabolic acidosis is a process that causes a primary decrease in the plasma bicarbonate concentration, leading to a low arterial pH This is associated with compensatory hyperventilation and subsequent lowering of the Pco2 The classical approach to metabolic acidosis is to classify the disorders as those with either elevated AG or normal AG, which continues to be a practical, although not pathophysiologically based, classification Using the physicochemical approach, metabolic acidosis can be considered an imbalance of strong ions (SID decrease) or from the presence of abnormal nonvolatile weak acids Using this approach, a metabolic acidosis can then be classified into two categories: from an excess of unmeasured anions (excess [XA2]; elevated AG acidosis) or from an excess of chloride or relative or absolute deficit of sodium-water excess (non-AG acidosis; see eBox 72.3).18 Elevated Anion Gap Acidoses Calculation of the AG can be useful in the differential diagnosis of metabolic acidosis As reviewed earlier, the AG is equal to the difference between the major plasma cation (Na1) and the major measured anions These are disorders with excessive acidic anion accumulation, which leads to an elevation in the AG Multiple mnemonics exist The most useful may be GOLD MARK (glycols, oxoproline, L-lactate, D-lactate, methanol, aspirin, renal failure, and ketoacidosis; see eBox 72.3).76,77 There are three major groups of clinically relevant examples that will be discussed in detail here: lactic acidosis, ketoacidosis, and acidosis from a toxin or drug Lactic Acidosis Lactic acidosis, or hyperlactatemia, is the most common cause of elevated AG acidosis in the critically ill patient.29 Causes of hyperlactatemia and lactic acidosis are numerous in the critical care setting.78,79 Lactate is the end product of anaerobic metabolism It is a product of pyruvate reduction via the enzyme lactate dehydrogenase and the reduced nicotinamide hypoxanthine dinucleotide/ nicotinamide hypoxanthine dinucleotide [NADH/NAD] cofactor system.80 It is primarily derived from skeletal muscle, gut, brain, and circulating red blood cells Normal individuals produce 15 to 20 mmol/kg of lactic acid per day.81 The liver uptakes most lactate and recycles it through conversion back to glucose (Cori cycle), oxidation back to pyruvate and subsequent oxidization to CO2 (Krebs cycle), or transamination into alanine.80 Because of its relationship with anaerobic metabolism, increased lactate has been largely considered a dead-end waste product in the setting of hypoxia.71,82 No matter the source or pathway, lactate accumulation results in acidemia With a pKa of 3.9, lactic acid behaves as a strong ion and will lower the SID, increase [H1], and decrease the pH Lactic acidosis also is associated with increased adenosine triphosphate (ATP) hydrolysis, another source of hydrogen ions.80 Lactate is an intermediary in numerous metabolic processes, and serves as a mobile fuel for aerobic metabolism using cell-tocell shuttles, allowing the coordination of intermediary metabolism in different tissues and between cells within those tissues.83 Skeletal muscle is a major source of lactate formation due to exaggerated aerobic glycolysis through Na1/K1-ATPase stimulation by circulating epinephrine.84,85 While elevated lactate levels in septic shock can serve as an indicator of disease severity, it should not necessarily be taken as proof of oxygen debt or hypoperfusion.85 Conversely, the brain is a lactate-consuming organ Lactate is an alternative and supplemental fuel for the injured brain and is important for regulating glucose metabolism and cerebral blood flow.86 Once simply considered a biomarker of cellular oxygen debt and the degree of critical illness, persistent lactate elevation often seen in critically ill patients may be the consequence of complex physiologic, inflammatory, and metabolic processes Lactic acidosis in pediatric critical illness is an indicator of trouble, regardless of patient age.78,87–90 Depending on the source, hyperlactatemia is commonly defined as a lactate level between and mmol/L, whereas lactic acidosis is defined as a lactate level above mmol/L and an arterial pH less than 7.35.79 While the lower limit of a normal blood lactate level, 0.5 mmol/L, is consistent among most clinical laboratories, the upper limit can vary substantially, from to 2.2 mmol/L depending on the assay used Levels at the upper tier of normal values have been associated with poor outcomes among seriously ill patients.79,82 Blood lactate concentration, both the extent and persistence of lactate elevation, correlate with mortality in critically ill patients in many situations, including pediatric and adult patients with septic and hemorrhagic shock, neonates with necrotizing enterocolitis, and those receiving mechanical ventilation.74,82,87–89 Lactate levels have also been used during early goal-directed therapy for adult patients with severe sepsis and septic shock to titrate inotropes and transfusions with a performance similar to that of mixed venous saturation.90 Hyperlactatemia may also occur following cardiac surgery in children, especially in the youngest infants.91 Lactate measurement has become a common attribute in point-of-care blood gas analyzers used at bedside in modern ICUs.92 For example, lactic acidosis appears to result in delayed left ventricular ejection and impairs ventricular relaxation, suggesting that lactate has an independent effect on myocardial function.93 Hyperlactatemia is commonly differentiated into either type A (associated with or caused by inadequate tissue oxygen delivery) or type B (adequate tissue oxygen delivery; see eBox 72.3) This nomenclature remains commonly used because of its simplicity, even though it is not necessarily a reflection of the underlying pathophysiology and considerable overlap exists between the two.78 Further classification can be made by the etiology of elevated lactate, either due to increased lactate production or a primary decrease in lactate use (eBox 72.4) 888.e1 • eBox 72.4 Etiology of Lactic Acidosis Increased Lactate Production Increased pyruvate production Enzymatic defects in gluconeogenesis or glycogenolysis Respiratory alkalosis, such as with salicylate intoxication Pheochromocytoma Sepsis Beta-agonist therapy Impaired pyruvate utilization Decreased enzymatic activity (congenital or may be due to Reye syndrome) Altered redox state that favors conversion to lactate Enhanced metabolic rate (seizure, exercise) Decreased oxygen delivery (shock, cardiac arrest, hypoxemia) Reduced oxygen utilization (cyanide intoxication, sepsis, acute lung injury) D-lactic acidosis Primary Decrease in Lactate Utilization Hypoperfusion and acidemia Alcoholism Liver disease Unclear Mechanism Malignancy Diabetes (including metformin use) Immunodeficiency Hypoglycemic Idiopathic Modified from Rose BD, Post TW Clinical Physiology of Acid-base and Electrolyte Disorders 5th ed New York: McGraw-Hill; 2001:594 CHAPTER 72 Acid-Base Disorders In many patients with critical illness, including those with liver failure and septic shock, the magnitude of lactate elevation does not always account for the observed acid-base imbalance.1,74 In severe sepsis, increases in the AG are often substantially greater than the actual lactate concentration There has been some research into these so-called unexplained or unmeasured anions ([XA2] or [UMAs]).21,74 Possible UMAs contributing to this may include succinate, citrate, and fumarate Other possible mechanisms include sepsis-mediated endothelial damage and a switch to an anion-release state during endotoxemia.21,58,78,94 Hyperlactatemia occurs in about 80% of cases of acute liver failure due to impaired hepatic clearance of lactic acid and increased hepatic production of lactate.94–96 In patients with hepatic failure, both the liver and intestine behave as net producers of lactate However, after transplantation, the grafted liver becomes a net consumer of lactate, as evidenced by a negative lactate gradient between hepatic and portal venous blood.96 The lung appears to be a potent source of lactate in various disease states with pulmonary manifestations In acute lung injury or ARDS, lactate levels may be high even in the absence of shock or sepsis, as the lung can serve as a source of lactate.97 Potential mechanisms of lactate production by the lung include anaerobic metabolism in areas of tissue hypoxia, cytokine effects on pulmonary cells, and enhanced glycolysis and lactate synthesis by both the parenchymal and nonparenchymal cells.97 Lactic acidosis in status asthmaticus is multifactorial and includes contributions from lactate production by overwhelmed respiratory muscles, tissue hypoxia, a hyperadrenergic state, and the metabolic effect of pharmacologic b2 agonists.98,99 Numerous drugs and toxins may cause or contribute to increased lactate, with or without acidemia Drugs associated with the release of endogenous catecholamines, such as cocaine, can stimulate lactate production.100 Sodium nitroprusside, a key vasodilator drug, may cause lactic acidosis if excessive drug is administered or cyanide clearance is impaired in hepatic and renal failure Through conversion to its breakdown products of cyanide and thiocyanate, nitroprusside inhibits mitochondrial respiratory chain activity and increases lactate production.80,101 Propofol toxicity, which occurs commonly with prolonged infusion and is known as propofol infusion syndrome, results in lactic acidosis; rhabdomyolysis (including the cardiac muscle); or myocardial, renal, and hepatic failure.102 Children who receive metformin for insulin resistance are at risk of developing metformin-associated lactic acidosis, particularly in the setting of intercurrent illnesses While the incidence of metformin-associated lactic acidosis is low, it has a high mortality rate Metformin causes uncoupling of the oxidative phosphorylation with acceleration of the glycolytic flux, which results in increased lactate production.103,104 Lactic acidosis plays an important role in salicylate intoxication Although salicylate toxicity occurs less frequently now because of the increased use of alternative antipyretics in young children, it remains as a potential pediatric health hazard Children are more susceptible to salicylate poisoning because of their reduced ability to buffer the acid stress.105 Salicylates uncouple oxidative phosphorylation, inhibiting Krebs cycle enzymes and amino acid synthesis, resulting in variable acid-base patterns: respiratory alkalosis, mixed respiratory alkalosis plus metabolic acidosis, or (less commonly) simple metabolic acidosis.105 A special observation should be made about D-lactic acidosis Dextroisomer (D)-lactate is produced by bacterial fermentation in the bowel lumen, which can then reach systemic circulation and lead to metabolic acidemia, especially if liver function (and lactate 889 clearance) is suboptimal.106 D-lactic acidosis should be considered in patients with a history of intestinal disease who present with confusion and ataxia, and have high AG metabolic acidosis with normal L-lactate levels Symptoms may worsen after high-carbohydrate meals or tube hyperalimentation Treatment focuses on decreasing gut bacteria overgrowth with antibiotics and the avoidance of high-carbohydrate or lactose feeding.107 Ketoacidosis Ketones are formed by beta-oxidation of fatty acids, a process that increases substantially in insulin-deficient states In the pediatric intensive care setting, this is most commonly seen in patients with DKA due to overproduction and underutilization of acetone, b-hydroxybutyrate (bOH-B), and acetoacetic acids (ketone bodies), which accumulate in plasma Ketoacidosis can also be seen in inborn errors of metabolism—typically, those with impaired amino acid and organic acid metabolism Mixed ketoacidosis and lactic acidosis can be seen in glycogen storage disease type I (glucose-6-phosphate deficiency) Notably, as the urinary dipstick assessing for ketones uses nitroprusside as a reagent, it detects only acetoacetate but not bOH-B In a patient with DKA and shock, bOH-B may be produced in ratios up to 3:1 While the urinary dipstick will initially show few ketones in the setting of DKA and shock, urinary ketone concentration may paradoxically rise as perfusion improves and the patient clinically improves and resolves the impaired perfusion.108 As the renal threshold for the ketone bodies is low, they are readily filtered through the glomerulus without a reabsorption mechanism This loss can shift the AG, which may appear less than expected, because of the anions eliminated though the urine, with renal retention of chloride and bicarbonate.48 While uncommon in pediatrics, alcoholic ketoacidosis (AKA) may be seen in patients with chronic alcohol intake and liver disease and occurs after a period of heavy drinking in association with reduced food intake AKA is quickly responsive to fluid administration, with faster resolution when dextrose and saline are infused together.109 Toxic Compounds That Directly Provoke Acidosis Alcohol intoxications, which include methanol, ethylene glycol, diethylene glycol, and propylene glycol, directly result in acidosis The acid-base disturbances most commonly seen include a high AG metabolic acidosis, a decrease in serum bicarbonate, and an increased serum osmolality and osmolal gap The acidosis and cellular dysfunction are direct effects of the metabolites (e.g., formic acid in ethylene glycol), whereas the parent compounds are associated with the increase in serum osmolality While toxic alcohol intoxications are infrequent problems in pediatric cases, they may occur as a result of accidental ingestion or in adolescents who ingest alcohol or illicit drugs (including inhalants) or engage in self-harm.110 Depending on the type and amount ingested, the clinical presentation may range from mild subclinical poisoning to a sudden onset of high AG acidosis, acute kidney injury, and encephalopathy, with a high risk of mortality and neurologic sequelae.110 Toxic alcohol ingestion is treated with supportive critical care, including urinary alkalinization to improve and expedite renal excretion In serious cases, early hemofiltration or hemodiafiltration should be considered A competitive inhibitor of alcohol dehydrogenase (either ethanol infusion or 4-methylpyrazole [fomepizole]) can be considered for ethylene glycol and methanol poisoning.110 890 S E C T I O N V I I Pediatric Critical Care: Renal Other Forms of Metabolic Acidosis With an Increased Anion Gap In the setting of chronic kidney disease (CKD), baseline metabolic derangements due to renal insufficiency may be exacerbated by critical illness In patients with CKD, hyperchloremic metabolic acidosis can occur due to impaired ammonium (NH41) generation and excretion When the glomerular filtration rate (GFR) falls below 20 mL/min, the kidneys are incapable of excreting fixed acids, causing accumulation of sulfates and other acids, which results in an increased AG These forms of acidosis are usually mild, producing an excess AG of approximately 10 mEq/L A mixed metabolic acidosis (high and normal AG mechanisms) is not uncommon in this setting.3 Another patient population in which metabolic acidosis may be more severe in the setting of critical illness is the premature neonate Premature neonates have renal tubules with a limited capacity to excrete H1 and Cl2 and to concentrate urine during the first month of life Late metabolic acidosis of prematurity occurs more frequently in the premature infant compared with the term infant (20% vs 5%).111 Although this level of renal tubular development is adequate for the breast-fed infant, if the protein intake or solute load is excessive, the renal capacity may be exceeded and metabolic acidosis may develop, particularly during critical illness.64 Hyperchloremic Acidosis: Nonanion Gap Metabolic Acidosis Hyperchloremic forms of acidosis occur either as a result of an increase in chloride concentration relative to strong cations (especially sodium) or because of the loss of cations with a retention of chloride (see eBox 72.3) The rise in chloride concentration is responsible for maintaining a “normal” AG in spite of a fall in bicarbonate levels (i.e., a nonanion gap acidosis is produced) When the pH drops, the normal response by the kidney is to increase chloride excretion as ammonium chloride (NH4Cl) in order to increase the SID and pH Failure of this mechanism identifies the kidney as the problem, as in renal tubular acidosis (RTA) There are four main causes of nonanion gap acidosis: (1) exogenous chloride loads (saline boluses, parenteral nutrition); (2) loss of cations from the lower gastrointestinal (GI) tract without proportional losses of chloride, as in secretory diarrhea, but also in conditions in which alkaline loss of small bowel, biliary, or pancreatic secretions are present (such as drainage from ostomies, tubes, or fistulas); (3) renal tubular acidosis and drug-mediated tubulopathies; and (4) urinary reconstruction using bowel segments Exogenous Chloride Load In patients with critical illness, hyperchloremic metabolic acidosis is often due to therapeutic interventions These include rapid infusion of isotonic saline (0.9% NaCl) and parenteral nutrition.50 Hyperchloremic acidosis should be expected whenever large volumes of normal saline are rapidly administered.1,74 Multiple studies have demonstrated the relationship between normal saline resuscitation and the development of hyperchloremia and acidosis (not necessarily acidemia).112 The effects of hyperchloremia and hyperchloremic acidosis may not influence outcome for most patients There is, however, a growing body of evidence showing that both hyperchloremia and hyperchloremic acidosis have subtle but potentially significant adverse physiologic and clinical effects, including kidney injury, and may impair a patient’s ability to recover from severe illness.113–117 In those with critical illness, use of isotonic fluids leads to hyperchloremic acidosis and a higher rate of adverse outcomes, including death (see also Chapter 71).118,119 Several groups have assessed the use of the so-called balanced fluids—that is, fluids with SID nearer to that of human plasma.120,121 However, this suggested change of practice is still inconclusive.122 At least one prospective study in adults suggested that the amount of fluids given, rather than the types of fluid, played a more important role in acid-base status.123 Given the current data, normal saline should be viewed as a potential hazard, especially in patients with previously known renal or liver dysfunction, those with shock, and in those requiring high volumes of saline for resuscitation.75 The appropriate fluid choice in the setting of critical illness remains a contentious debate; further studies—particularly in pediatric populations—are urgently needed.124,125 Postpyloric Gastrointestinal Fluid Losses The GI tract, liver, and pancreas can be conceptualized as a giant ion exchanger organ The main transport system is driven by Na1/ K1-ATPase across the basolateral membrane of the epithelial cells, with the participation of several key apical membrane electrolyte transporters, including Cl2/HCO32 and Na1/H1 ion exchangers and the so-called cystic fibrosis transmembrane conductance regulator, or CFTR Cl2 channel Under normal conditions, only a small net amount of alkali (30–40 mmol per day) is lost in stool Large losses of fluid from diarrhea may lead to a significant fall in extracellular fluid volume, reducing the GFR and limiting the ability of the kidneys to compensate Disruption of normal gut function can provoke disorders that vary from severe acidosis (most of postpyloric losses) to severe alkalosis (prepyloric losses, congenital chloridorrhea), depending on the segment of the GI tract affected and the nature of the losses.126 Secretory diarrheas (from cholera, enteropathic E coli, rotavirus, and other infectious causes) commonly produce this clinical scenario, presenting with hypovolemia, acute kidney injury, hyperchloremic metabolic acidosis, and hypokalemia If the hypovolemia is not corrected, lactic acidosis may occur due to tissue hypoperfusion.126 In secretory diarrheas, the lost fluid and electrolytes can be replaced with oral solutions (100 mL/kg body weight of a solution with 60 to 90 mEq/L of sodium) In cases of excessive losses or emesis, intravenous volume repletion should be implemented Both biliary and pancreatic secretions have alkaline pH Pancreatic or biliary drainages are usually low volume; thus, despite the loss of NaHCO3-rich fluid, metabolic acidosis does not commonly occur If drainage is excessive (.30 mL/kg per day), metabolic acidosis may develop and is often exacerbated by concomitant volume depletion Treatment with sodium will restore SID; bicarbonate administration can also be used.126 Patients with ileostomies usually adapt to the extra fluid obligatory loss through changes in salt and water intake as well as compensatory changes in electrolyte and fluid handling by the kidney If ileostomy drainage increases abruptly or if the patient is unable to change intake to match these losses due to illness, salt and water losses can easily lead to clinically significant volume depletion In this setting, metabolic acidosis is common, as [HCO32] in ileostomy fluid is higher than in plasma, causing disproportionate sodium and alkali loss Renal Tubular Acidosis and Drug-Mediated Tubulopathies RTA includes disorders with persistent normal AG, hyperchloremic metabolic acidosis with normal or minimally affected filtration rate (GFR), and a low capacity for net acid excretion RTA ... 72.1) The compensatory response must be correlated with the history Third, determine whether there is an elevation in the AG This step is most essential in metabolic acidosis (as will be reviewed... reduction via the enzyme lactate dehydrogenase and the reduced nicotinamide hypoxanthine dinucleotide/ nicotinamide hypoxanthine dinucleotide [NADH/NAD] cofactor system.80 It is primarily derived from... of the losses.126 Secretory diarrheas (from cholera, enteropathic E coli, rotavirus, and other infectious causes) commonly produce this clinical scenario, presenting with hypovolemia, acute kidney