Primary metabolic acidosis: pH < 7.4, Serum HCO3−< 24 mEq/L
Primary metabolic alkalosis: pH > 7.4, Serum HCO3− > 24 mEq/L
Simple AG acidosis
see text/Tables 25.2, 25.3 Simple non-AG acidosis see text/Tables 25.2, 25.4 Address
respiratory component if necessarya
Treat in order of clinical importance
Single disorder Treat with
bicarbonate/
hemodialysis
Treat in order of
clinical importance
Check AG, delta AGb is this a combined disorder?
Address respiratory component if
necessarya
Check UAG - see text
Check urine CI- see text/Table 25.5 Is there appropriate
respiratory compensation?
(see Table 25.1)
Is the pH life- threatening?
Is there appropriate respiratory compensation?
(see Table 25.1)
Check AG, delta AGb is this a combined disorder?
o N o
N
Yes
Yes
No No Yes
Yes Yes
No
AG, anion gap; UAG, urine anion gap.aMay require intubation and mechanical ventilation for patients with life-threatening acid–base disturbances unable to fully hyper- or hypoventilate appropriately.bSee text for details.
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TABLE 25.2 Causes of Anion Gap and Nonanion Gap Metabolic Acidosis
Mechanism Increased anion gap acidosisa Normal anion gap acidosis Increased acid
production or administration
Lactic acidosis—lactate,
D-lactate Ketoacidosis
Massive rhabdomyolysis
Ammonium chloride ingestion
Hyperalimentation fluids/
saline infusion Intoxications:
Methanol/formaldehyde—
formate
Ethylene glycol—glycolate, oxalate
Toluene—hippurate Salicylates
Paraldehyde—organic anions
L-5 oxoprolinuria Increased
bicarbonate loss or loss of bicarbonate precursors
GI losses (negative UAG) Diarrhea
Pancreatic, biliary, intestinal fistulas Ostomy
Cholestyramine Sevelamer Renal losses
Carbonic anhydrase inhibitors
Type 2 (proximal) RTA Treatment phase of
ketoacidosis Decreased acid
excretion (positive UAG)
Chronic renal failure Acute renal failure Chronic renal failure Type 1 (distal) RTA Hypoaldosteronism
(type 4 RTA) GI, gastrointestinal; UAG, urine anion gap; RTA, renal tubular acidosis.
aSee Table 25.3 for further discussion.
common causes of an anion gap metabolic acidosis include lactic acidosis, toxic inges- tions, ketoacidosis, rhabdomyolysis, and renal failure (Tables 25.2 and 25.3).
Of note, the normal range for the anion gap reflects the presence of physiologic unmeasured anions, such as albumin, in nonpathologic states. However, conditions that alter the concentrations of these unmeasured anions also alter the anion gap.
For example, a 1 g/dL decrease in the serum albumin would be expected to decrease the anion gap by 2.5 to 3 mEq/L. It is important to adjust the anion gap for these changes in order to properly detect an anion gap acidosis that may be present despite a calculated anion gap that appears within the normal range of 8 to 12 mEq/L. The
TABLE25.3CausesandTreatmentofAnionGapMetabolicAcidosis ConditionCauseandsymptomsTreatmentComments Lacticacidosis Pyruvate Lactate
Increasedlactateproduction 1.Increasedpyruvateproduction: enzymaticdefectsin glycogenolysisor gluconeogenesis. 2.Decreasedpyruvateutilization: enzymaticdefectsinpyruvate dehydrogenaseorcarboxylase. 3.Increasedconversionofpyruvate tolactate: Increasedmetabolicrate Grandmalseizure Severeexercise Hypothermicshivering Shock/cardiacarrest/acute pulmonaryedema Severehypoxemia COpoisoninga Cyanideintoxicationa Decreasedlactateutilization Hypoperfusion Alcoholisma Liverdisease Correctionoftheunderlyingdisorderandreversal ofcirculatoryfailureistheprimarytherapy. Roleofsodiumbicarbonateadministrationis controversial;maybeindicatedifsevere acidosis–pH<7.1orlossofbufferingcapacity (bicarbonate<5mEq/L).Hemodialysismaybe indicatedinresistantcases. Alternativetherapies(clinicalefficacyandsafetyfor thesehavenotbeendemonstratedinrandomized controlledhumanstudies). Tham(tromethamine)–inertaminoalcoholthat buffersacidswithoutgeneratingCO2.Renally excretedandmayproducehyperkalemia, hypoglycemia,andrespiratorydepressionin anuric/oliguricpatients. Carbicarb:equimolarmixtureofsodiumcarbonate andsodiumbicarbonate.Diminishedriskof hypercapniaandintracellularacidosiscompared withsodiumbicarbonate. Dichloroacetate:activatespyruvatedehydrogenase andincreasesoxidationofpyruvatethus decreasingitsconversiontolactate.
Cautionwithbicarbonate therapyinthefollowing settings: Volumeoverload Postrecoverymetabolicalkalosis Hypernatremia IncreasedCO2productionand possibleretentioninsettingof circulatoryfailurewith worseningofmixedvenous PCO2 Intracellularacidosis Reductioninionizedcalcium andworseningofcardiac contractility. (Continued)
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TABLE25.3CausesandTreatmentofAnionGapMetabolicAcidosis(Continued) ConditionCauseandsymptomsTreatmentComments Propyleneglycol toxicityaConvertstopyruvateandlactate. Vehicleforlorazepamandotheragents,and continuousinfusionmayresultinlactate accumulationandincreasedosmolargap.
Discontinueinfusion. Ketoacidosis (seeChapter28)Inthesettingofinsulindeficiency. Symptomsincludevomiting,abdominalpain, severevolumedepletion/dehydration.
Insulinandfluids—acidosiswillimprovewith insulin-inducedmetabolismofketoacidsand regenerationofserumHCO3−. SalicylatetoxicityaToxicitywhenplasmalevel>40–50mg/dL (therapeutic,20–35mg/dL). Mixedmetabolicacidosisandrespiratory alkalosis. Increasedketoacidandlactateproduction. Diagnosis—plasmasalicylatelevel.
Reducesalicylatelevelstoavoidneurotoxicity. AlkalinizationofplasmatoapH>7.45–7.5 convertssalicylatetoionizedformthat lowersCNSlevels. Alkalinizationofurinedecreasesrenaltubular reabsorptionofionizedsalicylate. Considerhemodialysisforplasma concentration>80mg/dL.
Ifrespiratoryalkalosis istheprimary disturbance,then furtheralkalinization isnotnecessary. Methanola Formaldehyde Formicacid
Minimallethaldoseis50–100mL. Symptomsincludeweakness,headache, blurredvision,andblindness. Diagnosis—plasmamethanolassay.
Thetreatmentforbothmethanolandethylene glycolisidentical. Prompttreatmentisnecessaryandincludes: Oralcharcoal Sodiumbicarbonate Simultaneoususeof bothethanoland fomepizoleisnot recommendedas fomepizole increasesthe half-lifeofethanol.
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Ethyleneglycola ↓ Glycolicand oxalicacid Componentofantifreezeandsolvents. Symptomsincludeneurologicand cardiopulmonaryabnormalities,flankpain, andrenalfailure.Envelope-and needle-shapedoxalatecrystalsmaybe visibleintheurine. Diagnosis—plasmaethyleneglycolassay.
Administrationofethanolorfomepizole competeswithorinactivatesmetabolism, respectively,ofparentcompoundand preventsformationoftoxicmetabolites. Administrationoffolicacid,thiamine,and pyridoxine.Hemodialysisforremovaloftoxic metabolitesandparentcompound. L-5oxoproline toxicityHighaniongapacidosisinchildren secondarytocongenitalglutathione synthetasedeficiency.Acquired oxoprolinuriaassociatedwith acetaminophenandothermedications. Renaldysfunctionandsepsispredispose. Diagnosis—negativetoxicityscreeningand highplasmaandurinelevelsof 5-oxoproline/urineorganicacidscreen.
Treatmentprimarilyincludescessationofthe offendingagent. N-acetylcysteinemaybebeneficial; restorationofglutathionestoresreducesL-5 oxoprolinelevels. D-Lacticacidosis Glucosebacterial overgrowthin thecolon D-Lactate
Associatedwithshortgutsyndromeand overproductionofD-lactate. Symptoms:episodicaniongapacidosis (usuallyoccurringafterhigh-carbohydrate meals)andneurologicabnormalities includingcerebellarataxia,confusion, slurredspeech. Diagnosis:enzymaticassayforD-lactate.
Treatmentincludessodiumbicarbonate administrationandantimicrobialagents. aSeeChapter32.
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serum osmolal gap may also be of value when a toxic ingestion (ethanol, methanol, ethylene glycol) is a suspected cause of an anion gap acidosis (Table 25.3). An increased osmolal gap is an otherwise nonspecific finding and may be seen in other forms of anion gap acidosis. The normal osmolal gap is approximately 10 mOsm/kg.
Osmolal gap=Measured serum osmolatity−calculated serum osmolality Calculated serum osmolality=2[Na+]+[BUN]/2.8+[glucose]/18 Nonanion Gap Acidosis
Nonanion gap acidosis occurs in the setting of bicarbonate loss, but without the pres- ence of an additional pathologic anion. In a nonanion gap acidosis [Cl−] is increased to maintain electroneutrality and the calculated anion gap remains normal. The differ- ential of nonanion gap acidosis includes gastrointestinal losses versus a renal etiology (Table 25.2).
The urine anion gap (UAG) is used to discern the source of bicarbonate loss in a nonanion gap acidosis when the cause is not clinically evident.
UAG=(Urine [Na+]+Urine [K+])−(Urine [Cl−])
The UAG is normally zero or slightly positive. In the setting of a nonanion gap acidosis, the appropriate renal response would be to increase ammonium excretion, as NH4Cl, which causes the UAG to become negative, usually ranging from –20 to –50 mEq/L. This is seen in nonrenal causes of nonanion gap acidosis, such as severe diarrhea. In conditions with impaired renal acid excretion, such as chronic kidney disease and distal renal tubular acidosis (RTA), the UAG will remain positive or become only slightly negative. The UAG has no utility in the setting of hypovolemia, oliguria, low urine [Na+], or in anion gap acidosis.
Renal Tubular Acidosis
These disorders are characterized by a hyperchloremic metabolic acidosis resulting from diminished capacity of the kidney to accommodate the acid load. A diagnosis of RTA cannot be made in the setting of acute renal failure or with moderate-to-severe chronic kidney disease. Although RTA is generally a chronic condition and rarely causes acute critical illness, the identification of a RTA in the critical care setting is important as it may point clinicians toward underlying conditions that are associated with the various forms of RTA. Distal (type 1) RTA is associated with drugs such as amphotericin and autoimmune conditions such as lupus and Sjogren syndrome.
Proximal (type 2) RTA is associated with multiple myeloma and may manifest with profound wasting of other solutes that are typically reabsorbed in the proximal tubule, such as glucose and phosphorus. And type 4 RTA, which is due to hyporeninemic hypoaldosteronism, is a commonly seen manifestation of diabetes and is closely linked to hyperkalemia. A detailed discussion of this topic is beyond the intent of this manual (Table 25.4).
Treatment
Treatment of the various disorders is outlined in Table 25.3. The primary goal in treating metabolic acidosis is reversal of the underlying process. Administration of bicarbonate is controversial, as some clinical parameters may actually worsen with correction of the acidosis. However, partial correction should be considered in the
TABLE25.4RenalTubularAcidosis(RTA) Distal(type1)RTAProximal(type2)RTAHyporeninemic hypoaldosteronism(type4)RTA CausesIdiopathic,familial,Sjogren syndrome,hypercalciuria, rheumatoidarthritis,sicklecell anemia,SLE,amphotericin Idiopathic,multiplemyeloma,carbonic anhydraseinhibitors,heavymetals(lead, mercury),amyloidosis,hypocalcemia,and vitaminDdeficiency Diabetes,ACEinhibitors,tubulointer- stitialnephritis,NSAIDS,heparin, adrenalinsufficiency,obstructive uropathy,K+-sparingdiuretics DefectImpaireddistaltubularH+ excretion(distalacidification)Impairedproximaltubularbicarbonate absorption±associatedglycosuria, aminoaciduria,phosphaturia
Aldosteronedeficiencyorresistance PlasmaHCO3−Variable;usuallymoresevere acidosiswithlevel<10mEq/L.LesssevereacidosisthandistalRTA;usually 12–20mEq/LUsually>15mEq/L UrinepHduring acidemiaa>5.3Variable;>5.3ifserumHCO3−isabovethe reabsorptivethreshold.Theexcessive bicarbonate“spillsout”intotheurine causingahighurinepH.<5.3ifserum HCO3−isbelowthreshold
Usually<5.3 PlasmaK+Usuallylow;usuallycorrectswith alkalitherapyLow;usuallyworsenedbybicarbonaturia seenwithalkalitherapyHigh UAGPositiveVariable;nothelpfulPositive AssociatedconditionsRenalstones/nephrocalcinosisRickets/osteomalacia/FanconisyndromeNone TreatmentAlkalitherapy:sodiumcitrate/ potassiumcitrate/sodium bicarbonate
Alkalitherapy:higherdosesareneeded becauseofbicarbonaturia.Thiazide diureticsmaybetriedinresistantcases
Treatthecauseof hypoaldosteronism/ lowpotassiumdiet/loopdiuretics aInmetabolicacidosiswithintactrenalacidexcretion,urinepHshouldbe<5–5.3. SLE,systemiclupuserythematosus;ACE,angiotensin-convertingenzyme;NSAIDs,nonsteroidalanti-inflammatorydrugs;UAG,urineaniongap. ModifiedfromRoseB,PostT.Clinicalphysiologyofacid-baseandelectrolytedisorders.5thed.NewYork:McGraw-Hill,2001.
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setting of life-threatening metabolic acidosis (pH<7.1) or when the serum bicarbonate is low enough (i.e.,<10 to 12 mEq/L) that loss of effective respiratory compensation would result in life-threatening acidosis. For example; the pH is approximately 7.2, the serum bicarbonate is 8 mEq/L, and the PCO2is appropriately compensated at 20 mm Hg. If respiratory compensation becomes inadequate and the PCO2increases to 55 mm Hg, the pH will suddenly decrease to approximately 6.9. To decrease the risk of either a further drop in the serum bicarbonate or a sudden inability to achieve appropriate respiratory compensation, a serum bicarbonate target of 10 to 12 mEq/L is recommended.
One caveat is the administration of bicarbonate in the setting of severe circu- latory failure. This may result in an apparent improvement in acidosis as measured by the arterial blood gas, but an actual worsening of the overall acidosis if a venous blood gas is obtained (given delayed elimination of the CO2produced as a result of the administered bicarbonate). Thus, both arterial and venous values should be mon- itored when bicarbonate is administered in this setting. Continuous or intermittent hemodialysis may also be used to correct severe, refractory acidosis particularly if the patient cannot accommodate the volume associated with administration of intravenous bicarbonate-containing fluids. In the setting of a combined metabolic and respiratory acidosis, correction of the respiratory acidosis component should be addressed prior to administration of bicarbonate or initiation of hemodialysis.
Bicarbonate Deficit
The amount of bicarbonate required to correct a metabolic acidosis can be estimated from the following formula:
Total body weight (kg)×[0.4+(2.4/[HCO3−])]=apparent volume of distribution Apparent volume of distribution×target change in [HCO3−]=mEq of NaHCO3 For example, to increase the serum bicarbonate to 12 mEq/L in a 60-kg patient with a serum bicarbonate level of 5 mEq/L:
60 kg×[0.4+2.4/5]=apparent VD of 53 L 53×target change in [HCO3−](12−5=7 mEq/L)=371 mEq Thus, in a static situation, almost 400 mEq of NaHCO3 would need to be administered in an attempt to increase the [HCO3−] to 12 mEq/L. This calculation is obviously an approximation and does not take into account ongoing bicarbonate losses or continued acid production. A standard ampule of sodium bicarbonate contains 50 mEq in 50 mL, given as an intravenous bolus or mixed with 5% dextrose containing sterile water.
M E T A B O L I C A L K A L O S I S
Most cases of metabolic alkalosis encountered in the intensive care unit are induced by loss of gastric secretions from gastric suctioning or vomiting, or from diuretic therapy. Other causes include bicarbonate administration, the posthypercapnic state, and citrate associated with centrifugal plasma exchange, massive transfusion, or fresh- frozen plasma administration. The condition is often aggravated by renal insufficiency, which delays bicarbonate excretion. Metabolic alkalosis may be the primary disorder, but likewise can be associated with an anion gap or nonanion gap acidosis as well as with a respiratory acidosis or alkalosis. Of note, however, is that a slight increase in the calculated anion gap can occur in some cases of metabolic alkalosis, often related to an
Acid–Base Disorders rMetabolic Acid–Base Disorders 2 1 9
TABLE 25.5 Chloride-Responsive and Chloride-Resistant Metabolic Alkalosis
Chloride responsive (urinary Cl−
≤25 mEq/L)
Chloride resistant (urinary Cl−
>25 mEq/L) Loss of gastric H+-vomiting or gastric
suction
Prior loop/thiazide diuretic use Chloride-losing diarrhea: villous
adenoma/some cases of factitious diarrhea due to laxative abuse Cystic fibrosis (high sweat Cl−) Posthypercapnia
Mineralocorticoid excess: primary hyperaldosteronism, Cushing or Liddle syndromes, exogenous steroid use, licorice ingestion Active loop/thiazide diuretic use Bartter or Gitelman syndromes Alkali load: exogenous bicarbonate
infusion, citrate-containing blood products, antacids (milk-alkali syndrome)
Severe hypokalemia Treatment includes administration of
0.9% or 0.45% NaCl and repletion of potassium stores.
Treatment is disease-specific and includes repletion of potassium stores.
increased albumin concentration resulting from a contracted volume state. Metabolic alkalosis can be broadly categorized into a chloride-responsive or chloride-resistant process (Table 25.5).
Common Causes of Metabolic Alkalosis Gastric Secretion Loss
Loss of gastric secretions occurs from removal of gastric contents by tube drainage or from vomiting. Normally, hydrogen ions released into the stomach reach the duode- num, where they stimulate pancreatic bicarbonate secretion into the gastrointestinal tract, maintaining acid–base balance. When gastric contents are lost, bicarbonate is not secreted, resulting in increased plasma bicarbonate and metabolic alkalosis. Self- induced vomiting is often denied by patients with eating or factitious disorders, and a low urine chloride supports the diagnosis.
Contraction Alkalosis
Contraction alkalosis occurs in the setting of excessive loss of chloride-rich, bicarbonate-free fluid. This is most commonly seen with the use of loop or thiazide diuretics, but can also occur with gastric losses or with cystic fibrosis (high sweat [Cl−]).
As a result of “contraction” of the extracellular volume, there is a relative increase in the bicarbonate concentration. Despite the relative intravascular volume depletion, there is an obligate urinary loss of sodium with bicarbonate in this setting. Therefore, urine chloride concentration is usually a better predictor of the volume status in this form of metabolic alkalosis than urine sodium.
Posthypercapnic Alkalosis
Chronic respiratory acidosis is associated with an appropriate compensatory increase in the serum bicarbonate concentration. Sudden normalization of a chronically elevated PCO2 via mechanical ventilation can result in an acute, potentially lethal increase in the pH. Therefore, the PCO2 should not be decreased rapidly in the setting of a well-compensated chronic respiratory acidosis.
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Refeeding Syndrome
Patients fed a high-carbohydrate diet after a prolonged fast can acutely develop metabolic alkalosis. Intracellular hydrogen ion shift is the proposed mechanism.
Refeeding may also be independently associated with hypophosphatemia.
Severe Hypokalemia
Severe hypokalemia via multiple renal mechanisms causes hydrogen ion secretion and bicarbonate reabsorption. The ensuing metabolic alkalosis is refractory to treatment until potassium stores are replaced.
Milk-Alkali Syndrome
Milk-alkali syndrome results from a chronic high calcium intake (usually in the form of calcium-containing antacids) and is usually associated with renal insufficiency.
Treatment
Intravenous sodium chloride fluid administration will reverse chloride-responsive metabolic alkalosis (Table 25.5). Response to treatment can be monitored via urine pH and urine chloride concentration. Concomitant hypokalemia may also play a critical role in the maintenance of metabolic alkalosis, as it increases tubular secretion of H+ and reabsorption of bicarbonate. Patients with hypokalemia and alkalosis may have a profound total body potassium deficit, and treatment of this will be necessary in the correction of metabolic alkalosis. If the patient is able to take medication by mouth, oral supplementation is preferred with potassium chloride 40 mEq every 4 to 6 hours.
Alternatively, if the patient is unable to take medication enterally, intravenous infusion of potassium chloride at a rate of 10 mEq/hr with close monitoring of serum potassium may be initiated.
Acetazolamide can be considered in cases of worsening metabolic alkalosis associ- ated with volume overload complicated by the need for continued attempts at diuresis (nonchloride responsive). Acetazolamide inhibits carbonic anhydrase, the enzyme that catalyzes the conversion of carbon dioxide and water into carbonic acid, causing renal excretion of hydrogen ions and retention of bicarbonate. Decreased bicarbonate excre- tion from carbonic anhydrase inhibition causes a metabolic acidosis to counter the alkalosis. Acetazolamide has minimal diuretic effects as a single agent, but can have additive effects when combined with loop and/or thiazide diuretics if the serum bicar- bonate concentration is elevated.
In cases of severe, refractory alkalosis (usually associated with bicarbonate admin- istration in the setting of renal failure), hydrochloric acid infusion through a central line is rarely needed, but can be used. Other alternatives include the use of intermittent hemodialysis with the bicarbonate bath decreased to the lowest allowable value (lim- ited bicarbonate gradient available with most systems) or a continuous hemofiltration modality using primarily a nonbicarbonate, noncitrate replacement fluid.
M I X E D A C I D – B A S E D I S O R D E R S
The delta anion gap is useful in determining the presence of other metabolic distur- bances superimposed on a known anion gap acidosis. It is calculated as follows:
Delta Anion Gap (/) : ∗AG (from normal, which is approximately 10) ∗HCO3(from normal, which is approximately 25 mEq/L)
*=Change
Acid–Base Disorders rMetabolic Acid–Base Disorders 2 2 1
The delta gap is based on the principle that the change in AG should roughly approximate the change in serum bicarbonate in a simple anion gap acidosis. A ratio
of <1 occurs if the change in serum bicarbonate is larger than the change in the
anion gap, and indicates that a nonanion gap acidosis may be present, causing the disproportionate fall in serum bicarbonate. A ratio>1 suggests a combined anion gap acidosis and metabolic alkalosis (which both raises the anion gap and attenuates the expected drop in serum bicarbonate from the anion gap acidosis).
Elucidation of double or triple acid base disturbances requires assessment of mul- tiple metabolic parameters. Because complex acid–base disorders may at first manifest with several normal appearing lab values, a methodical evaluation of all data (including the calculation of anion gap and delta gap) should be done routinely. The following patterns are often suggestive of a combined acid base disturbance despite a “normal”
pH:
Normal pH+ ↓PCO2+ ↓HCO3: respiratory alkalosis plus metabolic acidosis Normal pH+ ↑PCO2+ ↑HCO3: respiratory acidosis plus metabolic alkalosis Normal pH+normal PCO2 + normal HCO3+↑AG: metabolic acidosis and
alkalosis
S U G G E S T E D R E A D I N G S
Arroliga AC, Shehab N, McCarthy K, et al. Relationship of continuous infusion lorazepam to serum propylene glycol concentration in critically ill adults.Crit Care Med.2004;32:1709–
1714.
Prospective observational study evaluating the dose relationship between lorazepam infusion and propylene glycol accumulation.
Gauthier PM, Szerlip HM. Metabolic acidosis in the intensive care unit.Crit Care Clin.2002;18:
289–308.
An extensive review of diagnostic and therapeutic approach to metabolic acidosis with focus on critical care issues.
Gehlbach BK, Schmidt GA. Bench-to-bedside review: treating acid-base abnormalities in the intensive care unit—the role of buffers.Crit Care.2004;8:259–265.
This review article extensively discusses the role of bicarbonate therapy as well as alternative therapies in lactic acidosis.
Judge BS. Differentiating the causes of metabolic acidosis in the poisoned patient.Clin Lab Med.
2006;26:31–48, vii.
Describes toxicities due to methanol, ethylene glycol, and other ingestions, their effects on acid base balance, diagnosis, and treatment.
Rose B, Post T. Clinical physiology of acid base and electrolyte disorders. 5th ed. New York:
McGraw-Hill, 2001:615–619.
An extremely comprehensive text book describing pathophysiologic mechanisms, diagnoses, and treatment of metabolic acid–base disorders.
Tailor P, Raman T, Garganta CL, et al. Recurrent high anion gap metabolic acidosis secondary to 5-oxoproline (pyroglutamic acid).Am J Kidney Dis.2005;46:e4–e10.
Case report and discussion of a common but underdiagnosed cause of high anion gap acidosis-5 oxoproline toxicity.
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26 Respiratory Acid–Base Disorders
Andrew Labelle
Respiratory acid–base disorders are commonly seen in the intensive care unit, and can occur independently or coexist with metabolic acid–base disorders (see Chapter 24).
Respiratory acid–base disorders are characterized by altered plasma carbon dioxide levels, measured on arterial blood gas (ABG) analysis as the partial pressure of carbon dioxide (PaCO2). Respiratory acidosis is characterized by an elevated PaCO2 and decreased pH, and respiratory alkalosis by a decreased PaCO2and elevated pH. The PaCO2in healthy adults is 35 to 45 mm Hg and the normal pH is 7.35 to 7.45. For calculation purposes, it is reasonable to use 40 mm Hg as the baseline PaCO2 level and 7.4 as the baseline pH. In general, eachacute10 mm Hg change in the PaCO2 causes a 0.08 change in the arterial pH. For example, in a patient with a plasma pH of 7.4, an acute increase in the PaCO2from 40 to 50 mm Hg would be expected to decrease the plasma pH from 7.4 to 7.32. An acute 10 mm Hg decrease in the PaCO2
from 40 to 30 mm Hg would be expected to increase the pH from 7.4 to 7.48.
In respiratory acid–base disorders, the kidneys compensate for changes in the PaCO2 by increasing the plasma bicarbonate (HCO3−) in respiratory acidosis, or decreasing the plasma HCO3− in respiratory alkalosis. Acute respiratory acid–base disorders result in small changes in the HCO3−concentration, and cellular buffering predominates. Chronic renal compensation occurs during days to weeks, and results in a larger change in plasma HCO3−. Table 26.1 shows the expected change in the plasma HCO3−level in acute and chronic respiratory acidosis and alkalosis. The serum HCO3−in a healthy adult is approximately 22 to 26 mEq/L. Thus, it is reasonable to use a level of 24 mEq/L for calculation purposes. Compensatory change in HCO3−is associated with a shift in the pH back toward normal. A normal pH is not achieved by compensation alone andovercompensation does not occur.Therefore, a mixed respiratory and metabolic disorder is present if the pH is normal and the PaCO2is altered. For example, a pH of 7.4 with a PaCO2 of 60 mm Hg means that, in addition to the respiratory acidosis, a metabolic alkalosis is present that has moved the pH back to normal (see Step 4). Mixed acid–base disorders do not include the renal HCO3− compensation that occurs for acute and chronic respiratory acid–base disorder.
Evaluation of respiratory acid–base disorders can be relatively straightforward in patients with an isolated acute primary respiratory acidosis or alkalosis, such as occurs in a young patient with an acute asthma exacerbation or in an otherwise healthy patient with anxiety-induced hyperventilation, or more difficult when superimposed metabolic acid–base disorders are present in a critically ill patient. Further complicat- ing evaluation is the change that occurs in the serum HCO3−in acute and chronic
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