Acid-Base DisordersMara Nitu, MD,* GregMontgomery, MD,Howard Eigen, MDAuthor DisclosureDrs Nitu,Montgomery, andEigen have disclosedno nancialrelationships relevantto this article. Thiscommentary does notcontain a discussionof an unapproved/investigative use of acommercial product/device.Objectives After completing this article, readers should be able to:1. Understand the mechanisms for regulating acid-base physiology.2. Know the differential diagnosis of metabolic acidosis associated with high anion gapand plan for initial management.3. Know the differential diagnosis of normal anion gap metabolic acidosis.4. Describe pulmonary compensatory changes in metabolic acidosis and alkalosis.5. Understand how various diuretics can lead to acid-base imbalance.6. Describe renal compensatory changes in respiratory acidosis and alkalosis.Case StudyA16-year-oldgirl whohas nosignicantprevious medical historypresents totheemer-gency department witha4-day history of nausea, vomiting, fever, chills, diarrhea, legcramps, abdominal pain, andheadaches. Sheis nishinghermenstrual periodandar-rives with a tampon in place, which she reports that she inserted yesterday. Her vital signsinclude a heart rate of 165 beats/min, respiratory rate of 28 breaths/min, blood pressure65/30 mm Hg, and oxygen saturation of 100% on 4 L/min of oxygen. The most likely diag-nosis for this patient is toxic shock syndrome, which was later conrmed with a positive antibodytest.The initial arterial blood gas (ABG) values are:pH, 7.24Partial pressure of oxygen (PO2), 138 mm HgPartial pressure of carbon dioxide (PCO2), 19 mm HgBicarbonate (HCO3), 8 mEq/L (8 mmol/L)Base excess (BE), 18 mEq/L (18 mmol/L)Such ndings are suggestive of metabolic acidosis with respi-ratory compensation.Further laboratory results are:Serum sodium (Na), 133 mEq/L (133 mmol/L)Potassium (K), 4.2 mEq/L (4.2 mmol/L)Chloride (Cl), 109 mEq/L (109 mmol/L)HCO3, 12 mEq/L (12 mmol/L)Anion gap (AG), 12 mEq/L (12 mmol/L)Blood urea nitrogen (BUN), 49 mg/dL (17.5 mmol/L)Creatinine, 3.96 mg/dL (350 mol/L)Calcium, 5.2 mg/dL (1.3 mmol/L)Albumin, 2.0 g/dL (20 g/L)The apparently normal AG is misleading. After correctingthe AG for hypoalbuminemia, the adjusted AG is 17 mEq/L(17 mmol/L).Lacticacidemiaduetoshock, oneofthelikelycausesfor*Associate Professor of Clinical Pediatrics, Section of Pediatric Pulmonology, Critical Care and Allergy; Medical Director, PICU/Riley Hospital for Children; Medical Co-Director of Lifeline Transport Team, Indianapolis, IN.Assistant Professor of Clinical Pediatrics, Section of Pulmonology, Critical Care and Allergy; Medical Director, PediatricBronchoscopy Laboratory, James Whitcomb Riley Hospital for Children, Indianapolis, IN.Billie Lou Wood Professor of Pediatrics, Associate Chairman for Clinical Affairs; Director, Section of Pediatric Pulmonology,Critical Care and Allergy, James Whitcomb Riley Hospital for Children, Indianapolis, IN.AbbreviationsABG: arterial blood gasAG: anion gapBE: base excessBUN: blood urea nitrogenCa2: calciumCl: chlorideCNS: central nervous systemDKA: diabetic ketoacidosisGI: gastrointestinalH: hydrogenHCO3: bicarbonateK: potassiumMg2: magnesiumNa: sodiumNH3: ammoniaNH4: ammoniumPCO2: partial pressure of carbon dioxidePO2: partial pressure of oxygenRTA: renal tubular acidosisArticle uids and electrolytes240Pediatrics in Review Vol.32 No.6 June 2011 at Chulalongkorn University on December 8, 2014 http://pedsinreview.aappublications.org/ Downloaded from at Chulalongkorn University on December 8, 2014 http://pedsinreview.aappublications.org/ Downloaded from at Chulalongkorn University on December 8, 2014 http://pedsinreview.aappublications.org/ Downloaded from increasedAGmetabolicacidosis, is conrmedbyahighserumlactate value of 6.9 mg/dL (0.8 mmol/L). One hourlater, the ABG values are:pH, 7.06PO2, 63 mm HgPCO2, 47 mm HgHCO3, 13.2 mEq/L (13.2 mmol/L)BE, 16 mEq/L (16 mmol/L)This ABGpanel reveals metabolic acidosis withoutrespiratory compensationdue to developing respiratoryfailure.IntroductionThe loss of acid-base balance is an expression of variousconditions encounteredfrequentlyinclinical practice.Changes inhydrogenionconcentrationcanleadtounraveling of the protein tertiary structure, thereby caus-ingenzymedysfunction, enzymeloss, andcell death.Understandingthe physiology behindvarious distur-bances in acid-base balance is necessary for determining acorrect diagnosis and management plan.Maintaining acid-base homeostasis involves the lungs,kidneys, and a very complex system of buffers, all aimingto maintain the normal pH (7.35 to 7.45) of the arterialblood. Lowering the arterial pH below 7.35 is termedacidosis, and an increase of the arterial pH above 7.45constitutes alkalosis.Metabolic acidosis is associated with a lowpHand lowHCO3concentration. Metabolic alkalosis is associatedwith a high pH and high HCO3concentration. Respi-ratory acidosis is associated with a lowpHand high PCO2.Respiratory alkalosis is associated with a high pHand lowPCO2 (Fig. 1).Each acid-base disorder leads to countering respira-toryorrenal compensatoryresponsesthat attempt tonormalizethepH.Inmetabolicacidosis,forexample,ventilation is increased, resulting in a decrease in PCO2,which tends to raise the pH toward normal. These com-pensatoryattemptsneverovershootcorrectingthepH(Figs. 2 and 3).The process of acid-base regulation in-volvestherespiratorysystem(controlsPCO2), kidneys(regulates plasma HCO3by changes in acid excretion),andaverycomplexsystemof extracellular andintra-cellular buffers.The Respiratory System in Acid-Base BalanceThe respiratory system contributes to acid-base balancevia timely adjustments in alveolar minute ventilation thatmaintain systemic acid-base equilibrium in response toalterations in systemic pHand arterial PCO2. Systemic pHis monitored by central chemoreceptors on the ventro-lateral surface of the medulla oblongata and arterial PCO2(aswell asarterial PO2)byperipheral chemoreceptorslocated at the carotid and aortic bodies. These chemore-ceptors act through central respiratory control centers inthe pons and medulla to coordinate the respiratory mus-cle efforts of inhalation and exhalation, leading to adjust-ments in both components of minute ventilation: tidalvolume and respiratory cycle frequency. Lung-mediatedchanges in arterial PCO2 can lead to rapid alteration insystemic hydrogenions (H) because CO2is lipid-soluble and may readily cross cell membranes accordingtothe followingequation: HHCO37H2CO3(carbonicacid)7CO2H2O(water). Undernormalphysiologic conditions, this process allows for tight con-trol of arterial PCO2 near 40 mm Hg.Figure1. Acid-basechangesinmetabolicversusrespiratorydisorders.Figure2. Primary metabolic acidosis with subsequent respi-ratoryalkalosiscompensation. Theredarrowdoesnotcrossinto the alkalosis range, reecting the concept that overcom-pensation never occurs.uids and electrolytes acid-base disordersPediatrics in Review Vol.32 No.6 June 2011 241 at Chulalongkorn University on December 8, 2014 http://pedsinreview.aappublications.org/ Downloaded from The Kidneys in Acid-Base BalanceThe kidneys role in acid-base balance consists of reab-sorbing ltered HCO3and excreting the daily acid loadderived principally fromthe metabolismof sulfur-containing amino acids. Ninety percent of lteredHCO3is reabsorbed in the proximal tubules, primarilyby Na-Hexchange, and the remaining 10% is reab-sorbedinthedistal nephron, primarilyvia hydrogensecretion by a proton pump (H-ATPase). Under nor-mal conditions, no HCO3is present in the nal urine.The excretion of the daily Hload occurs in the distaltubule. Onceexcretedintheurine, theHmust bebound to a buffer to avoid excessive urine acidicationand promote further excretion. The two primary buffersin the urine are ammonia (NH3), which is excreted andmeasuredas ammonium(NH4) andphosphate(re-ferred to and measured as titratable acidity). The kidneyssynthesize and excrete NH3, which combines with Hexcretedbythecollectingduct cells toformNH4:HNH3NH4. NH3diffuses freely across mem-branes; NH4does not. Failure to produce and excretesufcient NH4, therefore, leads to the development ofmetabolic acidosis.Extracellular and Intracellular Buffers inAcid-Base BalanceThemostimportantbufferintheextracellularuidisHCO3, duebothtoitsrelativelyhighconcentrationand its ability to vary PCO2 via changes in alveolar venti-lation. Chemoreceptor analysis of arterial pH and PCO2allows for centrally mediated adjustments in minute ven-tilation to maintain arterial PCO2. The HCO3interactswithH, as demonstratedinthefollowingformula:H HCO37H2CO37CO2 H2O. This reactionserves as the basis for the Henderson-Hasselbalch equa-tion: pH6.1 log (HCO3/0.03 PCO2). Althoughthis equationdescribes apatients acid-basestatus, itdoes not provide insight intothe mechanismof theacid-base disorder.The Henderson-Hasselbalch equation lists PCO2 andHCO3as independent predictors of acid-base balance,but in reality they are interdependent (as suggested bythechemical reactionHHCO3describedprevi-ously). Furthermore, the Henderson-Hasselbalch equa-tion does not account for other important nonbicarbon-atebuffers present inthebody, suchas theprimaryintracellularbuffersofproteins, organicandinorganicphosphates, andhemoglobin. Inaddition, boneisanimportant site for buffering of acid and base loads.Laboratory Assessment of Acid-Base BalanceAcid-base balance is assessed by blood gas analysis andserummeasurement of several important electrolytes,leading to the calculation of the AG. Blood gas analyzersmeasurethepHandthePCO2directly. TheHCO3value is calculated fromthe Henderson-Hasselbalchequation. The BE value also is calculated as the amountof base/acid that should be added to a sample of wholeblood in vitro to restore the pHto 7.40 while the PCO2isheld at 40 mm Hg. The PCO2 not only points to the typeof disorder (respiratoryor metabolic) but alsocorre-sponds to the magnitude of the disorder.The AGmethodwas developedtoinclude othernonbicarbonatebuffers intheanalysis. Basedontheprincipleof electroneutrality, thesumof thepositivecharges should equal the sum of the negative charges asfollows: NaKMg2(magnesium) Ca2(cal-cium) HClHCO3proteinPO43(phos-phate) OH SO42(sulfate) CO32 conjugatebase. Sodium, chloride, andHCO3are measuredeasily in the serum. Therefore, the AGis calculated by theformula AG{Na} {ClHCO3}. A normal AGis122 mEq/L (12 mmol/L). Some clinicians and somepublished reports include potassiumas a measured cationin the calculation of AG, which raises the normal value by4 mEq/L (4 mmol/L).The AGis denedas the difference betweentheunmeasured plasma anions and the unmeasured plasmacations. Clinically, an elevated AGis believed to reect anincreaseofunmeasuredanionsand,therefore,ameta-bolic acidosis. This concept is explained by the fact thatunmeasuredcations(Mg2Ca2H)aremoreFigure 3. Primary respiratory acidosis with subsequent meta-bolic alkalosis compensation. The red arrow does not cross intothe alkalosis range, reecting the concept that overcompen-sation never occurs.uids and electrolytes acid-base disorders242Pediatrics in Review Vol.32 No.6 June 2011 at Chulalongkorn University on December 8, 2014 http://pedsinreview.aappublications.org/ Downloaded from tightlycontrolledandtheunmeasuredanions haveagreater tendency to uctuate. Theoretically, the AG alsocan increase following a decrease in serum K, Ca2, orMg2, but the normal concentration of these cations isso lowthat a reduction does not have a signicant clinicalimpact on the AG.Ingeneral,theseprinciplesholdtruefortheprevi-ouslyhealthyindividualwhodevelopsanacuteillness.However, for the critically ill host whose plasma proteinconcentrations are greatly reduced, the low protein val-ueshideanassociatedincreaseinunmeasuredanions.Without the correction for hypoalbuminemia, it is possi-ble tooverlooka true highAGacidosis, mistakenlyassuming it to be a normal AG acidosis.According to the Figge formula, each 1-g/dL reduc-tion in the serum albumin concentration is expected toreduce the AG by 2.5 mEq/L:Adjusted AGobserved AG (2.5 [normal albumin observed albumin]Metabolic Acid-Base DisturbanceMetabolic AcidosisMetabolic acidosis is dened as an acid-base imbalancethat leads to anion excess (low HCO3concentration)and subsequently to an arterial pH below 7.35. Severalmechanisms can lead to metabolic acidosis: excess acidproduction, increased acid intake, decreased renal acid ex-cretion, increasedHCO3lossfromthegastrointestinal(GI) tract, and excess HCO3excretion in the kidney.For a patient whohas intact respiratoryfunction,developing metabolic acidosis leads to respiratory com-pensation by hyperventilation. Each 1-mEq/L reductionin plasma HCO3concentration prompts a 1.2-mm HgcompensatoryfallinthePCO2.Clinically,thepatientsrespiratory rate increases within the rst hour of the onsetof metabolicacidosis, andrespiratorycompensationisachieved within 24 hours. Failure of the respiratory sys-tem to compensate for metabolic acidosis is an ominoussign that should trigger careful evaluation of the patientsmental status and cardiorespiratory function.CalculatingtheAGis a veryuseful initial stepindiagnosing various causes of metabolic acidosis.Metabolic Acidosis With Normal Anion GapMetabolic acidosis with normal AG reects an imbalanceof the measured plasma anions and cations. According tothe formula: AGNa (Cl HCO3), metabolicacidosis with normal AG can be explained by excessiveloss of HCO3(inthestool or intheurine) or byinability to excrete hydrogen ions. Table 1 lists the mostfrequent conditions leadingtonormal AGmetabolicacidosis.Of particular note is renal tubular acidosis (RTA), acomplex set of disorders of the kidney that can lead tonormal AGmetabolic acidosis. One disorder is the inabil-ity to excrete the daily acid load (type 1 RTA), leading toprogressiveHionretentionandlowplasmaHCO3concentration(10mEq/L[10mmol/L]). AnotherdisorderarisesfromtheinabilitytoreabsorbHCO3normally in the proximal tubule (proximal RTAor type 2RTA). HCO3is lost in the urine despite some reabsorp-tion in the distal nephron, leading to metabolic acidosisand alkaline urine.Normal AGmetabolicacidosiscausedbyexcessiveHCO3losses maybecorrectedbyslowinfusionofsodium bicarbonate-containing intravenous uids.Elevated Anion Gap Metabolic AcidosisElevated AG metabolic acidosis results from an excess ofunmeasuredanions. Various conditions that causeanTable 1. Causes of Normal AnionGap Metabolic AcidosisDisorders of the Gastrointestinal (GI) Tract Leading ToExcessive Bicarbonate Loss Diarrhea: the leading cause of normal anion gapmetabolic acidosis in children Surgical procedures that lead to an anastomosis of theureter with the GI tract, such as ureteroenterostomy/ureterosigmoidostomy, due to bicarbonate loss in theintestine Pancreatic stulaIatrogenic Hyperchloremic Metabolic Acidosis Result of excessive uid resuscitation with 0.9%sodium chloride or excessive use of 3% sodiumchloride to correct hyponatremiaRenal Loss of Bicarbonate Renal tubular acidosis type II (proximal) Iatrogenic: carbonic anhydrase inhibitor(acetazolamide) HyperparathyroidismMedications Acidifying agents: sodium chloride, potassiumchloride, enteral supplements Magnesium chloride Cholestyramine SpironolactoneHypoaldosteronismuids and electrolytes acid-base disordersPediatrics in Review Vol.32 No.6 June 2011 243 at Chulalongkorn University on December 8, 2014 http://pedsinreview.aappublications.org/ Downloaded from accumulation of unmeasured anions, leading to high AGmetabolic acidosis, are listed in Table 2.When faced with an elevated AG metabolic acidosis,calculatingthe osmotic gapmay helpdetermine theunderlying condition. Similar to the AG, the osmotic gapis the difference between the measured serum osmolalityandthecalculatedvalue. Thecalculatedserumosmo-lality is: 2[Na] glucose/18BUN/2.8. Anormal osmotic gap should be 122 mOsm/L. A highosmoticgapis asignof anexcess of anunmeasuredosmoticactivesubstancesuchasethyleneglycol(anti-freeze), methanol (wood alcohol), or paraldehyde.KetoacidosisKetoacidosis describes accumulationof ketonebodies(beta-hydroxybutyrateandacetoaceticacid) followingexcessiveintracellularuseoflipidsasametabolicsub-strate. This metabolic shift occurs during starvation orfasting or as a reection of a lack of appropriate metabolicsubstratefor energyproduction(duringspecicdietswherecarbohydratesarereplacedwithlipids). Hyper-ketotic diets sometimes are employedfor intractableepilepsy in an effort to decrease the seizure threshold.Diabetic ketoacidosis (DKA) results from a decreasein insulin production that leads to an inability to trans-port glucose into the cell. The cell shifts to lipid metab-olism, despite the surrounding hyperglycemia (also de-scribed as starvation in the middle of the plenty). Thediagnosis of DKA is conrmed by the ndings of hyper-glycemia, a high AG acidosis, ketonuria, and ketonemia.Theearliest symptoms of DKAarerelatedtohyper-glycemia. Older children and adolescents typically pres-ent with polyuria (due to the glucose-induced osmoticdiuresis), polydipsia (due to the increased urinary losses),fatigue, and weight loss. Hypovolemia may be severe ifurinarylosses arenot replaced, withthepresentationof very dry mucous membranes and prolonged capillaryrell time. As a result of worsening metabolic acidosis,thepatientdevelopshyperventilationanddeep(Kuss-maul)respirations, representingrespiratorycompensa-tion for metabolic acidosis. Hyperpnea develops from anincrease in minute volume (rate tidal volume) or fromincreased tidal volume alone without an increase in respi-ratory rate. When DKA is being managed, the patientschest excursion and respiratory rate should be observedcarefully to determine if hyperpnea is present. In infants,hyperpnea may be manifested only by tachypnea.Without prompt medical attention, DKA can prog-ress to cerebral edema and cardiorespiratory arrest.Neurologic ndings, ranging from drowsiness, lethargy,and obtundation to coma, are related to the severity ofhyperosmolality or to the degree of acidosis. Treatmentof DKA includes sensitive correction of the underlyinginsulin, volume, and electrolyte deciencies.Lactic AcidosisLactic acidosis, another cause of an elevated AG, occurswhencellsshifttoanaerobicpathwaysforenergypro-ductionas aresult of tissuehypoxiaduetoinappro-priate tissue perfusion, inappropriate oxygen supply, ormitochondrialdysfunction(asseenininbornerrorsofmetabolism or ingestion of drugs or toxins). The clinicalpresentation may involve seizures or symptoms consis-tent with the initial disorder that led to lactic acidosis,such as cyanosis, signs and symptoms suggestive of tissuehypoperfusion, and hypotension. As lactic acidosis wors-ens, further hemodynamic compromise occurs. Manage-ment shouldbetargetedtorestoringadequatetissueperfusion and oxygen supply by treating the underlyingcause of the lactic acidosis.Inborn Errors of MetabolismSeveral inbornerrors of metabolismcanpresent withhigh AG metabolic acidosis. Based on the affected met-abolic pathway, the increased AG is caused by a differentchemical substance: urea cycle defects present with hy-perammonemia; or inborn errors of amino acids, carbo-hydrate, or organic acid metabolism present either withketoacidosis, lactic acidosis (as in Krebs cycle defects), orincreased organic acids production. Symptoms often arenonspecic and include poor feeding, failure to thrive,seizures, and vomiting.Table 2. Causes of Elevated AnionGap Metabolic AcidosisKetoacidosis Starvation or fasting Diabetic ketoacidosisLactic Acidosis Tissue hypoxia Excessive muscular activity Inborn errors of metabolismIngestions Methanol Ethylene glycol Salicylates ParaldehydeRenal Failure Uremiauids and electrolytes acid-base disorders244Pediatrics in Review Vol.32 No.6 June 2011 at Chulalongkorn University on December 8, 2014 http://pedsinreview.aappublications.org/ Downloaded from Managing inborn errors of metabolism involves iden-tifying the defective or decient enzyme and limiting theintake of the metabolic substrate that requires the use ofthat particular enzyme. In selected cases, dialysis may bethe appropriate tool for removing the excess anion.IngestionsIngestions of various chemical substances areanothercauseofmetabolicacidosiswithanelevatedAG. Sali-cylateoverdoseis well knowntocauseincreasedAGmetabolicacidosisbyinterferingwithcellularmetabo-lism(uncouplingof oxidativephosphorylation). Earlysymptoms of salicylate overdose include tinnitus, fever,vertigo, nausea, vomiting, anddiarrhea. Moresevereintoxication can cause altered mental status, coma, non-cardiac pulmonary edema, anddeath. Most patientsshowsigns of intoxicationwhentheplasmasalicylateconcentration exceeds 40 mg/dL. Treatment of salicy-lateingestioninvolves promotingalkalinediuresis toenhance renal salicylate excretion. In severe cases, dialysismay be required (generally considered when plasma sa-licylate concentrations exceed 80 mg/dL in acute intox-ication and 60 mg/dL in chronic ingestions).Toluene inhalation also can lead to metabolic acidosiswith an increased AG. In patients who experience tolu-ene ingestion (glue snifng), the overproduced hippu-rate is both ltered and secreted by the kidneys, leadingto rapid elimination in the urine. As a result, the AG maybe near-normal or normal at the time of presentation andthe patient might be diagnosed mistakenly as having anormal AG acidosis.Ethylene glycol (antifreeze), methanol, and paralde-hyde ingestion lead to an increased AG metabolic acido-sis and an increased osmotic gap. Both the AG and theacidosis due to methanol and ethylene glycol ingestionsresult from metabolism of the parent compound. Nei-ther may be seeninpatients early inthe course ofingestion or when there is concurrent ingestion of etha-nol. Ethanol combines competitively with alcohol dehy-drogenase, thereby slowing the metabolism of methanolor ethylene glycol to their toxic metabolites and slowingtheappearanceofboththeacidosisandthehighAG.This effect explains why ethanol administration is used inthe medical management of methanol and ethylene gly-col ingestions, along with fomepizole (alcohol dehydro-genaseinhibitor).Managementofethyleneglycol andmethanol toxicity also involves hemodialysis, which re-movesboththeingestedsubstanceandthemetabolicbyproducts from the serum.Massiveingestions of creams containingpropyleneglycol (eg, silver sulfadiazine) also can lead to increasedAG metabolic acidosis.Renal FailureRenal failure causes an increased AG metabolic acidosisdue to the failure to excrete H. Normally, eliminationof the serum acid load is achieved by urinary excretion ofH, both as titratable acidity and as NH4. Titratableacid is a term used to describe acids such as phosphoricacidandsulfuricacidpresent intheurine. Thetermexplicitly excludes NH4as a source of acid and is part ofthe calculation for net acid excretion. The termtitratableacid was chosen based on the chemical reaction of titra-tion (neutralization) of those acids in reaction with so-dium hydroxide.Asthenumberoffunctioningnephronsdeclinesinchronic kidney disease and the glomerular ltration ratedecreases to below 25% of normal, the patient developsprogressive high AG metabolic acidosis (hyperchloremiamay occur transiently in the initial phases of renal failure).In addition to the decrease in NH4excretion, decreasedtitratable acidity (primarily as phosphate) may play a rolein the pathogenesis of metabolic acidosis in patients whoexperience advanced kidney disease. Of course, dialysisoften is employed to correct the severe uid and electro-lyte imbalances generated by renal failure.Management of Metabolic AcidosisRegardless of the cause, acidemia, if untreated, can leadto signicant adverse consequences (Table 3).Useof HCO3therapytoadjust thepHfor pa-tients who have metabolic acidosis is controversial. Slowinfusion of sodium bicarbonate-containing intravenousuids canbeusedincases of normal AGmetabolicacidosistoreplenishexcessiveHCO3losses(eg,asaresult of excessive diarrhea). However, infusing sodiumbicarbonate-containinguids for increasedAGmeta-bolic acidosis has questionable benet and should not beused clinically.As discussed, HCO3combines with H, leading toH2CO3that subsequently dissociates to CO2and H2O.Infusing HCO3decreases serum pH and raises CO2 andH2O. Neitherthecell membranesnortheblood-brainbarrier is very permeable to HCO3; CO2diffuses freely tothe intracellular space, where it combines with H2O, lead-ingtoH2CO3andworseningof theintracellular pH.Administering intravenous sodiumbicarbonate to a patientwho has an increased AG metabolic acidosis can lead to afalse sense of security because the underlying problem ishidden by an articially improved serum pH.uids and electrolytes acid-base disordersPediatrics in Review Vol.32 No.6 June 2011 245 at Chulalongkorn University on December 8, 2014 http://pedsinreview.aappublications.org/ Downloaded from Sodium bicarbonate once held a prominent positionin the management of cardiac arrest. Reversing the aci-dosis caused by global hypoperfusion made physiologicsense because severe acidemia may worsen tissue perfu-sionbydecreasingcardiaccontractility. However, themost effective means of correcting the acidosis in cardiacarrest is torestoreadequateoxygenation, ventilation,and tissue perfusion. Because most pediatric cardiac ar-rests are due to respiratory failure, support of ventilationthrough early intubation is the primary treatment, fol-lowedby support of the circulationwithuids andinotropic agents. Currently, the American Heart Associ-ation recommends that sodium bicarbonate administra-tion be considered only in children who suffer prolongedcardiac arrest and documented severe metabolic acidosisandwhofail torespondtooxygenation, ventilation,intravenous uids, andchest compressions combinedwith epinephrine in recommended doses.Metabolic AlkalosisMetabolic alkalosis is dened as an acid-base imbalanceleading to increased plasma HCO3and an arterial pHabove 7.45. Several mechanisms can lead to the elevationintheplasmaHCO3: excessivehydrogenloss, func-tional addition of new HCO3, and volume contractionaround a relatively constant amount of extracellularHCO3(called a contraction alkalosis). The kidneysare extremely efcient in eliminating excess HCO3intheurine. AconfoundingfactorisrequiredforserumHCO3to accumulate, such as impaired renal function,Kdepletion, or volume depletion.Ingeneral, a patient compensates for a metabolicalkalosis by decreasing ventilation. Respiratory compen-sation by hypoventilation raises PCO2 by 0.7 mm Hg forevery 1 mEq/L (1 mmol/L) of serum HCO3increase.Excessive Hlosses can occur either in the urine or GItract and lead to HCO3accumulation as the result ofthe following reactions:H2O7HHOHOCO27HCO3Increased loss of gastric content, which has high con-centrations of hydrogen chloride, as a result of persistentvomiting (eg, self-induced, pyloric stenosis) or highnasogastric tube drainage leads to metabolic alkalosis. Ifuid losses continue unreplaced, dehydration and lacticacidosis ultimately develop. Of note, infants of motherswho have bulimia have metabolic alkalosis at birth.HighHloss intheurinecanoccur inthedistalnephron.Increasedsecretionofaldosteronestimulatesthe secretory H-ATPase pump, increasing Nareabsorp-tion, therebymakingthelumenmoreelectronegativeand causing more Hand Kexcretion, which results inconcurrent metabolic alkalosis and hypokalemia. Patientswho have primary mineralocorticoid excess present withhypokalemiaandhypertension. Incontrast, secondaryhyperaldosteronismduetocongestiveheart failureorcirrhosis usually does not present with metabolic alkalosisorhypokalemiabecausetheabove-mentionedmecha-nism is blunted by decreased distal nephron Nadeliv-ery. Iatrogenicmetabolicalkalosis alongwithvolumecontractioncanoccurinpatientstreatedwithlooporthiazidediuretics, whichcauseCldepletionandin-creaseddeliveryof Natothecollectingduct, whichenhances Kand Hsecretion.Bartter and Gitelman syndromes present with meta-bolic alkalosis and hypokalemia due to a genetic defect inthe transporters in the loop of Henle and distal tubule,Table3. Consequences ofMetabolic AcidosisCerebral Inhibition of metabolism Cerebral edema Obtundation and comaCardiovascular Decreased cardiac contractility Decreased cardiovascular responsiveness tocatecholamine Decreased threshold for arrhythmias Reduction of cardiac output, blood pressure, andend-organ perfusion Pulmonary vasoconstrictionRespiratory Hyperventilation as a result of respiratorycompensation Decreased respiratory muscle strength Increased work of breathingHematologic Oxyhemoglobin dissociation curve shifts to the right(the oxygen is more easily released at the tissue leveldue to a lower pH)Metabolic Inhibition of anaerobic glycolysis Insulin resistance Decreased adenosine triphosphate synthesis Hyperkalemia Increased protein degradationuids and electrolytes acid-base disorders246Pediatrics in Review Vol.32 No.6 June 2011 at Chulalongkorn University on December 8, 2014 http://pedsinreview.aappublications.org/ Downloaded from respectively, thesamelocations as thoseinhibitedbyloop and thiazide diuretics.In addition to Hloss, metabolic alkalosis also can beinduced by the shift of Hinto the cells.As discussed previously, hypokalemia is a frequent nd-ing in patients who have metabolic alkalosis. Hypokalemiaby itself causes intracellular acidosis and increased serumalkalosis by the following mechanism: intracellular Kshifts into the serum to replete the extracellular stores, andto maintain electroneutrality, Henters the cells. Hydro-gen movement into the cells lowers the intracellular pHand leaves unbuffered excess HCO3in the serum. Theintracellularacidosisinrenal tubularcellspromotesHsecretion and, therefore, HCO3reabsorption.Metabolic alkalosis due to functional addition ofnewHCO3canoccurbyseveral mechanisms: de-creased renal excretion of HCO3, posthypercapnicalkalosis, or excessive intake or administration of alkali.Decreased Renal Bicarbonate ExcretionRenal failure can lead to metabolic alkalosis because thekidneys fail to excrete excess HCO3.Posthypercapnic AlkalosisChronic respiratory acidosis (retention of CO2) leads to acompensatory increase inhydrogensecretionandanensuing increase in the plasma HCO3concentration tocorrect the pH. When the PCO2 is decreased rapidly bymechanical ventilationof a patient whohas chronicrespiratoryacidosis, theensuingmetabolicalkalosis isslow to disappear. Because Clloss often is present inposthypercapnic alkalosis, repleting the Cldecit maybe essential to correct the alkalosis.Furthermore, the acute fall in PCO2 in a person whohas chronic respiratory acidosis raises the cerebral intra-cellular pHacutely, achangethat caninduceseriousneurologicabnormalities anddeathbecauseCO2candiffusefreelyacrosstheblood-brainbarrieroutoftheintracellularspace, leadingtoseverealkalosis. Accord-ingly, the PCO2 must be reduced gradually in mechani-cally ventilated patients who present initially with chronichypercapnia.Excessive Intake or Administration of AlkaliAlkali administration does not induce metabolic alkalosisin healthy people because the healthy kidney can excreteHCO3rapidly in the urine. However, metabolic alka-losiscanoccurif verylargequantitiesof HCO3areadministered acutely or if the ability to excrete HCO3is impaired. Theadministrationof largequantities ofcitrate is known to lead to metabolic alkalosis. Examplesof large administrations of citrate are infusion of morethan8units of bankedbloodor freshfrozenplasmaoradministrationofcitrateasananticoagulantduringdialysis.Contraction AlkalosisContractionalkalosisoccurswhenrelativelylargevol-umes of HCO3-free uid are lost, a situation frequentlyseen with administration of intravenous loop diuretics.Contraction alkalosis also may occur in other disorders inwhich a high-Cl, low-HCO3solution is lost, such assweat losses in cystic brosis, loss of gastric secretions inpatients who have achlorhydria, and uid loss from fre-quent stooling by patients who have congenital chlori-dorrhea, a rare congenital secretory diarrhea.Regardlessof thecause, alkalosis, if untreated, canlead to signicant adverse consequences (Table 4).Management of Metabolic AlkalosisThreegeneralprinciplesapplytothetherapyofmeta-bolic alkalosis: correct true volume depletion, correct Kdepletion, and correct Cldepletion (in Cl-responsivemetabolic alkalosis). For patients who have true volumeTable4. Consequences ofUntreated AlkalosisCerebral Cerebral vasoconstriction with reduction of cerebralblood ow Tetany, seizures, lethargy, delirium, and stuporCardiovascular Vasoconstriction of the small arterioles, includingcoronary arteries Decreased threshold for arrhythmiasRespiratory Compensatory hypoventilation with possiblesubsequent hypoxemia and hypercarbia (respiratoryfailure)Hematologic Oxyhemoglobin dissociation curve shifts to the left(the oxygen is bound more tightly to theoxyhemoglobin)Metabolic and Electrolyte Imbalances Stimulation of anaerobic glycolysis Hypokalemia Decreased plasma ionized calcium Hypomagnesemia and hypophosphatemiauids and electrolytes acid-base disordersPediatrics in Review Vol.32 No.6 June 2011 247 at Chulalongkorn University on December 8, 2014 http://pedsinreview.aappublications.org/ Downloaded from depletion, uid administration of normal saline replacesthe Cland free water decits. Potassium chloride ad-ministration for patients who have concurrent hypokale-mia is an important component of treatment. This agentbecomes particularly helpful in patients who are edema-tous due to heart failure or cirrhosis and cannot receivesodiumchloridebecauseaninfusioncanincreasethedegree of edema. Another method for treating metabolicalkalosis in an edematous patient is to administer acet-azolamide, a carbonic anhydrase inhibitor, which causesamildincreaseinproductionof urinethat has highHCO3content, thus reacidifying the blood.Correcting metabolic alkalosis (usually diuretic-induced) maybeparticularlyimportant for intubatedpatients who have chronic respiratory acidosis. Thehigher pHcaused by the metabolic alkalosis subse-quently impairs the respiratory drive and leads to hypo-ventilation that exacerbates hypoxemia, delaying wean-ing and extubation. In these patients, metabolic alkalosisusually is corrected by enteral supplements of potassiumchloride or sodium chloride. Very rarely, in the intensivecare unit setting, the metabolic alkalosis can be so severethat it impairs weaning from mechanical ventilation. Inthesecircumstances, intravenousinfusionof hydrogenchloride can correct the alkalosis.Measuring the urinary Clis the preferred method forassessing the renal response to Cltherapy. For patientsexperiencingCldepletion(urinaryCl10mEq/L[10 mmol/L]) (eg, GI losses, diuretic therapy, and sweatlosses in cystic brosis), every attempt should be made tocorrect hypochloremia. Conditions that cause metabolicalkalosis due to high aldosterone concentrations are un-responsive to Cland are associated with high urine Clconcentrations.Minimizingcontinuingacidandchloridelossesbyexcessivenasogastricuiddrainagewithahistamine2blocker or proton pump inhibitor also may be helpful.Respiratory Acid-Base DisturbancesAs noted, chemoreceptor analysis of arterial pHandPCO2 allows for centrally mediated adjustments in min-ute ventilation to maintain arterial PCO2near 40 mmHg.Primary respiratory disturbances in acid-base equilibriummay result from different pathologic scenarios. ArterialPCO2risesabnormally(respiratoryacidosis)ifsystemicCO2production exceeds the ventilatory capacity or whenefcient ventilation is inhibited by intrinsic or acquiredconditions. Conversely, arterial PCO2decreasesabnor-mally(respiratoryalkalosis)inresponsetophysiologicdisorders that result in excessive ventilation. Both respi-ratoryacidosisandalkalosismayappearinassociationwith other metabolic acid-base disturbances, often mak-ing accurate diagnosis and treatment of the underlyingdisease difcult to achieve.Respiratory AcidosisRespiratory acidosis occurs when arterial PCO2 increasesand arterial pH decreases due to a reduction in alveolarminuteventilationor,lesscommonly,anexcessivein-crease inCO2production. Acute respiratory acidosisoccurs withanacuteelevationinPCO2as aresult ofsuddenlimitationorfailureof therespiratorysystem.Chronic respiratoryacidosis is duetomoreindolentincreases in PCO2 as a consequence of systemic diseaseover thecourseof several days. Reductioninminuteventilation can result from depression of central nervoussystem (CNS) respiratory drive, anatomic obstruction ofthe respiratory tract, or intrinsic or acquired impairmentsof normal thoracic excursion (Table 5).Table 5. Common Causes ofRespiratory Acidosis inChildrenCentral Nervous System Depression Medication effects Sedative: benzodiazepines, barbiturates Analgesic: narcotics Anesthetic agents: propofol Central nervous system disorders Head trauma Infection Tumor Congenital central hypoventilationImpairments of Thoracic Excursion or VentilatoryEfciency Chest wall/lung disorders Asphyxiating thoracic dystrophy Progressive thoracic scoliosis Thoracic trauma Acute lung injury/pneumonia Pneumothorax/parapneumonic effusion Severe obesity Nerve/muscle disorders Congenital myopathies Spinal cord injury Toxin exposure: organophosphates, botulism Guillain-BarresyndromeRespiratory Tract Obstruction Upper airway obstruction Adenotonsillar hypertrophy Status asthmaticusuids and electrolytes acid-base disorders248Pediatrics in Review Vol.32 No.6 June 2011 at Chulalongkorn University on December 8, 2014 http://pedsinreview.aappublications.org/ Downloaded from The bodys compensatory changes inresponse toacute respiratory acidosis initially are limited to bufferingvia systemically available cellular HCO3stores. Becauseof this limitation, serumHCO3concentrations riseacutely by only 1 mEq/L (1 mmol/L) for every 10-mmHgelevationinarterial PCO2. Inresponsetochronicrespiratory acidosis, the kidney retains HCO3andsecretesacid, analterationinfunctionthat takessev-eral (3to5)daystohaveanoticeablephysiologicef-fect. Eventually, inchronicrespiratoryacidosis, serumHCO3concentrations ultimately rise by approximately3.5 mEq/L (3.5 mmol/L) for every 10-mm Hg eleva-tion in arterial PCO2.Respiratoryacidosis canaffect boththeCNSandcardiovascular system adversely. CNS effects include in-creasedcerebral bloodowandincreasedintracranialpressure, which can present clinically as disorientation,acute confusion, headache, andmental obtundation.Cardiovascular effects include peripheral vasodilationand tachycardia. Severe hypoventilation leads to higherarterial PCO2andmoreseverehypoxemia. Hypoxemiamay be partially compensated by improved tissue extrac-tion of oxygen via an acute acidosis-mediated rightwardshift in the oxyhemoglobin dissociation curve and releaseof oxygen to the tissues. However, as respiratory acidosispersists, areductioninredbloodcell 2,3diphospho-glycerate(anorganophosphatecreatedinerythrocytesduring glycolysis) results in a shift of the curve to the leftand an increase of hemoglobin afnity for oxygen.Management of Respiratory AcidosisTreatment of respiratory acidosis usually focuses on cor-recting the primary disturbance. Immediate discontinu-ationof medications that suppress central respiratorydriveor administrationof appropriatereversal agentsshould be considered. Noninvasive ventilation or intuba-tionwithmechanical ventilationmaybenecessarytoachieve adequate alveolar ventilationandappropriatereduction in arterial PCO2. As arterial PCO2 is corrected,individuals who experience excessive Cldepletion maysubsequently suffer poor renal clearance of HCO3,leading to a concomitant state of metabolic alkalosis.Respiratory AlkalosisRespiratory alkalosis occurs when there is reduction inarterial PCO2and elevation in arterial pHdue to excessivealveolar ventilation. Causes of excessive alveolar ventila-tion include medication toxicity, CNS disease, intrinsiclung diseases, and hypoxia (Table 6).Compensatory changes in response to respiratory al-kalosis involve renal excretion of HCO3. As in respira-tory acidosis, renal compensation improves as the disor-derpersists. SerumHCO3concentrationsdeclineby2 mEq/L (2 mmol/L) for every 10-mm Hg decrease inarterial PCO2inacuterespiratoryalkalosis. Inchronicrespiratory alkalosis, serum HCO3concentrations de-clineby4mEq/L(4mmol/L)forevery10-mmHgdecrease in arterial PCO2.Adverse Effects of Respiratory AlkalosisAdverse systemic effects of respiratory alkalosis includeCNS and cardiovascular disturbances. Respiratory alka-losis often provokes increased neuromuscular irritability,manifested as paresthesias or carpopedal spasms. In ad-dition,cerebralbloodvesselsvasoconstrictacutelyandimpede adequate cerebral blood ow. Myocardial con-tractility may be diminished and cardiac arrhythmias mayoccur.Theoxyhemoglobindissociationcurveshiftstothe left in response to acute respiratory alkalosis, impair-ing peripheral oxygen delivery.Management of Respiratory AlkalosisTreatment of respiratory alkalosis centers on correctingthe underlying systemic cause or disorder. Close assess-ment of oxygenation status and correction of hypoxemiaviaoxygenadministrationisparamount. Acutehyper-ventilation syndrome often is treated simply by havingthepatientbreatheintoapaperbag.Topreventhighaltitude-associatedrespiratoryalkalosis, slowascent toallowforacclimatizationisrecommended; administra-Table 6. Common Causes ofRespiratory Alkalosis inChildrenMedication Toxicity Salicylate overdose Central nervous system stimulants Xanthines (eg, caffeine) Analeptics (eg, doxapram)Central Nervous System Disorders Central nervous system tumor Head injury/stroke Hyperventilation syndrome: stress/anxietyRespiratory Disorders Pneumonia Status asthmaticus Pulmonary edema Excessive mechanical or noninvasive ventilation Hypoxia/high altitudeuids and electrolytes acid-base disordersPediatrics in Review Vol.32 No.6 June 2011 249 at Chulalongkorn University on December 8, 2014 http://pedsinreview.aappublications.org/ Downloaded from tionofacetazolamidebeforeascentshouldbeconsid-ered. The only cure for acute mountain sickness, once ithas developed, is either acclimatization or descent. How-ever,symptomsofacutemountainsicknesscanbere-duced with acetazolamide and pain medications forheadaches.Suggested ReadingBrandis K. Acid-Base Physiology. Accessed March 2011 at: http://www.anaesthesiamcq.com/AcidBaseBook/ABindex.phpCarrillo-Lopez H, Chavez A, Jarillo A, Olivar V. Acid-base disor-ders. In: FuhrmanB, ZimmermanJ, eds. PediatricCriticalCare. 3rd ed. Philadelphia, PA: Mosby Elsevier; 2005:958989Grogono AW. Acid-Base Tutorial. 2010. Accessed March 2011 at:http://www.acid-base.comKraut JA, Madias NE. Approach to patients with acid-base disor-ders. Respiratory Care. 2001;46:392403SummaryA wide array of conditions ultimately can lead toacid-base imbalance, and interpretation of acid-basedisorders always involves a mix of art, knowledge,and clinical experience.Solving the puzzle of acidbase disorders beginswith accurate diagnosis, a process requiring twotasks. First, acid-base variables in the blood must bereliably measured to determine the effect of multipleions and buffers. Second, the data must beinterpreted in relation to human disease to denethe patients acidbase status.History, physical examination, and additionallaboratory testing and imaging help the clinician toidentify the specic cause of the acid-basedisturbance and to undertake appropriateintervention.PIR QuizQuiz also available online at: http://www.pedsinreview.aappublications.org.9. Which of the following statements best describes the roles of the different nephron segments inmaintaining acid-base balance?A. The proximal and distal tubules are equally responsible for acid excretion.B. The proximal tubule is the primary segment responsible for bicarbonate reabsorption and acidexcretion.C. The distal tubule is the primary segment responsible for bicarbonate reabsorption and acid excretion.D. The proximal tubule is the primary segment responsible for bicarbonate reabsorption, and the distalnephron principally promotes acid excretion.E. The proximal tubule and loop of Henle are primarily responsible for both bicarbonate reabsorption andacid excretion.10. Which of the following constellation of choices best describes sequelae of metabolic acidosis?CardiacOutputRespiratoryRateOxyhemoglobinDissociationCurve ShiftAdenosineTriphosphateSynthesisA. Increased Decreased To the left IncreasedB. Decreased Increased To the right DecreasedC. Increased Increased To the left IncreasedD. Increased Decreased To the right IncreasedE. Decreased Decreased To the right Decreaseduids and electrolytes acid-base disorders250Pediatrics in Review Vol.32 No.6 June 2011 at Chulalongkorn University on December 8, 2014 http://pedsinreview.aappublications.org/ Downloaded from 11. Among the following, the most common mechanism leading to metabolic alkalosis is:A. Chronic diarrhea.B. Secondary hypoaldosteronism.C. Hypokalemia.D. Hypoventilation.E. Primary hyperaldosteronism.12. The most common sequelae of early acute respiratory acidosis are:IntracranialPressure Heart RateOxyhemoglobinDissociationCurve ShiftRenal BicarbonateReabsorptionA. Increased Decreased To the right IncreasedB. Decreased Increased To the right DecreasedC. Increased Increased To the left IncreasedD. Increased Increased To the right IncreasedE. Decreased Decreased To the left Decreased13. The most accurate statement about respiratory alkalosis is that:A. Cardiac arrhythmias are never observed.B. It occurs when there is a reduction in PCO2.C. It results in decreased renal excretion of alkali.D. It results in vasodilation of cerebral blood vessels.E. Oxygen delivery is generally unaffected.uids and electrolytes acid-base disordersPediatrics in Review Vol.32 No.6 June 2011 251 at Chulalongkorn University on December 8, 2014 http://pedsinreview.aappublications.org/ Downloaded from DOI: 10.1542/pir.32-6-2402011;32;240 Pediatrics in ReviewMara Nitu, Greg Montgomery and Howard EigenAcid-Base DisordersServicesUpdated Information &http://pedsinreview.aappublications.org/content/32/6/240including high resolution figures, can be found at: Referenceshttp://pedsinreview.aappublications.org/content/32/6/240#BIBLThis article cites 1 articles, 0 of which you can access for free at: Subspecialty Collections_subhttp://pedsinreview.aappublications.org/cgi/collection/endocrinologyEndocrinologyfollowing collection(s): This article, along with others on similar topics, appears in thePermissions & Licensinghttp://pedsinreview.aappublications.org/site/misc/Permissions.xhtmlin its entirety can be found online at: Information about reproducing this article in parts (figures, tables) orReprintshttp://pedsinreview.aappublications.org/site/misc/reprints.xhtmlInformation about ordering reprints can be found online: at Chulalongkorn University on December 8, 2014 http://pedsinreview.aappublications.org/ Downloaded from parenchyma is the result of the col-lateral ventilation through the poresof Kohn, the bronchoalveolar chan-nels of Lambert, or interbronchiolarchannels. Given that collateral circu-lation may not be developed until thesecond 6 months after birth, hyper-ination may not be apparent in theperinatal period. Alternatively, hy-perinationmayoccurshortlyafterbirthwiththe start of respiration,becausetheproposedpathwaysforcollateral ventilation favor the move-ment of air into the obstructed seg-mentbyacheck-valvetypemecha-nism. At the root of the involvedtissue, a mucus-lled cystic structure(the mucocele) with nger-like pro-jectionsrepresentstheatreticbron-chus, which is isolated fromthe prox-imal bronchial tree and is dilated bytheaccumulatedmucus. Thebron-chial patterndistal tothemucoceleusually is normal.The only physical nding may bedecreased breath sounds over the af-fected area. When a major bronchusis atretic, the affected distal lobe maybesignicantlyhyperinated, caus-ing compression of surroundinghealthy lung and shift of the medias-tinum to the opposite side. In suchpatients, symptoms of reduced exer-cise tolerance and possibly wheezingand shortness of breath may beprominent. CTor, less commonly,MRI is used to conrmthe diagnosis.Bronchoscopymaybeusedtoruleout other causes.ManagementIn many cases, bronchial atresia war-rants no intervention. Surgical exci-sion is indicated when overdistentionof the affected lung segment or lobeleads to compromise of surroundingnormallung(asincongenitallobaremphysema) and the patient has sig-nicant complications, such as recur-rent infections.Lessons for the ClinicianWhen a teenager presents with lo-bar or segmental hyperination ofthelung,bronchialatresiashouldbe considered in the differential di-agnosis.Congenital bronchial atresia is a rareand benign entity that might occa-sionally resemble serious underlyingdiseases onradiographic examina-tion. There are occasions when in-fectionmight result andantibiotictreatment might be necessary.CT scan of the chest is the proce-dureof choicefor thediagnosis,but indoubtful cases, bronchos-copy may be useful to excludeother conditions and infection.(Muhammad Adeel Rishi, MD,Rashid Nadeem, MD, RosalindFranklinUniversity of Science andMedicine, Chicago Medical School,Chicago, IL.)References1. Rennie G. Exophthalmic goiter com-binedwithmyastheniagravis. RevNeurolPsychiatry. 1908;6:2292332. Ramsay BH, Byron FX. Mucocele, con-genital bronchiectasis, andbronchiogeniccyst. J Thorac Surg. 1953;26:2130To view Suggested Reading lists forthe cases, visit pedsinreview.aappublications.org and click onIndex of Suspicion.ClaricationThe article entitled Acid-Base Disorders in the June issue (Pediatr Rev. 2011;32:240251) contains this statement: Lowering the arterial pHbelow7.35 is termed acidosis, andan increase of the arterial pH above 7.45 constitutes alkalosis. This terminology is indeedused in common clinical parlance with which readers are familiar. Technically, acidosis andalkalosis refer to the physiologic processes that affect the pH of the blood, with the termsacidemia and alkalemia designating abnormalities of the blood pH specically.CorrectionIn the In Brief article entitled Growth in the September issue (Pediatr Rev. 2011;32:404406), the formula for estimating height based on parental measurements for girlsshould read as follows: For girls: [fathers height (cm) 13 mothers height (cm)]/2 or[fathers height (in) 5 mothers height (in)]/2. The journal regrets the error.index of suspicionPediatrics in Review Vol.32 No.11 November 2011 501DOI: 10.1542/pir.32-6-2402011;32;240 Pediatrics in ReviewMara Nitu, Greg Montgomery and Howard EigenAcid-Base Disordershttp://pedsinreview.aappublications.org/content/32/6/240located on the World Wide Web at: The online version of this article, along with updated information and services, isl.pdfhttp://pedsinreview.aappublications.org/http://pedsinreview.aappublications.org/content/32/11/501.1.fulAn erratum has been published regarding this article. Please see the attached page for: http://pedsinreview.aappublications.org/content/suppl/2011/09/01/32.6.240.DC1.htmlData Supplement at: Pediatrics. All rights reserved. Print ISSN: 0191-9601. Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2011 by the American Academy of published, and trademarked by the American Academy of Pediatrics, 141 Northwest Pointpublication, it has been published continuously since 1979. Pediatrics in Review is owned, Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly at Chulalongkorn University on December 8, 2014 http://pedsinreview.aappublications.org/ Downloaded from