Acid-Base Disturbances in the Emergency Department

Home , Extracellular fluid, Respiratory compensation

A complete history and physical ex- amination are essential to determine the cause of a discovered disorder. Acid-base The initial laboratory investigation of a suspected acid-base disturbance is assessment of arterial blood gases disturbances in and serum electrolytes. Further tests to differentiate the various causes of an identified disorder might then be the emergency indicated. Physiology department Fluctuations in the acidity of body fluids are resisted by several buffer systems. A buffer is a substance that Part 1: Piecing the clues together is able to absorb or donate hydrogen (H') ions. Equation I represents buff- TIMI E RUTLEDC1)E, MID, C1CP(EM) ering; the reaction can be driven either way, depending on whether there is a deficit or an excess of H+ ions. 1. HA H++A cid-base disorders reflect effects, including confusion and The pH of a solution containing this 4 * disturbances of hydrogen seizures.-' buffer system is determined by the ion homeostasis. Human An acidosis is a pathologic process Henderson-Hasselbalch equation: extracellular fluid pH (the that tends to push blood pH dow-n- negative logarithm ofthe hydrogen ion ward. An alkalosis, on the other hand, 2. pH = pKa + log[A ]/[HA] concentration) is normally maintained pushes the pH upward. An acidosis between 7.35 and 7.45. A plasma pH and an alkalosis can co-exist in a mixed In this equation Ka is the dissociation below 7.35 is termed acidemia, and a acid-base disorder; the pH then de- constant of the weak acid HA. The pH above 7.45 is termed alkalemia. pends on the dominant process. Respi- negative logarithm ofthis constant, or Numerous disease states can alter ex- ratory disorders result when either of pKa, is inversely proportional to the tracellular fluid pH significantly with these processes are caused by an accu- strength of the acid. The most effec- adverse physiologic effects. mulation or reduction of volatile acid tive buffers are those with pKas close Severe acidemia (pH < 7.20) has (CO*). An accumulation or a deficit of to physiologic pH. been shown to decrease myocardial non-volatile (or fixed) acid will result in The buffers in human blood in- contractility,' lower the threshold for metabolic disorders. These are con- clude bicarbonate, proteins, hemoglo- ventricular fibrillation,2 and diminish ventionally indicated by changes in the bin, phosphates, and sulfates. Bone the pressor response to catechola- blood bicarbonate concentration, or contains a large reservoir of fixed bi- mines.3 Hypotension and pulmonary [HCO, ]. carbonate and is capable of buffering edema can result, further complicat- Any patient with markedly abnor- a significant proportion of acute acid ing the patient's course. mal vital signs should be suspected of loads.) The isohydric principle stipu- Alkalemia causes a shift in the oxy- having an acid-base disturbance. Par- lates that all buffer pairs in a mixed sys- gen dissociation curve to the left (due ticular attention should be given to tem are in equilibrium with the same to an increased affinity ofhemoglobin the patient's respiratory rate, breath- H+ ion concentration, or [H+]. Mea- for oxygen) which impairs oxygen de- ing pattern, and breath odor (eg, the surements of one buffer system will livery to tissues. Severe alkalemia acetone smell of ketoacidosis or therefore reflect changes in the whole (pH > 7.55) can result in tissue hypo- tell-tale odors of certain intoxicants). acid-base system. xia, muscular irritability, cardiac ar- Patients with evidence of impaired The bicarbonate-carbonic acid rythmias, and central nervous system peripheral vascular perfusion or a di- buffer system is used clinically for the . . e . . . * -. --*. . . O 0 0 O O 0 0 0 0 0 0 - 0 0 0 0 0 0 minished level of consciousness assessment of acid-base problems. It Dr Rudedge is a Iecturer in the Departenit should also have their acid-base status is the predominant extracellular fluid ofFamily and Commmuniy AIedicine, University determined. In general, the sicker pa- buffer system and is easily measured, of Tomnto, and is afull-time staff emegeny tients are, the more likely they are to providing information about both the physician at Alount Sinai Hospital, Towonto, Ont. have an acid-base disturbance. respiratory and metabolic factors de-

2254 Canadian Family Pyvsician \0I. 37(October 1991 termining acid-base status. The 1. FOR HYDROGEN IONS chemicalhermical equationeqationd fforisethissyus.Themsystem iS: Table RULES ESTIMATING FROM pH 3. HCO3 + H+ < H9CO1 =I11 _ H20 +C02I Carbon dioxide is produced daily Subtrat the last 2 digits of the pH pH [H+] in nmol/L by the complete metabolism of fat from 40. Then add the resul to 7.25 55 and carbohydrate; in solution it is hy- 40 = [HI in nmol/L drated by carbonic anhydrase, a 7.30 50 readily reversible reaction, to form 7.35 45 carbonic acid. The ventilatory system 7 under normal circumstances main- Rule 1 applies to pH values between 7.20 and 7.50 (in tihis 7.4040 tains the partial pressure of CO2 range the relationship between pH and [H ] is almost linear). 7.4535 (PC02) at 40 mmHg. Thus, carbonic acid has an open-ended ventilatory outlet (hence the term "volatile acid"). Non-volatile acid is produced dail by the metabolism of dietary precur- sors. These acids consume bicarbonate. Just as the lungs regulate carbon- When pH = 7.00, [H+I = 100 nmol/L pH [HI] in 1,1/Lam ic acid, the kidnieys are responsible for For each 0.10 incease in pH, HI is 80% 6.90 125 maintaining bicarbonate. Bicarbon- of the previous value (ie, multiply by 6 1 ate is generated in the kidney largely 0.8). Conversely, if the pH is < 7.00, 7.00 100 by metabolizing glutamine to ammo- divide by 0.8 (or multiply by 1.25) for 7.10 80 nium and bicarbonate, and excreting eac 0.10 unit decrease in pH. 7.20 64 ammonium ions in the urine." The Henderson-Hasselbalch 7_5 _ 32J_ erson-Hasselbequa- Rule 2 applies to pH values < 7.20 and pH volues > 7.50 (non- dlontionforthefor thiss buffer system is: * Iinear ranges). Adjust value for each 0.10 unit decrease in pH. 7.6026 log[HCO1 4. pH = pK + [H2C03] [H2CO3j1 a[H+] = 40 nmol/L at pH of 7.40. Laboratories do not routinely measure [HCO3] or [H2COjd. Total At present, the acidity of body cess ofthat disorder. For example, the CO2 is a measure of blood HCO3, fluids is commonly measured and ex- compensation for a primary respira- H2CO3, and dissolved CO2. It is com- pressed as pH. Because the use ofpH tory acidosis is a metabolic alkalosis, monly substituted for [HCO3 ], as has some theoretical8 and practical and vice versa. HCO3 accounts for most of the total disadvantages, an increasing number Respiratory compensation for a CO2. The pCO2 is directly propor- of laboratories are now making avail- primary metabolic disorder occurs tional to [H2CO3] and therefore can able [H+] in nmol/L. The rules in relatively quickly by an appropri- be substituted for it as long as the dis- Table I allow one to quickly estimate ate ventilatory response. Metabolic sociation constant is adjusted. Kassir- [H+] from pH. The Henderson equa- compensation, however, occurs in two er and Bleich7 rearranged equation 4, tion should always be used to check phases. Acute metabolic compensation cancelling the logarithms and using lab results for sampling errors, lab er- occurs within the first 12 to 24 hours. the above substitutions. The result rors, or transcription errors. It is predominantly achieved through was an equation of great clinical util- buffering by hemoglobin and by buff- ity known as the Henderson equation: Compensation ers in bone and other tissues. Plasma When buffering is not enough to pre- [HCO3] changes only slightly. vent a change in pH due to a primary Chronic metabolic compensation 5. [H+] = 24pCO2 [HCO3 ] acid-base disturbance, compensation takes 1 to 5 days, which is the time it occurs. Compensation is a physiolog- takes for the kidneys to adjust the This equation emphasizes the inter- ic response to a primary disorder and plasma [HCO3]. dependence of the three main indices is not a second acid-base disturbance. Primary acid-base disturbances routinely measured to assess acid- The compensation for a primary dis- have been studied extensively to de- base status. order is the opposite physiologic pro- termine expected degrees ofcompen-

Canadian Family Physician VOI 37: October 1991 2255 sation. Table 2 lists rules ofcompensa- Anesthesiologists who take part in tion that have been compiled from cardiac bypass surgery probably have previously published data.8-'2 If a the most experience with patients at compensatory process falls out of the hypothermic temperatures. Adult by- range of the expected response, then pass surgery is commonly done with a mixed acid-base disturbance exists. patients at 28°C and with neonates as low as 5°C. The trend among these Diagnosing acid-base anesthesiologists is to normalize the disturbances uncorrected arterial blood gases dur- A simple primary acid-base distur- ing these procedures. Corrected arte- bance always co-exists with a com- rial blood gas results in hypothermic pensatory process. The only compen- patients are difficult to interpret and satory process that is complete (ie, have little clinical relevance.'3 Until results in a normal pH) is the meta- proven otherwise, uncorrected arteri- bolic response to a sustained respira- al blood gas results should probably tory alkalosis.8 This requires at least be used to assess and manage 2 weeks and occurs at high altitudes acid-base disturbances in hypotherm- because of hypoxia-induced hyper- ic patients. ventilation. Therefore, with this ex- ception, the primary acid-base distur- The physiochemical approach bance is the process that is the furthest Within the last decade there has been from normal. Alternatively, the direc- increasing interest in a new quantitative tion the pH has moved from normal physiochemical approach to acid-base (7.40)' indicates the primary process physiology as developed by Stewart.'4"'5 (in simple disorders). After diagnosing According to Stewart, all chemical sys- the primary disorder, the degree of tems thought to affect [H+] are inte- compensation should be checked by grated by complex mathematical equa- using the rules in Table 2. tions made more manageable now with The hypothetical case example to the accessibility ofcomputers. The con- the left will demonstrate the diagnostic clusion is that acid-base balance is de- process. termined by three independent vani- ables: 1) pCO2; 2) the strong ion Assessing acid-base disorders difference (SID); and 3) the total con- in hypothermic patients. centration of non-volatile weak acids There remains some controversy and (A,,t). All other acid-base variables (in- confusion about how to interpret cluding [H+] and [HCO31) are consid- blood gas results of hypothermic pa- ered dependent on these variables. Re- tients. Should blood gases be cor- spiratory disorders are due to changes rected or uncorrected for tempera- in pCO2, whereas nonrespiratory (met- ture? Blood gas machines routinely abolic) disorders are due to changes in warm the blood to 37°C. The uncor- SID or Atot rected results are what the patient's The SID is the difference between blood gases would be if the patient's the sum ofconcentrations ofall strong temperature were normal. When cations (Na+, K+, Ca2+, Mg2+) and the blood gases are corrected for temper- sum of all strong anions (Cl, S042, ature, formulas derived from in vitro and organic acids, such as lactate-). It studies are used to estimate the values is what Singer and Hastings'6 named at the patient's temperature. For a the plasma buffer base, and in plasma given acid-base milieu, hypothermia SID is equivalent to [HCO31 + [Pj has the effect of increasing the pH (dissociated protein ions). When SID and decreasing the pCO2. Of course, is increased, there is a metabolic alka- in vivo there are numerous other losis; when SID is decreased, there is complicated effects (eg, changes in a metabolic acidosis. enzyme activities, pKs of buffer sys- The SID concept neatly predicts tems, and tissue sensitivities). the result ofwater imbalances in plas-

2256 Canadian Family Physician VOL 37: October 1991 Table 2. COMPENSATION RULES FOR PRIMARY ACID-BASE DISTURBANCES DISTURBANCEI~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~PRIMARY EVENT - ~ COMPENSATION l~~~~~, - Acute (<24 h) |410 mNg t pCO2 | + 1 m.oI/L I [HC031 ChroicK (3 to 5 d) :10 ..Hg T pCO2 - 3 to 4 mmol/L T [HCO3I1

Acute <12 h) | :i uNgI O2 - 1 to 3 mol/L -k [HCO31 Chronic (I to 2 d)a 1OImi;Hg I pCO2 -4 2 to 5 ..oI/L Ik HCO31

1 mmol/L [HCNCO31s 1 to 1.5 mmHg I pCO2 Last 2 digIts of pH = PCO2

1 mol/L I [HCO31 - 0.5 to I .Hg= I pCO2 Lost 2 digits of pH = [HC031 + 15

Af 2 weeks, compesation can be complete, resulting in a normal pH value. bIn pure T anion gap metabolic acidosis, T anion gap = k [HC037 Datafiom Narins and Emmett,8 Kaehny and Gabou9 Kaehny,10 JNarins and Gardner,1 and Bear and _yck.12 ma.'7 The SID is approximately [HC03] exerts some control of Part 2 ofthis article, which will ap- equal to ([Na+] + [K+]) - [Cl], be- [H+].18 They also point out that the pear in next month's issue, will discuss cause these are the predominant ions Henderson equation gives no insight differential diagnoses for the four pri- in plasma. In water excess states, the into how changes in ionic or protein mary acid-base disorders, as well as concentrations of these ions and the concentrations result in acid-base dis- how to diagnose mixed disorders. U value of SID are decreased by the turbances. However, the Henderson same proportion: equation is an accurate and valid de- Requestsfor reprints to: Dr Tim scription ofthe equilibrium that exists Rutledge, Room 323, Emergency Physicianl kSID = k([Na+] + [K+]) - k[Cl] between [H+], [HCO3], and pC02. Office, Mount Sinai Hospital, 600 University This decrease accounts for dilutional Its variables, independent or depen- Ave, Toronto, ONM5G IX5 acidosis as seen, for example, in pa- dent, are routinely measured and pro- References tients with a syndrome ofinappropri- vide very useful information about 1. Cingolani HE, Faulkner SL, Mattiazzi ate secretion ofantidiuretic hormone. acid-base status. AR, Bender HW, Graham TPJr. Depres- A water deficit likewise results in con- At present, the components of SID sion of human myocardial contractility centration alkalosis. and are not all easily measured. with "respiratory" and "metabolic" acido- A,o, sis. Surgery 1975;77:427-32. The main components of At0t in Furthermore, to be useful clinically, the plasma are the plasma proteins and calculations of the physiochemical ap- 2. Gerst PH, Fleming WH, MalinJA. A quantitative evaluation of the effects of aci- inorganic phosphate. When A,O, is de- proach would have to be prepro- dosis and alkalosis upon ventricular fibrilla- creased, as in hypoproteinemia, an al- grammed into a computer (altemative- tion threshold. Surgery 1966;59:1050-60. kalosis results; when is increased, ly, several nomograms could be used). A,,, 3. Houle DB, Weil MH, Brown EB Jr, Cam- as in hyperproteinemia or hyperphos- Thus, while the physiochemical ap- bell GF. Influence of respiratory acidosis phatemia, an acidosis results. proach has significantly advanced our on ECG and pressor responses to epineph- Proponents of the physiochemical understanding ofacid-base physiology, rine, norepinephrine, and metaraminol. approach argue that the Henderson it will likely be some time before it is Proc Soc Exp Biol Med 1957;94:561-64. equation (equation 5) is misleading applicable clinically in the emergency 4. Brewer ED. Disorders of acid-base bal- because it seems to indicate that department. ance. Pediatr Clin North Am 1990;37:429-47.

Canadian Family Physician VOL 37: October 1991 2257 5. Shaffcr MA. Acid-base homeostasis. In: Rosen P, Baker FJ II, Barkin RMI, Bracn Gr, Dailey RH, Levny RC, et al, editors. Emergeng medicine. 3rd ed. Toronto, Ont: The CV NMosby Com- pany, 1988:1949-67. Index to Advertisers 6. Halperin NIL, EthierJH, Kamel KS. The excretion of ammonium ions and acid base balancc. Clin Biochem 1990;23: 185-8. 7. KassirerJP, Bleich HL. Rapid estimation of plasma carbon dioxide ten- Abbott Laboratories, Ltd. Milupa sion from pH and total carbon diox- Pecdiazolc ....112113/2065 & ...... Aptamil NMilumil 2178 ide content. N Engl M,Wed Astra Pharma Inc. Nordic Laboratories Inc. 1965;272:1067-8. Losec . 2236 2237/2253 c Sulcrat .2245/2213 8. Narins RG, Emmett MI. Simple and Pulmicort .2248/2205 Norwich Eaton Canada Inc. mixed acid-base disorders: a practical Ayerst Laboratories Ditropan ...... 2095/2174 approach. Mfedicine 1980;59: 161-87. Inderal fA .2154/2198 Entcx-LA ..... 2062/2194 9. Kachny WD, Gabow PA. Pathoge- Berlex Ortho Pharmaceutical (Canada) nesis and management of metabolic Triquilar Ltd. acidosis and alkalosis. In: Schrier R\V, NMcmopak ..... 2196-2197/2301 Floxin 2176-2177/2284-2285 editor. Renal and electrolyte disorders. 3rd Boehringer Ingelheim (Canada) Terazol ...... 2068/2287 ed. Boston, Mass: Little, Brown and Ltd. Parke Davis Canada Company, 1986:141-86...... HC ...... Dixarit 2104 Anusol 2091 10. Kaehny WVD. Pathogenesis and Bristol-Myers Squibb Doryx...... 2083/2289 management of respiratory and mixed Buspar .... 2152 2153/2279-2280 Eryc...... 2125/2183 acid-base disorders. In: Schrier R\\, Capoten ...... IFC/2281-2282 Lopid.21...... 2175/2283 editor. Renal and Ponstan electrolyte disorders. 3rd Qucstran ...... 2066 2067/2299 ...... 2270/2235 ed. Boston, NMass: Little, Brown and Burroughs Weilcome Inc. Pfizer Canada Inc. Pizr Cada . Company, 1986:187-206. Coactifcd ...... 2093/2244 Vibra Tabs CTabs 2265/2078 11. Narins RG, Gardner LB. Simple Proctor and Zovirax 800 ..... 2214 2215/2296 Gamble acid-base disturbances. A1ed Clin North Crisco Oil ...... 2127 Ciba Pharmaceuticals Am 1981;65:321-46. Purdue Frederick Estraderm ...... OBC/2294 Inc. 12. Bear RA, Dyck RF. Clinical ap- Clinidata Inc...... 2123 MIS Contin ...... 2099/2286 proach to the diagnosis of acid-base ...... 2216/2293 Fisons Pharmaceutical Uniphyl disorders. Can AMed Assoc 3 Tiladc ...... 2223 2226 Rhone Poulenc 1979; 120: 173-82. C.E. Frosst C.E. FrosstOrudis...... 2097/2295 13. Delaney KA, Howland NIA, Vassal- Zocor ...... 2139- 2143 Roussel lo S, Goldfrank LR. Assessment of Surgam ...... 2086-2087/2204 Geilgy Pharmaceuticalsarmn Sandoz acid-base disturbances in hypothermia Voltaren SR ...... 22502251/2304 Zaditen ...... 2072 2073/2300 and their physiologic consequences. Glaxo Canada Inc. Smith Kline Ann Emerg tled 1989; 18:72-82. Ceftin 14. Stewart PA. How to understand ...... 2071/2292 Hemoccult ...... 2109 Hoechst Canada Inc. Clavulin ...... 2100 2101/2222 acid-base: a quantitative acid-base primerfor Loprox ...... 2081/2244 Solvay Kingswood biology and medicine. New York, NY: El- Trental ...... 2064/2126 Serc ...... 2259/2222 sevier, 1981. Janssen Pharmaceutica Inc. Sterling 15. Stewart PA. NIodern quantitative Nizoral Idarac...... 2111/2280 acid-base chemistry. Can J Physiol Shampoo ...... 2128 2129/2161 Syntex Inc. Phannacol 1983;61:1444-61. Lederle-Cyanamid Canada Inc. Anaprox ...... 2260-2261/2151 16. Singer RB, Hastings AB. An im- proved method for the of Suprax ...... 2107/2238/2302 Naprosyn SR ...... 2268/2076 estimation Mead Johnson Canada Synphasic ..... 2246-2247/2288 disturbances of the acid-base balance of human blood. Alactamil ...... IBC Ticid ... 2162-2166 Aledicine Infant Nutritionals ...... 2085 Toradol ... 2116-2121/2298 1948;27:223-42. Merck Sharp and Dohme Unilever Canada Limited 17. Fencl V, Rossing TH. Acid-base disorders in Mcvacor .... 2060/2290-2291 Beccl . 2102 critical care medicine. Merrell Dow Pharmaceuticals Upjohn Company of Canada Ann Rev Aled 1989;40:17-29. 18. Jones A Nicorette .... 2195/2174 Xanax ... 2186/2303 NL. quantitative physiochemical Miles Canada Inc. Whitehall Robbins approach to acid-base physi- Adalat PA.2184-2185/2297 ....Dimetapp . . ...I...2105.. ology. C/in Biochem 1990;23:189-95.

2258 Canadian Family Physician VOL. 37: October 1991