Base Excess & Strong Ion Theories

(the real truth about ABGs) Steve Anisman MD Renal Wolf Pack Jan 31, 2003

But first
Whats up with asparagus pee?
40% of the British population (based on a 1989 paper in British Journal of Clinical Pharmacology in which 115 people were studied) or 100% of the French population (103 subjects) make metabolites of asparagusic acid, a substance found only in asparagus. These metabolites are variants on methyl mercaptan, aka methanethiol, which is a sulfur-containing derivative of the amino acid methionine. Methyl mercaptan can also be metabolized via other pathways, and is responsible for the characteristic odors of garlic, onions, rotten eggs, and skunk secretions.

And another thing

10% of people (300 Israelis were tested) cant smell the odor in their urine or in other peoples urine even if the odor is present. So before you get all high & mighty and convinced that your pee doesnt smell, get a few people to accompany you to the bathroom. And be aware that there is a widely held belief that people with asparapee tend to have higher IQs then those bland folks who cant mount an appropriate response to an asparagus challenge.

..

The case
A 50 yo M psychiatrist is brought to the ED with recent vomiting, diarrhea, SOB/COPD exacerbation. He was believed to have been unconscious on the floor for two days after a lithium overdose. He has a long history of abuse of loop and thiazide diuretics. He has been self-medicating with bicarbonate tablets and Renagel. He has been taking 30 OscalD pills/day, in addition to 200mg of lisinopril in the belief that they would be renally protective protection he needs, given his chronic use of Gentamicin and 5g Motrin/day. He has a 120-pack/year smoking Hx, is S/P pulmonary lobectomy, is on 5L home O2, uses CPAP at night for his OSA, and has recently been experiencing hemoptysis. V/Q scan is high prob.

The case
In order to prevent his frequent episodes of DKA, he has begun a regimen of glyburide and lantus, the dosages of which he calculates daily after consulting a formula which he has devised, incorporating both the phase of the moon and the color of his aura. He is scheduled for MWF hemodialysis in Belchertown, but has not been for 2 weeks because he believes the nurses are putting too much acid in his dialysate.

How would you quantify the acid and base components in this mans blood?

Exam & Labs

Exam reveals an imaginary person. No JVD, no extra heart or lung sounds, no edema.

There is a way

Respiratory = PCO2
End of story. pCO2 is directly measured (not calculated), and is a reliable indicator of respiratory acid-base disturbances. The correlation between pCO2 and respiratory pH is direct, consistent, and linear.

And theres an equivalent measurement for metabolic

 and its NOT bicarb

In pure metabolic disorders, bicarb is a useful measurement, but if youll remember the equilibrium formula: H20 + CO2 H2CO3 H+ + HCO3youll notice that HCO3 can be affected by respiratory (CO2) or metabolic (H+) components, and therefore isnt a specific marker for either. In fact, the relationship between metabolic acidosis and bicarbonate is neither consistent nor linear.

Two approaches:

Strong Ion Theory

Base Excess
Lets begin, shall we?

Strong Ions
H+ + K+ + Na+ = Cl- + HCO3- + OHYou need electroneutrality, or you would glow. If your blood was saline, Na+ would have to equal Cl-. If you added potassium bicarbonate And then added a bunch of other ions Which ones of these matter, and which are clutter?

Strong Ions
Mg++ Ca++ K+ Na+ Cl- Others (lactate, etc) These are the Strong Ions, so-called because they do not readily combine with other ions or lose their charge. Conversely, H+ and HCO3- readily combine, and are called weak ions. The difference between the strong cations and strong anions is called the Strong Ion Difference (SID), and indicates the net ionic charge of the weak anions; so it indicates the relative strength of H+ and HCO3-.

Strong Ion Theory

Alright, already so far its basically anion gap with a new name. But, the Strong Ion Theory goes a step further and adds a few other factors: pCO2, SID, and non-volatile weak acids (buffers). Additionally, the Gibbs-Donnan equilibrium needs to be considered [Just for the record weve already considered pCO2 and were done with it. More on SID coming up 2 slides from now...]

The Non-Volatile Buffers

In blood, were dealing mainly with hemoglobin, albumin, and phosphate. Stick with me here
A- = Ionized weak acid buffer HA = Non-ionized weak acid buffer ATOT = Total weak acid buffer

ATOT = A- + HA A - + H+

Dissociation for these HAs is: HA so: HA * K A - * H+

so: You can calculate A- if you know pH & ATOT

Strong Ion Difference

Remember, SID = strong cations strong anions. It indirectly measures weak ions (HCO3 and A-).

SID = HCO3- + A[Just for the record, HCO3 + A- was called Buffer Base as far back as the 1950s SID was invented by Stewart in 1980.]

You can get HCO3 by Henderson-Hasselbach if you know pCO2 and pH (this is the calculated ABG value). You can get A- if you know ATOT and pH.

Base Excess
Definition: The amount of a strong acid (like HCl) needed to bring blood to 7.40.
Assumes 100% oxygenation, 37oC, and pCO2 of 40.

Normal = 0 Used to calculate the metabolic component of an acid-base disturbance.

Base Excess calculations

Calculated the same way, in practice, as SID: Buffer Base = HCO3- + AHCO3 calculated by pH & pCO2 (blood gas machine) A- calculated using pH & hemoglobin (whole blood) OR A- calculated using albumin & phos (plasma) BE = Buffer Base expected buffer base (expected if pH = 7.4 and pCO2 = 40)

Membranes & Ions you guys should feel right at home!

There are flavors of Base Excess: Base ExcessErythrocyte; Base ExcessPlasma; Base ExcessECF (entire extracellular fluid); Base ExcessWhole Blood how do we decide what to use? The Gibbs-Donnan equilibrium describes the behavior whenever a membrane separates impermeable ATOT buffer (Hgb) while allowing passage of other ions (Cl-, HCO3-).

Gibbs-Donnan
It means, for our purposes, that you can predict what will happen to plasma pH if you add acid to whole blood. Trust me on this part Base Excess of Extracellular Fluid is the one that we like. Extensively studied, reliable, good stuff. Siggaard-Andersen validated it extensively in actual people lots of them during the polio epidemics of the 1950s. Really, trust me. In fact, it even has its own name

Standard Base Excess

aka Base Excess of ECF. ECF includes plasma, red cells, and the surrounding interstitial fluid. Its where the action takes place in the body regarding acid-base movement. Blood-gas machines calculate SBE as: SBE = 0.9287 * (HCO3- - 24.4 + (14.83 * (pH 7.4))) And guess what it turns out that ATOT, while fascinating, doesnt really matter clinically. A nice advantage for SBE.

And SBE makes a pretty nomogram.

Compare & Contrast:

And the math is easier.

How do you figure out if compensation is normal? In metabolic acidosis, If pCO2 = SBE, then its normal. In metabolic alkalosis, If pCO2 = SBE * 0.6, then its normal.

And the math is easier.

In acute respiratory disorders, if SBE = 0 (+/- 5), then its normal. In chronic respiratory disorders, if pCO2 * 0.4 = SBE, then its normal.

How about an improved Anion Gap?

If you apply the same logic that weve already used, you can guess that there might be fancier ways to calculate anion gap than what we now do. This method should give you a gap of 12 (not 12-19):
AG = pH * ((1.16 * alb) + (0.42 * phos)) (5.83 * alb) (1.28 * phos)

Turns out this doesnt work so well, but its a version of a new trend called Strong Ion Gap. A nice version of this involves the

Fencl-Stewart corrections!!
Theres an interesting paper in Critical Care Medicine by Balasubramanyan [1999;27(8):157781] showing that this version of the Strong Ion Gap works. Fencl & Stewart basically said that BE had some virtues, but that it missed the beautiful things of the strong ion theory and that you could apply the strong ion concepts to Base Excess and pick disorders you might have missed otherwise.

Fencl-Stewart corrections!!
BE caused by free water (BEfw) = 0.3 * (Na 140) BE caused by changes in Cl- (BEcl) = 102 (Cl * 140/Na) BE caused by changes in albumin (BEalb) = 3.4 * (4.5 - albumin) BEnet = BEfw + BEcl + BEalb + BEUA [ua = unmeasured anions] BEUA = BEnet (BEfw + bEcl + BEalb)

If there were no abnormalities in sodium, choride, albumin, or unmeasured anions, then BE would be equivalent to BEUA.

Fencl-Stewart corrections!!
In a PICU, checking for BEUA picked up about 25% more abnormalities than BE alone, and about 15% more abnormalities than BE with normal gap (!!!!). And BEUA was the strongest predictor of mortality stronger than gap, stronger than BE, stronger than lactate. Even stronger than BEUA was the act of checking a lactate, but thats a different conversation

Controversies
The use of SBE was accepted decades ago by Europe (who published in Lancet), but shunned by the US (particularly Boston, NEJM), leading to the Great Trans-Atlantic Debate. This disagreement has since been replaced by derision for Strong Ions Says Siggaard-Andersen: this reveals that the Stewart approach is absurd and anachronistic this interpretationis contrary to all previous rational thinking...

And a few words about Hasselbach

Henderson was the real McCoy. Hasselbach was an miscreant, a rabble-rouser, and neer-do-well. Henderson: [H+] * [HCO3-] = K * [CO2] * [H2O] (1908) No muss, no fuss, no bother, no inverse relationships, nothing that a high-school student couldnt understand. In fact, if you remove H2O, which doesnt vary, and change [CO2] to pCO2, you get: Modified Henderson: [H+] * [HCO3-] = K * pCO2 Hasselbach: pH = pK + log ([HCO3-] / [CO2]) (1916)

And a few words about tight control

Youll read everywhere that pH is tightly controlled by the body in a narrow range. What a load of malarkey. Logarithms introduce a false sense of tight clustering. When the pH changes by 0.3 units, (say from 7.5 to 7.2), this represents a doubling of the hydrogen ion concentration (from 40 nMol/L to 80). Even normal variation between 7.35 and 7.45 represents 25% variation in [H+].That is not tight. Sorry, I just had to get that off my chest.

..

Example #1
21 yo M with cardiomyopathy, admitted with acute abdomen. Normal lytes, normal gap. Next day, cyanotic & hypotensive. 7.13 / 19 / 109 / -20 (SBE) Acidosis. Base Deficit = 20 (Base Excess = - 20), so metabolic. BE = 20, pCO2 = 21. No respiratory component.

Example #2
67 yo F with COPD admitted for dyspnea, intubated, soon extubated. Eats lunch, becomes lethargic, reintubated. First Intubation 7.19 / 70 / 249 / 0 Second Intubation 7.10 / 85 / 50 / 0 Acidosis. Base Deficit = 0, so purely respiratory.

Example #3
51 yo M nephrologist. Thats all we know. 7.49 / 44 / 90 / 6 (SBE) Na=148 Cl=98 Alb=2.1 Free water effect = 0.3 * (Na 140) = -2.4 Cl effect = 102 (Cl * 140/Na) = 9.3 Albumin effect = 3.4 * (4.5 alb) = 8.16 Explained ion effect = -2.4 + 9.3 + 8.16 = 15.06 BEua (Unexplained ions) = 6 15.06 = -9

Example #3
51 yo M nephrologist. Thats all we know. 7.49 / 44 / 90 / 6 (SBE) Na=148 Cl=98 Alb=2.1 BEua = -9 Alkalosis. SBE = pCO2 * 0.6, so pure metabolic. Unexplained ions are anions metabolic acidosis is also present need to check lactate, -OHb

Thank you! At this time, Im happy to refer any questions to Dr. OShea