Acid Base has been one of the more confusing topics during my medical school days. Here i hope to simplify some of the concepts:

Remember body must always maintains neutrality, so anions in the body = cations in the body

In traditional approach:

Na + UC = Cl + HCO3 + UA

UA – UC (anion gap) = Na – Cl – HCO3

In Stewart’s method:

A number of independant and dependant variables have been proposed

- HCO3+ and H+ are dependant variables. Other dependant variables are [OH-], [CO32-], [HA], [A-]. These dependant variables are governed by the independant variables.
- SIG, Atot, PCO2 are the independant variables. They could be calculated.

– SID = (Na+ + K+ + Ca2+ + Mg2+) – (Cl- – other strong anions)

– ATOT = [PiTOT] + PrTOT] + albumin - The influence of these independant variables can be presented in these simultaneous equations:

[H+] x [OH-] = K ‘w (water dissociation equilibrium)

[H+] x [A-] = KA x [HA] (weak acid)

*[HA] + [A-] = [ATOT] (conservation of mass for “A”)*

[H+] x [HCO3-] = KC x PCO2 (bicarbonate ion formation equilibrium)

[H+] x [CO32-] = K3 x [HCO3-] (carbonate ion formation equilibrium)

**[SID] + [H+] – [HCO3-] – [A-] -[CO32-] – [OH-] = 0 (electrical neutrality)**

To simplify Stewart’s approach, as mentioned, body must always maintained neutrality, so any alteration in independant variables will result in an alteration in concentration of H+ and HCO3-, contributing to an increase/decrease in pH.

- Eg an increase in Cl- (decrease in SID) will be followed by an increased in H+ to maintain the neutrality.
- Assuming the equation:

Initial SID = 2, H+ = 2, HCO3-, A-, CO32-, OH- = 1, the equation would be 2+2-1-1-1-1=0 - If SID is decreased to 1, H+ would have to increase by 1 (2+1=3) to maintain the electrical neutrality.

SIG = SIDa – SIDe

- SIDa = ([Na+] + [K+] + [Mg2+] + Ca2+) – ([Cl-] + [Lactate-])
- SIDe = (2.46 x 10-8 x PCO2/10-pH) + ([albumin in g/dL] x (0.123 x pH – 0.631)) + ([PO4 in mmol/L] x (pH – 0.469))
- A simplified formula SIG has been proposed and has been shown to show good correlation:

SIG = (Na+K) – (CL+HCO3) – 2.5(albumin) – Lactate

Relationship between SIG and AG

**SIG = AG – (A- + Lact)**- SIDa – HCO3 = AG

A suggested approach using Stewart’s approach:

- Metabolic acidosis = SBE < -2
- PREDOMINANT lactic acidosis if lactate > 50 percent of the SBE
- PREDOMINANT SIG acidosis if SIG is > 50 percent of the SBE
- PREDOMINANT NAGMA if (SBE-Lact-SIG) > 50 percent of the SBE; this is represented by an excess of CL- relative to Na+
- If neither > 50 percent of the SBE, then the acidosis is mixed.

Note that, in this approach, we try to find the PREDOMINANT type of metabolic acidosis

- SIG is normally 0, but wide range (0-11) has been reported in literature.

The way I use it is slightly different: I mainly use it to find if there is any anions left after i substrate lactate and delta SID (excess chloride = 38-SID) from BE:

Delta SID

- Delta SID = 38 – SID (i.e Na-CL)
- SIG = Base deficit (Or negative Base Excess) – Delta SID – Lactate
- Since albumin loss will be replaced by unexplained anions, we should correct for low albumin:

Calculated SIG + albumin [2.5 (4.2-alb level)] = Actual SIG - This actual SIG is also know as base excess of unmeasured anions (BEua).

If SIG >2, it is SIG acidosis (= HAGMA)

Practical case:

From emcrit

- Check out the excellent podcasts from Emcrit about acid base in critically ill patients (http://emcrit.org/podcasts/acid-base-part-iii/)

122 – 88 = 34

Delta SID = 38 – Calculated SID = 38 – 34 = 4

BE = -18 (metabolic acidosis)

SIG = 18 – 4 – 0.5 = 13.5 mmol/L

True SIG = 13.5 + (2.5)(4.2-5.2) = 13.5 + (2.5)(-1) = 11 mmol/L

We have 11 mmol/L of anions to account for……..This is SIG acidosis.

MUDPILES to remember for SIG acidosis

- Methanol
- Uremia
- DKA
- Prophylene glycol (solvent of IV meds), propofol, paracetamol (replacing the rare paraldehyde and phenformin)
- Iron, Isoniazid
- Lactic acidosis
- Ethylene glycol
- Salicyclic acid

Alternatively, traditional method also works:

Na – Cl – HCO3 = 122 – 88 – 5 = 29

We know albumin 5.2 g/dL has 13 mmol/L of anions, so 29-13=16 mmol/L

Lactate is 0.5 mmol/L, so we have remaining 15.5 mmol/L of unexplained anions

- Because this is a made-up example, some discrepancies may happen. But importantly, we know this is a HAGMA and there are unexplained anions for us to find out !

Base deficit

The utility of base excess/base deficit

- Base Excess/Deficit is used to “quantify” the magnitude of metabolic component of an acid base derangement.
- Problem with base excess/deficit is
**it assumes all other blood components and electrolytes eg albumin are normal**; so correction of hypo/hyperalbuminemia needs to be done. - Normal = -2 to 2 mEq/L
- Base deficit normal + abnormal AG: alkalosis + acidosis OR HAGMA not corrected for hypoalbuminemia.

Danger of hypoalbuminemia:

- A “lost” albumin will be replaced by other anions.
- A low albumin without the presence of other UA is normal in NAGMA. The “space” is replaced by an increase in HCO3- level
**(low albumin level is alkalinizing in NAGMA).** - If an anionic acid is present like lactate or ketones,
**a low CL or in combination with a low albumin may partially buffer acidosis by allowing more space for bicarb to be in.**

Hypoalbuminemia may therefore falsely lower the AG.

**– True AG = Calculated AG + 2.5 (4.2 – albumin in g/dL)**

– Consider albumin of 4 with albumin of 1 in a patient with an AG of 12 (normal) with pH of 7.10

- True AG = 12 + (2.5)(4-4) = 12 (normal)
- True AG = 12 + (2.5)(4-1) = 19.5 (HAGMA)

Because base excess assume normal albumin, a low albumin may actually lead to falsely lowered base excess

- Imagine a BE of 3, an albumin of 3.2 (N=4.2) will actually increase the BE by 2.5 mmol/L (Real BE = 5.5) -> low albumin is alkalinizing.
- Vice-versa, base deficit will be false elevated in hypoalbuminemia.

**Na/CL ratio**

- Na/CL ratio is important in determining whether the CL- is acidifying or alkalinizing. Chloride concentration should always be compared relative to sodium. An increased CL- does not ALWAYS mean there is acidosis.
- Na/CL normal = 140/102 = 72 percent
- Ratio < 70% = alkalizing effect, > 80% = acidifying effect

A good practical question can be found here: http://www.pbfluids.com/2015/08/big-anion-gap-or-biggest-anion-gap.html

Reference:

- http://lifeinthefastlane.com/ccc/base-excess-vs-standard-base-excess/
- Kyle J Gunnerson. Clinical review: The meaning of acid–base abnormalities in the

intensive care unit – epidemiology. Critical Care 2005, 9:508-516 - Lewis J Kaplan and Spiros Frangos. Clinical review: Acid–base abnormalities in the intensive care

unit. Critical Care 2005, 9:198-203 - D. A. Story, H. Morimatsu and R. Bellomo. Strong ions, weak acids and base excess: a simplified Fencl-Stewart approach to clinical acid-base disorders. British Journal of Anaesthesia 92 (1): 54±60 (2004)