Acidemia – Metabolic and Respiratory Acidosis and General Approach to Acid / Base


Best Sources for analyzer incredible online text

My Acid/Base Sheet

Sodium Bicarb Review

Pharm induced Acidosis

Great Lactate Review

Kerry Bradshaw’s amazing Online Text

NEJM 1998;338(1):26

NEJM 1998;338(2):107

Quantitative Approach: (Crit Care 2005;9(2):204) and anaesthesia 2002;57(4):348

Anaesthesia 2002;57(4):348 Acid-€™base physiology: the œtraditional and the œmodern approaches


albumin (g/L) x (0.123 x pH – 0.631)

phosphate (mg/dL) x (0.309 x pH – 0.469)



bicarb is only an effective buffer at pH

at this pH, give 50% of bicarb deficit

HCO3 deficit=0.6 x wt (kg) x (15-current HCO3)


HCl Infusions

calculate H deficit

H (meq) deficit=0.5 x wt (kg) x (measured HCO3 – desired HCO3)

volume of 0.1N HCl (L) = H deficit/100

set desired at halfway between actual and normal

0.1N contains 100 mEq of H+ per liter

must go in central vein

infusion rate should not exceed 0.2 mEq/kg/hour



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Interpreting ABGs

Corrected Aa Gradient=10+Age/10


Metabolic Acidosis

PCO2=(1.5xBicarb) + 8 (+-2)

Metabolic Alkalosis

PCO2=(0.7xBicarb) + 21 (+-1.5)

Respiratory Alkalosis

Acute Bicarb=((CO2-40)/10) + 24

Chronic Bicarb=((CO2-40)/3) + 24

Respiratory Acidosis

Acute Bicarb=((40-CO2)/5) + 24

Chronic Bicarb=((40-CO2)/2) + 24


Normal Anion Gap=2 (Albumin) + 0.5 (Phosphate)

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impairs cardiac contractility

arterial dilation, venous constriction


inhibits anaerobic metabolism


sympathomimetic release, but attenuates the response to catecholamines (consider in b-agonists in asthmatics)

decreases the uptake of glucose into cells and induces insulin resistance


Metabolic Acidosis

The body will buffer any acid load with proteins, Hb, and creatinine.  If the bicarb drops, it is b/c these buffers have been overwhelmed.


In disease states where tissue hypoxia causes the acidosis, exogenous bicarb administration is actually harmful, but if tissue hypoxia is not present, bicarb can be beneficial.

Bicarb can be harmful in 5 ways:

  1. Venous hypercapnea with decreased tissue pH
  2. A decline in the pH of CSF
  3. Tissue Hypoxia
  4. Hypernatremia
  5. Hyperosmolality with resultant CNS dysfunction


Hypercapnic Metabolic Acidosis

increased CO2 not due to pulmonary dysfunction, so the PaCO2 will remain normal, but the mixed venous will not be.  ABGs are poorly representative of tissue acid/base status or oxygenation.  Central venous or mixed venous (pulmonary artery) are much more representative.



in this state the body has 400-500 mmol of available bicarb precursor in the form of lactate and ketoacid anions.  The addition of exogenous bicarb does not help, what helps is reversal of the process of ketosis with insulin allowing the liver to produce bicarb.


Severe acidemia will be associated with bicarb of

In keto or lactic acidosis, treat the underlying disorder because endogenous anions will be converted back to bicarb

In hyperchloremic, patient needs bicarb


Alkalizing salts like sodium lactate, citrate, or acetate depend on oxidation of salts to bicarb


NaBicarb Administration

Give Bicarb to get pH to 7.2, so bicarb must be increased to between 8 and 10

Consider bicarb space to be 50% of body weight as starting point

so give 8-Bicarb * kg * 0.5=mmol of bicarb needed

Bicarb normally comes as a 1N solution (1 mmol per cc)

Remember admin of bicarb increases CO2 so only give if intubated or patient has compensatory reserve to blow off excess



Lactic Acidosis

Best Review of Lactate

Elevated lactate may be from alcohol alone (Am Surg. 2011 Dec;77(12):1576-9.)

Most pathways to excess lactate are from decreased elimination as opposed to solely increased production


1/2 life of lactate is 3 hours


At pH

Type A (Anaerobic) caused by tissue hypoxia


Type B (Aerobic)  no evidence of hypoxia


Type B is seen in DKA, certain cancers, and congenital diseases of the liver.

Lactates >9 are associated with a mortality of >75%


Another review (Curr Opin Crit Care 2006;12:315)


D-lactic acidosis is the stereoisomer seen in patients with short gut syndrome.

Uribarri J, Oh MS, Carroll HJ: D-lactic acidosis. A review of clinical presentation, biochemical features, and pathophysiologic mechanisms. Medicine (Baltimore) 1998; 72: 73-82


D-Lactic acidosis Emergency physicians frequently are called upon to evaluate patients with an acute change in mental status. If the patient exhibits a metabolic acidosis, the clinician should consider D-Lactic acidosis as part of the differential diagnosis. Patients with this condition may complain of or appear to be drunk in the absence of ethanol intake. A unique form of lactic acidosis can occur in patients with jejunoileal bypass or, less commonly, small bowel resection or another cause of the short bowel syndrome. In these settings, glucose and starch are metabolized in the colon into D-lactic acid, which is then absorbed into the systemic circulation. Patients typically present with episodic metabolic acidosis (usually occurring after high carbohydrate meals) and characteristic neurologic abnormalities including confusion, cerebellar ataxia, slurred speech, and loss of memory. It is not clear if these symptoms are due to D-lactate itself or to some other toxin produced in the colon and then absorbed in parallel with D-lactate. The diagnosis of D-lactic acidosis should be strongly considered in the patient presenting with an increased serum anion gap, normal serum concentrations of lactate, and one or more of the following: Short bowel or other malabsorption syndrome Acidosis that is preceded by food intake and resolves with its discontinuation Characteristic neurologic symptoms and signs The standard assay for lactate will not detect D-lactate, hence serum concentrations of lactate will appear normal. Confirmation of the diagnosis requires a special enzymatic assay specifically testing for D-lactate. Therapy in this disorder consists of acute sodium bicarbonate administration to correct the acidemia and oral antimicrobial agents (such as metronidazole, neomycin, or vancomycin) to decrease the number of D-lactate producing organisms in the gut.


D-Lactic AcidosisEmergency physicians frequently are called upon to evaluate patients with an acute change in mental status.  If the patient exhibits a metabolic acidosis, the clinician should consider D-Lactic acidosis as part of the differential diagnosis.  Patients with this condition may complain of or appear to be drunk in the absence of ethanol intake.A unique form of lactic acidosis can occur in patients with jejunoileal bypass or, less commonly, small bowel resection or another cause of the short bowel syndrome. In these settings, glucose and starch are metabolized in the colon into D-lactic acid, which is then absorbed into the systemic circulation. Patients typically present with episodic metabolic acidosis (usually occurring after high carbohydrate meals) and characteristic neurologic abnormalities including confusion, cerebellar ataxia, slurred speech, and loss of memory. It is not clear if these symptoms are due to D-lactate itself or to some other toxin produced in the colon and then absorbed in parallel with D-lactate. The diagnosis of D-lactic acidosis should be strongly considered in the patient presenting with an increased serum anion gap, normal serum concentrations of lactate, and one or more of the following:

  • Short bowel or other malabsorption syndrome
  • Acidosis that is preceded by food intake and resolves with its discontinuation
  • Characteristic neurologic symptoms and signs

The standard assay for lactate will not detect D-lactate, hence serum concentrations of lactate will appear normal. Confirmation of the diagnosis requires a special enzymatic assay specifically testing for D-lactate.Therapy in this disorder consists of acute sodium bicarbonate administration to correct the acidemia and oral antimicrobial agents (such as metronidazole, neomycin, or vancomycin) to decrease the number of D-lactate producing organisms in the gut. References: (1) Stolberg, L, et al. D-Lactic acidosis due to abnormal gut flora  N Engl J Med 1982; 306:1344. (2) Halperin, ML, Kamel, KS. D-lactic acidosis: Turning sugars into acids in the gastrointestinal tract. Kidney Int 1996; 49:1. (3) Uribarri, J, et al. D-lactic acidosis. Medicine 1998; 77:73. (4) Mayne, AJ, et al. Dietary management of D-lactic acidosis in short bowel syndrome. Arch Dis Child 1990; 65:229. (5) Coronado, BE, Opal, SM, Yoburn, DC. Antibiotic-induced D-lactic acidosis.Ann Intern Med 1995; 122:839.

from emedhome




In the River’s study, 1/3 of folks with lactate>4 had bicarb >22 and anion gap≤15



References: (1) Stolberg, L, et al. D-Lactic acidosis due to abnormal gut flora N Engl J Med 1982; 306:1344. (2) Halperin, ML, Kamel, KS. D-lactic acidosis: Turning sugars into acids in the gastrointestinal tract. Kidney Int 1996; 49:1. (3) Uribarri, J, et al. D-lactic acidosis. Medicine 1998; 77:73. (4) Mayne, AJ, et al. Dietary management of D-lactic acidosis in short bowel syndrome. Arch Dis Child 1990; 65:229. (5) Coronado, BE, Opal, SM, Yoburn, DC. Antibiotic-induced D-lactic acidosis. Ann Intern Med 1995; 122:839.

Lactate Metabolism

(Current Anaesthesia & Critical Care (2006) 17, 71–76)

pH = pKa+ log (H A/HA)

7:4 = 3.85 + log lactate /lactic acid


lactate to lactic acid 3548:1 at pH 7.4

Diagram from

lactate from

Shoshin Beri Beri

Most severe form; pt will have enormous degree of lactic acidosis with hyperdynamic cardiac function. Should respond immediately to 100 mg thiamine. (Intensive Care Med (2005) 31:1004)

Thiamine deficiency should be considered in every case of severe lactic acidosis without an obvious cause, especially in high-risk populations (malnourished, alcoholics, Far-East workers, etc). (Journal of Emergency Medicine Volume 26, Issue 3 , April 2004, Pages 301-303)


Alakalosis can cause lactate production because it stimulates glycolysis

Liver fx by itself can cause high blood lactate

Lactate ion itself in addition to the acidemia mat contribute to circulatory fx

If you give bicarb at all, give 1-2 mmol per kg by slow infusion


Drugs known to be associated with type B2 lactic acidosis: acetaminophen, alcohols and glycols (ethanol, ethylene glycol, methanol, propylene glycol), almitrine, antiretroviral nucleoside analogs (zidovudine, delavirdine, didanosine, lamivudine, stavudine, zalcitabine), beta-adrenergic agents : epinephrine, ritodrine, terbutaline – but not salbutamol…, biguanides (phenformin, metformin), cocaine, cyanogenic compounds (eg, cyanide, aliphatic nitriles, nitroprusside), diethyl ether, 5-fluorouracil, halothane, iron, isoniazid, nalidixic acid, propofol, sugars and sugar alcohols (fructose, sorbitol, and xylitol), salicylates (eg, Reye syndrome), strychnine, sulfasalazine, and valproic acid. As you see, beta adrenergics can cause it, but salbutamol seems not to be reported yet. (Claudia)

Cori Cycle




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Anion Gap

=(Na (? + K)) – (Cl + Bicarb)

Correct for albumin by equation of Figge: AG + (0.25 x (42 – albumin))   g/L; if given in g/dL, the factor is 2.5 (Crit Care Med 1998; 26:1807-1810)

Normal Gap 8-12 mEq/L

Delta Gap=(AG-12)-(24-Bicarb) The increase in the AG should equate with the decrease in bicarb.

The concept is that there is a one to one relationship between the anion gap and decreased bicarb in pure anion gap acidosis.  If there is not then there is either a combined non-anion gap acidosis or a metabolic acidosis depending on whether the delta gap is positive or negative.


Anion Gap (AG)=2 x ALB + 0.5 (Phos)


one article showed no increased discriminatory ability from correcting the anion gap for hypoalbuminemia (Emerg Med J 2006;23:627)


With bicarbs>8 there should be a 1 mmHg drop in PaCO2 for every 1 meq/dl fall in Bicarb.  PCO2 can drop to ~12.


Sodium Dichloroacetate (DCA):  has the potential to decrease lactate levels and increase pH without the negative effects seen with bicarb.

Carbicarb:  equimolar mixture sodium bicarb and sodium carbonate.  Decrease CO2 instead of increasing it.

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an exogenous buffer. Can lower PaCO2 and resolve acidosis. Lowers Sodium

Most Recent Study (J NEPHROL 2005; 18: 303-307) sodium bicarbonate is contraindicated and THAM preferred in patients with mixed acidosis with high PaCO2 levels.

Review (acta anaes scand 2000;44:524)


High Anion Gap (CAT MUDPILES)

Uremia-From H+ retention and from other organic acids

Salicylates-respiratory alkalosis, then met acidosis (uncoupling of oxidative phosporylation)

Methanol-wood alcohol.  Becomes Formaldehyde and Formic Acid (blindness)

Ethylene Glycol-antifreeze.  Urine will fluoresce.  Kidney failure

Paraldehyde-Old medication



Cyanide, Carbon Monoxide

Alcoholic Ketoacidosis

Toluene, theophylline


Methanol, Metformin, MetHb

Uremia (need BUN 50/Cr 5)

Diabetic Ketoacidosis, Starvation Ketoacidosis

Paraldehyde,  phenformin, Propylene Glycol

INH, Ibuprofen (high dose), IRON

Lactic Acidosis D (Blind GI Loops) and L (consider metformin, Type I), Lithium

Ethylene Glycol

Salicylates, strychnine


If gap from lactate, should be 1:1, if not other acids are present.



High-dose lorazepam infusion is associated with high propylene glycol concentration, which may cause adverse effects. Therefore, PG accumulation and toxicity should be monitored for all patients receiving high-dose lorazepam for more than 48 hours. Potential adverse effects associated with high doses of PG include hyperosmolar metabolic acidosis, renal dysfunction, and intramuscular hemolysis in critically ill patients with normal renal function.


Ativan and diazepam will cause propylene glycol toxicity causing anion gap and osmal gap acidosis. Anions are lactic acid. Versed does not need the propylene glycol because it is water soluble at low pH and fat soluble at body pH.


A good portion of anion gap acidosis is probably caused by circulating members of the krebs cycle. These low molecular weight molecules were found in patients with lactic acidosis and DKA (Critical Care 2005;9:R591)

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Unknown Cause of High Sig in the Critically Ill

Sig in the critically ill

Normal Anion Gap

Any intestinal loss or RTAs


Renal Tubular Acidosis

physicochemical approach


Impaired distal hydrogen ion secretion. Often accompanied by hypokalemia, low urinary NH4+, and hypocitraturia. Nephrolithiasis often occurs. Transient or persistent (classic adult form is associated with bicarb wasting and nerve deafness.) Mineral metabolism, hyperglobulinemic states, renal disease Myeloma.  Urine pH



impaired prox bicarb reabsorb. Vit d deficiency. Fanconi syndrome drugs like diamox, hyperparathyroidism, nephrotic syndrome   U pH>5.55 with bicarbonaturia. Bicarb is exhanged for Cl, which actually causes the acidosis



Intact acidification but impaired ammoniagenesis. Aldosterone deficienct. heparin, captopril, prostaglandin inhibitors. Increased K.  Diabetics.



get UA and U lytes.  Calculate urine anion gap.  Urine (Na+K)-Cl.  If negative then most likely a non-renal cause of non-anion gap acidosis.  If positive, consider RTA.


article on quant approach to RTA (crit care 2005;9)


In pure met acidosis c compensation, last two digits of pH should=CO2

If pH


Loss of HCO3 -




Proximal renal tubular-acidosis

Renal insufficiency

Acetazolamide (Diamox)


Inability to excrete H+

Obstructive uropathy



Distal-renal tubular acidosis

Ingestion of ammonium chloride



The administration of sizable amounts of sodium bicarbonate is associated with certain risks. Infusion of the usual undiluted 1N preparation (containing 1000 mmol of sodium bicarbonate per liter) can give rise to hypernatremia and hyperosmolality. This complication can be avoided by adding two 50-ml ampules of sodium bicarbonate (each containing 50 mmol of sodium bicarbonate) to 1 liter of 0.25 N sodium chloride or three ampules to 1 liter of 5 percent dextrose in water, thereby rendering these solutions nearly isotonic. (NEJM 1998, 338(1), 26-34)



Forsythe SM, Schmidt GA. Sodium bicarbonate for the treatment of lactic acidosis. Chest 2000;117(1):260-7. Circumstances where it is appropriate to give bicarbonate:

  • Hyponatraemic acidosis, without hypochloraemia (if respiratory system ok)
  • Hyperchloraemic acidosis, without hypernatraemia (if respiratory system ok)
  • And possibly, although evidence against mounting, rhabdomyolysis to alkalinize urine and prevent pigment nephropathy (as Tamm-Horsfall protein only precipitates at acid pH).
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Low Anion Gap

Sources of Error: Pseudo-Met Acidosis

Increased AG

excessive exposure of sample to air causing carbonic acid decrease secondary to CO2 release

administration of poorly absorbed anionic abx (carbenicillin)


Decreased AG

halide, bromide, or iodide intox causing a false elevation of Cl

Hypertriglyceridemia causing false elev of Cl

Poorly absorbed cationic abx (polymyxin B)



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Strong Ion Approach

proof that stewart is much better than conventional s albumin correction (Crit Care Med 2007;35:1264)


Reunification of Acid-base physio (Critical Care 2005;9(5): )

Best Article on utility of Stewarts (Crit Care 2005;9(2):204)

Effects of Fluids

Acid Base in the ICU


  1. Is there an acid base problem?
  2. Is it primarily respiratory or metabolic?
  3. Is the compensation appropriate [using the rules of thumb for expected pCO2 resoponse to a metabolic problem and expected HCO3 change in response to a respiratory problem]?
  4. Are there any gaps? [calculate the anion gap and osmolar gap] 5. Do things not add up? [look at delta AG: delta HCO3, calculate the Na/Cl effect, calculate the albumin effect]

Obeserved BE + (sodium/cl effect) – (albumin correction)=true base excess



When albumin is decreased, blood becomes more alkaline b/c it is a weak acid



BE in whole blood, defined as the quantity (mM) of strong acid needed to restore pH to 7.4 in a blood sample equilibrated at PaCO2 = 40 mm Hg using the Van Slyke equation


narrow Na Cl gap acidosis

It doesn’t change the H ion concentration. It causes more of the H ions to get dissociated. In other words the total H ions remain the same, but the free H ion activity increases. This changes the pH Lets imagine a container of pure water. Unlimited number of H ions, but almost no H is dissociated. Unlimited number of OH ions, but almost no OH is dissociated. Neutral pH . Neutral as in chemically neutral, not physiologically neutral. Add some strong ions to this pure water, say NaCl. Being strong ions, these will dissociate. The free Na will cause some OH to dissociate & the free Cl will cause an equal amount of H to dissociate. The amount of H & OH dissociated will be the same & hence the pH will still be “neutral”. Now take a fluid like blood with more Na (135) than Cl (100). More OH (135) is dissociated compared to H (100) & the pH will be alkalotic. Say the pH is 7.4. This is chemically alkalotic, but taken as the physiological neutral value. If this solution now had more Cl, with the same Na, relatively more H will be dissociated & the pH will fall, maybe to 7.3. The fall of the SID resulted in the pH becoming more acidic. This is because there were relatively more free or dissociated H ions are present in the solution after the SID decreased.

It does not use ATP. The equilibrium between lactate and pyruvate depends on the pH. If H+ concentration is high the equilibrium shifts to more lactate, if low, more pyruvate. Pyruvate is reduced to lactate by LDH (changes NADH to NAD) pH is -log[H+]


Br J Anesthesia 2004;92(1):54-60

Am J Respir Crit Care Med 2000;162:2246.


Lactic Acid (HLa) = Lactate- + H+ (99% disassociated at physiologic pH)

Heart and Brain can take up lactate and use for energy

RBCs shuttle lactate and take it to other areas of the body

Plasma carries 70% while RBCs carry 30%


lactic acid metabolism (j applied physio  558(1):29)

About erythrocyte metabolism. Erythrocytes use the Pentose Phosphate shunt (PPS) because it is the only way they can generate NADPH. Erythrocytes need NADPH to maintain a ready supply of reduced gluthathione, which is needed to combat oxidative stress. If the erythrocytes cannot use the PPS, they hemolyze. This is why people with G6PD deficiency (which is part of the PPS) hemolyze. Both Glycolysis and the PPS produce 3-P-glyceraldehide, which can be either converted to 2,3 DPG, or to Pyruvate and lactate. But the erythocyte contains as much 2,3 DPG as it does hemoglobin. So it produces relatively small quantities of lactate, as most of the 3-P-glyceraldehide is converted to 2,3 DPG.


In patients with hepatic fx, lactate in solutions can increase serum lactate levels. Liver can process 100 mmol/hour (Clin Endocrinol Metab 1980;9:513)


Most commercial solutions have racemic lactate mixtures, the D-form is not measured by serum assay


Lactate in Sepsis

(Curr Opin Crit Care 1999;5(6):452)

is not a reliable indicator of anaerobic glycolysis

Dichloroacetate stims pyruvate dehydrogenase which converts pyruvate to acetyl CoA. This decreases lactate in septic patients without increasing oxygenation

another theory is regional anaerobiosis

more likely is that lactate metabolism is decreased in sepsis

Hyperventilation triples lactate in normal individuals: this is because cells do not take up lactate not b/c of increased prod.

lungs may be source of excess lacate in sepsis

production may be aerobic representing cell stress from catecholamines


Hyperchloremic Acidosis

(Anesth Analg 2003;96:919)


Massive NaCl infusion causes met acidosis (J Trauma 2001;51(1):175)



Acid Base Physiology of Crystalloids

(Curr Opin Crit Care 1999;5(6):436)

water is a weak acid (pKa 13.5 at 40 C) as temp goes up, it gets more acidic

free water therefore causes acidosis when given to correct hyponatremia

This is because free water causes Na to fall in greater degree than Cl


Dextrose makes solutions even more acidic, b/c it forms acid after oxidation. That is until it is metabolized


Multicarbon ions such as acetate and gluconate are usually taken up by cells within minutes. The actual metabolism of these ions may further decrease acidosis.


If packaging is in bags instead of glass, CO2 will diffuse in, which alters bicarb concentrations; this is why multicarbons are used



Acid Base of Colloids

(Curr Opin Crit Care 1999;5(6):440)

colloid is a state of matter that is neither solution or suspension; defined by ability to move molecules across membranes

Albumin 20% has a mild acidifying effect (Intensive Care Med (2005) 31:1123–1127)



Acid Base and Renal Failure, CVVH  and Hemodialysis

(Curr Opin Crit Care 1999;5(6):443)

In patients with liver failure, multicarbon anions will not be metabolized and CVVH will cause acidosis. In these folks, bicarb solutions must be used

Lactate is not cleared by hemofilter, so serum levels are still accurate if substitution fluid is not lactate containing


Bicarb solutions can be kept shelf-safe by using two bags, one with 4.75 L of bicarb-free solutions and a 250 cc glass bottle of bicarb solution containing 160 mmol NaBicarb (Hemosol) Double spike delivers bicarb to bag just before use.


Acid Base of HD (Curr Opin Crit Care 1999;5(6):468)

four defense mechanisms to our daily acid load:

ion transport across cell membranes

removal of co2 by lungs

kidney ion elimination

liver metabolism


renal failure causes hyperchloremic acidosis and then high anion gap acidosis

this causes decreased cardiac contractility

and altered response to drugs


SID of HD dialysate is usually 40


Lactate and the Kidney (Critical Care 2002;6(4))

kidney second only to the liver in the ability to remove lactate from the circulation and metabolizing it

very little is actually excreted in the urine confined to cortex; medulla actually creating lactate from glycolysis



Diamox works by excretion of sodium without chloride (Critical Care 2006;10:R14)



SBE = 0.9287 × (HCO3- – 24.4 + 14.83 × [pH - 7.4])


Corrected Base Excess=BE-(Na-Cl-38)-(2.5(4.2-Albumin in g/dl))


Each 1 g/dl albumin has a charge of 2.8 mEq/l at pH 7.4 (2.3 mEq/l at 7.0 and 3.0 mEq/l at 7.6), and each 1 mg/dl phosphate has a charge of 0.59 mEq/l at pH 7.4 (0.55 mEq/l at 7.0 and 0.61 mEq/l at 7.6). Thus, in much the same way that the corrected SBE equation (Eqn 5) updates BE to allow for changes in ATOT, the AG may be corrected to yield a corrected AG (AGc)


SIG = ([Na+ + K+ + Ca2+ + Mg2+] – [Cl- + lactate-]) – (2.46 × 10-8 × PCO2/10-pH + [albumin (g/dl)] × [0.123 × pH - 0.631] + [PO4- (mmol/l) × (pH - 0.469)])


SIDm=Na + K + 2(Mg) +2(Ca) – Cl – lactate – urate


Importantly, all the strong ions are expressed in mEq/l and only the ionized portions of Mg2+ and Ca2+ are considered (to convert total to ionized Mg2+, multiply by 0.7). Note also that we do not consider lactate as unmeasured. Because the concentration of unmeasured anions is expected to be quite low (


Br J Anaesth 2004;92(1):54-60)

Sodium Cl effect (meq/l)=Na – Cl – 38

Albumin Effect (meq/l)=(0.123 x pH – 0.631) x (42-albumin (g/l))

=0.25 x (42-albumin (g/l)

=2.5 x (4.2 – albumin (g/dl)

Corrected Base Excess (meq/l)=BEm – (Na – Cl – 38) – (2.5 x (4.2-albumin)

Am J Respir Crit Care Med 2000;162:2246

Pi-=(Pi) x (0.309 x pH -0.469)

XA-=other strong ions: lactate, ketoacids, sulfate

1.8 (Pi mmol/L)

Mixing Dialysis fluids can use NaAcetate or NaBicarb to balance NaCl

In massive fluid resus such as cardiopulmonary bypass priming, then move closer to 24 for SID to make up for dilution of albumin

Hyproteinemia, SID, and acid base in the crit ill (J appl physio 1998;1740)

serum acid-base may be misaltered b/c of compensation for csf acid-base

so hypoproteinemia may actually result in hyperventilation


Fundamental Principles of Acid-Base (Critical Care 2005;9(2):)



SIG=AG – [albumin (g/dl)] (1.2 × pH-6.15) – [phosphate (mg/dl)] (0.097 × pH-0.13)


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Method IV Fencl-Stewart

see above


Disease states classified according to the Stewart approach  Acid–base disturbance   Disease state   Examples   Metabolic alkalosis   Low serum albumin   Nephrotic syndrome, hepatic cirrhosis     High SID+   Chloride loss: vomiting, gastric drainage, diuretics, post-hypercapnea, Cl- wasting diarrhea due to villous adenoma, mineralocorticoid excess, Cushing’s syndrome, Liddle’s syndrome, Bartter’s syndrome, exogenous corticosteroids, licorice Na2+ load (such as acetate, citrate, lactate): Ringer’s solution, TPN, blood transfusion  Metabolic acidosis   Low SID+ and high SIG   Ketoacids, lactic acid, salicylate, formate, methanol     Low SID+ and low SIG   RTA, TPN, saline, anion exchange resins


gelatin from some colloids is a weak acid

free water is an acid, b/c it has a SID of 0


SBE=0.93 x ((Bicarb) + 14.84 x (pH – 7.4) – 24.4)


Equivalent strong ion difference reductions by adding 1 l water or 1 l of 0.15 mol/l NaCl to a 3 l sample of mock extracellular fluid    ‘ECF’   After saline dilution   After water dilution   [Na+]   140   142.5   105  [Cl-]   100   112.5   75  [A-] + [HCO3 -]   40   30   30  SID   40   30   30



If met alkalosis is assoc c decreased serum K, then KCl is a great way to correct as it has a SID of 0 which actually becomes neg as k is taken up


‘Balanced’ crystalloids To avoid crystalloid induced acid–base disturbances, plasma SID must fall just enough during rapid infusion to counteract the progressive ATOTdilutional alkalosis. Balanced crystalloids thus must have a SID lower than plasma SID but higher than zero. Experimentally, this value is 24 mEq/l [23,43]. In other words, saline can be ‘balanced’ by replacing 24 mEq/l of Cl- with OH-, HCO3 – or CO3 2-. From this perspective, and for now ignoring pH, solutions 1 and 3 in Table 4 are ‘balanced’. However, it is noteworthy that, unless stored in glass, solutions 1 and 3 both become solution 2 by gradual equilibration with atmospheric CO2 (Table 4). Solution 2 is also ‘balanced’. To eliminate the issue of atmospheric equilibration, commercial suppliers have substituted various organic anions such as L-lactate, acetate, gluconate and citrate as weak ion surrogates. Solution 4 (Table 4) is a generic example of this approach (for actual examples, see Table 5). L-lactate is a strong anion, and the in vitro SID of solution 4 is zero. However, solution 4 can also be regarded as ‘balanced’, provided L-lactate is metabolized rapidly after infusion. In fact, in the absence of severe liver dysfunction, L-lactate can be metabolized at rates of 100 mmol/hour or more [44,45], which is equivalent to nearly 4 l/hour of solution 4. The in vivo or ‘effective’ SID of solution 4 can be calculated from the L-lactate component subject to metabolic ‘disappearance’. If the plasma [lactate] stays at 2 mmol/l during infusion, then solution 4 has an effective SID of 24 mEq/l. Hence, despite wide variation in pH, solutions 1–4 in Table 4 have identical effective SID values. They are all ‘balanced’, with identical systemic acid–base effects. However, other attributes must be considered. Solution 1 (pH 12.38) is too alkaline for peripheral or rapid central administration. The situation for solution 2 is less clear. Atmospheric equilibration has brought the pH to 9.35, which is less than that of sodium thiopentone (pH 10.4) [46] – a drug that is normally free of venous irritation. Similarly Carbicarb, a low CO2TOT alternative to NaHCO3 preparations [47], has a pH of 9.6 [48]. Thus, the pH of solution 2 may not preclude peripheral or more rapid central administration. On the downside, and like Carbicarb, solution 2 contains significant concentrations of carbonate, which precipitates if traces of Ca2+ or Mg2+ are present. A chelating agent such as sodium edetate may be required.


Four balanced crystalloids (see text)    Solution 1   Solution 2   Solution 3   Solution 4   [Na+]   140   140   140   140  [Cl-]   116   116   116   114  [HCO3 -]     19.2   24    [CO3 2-]     4.8      [OH-]   24        [L-lactate]         26  PCO2 (mmHg)   0   0.3a   760   0.3a  pH   12.38   9.35   6.04   6.49  Effective SID   24   24   24   24




Six colloid solutions    Albumex 4   Haemaccel   Gelofusine   PENTASPAN   HESpan   Hextend   [Albumin]b   40 g/l            [Gelatin urea-linked]b     35 g/l          [Gelatin succinylated]b       40 g/l        [Pentastarch]         100 g/l      [Hetastarch]           60 g/l   60 g/l  [Na+]   140   145   154   154   154   143  [K+]     5.1         3  [Ca2+]     12.5         5  [Mg2+]             0.8  [Cl-]   128   145   120   154   154   124  [L-lactate]             28  [Glucose]             5.5  [Octanoate]   6.4            Effective SID   12   17.6   34   0   0   26a   aAssumes stable plasma lactate concentrations of 2 mmol/L (see text). bWeak acid. Electrolyte concentrations are given in mEq/l. SID, strong ion difference.



Blood At collection, blood is mixed with a preservative, normally CPDA-1 [68], providing approximately 17 mEq trivalent citrate anions per unit, and a small amount of phosphate [69]. The accompanying sodium cation adds about 40 mEq/l to the effective SID of whole blood. For this reason it is not surprising that large volume whole blood transfusion commonly results in a post-transfusion metabolic alkalosis (following citrate metabolism). With packed red cells, the standard red cell preparation in most countries, the preservative load per blood unit is reduced. Nevertheless, large volume replacement with packed red cells still produces metabolic alkalosis [69]. Conversely, if liver dysfunction is severe enough to block or grossly retard citrate metabolism, then the problem becomes ionized hypocalcaemia and metabolic acidosis [70]. sulphates are the strong anions in renal failure


ng suction without proton pump inhibition cause alkalosis from cl loss


lactic acidemia vs. hyperlactatemia


acidosis screws up coagulation

van slyke is accurate in vivo (crit care med 2000;28(8):2932)


Acid Base of RRT

phosphate x (0.309 x (pH-0.469))


1000 x 2.46 x 10-11 x PCO2/( 10-pH )


possible unmeasured anions in uremia are sulfate, urate, hydroxypropionate, oxalate, furanpropionate


if pt’s liver can not metabolize citrate, it will stay in the blood stream and chelate calcium and act as a strong anion causing met acidosis


CVVH may have a sieving constant of >1 causing met alkalosis even with well designed fluids


Acidosis of Cardiac Arrest

not due to hyerlactatemia alone, a good portion is from organic acids such as: phosphate, sulphate, urate, oxo acids. This response is attenuated by hypochloremia, hyperkalemia, hypermagnesemia (Critical Care 2005;9:R357-62)



Technologic advances in the measurement of electrolytes have an influence on how quantitive acid–base parameters are calculated. Currently, there are three techniques commonly used to measure quantitive acid–base variables: flame photometry and potentiometry using direct ion selective electrodes (ISEs) or indirect ISEs. Flame photometry is used infrequently in developed countries. It is the measurement of the wavelength of light rays emitted by excited metallic electrons exposed to the heat energy of a flame. The intensity of the emitted light is proportional to the concentration of atoms in the fluid, such that a quantitative analysis can be made on this basis. Examples are the measurements of sodium, potassium, and calcium. The sample is dispersed into a flame from which the metal ions draw sufficient energy to become excited. On returning to the ground state, energy is emitted as electromagnetic radiation in the visible part of the spectrum, usually as a very narrow wavelength band (e.g. sodium emits orange light, potassium purple, and calcium red). The radiation is filtered to remove unwanted wavelengths and the resultant intensity measured. Thus, the total concentration of the ion is measured. Flame photometry has several limitations, one of the more common being the influence of blood solids (lipids). These lipids have been shown to interfere with the optical sensing (due to increased turbidity) and by causing short sampling errors (underestimating true sample volume) [75]. Flame photometry also measures the concentration of ions, both bound and unbound, whereas newer techniques (ISEs) measure the disassociated form (or ‘active’ form) of the ion. An ISE measures the potential of a specific ion in solution, even in the presence of other ions. This potential is measured against a stable reference electrode of constant potential. By measuring the electric potential generated across a membrane by ‘selected’ ions and comparing it with a reference electrode, a net charge is determined. The strength of this charge is directly proportional to the concentration of the selected ion. The major advantage that ISEs have over flame photometry is that ISEs do not measure the concentration of an ion; rather, they measure its activity. Ionic activity has a specific thermodynamic definition, but for most purposes it can be regarded as the concentration of free ion in solution. Because potentiometry measures the activity of the ion at the electrode surface, the measurement is independent of the volume of the sample, unlike flame photometry. In indirect potentiometry, the concentration of ion is diluted to an activity near unity. Because the concentration will take into account the original volume and dilution factor, any excluded volume (lipids, proteins) introduces an error (usually insignificant). When a specimen contains very large amounts of lipid or protein, the dilutional error in indirect potentiometric methods can become significant. A classic example of this is seen with hyperlipidemia and hyperproteinemia resulting in a pseudo-hyponatremia by indirect potentiometry. However, direct potentiometry will reveal the true sodium concentration (activity). This technology (direct potentiometry) is commonly used in blood gas analyzers and point-of-care electrolyte analyzers. Indirect ISE is commonly used in the large, so-called chemistry analyzers located in the central laboratory. However, there are some centralized analyzers utilizing direct ISE. The methodologies can produce significantly different results [72-74,76]. Recent evidence reinforces how technology used to measure acid–base variables affects results and may affect interpretation of clinical studies. Morimatsu and colleagues [77] have demonstrated a significant difference between a point-of-care analysis and the central laboratory in detecting sodium and chloride values. These differences ultimately affect the quantitative acid–base measurements. The study emphasizes that differences in results may be based on technology rather than pathophysiology. One reason may be related to the improving technology of chloride and sodium specific probes. On a similar note, it also appears that there is variation in the way in which the blood gas analyzers calculate base excess [78]. Unfortunately, many studies evaluating acid–base balance have failed to report details of the technology used to measure these variables. This limitation was discussed by Rocktaeschel and colleagues [24] in 2003. Since then, detailed methods sections that include specific electrode technology have become more common when acid–base disorders are evaluated [23,40,79,80]. (Critical Care 2005;9(5):508)



Lactate and increased SIG assoc with mortality (Gunnerson Crit Care 2006,10:R22)


Unidentified Strong Acids associated with increased mortality in severe malaria (Crit Care Med 2004;32(8):1683)


Urinary SID

Unfortunately, it is not easy to consider the urinary SID. In

fact, although 40–42 mEq/l of plasmatic negative charge may

–], [HCO






+], [Na+] and [Cl–


+] + [K+] + [Un+] = [Cl–] + [Un–


+ and Un–


+] + [K+] – [Cl–] = [Un–] – [Un+






+] + [K+] – [Cl–


+] and [K+


–] and [Un+



, which is a way to augment elimination of Cl–




(Crit Care 2006;10:137)




Acid–base patterns observed in humans   Disorder   HCO3- (mEq/l)   PCO2 (mmHg)   SBE (mEq/l)   Metabolic acidosis     = (1.5 × HCO3-) + 8 = 40 + SBE    Metabolic alkalosis   >26   = (0.7 × HCO3-) + 21 = 40 + (0.6 × SBE)   >+5  Acute respiratory acidosis   = ([PCO2 - 40]/10) + 24   >45   = 0  Chronic respiratory acidosis   = ([PCO2 - 40]/3) + 24   >45   = 0.4 × (PCO2 – 40)  Acute respiratory alkalosis   = 24 – ([40 - PCO2]/5)     = 0  Chronic respiratory alkalosis   = 24 – ([40 - PCO2]/2)     = 0.4 × (PCO2 – 40)   Adapted with permission from Kellum [7]. PCO2, partial carbon dioxide tension; SBE, standard base excess. Am J Surg. 1996 Feb;171(2):221-6.

Serial blood lactate levels can predict the development of multiple organ failure following septic shock.Bakker J, Gris P, Coffernils M, Kahn RJ, Vincent JL. Department of Intensive Care, Erasme University Hospital, Brussels, Belgium. BACKGROUND: Despite successful initial resuscitation, septic shock frequently evolves into multiple system organ failure (MSOF) and death. Since blood lactate levels can reflect the degree of cellular derangements, we examined the relation between serial blood lactate levels and the development of MSOF, or mortality, in patients with septic shock. PATIENTS AND METHODS: In 87 patients with a first episode of septic shock, we measured initial lactate (at onset of septic shock), final lactate (before recovery or death), “lactime” (time during which blood lactate was > 2.0 mmol/L, and the area under the curve (AUC) for abnormal values (above 2.0 mmol/L). These measurements were correlated with survival and organ failure and scored for four systems (ie, respiratory, renal, hepatic, and coagulation), adding to a maximal score of 8. RESULTS: Thirty-three (38%) patients survived. Of the 54 (62%) nonsurvivors, the 13 patients who died during the first 24 hours of septic shock had higher initial blood lactate levels than those who died later (mean +/- standard deviation 9.6 +/- 5.3 mmol/L versus 5.6 +/- 3.7 mmol/L, P


Crit Care Med. 2004 Aug;32(8):1637-42  Early lactate clearance is associated with improved outcome in severe sepsis and septic shock.Nguyen HB, Rivers EP, Knoblich BP, Jacobsen G, Muzzin A, Ressler JA, Tomlanovich MC. Department of Emergency Medicine (HBN), Loma Linda University and Medical Center, 11234 Anderson Street, Loma Linda, CA 92354, USA. OBJECTIVE: Serial lactate concentrations can be used to examine disease severity in the intensive care unit. This study examines the clinical utility of the lactate clearance before intensive care unit admission (during the most proximal period of disease presentation) as an indicator of outcome in severe sepsis and septic shock. We hypothesize that a high lactate clearance in 6 hrs is associated with decreased mortality rate. DESIGN: Prospective observational study. SETTING: An urban emergency department and intensive care unit over a 1-yr period. PATIENTS: A convenience cohort of patients with severe sepsis or septic shock. INTERVENTIONS: Therapy was initiated in the emergency department and continued in the intensive care unit, including central venous and arterial catheterization, antibiotics, fluid resuscitation, mechanical ventilation, vasopressors, and inotropes when appropriate. MEASUREMENTS AND MAIN RESULTS: Vital signs, laboratory values, and Acute Physiology and Chronic Health Evaluation (APACHE) II score were obtained at hour 0 (emergency department presentation), hour 6, and over the first 72 hrs of hospitalization. Therapy given in the emergency department and intensive care unit was recorded. Lactate clearance was defined as the percent decrease in lactate from emergency department presentation to hour 6. Logistic regression analysis was performed to determine independent variables associated with mortality. One hundred and eleven patients were enrolled with mean age 64.9 +/- 16.7 yrs, emergency department length of stay 6.3 +/- 3.2 hrs, and overall in-hospital mortality rate 42.3%. Baseline APACHE II score was 20.2 +/- 6.8 and lactate 6.9 +/- 4.6 mmol/L. Survivors compared with nonsurvivors had a lactate clearance of 38.1 +/- 34.6 vs. 12.0 +/- 51.6%, respectively (p =.005). Multivariate logistic regression analysis of statistically significant univariate variables showed lactate clearance to have a significant inverse relationship with mortality (p =.04). There was an approximately 11% decrease likelihood of mortality for each 10% increase in lactate clearance. Patients with a lactate clearance> or =10%, relative to patients with a lactate clearance


Surg Today. 2001;31(10):853-9.  Serial measurement of arterial lactate concentrations as a prognostic indicator in relation to the incidence of disseminated intravascular coagulation in patients with systemic inflammatory response syndrome.Kobayashi S, Gando S, Morimoto Y, Nanzaki S, Kemmotsu O. Department of Anesthesiology and Critical Care Medicine, Hokkaido University School of Medicine, Sapporo, Japan. To demonstrate the prognostic value of measuring blood lactate concentrations and to investigate the mechanisms of lactate production in patients with systemic inflammatory response syndrome (SIRS), we conducted a prospective cohort study. Among 22 patients with SIRS, there were 9 survivors and 13 nonsurvivors. Serial arterial lactate concentrations were measured on the day of admission to the intensive care unit (day 0). then on days 1-4. The subjects of this study consisted of 14 patients with SIRS, 6 with severe sepsis, and 2 with septic shock. On admission, the lactate concentrations did not differ between the two groups, but remained high in the nonsurvivors throughout the study period, while they progressively decreased in the survivors. The incidence of disseminated intravascular coagulation (DIC) was significantly higher in the nonsurvivors than in the survivors. The nonsurvivors had persistently higher DIC scores and lower platelet counts than the survivors. The changes in lactate concentration over time were statistically different between the patients with DIC and those without DIC. The findings of this study clearly demonstrated that serial arterial lactate measurements can predict a poor outcome in patients with SIRS, severe sepsis, or septic shock. DIC might play an important role in the pathogenesis of lactate production in these newly defined critically ill patients.

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Respiratory Acidosis

Winter’s Formula:  PCO2=(1.5 x HCO3) + 8 ± 2

Respiratory acidosis


a. HCO3- increases 1 (range: 0.25 to 1.75) mEq/L for every 10 mm Hg increase in P CO2 .

b. pH drops 0.08 for every 10 mEq/L rise in HCO3- .

Chronic (greater than 5 days of hypercapnia)

a.HCO3- increases 4 mEq/L for every 10 mm Hg increase in P CO2 (±4).

Limit of compensation: bicarbonate will rarely exceed 45 mEq/L.

Metabolic acidosis:

Note: It may take 12 to 24 hours for maximal respiratory response to develop:

a. Pa CO2 =(1.5×HCO3- ) +8±2.

b. Pa CO2 is equivalent to the last 2 digits of the pH (i.e., if P CO2 is 20, the pH should be 7.20).

c. Delta P CO2 =1-[1.3×(DeltaHCO3- )].

d. For a pure anion gap acidosis; the rise in the anion gap should be equal to the fall in the bicarbonate concentration (i.e., the Deltagap should equal 0).

e. For a pure non-anion gap (hyperchloremic) acidosis, the fall in the bicarbonate should be equal to the rise in the chloride concentration (i.e., Delta bicarb= -Delta chloride).

Limit of compensation: Pa CO2 will not fall below 10 to 15 mm Hg.


a. P CO2 =0.9(HCO3- )+9

b. P CO2 increases 0.6 mm Hg for each mEq/L increase in HCO3- .

Limit of compensation: P CO2 rarely exceeds 55 mm Hg.

pH>7.55 associated with mortality of >45%

suppresses respiration with increased O2/Hb binding decreasing tissue available O2

Consider contraction alkalosis from volume depletion


Many times, merely correcting the contraction alkalosis with NaCl can correct KCl levels if the patient is put into K sparing drugs like ACE inhibitors and spironolactone, and offered the basic K daily minimum K recquirements on the diet or on IV hydration.However, as I stated before, below 2.5 serum K levels, sinoventricular conduction ensues and there is AV node and His-Purkinje conduction depression. Risk of heart block – and below 2.0 sinusal arrest.I would take a good look at the patient?s EKG, start NaCl administration, and decide upon her clinical signs of dehydration whether I would give her a 3% solution NaCl or saline infusion


Pyroglutamic Acidemia


High anion gap metabolic acidosis is frequently encountered in critical care practice. Recently, there have been several reports of high anion gap acidosis resulting from excess production of 5-oxoproline, and termed “pyroglutamic acidaemia”.1-5 This acidaemia is most frequently reported with paracetamol therapy,1 but has also been associated with flucloxacillin2 and vigabatrin,3 particularly in the setting of severe sepsis, renal or hepatic dysfunction.4

The reported inciting dose of paracetamol has been variable: 8 g of paracetamol daily for 3 weeks in one study,6 and a cumulative dose of 20.8 g of paracetamol over 2 weeks in another.7 In a series of 11 patients with transient oxoprolinuria, all patients were taking paracetamol, with most receiving therapeutic dosages.8 A serum paracetamol level of > 200 μmol/L was seen in only one of the eight patients in whom paracetamol levels were checked. Our patient received a cumulative dose of 8 g of paracetamol over 4 days, and it is likely that PGA was precipitated by a combination of factors, including sepsis, renal dysfunction, and co-administration of flucloxacillin.



Primary Versus Mixed ConditionsThis is guaranteed to keep coming up on every exam for the rest of your life, so you might as well learn it.

This page provides two ways to consider acid-base disturbances:

Method I.  A rigorous method which involves calculation of the expected compensations. Method II.  A quick and dirty method to tell from a blood gas if a respiratory condition is simple or compensated. Method III.  Look on a nomogram.

Also see the discussion of how to interpret the base deficit on a blood gas.

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Method I.  Expected compensations

Condition HCO3- pCO2Metabolic Acidosis Lower LowerRespiratory Acidosis higher if chronic HigherMetabolic Alkyosis Higher higherRespiratory Acidosis lower if chronic LowerAdapted from Peds Nephrol 42:1365-1395

In acid-base disorders, there are expected compensatory mechanisms.  For instance, bicarbonate is lost the primary process is metabolic alkalosis and the normal response is compensatory respiratory acidosis (retention of CO2).  If the change in pCO2 or HCO3- is equivalent to the expected compensatory response, the disorder is “simple”.  However, if the compensation is outside the normal range, it is a mixed disorder; that is, two primary processes are taking place simultaneously.  The expected compensation is for each condition is defined below:



Expected pCO2 = 1.5 x [HCO3-] + 8 ± 2


Expected pCO2 = increase6 mmHg per 10 mEq/L increase in HCO3-



  Acute  Expected increaseHCO3- = increase1 mEq/L for each 10 mm increasepCO2Chronic  Expected increaseHCO3- = increase3.5mEq/L for each 10 mmHg increasepCO2


  Acute  Expected decreaseHCO3- = decrease2 mEq/L for each 10 mm Hg decreasepCO2Chronic  Expected decreaseHCO3- = decrease5 mEq/L for each 10 mmHg decreasepCO2

Some examples:

1.  If the bicarbonate is 10 due to a purely metabolic acidosis, it would be expected that the pCO2 would be about 23.  If, however, it were measured as 30, there must a component of respiratory acidosis complicating the matter.

2.  pH=7.08, pCO2=14, HCO3-=4, Na=140, Cl=104:

  • Primary disorder is a metabolic acidosis
  • The pH is low indicating the primary disorder is acidosis.
  • The pCO2 is low, the expected compensation, trying to “blow off” CO2.
  • The compensation does not fully correct the primary problem.
  • The predicted pCO2 by the above equation is 1.5*4+8 = 14.
  • This is the observed pCO2
  • The anion gap is 140 – (104 + 4) = 32, thus elevated.

Therefore, this is a simple increased anion gap metabolic acidosis.

3.  pH 7.08, pCO2=14, HCO3-=4, Na=140, Cl=124:

  • AG = 140 – (124 + 4) = 12
  • Same situation as above, but chloride has replaced bicarbonate.

4.  pH 7.37, pCO2=18, HCO3-=10, Na=140, Cl=114

  • For the pH to be normal, this must be mixed disorder (respiratory compensation can never fully correct a simple metabolic acidosis).
  • The anion gap is 16, thus increased.
  • Expected pCO2 is 1.5*10+8 = 23 (21 at minimum).
  • Thus, there must be an element of respiratory alkalosis too.

Therefore, this is a combination of increased anion gap metabolic acidosis and a respiratory acidosis.

5.  In a patient with severe BPD, cor pulmonale, and who is diuretics, the pH=7.42, pCO2 = 65, HCO3-=41, Na 143, K 3.1, Cl 88:

This chronic condition can be approached from either the viewpoint of a a respiratory acidosis, or a metabolic alkalosis — it doesn’t matter which one you start with, the result is the same: this is a mixed condition.  To prove it:

A)  Start with a metabolic alkalosis, the patient has too much bicarbonate…

  • The expected compensation would be retention of CO2, 6 mmHg for each 10 mEq/L HCO3-.
  • Given a HCO3- of 41, with normal of 24: 41-24 = 17
  • Therefore, pCO2 should be 1.7 * 6 + 40 = 50.2 mmHg
  • However, pCO2 is measured at 65
  • Thus, there is a respiratory acidosis (due to CO2 retention) which complicates the metabolic alkalosis which has come about secondary to diurectic use.

B)  Start with respiratory acidosis, the patient is a CO2 retainer…

  • The expected renal compensation would be a 3.5 mEq/L increase for every 10 mmHg increase in pCO2.
  • Thus, 65-40=25
  • The HCO3- should be 2.5*3.5+24 = 32.75
  • However, it is measured as 41
  • Thus, there is a metabolic alkalosis (due to diuretic use) which complicates the respiratory acidosis due to CO2 retention.
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Method II.  Estimating by pH and pCO2

This method relies on following observation which is consistently true for uncompensated respiratory conditions: The pH varies by 0.008 units for every 1 mmHg change in pCO2.

In children

  • the normal pH ranges from 7.35 to 7.45
  • the normal pCO2 ranges from 35 to 45

For a given condition, if the pCO2 makes sense in light of the pH, the condition is of uncompensated respiratory origin.  Metabolic compensation for a primary respiratory condition usually takes between 8 and 48 hours to occur.

This is a useful way to analyze the situation when all you have is a blood gas, and the bicarbonate value is not directly measured as in the above examples.


1.  Given the ABG of 7.5/29/94/25 (pH/pCO2/pO2/HCO3-)

  • Since it is alkalemia, start at the upper end of normal, 7.45
  • Add 0.008 for each mmHg that the pCO2 differs from normal
  • The lower limit of normal pCO2 is 35, so
  • (35 – 29) = 6 mmHg less than normal pCO2
  • 6  * 0.008 = 0.048
  • thus, predicted pH is 7.45 + 0.048 = 7.498
  • this jibes well with the measured 7.5
  • thus, this is an uncompensated respiratory alkalosis

2.  Given the ABG of 7.2/64/75/25

  • Since it is acidemia, start at the lower limit of normal, 7.35
  • Subtract 0.008 for each mmHg that the pCO2 differs from normal
  • The upper limit of normal pCO2 is 45, so
  • (64-45) = 19 mmHg more than normal pCO2
  • 19 * 0.008 = 0.152
  • thus, predicted pH is 7.35 – 0.152 = 7.198
  • this agrees well with the measured 7.2
  • thus, this is an uncompensated respiratory acidosis

3.  Given the ABG of 7.31/72/52/35

  • Start with 7.35 because it is acidemia
  • The pCO2 differs from the maximum by (72 – 45) = 27
  • Expected pH = 7.35 – (0.008 * 27) = 7.13
  • Thus, this is not a simple respiratory acidosis; some compensation is present

4.  Given the ABG of 7.50/59/60/41

  • The pH is elevated but the pCO2 is also elevated.  This cannot be a primary respiratory problem, but must be a metabolic alkalosis.  The degree to which each contribute requires additional information, either a serum bicarbonate and the application of method one (above) or interpretation of the base deficit.
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Method III.  Acid-Base Nomograms

The following nomogram can be used to classify a condition based on blood gas measurements:


BD = – [(HCO3) - 24.8 + (16.2 × (pH - 7.4))].

Alterations of consciousness with pH. 7.2 drowsy, 6.98 stuporous, 6.9 comatose (pediat diabetes 2006;7:11)

Bicarb use in acidosis

In clinical practice, particularly in critically ill patients, lactic acidosis is essentially always an adverse finding. Elevated lactate in these patients generally results from a combination of increased production (also known as type A lactic acidosis) and impaired clearance (type B lactic acidosis).

Lactate clearance has been well characterized, with metabolism to pyruvate in the liver responsible for over 50% of the clearance [5,6], while the kidney and to a lesser extent skeletal muscle, red blood cells and the heart metabolize the remainder. Due to resorption in the proximal convoluted tubule, urinary excretion of lactate is normally under 2%, rising to at least 10% with markedly elevated lactate levels [7]. While lactate clearance in healthy individuals is well understood, the mechanism behind impaired clearance in critically ill patients remains only partly defined. When confronted with hypoperfusion resulting in outright organ dysfunction such as ‘shock liver’, impaired hepatic clearance is easily attributable to the hepatic manifestation of global organ impairment. However, lactic acidosis can occur in patients who are hemodynamically normal but suffering from systemic inflammatory states such as early sepsis. It appears as though circulating inflammatory mediators change the liver from an organ which extracts lactate to one which actually produces excess lactate [8,9].

Internal homeostasis is fundamental for maintaining life, so significant deviations from normal biochemical concentrations of electrolytes and other molecules generally indicate a physiologically important abnormality in homeostatic function. Hydrogen ion concentration is particularly tightly regulated both intracellularly and extracellularly. Normal hydrogen ion concentration is approximately 40 nmol/l. Interestingly, the life sciences have adopted the practice of expressing hydrogen ion concentration as -log10([H+]) = pH from the physical sciences in which hydrogen ion concentrations vary so dramatically that a logarithmic scale was required. This has the effect of obscuring the extent of deviations from normal. For example, a change in pH from a normal value of 7.4 to 7.2 results in a 60% increase in hydrogen ion concentration from 40 to 63 nmol/l and a further increase to 100 nmol/l at a pH of 7.0.

When we consider other tightly regulated cation concentrations such as Na+ or K+, this H+ ion concentration increase is substantial. Changes in ion concentrations depend upon the flux in to and out of the volume of distribution of the ion and, importantly, the size of the volume of distribution. As a result, Na+ concentrations can change only slowly. For example, infusion of 250 ml of 3% saline over 1 h (a very high Na+ flux) will contribute ~80 mEq compared with a total body pool of typically ~6000 mEq (140 mEq/l × 60% × body weight) so that Na+ concentration changes only slightly. Thus, Na+ concentrations depend on the large size of total body Na+ and water pools, and only very marginally on hourly or daily Na+ or water fluxes through these pools. When Na+ concentration is abnormal, is the problem with Na+ flux or Na+ or water pools? Clearly, it is a problem with the Na+ or water pools.

In contrast the H+ pool of 40 nmol/l in the extracellular space and approximately the same concentration in the intracellular space totals less than 0.01 mEq. Extensive extracellular and intracellular buffer systems increase the effective H+ pool substantially to about 1000 mEq. In comparison, the flux of H+ through this pool of normal health is high (see below) and can easily increase 10-fold during stress and muscle exertion. Thus, production and clearance of H+ become dominant mechanisms of regulation. When H+ concentration is abnormal, is the problem with H+ flux or H+ and buffer pools? In acidoses that are stable over days and weeks, the problem may be with the buffer pool but in lactic acidosis due to shock the problem is clearly with H+ flux.

H+ titrated by bicarbonate administration: in context

The primary source of H+ production is simply metabolism. For example, approximately 200 ml of CO2 is produced per minute by a typical human, which is the same amount of CO2 produced by bicarbonate buffering of 9 mEq H+ per minute or 540 mEq H+ per hour. For higher metabolic rates (which can increase 10-fold or more), the effective rate of acid production increases proportionately. For anaerobic metabolism, this same acid flux no longer is manifest solely as CO2 production but is also converted into lactic acid production, where clinicians consider bicarbonate administration to increase the buffer pool size.

The problem is not in the buffer pool size. The buffer pool size is overwhelmed by the H+ flux in to the pool. The 50 mEq per ampule of bicarbonate is small in comparison to the H+ flux in to the pool. Thus, in the context of the magnitude of the acid flux that is associated with metabolism (hundreds of mEq per hour), it is clear that use of buffers will never keep up and, ultimately, always fails unless aerobic metabolism is restored.

While H+ and HCO3-, as charged ions, do not readily diffuse across cell membranes, CO2 does readily diffuse. In the intracellular compartment, the high CO2 concentration will drive this same equation in reverse and generate intracellular H+ (Fig. 1 [10]). Thus, bicarbonate administration will cause intracellular acidosis unless PCO2 can be controlled by increased ventilation. One ampule of bicarbonate fully reacted will generate over 1 l of CO2. As normal CO2 production is about one fifth of a liter per minute this means that one ampule of bicarbonate should be infused over 5 min or more if alveolar ventilation can be doubled – which is often challenging in a critically ill patient. Increasing alveolar ventilation up to five-fold to allow infusion of bicarbonate over 1 min is generally not possible. The practice of bolus infusion of an ampule of bicarbonate will result in mixing of the bicarbonate with a relatively small volume of blood, which will then have a very high local PCO2. When this volume of blood transits the lungs and heart and perfuses the coronary arteries, the cardiac myocytes will be transiently exposed to this very high local PCO2. This high PCO2 will decrease myocardial contractility [11] and, in anecdotal animal experiments, can cause cardiac arrest.


Table 1 Change in blood chemistry 15 min following 2 mmol/kg bicarbonate infusion [10] From:   Boyd: Curr Opin Crit Care, Volume 14(4).August 2008.379–383

The increase in pH was transient so that much of the bicarbonate effect was gone after 30 min. As all patients were being treated with catecholamines, the observed lack of clinical sensitization following substantial reversal of the acidosis was puzzling, given good evidence that acidosis significantly attenuates the effect of catecholamines [13]. This led the authors to suggest that the 10% decrease in plasma ionized calcium countered any positive inotropic effect conferred from an increase in pH [10]. This hypothesis has yet to be tested clinically.



A summary in 12 short points


  1. An acid is a proton donor  — it’s conjugate base  accepts the proffered proton!
  2. pH is a convenient logarithmic way of representing large changes in hydrogen ion activity.
  3. Exam candidates should probably learn how the glass pH electrode works.
  4. The body tightly regulates pH, to maintain normal metabolic functions and trap certain ions inside cells, at least, this is what we believe!
  5. In examinations, an FAQ (by examiners) is buffering, especially buffering by haemoglobin (and the role of this protein in CO 2  transport). Know this.
  6. The terms acidosis and alkalosis are general terms that refer to states where the pH has changed, and either been compensated for, or not! If the blood pH is outside the normal limits of 7.36–7.44, then only are we justified in using the terms acidaemia or alkalaemia.
  7. The lungs, kidney and liver are crucial to maintenance of acid-base homeostasis. For example, metabolic alkalosis doesn’t usually persist unless the kidneys are somewhat whacked!
  8. Derangement in lung function/control results in respiratory acidosis/alkalosis; metabolic derangement due to renal dysfunction, gastrointestinal abnormalities, or ingestion, production or failure of removal of acids (or alkali) results in metabolic acidosis/alkalosis. The body usually compensates as best it can.
  9. Conventional lore lays great emphasis on the Henderson-Hasselbalch equation, and exam candidates ignore it and its derivation at their peril.
  10. The anion gap is the amount of unmeasured negative ions that make up the difference (balances charge) between the measured concentrations of positive and negative ions in plasma. Normally the AG is mainly due to albumin, and about 8–12 mmol/l. The AG is important in the evaluation of metabolic acidosis , but beware of missing a high anion-gap acidosis masked by hypoalbuminaemia!
  11. Compensation for acid-base derangement can be simply guesstimated using the Boston formulae: The Boston formulae*StateRuleFormulaRange metabolic acidosis 1.5+8 PCO 2  (mmHg) = 1.5*bicarbonate + 8 ± 2 metabolic alkalosis 0.7+20 PCO 2  (mmHg) = 0.7*bicarbonate + 20 ± 5 acute respiratory alkalosis 2 for 10 bicarbonate (mmol/l) drops 2 mmol/l     for every 10 mmHg PCO 2  drop ? chronic respiratory alkalosis 5 for 10 likewise, but 5 mmol/l ? acute respiratory acidosis 1 for 10 bicarbonate (mmol/l) increases 1 mmol/l     for every 10 mmHg ? chronic respiratory acidosis 4 for 10 likewise, but 4 mmol/l ? * The values are derived from Brandis
  12. The Stewart approach seems a little more complex, but may well be better than the conventional approach, especially for cutting through confusion. With Stewart, a low SID , high albumin concentration and/or high PCO 2  may all contribute to acidosis; the reverse for alkalosis.






NaOH (sodium hydroxide) has the same effects as sodium bicarb, but its alkalinity precludes clinical use (pH 14)Bicarb is just carbonated NaOHwe can metabolize 100 mMol/h of lactate with healthy liversNaOH and THAM are CO2 consuming, bicarb is CO2 generatingGive bicarb slowly to avoid delerterious effectsformate and glycolate cause cerebral edemasevere perturbations of pH alter A- component of AtotSID + H+ – HCO3- – CO3– – A- – OH- = 0HCO3 = SID – A-CO2 is present in bicarb vial to lower the pH, if bicarb is in plastic, it will become NaOH pH (8-9.4)unless bicarb disappears, the SID of NaBicarb is 0 and it is an acidic solutionplasmalyte is very basicliver metabolzies citrate blood products are acidoticpyruvate + NADH + H+ L-Lactate + NAD+ to excrete Cl-, the kidney also excretes NH4+acidosis=liver increases glutamine allowing greater Cl- excretionRenal Fx acidosis=Citrate, Acetate, Fumurate, hyperphosphatemiaIf SID is negative, incrasing CO2 has no effect on pH, if positive, dramatic effectCO2 + H20 = H2CO3 = H+ + HCO3-CO2 + OH- = HCO3-Dissolved CO2 is several hundredfold greater than H2CO3Only because of carbonic anhydrase is CO2 to bicarb near instantaneouspressure of CO2 in blood is independent of SID changespH = 7.6 + log10 {SID/Pc} meq/l/mmHgHCO3 IS INDEPENDENT of PcCO2 has no chargeCO2 + H20CO3– + H+ + H+As CO2 decreases CO3– increases and chelates calciumhence the hyperventilation syndrome5% change in either Pc or SID yields 5% change in H+ or 0.3% change in pHBicarb seemed important to the old folks b/c it was the only way to measure PaCO2CO2 + H20 = CO2 (dissolved) or H2CO3 or HCO3- or CO3++CO2 dissolved and H2CO3 is proportional to the PcHCO3- and CO3– determined by SIDcarbonic acid is present in only inconsequential amountspH = 7.6 + log10 {SID / Pc} mEq/liter/mm HgFor positive [SID] values, [OH-] is always larger than [H+] and be`haves qualitatively in the opposite way to [H+], as Figures 6.1 and 6.3 show. The effect of the added CO2 is to decrease [OH-] for it is no longer the only weak anion present, so that some, in fact most, of the excess strong ion positive charge measured by [SID] can be balanced by [CO3 2-] and [HCO3-]. Another puzzling feature of Equation (6.4.9) is that it says that [HCO3-] is independent of Pc. This is clearly counterintuitive, but Figure 6.2 shows it to be true. A deeper view is provided by Figure 6.3, which shows that [HCO3-] does indeed vary with Pc but only when Pc is very small, well below any physiological value. For all biological purposes, [HCO3-] in ISF is indeed independent of Pc and just equal to [SID]. This conclusion means that if [SID] is constant, but Pc changes, [CO3 2-], [OH-] and [H+] will all change, but [HCO3-] will not. [HCO3-] is therefore not a very useful quantity in the analysis or understanding of interstitial fluids.


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Bicarbonate Challenge

(Current Anaes and Crit Care 2009;20:259)

when the pt is acidotic, urinary pH should be < 5.5

complete renal fx with RRT leads to only 100 mmol acid clearance per day. This much can be made per hour in hypoperfusion

1. correct hypoperfusion

2. achieve buffer baseline with bicarb admin to BD <5

3. Observe after 1-2 hours to see if ongoing process. If < 5 rise in 2 hours then not ongoing

weight in kg x 0.2 x BD = NaBicarb dose in mmol

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Treating Non-Anion Gap

from Centor’s blog

3. Would you treat, and how?

We did decide to treat acutely to return the bicarbonate to approximately 22.  Since he weighed 70 kg, and is a relatively young man, we estimated that his total body water was around 40 liters.  Remember that the “bicarbonate space” is the total body water.  Given a deficit of 6 mEq per liter, we assumed that we needed to provide approximately 240 mEq of bicarbonate.

As a rule we try to correct halfway over the first day.  We added 2 amps of bicarbonate to a liter of D5/0.5 NS.  The next day his bicarbonate was 19.  We repeated on day 2.  His electrolyte panel after repletion:

Electrolyte panel Na 145 Cl 114 BUN 22 K 2.9 HCO3 23 creat 2.1 Blood Sugar 99

4. Will he need long term treatment?

I believe that we should treat long term. I know of 3 reasons to treat persistent normal gap acidosis in CKD patients:

  1. Decrease bone destruction
  2. Improve overall nutrition – Some research data show a correlation between chronic acidosis and malnutrition.  This reason may be soft, but the treatment is very benign.
  3. Delay dialysis – a recent study suggests that treating metabolic acidosis delays dialysis.  The article and the abstract:

Bicarbonate Supplementation Slows Progression of CKD and Improves Nutritional Status

Bicarbonate supplementation preserves renal function in experimentalchronic kidney disease (CKD), but whether the same benefit occursin humans is unknown. Here, we randomly assigned 134 adult patientswith CKD (creatinine clearance [CrCl] 15 to 30 ml/min per 1.73m2) and serum bicarbonate 16 to 20 mmol/L to either supplementationwith oral sodium bicarbonate or standard care for 2 yr. Theprimary end points were rate of CrCl decline, the proportionof patients with rapid decline of CrCl (>3 ml/min per 1.73m2/yr), and ESRD (CrCl <10 ml/min). Secondary end pointswere dietary protein intake, normalized protein nitrogen appearance,serum albumin, and mid-arm muscle circumference. Compared withthe control group, decline in CrCl was slower with bicarbonatesupplementation (5.93 versus 1.88 ml/min 1.73 m2; P < 0.0001).Patients supplemented with bicarbonate were significantly lesslikely to experience rapid progression (9 versus 45%; relativerisk 0.15; 95% confidence interval 0.06 to 0.40; P < 0.0001). Similarly, fewer patients supplemented with bicarbonate developed ESRD (6.5 versus 33%; relative risk 0.13; 95% confidence interval0.04 to 0.40; P < 0.001). Nutritional parameters improvedsignificantly with bicarbonate supplementation, which was welltolerated. This study demonstrates that bicarbonate supplementationslows the rate of progression of renal failure to ESRD and improvesnutritional status among patients with CKD.

I would treat this patient to maintain a bicarbonate of 22.  I would start either with 5 tablets of sodium bicarbonate each day.  Remember that a 650 mg bicarbonate tablet has 7.7 mEq of bicarbonate.  I usually start with approximately 0.5 mEq per kg.  This assumes a normal diet of 1 mEq per kg of acid that needs buffering and some remaining buffering from phosphate.

If the patient cannot tolerate sodium bicarbonate I use sodium citrate (Shohl’s solution or Bicitra) and would start with 15 cc twice a day.  Each cc converts to 1 mEq of bicarbonate.

Regardless of our starting point, we need to follow the patient closely and titrate our therapy to maintain the bicarbonate around 22.

I would appreciate comments, especially from those nephrologists who frequent this blog.  If any of my discussion remains obtuse, please call me out and I will try to explain better.


Study which corrects the SBE for the changes in chloride from PaCO2 buffering in erythrocytes (when CO2 goes up, it changes chrloride (chloride tide) in plasma with RBCs) Journal of Crit Care 2009;24:484)


Article examining the respiratory compensations for acidoses in Fencl-Stewart method (Crit Care Med 1998;26(7):1173)

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