Dr. T.R. Chandrashekar Intensivist, Liver transplantation,

BMC & RI super-specialty Hospital,

Bangalore.

Metabolic Acidosis-Systematic Approach

The art of transferring information from the notes of the lecturer to the notes of the students without passing through the minds of either.

The confusion of one man multiplied by the number present.

Conference

Lecture

Metabolic Acidosis-Definition • Primary reduction in serum bicarbonate

(HCO3-)

• Compensatory decrease in the arterial partial pressure of carbon dioxide (PaCO2 of ~1mmHg for every 1mmol/l fall in serum HCO3

-concentration).

• Reduction in blood pH.

Low HCO3- can be due to renal compensation to chronic

respiratory alkalosisLook for pHHCO3

- < than 10 mEq/L is diagnostic of metabolic acidosis

CO2 + H2O H2CO3 H+ + HCO3-

CO2H+

HCO3-

Acid-Base physiology

Respiratory

Metabolic

Bicarbonate is the transport from of CO2 hence both should move in the same direction

Ventilation controls PCO2

Kidney losses H+ and reabsorbs bicarbonate (HCO3-)

PCO2-Respiratory acidosis (Hypoventilation)

PCO2-Respiratory alkalosis(Hyperventilation)

HCO3- - Metabolic acidosis

HCO3- - Metabolic Alkalosis

Metabolic acidosis is caused by either a gain of acid or a loss of HCO3

-

Gain of acid may result from

• Over production of organic acids such as Ketoacids or lactic acid

• Metabolism of ingested toxins such as methanol, ethylene glycol, and paraldehyde.

• Decreased renal excretion of hydrogen ion as in uremic acidosis and distal (type I) renal tubular acidosis.

Loss of HCO3- may result from

• Renal loss in proximal renal tubular acidosis.

• Gastrointestinal loss in diarrhea.

Common causes of Metabolic acidosis we encounter areLactic acidosis-Hypoperfusion –sepsisDiabetic ketoacidosisAcute kidney injuryUremia

Metabolic acidosis- compensatory responseDISORDER PRIMARY

RESPONSES

COMPENSATORY RESPONSE Respiratory alkalosis

Metabolic acidosis

PH HCO3- pCO2

The PaCO2 begins to fall within 1–2hr Should reach a steady–state value by 12–24hrIf not patient has hypoventilation- Resp Acidosis

Normal Compensatory Response- Numbers

• Winters formula

• PaCO2 = 1.5 x [HCO3-] + 8 ± 2

If Serum (HCO3-) = 10mEq/L

• PaCO2 = 1.5 x [10] + 8 ± 2 = between 21 and 25mmHg.

• Respiratory alkalosis (if PCO2 < 21) or Respiratory acidosis (if PCO2>25)

• Last two digits of pH = PaCO2

• pH being 7.23 = PaCO2should fall to 23mmHg

Adverse effects of Metabolic acidosis

Impaired cellularenergy production

Stimulation ofinterleukin production

Decreased cardiac contractilityand cardiac output

Predisposition to ventricular arrhythmias

Alteration in oxygen binding to hemoglobinImpaired leukocyte functionSuppression of lymphocyte function

Resistance to action of infused Catecholamines & Insulin

Arterial vasodilation and hypotension

Diagnosis of metabolic acidosis

• History

• 40 year presents with 3 day old peritonitis septic BP 80/60mmHg

• RR 40/min

• Metabolic acidosis

• ABG- pH 7.21 / PCO2 = 22 / HCO3- = 9 mEq/l

• Lactate 6 mmol/L

• Post operative cardiac arrest

• Metabolic + respiratory acidosis

Metabolic acidosis-is suspected when• HCO-

3 is low

• Serum chloride is elevated

• Increased Anion gap

• There is electrochemical balance

• Sum of all negatively charged electrolytes (anions) = Sum of all positively charged electrolytes (cations).

• More anions are unmeasured than are cations

• Anion gap is thus an artifact of measurement, and not a physiologic reality

???

More anions are unmeasured than are cations

• Major unmeasured anions• albumin• phosphates• sulfates• organic anions- ketones and

lactate

Anion gap …

Anion gap is based on only three electrolytes:sodium, chloride and bicarbonate

• AG = [Na+] - [Cl- +HCO3-] =

• 140 - 128 = 12mEq/L

(venous CO2 = HCO-3 can be used).

Anion gap issues

• A 1 gm/dl decrease in serum albumin causes a 2.5 mEq/L drop in the AG.

• One problem with the anion gap is deciding what value is truly abnormal.

• In the majority of patients with anion gap between 16 and 20 mEq/L, no specific anion gap acidosis can be diagnosed.

• Above 20 mEq/L the probability of a true anion gap acidosis increases markedly (and is 100% if the AG is above 29 mEq/L)

• As a practical matter, you should consider an AG 20 mEq/L as reflecting an anion gap metabolic acidosis and search for the cause should be instituted

Method to identify mixed disorders in elevated Anion Gap Metabolic acidosis

The Delta Ratio (∆/∆)

THE DELTA RATIO (∆/∆)

• Increase in the AG should be equal to the decrease in bicarbonate so the ratio between these two changes (which we call the delta ratio) should be equal to one.

• anion gap / [HCO3-]

• = Measured anion gap – Normal anion gap

• Normal [HCO3-] – Measured [HCO3-]

•

(AG – 12) (24 - [HCO3-])

=

• More than 50% of excess acid is buffered intracellularly and by bone, not by HCO3-.

• Most of the excess anions remain in the ECF - because anions cannot easily cross the lipid bilayer of the cell membrane.

• As a result, the elevation in the anion gap usually exceeds the fall in the plasma [HCO3- ].

 

Delta ratio

 

Assessment Guidelines

     < 0.4   Hyperchloremic normal anion gap acidosis

     < 1  High AG & normal AG acidosis

   1 to 2  Pure Anion Gap Acidosis Lactic acidosis: average value 1.6DKA more likely to have a ratio closer to 1 due to urine ketone loss

     > 2  High AG acidosis and a concurrent metabolic alkalosis

or a pre-existing compensated respiratory acidosis

The Delta Ratio (∆/∆)…..

• Excessive normal saline infusion

• Chronic kidney disease

• Adrenal insufficiency (primary or secondary)

• Diarrhea

• Intestinal, pancreatic, or biliary fistulae

• Proximal RTA // Distal RTA

• Ureterosigmoidostomy / Ureteroileostomy

• Methanol intoxication

• Uremic acidosis

• Diabetic ketoacidosis

• Paraldehyde intoxication

• Iron/ INH

• Lactic acidosis

• Ethylene glycol intoxication

• Salicylate intoxication

Causes of metabolic acidosis

Increased anion gap Normal (hyperchloremic) anion gap

• A previously well 55 year old woman is admitted with a complaint of severe vomiting for 5 days sec to intestinal obstruction. BP 80/60 mmHg RR 28/min

• ABG: Electrolytes

• pH 7.23 , Na 140

• PCO2 22mmHg K 3.4,

• HCO3- 9 Cl 77Creatinine 2.1

• History : Elevated anion gap acidosis secondary to lactic acidosis in the setting of severe persistent vomiting which may lead to hypovolemia, and/or Metabolic alkalosis in the setting of persistent vomiting

• Look at the pH. The pH is low, (less than 7.35) therefore by definition, patient is acidemic.

• What is the process? Look at the PCO2, HCO3- .

P acidosis

• Distinguish the initial change from the compensatory response.

• A low HCO3- represents acidosis and is consistent with the pH, therefore it must be the initial change.

• The low PCO2 must be the compensatory response.

• Since the primary change involves HCO3-, this is a metabolic process, i.e. Metabolic Acidosis.

• Calculate the anion gap The anion gap is Na - (Cl + HCO3-) = 134 -(77 + 9) = 48 Is compensation adequate? Calculate the estimated PCO2. Using Winter's formula; PCO2 = 1.5 × [HCO3-]) + 8 ± 2

• 1.5 × 9 + 8 ± 2 = 19.5 - 23.5. (23)

• Since the actual PCO2 falls within the estimated range, we can deduce that the compensation is adequate and there is no

• separate respiratory disorder present.

• Delta ratio = Measured anion gap – Normal anion gap

• Normal [HCO3-] – Measured [HCO3-]

•

• 48-12 36

• 24-9 14

• Since the delta ratio is greater than 2, we can deduce that there is a concurrent metabolic alkalosis. This is likely due to vomiting.

• Mixed elevated anion gap metabolic acidosis and metabolic alkalosis likely due to lactic acidosis and vomiting.

(AG – 12) (24 - [HCO3-])

2.6==

=

Since anion gap elevated, calculate the delta-ratio to rule out concurrent metabolic alkalosis

There is always a underlying cause- treatment of which is the most important step in acid base problems

Deodorant

Flush

Problem

.Patient has Peritonitis/ SepsisBP 80/60 mmHgpH of 7.12, HCO3 14, Lactate of 6

Metabolic acidosis

NAHCO3

Infusion to correct pH

Fluid resuscitationInotropes/ vasopressorsSurviving Sepsis bundleSugar controlEtc..

Treatment of metabolic acidosis

• Some types of metabolic acidosis will require HCO3- therapy and some will not. Therefore, determining the cause of the metabolic acidosis is central to appropriate management.

• Using base to treat is controversial because of a lack of definitive benefit and because of potential complications.

• The failure of sodium bicarbonate administration to improve cardiovascular function, morbidity and mortality could result, in part, to adverse effects of the therapy.

Adverse effects of IV bicarbonate therapy

• Exacerbation of intracellular acidosis caused by generation of the permeable gas CO2 in the process of buffering,

• Hypertonicity of the extracellular fluid when bicarbonate is given as a hypertonic solution, volume overload,

• Overshoot metabolic alkalosis,

• Potentiation of organic acid synthesis,

• Acceleration of cellular Na+–H+ exchange causing deleterious increments in cellular Na+ and Ca2+.

IV bicarbonate therapy• pH falls below 7.10 + Respiratory fatigue or developing hemodynamic

instability emergency HC03- administration, regardless of the cause of the acidosis.

• HCO3- deficit = .5 X Body weight (kg) X ([HCO3-(desired)] - [HCO3-(measured))

• Give this calculated amount slowly and re-measure pH, HCO 3-and PCO2 after the HCO3- is given to assess the effect of therapy on the acid-base status.

• In the case of an ongoing acidosis, repeated doses of HCO 3- may be required until the underlying cause of the acidosis can be corrected.

• 8.4% NaHCO3 solution is used (50ml = 50 mEq) (osmolality of 2,000 mOsm/kg.)

IV Bicarbonate therapy

• In patients with renal impairment or evidence of volume overload, consider utilization of hemofiltration or dialysis

• In patients with CO2 retention and adequate renal function, consider administration of THAM.(tris-hydroxymethyl aminomethane)

Lactic acidosis• Lactic acid in not bad – is an alternate energy shuttle in

stress situations.

• A lactate of > 2 is significant in sick patients

• Is a very good prognostic indicator

• Lactate normalisation time is a better prognostic indicator

• Studies indicate use of lactate levels in goal-directed therapy may improve clinical outcome. lactate monitoring is a valuable parameter in the early resuscitation

• Can be present in whom systemic hypoperfusion is not present

THANKS

chandrakavi@gmail.com

• Too much normal saline hyperchloremic acidosis

• Can we explain why increased Cl- causes Acidosis??

NORMAL SALINE INFUSION LEADS TO HYPERCHLOREMIC ACIDOSIS

Increase in Cl- more than Na+

Increase in Cl- more than Na+

SID fallsSID falls

Dilution of HCO3

-

CO2

CO2 increasesHCO3

- unchanged

pH falls

Metabolic CO2 production

pH falls

Water H2O dissociates and adds H+

Explanation of acidosis by HH method Explanation of acidosis by Stewart

In NS- Na/Cl is 150 mEq/LIn ECF -Na 145/ Cl 102

TWO APPROACHES USED IN ACID BASE EVALUATION

HCO3- ( KIDNEY)

20 PaCO2 (LUNG) 1

pH --------- ------------~

Metabolic’ component of acid-base physiology is bicarbonate

Stewart approachTraditional approachHenderson-Hasselbalch Water is an important source of H +

Ionic Strength: weak and strong

Electrical Neutrality is maintained at all timesMetabolic’ component of acid-base physiology is Strong Ion Difference (SID)

SID=(Na+ +K+ +Ca2++Mg2+)-(Cl-+Lactate) is 40 to 42 mEq/L

TWO COMMONLY USED APPROACHES

pH rely on three independent Factors

1. SID- Strong ion difference

2. (ATOT)- total concentration of weak acids (albumin and phosphate)

3. PCO2

‘Metabolic’ component of acid-base physiology is not dependent on bicarbonate but instead, predominately on SID

Henderson-Hasselbalch Stewart approach

HCO3-

( KIDNEY)

PaCO2 (LUNG)

pH --------- ------~

STEWART APPROACH• Stewart (physical chemistry principles) suggested that the

traditional Henderson-Hasselbalch explanation of the underlying physiology and pathophysiology is wrong.

• “Traditional” approach merely looks at a mirror image of that proposed by Stewart. In fact HH equation is a component of Stewart approach

• The ‘‘modern’’ approach is clinically difficult, more CPU based

• Requires knowledge of protein and phosphate concentrations and more electrolytes than may be routinely measured

MODIFIED STEWART APPROACH

= ([Na+] – [Cl-]) – 38 (1)

= 0.25x [4.2–albumin] (2)

Thus true BE = BE – [1 + 2]

At bedside- it works well!

{where 38 is normal average difference in strong ions – Na and Cl}

NaCl effect

Albumin effect

Story, Belmo, Balasubramanyam

where 4.2 is normal serum albumin

Diagnosis of metabolic acidosis

• History

• 40 year presents with 3 day old peritonitis septic BP 80/60mmHg

• RR 40/min

• ABG- pH 7.21 / PCO2 = 21/ HCO3- = 9 mEq/l

• Lactate 6 mmol/L

• Metabolic acidosis with compensation

• Same patient is drowsy has pneumonia RR 12/mt

• ABG- pH 7.11 / PCO2 = 41 / HCO3- = 9 mEq/l

• Metabolic acidosis + Respiratory Acidosis

METABOLIC ACIDOSIS……. + ADDITIONAL DISORDERS

Equivalent rise of AG and Fall of HCO3……

….Pure Anion Gap Metabolic Acidosis

Discrepancy…….. in rise & fall

+ Non AG M acidosis, + M Alkalosis

PURE ANION GAP ACIDOSIS +

Delta gap = HCO3 + ∆ AG

∆ AG =Measured Anion gap-12

Delta Gap = 24 …… AG Met Acidosis < 24 ….. Non AG Met acidosis > 24 ….. Non AG Met acidosis + Meta. Alkalosis