This document discusses metabolic acidosis and provides a systematic approach to diagnosis and treatment. Key points include: 1. Metabolic acidosis is defined by a primary reduction in serum bicarbonate and low blood pH. Common causes seen in practice include lactic acidosis, diabetic ketoacidosis, and acute kidney injury. 2. Evaluation involves assessing the anion gap, bicarbonate levels, electrolytes, and clinical context to determine the underlying etiology. Mixed disorders can occur. 3. Treatment focuses on correcting the primary cause. Bicarbonate therapy may be used in severe cases to raise the pH, but adverse effects are possible and the underlying condition still needs treatment.

1. Metabolic Acidosis-Systematic
Approach
Dr. T.R. Chandrashekar
Intensivist, Liver transplantation,
BMC & RI super-specialty Hospital,
Bangalore.

2. Conferenc
e
The confusion of one man multiplied
by the number present.
Lecture
The art of transferring information from the
notes of the lecturer to the notes of the
students without passing through the minds of
either.

3. Metabolic Acidosis-
Definition
• Primary reduction in serum
bicarbonate (HCO-)
3
Low HCO3
- can be due to renal compensation
• Compensatory decrease in the
arterial partial pressure of carbon
dioxide (PaCO2 of ~1mmHg for
every 1mmol/l fall in serum HCO3
-
to chronic respiratory alkalosis
Look for pH
HCO3
- < than 10 mEq/L is diagnostic of
metabolic acidosis
concentration).
• Reduction in blood pH.

4. CO2 + H2O H2CO3 H+ + HCO3
-
CO2
H+
HCO3
-
Acid-Base physiology
Respiratory
Metabolic
Bicarbonate is the transport from of COhence both should
2 move in the same direction
Ventilation controls PCO2
Kidney losses H+ and reabsorbs bicarbonate (HCO-)
3
PCO2-Respiratory acidosis
(Hypoventilation)
PCO2-Respiratory alkalosis
(Hyperventilation)
HCO3
- - Metabolic acidosis
HCO3
- - Metabolic Alkalosis

5. Metabolic acidosis is caused by either a
gain of acid or a loss of HCO-
3
Gain of acid may result from
• Over production of organic acids such as
Common causes of Metabolic acidosis we
encounter are
Lactic acidosis-Hypoperfusion –sepsis
Diabetic ketoacidosis
Acute kidney injury
Uremia
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.

6. Metabolic acidosis-compensatory
response
DISORDER 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–
24hr
If not patient has hypoventilation- Resp
Acidosis

7. 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

8. Resistance to action of infused
Catecholamines & Insulin
Adverse effects
of Metabolic
acidosis
Impaired cellular
energy production
Stimulation of
interleukin
production
Decreased cardiac
contractility
and cardiac output
Predisposition to
ventricular arrhythmias
Alteration in oxygen binding to
hemoglobin
Arterial vasodilation and
hypotension
Impaired leukocyte function
Suppression of lymphocyte function

9. 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

10. 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

11. More anions are unmeasured than are
cations
• Major unmeasured anions
• albumin
• phosphates
• sulfates
• organic anions- ketones
and lactate
Anion gap …

12. 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).

13. 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

14. Method to identify mixed
disorders in
elevated Anion Gap Metabolic
acidosis
The Delta Ratio
(Δ/Δ)

15. THE DELTA RATIO (Δ/Δ)
• 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-])
=

16. The Delta Ratio (Δ/Δ)…..
• 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 1.6
DKA 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

17. Causes of metabolic acidosis
• Excessive normal saline infusion
• Chronic kidney disease
• Adrenal insufficiency (primary or
secondary)
• Diarrhea
• Intestinal, pancreatic, or biliary
fistulae
• Proximal RTA // Distal RTA
• Ureterosigmoidostomy /
Ureteroileostomy
Increased anion gap
• Methanol intoxication
• Uremic acidosis
• Diabetic ketoacidosis
• Paraldehyde intoxication
• Iron/ INH
• Lactic acidosis
• Ethylene glycol
intoxication
• Salicylate intoxication
Normal (hyperchloremic) anion
gap

18. • 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 77
P
acidosis
Creatinine 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- .

19. • 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
The anion gap is Na - (Cl + HCO3-) = 134 -(77 + 9) =
48
Is ? 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 PCOfalls within the estimated range,

20. Since anion gap elevated, calculate the to rule out
concurrent metabolic alkalosis
• Delta ratio = Measured anion gap – Normal anion gap
• Normal [HCO3-] – Measured [HCO3-]
•
(AG – 12)
(24 -
[HCO3-])
=
• 48-12 36
= = 2.6
• 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.

21. There is always a underlying cause- treatment
of which is the most important step in acid
base problems
Deodorant
Flush
Problem
.Patient has
Peritonitis/ Sepsis
BP 80/60 mmHg
pH of 7.12, HCO3
14, Lactate of 6
Metabolic acidosis
NAHCO3
Infusion to
correct pH
Fluid
resuscitation
Inotropes/
vasopressors
Surviving
Sepsis bundle
Sugar control
Etc..

22. 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.

23. 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+.

24. 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,
HCO3-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
HCO3- 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.)

25. 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)

26. 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

27. chandrakavi@gmail.c
om

28. • Too much normal saline hyperchloremic acidosis
• Can we explain why increased Cl- causes Acidosis??

29. NORMAL SALINE INFUSION LEADS
TO HYPERCHLOREMIC ACIDOSIS
Explanation of acidosis by HH method Explanation of acidosis by Stewart
Increase in
Cl- more than Na+
SID falls
Dilution
of HCO3
-
CO2
CO2 increases
HCO3
- unchanged
pH falls
Metabolic
CO2
production
pH falls
Water H2O
dissociates
and adds H+
In NS- Na/Cl is 150 mEq/L
In ECF -Na 145/ Cl 102

30. TWO APPROACHES USED IN ACID BASE
EVALUATION
Traditional approach Stewart approach
Henderson-
Hasselbalch
Metabolic’ component
of
acid-base physiology is
bicarbonate
HCO3
- ( KIDNEY) 20
pH ~ --------- ------------
PaCO2 (LUNG) 1
Water is an important source of H +
Ionic Strength: weak and strong
Electrical Neutrality is maintained at
all times
Metabolic’ component of acid-base
physiology is Strong Ion Difference
(SID)
SID=(Na+ +K+ +Ca2++Mg2+)-(Cl-+Lactate)
is 40 to 42 mEq/L

31. TWO COMMONLY USED APPROACHES
Henderson-Hasselbalch Stewart approach
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
HCO3
- ( KIDNEY)
pH ~ --------- ------
PaCO2 (LUNG)

32. 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

33. MODIFIED STEWART APPROACH
= ([Na+] – [Cl-]) – 38 (1)
{where 38 is normal average difference in strong ions – Na and Cl}
= 0.25x [4.2–albumin] (2)
Thus true BE = BE – [1 + 2]
At bedside- it works well!
NaCl effect
Albumin effect
Story, Belmo, Balasubramanyam
where 4.2 is normal serum albumin

34. 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

35. Equivalent rise of AG and Fall of HCO3……
….Pure Anion Gap Metabolic Acidosis
Discrepancy…….. in rise & fall
+ Non AG M acidosis, + M Alkalosis

36. Δ AG =Measured Anion gap-12
Delta gap = HCO3 + Δ AG
Delta Gap = 24 …… AG Met Acidosis
< 24 ….. Non AG Met acidosis
> 24 ….. Non AG Met acidosis + Meta. Alkalosis