Nephrology Lecture
Acid - Base Balance
Presented by
Anas Diab MD
US Board Certified in Nephrology
University of Michigan Graduate
Acid – Base Balance
Each day approximately 15,000 mmol of carbon dioxide
form ,from oxidation of carbohydrates, amino acids, and
fatty acids, and this can rapidly excreted by the lung.
60-70 meq or approximately 1 meq/kg body weight ,of
fixed nonvolatile acid (mineral acid) mostly sulfuric acid,
derived from the metabolism of sulfur-containing amino
acids), and phosphate.
The concentration of free hydrogen ion in body fluid is
40 nanoequivalents /L, so adding 60-70 meq of
hydrogen ion produced daily would be rapidly fatal, if not
immediately buffered
Acid-base balance is maintained to the normal by renal
excretion of acid, through a number of intra and extra
cellular buffers .
Assessment of Acid – Base
Balance
Bicarbonate-carbon dioxide buffer system:
Dissolved CO2 +H2O <-->
H2CO3 <-> HCO3- + H+
The Henderson - Hasselbalch equation:
pH = 6.10 + log ([HCO3] ÷ [0.03 x PCO2])
Renal excretion of acid
• One third of net acid secretion involves the
combination of hydrogen ions with urinary titratable
acids, particularly phosphate (HPO4 + H+ —>
H2PO4) .
Two third of net acid secretion involves the excretion
of excess hydrogen ions as Amonium ions.
Electroneutrality is preserved by coupling amonium
ions to chloride forming Amonium chloride , and
the end result that appropriate titration of renal acidity
should result in high levels of urinary chloride.
DEFINITIONS
Acidosis — A process that tends to lower the
extracellular fluid pH :
this can be induced by a fall in the extracellular
(or plasma ) bicarbonate concentration or by an
elevation in the PCO2.
Alkalosis — A process that tends to raise the
extracellular fluid pH
this can be induced by an elevation in the
extracellular (or plasma ) bicarbonate
concentration or by a fall in the PCO2.
Type of Acidosis
Metabolic acidosis — A disorder
associated with a low pH and low
bicarbonate concentration.
Respiratory acidosis — A disorder
associated with a low pH and high PCO2.
Type of Alkalosis
Metabolic alkalosis — A disorder
associated with a high pH and high
bicarbonate concentration.
Respiratory alkalosis — A disorder
associated with a high pH and low PCO2.
Causes of Metabolic Acidosis
Overproduction of Endogenous acid
(Diabetic Ketoacidosis)
Loss of Alkali stores (Diarrhea or Renal
Tubular Acidosis)
Failure of Renal Acid Secretion or base
synthesis ( Renal Failure)
Compensatory responses
Each of the simple acid-base disorders is also
associated with a compensatory response.
The Henderson-Hasselbalch equation shows
that the pH is determined by the ratio between
the HCO3 concentration and PCO2, not by the
value of either one alone.
The body responds to an acid-base disorder by
making compensatory respiratory or renal
responses in an attempt to normalize the pH.
This response is mediated at least in part by
parallel alterations in regulatory cell (renal
tubular or respiratory center) pH
Compensation in Met. Acidosis
Ventilation is increased, resulting in a fall in PCO2, which
tends to raise the pH toward normal.
Note that protection of the HCO3/PCO2 ratio and
therefore the pH requires a compensatory response that
varies in the same direction as the primary disorder (low
bicarbonate leads to low PCO2).
The respiratory compensation results in a 1.2 mmHg fall
in the PCO2 for every 1 meq/L reduction in the plasma
bicarbonate concentration . This response begins in the
first hour, and is complete by 12 to 24 hours .
Compensation in Met. Alkalosis
The respiratory compensation tends to raise the
PCO2 by 0.7 mmHg for every 1 meq/L elevation
in the plasma bicarbonate concentration
This response may not be seen in all patients
because of concurrent problems.
For example, diuretics tend to induce metabolic
alkalosis in heart failure or cirrhosis; both of
these disorders, however, are associated with
hyperventilation and a low PCO2. Thus, the
expected rise in PCO2 with metabolic alkalosis
may not be seen due to the underlying
respiratory alkalosis.
Compensation in Respiratory
acidosis
The compensatory response to respiratory acid-base disorders occurs in
two stages:
1- Cell buffering that acts within minutes to hours
2- The renal compensation that is not complete for 3 to 5 days.
As a result, different responses are seen with acute and chronic disorders.
In acute respiratory acidosis, The [HCO3] will increase by 1
mmol/l for every 10 mmHg elevation in pCO2 above 40
mmHg.
Expected [HCO3] = 24 + { (Actual pCO2 - 40) / 10 }
In chronic respiratory acidosis The [HCO3] will increase by 4
mmol/l for every 10 mmHg elevation in pCO2 above
40mmHg.
Expected [HCO3] = 24 + 4 { (Actual pCO2 - 40) / 10}
The renal response is carefully regulated, so that administering extra
bicarbonate results in the urinary excretion of the excess alkali without
elevation in the plasma bicarbonate concentration
Compensation in Respiratory
alkalosis
In acute respiratory alkalosis, The [HCO3] will
decrease by 2 mmol/l for every 10 mmHg
decrease in pCO2 below 40 mmHg.
Expected [HCO3] = 24 - 2 { ( 40 - Actual
pCO2) / 10 }
In chronic respiratory alkalosis,The [HCO3] will
decrease by 5 mmol/l for every 10 mmHg
decrease in pCO2 below 40 mmHg.
Expected [HCO3] =24 - 5 { ( 40 - Actual
pCO2) / 10 } ( range: +/- 2)
Reductions in both bicarbonate reabsorption and in
ammonium excretion contribute to the compensatory
reduction in the plasma bicarbonate concentration
MIXED ACID-BASE DISORDERS
Some patients have two or more acid-base
disorders.
An understanding of the approach to this
problem requires knowledge of the renal and
respiratory compensations that have been
empirically observed in patients with simple
acid-base disorders.
Values substantially different from those that are
expected indicates the presence of a mixed
disturbance
How to reach a diagnosis?
Evaluation of an acid-base disorder begins with
measurement of the extra cellular pH
Measurement of the plasma bicarbonate
concentration,
A low plasma bicarbonate concentration can be
seen as the primary change in metabolic
acidosis and as the compensatory response in
respiratory alkalosis.
Once the primary change is determined, the
degree of compensation should then be
assessed.
You can not over- compensate, as a golden rule.
Establishing a diagnosis requires a
careful history :
Diarrhea would suggest metabolic acidosis
Vomiting would suggest metabolic
alkalosis
History of COPD would suggest
respiratory acidosis
History of Psychosis would suggest
respiratory alkalosis.
Normal Anion Gap Metabolic
Acidosis
Defined in terms of the serum potassium
concentration:
Hypokalemic : - Diarrhea, Ureteral
diversion, Use of Carbonic inhydrase
inhibitors
- Renal Tubular Acidosis:
Type I, or Type II
Hyperkalemic : Total parenteral nutrition
oral Calcium chloride , obstructive
uropathy, addison disease , Type IV RTA.
High Anion Gap Metabolic Acidosis
MUDPILES : Methanol, Uremia, Diabetic
Ketoacidosis, Paraldehyde, Isoniazide,
Lactic Acidosis, Ethanol Ethylene glycole,
Salicylates.
In chronic renal failure the anion gap is
less than 25, if more than 25 we should
think about ingestion of poison.
When to measure The Anion Gap
Anion Gap = NA –(Cloride+Bicarb)
We measure it in each case of metabolic
acidosis
Normal anion gap 10-14mEq/L
Elevated in cases of overproduction of
endogenously produced organic acids such Keto
Acidosis or Lactic Acidosis, or the ingestion of
certain toxins such as Salicylate, Metanol, or
Ethylene Glycol.
In advance renal failure because decreased
ability of the kidneys to regenerate bicarbonate
through the Amoniagenesis.
Hints
An elevated Anion Gap always
strongly suggests a Metabolic
Acidosis.
If AG is 20-30 then high chance
(67%) of metabolic acidosis
If AG is > 30 then a metabolic
acidosis is definitely present
The delta anion gap / delta bicarbonate in
metabolic acidosis
We use this concept to determine a mix acid base
disorder.
The delta /delta ratio in an uncomplicated high AG
metabolic acidosis should be between 1 and 2.
A lower value (in which the delta AG is less than
expected from the delta HCO3) reflects either urinary
ketone losses (as in diabetic ketoacidosis)or in CKD. or
a combined high and normal AG acidosis, as might occur
if diarrhea were superimposed upon chronic renal failure
a delta /delta ratio above 2 indicates the plasma HCO3
is lower than expected from the rise in the AG; this
usually reflects a concurrent metabolic alkalosis, as with
vomiting.
If a metabolic acidosis is diagnosed, then the
Delta Ratio should be checked
Delta Ratio Assessment Guidelines in patients with a
metabolic acidosis :
< 0.4 - Hyperchloraemic normal anion gap acidosis
0.4 to 0.8 - Combined high AG and normal AG acidosis
1 - Common in DKA due to urinary ketone loss
1 to 2 - Typical pattern in high anion gap metabolic
acidosis
> 2 Check for either a co-existing Metabolic Alkalosis
(which would elevate [HCO3]) or a co-existing Chronic
Respiratory Acidosis (which results in compensatory
elevation of [HCO3])
Urinary Anion gap
In metabolic acidosis with a normal serum Anion
Gap we have to determine weather the loss in
Bicarbonate is renal or extra renal from GI loss
as in Diarrhea.
Urinary Anion Gap= Ur Cl- (Ur Na + Ur K)
It estimates the Amonium Excretion .
If it is more negative than -30 it reflect normal
response to severe GI loss
If it is positive it means impaired urinary
Acidification as in Type I RTA
Osmolal Gap
Serum Osm= 2X(NA)+ glu/18 +BUN/2.8
Osmolal Gap = Measured Osm-Calculated
Osm.
An elevated Osmolal gap in the setting of
a metabolic acidosis with elevated Anion
Gap suggests intoxication with a low
molecular-weight substance such as
Methanol or Ethylene glycol.
Indication to use bicarbonate
therapy
Reserved for patient with severe metabolic acidosis pH
less than 7.15, or serum bicarb less than 12 mEq/L.
Most beneficial in cases of loss of bicarb as in diarrhea
Not indicated if in lactic acidosis .
Calculated based on the Serum bicarb to be corrected to
15
Bicarb needs = body weight X volume of distribution X (
15 – the measured bicarb)
50% of the calculated bicarb dose should be
administered bollus, and the rest over 6-12 hours.
Case study- 1
A patient with diarrhea has an arterial pH of
7.23, bicarbonate concentration of 10 meq/L,
and PCO2 of 23 mmHg
What is your diagnosis?
The low pH indicates acidemia, and the low
plasma bicarbonate concentration indicates
metabolic acidosis.
The plasma bicarbonate concentration is 14
meq/L below normal, which should lead to a 17
mmHg fall in the PCO2 (14 x 1.2 = 17) from 40
to 23 mmHg.
Case study 1 cont.
This patient has a simple metabolic
acidosis .
A PCO2 significantly higher than this level
would indicate a concurrent respiratory
acidosis.
If, on the other hand, the PCO2 were
lower than 20 mmHg, then a concurrent
respiratory alkalosis would be present, as
might be seen with salicylate intoxication.
Case study 2
D.D is a 56 Y/O smoker 1PP/D for 25 years has
the following arterial blood values: pH equals
7.27; PCO2 equals 70 mmHg; and bicarbonate
concentration equals 31 meq/L.
What is your diagnosis?
The low pH and hypercapnia indicate that the
patient has some form of respiratory acidosis.
In view of the 30 mmHg rise in the PCO2, the
plasma bicarbonate concentration should be
elevated by 3 meq/L (to 27 meq/L) in with acute
hypercapnia, and by 11 meq/L (to 35 meq/L) with
chronic hypercapnia.
Case study 2 cont.
The observed value of 31 meq/L is between these expected levels
and could be explained by one of three disorders :
1-Chronic respiratory acidosis with superimposed metabolic acidosis
to lower the plasma bicarbonate concentration, as might occur in a
patient with chronic obstructive pulmonary disease who develops
diarrhea due to viral gastroenteritis.
2- Acute respiratory acidosis with superimposed metabolic alkalosis
to elevate the plasma bicarbonate concentration, as might occur in a
patient with vomiting due to theophylline toxicity who then develops
an acute asthmatic attack.
Acute, superimposed on mild chronic respiratory acidosis, as can be
induced by pneumonia in a patient with chronic hypercapnia.
Case study 2-cont.
Thus, the correct diagnosis in a primary respiratory acidbase disorder can be established only when correlated
with the clinical history.
This is true even when the arterial blood values appear
to represent a simple disorder. If, for example, the
plasma bicarbonate concentration had been 35 meq/L
then the results would have been compatible with an
uncomplicated chronic respiratory acidosis. However,
similar findings could have been induced by the
combination of acute hypercapnia and metabolic
alkalosis. The history should allow these possibilities to
be distinguished.
Case Presentation
A 28 Y/O woman presents for evaluation of malaise fatigue and
weakness she is always thirsty and her eyes are gritty. The serum
levels of electrolytes are as follows : Na 135 mEq/l, K 1.2 mEq/l, Cl
118 mEq/L, Bicarb 10 mEq/L, BUN 12 mg/dl, Cr 1.2 mg/dl. ABG’s
pH 7.28 PaCo2 25 mm hg. Urinalysis shows pH 6.6, U.Na 35
mEq/l, U.K 20 mEq/L U.Cl 50 mEq/L .
What should be your next recommendation?
1- Order diuretic screen
2- Order psychiatric consult
3- Order stool electrolytes
4- Begin sodium bicarbonate 450 mEq tablets 2 tabs orally X 4/d
5- Initiate potassium repletion, followed by potassium ctrate.
The answer is potassium repletion
The patient has Sicca complex and Renal Tubular
Acidosis likely due to Sjogren syndrome
Normal Anion gap Metabolic acidosis
Urinary Anion Gap is positive
Repletion of potassium is foremost in these situation
because a potential disastrous exacerbation of this
patient’s hypokalemia may occur with base
supplementation alone.
Diuretic abuse often leads to hypokalemia but not
metabolic acidosis, except with Acetazolamide.
Quick Case
select the correct interpretation for the given
arterial blood gas set:
pH 7.51, pCO2 40, HCO3- 31:
a. Normal
b. Uncompensated metabolic alkalosis
c. Partially compensated respiratory acidosis
d. Uncompensated respiratory alkalosis
Quick case
pH 7.33, pCO2 29, HCO3- 16:
a. Uncompensated respiratory alkalosis
b. Uncompensated metabolic acidosis
c. Partially compensated respiratory
acidosis
d. Partially compensated metabolic
acidosis
Quick case
pH 7.40, pCO2 40, HCO3- 24:
a. Normal
b. Uncompensated metabolic acidosis
c. Partially compensated respiratory
acidosis
d. Partially compensated metabolic
acidosis
Quick case
pH 7.12, pCO2 60, HCO3- 29:
a. Uncompensated metabolic acidosis
b. Uncompensated respiratory acidosis
c. Partially compensated respiratory
acidosis
d. Partially compensated metabolic
acidosis
Quick case
pH 7.48, pCO2 30, HCO3- 23:
a. Uncompensated metabolic alkalosis
b. Uncompensated respiratory alkalosis
c. Partially compensated respiratory
alkalosis
d. Partially compensated metabolic
alkalosis
Quick case
pH 7.62, pCO2 47, HCO3- 30:
a. Uncompensated metabolic alkalosis
b. Uncompensated respiratory alkalosis
c. Partially compensated respiratory
alkalosis
d. Partially compensated metabolic
alkalosis
Last case
pH 7.30, pCO2 59. HCO3- 28:
a. Uncompensated metabolic acidosis
b. Uncompensated respiratory acidosis
c. Partially compensated respiratory
acidosis
d. Partially compensated metabolic
acidosis