Acid Base Balance
• Stephen P. DiBartola, DVM
• Department of Veterinary Clinical
Sciences
• College of Veterinary Medicine
• Ohio State University
• Columbus, OH 43210
The Nephronauts
Acid Base Balance
• Who cares about
acid base
Now that I have
this data, what
balance?
does it mean?
Acid Base Balance: Why pH?
• Nanoequivalent concentration of H+
versus milliequivalent concentrations
of other electrolytes (Na+, K+, Cl-,
HCO3-) in body fluids
• Normal ECF [H+] is 40 nEq/L or
0.00004 mEq/L versus [K+] of 4.0
mEq/L
Acid Base Balance
• pH = -log10[H+] = log10(1/[H+])
• [H+] = 40 nEq/L = 4 X 10-8 Eq/L
• pH = -log10(4 X 10-8) = 7.4
• Normal pH = 7.37-7.42 and extreme
range compatible with life is 6.8 to 8.0
Acid Base Balance
• HA =
+
• Acid = Proton donor (HA)
• Base = Proton acceptor (A-)
+
H
A
Acid Base Balance: Daily
metabolism
• Metabolism of sulfur-containing
amino acids in proteins yields
sulfuric acid and metabolism of
phospholipids yields phosphoric
acid: 40-80 mEq/day of FIXED or
NON-VOLATILE acid
• Metabolism of carbohydrates and
fats yields 15,000-20,000 mMol CO2 or
VOLATILE acid
Acid Base Balance
• Why is CO2 an acid? (How can it be a
proton donor?)
• Carbonic anhydrase in red cells and
renal tubular cells facilitates the
reaction: CO2 + H2O = H2CO3
• Carbonic acid is an obvious proton
donor: H2CO3 = H+ + HCO3-
Acid Base Balance: Buffers
• A substance that can accept
protons (H+ ions) and minimize a
change in pH
• A solution of a weak acid and its
salt
mEq strong
Titration curve of a buffer
solution
Buffer zone
pKa +/- 1.0 pH unit
pKa
pH
Acid Base Balance: Buffers
• Effectiveness of a buffer depends
upon:
• Prevailing pH of body fluid to be
defended
• Concentration of buffer in that body
fluid
• pKa of buffer
• “Special circumstances” (e.g.,
bicarbonate is part of an open system)
Important body buffers
• Extracellular fluid (ECF)
• Bicarbonate
• Intracellular fluid (ICF)
• Phosphates
• Proteins (e.g., Hb in RBC)
• Bone carbonate
Important body buffers:
Bicarbonate
• pKa is 1.3 units below
physiologic pH
• ECF concentration is high (24
mEq/L)
• In equilibrium with CO2 (i.e. part
of an open system)
CO2 + H2O = H2CO3 = H+ + HCO3-
Important body buffers:
Phosphate
• Important in ICF where concentration
is high (40 mEq/L)
• Relatively unimportant in ECF where
concentration is low (2 mEq/L)
• Important in urine (titratable acidity)
due to pKa of 6.8 (distal tubular fluid
pH = 6.0 to 7.0)
Important body buffers:
Proteins
• Plasma proteins play limited role
in ECF buffering
• Intracellular proteins (especially
Hb in RBC) play major role in
buffering
Important body buffers:
Bone carbonate
• Very large store of potential
buffer
• Important role in long term
response to chronic acidosis
Henderson-Hasselbach
equation
•
•
•
•
•
HA  H+ + A- (v1 = k1[HA])
H+ + A-  HA (v2 = k2[H+][A-])
At equilibrium: v1 = v2
k1[HA] = k2[H+][A-]
k1/k2 = Ka = [H+][A-]/[HA]
Henderson-Hasselbach
equation
• Ka = [H+][A-]/[HA]
• pH = pKa + log([A-]/[HA])
Henderson-Hasselbach
equation
• pH = pKa + log([HCO3-]/[H2CO3])
• CO2 dissolved in plasma potentially
can form H2CO3 so:
pH = pKa + log([HCO3-]/[dissolved CO2 + H2CO3])
Henderson-Hasselbach
equation
• At the temperature and ionic strength
of ECF there are 6,800 HCO3- ions
and 340 molecules of dissolved CO2
for each molecule of H2CO3.
Therefore, H2CO3 can be neglected.
• Dissolved CO2 is related to pCO2 by
its solubility coefficient:
Dissolved CO2 = 0.03 X pCO2
Henderson-Hasselbach equation
(clinically relevant form)
• pH = pKa + log([HCO3-]/.03xpCO2)
• pH = 6.1 + log([HCO3-]/.03xpCO2)
• Shows that pH is a function of the
RATIO between bicarbonate and
pCO2
Acid Base Balance: Physiologic
lines of defense
• Physicochemical buffering by ECF
and ICF buffers (seconds)
• Alterations in ventilation to produce a
change in pCO2 (seconds to minutes)
• Renal readjustment of body HCO3stores (hours to days)
• pH = pKa + log(KIDNEYS/LUNGS)
Primary Acid Base Disorders
• Metabolic disturbances
• Metabolic acidosis
• Metabolic alkalosis
• Respiratory disturbances
• Respiratory acidosis
• Respiratory alkalosis
Acid Base Disorders
Acidosis and alkalosis
versus
Acidemia and alkalemia
Acid Base Disorders:
Principles of interpretation
• Each primary (metabolic or respiratory)
disturbance is accompanied by a
secondary (opposing) response in the
other system (respiratory or metabolic)
• pH is returned nearly but not completely
to normal
• Overcompensation does not occur
Acid Base Disorders
Disorder
Metabolic
acidosis
Metabolic
alkalosis
Respiratory
acidosis
Respiratory
alkalosis
pH [H+]
Primary
Secondary
disturbance response


 [HCO3-]
 pCO2


 [HCO3-]
 pCO2


 pCO2
 [HCO3-]


 pCO2
 [HCO3-]
Acid Base Disorders
• Simple Primary disturbance and expected
adaptive (secondary) response
• Mixed Two separate primary disturbances
present simultaneously in the same
individual
Must know expected adaptive
(compensatory) response to recognize
mixed disturbances
Acid Base Disorders
Primary disorder
Compensatory response
Metabolic acidosis
0.7-1.2 mm  pCO2 per 1.0 mEq/L  HCO3-
Metabolic alkalosis
0.7 mm  pCO2 per 1.0 mEq/L  HCO3-
Acute respiratory acidosis
0.15  mEq/L HCO3- per 1.0 mm  pCO2
Chronic respiratory acidosis
0.35  mEq/L HCO3- per 1.0 mm  pCO2
Acute respiratory alkalosis
0.25 mEq/L  HCO3- per 1.0 mm  pCO2
Chronic respiratory alkalosis
0.55 mEq/L  HCO3- per 1.0 mm  pCO2
Compensation for metabolic acidosis
• H+ buffered by ECF HCO3- &
Hb in RBC; Plasma Pr and Pi:
negligible role (sec-min)
• Ventilation lowers pCO2 (min)
• H+ buffered by interstitial
HCO3- (30 min)
• H+ buffered by ICF Pr and Pi
(hrs)
• Renal regeneration of HCO3(2-6 days)
Compensation for metabolic acidosis
• H+ buffered by ECF HCO3& Hb in RBC; Plasma Pr
and Pi: negligible role
(sec-min)
• Ventilation lowers pCO2
(min)
• H+ buffered by interstitial
HCO3- (30 min)
• H+ buffered by ICF Pr and
Pi (hrs)
• Renal regeneration of
HCO3- (2-6 days)
Compensation for respiratory acidosis
Bicarbonate cannot participate in
buffering of H+ arising from
respiratory acidosis:
CO2 + H2O = H2CO3 = H+ + HCO3-
From respiratory acidosis
Compensation for respiratory acidosis
• Bicarbonate is formed as the CO2 + H2O =
H2CO3 = H+ + HCO3- equilibrium is pushed
to the right
• H+ formed is buffered by Hb in RBC
(seconds to minutes)
• H+ enters other cells and is buffered by
proteins and phosphates (hours)
• Renal excretion of H+ and generation of
new bicarbonate follows (2 to 6 days)
Compensation for acid base
disturbances
• Respiratory compensation for
metabolic disorders should be
complete in 24 hours
• “Acute” is < 24-48 hrs
• “Chronic” is > 24-48 hrs
• Metabolic (renal) compensation for
respiratory disorders is slower and
requires 2 to 6 days
Concept of
Anion Gap
Acid Base Disorders:
Interpretation
• Is an acid base disturbance present?
• What is the primary disturbance?
• Is the secondary (adaptive) response
as expected?
• What underlying disease process is
responsible for the acid base
disturbance?
Acid Base Disorders: Interpretation
• Arterial blood gas from a dog: pH 7.27, HCO312 mEq/L, pCO2 27 mmHg (normal: pH 7.39,
HCO3- 22 mEq/L, pCO2 37 mmHg)
• Is an acid base disturbance present?
• YES (look at the pH)
• Of what general type?
• ACIDOSIS (pH 7.27 < 7.39)
• Metabolic or respiratory?
• pCO2 is LOW (can’t be respiratory acidosis)
• HCO3- is LOW (must be METABOLIC ACIDOSIS)
Acid Base Disorders: Interpretation
• Is secondary (adaptive) response as expected?
• Observed HCO3- is 10 mEq/L lower than
“normal” (22-12)
• “Normal” dog can lower pCO2 1 mmHg for every
0.7-1.2 mEq/L decrement in HCO3- (use 1.0
mEq/L as “average”)
• Expected pCO2 = 37-10 = 27 mmHg
• Observed pCO2 = 27 mmHg
• Conclusion: YES, adaptive response is as
expected. This is a simple metabolic acidosis
with respiratory compensation
Acid Base Disorders: Interpretation
• Arterial blood gas from a dog sick for 1 week:
pH 7.33, HCO3- 29 mEq/L, pCO2 57 mmHg
(normal: pH 7.39, HCO3- 22 mEq/L, pCO2 37
mmHg)
• Is an acid base disturbance present?
• YES (look at the pH)
• Of what general type?
• ACIDOSIS (pH 7.33 < 7.39)
• Metabolic or respiratory?
• HCO3- is HIGH (can’t be metabolic acidosis)
• pCO2 is HIGH (must be RESPIRATORY ACIDOSIS)
Acid Base Disorders: Interpretation
• Is secondary (adaptive) response as expected?
• Observed pCO2 is 20 mmHg higher than
“normal” (57-37)
• “Normal” dog can increase HCO3- 3.5 mEq/L for
every 10 mmHg increment in pCO2 (in “chronic”
disturbance)
• Expected HCO3- = 22+7 = 29 mEq/L
• Observed HCO3- = 29 mEq/L
• Conclusion: YES, adaptive response is as
expected. This is a simple respiratory acidosis
with metabolic compensation
Acid Base Disorders: Interpretation
• Even in simple disturbances,
calculated compensatory pCO2 and
HCO3- values usually won’t match
observed values because calculations
are based on “average” values
• Do not diagnose a mixed disturbance
unless calculated value is > 2 to 3
mmHg (pCO2) or mEq/L (HCO3-)
different from observed value
Acid Base Disorders: Interpretation
• Arterial blood gas from a dog: pH 7.05, HCO312 mEq/L, pCO2 44 mmHg (normal: pH 7.39,
HCO3- 22 mEq/L, pCO2 37 mmHg)
• Is an acid base disturbance present?
• ABSOLUTELY! (look at the pH)
• Of what general type?
• ACIDOSIS (pH 7.05 << 7.39)
• Metabolic or respiratory?
• pCO2 is HIGH (could be respiratory acidosis)
• HCO3- is LOW (could be metabolic acidosis)
Acid Base Disorders: Interpretation
• Is secondary (adaptive) response as expected?
• NO
• If simple metabolic acidosis, pCO2 should
be low in response
• If simple respiratory acidosis, HCO3- should
be high in response
• Conclusion: This is a mixed metabolic and
respiratory acidosis. The extremely low pH
alerts you to the possibility of a mixed
disturbance
Acid Base Disorders: Interpretation
• Arterial blood gas from a dog with sudden onset
of gastric dilatation/volvulus: pH 7.38, HCO3- 12
mEq/L, pCO2 21 mmHg (normal: pH 7.39, HCO3- 22
mEq/L, pCO2 37 mmHg)
• Is an acid base disturbance present?
• If so, it’s not obvious from pH
• Of what general type?
• From pCO2 could be respiratory alkalosis or from
HCO3- could be metabolic acidosis
• Metabolic or respiratory?
• pCO2 is LOW (could be respiratory alkalosis)
• HCO3- is LOW (could be metabolic acidosis)
Acid Base Disorders: Interpretation
• Is secondary (adaptive) response as expected?
• If primary metabolic acidosis
• 10 mEq/L decrement in HCO3- (22-12)
• Expected pCO2 = 27 mmHg (37-10)
• Observed pCO2 = 21 mmHg
• If primary acute respiratory alkalosis
• 16 mmHg decrement in pCO2 (37-21)
• Expected HCO3- = 18 mEq/L (22-4)
• Observed HCO3- = 12 mEq/L
• Conclusion: Mixed metabolic acidosis and
respiratory alkalosis
Acid Base Disorders: Interpretation
• Is mixed metabolic acidosis and
respiratory alkalosis compatible with
acute gastric dilatation/volvulus?
• YES
• Metabolic acidosis due to shock and
decreased tissue perfusion
• Respiratory alkalosis due to
hyperventilation induced by pain or
septicemia
Acid Base Disorders: Interpretation
• What if dog had been sick with some
other disorder for 1 week?
• If primary chronic respiratory alkalosis
• 16 mmHg decrement in pCO2 (37-21)
• Expected HCO3- = 13.2 mEq/L (22-8.8)
• Observed HCO3- = 12 mEq/L
• Difference is < 2 mEq/L
• Conclusion of simple chronic respiratory
alkalosis would be justified
Renal regulation of acid base balance
• Role of kidneys is preservation of body’s
bicarbonate stores. Accomplished by:
• Reabsorption of 99.9% of filtered bicarbonate
• Regeneration of titrated bicarbonate by
excretion of:
• Titratable acidity (mainly phosphate)
• Ammonium salts
All of these things are accomplished
by secretion of hydrogen ions
All of these things are accomplished
by secretion of hydrogen ions …
• If secreted H+ ions combine with filtered
bicarbonate, bicarbonate is reabsorbed
• If secreted H+ ions combine with
phosphate or ammonia, net acid
excretion and generation of new
bicarbonate occur
It all depends on what buffer the secreted H+
encounters in the tubular fluid, which in turn
is a function of where we are in the nephron!
Renal reabsorption of bicarbonate
• Proximal tubule:
70-85%
• Loop of Henle:
10-20%
• Distal tubule and
collecting ducts:
4-7%
Factors affecting renal bicarbonate
reabsorption
•
•
•
•
Filtered load of bicarbonate
Extracellular fluid volume
Prolonged changes in pCO2
Plasma chloride
concentration
• Plasma potassium
concentration
• Hormones (e.g.,
mineralocorticoids,
glucocorticoids)
Titratable acidity
• Occurs when secreted H+
encounter & titrate
phosphate in tubular fluid
• Refers to amount of strong
base needed to titrate urine
back to pH 7.4
• 40% (15-30 mEq) of daily
fixed acid load
• Relatively constant (not
highly adaptable)
Ammonium excretion
• Occurs when
secreted H+ combine
with NH3 and are
trapped as NH4+ salts
in tubular fluid
• 60% (25-50 mEq) of
daily fixed acid load
• Very adaptable (via
glutaminase
induction)
Ammonium excretion
• Large amounts of
H+ can be excreted
without extremely
low urine pH
because pKa of
NH3/NH4+ system is
very high (9.2)