Henderson-Hasselbalch
Equation
Acid-base Balance
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1
The Key to Blood Gas Interpretation:
Four Equations, Three Physiologic Processes
Equation
1)
2)
3)
4)
PaCO2 equation
Alveolar gas equation
Oxygen content equation
Henderson-Hasselbalch equation
Physiologic Process
Alveolar ventilation
Oxygenation
Oxygenation
Acid-base balance
These four equations, crucial to understanding and interpreting arterial blood
gas data.
Bicarbonate Buffer System
ECF: H+ + HCO3-  H2O + CO2  lungs
ICF: H+ + HCO3-  H2O + CO2
B
+
HB
(falls)
Henderson-Hasselbalch Equation
-
pH = pK + log
[HCO3 ]
---------------------0.03 [PaCO2]
For teaching purposes, the H-H equation can be shortened to its
basic relationships:
-
HCO3
pH ~ ---------------PaCO2
pH is inversely related to [H+]; a pH change
of 1.00 represents a 10-fold change in [H+]
pH
7.00
7.10
7.30
7.40
7.52
7.70
8.00
[H+] in nanomoles/L
100
80
50
40
30
20
10
Methods to Interconvert pH and [H+]:
Drop the 7 and Decimal Point Rule
pH
7.40
7.38
7.42
7.10
Drop 7 and
Decimal Point
40
38
42
10
Difference
from 40
0
-2
+2
-30
[H+] nmol/L
40
40-(-2)=42
40- (2)=38
40-(-30)=70
Methods to Interconvert pH and [H+]:
The 0.1 pH Change Rule
PH
Conversion Factor
[H+] nmol/L
6.90
100 / 0.8
125
7.00
100
100
7.10
100 X 0.8
80
7.20
100 X 0.8 X 0.8
64
Basis of Metabolic Acidosis
H+
+ HCO3  H2O + CO2
(Exhaled)
Added
acids
Loss of
NaHCO3
New A(rise in plasma AG)
No New A(no rise in plasma AG)
Henderson Equation:
24 X Pco2
[H+] = ---------------[HCO3-]
A patient has diabetic ketoacidosis and the following
laboratory data: pH=7.10, PaCO2= 30 mm Hg, [HCO3-] =
13 mmol/L, AG= 25 mEq/L, what do you conclude?
•
•
•
•
pH= 7.10, thus [H+] is 70-80 nmol/L
AG is 25, thus added anion concentration is 25-12= 13
8024 X 30/ 13
8056
Primary Acid-base Disorders:
Respiratory Alkalosis
A primary disorder where the first change is a lowering of PaCO2, resulting
in an elevated pH. Compensation (bringing the pH back down toward
normal) is a secondary lowering of bicarbonate (HCO3) by the kidneys;
Primary Event
Compensatory Event
HCO3-
↑pH ~ -------------↓PaCO2
↓HCO3-
pH ~ --------------
↑
↓PaCO2
Hypoxemia (includes altitude)
Anxiety, sepsis
Any acute pulmonary insult (e.g., pneumonia, mild asthma attack, early
pulmonary edema, pulmonary embolism)
Primary Acid-base Disorders:
Respiratory Acidosis
A primary disorder where the first change is an elevation of PaCO2, resulting
in decreased pH. Compensation (bringing pH back up toward normal) is a
secondary retention of bicarbonate by the kidneys; this
Primary Event
Compensatory Event
HCO3-
↓pH ~ -------------↑PaCO2
↑HCO3-
pH ~ --------------
↓
↑PaCO2
Central nervous system depression (e.g., drug overdose)
Chest bellows dysfunction (e.g., Guillain-Barré syndrome, myasthenia gravis)
Disease of lungs and/or upper airway (e.g., chronic obstructive lung disease, severe asthma
attack, severe pulmonary edema)
Primary Acid-base Disorders:
Metabolic Alkalosis
A primary acid-base disorder where the first change is an elevation of HCO3-,
resulting in increased pH. Compensation is a secondary hypoventilation
(increased PaCO2),Compensation for metabolic alkalosis (attempting to bring
pH back down toward normal) is less predictable than for the other three acidbase disorders.
Primary Event
Compensatory Event
↑HCO3-
↑pH ~ -------------PaCO2
↑HCO3-
pH ~ --------------
↑
↑PaCO2
Chloride responsive (responds to NaCl or KCl therapy): contraction alkalosis, diuretics, corticosteroids,
gastric suctioning, vomiting
Chloride resistant: any hyperaldosterone state (e.g., Cushing’s syndrome, Bartter’s syndrome, severe K+
depletion)
Primary Acid-base Disorders:
Metabolic Acidosis
A primary acid-base disorder where the first change is a lowering of
HCO3-, resulting in decreased pH. Compensation (bringing pH back up
toward normal) is a secondary hyperventilation; this lowering of PaCO2 is
not respiratory alkalosis since it is not a primary process.
Primary Event
Compensatory Event
↓HCO3-
↓pH ~ -------------PaCO2
↓HCO3-
pH ~ --------------
↓
↓PaCO2
Anion Gap
Serum Cations (+)
Serum Anions (-)
Na+
Cl-
K+
HCO3-
Mg++
HPO4--
Ca++
SO4-Proteins-
Na+ + K+ + Mg++ + Ca++ + Protein+ = Cl- + HCO3- + HPO4-- + SO4-- + ProteinsNa+ + K+ + UC+= Cl- + HCO3- + UA-AG = Na+ - (Cl- + CO2)
Note: CO2 in this equation is the “total CO2” measured in the chemistry lab as part of routine
serum electrolytes, and consists mostly of bicarbonate. Normal AG is typically 12 ± 4 mEq/L. If
AG is calculated using K+, the normal AG is 16 ± 4 mEq/L..
Normal Ionic Anatomy of Serum
15
Anion Gap
cations
A-
Other
anions
cations
Normal AG
A-
Other
anions
HCO3-
HCO3Na+
(140)
Cl(103)
cations
AAdded anions
HCO3(25)
Na+
(140)
Other
anions
Cl(103)
Increased AG acidosis
Na+
(140)
Cl(112)
Normal AG with acidosis
Low AG
+
+
+
+
- +- UA
Na + K + UC
= -Cl
+ HCO
+ UA-UC = Cl
+- HCO
3
↑UC+
Hypercalcemia
3
↓UA-Hypoalbuminemia (2.5 / 1g/dL)
Lithium intoxication
Monoclonal IgG gammopathy
Polyclonal gammopathy
Polymyxin B (Cl- prepaeration)
Hypermagnesemia
Underestimation of Na+
Overestimation of Cl-- or HCO3-
Hypertriglyceridemia (↓Na)
Bromide Intoxication (↓Cl)
Severe Hyponatremic (↓Na)
Iodide Intoxication (↓Cl)
Lab error
Cells not separated from sera (HCO3)
Lab error
--
High AG
Na++
+
K++
+
-UA
- +
- +
- +HCO
- +
UC=+=ClCl
HCO
33
UC+
↓UC+
UA--
↑UA-L-Lactic acid (Type A and B)
D-Lactic acid
Ketoacidosis (-hydroxybutyric acid))
Hyperlbuminemia
Severe hyperphosphatemia
Hypocalcemia
Increased anionic paraproteins (IgA-)
Hypomagnesemia
Drug poisonings (e.g., aspirin, ethylene
glycol, methanol)
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Lactic Acidosis
Type A
• Severe hypoxemia
• Acute circulatory shock
(poor delivery of O2)
• Severe anemia (low
capacity of blood to
carry O2)
• Prolonged seizures
• Exhausting exercise
Type B
• PDH problems: thiamin
deficiency or an inborn error
• Decreased gluconeogenesis,
liver failure, biguanide, alcohol
• Excessive formation of lactic
acid: malignant cells, low ATP,
inhibition of mitochondrial
generation of ATP: cyanide,
uncoupling oxidation and
phosphorylation, alcohol
intoxication
Normal AG
↑Cl
+ + K++ + UC++= Cl- + -HCO - +- UA-- -+
Na
Na + K + UC =
+ ↓HCO
3 3 + UA
GI HCO3- Loss
Renal HCO3- Loss (direct or indirect)
Diarrhea
Renal tubular acidosis
Ileus
Use of carbonic anhydrase inhibitors
Fistula or T-tube drainage,
Failure of renal generation of new bicarbonate (low
NH4+ excretion)
Villous adenoma
Low production of NH4+ (renal failure,
hyperkalemia)
Ileal conduit combined with
delivery of Cl- from urine
Low transfer of NH4+ to the urine (medullary
interstitial disease, low distal net H+ secretion)
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Is it Mixed Disorder?
22
Tips to Diagnosing Mixed Acid-base
Disorders
• Examine serum electrolytes: Na+, K+, Cl-,
and CO2.
• Normal pH in acid-base abnormality indicate
mixed disease!
• Calculate the expected compensatory values
for the disorder and compare with actual
• ∆ ∆ in metabolic acidosis
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Acute Respiratory Acidosis
↑ 1 mEq/LHCO3-
↓ 0.07 pH ~ -----------------------------
↑10 PaCO2
Chronic Respiratory Acidosis
↑ 3-4 mEq/LHCO3-
↓ 0.03 pH ~ -----------------------------
↑10 PaCO2
Acute Respiratory Alkalosis
↓ 2 mEq/LHCO3-
↑ 0.08 pH ~ -----------------------------
↓10 PaCO2
Chronic Respiratory Alkalosis
↓ 5 mEq/LHCO3-
↑ 0.03 pH ~ -----------------------------
↓10 PaCO2
Metabolic Acidosis
↓
HCO3
↓ pH ~ -----------------------------------
∆PaCO2= [1.5 x serum CO2] + (8 ± 2)
∆∆
24-HCO3- = AG-Normal AG
∆ HCO3- = ∆ AG
No other metabolic abnormality coexists
∆
HCO3 >
∆ AG
A normal anion gap metabolic acidosis (hyperchloremic acidosis) coexists
∆ HCO3- < ∆ AG
A metabolic alkalosis (or other hyperbicarbonatemic disorder) is said to coexist
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Acid-base Disorders:
A patient’s arterial blood gas shows pH of 7.14, PaCO2
of 70 mm Hg, and HCO3- of 23 mEq/L. How would you
describe the likely acid-base disorder(s)?
1.
2.
3.
4.
5.
6.
7.
Acute elevation of PaCO2 leads to reduced pH: acute respiratory
acidosis.
For every 10-mm Hg rise in PaCO2 pH falls about 0.07 units.
Expected fall in pH: 0.21 thus pH should be = 7.19
Actual pH: 7.14 suggesting combined metabolic acidosis
HCO3- should be elevated 1 mEq/L for each 10 mm Hg= 3 mEq/L
Expected HCO3- should be 27, actual is 23 suggesting combined
metabolic acidosis
Decreased perfusion leading to mild lactic acidosis would explain the
metabolic component.
Acid-base Disorders
A 45-year-old man comes to the hospital complaining of dyspnea
for three days. Arterial blood gas reveals pH 7.35, PaCO2 60 mm
Hg, PaO2 57 mm Hg, HCO3- 31 mEq/L. How would you
characterize his acid-base status?
1.
2.
3.
4.
5.
6.
7.
8.
Since the patient has been dyspneic for several days it is fair
to assume a chronic acid-base disorder
For every 10-mm Hg rise in PaCO2 pH falls about 0.03 units.
Expected fall in pH: 0.06 thus pH should be = 7.34
Actual pH: 7.35 close to expected
HCO3- should be elevated 3-4 mEq/L for each 10 mm Hg= 3
mEq/L
Expected HCO3- should be 31
Actual is 31 as expected
Chronic respiratory acidosis with adequate compensation
Acid-base Disorders
• 60 year old man with history of ethanol abuse
was admitted to the hospital with severe
acute pancreatitis.
• Developed progressive hypotension and
respiratory failure and required intubattion
and mechanical ventilation.
• He was sedated with lorazepam using bolus
and infusion dosing and paralyzed using cisatracurium.
• As a result of marked agitation, possibly
associated with ethanol withdrawal,
escalating doses of sedation were required.
Acid-base Disorders:
Test Your Understanding
• Other medication included norepinephrine
infusion, intravenous pantoprazole and
piperacillin/tazobactam.
• On the 6th hospital day, WBC 21,000, Hg
106, Na 135, K 5, Cl 99, total CO2 15, BUN
12.5, creatinine 70 and glucose 18
• Plasma lactic acid was 4.7 mmol/L, serum
osmolality 327 mOsm/kg H2O
• pH 7.26, PCO2 35 and PO2 126, [H+]= 55
Acid-base Disorders:
Test Your Understanding
a)
b)
c)
d)
e)
Sepsis
Propylene glycol intoxication
Isopropyl alcohol intoxication
Ethylene glycol intoxication
Hypoventilation
Acid Base Disturbance Approach
• [H+]=24 X PCO2/HCO3: 55= 24 X 35/15
• pH= 7.26: Acidosis
• Predicted PCO2 (Respiratory compensation): PCO2= 1.5
X[HCO3]+8 2: therefore PCO2 should have been 1.5X15+8=
30.5 2: combined respiratory and metabolic
• AG= Na-(Cl+HCO3)= 135-(99+15)= 21
• ∆ AG= 21-12= 9
• ∆ HCO3= 24-15= 9
• ∆ HCO3 = ∆ AG
• Added anions= 9 mmol/L= 4.5 Lactic acid + 4.5 ??
• Calculated osmolality= 2Na+Glucose+BUN=2(135)+18+12.5=
301
• Osmolar gap= 327-301=26
• Metabolic acidosis with high anion gap due to lactic acidosis
high osmolality acid in addition to mild respiratory acidosis
pH 7.26, PCO2 35 and PO2 126, [H+]= 55
Na 135, K 5, Cl 99, total CO2 15, BUN 12.5, creatinine 70 and glucose 18
Plasma lactic acid was 4.7 mmol/L, serum osmolality 327 mOsm/kg H2O
Arterial Blood Gases:
Test Your Overall Understanding
Case 1. A 55-year-old man is evaluated in the pulmonary lab for
shortness of breath. His regular medications include a
diuretic for hypertension and one aspirin a day. He smokes a
pack of cigarettes a day.
FIO2
pH
PaCO2
PaO2
SaO2
.21
7.53
37 mm Hg
62 mm Hg
87%
HCO3%COHb
Hb
CaO2
30 mEq/L
7.8%
14 gm%
16.5 ml O2/dl
How would you characterize his state of oxygenation, ventilation,
and acid base balance?
Arterial Blood Gases:
Test Your Overall Understanding
Case 1 - Discussion
OXYGENATION: The PaO2 and SaO2 are both reduced on room air. Since
P(A-a)O2 is elevated (approximately 43 mm Hg), the low PaO2 can be
attributed to V-Q imbalance, i.e., a pulmonary problem. SaO2 is reduced, in
part from the low PaO2 but mainly from elevated carboxyhemoglobin, which
in turn can be attributed to cigarettes. The arterial oxygen content is
adequate.
VENTILATION: Adequate for the patient's level of CO2 production; the
patient is neither hyper- nor hypo-ventilating.
ACID-BASE: Elevated pH and HCO3- suggest a state of metabolic alkalosis,
most likely related to the patient's diuretic; his serum K+ should be checked
for hypokalemia.
Arterial Blood Gases:
Test Your Overall Understanding
Case 2. A 46-year-old man has been in the hospital two days
with pneumonia. He was recovering but has just become
diaphoretic, dyspneic, and hypotensive. He is breathing
oxygen through a nasal cannula at 3 l/min.
pH
7.40
PaCO2
20 mm Hg
%COHb
1.0%
PaO2
80 mm Hg
SaO2
95%
Hb
13.3 gm%
HCO312 mEq/L
CaO2
17.2 ml O2/dl
How would you characterize his state of oxygenation, ventilation, and
acid-base balance?
Arterial Blood Gases:
Test Your Overall Understanding
Case 2 - Discussion
OXYGENATION: The PaO2 is lower than expected for someone
hyperventilating to this degree and receiving supplemental oxygen,
and points to significant V-Q imbalance. The oxygen content is
adequate.
VENTILATION: PaCO2 is half normal and indicates marked
hyperventilation.
ACID-BASE: Normal pH with very low bicarbonate and PaCO2
indicates combined respiratory alkalosis and metabolic acidosis. If
these changes are of sudden onset, the diagnosis of sepsis should
be strongly considered, especially in someone with a documented
infection.
Arterial Blood Gases:
Test Your Overall Understanding
Case 3. A 58-year-old woman is being evaluated in the
emergency department for acute dyspnea.
FIO2
.21
pH
7.19
PaCO2
65 mm Hg
%COHb
1.1%
PaO2
45 mm Hg
SaO2
90%
Hb
15.1 gm%
HCO324 mEq/L
CaO2
18.3 ml O2/dl
How would you characterize her state of oxygenation, ventilation, and
acid-base balance?
Arterial Blood Gases:
Test Your Overall Understanding
Case 3 - Discussion
OXYGENATION: The patient's PaO2 is reduced for two reasons hypercapnia and V-Q imbalance - the latter apparent from an
elevated P(A-a)O2 (approximately 27 mm Hg).
VENTILATION: The patient is hypoventilating.
ACID-BASE: pH and PaCO2 are suggestive of acute respiratory
acidosis plus metabolic acidosis; the calculated HCO3- is lower than
expected from acute respiratory acidosis alone.
Arterial Blood Gases:
Test Your Overall Understanding
Case 4. A 23-year-old man is being evaluated in the emergency
room for severe pneumonia. His respiratory rate is 38/min
and he is using accessory breathing muscles.
FIO2
.90
Na+
154 mEq/L
pH
7.29
K+
4.1 mEq/L
PaCO2
55 mm Hg
Cl100 mEq/L
PaO2
47 mm Hg
CO2
24 mEq/L
SaO2
86%
HCO323 mEq/L
%COHb
2.1%
Hb
13 gm%
CaO2
15.8 ml O2/dl
How would you characterize his state of oxygenation, ventilation,
and acid-base balance?
Arterial Blood Gases:
Test Your Overall Understanding
Case 4 - Discussion
OXYGENATION:
The PaO2 and SaO2 are both markedly reduced on 90% inspired
oxygen, indicating severe ventilation-perfusion imbalance.
VENTILATION:
The patient is hypoventilating despite the presence of tachypnea,
indicating significant dead-pace ventilation. This is a dangerous situation that
suggests the need for mechanical ventilation.
ACID-BASE:
The low pH, high PaCO2, and slightly low calculated HCO3- all point to
combined acute respiratory acidosis and metabolic acidosis. Anion gap is elevated
to 30 mEq/L indicating a clinically significant anion gap (AG) acidosis, possibly from
lactic acidosis. With an of AG of 30 mEq/L, his serum CO2 should be much lower, to
reflect buffering of the increased acid. However, his serum CO2 is near normal,
indicating a primary process that is increasing it, i.e., a metabolic alkalosis in addition
to a metabolic acidosis. The cause of the alkalosis is as yet undetermined. In
summary: this patient has respiratory acidosis, metabolic acidosis, and metabolic
alkalosis.
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