Transcript acidosis/alkalosis biochemistry

Biochemical basis of acidosis and alkalosis:
evaluating acid base disorders
Eric Niederhoffer, Ph.D.
SIU-SOM
Outline
• Approach
history
physical examination
differentials
clinical and laboratory studies
compensation
• Respiratory
acidosis
alkalosis
• Metabolic
acidosis
alkalosis
Approach
• History - subjective information concerning events,
environment, trauma, medications, poisons, toxins
• Physical examination - objective information
assessing organ system status and function
• Differentials - potential reasons for presentation
• Clinical and laboratory studies - degree of changes
from normal
• Compensation - assessment of response to initial
problem
Evaluation of Acid-Base Conditions
• Examine serum electrolytes (increased or decreased
total CO2, increased AG, abnormal HCO3- gap) and
ABGs (directional changes in pH, HCO3-, and PCO2).
• Examine ABG data for mixed acid-base conditions.
• Complete clinical assessment of history, physical
examination, previous ABGs and serum electrolytes,
along with other laboratory data.
• Identify underlying clinical cause(s) for each acid-base
disorder.
• Treat the clinical conditions.
Reference ranges and points
Parameter
Reference range Reference point
Na+
135-147 mEq/L
K+
3.5-5.0 mEq/L
Cl-
95-105 mEq/L
CO2, total
24-30 mEq/L
pH
7.35-7.45
7.40
PCO2
33-44 mm Hg
40 mm Hg
PO2
75-105 mm Hg
HCO3-
22-28 mEq/L
24mEq/L
Anion gap
8-16 mEq/L
12 mEq/L
Bicarbonate gap
Osmolar gap
-6-6 mEq/L
<10 mOsm/L
Evaluation of Serum Electrolytes
Total CO2
Increased, >30 mEq/L


Normal
Decreased, <24 mEq/L


metabolic alkalosis
HCO3- retention for respiratory acidosis
metabolic acidosis (AG or HCA)
HCO3- excretion for respiratory alkalosis
Anion Gap
Increased, >20 mEq/L

Normal
Decreased, <8 mEq/L

consider potential cause
consider hypoproteinemia,
abnormal proteins or cations
Bicarbonate Gap
Positive, > 6 mEq/L
Negative, < -6 mEq/L




metabolic alkalosis and/or
HCO3- retention for respiratory acidosis
hyperchloremic acidosis (HCA) and/or
HCO3- excretion for respiratory alkalosis
Evaluation of Arterial Blood Gas
Primary process
Compensatory response
[HCO-3 ]
¯pH @
-PCO 2
Respiratory acidosis
-[HCO-3 ]
-pH @
-PCO2
Respiratory alkalosis
¯[HCO-3 ]
¯pH @
¯PCO2
Metabolic acidosis
¯[HCO-3 ]
-pH @
¯PCO2
Metabolic alkalosis
-[HCO-3 ]
¯pH @
-PCO2
[HCO-3 ]
-pH @
¯PCO 2
¯[HCO-3 ]
¯pH @
PCO2
-[HCO-3 ]
-pH @
PCO2
Delta ratio
𝛥 ratio = 𝛥Anion gap/𝛥[HCO3-] = (AG – 12)/(24 - [HCO3-])
Delta ratio
Assessment
<0.4
Hyperchloraemic normal anion gap acidosis
0.4 – 0.8
1-2
>2
Combined high AG and normal AG acidosis
Note that the ratio is often <1 in acidosis associated
with renal failure
Uncomplicated high-AG acidosis
Lactic acidosis: average value 1.6
DKA more likely to have a ratio closer to 1 due to urine
ketone loss (if patient not dehydrated)
Pre-existing increased [HCO3-]:
concurrent metabolic alkalosis
pre-existing compensated respiratory acidosis
Compensation
Primary
Disturbance
pH
HCO3-
PCO2
Compensation
Respiratory acidosis
<7.35
Compensatory
increase
Primary
increase
Acute: 1-2 mEq/L increase in
HCO3- for every 10 mm Hg increase
in PCO2
Chronic: 3-4 mEq/L increase in
HCO3- for every 10 mm Hg increase
in PCO2
Respiratory alkalosis
>7.45
Compensatory
decrease
Primary
decrease
Acute: 1-2 mEq/L decrease in
HCO3- for every 10 mm Hg
decrease in PCO2
Chronic: 4-5 mEq/L decrease in
HCO3- for every 10 mm Hg
decrease in PCO2
Metabolic acidosis
<7.35
Primary
decrease
Compensatory
decrease
1.2 mm Hg decrease in PCO2 for
every 1 mEq/L decrease in HCO3-
Metabolic alkalosis
>7.45
Primary
increase
Compensatory
increase
0.6-0.75 mm Hg increase in PCO2
for every 1 mEq/L increase in HCO3, PCO2 should not rise above 55 mm
Hg in compensation
Respiratory acidosis
PCO2 greater than expected
Acute or chronic
Causes
 excess CO2 in inspired air
(rebreathing of CO2-containing expired air, addition of
CO2 to inspired air, insufflation of CO2 into body
cavity)
 decreased alveolar ventilation
(central respiratory depression & other CNS
problems, nerve or muscle disorders, lung or chest
wall defects, airway disorders, external factors)
 increased production of CO2
(hypercatabolic disorders)
Racid acute
A 65-year-old man comes to the physician with a 3-hour history of
shortness of breath after feeling ill for the past week. His BMI is 30 kg/m2.
His temperature is 38.3°C (101°F), pulse is 96/min, respirations are
20/min and shallow, and blood pressure is 145/90 mm Hg.
Na+
138 mEq/L
pH
7.33
K+
4.2 mEq/L
PO2
61 mm Hg
Cl-
101 mEq/L
PCO2
50 mm Hg
CO2, total 28 mEq/L
HCO3- 26 mEq/L
History suggests hypoventilation, supported by increased PCO2 and
lower than anticipated PO2.
Respiratory acidosis (acute) due to no renal compensation.
Description
Na+
138 mEq/L
pH
7.33
K+
4.2 mEq/L
PO2
61 mm Hg
Cl-
101 mEq/L
PCO2
50 mm Hg
CO2, total 28 mEq/L
HCO3- 26 mEq/L
AG = 11 mEq/L
BG = 1 mEq/L
1-2 mEq/L increase in HCO3- for every 10 mm Hg increase
in PCO2.
PCO2 increase = 50-40 = 10 mm Hg.
HCO3- increase predicted = (1-2) x (10/10) = 1-2 mEq/L
add to 24 mEq/L (reference point) = 25-26 mEq/L
Racid chronic
A 56-year-old woman with COPD is brought to the physician with a 3hour history of shortness of breath. Her temperature is 37°C
(98.6°F), pulse is 90/min, respirations are 22/min and shallow, and
blood pressure is 135/80 mm Hg.
Na+
145 mEq/L
pH
7.33
K+
4.5 mEq/L
PO2
52 mm Hg
Cl-
99 mEq/L
PCO2
62 mm Hg
CO2, total 34 mEq/L
HCO3- 32 mEq/L
History suggests hypoventilation, supported by increased PCO2.
Respiratory acidosis (chronic) with renal compensation.
Description
Na+
145 mEq/L
pH
7.33
K+
4.5 mEq/L
PO2
52 mm Hg
Cl-
99 mEq/L
PCO2
62 mm Hg
CO2, total 34 mEq/L
HCO3- 32 mEq/L
AG = 14 mEq/L
BG = 10 mEq/L
3-4 mEq/L increase in HCO3- for every 10 mm Hg increase
in PCO2.
PCO2 increase = 62-40 = 22 mm Hg.
HCO3- increase predicted = (3-4) x (22/10) = 7-9 mEq/L
add to 24 mEq/L (reference point) = 31-33 mEq/L
Respiratory alkalosis
PCO2 less than expected
Acute or chronic
Causes
 increased alveolar ventilation
(central causes, direct action via respiratory center;
hypoxaemia, act via peripheral chemoreceptors;
pulmonary causes, act via intrapulmonary receptors;
iatrogenic, act directly on ventilation)
Ralk acute
A 17-year-old woman is brought to the physician with a 3hour history of epigastric pain and nausea. She admits
taking a large dose of aspirin. Her respirations are 20/min
and full.
Na+
136 mEq/L
pH
7.55
K+
3.7 mEq/L
PO2
104 mm Hg
Cl-
101 mEq/L
PCO2
25 mm Hg
CO2, total 23 mEq/L
HCO3- 22 mEq/L
History suggests hyperventilation, supported by decreased
PCO2.
Respiratory alkalosis (acute) due to no renal compensation.
Description
Na+
136 mEq/L
pH
7.55
K+
3.7 mEq/L
PO2
104 mm Hg
Cl101 mEq/L
PCO2 25 mm Hg
CO2, total 23 mEq/L
HCO3- 22 mEq/L
AG = 12 mEq/L
BG = -2 mEq/L
1-2 mEq/L decrease in HCO3- for every 10 mm Hg decrease
in PCO2.
PCO2 decrease = 40-25 = 15 mm Hg.
HCO3- decrease predicted = (1-2) x (15/10) = 2-3 mEq/L
subtract from 24 mEq/L (reference point) = 21-22 mEq/L
Ralk chronic
A 81-year-old woman with a history of anxiety is brought to
the physician with a 2-day history of shortness of breath.
She has been living at 9,000 ft elevation for the past 1
month. Her respirations are full at 20/min.
Na+
133 mEq/L
pH
7.48
K+
4.9 mEq/L
PO2
69 mm Hg
Cl-
105 mEq/L
PCO2
22 mm Hg
CO2, total 17 mEq/L
HCO3- 16 mEq/L
History suggests hyperventilation, supported by decreased
PCO2.
Respiratory alkalosis (chronic) with renal compensation.
Description
Na+
133 mEq/L
pH
7.48
K+
4.9 mEq/L
PO2
69 mm Hg
Cl105 mEq/L
PCO2 22 mm Hg
CO2, total 17 mEq/L
HCO3- 16 mEq/L
AG = 12 mEq/L
BG = -8 mEq/L
4-5 mEq/L decrease in HCO3- for every 10 mm Hg decrease
in PCO2.
PCO2 decrease = 40-22 = 18 mm Hg.
HCO3- decrease predicted = (4-5) x (18/10) = 7-9 mEq/L
subtract from 24 mEq/L (reference point) = 15-17 mEq/L
Metabolic acidosis
Plasma HCO3- less than expected
Gain of strong acid or loss of base
Alternatively, high anion gap or normal anion gap metabolic acidosis
Causes
 high anion-gap acidosis (normochloremic)
(ketoacidosis, lactic acidosis, renal failure, toxins)
 normal anion-gap acidosis (hyperchloremic)
(renal, gastrointestinal tract, other)
Macid increased AG
A 75-year-old man with severe congestive heart failure is brought to the
emergency department. He takes none of his prescribed medications.
His respirations are 24/min and blood pressure is 80/50 mm Hg. He
has decreased urine output; his baseline creatinine concentration has
been 1.6 mg/dL.
Na+
K+
ClCO2, total
Lactate
Urea
Creatinine
135 mEq/L
4.0 mEq/L
97 mEq/L
8 mEq/L
20 mEq/L
54 mg/dL
2.5 mg/dL
pH
PO2
PCO2
HCO3-
7.19
80 mm Hg
21 mm Hg
8 mEq/L
History suggests congestive heart failure (poor perfusion).
Metabolic acidosis with appropriate respiratory compensation.
Description
Na+
135 mEq/L
pH
7.19
K+
4.0 mEq/L
PO2
80 mm Hg
Cl97 mEq/L
PCO2 21 mm Hg
CO2, total 8 mEq/L
HCO3- 8 mEq/L
Lactate
20 mEq/L
Urea
54 mg/dL
AG = 30 mEq/L
Creatinine 2.5 mg/dL
BG = 2 mEq/L
1.2 mm Hg decrease in PCO2 for every 1 mEq/L decrease in
HCO3-.
HCO3- decrease = 24-8 = 16 mEq/L
PCO2 decrease predicted = 1.2 x 16 = 19 mm Hg.
subtract from 40 mm Hg (reference point) = 21 mm Hg
Macid normal AG
A 2-year-old girl is brought to the physician because of a 1week history of diarrhea. She is at the 30th centile for height
and weight. Physical examination shows no abnormalities.
Laboratory studies show a fractional excretion of HCO3- of
2.5%.
Na+
139 mEq/L
pH
7.34
K+
4.3 mEq/L
PO2
96 mm Hg
Cl112 mEq/L
PCO2 29 mm Hg
CO2, total 16 mEq/L
HCO3- 15 mEq/L
Urine pH
5.0
History suggests intestinal electrolyte loss.
Metabolic acidosis with respiratory compensation.
Description
Na+
139 mEq/L
K+
4.3 mEq/L
Cl112 mEq/L
CO2, total 16 mEq/L
Urine pH
5.0
FEHCO32.5%
AG = 12 mEq/L
pH
PO2
PCO2
HCO3-
7.34
96 mm Hg
29 mm Hg
15 mEq/L
BG = -9 mEq/L
1.2 mm Hg decrease in PCO2 for every 1 mEq/L decrease in
HCO3-.
HCO3- decrease = 24-15 = 9 mEq/L
PCO2 decrease predicted = 1.2 x 9 = 11 mm Hg.
subtract from 40 mm Hg (reference point) = 29 mm Hg
Metabolic alkalosis
Plasma HCO3- greater than expected
Loss of strong acid or gain of base
Causes (2 ways to organize)
 loss of H+ from ECF via kidneys (diuretics) or gut (vomiting)
 gain of alkali in ECF from exogenous source (IV NaHCO3
infusion) or endogenous source (metabolism of ketoanions)
or
 addition of base to ECF (milk-alkali syndrome)
 Cl- depletion (loss of acid gastric juice)
 K+ depletion (primary/secondary hyperaldosteronism)
 Other disorders (laxative abuse, severe hypoalbuminaemia)
Urinary Chloride
Spot urine Cl- less than 10 mEq/L
 often associated with volume depletion
 respond to saline infusion
 common causes - previous thiazide diuretic therapy, vomiting
(90% of cases)
Spot urine Cl- greater than 20 mEq/L
 often associated with volume expansion and hypokalemia
 resistant to therapy with saline infusion
 causes: excess aldosterone, severe K+ deficiency, current
diuretic therapy, Bartter syndrome
Malk low Urine ClAn 24-year-old woman is brought to the physician with a 3month history of weakness and fatigue. She has binges of
eating followed by self-induced vomiting. Blood pressure is
90/60 mm Hg. Physical examination shows erosions of the
lingual surface of the teeth.
Na+
137 mEq/L
pH
7.52
K+
2.6 mEq/L
PO2
78 mm Hg
Cl90 mEq/L
PCO2 49 mm Hg
CO2, total 41 mEq/L
HCO3- 39 mEq/L
Urine Cl- 5 mEq/L
History and physical examination suggests bulimia nervosa.
Metabolic alkalosis with respiratory compensation.
The cause is most likely bulimia nervosa.
Description
Na+
K+
ClCO2, total
Urine Cl-
137 mEq/L
2.6 mEq/L
90 mEq/L
41 mEq/L
5 mEq/L
AG = 8 mEq/L
pH
PO2
PCO2
HCO3-
7.52
78 mm Hg
49 mm Hg
39 mEq/L
BG = 11 mEq/L
0.6-0.75 mm Hg increase in PCO2 for every 1 mEq/L
increase in HCO3-.
HCO3- increase = 39-24 = 15 mEq/L
PCO2 increase predicted = 0.6-0.75 x 15 = 9-12 mm Hg.
add to 40 mm Hg (reference point) = 49-52 mm Hg
Malk high Urine ClAn 83-year-old woman is brought to the physician with a 1week history of weakness, nausea, and poor appetite. Her
current medications are aspirin and hydrochlorothiazide.
Her blood pressure is 110/70 mm Hg.
Na+
130 mEq/L
pH
7.48
K+
1.9 mEq/L
PO2
66 mm Hg
Cl77 mEq/L
PCO2 49 mm Hg
CO2, total 38 mEq/L
HCO3- 36 mEq/L
Urine Cl- 74 mEq/L
History and physical examination suggest electrolyte
imbalance.
Metabolic alkalosis with respiratory compensation.
The cause most likely is current diuretic therapy.
Description
Na+
K+
ClCO2, total
Urine Cl-
130 mEq/L
1.9 mEq/L
77 mEq/L
38 mEq/L
74 mEq/L
AG = 17 mEq/L
pH
PO2
PCO2
HCO3-
7.48
66 mm Hg
49 mm Hg
36 mEq/L
BG = 17 mEq/L
0.6-0.75 mm Hg increase in PCO2 for every 1 mEq/L
increase in HCO3-.
HCO3- increase = 36-24 = 12 mEq/L
PCO2 increase predicted = 0.6-0.75 x 12 = 7-9 mm Hg.
add to 40 mm Hg (reference point) = 47-49 mm Hg
Review Questions
• What is an effective approach to acid base problems?
• What are the reference ranges and reference points?
• What are the anion, bicarbonate, and osmolar gap?
• What is the delta ratio?
• What is compensation?
• What are the characteristics of respiratory acidosis and alkalosis?
• What are the characteristics of metabolic acidosis and alkalosis?
• What is the utility of spot urine Cl-?