Acid Base Disorders
‫הפרעות בסיס חומצה‬
Karl Skorecki
skorecki@tx.technion.ac.il
Tel: 8543250
.1 asterisk indicates optional
.2 you may contact me as noted above with questions
Hey- What’s the
peeH here
anyway?
Definitions and Equations
1. Medical definition of acid-base status of a
patient refers to [H+] of the extracellular fluid.
2. Normal [H+]ECF is 40nM/Litre (equivalent to pH
7.40)
3. Acidemia is a state wherein the [H+]ECF > 40
(pH < 7.40)
Alkalemia is a state wherein the [H+]ECF < 40
(pH > 7.40)
(Euphemia is a state wherein the [H+]ECF is
normal).
Definitions and Equations (Cont.)
4. H+ + HCO340nM
H2O+CO2
40
25mM
H+nmol/L=25
40
H2CO3
•
PCO2 =
40mmHg
PCO2mmHg
HCO3mmol/L
25
5. The ratio PCO2/HCO3 determines the [H+] (pH)
Acidosis  any process which increases PCO2/HCO3- ratio
Alkalosis  any process which decreases PCO2/HCO3- ratio
Definitions and Equations (Cont.)
PCO2
H+ = 25 • HCO3
6.
Acidosis
increases PCO2/HCO3 ratio
Metabolic: by lowering HCO3
Respiratory: by raising PCO2
Alkalosis
decreases PCO2/HCO3 ratio
Metabolic: by raising HCO3
Respiratory: by lowering PCO2
‫מדינת ישראל‬
‫הצעת חוק בסיסי החומצה‬
‫שם החוק‪ :‬חוק איסור השימוש ב‪ ”Base Excess”-‬וחוק איסור שימוש‬
‫בשמות הנדרסון‪ ,‬הסלבך‪.‬‬
‫הואיל וסטודנטים לרפואה בישראל כבר מספיק מסכנים ומבולבלים‬
‫והואיל ואין מרצה או פרופסור בעולם שמבינ‪/‬ה בעצמו‪/‬ה את המונחים‬
‫הנ"ל‬
‫הצעת חוק זו באה לאסור לחלוטין את השימוש במונחים הנ"ל בכתב‬
‫בעל‪-‬פה‪ ,‬במצגת‪ ,‬בביקור רופאים‪ ,‬בבית‪ ,‬בעבודה‪ ,‬ובכל מקרה (למעט‬
‫בהצעת החוק הנוכחית)‬
‫עונש‪ :‬המפר את החוק לא יוכל לעשות רוטציה בשום מחלקה‬
‫לנפרולוגיה המכבדת את עצמה‪ ,‬ויחוייב ללמוד את נושא בסיסי‬
‫החומצה אך ורק במסגרת המחלקות הכירורגיות‪.‬‬
‫נערך ונחתם היום ע"י השר לענייני בסיסי חומצה‬
‫*‬
Definitions and Equations (Cont.)
PCO2
H+ = 25 • HCO3
7. The four primary acid-base disturbances are:
 Metabolic acidosis (primary decrease in HCO3)
 Metabolic alkalosis (primary increase in HCO3)
 Respiratory acidosis (primary increase in PCO2)
 Respiratory alkalosis (primary decrease in PCO2)
8. - Can have none, one, two, or three of the above
in
combination.
- Can have any combination except?
- The net result can leave [H+] normal/high
(acidemia) or low (alkalemia)
Metabolic Acidosis
15 year-old with three week history of polyuria,
polydipsia and 2 day history of nausea,
abdominal pain, and weakness progressing to
extreme drowsiness. Physical exam remarkable
for rapid breathing, low blood pressure, and
decreased level of consciousness.
Lab:
Glucose
[H+]
PCO2
HCO3
Na+
K+
Cl-
220
62.5 (pH 7.2)
25
10
142
3.4
105
Metabolic Acidosis (Cont.)
PCO2
H+ = 25 • HCO3
62.5
25
10
BUT: HCO3 is low
PCO2 is also low
[H+] is high (low pH; patient is acidemic)
• Metabolic acidosis  primary decrease in HCO3
• Maybe the patient has a metabolic acidosis
• What about the  PCO2 ?
“Compensation” Rules
• Each primary acid base disturbance is associated with an
expected compensation
• If the primary disturbance is metabolic (HCO3), the
expected compensation is respiratory (PCO2)
• If the primary disturbance is respiratory (PCO2), the
expected compensation is metabolic (HCO3)
• The compensation “tries” to restore the H+ (pH) toward
normal, but never quite makes it (why ?  see later)
• The “expected” amount of compensation is different for
each of the four primary acid-base disturbances and
needs to be memorized
• The direction of the expected compensation is
always in the same direction as the primary
disturbance
Metabolic Acidosis
PCO
2
+
H = 25 • HCO
3
 compensation
 primary
Metabolic Alkalosis
PCO
2
+
H = 25 • HCO
3
 compensation
 primary
Respiratory Acidosis
PCO
2
+
H = 25 • HCO
3
 primary
 compensation
Respiratory Alkalosis
PCO
2
+
H = 25 • HCO
3
 primary
 compensation
15 year-old with diabetic coma
H+ 62.5 (pH 7.2), PCO2 25, HCO3 10
PCO2
H+ = 25 • HCO3
62.5
25
10
If primary metabolic acidosis, does the decrease in PCO2
represent an “appropriate” expected compensation ?
Metabolic acidosis:
Rule: for every decrease of 1 mmol/Litre in HCO3
there should be a decrease of 1 mmHg PCO2
Did this happen ?
PCO2
H+ = 25 • HCO3
62.5
25
pH = 7.2
10
 HCO3  25 - 10 = 15
 PCO2  40 - 25 = 15
Therefore: Respiratory compensation is
appropriate
*
If respiratory compensation is appropriate,
WHY is the patient still acidemic (p = 7.2) ?
After all, most people could hyper-ventilate
further, even down to PCO2 of < 10
Answer:
*
The capacity for “respiratory compensation”
is what makes the bicarbonate buffer system
so useful, even though the pK for H2CO3
is 6.8 (far from 7.4)
CO2
HCO3-
PCO2
H+ = 25 • HCO3
62.5
25
pH = 7.2
10
 Perfectly compensated metabolic acidosis
 What if PCO2 remained “normal” ?
PCO2
H+ = 25 • HCO3
40
 H+ = 100  pH = 7.00
10
 Metabolic acidosis + respiratory acidosis
clinical example ?
 What if PCO2 fell to 16 ?
PCO2
H+ = 25 • HCO3
16
 H+ = 40  pH = 7.4
10
 Metabolic acidosis + respiratory alkalosis
clinical example ?
Extracellular pH looks good, but
patient is very sick
Steps in Assessment of Metabolic
Acidosis
Step 1: Is metabolic acidosis present ?
 HCO3 low and PCO2 low
(also occurs in respiratory alkalosis)
 But patient acidemic
Step 2: Is the respiratory compensation…
 as expected (PCO2: HCO3 = 1:1)
 too much (PCO2: HCO3 > 1:1)
(then also respiratory alkalosis)
 too little (PCO2: HCO3 < 1:1)
(then also respiratory acidosis)
Step 3: Differential diagnosis
“anion gap”
Metabolic Acidosis
15 year-old with diabetic coma and metabolic acidosis
H+
62.5
PCO2 25
HCO3 10
Na+ 142
K+
3.4
Cl105
Anion Gap = [Na+] - ([Cl-] + [HCO3-])
= 142 - (105 +10)
= 27
So what ?
Differential Diagnosis of Metabolic
Acidosis “anion gap”
• Metabolic acidosis results from decrease in HCO3• There are two ways whereby  HCO3(a) titration of HCO3- by an acid
e.g. H+Ac + Na+HCO3-  NaAc + H2O + CO2
(b) loss of NaHCO3 in urine or stool
• Process (a) and process (b) leave different “imprints”
in the plasma chemistries
Process A  titration of HCO3- by an acid
H+X- + NaHCO3-  NaX + H2O + CO2
• Designate Na+, Cl-, and HCO3- as electrolytes
whose concentrations we chose to measure
• Normally: Na+ - (Cl- + HCO3-) = “anion gap”
140 - (103 + 25) = 12
• Process A: We do not routinely measure X(we don’t know what it is at the beginning)
• Therefore, for every “X-” gained, there is one
“HCO3-” lost
• Therefore, “anion gap” will rise by one for
every HCO3 titrated away
Metabolic Acidosis
15 year-old with diabetic coma and metabolic acidosis
H+
62.5
PCO2 25
HCO3 10
Na+ 142
K+
3.4
Cl105
Anion Gap = 27
Normal anion gap is 12
 anion Gap is 27 - 12 = 15
HCO3- has decreased by 40 - 25 = 15
 Gap =  HCO3Therefore: anion gap type metabolic acidosis
Anion Gap Metabolic Acidosis
Only 4 categories:
Ketoacidosis
Lactic
- Diabetic
- Alcoholic
- Starvation
- Type A (ischemia, anoxia)
- Type B (metabolic)
Uremic
Poisons
- Methanol
- Ethylene glycol
- Salicylic acid
- Other
Metabolic Acidosis
15 year-old with diabetes, coma and extensive vomiting
H+
62.5 (pH 7.2)
PCO2 25
HCO3 10
Na+ 142
K+
3.4
Cl95
Anion Gap = 142 - (95 + 10) = 37
 Gap 37 - 12 = 25
 HCO3- = 15
How can that be ?
Answer:
• Occult metabolic alkalosis
• If no metabolic acidosis, HCO3 would have been 35
• Metabolic acidosis is much more severe than
reflected in HCO3 of 10 (35  10 Vs. 25  10)
• Consistent with vomiting
• More on metabolic alkalosis and vomiting after lunch
Metabolic Acidosis
Anion Gap
• Ketoacidosis
• Lactic
• Uremic
• Poison
Non-Anion Gap
• Rare: HCl poisoning
• Primary loss of HCO3renal - complicated
external (diarrhea, uretero-sigmoidostomy)
42 year-old
presents with a 5-day history of severe
watery diarrhea beginning 10 days after completing
antibiotics for pyelonephritis
H+
62.5 (pH 7.2)
PCO2 25
HCO3 10
Na+ 140
K+
3.4
Cl118
Anion gap
140 - (118 + 10) = 12
*
Why doesn’t the anion gap rise in a non-anion
gap acidosis?
Anion gap = Na+ - (Cl- + HCO3-)
By definition, the HCO3- has decreased.
Therefore, if the anion gap hasn’t changed:
• Either the Na+ has decreased
• Or, the Cl- has increased
Answer: The Cl- rises (hyperchloremic
metabolic acidosis)
*
How does the Cl- know to increase ?
Anion gap = Na+ - (Cl- + HCO3-)
In a non-anion gap metabolic acidosis there is either:
 Gain of HCl (rare HCl poisoning)
• So each HCO3- lost is accompanied by a Cl- gained
• Therefore no change in anion gap
 Primary loss of Na+ with HCO3• So each HCO3- lost is accompanied by a Na+ lost
• If the Na+ really decreased 1:1 with the HCO3-, then
the anion gap wouldn’t change
• But, that doesn’t happen (the body defends its
volume and osmolality and hates hypo Na+)
• Therefore, the kidney reabsorbs Na+ with Cland the Cl- increases
Non Anion Gap (Hyperchloremic)
Metabolic Acidosis
• HCl gain
• HCO3- loss
 Extraneal
 Renal
Diarrhea
Uretero-sigmoidostomy
Renal Acidosis
Renal Vein Na+HCO3- 5,070mmol/day
Kidney’s Job:
1) Reclaim all of filtered
HCO32) Generate new HCO3corresponding to
HCO3- lost with dietary
acid
3) Each new HCO3generated
corresponds to NH4+
excreted
Na+HCO35,000mmol/day
Renal Artery
NH4+
Zero HCO3-
Renal Tubular Acidosis
Proximal
• Failure to reclaim HCO34,000
HCO35,000
4,000
genesis
• bicarbonaturia
• urine pH > 7
Distal
• Failure to excrete H+(NH4+)
and hence generate HCO3-
HCO34,000
steady-state
• no bicarbonaturia
• urine pH < 6
Metabolic Acidosis
70 year-old with glaucoma treated with acetazolamide
(carbonic anhydrase inhibitor) presents with weakness.
Physical examination: BP 100/50 (baseline 150/90)
H+
75 (pH 7.12)
PCO2 45
HCO3 15
Na+ 139
K+
2.1
Cl108
Anion gap 12
Urine pH
8
• Bicarbonate low, patient very
acidemic
• Respiratory compensation 
respiratory acidosis
• Anion gap normal
Diagnosis:
acetazolamide  proximal RTA
Hypokalemia  respiratory muscle weakness
Mixed Anion Gap + Non Anion Gap
Metabolic Acidosis
70 year-old with glaucoma treated with acetazolamide
(carbonic anhydrase inhibitor) presents with fever,
severe abdominal pain (RUQ), jaundice and collapses.
BP 60 systolic extremities; breathing: distressed.
Lab:
WBC 24,000 92% neutrophils
H+
100 (pH 7.00)
PCO2 20
HCO3 5
Na+ 140
Cl113
Anion gap 22
Urine pH
8
Acid-base diagnosis:
Likely scenario:
An anion gap metabolic acidosis can
turn into a non-anion gap metabolic
acidosis
HOW ?
If the anion accumulated in the plasma is
excreted in the urine
Example:
15 year-old DKA treated with saline (isotonic NaCl)
initial:
H+
62.5 (pH 7.2; glucose 220)
PCO2 25
HCO3 10
Na+ 142
Cl103
Anion gap 27
 gap = 15
 HCO3 = 15
Post Rx:
H+
62.5 (pH 7.2)
PCO2 25
HCO3 10
Na+ 138
Cl110
Anion gap 18
 gap = 6
 HCO3 = 15
Where have all the extra unmeasured
anions gone ?
Answer:
Pissed away as a result of saline
volume expansion
Hint: Can measure gap in urine
The “Normal” or “Baseline”
Anion Gap
*
“unmeasured”
6
K++Ca2++Mg2+
gap
“measured”
140
albumin
phosphate
sulfate
HCO3
Na+
ClALL CATIONS
=
“unmeasured”
18
“measured”
128
ALL ANIONS
Gap: Measured Cations (Na+) - Measured Anions (Cl- + HCO3-)
Equals
Unmeasured Anions - Unmeasured Cations
Example:
Hypoalbuminemia lowers the baseline anion gap
Metabolic Acidosis
• Look at [H+] (pH)
HCO3PCO2
PCO2
+
H = 25 • HCO
3
• [H+] high (pH low)  metabolic acidosis
HCO3- low
• Look at PCO2 to assess respiratory
compensation
• Calculate anion gap
• Compare  anion gap to  bicarbonate
*
1.
2.
3.
pH  [H+] – not really
necessary
Table on PALM
Between 7.25  7.50
for every deviation of one pH unit from 7.40, the [H+]
deviates correspondingly by 1mmol/litre in the
opposite direction
Rule of 80%
7.00  100
7.10  80
7.20  8 X 80 = 64
7.30  8 X 64 = 51
7.40  8 X 50 = 40
7.50  8 X 40 = 32
7.60  8 X 32 = 26
7.70  8 X 26 = 21
*
H+ (mMol/Litre)
pH
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
Table
[H+]  pH
*
Causes of Metabolic Acidosis
Inability to excrete the dietary H+ load
A.
Diminished NH4+ production
1. Renal failure
2. Hypoaldosteronism (type 4 renal tubular acidosis)
B.
Diminished H+ secretion
1. Type 1 (distal) renal tubular acidosis
Increased H+ load or HCO3- loss
A.
Lactic acidosis
B.
Ketoacidosis
C.
Ingestions
1. Salicylates
5. Sulfur
2. Methanol or formaldehyde
6. Toluene
3. Ethylene glycol
7. Ammonium chloride
4. Paraldehyde
8. Hyperalimentation fluids
D.
Massive rhabdomyolysis
E.
Gastrointestinal HCO3- loss
1. Diarrhea
3. Ureterosigmoidostory
2. Pancreatic, billiary or intestinal fistulas
4. Cholestyramine
F.
Renal HCO3- loss
type 2 (proximal) renal tubular acidosis
Most common causes shown in purple
Anion Gap in Major Causes of
Metabolic Acidosis
*
High anion gap
A. Lactic acidosis: lactate, D-lactate
B.
Ketoacidosis: -hydroxybutyrate
C. Renal failure: sulfate, phosphate, urate, hippurate
D. Ingestions
1. Salicylate: ketones, lactate, salicylate
2. Methanol or formaldehyde: formate
3. Ethylene glycol: glycolate, oxalate
E.
4. Paraldehyde: organic anions
5. Toluene: hippurate (usually presents with anion gap)
6. Sulfur: SO42Massive rhabdomyolysis
The substances after the colon represent the major retained
anions in the high anion gap acidosis
*
Anion Gap in Major Causes of
Metabolic Acidosis (cont.)
Normal anion gap (hyperchloremic acidosis)
Gastrointestinal loss of HCO31. Diarrhea
Renal loss of HCO31. Type 2 (proximal) renal tubular acidosis
C. Renal dysfunction
1. Some cases of renal failure
2. Hypoaldosteronism (type 4 renal tubular acidosis)
3. Type 1 (distal) renal tubular acidosis
Ingestions:
1. Ammonium chloride
2. Hyperalimentation fluids
E.
Some cases of ketoacidosis, particularly during treatment
with insulin
Respiratory Acidosis
PCO
2
+
H = 25 • HCO
3


• Primary increase in PCO2 (hypoventilation)
• Compensatory increase in HCO3 (metabolic)
• In metabolic acidosis the compensation is respiratory and
occurs instantly
• In respiratory acidosis the compensation is metabolic and
it takes time and can be divided into acute/chronic
• The combination of increased PCO2 and increased HCO3can also be seen in metabolic alkalosis with respiratory
compensation, but don’t be fooled because…
Metabolic Compensation for
Respiratory Acidosis
Primary
 PCO2
Compensation
 HCO3-
Acute
10mmHg
1mmol/L
Chronic
10mmHg
3mmol/L
(memorize)
Mechanisms of Metabolic
Response
Enhanced HCO3 reclamation
H+
Na+
H+
PCO2
Causes of Respiratory Acidosis
(Hypoventilation)
Brain
Airway
Chest wall +
diaphragm
Lungs
*
Causes of Acute and Chronic
Respiratory Acidosis
Inhibition of the medullary respiratory center
A. Acute
1. Drugs: opiates, anesthetics, sedatives
2. Oxygen in chronic hypercapnia
3. Cardiac arrest
4. Central sleep apena
B. Chronic
1. Extreme obesity (Pickwickian syndrome)
2. Central nervous system lesions (rare)
3. Metabolic alkalosis (although hypercapnia is an
appropriate response to the rise in pH in this setting)
*
Causes of Acute and Chronic
Respiratory Acidosis (cont.)
Disorders of the respiratory muscles and chest wall
A. Acute
1. Muscle weakness: crisis in myasthenia gravis, periodic paralysis,
aminoglycosides, Guillain-Barré syndrome, severe hypokalemia or
hypophosphatremia
B. Chronic
1. Muscle weakness: spinal cord injury, poliomyelitis, amyotrophic
lateral sclerosis, multiple sclerosis, myxedema
2. Kyphoscoliosis
3. Extreme obesity
Upper airway obstruction
A. Acute
1. Aspiration of foreign body or vomitus
2. Obstructive sleep apena
3. Laryngoispasm
*
Causes of Acute and Chronic
Respiratory Acidosis (cont.)
Disorders affecting gas exchange across the pulmonary
capillary
A. Acute
1. Exacerbation of underlying lung disease (including
Increased CO2 production with high-carbohydrate diet)
2. Adult respiratory distress syndrome
3. Acute cardiogenic pulmonary edema
4. Severe asthma or pneumonia
5. Pneumothorax or hemothorax
B. Chronic
1. Chronic obstructive pulmonary disease: bronchitis,
emphysema
2. Extreme obesity
Mechanical ventilation
28 year-old
brought into ER because of found
stuporous on the floor at home with an empty bottle of
diazepam and a suicide note. Previously healthy.
Physical examination: stuporous, but otherwise
unremarkable.
Lab:
H+
60 (pH 7.22)
PCO2 68
HCO3 28
PO2 80
• Patient acidemic with elevated PCO2 and
HCO3  must at least have respiratory
acidosis
• Compensation
 PCO2 28 appropriate for acute
 HCO3 3 respiratory acidosis
•
•
•
•
•
•
28 year-old
overdose has been lying on the floor for two
days. Physical examination reveals extensive edema on the
right side of the body. No urine in bladder
Lab:
H+
100 (pH 7.00)
PCO2
68
HCO3
17
Na+
138
gap: 138 - (98+17) = 23
Cl98
+
K
5.6
Creat
4.8
CK
68,000 I.U.
Patient very acidemic, with high PCO2 and low HCO3Combined respiratory and metabolic acidosis
Respiratory acidosis from drug overdose
Expected compensation: HCO3- 28, but in reality:
HCO3- 17   HCO3  11
Anion gap 23:  gap = 11
Anion gap metabolic acidosis:
rhabdomyalysis + renal failure
62 year-old
with stable COPD
Lab:
H+
50 (pH 7.3)
PCO2 60
HCO3 30
PO2 60
• Patient acidemic with elevated PCO2
elevated bicarbonate
• Chronic respiratory acidosis
• Expected compensation:
 PCO2 20
 HCO3 6
62 year-old
with stable COPD and 1-day history of
worsening cough, fever and dyspnea with drowsiness
Lab:
H+
60 (pH 7.22)
PCO2 80
HCO3 33
PO2 45
• Acute worsening of respiratory acidosis
• Expected compensation:
Chronic  as before  HCO3 to ~31
Acute  further smaller  HCO3 to ~33
• What is the most dangerous intervention, and if
you make this mistake, what should you do ?
62 year-old
with COPD and acute worsening
reaches respiratory failure and is ventilated. ABG’s
measured immediately after
Lab:
H+
30 (pH 7.5)
PCO2 40
HCO3 33
PO2 380
• What happened ?
• How will this affect weaning from ventilator ?
• What will her ABG’s look like if she extubates
herself ?
62 year-old
with COPD and respiratory failure on
ventilator is treated with antibiotics and develops
severe watery diarrhea
Lab:
H+
62.5 (pH 7.2)
PCO2 50
HCO3 20
Na+ 142 (gap 12)
Cl- 110
• Respiratory acidosis appropriately ventilated to
PCO2 50
• Expected HCO3- is 25 + 3 = 28
Observed HCO3- is 20
Therefore: Metabolic acidosis 28  20
• Anion gap not elevated:
antibiotic induced diarrhea
Respiratory Alkalosis
PCO
2
+
H = 25 • HCO
3


• Primary decrease in PCO2 (hyperventilation)
• Compensatory decrease in HCO3 (metabolic)
• The metabolic compensation can be divided into
acute (minutes) and chronic (hours to days)
• The compensation for chronic respiratory alkalosis
is the most complete, and nearly normalizes the pH
• The combination of low  PCO2 and  HCO3 was
also seen in metabolic acidosis, but don’t be
fooled, because…
Metabolic Compensation
for Respiratory Alkalosis
Primary
 PCO2
Compensation
 HCO3-
Acute
10mmHg
2mmol/L
Chronic
10mmHg
5mmol/L
(memorize)
Mechanism for Metabolic
Compensation
• Low PCO2 in proximal tubule
• Inhibition of Na+-H+ exchanger
• Decreased proximal reabsorption of filtered
HCO3• Bicarbonaturia
It’s always easier to lose something then to win
something – that’s why this compensation is so
complete
*
Causes of Respiratory Alkalosis
Hypoxemia
A. Pulmonary disease: pneumonia, interstitial fibrosis emboli,
edema
B. Congestive heart failure
C. Hypotension or severe anemia
D. High-altitude residence
Pulmonary disease
Direct stimulation of the medullary respiratory center
A. Psychogenic or voluntary hyperventilation
B. Hepatic failure
C. Gram-negative septicemia
D. Salicylate intoxication
E. Postcorrection of metabolic acidosis
F. Pregnancy and the lutheal phase of the menstrual cycle
(due to progesterone)
G. Neurologic disorders: cerebrovascular accidents,
pontine tumors
Mechanical ventilation
58 year-old hypertensive man presents to ER with
abrupt loss of consciousness and paralysis.
Pex: hypertension, rapid breathing (hyperpnea),
unresponsive, pinpoint pupils. CT reveales pontine
hemorrhage
After one week in hospital:
H+
37 (pH 7.43)
PCO2 30
HCO3 20
• Patient mildly alkalemic with low PCO2 and low HCO3,
therefore: respiratory alkalosis
• Compensation
 PCO2  10
 HCO3  5
perfect compensation
58 year-old man from previous slide has a bladder
catheter and develops fever and WBC’s noted in urine
Repeat ABG’s
H+
28 (pH 7.52)
PCO2 20
HCO3 18
• Patient more alkalemic with further fall in PCO2 by
additional 10 and compensating further fall in HCO3
by additional  2
• Acute on chronic respiratory alkalosis
58 year-old man from previous slide now develops
hypotension and shock
Repeat ABG’s and chemistry
H+
50 (pH 7.30)
PCO2 20
HCO3 10
Na+ 140
Cl110
 20 ( 8)
• L-lactate 8mmol/L
• Superimposed anion gap metabolic acidosis from
septic shock lactic acidosis
• What if not aware of prior history and no prior
ABG’s and given these values for the first time
H+
50 (pH 7.30)
PCO2 20
HCO3 10
Na+ 140
Cl110
 20
• Patient acidemic with low bicarbonate  metabolic
acidosis
• Expected PCO2 25
Observed PCO2 20
Therefore  respiratory alkalosis
• Anion gap 20  gap  8
 Anion gap metabolic acidosis
• But  HCO3 15 >  gap 8
• Therefore: non anion gap metabolic acidosis
or compensation for respiratory alkalosis
58 year-old man from previous slide experiences
cardiopulmonary arrest. After some initial confusion he
is intubated and ventilated.
Repeat lab tests
H+
100 (pH 7.00)
PCO2 40
HCO3 10
Na+ 140 (gap 20)
Cl110
• Why has pH dropped ?
• Essentially behaving as uncompensated
metabolic acidosis
Anion gap component: sepsis and lactate
Non-anion gap component: “post
compensation for respiratory acidosis”
58 year-old man from previous slide with pontine
hemorrhage, septic shock and ventilated, is given 3
ampules of NaHCO3 for acidemia
Repeat values
H+
40 (pH 7.40)
PCO2 40
HCO3 25
Na+ 150
Cl100
Anion gap 25
• pH, PCO2 and HCO3 are normal
• Is there an acid-base disturbance ?
• Was it right to give this much bicarbonate ?
• What would have been the right treatment ?
Metabolic Alkalosis
Probably the worst thing to have and most
complicated to understand
PCO
2
+
H = 25 • HCO
3


• Primary increase in HCO3• Compensatory increase in PCO2
Compensation
• Not very consistent or reliable
• Approximately:
for every  1 HCO3
  0.7 PCO2
• What limits this compensation and how
could you prove it?
Pathogenesis
• Complicated and variable
• Two major categories:
 Boring
 Interesting
Boring
 Bicarbonate load to someone
with no kidneys
 converse: if renal function is
normal, the presence of
metabolic alkalosis severe
(interesting) homeostatic
disturbance
Pathogenesis of Interesting
Metabolic Acidosis
• “Contraction” around HCO3- space
• KCl depletion states
Volume expansion
• mineralo corticoid
excess
Volume contraction
• GI loss
- vomiting
- GI suction
- chloridorrhea (rare)
• Diuretics
- loop
- thiazide
“Contraction” Around HCO3 Space
Normal 70Kg
TBW 42L
ECF
14L
[HCO3]
HCO3
ICF
28L
25mmol/L
350
10mmol/L
280
Total: 630
“Contraction” Around HCO3 Space
Heart failure: ECF expansion
ECF 14  22L
[HCO3-] 25
Total 500
Treat with diuretics to  ECF
ECF 15
15 Litres
[HCO3-] 37
550/15 = Shrink
7L
More to it!
• Diuretics also remove K+ with Cl-
• Where does the K+ come from ?
• Total body K+
ICF
ECF
[150] X 28
4,200meq
4 X 14
56meq
• Patient on diuretic usually has a
300-800mmol K+ deficit
Key Role of K+Cl- Depletion in
Metabolic Alkalosis
ICF
K+
AnionECF
Na+
K+ lost from ICF
Cl- lost from ECF
Cl-
H+
+
K+
HCO3
Anion- H2O
+
CO2
K+ lost in urine with Cl Gain of intracellular H+
(intracellular acidosis)
Gain of extracellular HCO3(metabolic alkalosis)
No  in total body buffer
H2O + CO2

H2CO3

H+ + HCO3-
Why do we care about acid-base
disturbances ?
 Clue to underlying disease
But are they bad in their own right ?
Answer: YES !
WHY ?
Main Reason:
Metabolic acidosis
Respiratory acidosis
Metabolic alkalosis
Intracellular
acidosis
-
Intracellular Acidosis H+
buffered in Histidines
-
H+ 
histidine
• Met acidosis
• Resp acidosis
• met alkalosis
Intracellular
protein
function-conformation
Changed
conformation
and function
Summary of Diuretic-Induced
Metabolic Alkalosis
1. Contraction
2. K+ depletion
3. Cl- depletion
4. Mineralocorticoid  secondary
to volume depletion
Two Most Common Causes of
Metabolic Alkalosis
(with hypokalemia)
1. Diuretics (loop, thiazide)
2. Vomiting (GI suction)
*
Key Ion transport Protein in the
Nephron
*
Principal Cell
*
Transport of Na+ in the Principal
Cell of the Cortical Collecting Duct
*
Secretion of H+ in the 
Intercalated Cell of the Cortical
Collecting Duct
*
Secretion of HCO3- in the 
Intercalated Cell of the Cortical
Collecting Duct
Key Ion transport Proteins Relevant
to
Metabolic
Alkalosis
Luminal fluid
*
 Cl HCO3
 Cl + HCO
-
3
-
Reabsorbed
proximally due to:
 Volume
 AII
 Aldo
Na+
1. Negative potential
2. Low Cl3. High K+
favours
H+secrection
H+ATPase
H+-K+ATPase
paradoxical acid urine
Cl--HCO3- exchanger
*
Renal ion transport Derangements
and Metabolic Alkalosis
45 year-old male smoker repeats reports one
week of intractable profuse vomiting
H+
31 (pH 7.49)
PCO2 55
HCO3 45
PO2 68
 PCO2 and  HCO3-
• Metabolic alkalosis with respiratory compensation
• Respiratory acidosis with metabolic compensation
Two ways to figure out:
1. Calculate A-a O2 gradient
= PIO2 – 1.25PCO2 – PaO2
= 150 – 69 – 68
= 13
Normal: lung disease not sufficient to
cause chronic respiratory acidosis
2. Treat presumed metabolic alkalosis and
expect PCO2 to normalize (and PO2 to
rise)
Pathogenesis of Metabolic
Alkalosis
• Diuretics
• Vomiting (or NG suction)
Vomiting
Normal
H+
ClNaCl + H2O + CO2
Na+
HCO3Na+
HCO3
H+
Cl-
Na+
HCO3-
to
kidney
Pathogenesis of Metabolic Alkalosis
and Hypokalemia of GI Origin
1.
2.
3.
4.
HCl- loss accompanied by NaHCO3 gain
Excess of NaHCO3 excreted in urine
Equivalent to NaCl (volume) depletion
Hypovolemic stimulus to Na+
reabsorption and aldosterone secretion
5. No Cl- to accompany Na+
6. Na+ reabsorption accompanied by
urinary excretion of H+ and K+
Urine Electrolytes in Vomiting
Time
Na+
K+
Cl-
HCO3
Days 1-3




> 6.8
Late




< 5.5
• Low urine chloride is key
• K+ loss in vomiting is urinary
pH
*
Causes of Metabolic Alkalosis
Loss of hydrogen
A. Gastrointestinal loss
1. Removal of gastric secretions - vomiting or nasogastric
suction
2. Antacid therapy, particularly with cation-exchange resin
3. Chloride-losing diarrhea
B. Renal Loss
1. Loop or thiazide-type diuretics
2. Mineralocorticoid excess
3. Postchronic hypercapnia
4. Low chloride intake
5. High-dose carbenicillin or other penicillin derivative
6. Hypercalcemia, including the milk-alkali syndrome
C. H+ movement into cells
1. Hypokalemia
2. Refeeding (?)
Most common causes shown in blue
*
Causes of Metabolic Alkalosis
(Cont.)
Retention of bicarbonate
A. Massive blood transfusion
B. Administration of NaHACO3
C. Milk-alkali syndrome
Contraction alkalosis
A. Loop or thiazide-type diuretics
B. Gastric losses in patients with achlorhydia
C. Sweat losses in cystic fibrosis
*
A 63 year old man with a 15 year history of chronic
obstructive lung disease developed ankle edema one year
prior to admission and therapy was instituted with salt
restriction, digoxin and furosemide. He complained of
increasing weakness and drowsiness and was admitted for
evaluation. On admission, the patient was slightly drowsy,
cyanotic and in mild respiratory distress. The chest
demonstrated the findings of chronic bronchitis and
emphysema. There was no ankle edema and periods of
bigeminal rhythm were confirmed by ECG.
pH
Pco2
Po2
HCO3
7.43 (H+ 37)
70 mm Hg
50
46 mmol/L
Urine:
Sodium
Potassium
Chloride
2 mmol/L
30
1
Sodium140 mmol/L
Potassium
2.5
Chloride
74
Acid – Base Diagnoses? Relation to potassium? Urine electrolytes?
*
The patient’s diuretic was discontinued, he was given
supplemental KCl by mouth, and within four days his rhythm
and ECG had normalized, and he felt stronger and more
alert. Repeat evaluation showed:
pH
Pco2
Po2
HCO3
7.32
65 mm Hg
60
33 mmol/L
Sodium
Potassium
Chloride
140 mmol/L
4.4
100
Is he better or worse now with the lower pH?
What treatment helped him?
Match Clinical Histories with
Lab Results
1.
2.
3.
4.
5.
H+
66
52
56
32
31
pH
7.18
7.29
7.25
7.48
7.49
PCO2
40
60
27
46
20
HCO3
15
29
12
36
16
___ Other________
gap 12, K+ 2.0
gap 24, L-lactate 1
PK+ 1.9, UCl- 2
gap 21
a. 30 year old with Crohn’s disease and intestinal blind loop resumes
enteral intake
b. 58 year old, dyspnea and hypotension after long air travel
c. 21 year old woman, BMI 19, amenorrhea, weakness
d. 28 year old status asthmaticus requiring intubation and sedation
e. 70 year old started one month ago on a new tablet to treat
glaucoma
pHank You!
*
Bon
Apetit!