Dr. Suzana Voiculescu
AB balance parameters
Extracellular pH (plasmatic pH)=
7.35- 7.45
< 7.35= acidosis
>7.45= alkalosis
Kassirer-Bleich equation
 [H+] = 24 × PCO2/ [HCO3-]
 predicts that the ratio of
dissolved CO2 to HCO3- ,
rather than their actual
concentrations, determines
hydrogen ion concentration
and thus pH.
 A drop or rise in PCO2 will result in a drop or rise in
[H+] respectively.
 [HCO3-] on the other hand is inversely related to H+
concentration whereby a drop in bicarbonate levels
result in an increase in H+ concentration while a rise
in bicarbonate levels result in a reduction in H+
concentration.
 This buffer system is of physiologic importance
because both the pulmonary and renal mechanisms
for regulating pH work by adjusting this ratio.
 The PCO2 can be modified by changes in alveolar
ventilation, while plasma [HCO3-] can be altered by
regulating its generation and excretion by the kidneys.
The Henderson-Hasselbach
equation
 The ratio of bicarbonate to carbonic acid determines
the pH of the blood.
 Normally the ratio is about 20:1 bicarbonate to
carbonic acid.
 This relationship is described in the HendersonHasselbach equation:
pH = pK + log (HCO3-/H2CO3)
 (pK is the dissociation constant of the buffer, 6.10 at
body temperature)
pH physiological variations:
 Age: newborn babies and children have a pH closer to
the superior limit of the interval (7.42)- this favors
anabolic processes (growth), while older people have
more acidic pH due to the catabolic processes
 Digestion phases:
 gastric digestion, there is a more basic pH (elimination
of H+ in the gastric secretions)
 intestinal digestion, the pH is more acid (HCO3- in the
intestinal secretions)
pH physiological variations
 Circadian rhythm – in the morning and at night- more
acidic pH- CO2 accumulation during sleep
 Altitude- more basic pH-physiologic alkalosis- low pO2
causes hyperventilation and low CO2.
 Effort- lactic acid
AB balance parameters
 Sampling of arterial blood
 Oxygenation of blood level through gas exchange in
the lungs (SaO2, pO2)
 CO2 elimination through respiration
 AB balance/imbalace in ECF
Oxygenation
 4 ml/kg/min normal healthy person
 X10 fit
 X20 athletes
 Oxidative metabolism of carbohydrates/fats Co2
(15000-20000 mEq/day)
 When hypoxia lactic acid
 Check if patient is breathing room air (21% O2) or not
Oxygenation
 pO2
 Normal= 100 mmHg young healthy adult breathing
room air; falls with age (V/Q missmatch)
 pO2= 104- (age
x 0,27)
 Hypoxia pO2< 90 mmHg
 Hyperoxia pO2>100 mmHg
 SaO2 derived from pO2 using Hb dissociation curve
 Hypoxia < 95%
AB balance parameters
 pCO2= 38- 42 mmHg= mean pressure of carbon
dioxide in arterial blood
 Alkaline reserve= actual bicarbonate= 21- 24 mEq/l=
content of HCO3- in patients’ blood at actual pCO2; it
represents the metabolic component of the buffer
system, and it is usually modified by kidneys.
AB balance parameters
 pH
 Blood H+ conc= 0.00004 mEq/l
 [H+] concentration is expressed on a logarithm scale
as pH units
Standard bicarbonate
 [HCO3-] in standard conditions: standard pCO2 and complete
Hb oxygenation (thus eliminating the influence of the lungs on
blood base concentration); normal values= 21-27 mEq/l;
 What bicarbonate concentration would heve been after pCo2 is
corrected to 40 mmHg
 It is derived from actual bicarbonate value after changes
associated with respiratory disturbances have been eliminated;
reflects pure metabolic changes
 high [HCO3-] means metabolic alkalosis and low [HCO3-]
means metabolic acidosis.
Base excess
 Base excess (BE)- the amount of base that needs to be
removed to bring pH level back to normal when pCO2
is corrected to 40 mmHg
 Negative (base deficit) in metabolic acidosis and
positive in metabolic alkalosis.
 Normal value= +2.5 -2.5 mmol/l.
Anionic gap
 Anionic gap- the difference between cations and
anions which are normally determined in the plasma.
AG = (Na+ + K+) – [(Cl-) + (HCO3-)]; normal value = 16 ±
2 mmol/l.
AG = (Na+) – [(Cl-) + (HCO3-)]; normal value= 12 ± 4
mmol/l.
 Corrected AG in case of low albumin level: AG
corrected = AG + 0,25×(Albumin normal – Albumin
measured)
AB balance disorder
 An acid base disorder is a change in the normal value
of extracellular pH that may result when renal or
respiratory function is abnormal or when an acid or
base load overwhelms excretory capacity.

pH
Range:
7.35- 7.45
Optimal value
7.40
PCO2
36-44
40
HCO322-26
24
 Acid base status is defined in terms of the plasma pH.
 Acidemia - decrease in the blood pH below normal range
of 7.35 -7.45
Alkalemia - Elevation in blood pH above the normal range
of 7.35 – 7.45
 Clinical disturbances of acid base metabolism
classically are defined in terms of the HCO3/CO2 buffer system.
 Acidosis – process that increases [H+] by increasing PCO2
or by reducing [HCO3-]
Alkalosis – process that reduces [H+] by reducing PCO2 or
by increasing [HCO3-]
IMPORTANT
 It is important to note that though acidosis and
alkalosis usually leads to acidemia and alkalemia
respectively, the exception occurs when there is a
mixed acid base disorder. In that situation,
multiple acid base processes coexisting may lead
to a normal pH or a mixed picture
Respiratory versus metabolic
 Since PCO2 is regulated by respiration, abnormalities
that primarily alter the PCO2 are referred to as
respiratory acidosis (high PCO2) and respiratory
alkalosis (low PCO2).
 In contrast, [HCO3-] is regulated primarily by renal
processes. Abnormalities that primarily alter the
[HCO3-] are referred to as metabolic acidosis (low
[HCO3-]) and metabolic alkalosis (high [HCO3-]).
Simple vs mixed
 Simple acid base disorders : Disorders that are
either metabolic or respiratory.
 Mixed acid base disorders: More than one acid base
disturbance present. pH may be normal or abnormal
Compensation
 Acid Base disoders are associated with defense
mechanisms referred to as compensatory responses
that function to reduce the effects of the particular
disorder on the pH.
 They do not restore the pH back to a normal
value. This can only be done with correction of the
underlying cause. In each of these disorders,
compensatory renal or respiratory responses act to
minimize the change in H+ concentration by
minimizing the alteration in the PCO2 /[HCO3-] ratio.
Compensatory resposes
 1. Compensatory responses never return the pH to
normal.
 2. The basis of compensatory responses is to maintain
the PCO2/[HCO3-] ratio.
 3. Therefore, the direction of the compensatory
response is always the same as that of the initial
change.
 4. Compensatory response to respiratory disorders is
two-fold; a fast response due to cell buffering and a
significantly slower response due to renal adaptation.
 5. Compensatory response to metabolic disorders
involves mainly an alteration in alveolar ventilation.
 6. Metabolic responses cannot be defined as acute or
chronic in terms of respiratory compensation because
the extent of compensation is the same in each case.
Respiratory acidosis
 Increase of pCO2 in respiratory diseases
 Elevation in the PCO2/[HCO3-] ratio which subsequently
increases the hydrogen ion concentration according to the
following equation:
[H+] = 24 × PCO2 / [HCO3-]
 Compensation- increase of HCO3- by
 a) rapid cell buffering of H+ (HB and proteins) ACUTE
H2CO3 + Hb- → HHb + HCO3 b) an increase in net acid excretion CHRONICAL
ACUTE vs CHRONIC Respiratory
Acidosis
ACUTE - buffers
 As shown above, each buffering reaction produces HCO3-,
which leads to an increase in plasma [HCO3-].
 Due to this process, acutely, there is an increase in the
plasma [HCO3-], averaging 1 mEq/L for every 10 mmHg rise
in the PCO2.
CHRONIC- kidneys
 A 3.5 mEq/L increase in the plasma HCO3concentration for every 10 mmHg increase in the
PCO2; metabolic comp is not obvious for a few hours
and takes 4 days to complete
Thus...
 Renal compensation offers more significant pH
protection in the setting of chronic respiratory acidosis
in contrast to intracellular buffering in the acute
situation.
 Chronic respiratory acidosis is commonly caused by
COPD. These patients can tolerate a PCO2 of up to 90110 mmHg and not have a severe reduction in pH due
to renal compensation.
Respiratory acidosis
 Causes:
 Alveolar hypoventilation
 CNS depression (meds, trauma)
 Miopathic diseases
 Restrictive pulmonary disease
 Obstructive pulmonary disease
 High CO2 production- hyper thyroidism,
malignant hyperthermia, seizure VERY RARE
Respiratory alkalosis
 Decrease of pCO2 due to hyperventilation is followed
by increased pH.
 Net reduction in PCO2 and subsequently a reduction
in the PCO2 / [HCO3-] ratio which reduces the
hydrogen ion concentration (and increases the pH)
according to the following equation: [H+] = 24 × PCO2
/ [HCO3-]
Respiratory alkalosis
Compensation
 Rapid cell buffering ACUTE
 Kidneys decrease H+ secretion and increased
HCO3- excretion. CHRONICAL
Causes:
 Peripheric stimulation (hypoxemia, anemia, altitude)
 Central stimulation (pain, anxiety, meds)
 Metabolic encephalopathy (hepatic cirrhosis)
ACUTE Respiratory alkalosis
 About 10 minutes after the onset of respiratory alkalosis,
hydrogen ions move from the cells into the extracellular
fluid, where they combine with HCO3-
 The hydrogen ions are primarily derived from intracellular
buffers such as hemoglobin, protein and phosphates. The
reaction with bicarbonate ions in this reaction leads to a
mild reduction in plasma [HCO3-].
 In acute respiratory alkalosis, as a result of cell
buffering, for every 10 mmHg decrease in the PCO2,
there is a 2mEq/L decrease in the plasma HCO3concentration.
CHRONIC Respiratory alkalosis
 If respiratory alkalosis persist for longer than 2- 6 hours,
the kidney will respond by lowering hydrogen secretion,
excretion of titratable acids, ammonium production and
ammonium excretion. There will also be an increase in the
amount of HCO3 in the urine- excreted due to decreased
reabsorption of filtered HCO3- .
 Completion of this process occurs after 2-3 days after which
a new steady state is achieved.
 Renal compensation result in a 4 mEq/L reduction in
plasma [HCO3-] for every 10 mmHg reduction in PCO2.
Metabolic acidosis
 Decrease in [HCO3-] followed by plasma pH decrease.
 Elevation in the PCO2/HCO3- ratio and thus an
elevation in hydrogen ion concentration according to
the following equation:
[H+] = 24 ×(PCO2 / [HCO3-])
 Compensation
 Respiratory- LOW CO2 through hyperventilation
 Renal- if the cause is not kidney disfunction- H+ excretion
enhanced high ammonia (NH4+)
 The reduction in PCO2 is accomplished by increasing
alveolar ventilation- quick response
 The drop in arterial pH stimulates central and
peripheral chemoreceptors controlling respiration,
resulting in an increase in alveolar ventilation.
 The increase in ventilation is characterized more by an
increase in tidal volume than by an increase in
respiratory rate, and may if the acidemia is severe,
reach a maximum of 30L/min (nl = 5-6 L/min).
Kussmaul breathing
 Kussmaul breathing is respiratory compensation for a
metabolic acidosis, most commonly occurring in
diabetics in diabetic ketoacidosis.
 https://www.youtube.com/watch?v=TG0vpKae3Js
Metabolic acidosis causes
 1. most frequent
 Increased extracellular buffering of an increased
acid load
 2. less frequent
 loss of bicarbonate ions in the urine
Cause evaluation of metabolic
acidosis
 Anionic gap= Na+ - [Cl- - HCO3-]= 12 +/- 4
 High AG= H+ excess
 AG↑ = (Na+) – [(Cl-) + (HCO3-↓)]
 Exogenous intoxication (ethylene glycol, salicylates,
methanol)
 Endogenous ketoacidosis, lactic acidosis, renal failure
 Normal AG (hyperchloremic acidosis)= HCO3- loss
 AG normala = (Na+) – [(Cl-↑) + (HCO3-↓)]
 Organism retains one Cl- for each lost HCO3

Digestive (intestinal fluid)
Renal (renal tubular acidosis)
If metabolic acidosis with high
anionic gap- Delta ration
If metabolic acidosis with normal
AG- renal or digestive??
Urinary Anionic Gap= UAG
 Cations in the urine Na+, K+, NH4+, Ca++, Mg++.
 Anions in urina Cl-, HCO3-, sulfate, phosphate,
organic.
 Usually measured Na+, K+ , Cl The unmeasured ones= UA/UC (unmeasured A/C)
 Cl- + UA = Na+ + K+ + UC
 UA-UC= [Na+]+ [K+] - [Cl-]
 Urinary Anion Gap normal value >0
UAG
 Index of NH4+ excretion in the urine
 If digestive loss of bases (extrarenal) normal renal
function urinary ammonia excretion UAG <0
 If renal loss of bases- kidneys cannot eliminate the
excess H+ through ammonia low ammonia
excretion UAG >0
UAG
Hyperchloremic metabolic acidosis:
 UAG <0 bicarbonate digestive loss
 UAG> 0 loss of renal acidifiation capacity
 ‘neGUTive’ - negative UAG in bowel (GUT) causes.
Metabolic alkalosis
 Increased [HCO3-], followed by increased
arterial blood pH.
 [H+] = 24 ×(PCO2 / [HCO3-]) organism tries
to increase pCO2 low alveolar ventilation
 Compensation:
 Respiratory- hypoventilation
 On average the pCO2 rises 0.7 mmHg
for every 1.0 meq/L increase in the
plasma [HCO3-].
Metabolic alkalosis
Causes:
 Digestive loss (gastric acid)
 Renal loss (diuretics)
 Primary hyperaldosteronism
 Next?
 Cause evaluation
Cause evaluation in metabolic
alkalosis
 Cl responsive- urinary Cl < 20 mEq/l
 Digestive- gastric acid loss (vomiting)
 Renal – use of diuretics
 Cl unresponsive- urinary Cl> 20 mEq/l
 Endocrine- primary
hyperaldosteronism
Cause evaluation in metabolic
alkalosis
 Cl responsive-urinary Cl < 20 mEq/l
 Digestive- vomiting- gastric acid loss (loss of fluid and
NaCl higher HCO3- reabsoption to compensate Clloss)
 Renal- diuretics (Cl- loss in the urine)- furosemide,
thiazide
 Cl unresponsive- urinary Cl > 20 mEq/l
 Endocrine- primary hyperadosteronism
Mixed
 Mixed acid base disorders occur when there is more
than one primary acid base disturbance present
simultaneously. They are frequently seen in
hospitalized patients, particularly in the critically ill.
When to suspect a mixed acid
base disorder:
 The expected compensatory response does not occur
 Compensatory response occurs, but level of compensation
is inadequate or too extreme
 Whenever the PCO2 and [HCO3-] becomes abnormal in
the opposite direction. (i.e. one is elevated while the other
is reduced). In simple acid base disorders, the direction of
the compensatory response is always the same as the
direction of the initial abnormal change.
 pH is normal but PCO2 or HCO3- is abnormal
 In simple acid base disorders, the compensatory response
should never return the pH to normal. If that happens,
suspect a mixed disorder.
Steps to follow in diagnosis of AB
disorders
 1. pH evaluation- acidosis or alkalosis
 2. establish cause- metabolic/respiratory in simple ones
 3. compensation degree present/absent
 4. AG calculus
 If metabolic acidosis
 If AG is high delta ratio
 If AG is normal- Urinary AG- renal or digestive?
 5. Urinary Cl
 If metabolic alkalosis
 6. think of possible diagnosis and order further tests
Case study
 A 50 year old man came to emergency department after returning from foreign
travel. His symptom included persistent diarrhea (over the past 3 days) and
rapid respiration . Blood gases were drawn with following results :
 pH- 7.21 (
)
 pCO2 - 19 mmHg (
 pO2 - 96 mmHg
 HCO3- 7 mmol/l
)
Questions:
1. What is the patient acid base status?
2. Why is the HCO3 level is so low?
3. Why does the patient have rapid respiration?
Clinical case 1
 A 44 year old moderately dehydrated man was admitted
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with a two day history of acute severe diarrhea.
Electrolyte results:
Na+ 134,
K+ 2.9,
Cl- 108,
HCO3- 16,
BUN 31,
Cr 1.5.
 ABG: pH 7.31
pCO2 33 mmHg
HCO3 16 pO2 93 mmHg
Is compensation adequate?
 Estimated PCO2
 = 1.5 × [HCO3-]) + 8 ± 2 = 1.5 ×16 + 8 ± 2 = 30-34.
 So... Respiratory compensation is present (no
respiratory disorder is present)
Clinical case 2
 A 22 year old female with type I DM, presents to the
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emergency department with
a 1 day history of nausea,
vomiting,
polyuria,
polydypsia and
vague abdominal pain.
P.E. noted for deep sighing breathing, orthostatic
hypotension, and dry mucous membranes
 Labs:
 Na 132 , K 6.0, Cl 93, HCO3- 11
 glucose 720,
 BUN 38,
 Cr 2.6.
 Urine: pH 5, SG 1.010, ketones negative, glucose
positive . Plasma ketones trace.
 Acid base: pH 7.27 HCO3- 10 PCO2 23
Likely ab disorders based on clinical
scenario
 Elevated anion gap acidosis secondary to DKA, or
 Elevated anion gap acidosis secondary to lactic
acidosis in the setting of vomiting and polyuria which
may lead to hypovolemia, and/or
 Metabolic alkalosis in the setting of vomiting
First step- pH
 ACIDOSIS
 How to distinguish initial change from compensatory
response?
 Low HCO3- is consistent with pH change initial
change
 To maintain the PCO2/HCO3-, the PCO2 is reduced in
response
Diagnostic- METABOLIC ACIDOSIS
 Calculate the anion gap
 The anion gap is Na - (Cl + HCO3-) = 132 -(93 + 11) = 28
 Since gap is greater than 16, it is therefore HIGH.
Is compensation adequate?
 PCO2 = 1.5 × [HCO3-]) + 8 ± 2 = 1.5 ×11 + 8 ± 2 = 22.5 -
26.5.
 Since the actual PCO2 falls within the estimated range,
we can deduce that the compensation is adequate and
there is no separate respiratory disorder present.
 Compensated high anionic gap metabolic acidosis
(diabetic ketoacidosis)
!!
 Note the absence of ketones in the urine. This is
sometimes seen in early DKA due to the predominance
of beta-hydroxybutyrate.
 The dipstick test for ketones detect acetoacetate but
not beta-hydroxybutyrate.
Clinical case 3
 A previously well 55 year old woman is admitted with a
complaint of severe vomiting for 5 days.
 Physical examination reveals postural hypotension,
tachycardia, and diminished skin turgor.
 The laboratory finding include the following:
 Electroyes: Na 140 , K 3.4, Cl 77 HCO3- 9, Cr 2.1
ABG: pH 7.23 , PCO2 22mmHg
Likely ab disorders
 Elevated anion gap acidosis secondary to lactic
acidosis in the setting of severe persistent vomiting
which may lead to hypovolemia, and/or
 Metabolic alkalosis in the setting of persistent
vomiting
 The pH is low, (less than 7.35) therefore by definition,
patient is acidemic.
What is the process? Look at the
PCO2, HCO3- .
 PCO2 and HCO3- are abnormal in the same
direction, therefore less likely a mixed acid base
disorder but not yet ruled out.
 Need to distinguish the initial change from the
compensatory response
 Low HCO3- represents acidosis and is consistent with
the pH, therefore it must be the initial change.
 The low PCO2 must be the compensatory response.
Anionic gap
 The anion gap is Na - (Cl + HCO3-) = 134 -(77 + 9) = 48
 Since gap is greater than 16, it is therefore abnormal.
Is compensation adequate
 PCO2 = 1.5 × [HCO3-]) + 8 ± 2 = 1.5 × 9 + 8 ± 2 = 19.5 -
23.5.
 Since the actual PCO2 falls within the estimated range,
we can deduce that the compensation is adequate and
there is no separate respiratory disorder present.
Delta ratio
 Delta ratio= delta AG/ delta [HCO3-]=
 DR= AG-12/ 24-[HCO3-]= 48-12/24-9= 2.6
 Concurrent metabolic alkalosis (vomiting)
 Mixed elevated anion gap metabolic acidosis and metabolic
alkalosis likely due to lactic acidosis and vomiting.
Clinical case 4
 A 70 year old man with history of CHF presents with
increased shortness of breath and leg swelling.
 ABG: pH 7.24, PCO2 60 mmHg,
 PO2 52
 HCO3 27
pH
 The pH is low, (less than 7.35) therefore by definition,
patient is acidemic.
 PCO2 and HCO3- are abnormal in the same direction,
therefore less likely a mixed acid base disorder but not yet
ruled out.
 HCO3- is on the high side of normal and is not consistent
with the pH. PCO2 is high and represents acidosis and is
consistent with the pH. Therefore it must be the initial
change. The high normal HCO3- must be the
compensatory response= RESPIRATORY ACIDOSIS
Clincal case 5
 A 28 year old female with history of Sjogren’s
syndrome presents to her PCP for a check up visit. In
review of systems, she reports a 2 day episode of
watery diarrhea 2 days ago.
 She is otherwise doing well. Physical examination is
unremarkable. She is noted to have the following
serum chemistry:
 Na 138, K 4.2, Cl 108, HCO3- 14
Urine
 Because of her history, the physician decides to check
her urine electrolytes.
 Urine chemistry: K 31, Na 100, Cl 105
 Note that in this scenario, we are not given an arterial
blood gas. Therefore we must deduce the diagnosis
primarily from the history and the limited workup
available.
 The patients presents to an outpatient visit very
asymptomatic.
 Besides the history of diarrhea, there is nothing else in
the history to suggest an active acid base disorder.
 However, her serum electrolytes indicate a low HCO3concentration which suggests acidosis. We can safely
rule out a chronic respiratory alkalosis as basis of the
low HCO3- since hyperventilation would be evident on
exam. In the absence of other data, we have to assume
that the patient has a metabolic acidosis.
 We are not given serum electrolytes and therefore we
cannot calculate the anion gap,
 Based on the history, we can assume that the patient
does not have lactic acidosis, ketoacidosis, uremia and
has not ingested any toxins.
 Assuming the patient has normal anion gap acidosis,
our differential becomes diarrhea vs RTA.
 We have to consider RTA in this patient, because of
the history of Sjogren's.
UAG
 UAG = Na + K - Cl
UAG = 100 + 31 - 105 = 26.
 A positive UAG suggest RTA because in the setting of
diarrhea, ammonium chloride concentration in the urine
would be high and the UAG would be negative. A postive
value suggests that the kidney is unable to adequately
excrete ammonium, leading to a reduction in net acid
excretion and thus metabolic acidosis.
 Metabolic acidosis likely secondary to renal tubular
acidosis.