Acid-base Physiology

Additional lab data: Previous ABG reports, electrolytes,

Acid-base balance is an essential part of fluid and electrolyte
management. Acid is a substance that tends to dissociate
or give a hydrogen ion (proton donor) whereas base is a
substance that tends to bind or associate a hydrogen ion
(proton acceptor).
Normal pH of blood is 7.40 (range 7.357.45). As a rule
of thumb, 1 mm Hg increase in paCO2 decreases pH by 0.01
and 1 mEq/L decrease in HCO3 decreases pH by 0.02.
Disturbances in acid-base balance can occur due to
primary respiratory or metabolic events. In general, if acid-
base imbalance is predominantly metabolic in nature,
changes in pH, HCO3 and paCO2 occur in the same direction
(all are reduced or increased and the main alteration is in
HCO3). In contrast if the disturbance is predominantly
respiratory in origin, changes in HCO3 and arterial paCO2
are opposite to changes in pH and main alteration is in
paCO2. The primary and compensatory changes always
occur in the same direction.
Assessment and Identification of the
Acid-base Disorder
Comprehensive History and Clinical Examination
Information about patients immediate environment
FiO2, barometric pressure
Clinical information, including the history and physical
examination with emphasis on patients respiratory
rate and vital signs, degree of respiratory effort, mental
status and state of tissue perfusion
blood sugar, BUN, hemoglobin or hematocrit, chest
X-ray, pulmonary function tests (if available).
Identify the Disturbance
Assess pH: High/low
Low pH: pH <7.38: acidemia
High pH: pH >7.42: alkalemia
Determine the primary acid-base disturbance (Table
17.6.14)
Calculate the degree of compensation (Table 17.6.15)
Calculate anion gap.
Calculate the Anion Gap
Anion gap = Na+ [Cl + HCO3]. Normal anion gap ranges
from 8 mEq/L to 16 mEq/L (12 4) but it is variable in different
laboratories. The patient may have high anion gap metabolic
acidosis when the calculated anion gap is more than 16.
Metabolic Acidosis
Metabolic acidosis is a clinical disturbance characterized
by decrease in plasma bicarbonate concentration and low
PaCO2 resulting from compensatory hyperventilation.
causes
normal anion gap acidosis: Diarrhea, renal tubular
acidosis, ureterosigmoidostomy, early stage of acute
renal failure.
increased anion gap acidosis: Diabetic ketoacidosis,
lactic acidosis, inborn errors of metabolism, salicylate
poisoning, methanol poisoning, uremia, starvation.

Table 17.6.14 Identification of the primary disturbance

Primary disorder pH HCO3 PaCO Compensation
Metabolic acidosis Low Low N/low Fall in paCo2
Acidic urine
Metabolic alkalosis High High N/high Rise in paCo2, Alkaline urine
Respiratory acidosis Low N/low High Acidic urine
Respiratory alkalosis High N/high High Alkaline urine
Examples:
1: pH 7.3, HCO3 14 = Primary metabolic acidosis
2: pH 7.57, HCO3 42, PaCO2 47 = Primary metabolic alkalosis
3: pH 7.57, HCO3 18, PaCO2 18 = Primary respiratory alkalosis
4: pH 7.2, HCO3 28, PaCO2 58 = Primary respiratory acidosis

Table 17.6.15 Compensatory changes in Paco2 and HCO3 in response to acidosis and alkalosis
Primary disorder Compensatory change Expected compensation
Metabolic acidosis Fall in PaCO2 PaCO2 = 1.2 x HCO3
Fall in HCO3
Metabolic alkalosis Rise in PaCO2 PaCO2 = 0.7 x HCO3
Rise in HCO3
Respiratory acidosis Rise in HCO3 Acute : HCO3 = 0.1 x PaCO2
Rise in PaCO2 Chronic : HCO3 = 0.3 x PaCO2
Respiratory alkalosis Fall in HCO3 Acute : HCO3 = 0.2 x PaCO2
Fall in PaCO2 Chronic : HCO3 = 0.5 x PaCO2

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Clinical Features
Manifestations of acidosis are related to the degree of
acidosis. Worsening acidosis may produce hypotension,
lethargy, stupor and progresses to coma. pH <7.2 is
associated with increased risk of cardiac arrhythmias.
Increased work of breathing (kussmauls breathing) may
predispose to superimposed respiratory acidosis. Chronic
acidemia results in osteopenia, muscle wasting, and growth
retardation.
Management
Emergency measures: Prevent further production of
H+ by ensuring a proper airway, adequate peripheral
perfusion, oxygen delivery
Treat underlying disorder if possible
Bicarbonate therapy: Intravenous bicarbonate should
be used very judiciously if the pH is <7.2 and/or HCO3
5 mEq/L aiming to raise pH to 7.2. NaHCO3 needs to
be diluted at 1:1 concentration for IV infusion and the
amount of bicarbonate to be given = 0.3 x body weight
x base deficit.
Disadvantages of NaHCO3 therapy are hyperosmolality,
hypernatremia, hypokalemia, decrease in ionized calcium,
intracerebral acidosis, shift of oxygen dissociation curve
resulting in worsening of tissue hypoxia and worsening of
intracellular acidosis.
Hemodialysis or peritoneal dialysis can be done to treat
metabolic acidosis if severe or if associated with renal
failure (uremic acidosis), or in poisonings.
Metabolic Alkalosis
Metabolic alkalosis is defined as HCO3 >2830 mEq/L,
usually with a rise in pH >7.45.
Clinical Features
Symptoms are due to hypokalemia and decreased ionized
calcium levels.
Mild metabolic alkalosis (HCO3 < 36) is asymptomatic.
Moderate metabolic alkalosis: (HCO3 3642 mEq/L) can
cause paresthesia, weakness, orthostatic hypotension,
fatigue, muscle cramps, lethargy, hyporeflexia, muscular
irritability.
Severe metabolic alkalosis: (HCO3 > 4550 mEq/L)
arrhythmias, tetany, seizures, delirium, stupor. Child may
develop hypoventilation which could result in hypoxemia,
difficulty in weaning from ventilator, increased digoxin
toxicity, worsening of hepatic encephalopathy.
Management
Chloride responsive: Treating the underlying cause is
the primary therapy. Correct the hydration status with
intravenous 0.9% saline infusion at 10 mL/kg over 10
30 minutes and if there is coexisting hypokalemia, that
needs to be corrected with KCl supplementation. In case
of diuretic-induced metabolic alkalosis, stop the loop
diuretic and it can be replaced by K sparing diuretics.
Chloride resistant metabolic alkalosis: Treat the
underlying cause and give potassium supplementation
or potassium sparing diuretic.
Respiratory Acidosis
In respiratory acidosis there is decreased elimination of
carbon dioxide from the body due to poor ventilation, which
leads to accumulation of carbon dioxide. Acute respiratory
acidosis is characterized by a primary rise in paCO2 above
45 mm Hg that remains at this high value up to 612 hours.
Sustained elevation of paCO2 beyond 12 hours is defined as
chronic respiratory acidosis.
Clinical Features
Signs and symptoms are related to the degree of
hypercapnia. Child develops headache with either
irritability or depression due to increase in intracranial
pressure (ICP). There is impairment of consciousness
varying from drowsiness to deep coma. Muscular tremors
can occur. Tachycardia, flushing of skin or perspiration may
be present. Blood pressure may be low with signs of shock.
Ventricular fibrillations may occur.
Management
Treatment is directed at the underlying cause and
improvement of alveolar gas exchange by assisted
ventilation. Oxygen administration with high flow rates
may help to wash out carbon dioxide. If hyperkalemia
or ventricular fibrillation develops in a child with acute
respiratory acidosis, sodium bicarbonate may be life saving.
It should be administered after establishing ventilation.
Respiratory Alkalosis
It usually occurs due to hyperventilation; psychogenic or
neurogenic. It may be one of the earliest signs of sepsis.
Acute respiratory alkalosis last no longer than 612
hours. The compensatory response to this phase involves
consumption of HCO3 by body buffers. In the chronic phase
renal suppression of H+ ion excretion and chloride retention
occurs.
clinical feature
Usually there is hyperventilation with features of tetany as
alkalosis decreases blood levels of ionized calcium.
Treatment
Breathing in a closed circuit would cause accumulation
of carbon dioxide. The underlying condition should be
treated. Sodium bicarbonate therapy is not indicated.
Mixed Acid-base Disorders
Mixed acidbase disturbances are conditions where
more than one primary acid disturbance occurs. The four
commonly encountered mixed acidbase disorders are: (1)
respiratory acidosis + metabolic acidosis, (2) respiratory
acidosis + metabolic alkalosis, (3) respiratory alkalosis +
metabolic acidosis and (4) respiratory alkalosis + metabolic
alkalosis (Table 17.6.16). The most serious acidbase
disorders are of mixed type when respiratory and metabolic
disturbances result in a pH change in the same direction.
 4 Acid-Base Balance and
INTRODUCTION
Acid-base disorders are common in pediatric intensive
care unit (PICU) patients. Acidosis both metabolic and
respiratory, are the hallmarks of multiple organ failure and
seen in sepsis, trauma, and postoperative patients (particularly
cardiac surgery) as well as in renal, metabolic and endocrine
conditions. Both respiratory and metabolic alkaloses also occur
with regularity in PICU. Thus it is important that the intensivist
not only understands the underlying processes involved
in acid-base disorders but can also apply this to managing
conditions properly. This is vital as there is compelling
research base evidence that misinterpretation and consequent
mismanagement of acid-base disorder is common in hospital
medicine.
DEFINITIONS
Acidosis is an abnormal process or condition which lowers
the arterial pH if there is no compensatory response
Alkalosis is an abnormal processes condition which raises
the arterial pH if there is no compensatory response
Acidemia is arterial pH lower than 7.35. It can cause
hyperkalemia as potassium exits cells to preserve trans
membrane potential
Alkalemia is arterial pH greater than 7.45. It is associated with
hypokalemia due to potassium movement into cells
In mixed acid-base disorders, coexisting disorders may
have opposite effects on pH. Generally the most severe
disorder dictates the pH.
ph AND HYDROGEN IONS
Hydrogen ion concentration [H+] is expressed in nmol/L, i.e. a
millionth of a mmol. Thus, the concentration of Na+, Cl , K+ and
other strong ions are a factor of a million times more concentrated
in extracellular fluid (ECF) and intracellular fluid (ICF) than H+.
Due to the scale of this, the [H+] is routinely expressed as the
negative logarithm of [H+].
pH 7.4 corresponds to [H+] 40 nmol/L
The normal range for pH is 7.357.45 ([H+] 4535 nmol/L),
i.e. the change in [H + ] is only 10 nmol/L. This is an
indication of how tightly controlled [H+] is in normal daily
processes, e.g. exercise.
Due to the logarithmic nature of pH, at the acidotic end
of the scale, the change in [H+] is much higher than at
the alkalotic end, i.e. pH 7.1 = 80 nmol/L [H+]; pH 7.7 =
20 nmol/L. A drop in pH from 7.4 to 6.8 involves a 6-fold
increase in [H+].
Disturbance
PHYSIOLOGICAL PRINCIPLES
Acid Production
As fire makes smoke, so metabolism makes acids. Acids are
primarily:
Respiratory acid: CO2 which is excreted via the lungs. This
combines with H2O to produce H2CO3 which dissociates
into HCO3 and H+ ions
Metabolic acid: Fixed organic acids (not excreted by lungs),
which dissociate into anions (A) and H+ ions, are excreted
in the urine
Lactate from carbohydrate metabolism
Ketoacids (acetoacetate and -hydroxybutyrate) from
fat metabolism
Phosphates and sulfates from protein metabolism.
Acid-Base Regulation
For acid-base balance, the amount of acid excreted must equal
the acid produced. The body has three processes to regulate
acid-base balance:
1. Buffer
2. Ventilatory
3. Renal
Immediate buffering: The body has a huge capacity to
buffer via the process: A + H+ HA. Thus, a 1 mmol/L
fall in A requires 106 nmol/L (1 mmol/L) of H+ ions to
be mopped up by another buffer. The main buffers
are bicarbonate (HCO3), plasma proteins, hemoglobin
and phosphates
Immediate respiratory response: H + ions stimulate
chemoreceptors to increase ventilation, and more CO2
is excreted (lowering PaCO2) as follows:
H++ HCO3 H2CO3 CO2 + H2O
Slow renal response: The kidney reabsorbs filtered
HCO3 ions (raising plasma HCO3) and excretes fixed
acids in response to respiratory acidosis. This response
takes between 12 hours to several days (acute or
chronic renal response).
Simple and Mixed Acid-Base Disturbances
A simple acid-base disturbance denotes the presence of one
primary process, coupled with its appropriate physiologic
response. For example, in primary respiratory acidosis with
PaCO 2 of 50 mm Hg, plasma HCO3 generally increases
appropriate by 23 mEq/L in an attempt to balance acidemia,
caused by increased PaCO2 (partially compensated).
A mixed acid-base disturbance refers to coexistence of two
or more primary processes. These processes may have additive
or nullifying effect on plasma acidity. For example, if in above
condition of PaCO2 50 mm Hg, plasma HCO3 decreases instead
of increasing, then metabolic acidosis together with respiratory
acidosis have taken place, for example such conditions
occur in respiratory distress syndrome (RDS), cystic fibrosis,
unresponsive or untreated acute severe bronchial asthma.
METABOLIC ACIDOSIS
Acid derives from the Latin word acidus, which means sour.
Examination of Acid-Base Status
There are three accepted models for quantifying acid-base
status in common use:
HCO3/PaCO2 relationship, i.e. Henderson-Hasselbalch
equation
BE and AG calculation
Stewarts quantitative approach, i.e. strong ion difference
(if indicated and available).
Bicarbonate/PaCO2
CO2 is directly measured in blood gas analyzers
CO2 combines with water to form carbonic acid which can
dissociate:
CO2 + H2O H2CO3 H++ HCO3
HCO3 is not directly measured but is calculated from the
Henderson-Hasselbalch equation:
pH = pK + Log10[HCO3]/[CO2]
where K is the equilibrium constant (6.1)
The normal range for HCO3 concentration is 1826 mmol/L
but can be lower (1216 mmol/L) in preterm babies.
Base Excess
The BE is a single calculated variable that is used to quantify
the metabolic (nonrespiratory) component of a patients
acid-base status
Base excess is defined as the quantity of alkali (HCO3)
required to titrate blood to a pH of 7.4 with a fixed PaCO2 of
5.3 kPa (i.e. normal) at 37C. In practice, this is calculated
from the Siggaard-Andersen nomogram by most modern
blood gas analyzers
A negative BE (base deficit) implies metabolic acidosis.
A positive BE implies metabolic alkalosis.
Anion Gap
This is a parameter used to establish the cause of a patients
metabolic acidosis, i.e. the underlying problem is:
Secondary to accumulation of unmeasured anions and
thus H+ ions, i.e. raised AG.
or
Secondary to accumulation of chloride ions (Cl-), i.e.
normal AG.
AG = ([Na+] + [K+]) ([Cl] + [HCO3])
Normal AG is 816 mmol/L. If this is clearly raised, i.e.
more than 20 mmol/L, then this represents significant
unmeasured anions in plasma/ECF.
Causes of metabolic acidosis with increased AG (due to
unmeasured anions):
Shock status (lactic acidosis from septic shock, hypovolemic
shock)
Diabetic ketoacidosis (increase ketones) 163
Renal failure (increase SO42 and PO43 accumulation).
Poisons, e.g. ethanol, methanol, salicylates, ethylene glycol
Metabolic disorders: Inborn error of metabolism like
Acid-Base Balance and Disturbance
organic acidemia, fatty acid oxidation defect. A useful
aide to remember is MULEPACK for different causes of
metabolic acidosis with increased AG.
M = Metabolic defects, e.g. organic acidemia, fatty acid
oxidation
U = Uremia
L = Lactic acidosis: Tissue ischemia in shock (hypovolemic
or septic shock)
E = Ethanol, methanol
P = Paraldehyde
A = Aspirin
C = Carbon monoxide
K = Ketones in diabetic ketoacidosis (DKA)
Normal AG metabolic acidosis occurs in following
conditions. This is commonly due to the loss of HCO3 from
the gut or kidney, or impaired acid secretion by the kidney.
Diarrhea (most frequent cause in children)
Type I (distal) renal tubular acidosis (RTA): Inability to
excrete hydrogen ion, urine pH is always high (>6.5);
caused by a variety of medications or is inherited; often
associated with hypokalemia and hypercalciuria
Type (proximal) II RTA: Impaired reabsorption of HCO3
from proximal tubule, usually associated with other
proximal tubular dysfunction such as phosphaturia or
glycosuria (Fanconi syndrome)
Type IV (hyperkalemic) RTA: Inadequate aldosterone
production or inability to respond to it, seen in acute
pyelonephritis or obstructive uropathy.
Approach to Diagnosis and
Management of Metabolic Acidosis
Clinical Assessment
History:
A thorough history is important. One will need to identify any
symptoms of fever, flank pain and vomiting (pyelonephritis),
lethargy, or altered mental state (metabolic disease, sepsis
or poisoning). Then specific question should be asked about
the gastrointestinal symptoms particularly of diarrhea and
renal tracts, and growth. Lastly, there may be a significant
family history of renal disease, kidney stones or early infant
death.
Examination
A full examination is needed (Fig. 1). Assess:
Cardiovascular system: Warm, flushed skin or cold
clamming extremities, increased pulse rate, decreased
blood pressure
Respiratory system: Tachypnea, deep rapid respiration in
absence of clinical respiratory features like cough and no
added sound on chest auscultation (suggestive of renal
failure, DKA)
Hydration:
Significant dehydration associated with diarrheal
disease and DKA
Severe dehydration, deep rapid breathing with
abdominal pain is suggestive of DKA.
164
Illustrated Textbook of Pediatrics
Fig. 1: Clinical features of metabolic acidosis
CNS: Altered sensorium in sepsis, poisoning and metabolic
disorder associated with metabolic acidosis
Abdomen
Growth: Usually retarded in renal failure, untreated
diabetes mellitus
1. Confirm diagnosis (blood gas analysis):
Arterial pH less than 7.34
Base excess less than 3 mmol/L
PaCO2 appropriate for acidosis, i.e. it is usually low
when hyperventilatory compensation occurs but
is often high if there is also a respiratory acidosis
component or normal in ventilated paralyzed patients.
2. Check blood and urine:
Measure serum Na, K, Cl, urea, creatinine, lactate,
glucose and albumin
Check urine for pH, ketones
Imaging: Renal ultrasound scan looking for nephro
calcinosis (type I RTA)
Once diagnosis of metabolic acidosis is confirmed,
attempt to identify the underlying cause by calculation of
corrected AG.
3. AG more than 16consider clinical context and treat cause:
Lactic acidosis: Does this fit with clinical context, e.g.
hypotension, fluid/blood loss, myocardial dysfunction,
septic shock, seizures, etc.
Ketoacidosis ( blood sugar)
Renal failure ( urea, creatinine)
If none of these, consider underlying metabolic disease
or poisoning.
4. AC less than 16 consider clinical context and treat cause:
HCO3 loss from gastroenteritis (GIT).
HCO3 loss from kidneys (RTA).
Check chloride, whether it is raised.
Excess chloride from drugs, infusions.
Treatment
Most metabolic acidoses seen in PICU are lactic acidosis
with normal plasma lactate. This only rises in more severe
cases, secondary to shock (reduced oxygen delivery)
or seizures (oxygen consumption) and improves with
attention to fluid resuscitation and oxygen.
Aim for target pH more than 7.25, if possible. Consider
ventilatory support if pH less than 7.2.
Maintain supportive measures and organ support even in
the absence of diagnosis until pH improves.
Consider HCO3 therapy if indicated.
Monitoring
Ensure the airway breathing circulation (ABC). Then, the
form and type of monitoring will be dictated by the patients
condition. Start with continuous pulse oximetry and ECG
monitoring, and intermittent BP monitoring. Follow hourly
output.
Therapy
Correction of Dehydration
If the patient is dehydrated then this problem should be treated
with oral or IV replacement. This alone may improve serum
HCO3. Other interventions if required are follows:
Inotropes in persistent hypotension after fluid resuscitation
Identify the underlying cause and treat accordingly
(antibiotic in sepsis)
The use of buffers is common but lacks consensus on
indications and possible benefits
Sodium bicarbonate (NaHCO3) may worsen intracellular
acidosis, hypokalemia and hypocalcemia. It may increase
the risk of cerebral edema in diabetic ketoacidosis.
However, HCO 3/alkali therapy may be used for specific
metabolic disorders.
Metabolic Acidosis with Increased AG
Identify the cause and treatment; IV NaHCO 3 is only
given as last resort (child must be able to excrete the CO2
generated)
Sodium bicarbonate 8.4% (1 mmol/mL) is commonly used
and may be indicated in:
Severe acidosis (pH <7.1) and hypotension when
inotropes appear to be ineffective due to receptor
dysfunction
Sodium bicarbonate should not be given as rapid bolus
but as slow infusion (i.e. 12 mL/kg/hr of 8.4% NaHCO3 =
12 mmol/kg/hr) and titrate to effect, i.e. target pH more
than 7.2
Estimate the deficit = (20 [HCO3]) weight (kg) 0.5 mmol
Replace over 2448 hours with oral supplements
Tham (tromethamine) is a sodium-free buffer that does
not generate CO2. Despite its attractive qualities, it has
not yet been shown to have clinical advantages over
NaHCO3. It has also been linked with the adverse effects
of hyperkalemia, hypoglycemia and apnea.
Metabolic Acidosis with Normal Anion Gap
This indicates HCO3 loss. Diarrhea is the most common cause;
acidosis is corrected by fluid and electrolyte correction by oral
rehydration salt or in severe rehydration by IV polyelectrolyte
solution. Usually do not require extra IV NaHCO3.
Other causes of metabolic acidosis with normal AG are:
Distal or proximal RTA: Treatment includes HCO 3
supplementation
Hyperkalemic RTA: Correct serum HCO3 and increased
fluids to improve sodium delivery to the distal tubule (this
will enhance potassium secretion).

Fig. 2: Clinical features and etiology of metabolic alkalosis
METABOLIC ALKALOSIS
Causes
Often results from chloride depletion (secondary to
vomiting or loop diuretic therapy)
It is rarely due to alkali administration, laxative, or diuretic
abuse
Both severe vomiting and diuretics can cause hypokalemia
and an aggravating paradoxical aciduria which worsens
the alkalosis as seen in pyloric stenosis. Clinical features
and etiology of metabolic alkalosis are shown in Figure 2.
Treatment
Standard rehydration with 0.9% normal saline and
potassium supplementation is usually an adequate therapy
Some causes of chloride depletion are resistant to
replacement therapy such as renal tubular defects (Bartter
syndrome should be treated with indomethacin)
Administration of acid is very occasionally needed for
metabolic alkalosis:
0.5 mL/kg of 5.35% ammonium chloride into a central
vein over 1 hour (do not give in liver impairment)
In liver impairment, use 5 mL/kg of 100 mmol/L
hydrochloric acid into a central vein over 1 hour.
RESPIRATORY ACIDOSIS AND RESPIRATORY
ALKALOSIS
When an increase or decrease in PaCO2 initiates a disturbance,
it is referred to as respiratory acidosis or respiratory alkalosis.
Also consider primary clinical conditions as respiratory
disorders like pneumonia, asthma, bronchiolitis, etc.
Acid-Base Balance Involving Respiratory System
1. Acid-base disorders involving primary respiratory diseases
(pneumonia, bronchial asthma, etc.) with hyperventilation
causing respiratory alkalosis (pCO2) due to washing out
of CO2
2. Acid-base disorders due to hypoventilation associated with
primary lung function and hypoventilation due to CNS
depression. It results in respiratory acidosis (pCO2) due
to CO2 retention
165
Acid-Base Balance and Disturbance
Fig. 3: Etiology and clinical features of respiratory acidosis
3. Obstructive airway disease (severe acute bronchial asthma
as late finding, severe pneumonia; retention of CO2 cause
pCO2 with respiratory acidosis)
4. Respiratory functions in primary metabolic disorders
(metabolic acidosis like diabetic ketoacidosis and
metabolic alkalosis like hepatic failure). In metabolic
acidosis, hyperventilation washout CO2 in an attempt to
compensate metabolic acidosis. In metabolic alkalosis,
hypoventilation occurs, retaining CO2 in an attempt to
compensate metabolic alkalosis.
Respiratory Acidosis
Step 1: Confirm the pH (<7.35)
Step 2: Determine the PaCO2 (>5.3 kPa or >40 mm Hg)
Step 3: Increased BE. Slightly high (23 mmol higher
HCO3 than normal) in acute condition. In chronic
condition, kidney gets more time to conserve more
HCO3 (BE), to compensate acidemia and pH almost
become normal (compensated respiratory acidosis)
Step 4: Clinical condition: Primary clinical condition should
be respiratory, like pneumonia, bronchiolitis or
hypoventilation due to primary respiratory condition
or CNS depression.
Remember if PaCO 2 increases, BE also increases and
if PaCO2 decreases, BE also decreases as a compensatory
mechanism (Fig. 3).
Causes of Respiratory Acidosis
(Following Steps are Essential Characteristics)
Any process (other than alkalemia) that produces alveolar
hypoventilation results in respiratory acidosis. The causes are:
Central Nervous System Disease
Sedative overdose
Narcotic poisoning
Respiratory arrest secondary to brain damage due to
intracranial lesion
Brain tumor
Pulmonary Diseases
Primary alveolar hypoventilation in late complicated acute
bronchiolitis, life-threatening bronchial asthma due to
exhaustion
166 Acute airway obstruction (foreign body obstruction)
Acute obstructive lung diseases (late stage of severe acute
bronchial asthma)
Chronic obstructive pulmonary disease
Illustrated Textbook of Pediatrics
Severe and very severe pneumonia (pneumonia usually
causes respiratory alkalosis due to hyperventilation)
Severe pulmonary edema
Tension pneumothorax
Respiratory muscle disorders like Guillain-Barr syndrome
(GBS), poliomyelitis, myopathies, spinal muscular atrophy
Restrictive disease of thorax (scoliosis, pectus excavatum).
Acute versus Chronic Respiratory Acidosis
Most of the acute respiratory acidoses are short-lived with short
lived increased PaCO2. There is a small secondary increment of
HCO3 (23 mEq/L), and pH still remains low (acidic).
In chronic respiratory acidosis (most often the consequence
of chronic obstructive lung disease), secondary renal responses
result in more marked increase in plasma HCO3 concentration.
The mean increment in HCO3 concentration in an individual
fully adapted to chronic hypercapnia is approximately 0.4
mEq/L for each mm Hg increment in PaCO2. The coexistence
of metabolic acid-base disturbance in patients with primary
respiratory acidosis can be assessed by determining whether
the level of plasma HCO3 concentration corresponds to the
level anticipated for the observed degree and duration of
hypercapnia.
Example
A child with long-standing chronic lung disease (cystic
fibrosis) has a PaCO 2 of 55 mm Hg, pH 7.34 and plasma
HCO 3 concentration of 30 mEq/L. The increment above
normal PaCO2 is approximately 15 mm Hg (5540 mm Hg).
Thus one might anticipate an increment in plasma HCO3
concentration of approximately 6 mEq/L just on the basis of
chronic hypercapnia (15 0.4 mEq/L). The increment in HCO3
concentration will make serum HCO3 (considering mean
serum HCO3 as 24 mEq/L) level to be (24 + 6) 30 mEq/L, which
is called partially or completely compensated (if pH becomes
normal) respiratory acidosis. This sort of compensated
respiratory acidosis may also be found in chronic obstructive
airway disease in adult and sometimes in persistent (moderate
to severe) asthma in children. Compensatory respiratory
acidosis is unusual in acute respiratory conditions. If HCO3
level increases more than 30 mEq/L, than independent
process also works, which is an evidence of mixed acid-base
disturbance in which an element of metabolic alkalosis is
present (the respiratory acidosis + metabolic alkalosis).
Mixed Respiratory Acidosis with
Metabolic Acidosis
This is not an uncommon mixed acid-base disturbance, where
two primary mechanisms work. Important steps are:
Clinical settings
+ hypercapnia. If condition continues further (chronic), 8 mEq/L
Step 1: Confirm the pH (<7.5)
Step 2: Confirm the PaCO2 (>5.3 kPa or >40 mm Hg)
Step 3: High negative BE (base deficit) and decreased
HCO3 instead of usual increased BE and increased
HCO3 found in chronic respiratory acidosis with its
appropriate physiological response.
Clinical settings associated with mixed respiratory and
metabolic acidosis with Type 2, respiratory failure (pO2,
pCO2) are found in severe complicated acute bronchiolitis,
final stage of acute severe bronchial asthma, cystic fibrosis,
respiratory distress syndrome, etc. In both acute severe
bronchiolitis and acute severe bronchial asthma, initially there
is decreased pO2 and decreased pCO2 due to hyperventilation
and respiratory alkalosis follows. As bronchial obstruction
and hypoventilation finally occur due to exhaustion, pCO 2
increased. If increased pCO 2 and decreased pO 2 are not
corrected timely by assisted ventilation, respiratory acidosis
takes place. If respiratory acidosis and hypoxemia continue
then anaerobic glycolysis and lactic acidosis take place causing
metabolic acidosis. Serum HCO3 then falls inappropriately
to increased pCO2 and decreased pH. Here increased pCO2 is
associated with decreased HCO3. Such clinical setting sets in
mixed respiratory and metabolic acidosis.
Example
A 1-year-old child with acute severe bronchiolitis, developed
type II respiratory failure with pO2 of 50 mm Hg and pCO2 60
mm Hg, serum HCO3 of 12 mEq/L and pH of 6.9. A rise of pCO2
of 20 (6040 mm Hg) is supposed to increase serum HCO3 to
20 0.4 = 8 mEq/L, that is serum HCO3 is expected to be (24 +
8) = 32 mm Hg. However, serum HCO3 (base deficit) was found
to be 12 mEq/L. This indicates another primary process (here
lactic acidosis due to hypoxia) working in opposite direction
to make acidemia worse.
Practice
A 4-day-old preterm newborn baby presented with respiratory
distress, since birth with pO2 of 55 mm Hg and pCO2 60 mm
Hg. His HCO3 level is 8 mEq/L and pH is 6.9. X-ray shows air
bronchogram.
1. What is his respiratory status?
2. What is the most likely clinical diagnosis?
3. What is the acid-base status?
Answers:
1. The baby has developed type II respiratory failure (pO2
and pCO2)
2. Most likely, diagnosis is respiratory distress syndrome
(RDS) as evidenced by air bronchogram on chest X-ray
3. Mixed respiratory acidosis and metabolic acidosis.
Explanation:
pH: Less than 7.4 (Acidemic).
pCO2: More than 40 mm Hg respiratory acidosis as primary
clinical setting is respiratory problem (RDS)
Plasma HCO3: Decreased instead of physiological response
of increased HCO3.
pCO2 is 20 mm Hg (6040 mm Hg) more than normal. In
simple respiratory acidosis, there will be increase of 23 mEq/L
of serum HCO 3 in acute hypercapnia (within few hours)
and 0.4 mEq/L for each mm Hg increase of pCO2 in chronic
(20 0.4) increase in serum HCO3 above normal is expected. If
normal mean serum HCO3 is considered to the 24 mEq/L than
HCO3 is expected to be 32 mEq/L (24 + 8). However, the baby
had serum HCO3 of 8 mEq/L which indicates another primary
process, which has inappropriately decreased serum HCO3.
Here, prolonged hypoxia has caused tissue hypoperfusion
and lactic acidosis. Therefore mixed respiratory acidosis with
metabolic acidosis occurred instead of respiratory acidosis
with usual physiological compensated (partially or completely)
metabolic alkalosis.
Respiratory Alkalosis
Clinical conditions : Pneumonia, bronchial asthma,
bronchiolitis associated with hyperventilation (Fig. 4).
Although respiratory disorders, like pneumonia, bronchial
asthma, bronchiolitis commonly cause respiratory alkalosis,
very severe pneumonia, acute severe bronchiolitis and
untreated or medically unresponsive acute severe bronchial
asthma (hypoventilation due to exhaustion and severe
bronchial obstruction), may eventually cause respiratory
acidosis due to CO2 retention.
Step 1: Confirm the pH (>7.45)
Step 2: Determine the PaCO2, it should be less than 4.5 kPa
or 33 mm Hg
Step 3: Increase in plasma HCO3 (BE)
Degree of decreased BE depends on acute or chronic
clinical condition. In acute clinical condition (acute respiratory
alkalosis), there will be slight fall in decreased BE (HCO3).
However, in prolonged clinical condition (chronic lung
disease), kidney gets more time to adjust HCO 3 (excretes
HCO3) and pH may become almost normal (compensated
respiratory alkalosis).
Example of Acute versus Chronic Respiratory
Alkalosis
Many respiratory diseases causing respiratory alkalosis, like
pneumonia and bronchial asthma, are short-lived. In this
instance, the acid-base disturbance is manifested by primary
decrement in PaCO2 (due to primary hyperventilation and
tachypnea) and a small secondary physiological decrement
in HCO 3 concentration that results from the titration of
nonbicarbonate tissue buffers. A decrement of only 34 mEq/L
(considering mean serum HCO3 24 mEq/L as normal) may be
expected to occur with several minutes after PaCO2 is lowered
to 2025 mm Hg.
Less commonly if respiratory alkalosis lingers enough (a
few days or more), renal adjustment in HCO3 concentration
occurs, e.g. in patients with hepatic insufficiency, chronic
hyperoxic states, chronic salicylate poisoning, etc. When
secondary renal adjustments are fully established and a new
Fig. 4: Etiology and clinical features of respiratory alkalosis
steady state is maintained, the average reduction in plasma 167
HCO3 is approximately 0.5 mEq/L for each mm Hg reduction
of PaCO2.
For example, if PaCO2 is 20, than fall in HCO3 will be 4020
Acid-Base Balance and Disturbance
0.5 = 10 mEq/L, plasma HCO3 will be 2410 = 14 mEq/L.
Pulmonary Function in Primary Metabolic
Acid-Base Disturbance
Lungs also play secondary important role by increasing or
decreasing ventilatory rate in primary metabolic acidosis or
alkalosis. In metabolic acidosis, there will be hyperventilation
with CO2 washout (pCO2), and in metabolic alkalosis, there
will be hypoventilation, with CO2 retention and increased
PaCO2.
In metabolic acidosis for each mEq/L, reduction of
HCO3 there will be a fall of pCO2 of 1.0 to 1.3 mm Hg through
hyperventilation. For example, if serum HCO3 is 12 mEq/L,
then decrease of pCO2 will be 14.4 (12 1.2), considering mean
serum HCO3 as 24 mEq/L. Therefore anticipated pCO2 will
be 25.6 mm Hg (4014.4 mm Hg), considering mean normal
PaCO2 as 40 mm Hg. This is primary metabolic acidosis with
appropriate physiological response, which tends to compensate
acidemia.
However, lungs may also act as another primary process
in addition to metabolic disturbance. Like mixed metabolic
acidosis with respiratory alkalosis, when lung hyperventilates
disproportionately. This commonly occurs in Gram-negative
septicemia.
Examples of Mixed Metabolic Acidosis and
Respiratory Alkalosis
A child with Gram-negative septicemia with shock found to
have rapid deep respiration. Arterial blood studies revealed
a PaCO2 of 15 mm Hg, a pH of 7.35 and a plasma HCO3 of
8 mEq/L. Plasma HCO3 is 16 mEq/L below normal (248
mEq/L); as a result of metabolic acidosis, presumably as the
result of lactic acid over production. Thus one might expect a
reduction of PaCO2 of approximately 19 mm Hg just as the result
of physiologic response to this degree of metabolic acidosis (16
mEq/L 1.2 = 19 mEq/L). However, the observed reduction of
pCO2 is 25 mm Hg (4015), instead of anticipated reduction of
PaCO2 of 19 mm Hg. This discrepancy between the observed
and expected degree of pCO2 signifies an independent process
stimulating ventilation and thus evidence of mixed disturbance
in which metabolic acidosis and respiratory alkalosis coexist.
This condition may be found in Gram-negative septicemia.
Management of Respiratory Acidosis
Usually occurs secondary to respiratory failure, e.g.
ventilation perfusion abnormalities, low compliance,
increased airway resistance, decreased respiratory drive,
airway obstruction, increased dead space
In chronic setting, metabolic compensation (provided
renal function is adequate) usually normalizes pH
Pay attention to ABCs, i.e. intubate and ventilate if necessary
and treat underlying cause of respiratory failure
Heparin contamination of a gas sample can lower
PaCO2 and HCO3 measurements and can mask renal
compensated respiratory acidosis.
168 Management of Respiratory Alkalosis
(pCO2 <25 mm Hg)
Disorders of high pH are classified into those resulting from
Illustrated Textbook of Pediatrics
excess removal of CO 2 (respiratory alkalosis), and those
resulting from loss of nonvolatile acids or accumulation of
buffer (metabolic alkalosis). Respiratory alkalosis can occur
due to:
Hyperventilation from different causes leading to
respiratory alkalosis (pneumonia, bronchiolitis, bronchial
asthma)
Other causes include anxiety, hysterical hyperventilation
and central hyperventilation from brain injury, encephalo
pathy, encephalitis, salicylate toxicity, hypoxia
Also commonly occurs in ventilatory support from excessive
minute volume when a patient is initially intubated and
ventilated. It can be minimized from monitoring early
arterial gases or from use of EtCO2 monitoring-severe
hypocapnia. Respiratory alkalosis from overventilation can
significantly reduce brain perfusion and aggravate cerebral
ischemic injury.
Clinical Features of Respiratory Alkalosis
In addition to hyperventilation symptomatic respiratory
alkalosis appear only in acute severe respiratory alkalosis
which are one or more of the followings:
Tingling around mouth and fingers
Parasthesias, numbness
Tetany and convulsion due to decrease in ionic calcium
commonly found in hysteric hyperventilation.
Treatment
Treatment consists of treating specific underlying causes
Check oxygen saturation to exclude hypoxia
Try to find the source of anxiety and take steps accordingly
If occurs in patients on ventilators due to excessive minute
volume then measures to be taken include reducing minute
volume and/or introducing dead space into the ventilator
circuit.
KEY POINTS OF ACID-BASE DISTURBANCE AS A WHOLE
Regulation of normal extracellular pH (7.4) and intracellular
pH (7.0) is vital for organ function in the long-term
Apart from primary metabolic disorders, most acid-base
disorders in PICU should be viewed as a complex physiological
response to an underlying pathological abnormality
Despite some controversy in mechanisms, it is best to
approach acid-base disorders via the principles of:
pH
PaCO2 relationship (Henderson-Hasselbalch equation) to pH
Calculation of the base excess (BE)
Anion gap (AG)
Bibliography
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