3. Introduction
Acid-Base chemistry
• An acid is a substance that can donate protons [H+]:
(Acid) HCl → H+ + Chloride ion (Cl)
• A base is a substance that can accept protons [H+]:
Ammonia (NH3) + H+ → NH+
4 (base)
• The acidity of body fluids is quantified in terms of the
hydrogen ion concentration.
– By convention, the degree of acidity is expressed
as pH
4. • Normally, the pH of blood is maintained at 7.40 ([H+]
of 4 × 10–8 M) with a range of 7.35 to 7.45.
• A condition incompatible with life can occur when:
– PH < 6.7, representing a fivefold increase in
hydrogen ion concentration.
– PH > 7.7, representing a 50% decrease in
hydrogen ion concentration, is considered in.
• The hydrogen ion concentration in blood may not be
indicative of that in other body compartments.
5. Buffers
• Buffering: the ability of a weak acid and its
corresponding anion (base) to resist change in the pH
of a solution with the addition of a strong acid or
base.
• The principal extracellular buffer is the carbonic
acid/bicarbonate (H2CO3/HCO3
–) system.
• Other physiologic buffers include plasma proteins,
hemoglobin, and phosphates.
6. 6
Why concerned?
Disturbances of acid-base equilibrium occur in a wide
variety of illnesses and are among the most commonly
encountered disorders in critical care medicine.
Although severe derangements may affect virtually any
organ system, the most serious clinical effects are
- cardiovascular (arrhythmias and impaired contractility)
- neurologic (coma and seizures),
- pulmonary (dyspnea, impaired oxygen delivery, and
respiratory fatigue), and/or
- renal (hypokalemia).
Changes in acid-base status also affect multiple aspects
of pharmacokinetics (clearance and protein binding)
and pharmacodynamics.
7. Acid-base homeostasis
7
• Acid-base homeostasis is responsible for maintaining blood
hydrogen ion concentration [H+] near normal despite the daily
acidic and/or alkaline loads derived from the intake and
metabolism of foods.
• Blood pH is normally tightly regulated by three distinct
mechanisms:
1. Extracellular bicarbonate and intracellular protein buffering
systems
2. Pulmonary regulation of PaCO2, effectively allowing carbonic
acid to be eliminated by the lungs as CO2
3. Renal reclamation or excretion of HCO3- and excretion of acids
such as ammonium.
9. 9
Basic pathophysiology
• Under normal circumstances the arterial pH is tightly
regulated between 7.35 and 7.45.
• Acidemia
• Acidosis
• Alkalemia
• alkalosis
• Changes in the arterial pH are driven by changes in the
PaCO2 and/or the serum HCO3–.
• Carbon dioxide is a volatile acid that is regulated by the
depth and rate of respiration------respiratory controlled.
10. BASIC PATHOPHYSIOLOGY— con’d
• A respiratory acid-base disorder is a pH disturbance caused
by pathologic alterations of the respiratory system or its
central nervous system control.
– Respiratory acidosis
– Respiratory alkalosis
• Variations in respiratory rate and/or depth allow the lungs to
achieve changes in the PaCO2 very quickly (within minutes).
• Bicarbonate is a base that is regulated by renal metabolism
via the enzyme carbonic anhydrase---metabolic control
11. BASIC PATHOPHYSIOLOGY---con’d
• A metabolic acid-base disorder is a PH disturbance
caused by derangement of the pathways responsible
for maintaining a normal HCO3 – level.
Metabolic acidosis
Metabolic alkalosis
14. 14
APPLICATION OF BASIC
PATHOPHYSIOLOGY
• The best way to assess a patient’s acid-base status is to
review the results of an arterial blood gas (ABG)
specimen.
• Blood gas analyzers directly measure the pH and PaCO2
while the HCO3 – value is calculated using the
Henderson- Hasselbalch equation.
- pH = 6.1 + ([HCO3–]/[H2CO3])
- pH = 6.1 + log([HCO3–]/(PCO2 × 0.03))
• When given an ABG for interpretation, it is essential to
use an approach that is focused yet comprehensive.
18. 18
Examples
Case Study 1
• First, consider a patient with a pH of 7.16, a PaCO2 of 70 mmHg
(9.3 kPa), and an HCO3– of 27 mEq/L (mmol/L).
Case Study 2
• The next patient has a pH of 7.34, a PaCO2 of 70 mm Hg (9.3
kPa), and an HCO3 – of 35 mEq/L (mmol/L).
Case Study 3
• Now consider a patient whose ABG shows a pH of 7.50, a
PaCO2 of 29 mm Hg (3.86 kPa), and an HCO3 – of 22 mEq/L
(mmol/L).
19. 19
Examples
Case Study 4
• This patient has an ABG with the following values: pH of 7.50,
a PaCO2 of 47 mm Hg (6.3 kPa), and an HCO3– of 36 mEq/L
(mmol/L).
Case Study 5
• The final patient in this section has an ABG with a pH of 7.20, a
PaCO2 of 20 mm Hg (2.7 kPa), and an HCO3– of 8 mEq/L
(mmol/L).
20. 20
METABOLIC ACIDOSIS
• is characterized by a decrease in pH as the result of a
primary decrease in serum bicarbonate concentration.
• This can result from:
The buffering (consumption of HCO3–) of exogenous acid
An organic acid accumulating because of a metabolic disturbance
(e.g., lactic acid or ketoacids), or
The progressive accumulation of endogenous acids secondary to
impaired renal function (e.g., phosphates and sulfates).
• The serum HCO3– can also be decreased as the result
of;
A loss of bicarbonate-rich body fluids (e.g., diarrhea,
biliary drainage, or pancreatic fistula) or
Occur secondary to the rapid administration of non–
alkali-containing intravenous fluids (dilutional acidosis).
21. 21
Serum anion gap
• To maintain electroneutrality, the total concentration of cations
in the serum must equal the total concentration of anions.
• The SAG can also be elevated in the metabolic acidosis & helps
in
Identification of etiology of acid base disorders
Facilitate determination of excess gap or the degree to which the
calculated anion exceeds the normal anion gap.
• The excess gap represents the amount of HCO3– that has been
lost due to buffering unmeasured cations. The excess gap can
be added back to the measured HCO3 – to determine what the
patient’s bicarbonate would be if these endogenous acids were
not present.
22. 22
Urine anion gap
In hyperchloremic metabolic acidosis, bicarbonate losses
from the ECF are replaced by chloride, and the SAG remains
normal.
In patients with a normal anion gap metabolic acidosis it is
often helpful to calculate the urine anion gap (UAG).
The UAG is calculated as follows:
Value 0 to 5 mEq/L---POSITIVE
Values -20 to -50 mEq/L---NEGATIVE
IMPLICATIONS
25. 25
Clinical presntation
• Symptoms of metabolic acidosis are attributable to
changes in:
Respiratory compensation requires marked increases in
minute ventilation and may lead to dyspnea.
Acidemia predisposes to ventricular arrhythmias and
reduces cardiac contractility, each of which can result in
pulmonary edema and/or systemic hypotension
Neurologic symptoms range from lethargy to coma and
are usually proportional to the severity of the pH
derangement.
Chronic metabolic acidosis leads to a variety of
musculoskeletal problems including impaired growth,
rickets, osteomalacia, or osteopenia.
26. 26
Diagnosis
• The diagnosis of metabolic acidosis is
established from;
– the health history,
– clinical symptoms, and
– laboratory findings: arterial PH<7.35 and
bicarbonate concentration<24 mEq/L
27. 27
Treatment
• In order to effectively treat metabolic acidosis, the causative
process must be identified and treated.
• The role of adjunctive therapy with sodium bicarbonate
(NaHCO3) is not universally agreed upon.
• The metabolic acidosis seen with lactic acidosis and
ketoacidosis generally resolves with therapy targeted at the
underlying cause and NaHCO3 may be unnecessary
regardless of the pH.
• The metabolic acidosis of renal failure, renal tubular
acidosis, or intoxication with ethylene glycol, methanol, or
salicylates is much more likely to require NaHCO3 therapy.
28. 28
Treatment
• Another option for patients with severe acidemia is
tromethamine (THAM).
• This inert amino alcohol buffers acids and CO2 through its
amine (−NH2) moiety:
- THAM-NH2 + H+ = THAM-NH3+
- THAM-NH2 + H2O + CO2 = THAM-NH3+ + HCO3–
• THAM is less effective in patients with renal failure and
toxicities may include hyperkalemia, hypoglycemia, and
possible respiratory depression.
29. 29
Metabolic alkalosis
• Metabolic alkalosis is characterized by:
1. an increased arterial pH
2. a primary increase in the HCO3– concentration, and
3. compensatory increase in the PaCO2.
• Common Causes of Metabolic Alkalosis
30. 30
Clinical presentation
• Patients with metabolic alkalosis rarely have
symptoms attributable to alkalemia.
• Rather, complaints are usually related to volume
depletion (muscle cramps, positional dizziness,
weakness) or to hypokalemia (muscle weakness,
polyuria, and polydipsia).
• Respiration will be slow and shallow to increase
carbondioxide content
• Cofusion and convulsion with severe alkalosis
32. 32
TREATMENT
• In order to effectively treat metabolic alkalosis, the
causative process must be identified and treated.
• Always look for administration of compounds such as
citrate in blood products and acetate in parenteral nutrition
that can raise the HCO3− level.
• If the etiology of the metabolic alkalosis is still unclear,
measurement of the urinary chloride may be useful.
Some processes leading to metabolic alkalosis (vomiting,
nasogastric suction losses, and factitious diarrhea) will have
low urinary Cl– levels (less than 25 mEq/L or mmol/L)
While others (diuretics, hypokalemia, and
mineralocorticoid excess) will have higher urinary Cl– levels
(greater than 40 mEq/L or mmol/L).
33. 33
TREATMENT
• In general, contributing factors such as diuretics, nasogastric
suction, and corticosteroids should be discontinued if
possible
• Any fluid deficits should be treated with IV normal saline.
• Potassium supplementation should always be given if it is
also deficient.
• In patients with mild or moderate alkalosis who require
ongoing diuresis but have rising HCO3 – levels, the carbonic
anhydrase inhibitor acetazolamide can be used to reduce the
HCO3 – concentration.
– Acetazolamide is typically dosed at 250 mg every 6 to 12 hours as
needed to maintain the pH in a clinically acceptable range.
• If alkalosis is profound and potentially life-threatening (due
to seizures or ventricular tachyarrhythmias) consideration
can be given to hemodialysis.
34. 34
Respiratory Acidosis
• Respiratory acidosis is characterized by :
1. a reduced arterial pH
2. a primary increase in the arterial PaCO2 and, when
present for sufficient time
3. a compensatory rise in the HCO3– concentration.
• Because increased CO2 is a potent respiratory stimulus,
respiratory acidosis represents ventilatory failure or
impaired central control of ventilation as opposed to an
increase in CO2 production.
• As such, most patients will have hypoxemia in addition
to hypercapnia.
36. 36
Clinical presentation
• Severe, acute respiratory acidosis produces a variety of
neurologic abnormalities.
• Initially these include headache, blurred vision, restlessness,
and anxiety.
• These may progress to tremors, asterixis, somnolence, and/or
delirium.
• If untreated, terminal manifestations include peripheral
vasodilation leading to hypotension and cardiac arrhythmias.
• Chronic respiratory acidosis is typically associated with cor
pulmonale and peripheral edema.
38. 38
Treatment
• In order to effectively treat respiratory acidosis, the
causative process must be identified and treated.
• If a cause is identified, specific therapy should be started
- This may include naloxone for opiate-induced
hypoventilation or bronchodilator therapy for acute
bronchospasm
- Because respiratory acidosis represents ventilatory failure,
an increase in alveolar ventilation is required
- Sodium bicarbonate????
- Excessive oxygen???
39. 39
Respiratory Alkalosis
• Respiratory alkalosis is characterized by :
1.an increased arterial pH
2.a primary decrease in the arterial PaCO2 and,
when present for sufficient time
3. a compensatory fall in the HCO3–concentration.
• Respiratory alkalosis represents hyperventilation
and is remarkably common.
41. 41
Clinical presentation
• The symptoms produced by respiratory alkalosis result
from increased irritability of the central and peripheral
nervous systems.
• These include light-headedness, altered consciousness,
distal extremity paresthesias, circumoral paresthesia,
cramps, carpopedal spasms, and syncope.
• Various supraventricular and ventricular cardiac
arrhythmias may occur in extreme cases, particularly in
critically ill patients.
• Hypophosphatemia , reflecting a shift of phosphate from
the extracellular space into the cells.
42. 42
Treatments
• Respiratory alkalosis is usually not a severe disorder;
teatment involves correcting the underlying causes.
• In case of acute anxiety the patient should rebreath
expired air from a paper bag.
Bicarbonate administration is rarely necessary and is potentially harmful.
Oxygen therapy should be initiated carefully and only if the PaO2 is less than 50 mm Hg because the drive to breathe depends on hypoxemia rather than hypercarbia.
