ACID-BASE BALANCE

Terminologies:
1. Acid – a substance that can yield a hydrogen ion (H+) or hydronium ion when dissolved in water.
2. Base – a substance that can yield hydroxyl ions (OH−).
3. Buffer – the combination of a weak acid or weak base and its salt, is a system that resists changes in
pH.
4. pKa - the negative log of the ionization constant, is also the pH in which the protonated and unprotonated
forms are present in equal concentrations.
• Strong acids – pKa is less than 3.0
• Strong bases – pKa is greater than 9.0
5. Acidemia – excess acid or H+ concentration in blood.
6. Alkalemia – excess base in blood.
7. Compensation – the body’s response to an alteration in pH which aims to return it to normal levels.
• Fully compensated – implies that the pH has returned to normal range (20:1 ratio has been restored).
• Partially compensated – implies that the pH is approaching normal.
• While compensation may successfully return the ratio to the normal 20:1, the primary abnormality is
not corrected.

Regulation of Acid-Base Balance: Lungs and Kidneys

• Most of the CO2 combines with H2O to form carbonic acid (H2CO3), which dissociates immediately into
H+ and bicarbonate (HCO3−) – the reaction is accelerated by carbonic anhydrase.
• The dissociation of H2CO3 increases HCO3− in RBC causing it to diffuse into the plasma.
• HCO3− and H2CO3 are renewable – even before renal mechanisms restore the constituents, the lung
alters the ratio of numerator (HCO3−) to denominator (H2CO3) by blowing off CO2.

Lungs
• Respiratory control of CO2 excretion allows rapid and very sensitive adjustments in blood pH.
• As the lungs eliminate excess CO2 to resist accumulating H+, the proportion between HCO3− and H2CO3
readjusts to 20:1, although the absolute concentrations of each can fall below normal.
• By regulating the rate of CO2 excretion, the lungs can maintain the ratio at about 20:1, thereby minimizing
pH changes.
• The CO2 diffuses into the alveoli and is eliminated through ventilation.
• Slow or non-removal of CO2 by the lungs results to increase in H+ ion concentration – respiratory acidosis.
• Rapid or fast elimination of CO2 results to decrease H+ ion concentration – respiratory alkalosis.

Kidneys
• The most important function of the kidneys in acid-base homeostasis is excretion of acid, which is
equivalent to generation of alkali or reabsorption of HCO3− from the glomerular filtrate (proximal tubules
of the kidneys) and add it to the blood.
• Acid is excreted in the form of NH4+ and titratable acid.
• Hydrogen ions are also excreted by the kidney, both by direct excretion and through indirect disposal in
the form of ammonium ion.
• HCO3− concentration is under renal control, in that the kidneys regulate both the generation of HCO3−
ions and their rate of urinary excretion.
• Fifty to one hundred percent (50 – 100) mmol/L of acid must be excreted daily by the kidneys resulting
to urine pH of 4.5.

Plasma and Urine Bicarbonate:

• ↑ HCO3− : IV infusion of lactate, acetate and HCO3−
• ↓ HCO3− : use of diuretics, reduced reabsorption, and chronic nephritis
• If HCO3− is below 25 mmol/L or if plasma CO2 rises above normal, the tubule can reabsorb all the HCO3−
in the glomerular filtrate, leaving none for the excretion in urine.
• A small amount of bicarbonate is normally excreted in the urine (about 10 mEq/day).
• The kidneys excrete considerable amounts of acid and base for acid-base regulation.
• Urinary excretion of HCO3− : when plasma levels reach 26 – 30 mmol/L

Blood Buffers:
1. Bicarbonate and carbonic acid (HCO3− : H2CO3) – major extracellular blood buffer
2. Plasma proteins
3. Hemoglobin
4. Inorganic phosphate

• H2CO3 is a weak acid because it does not completely dissociate into H+ and HCO3−.
• When an acid is added to the bicarbonate-carbonic acid system, the HCO3− will combine with the H+ from
the acid to form H2CO3.
• Plasma proteins have buffering capacity through charges on their surfaces.
• Hemoglobin is an effective buffer because it can off-load its oxygen and combine with CO2 that diffuses
across gradients.
• 1 gram of hemoglobin carries 1.39 mL of oxygen; each mole of hemoglobin binds 1 mole of oxygen –
more than 95% of the hemoglobin binds oxygen.
• All the above-mentioned blood buffers also contribute to buffer base.

Henderson-Hasselbalch Equation
• It expresses the acid-base relationship and relates the pH of a solution to the dissociation properties of
the weak acid.
• It indicates that pH depends on the ratio of HCO3−/pCO2.
• When the kidneys and the lungs are functioning properly, a 20:1 ratio of HCO3− to H2CO3, will be
maintained, and it is expressed by the Henderson-Hasselbalch equation.

conjugate base HCO−

3 kidneys
pH = pKa + log pH = 6.1 + log H pH = 6.1 + log
weak acid 2 CO3 lungs

where:
pKa = is 6.1; combined hydration and dissociation constants for CO2 in blood
conjugate base = bicarbonate
weak acid = carbonic acid
Parameters in the Assessment of Acid-Base Balance:
1. pH
2. pCO2
3. HCO3−
4. pO2

1. Evaluate the pH
Normal pH: 7.35 – 7.45
<7.35 – Acidosis
>7.45 – Alkalosis
• pH 7.40 is the optimum level for arterial blood.
• To preserve pH within the narrow physiologic range, short-term buffering capacity must neutralize acids
as they are generated, and long-term corrective measures must eliminate the acid permanently, but on
a continuous basis.
• The reference range for arterial blood pH (7.35 – 7.45) is only 0.03 pH unit lower for venous blood owing
to the buffering effects of hemoglobin known as chloride-isohydric shift.
• The pH decreases by 0.015 each Celsius above 37°C.
• 3 major causes of extrarenal acidosis: organic acidosis, diarrheal loss of bicarbonate, and acidosis due
to exogenous toxins.

2. Evaluate the ventilation (Lungs)

Normal pCO2: 35 – 45 mmHg
<35 mmHg – Respiratory Alkalosis
>45 mmHg – Respiratory Acidosis
• pCO2 is an index or efficiency of gas exchange and not a measure of CO 2 concentration in blood.
• The lungs regulate pH through the retention or elimination of CO2.
• An increasing ratio of heparin to blood can cause marked artifactual rise on measured pCO2 (12 – 15%)
and the parameters calculated from it.
• Whole blood total CO2 is equal to dissolved CO2 + H2CO3 + HCO3.
• Increased pO2: use of illicit drugs like barbiturates and morphine, and alcoholism

3. Evaluate the metabolic process (Kidneys)

Normal HCO3− : 21 – 28 mEq/L
<21 mEq/L – Metabolic Acidosis
>28 mEq/L – Metabolic Alkalosis
• The kidneys regulate pH by excreting acid (NH4+ ions) and reabsorbing HCO3− from the glomerular
filtrate.

4. Evaluate the degree of oxygenation

Normal pO2: 81 – 100 mmHg (adequate oxygenation)
3 levels of hypoxemia:
Mild = 61 – 80 mmHg
Moderate = 41 – 60 mmHg
Severe = 40 mmHg or less
• Hypoxemia is low pO2.
• pO2 reflects the availability of the gas in blood but not its content.
• pO2 changes more rapidly than pCO2 or pH.
• pO2 is 60 – 70% lower in venous blood after oxygen is released in the capillary tissues.
• The degree of association or dissociation of oxygen with hemoglobin is determined by pO2 and the affinity
of hemoglobin for O2.
• Low pO2 is seen in myocardial infarction, interstitial pneumonia, and severe congestive heart failure.
• Healthy persons living at higher altitudes will show lower ranges of arterial pO2 because of the naturally
lower partial pressure of oxygen in the atmosphere and so in the inspired air.

Four Basic Abnormal States

1. Metabolic Acidosis
• It is caused by bicarbonate deficiency.
• It is seen in diabetic ketoacidosis (DKA), lactic acidosis (alcoholism), renal failure and diarrhea.
• In DKA, the chloride remains normal (normochloremic acidosis) or low with elevated anion gap.
• Diarrhea results in metabolic acidosis via bicarbonate loss.
• Metabolic acidosis causes greater potassium efflux than respiratory acidosis.
• Metabolic acidosis due to inorganic acids (e.g., sulfuric acid, hydrochloric acid) causes greater
potassium efflux than that due to organic acids (e.g., lactic acid, keto acids) – because organic anions
accumulate substantially in the cell, as well as in the ECF, whereas inorganic anions accumulate
mainly in the ECF.
• Compensation: Breathing rate increases to lower pCO2 – hyperventilation
• After compensation: low HCO3− + low pCO2 + pH <7.4 (↓pCO2 10 – 15 mmHg)
• The maximal compensation is completed within 12 to 24 hours.
• pCO2 drops 1 to 1.3 mmHg per mEq/L fall in HCO3−.
• Electrolyte imbalance: hyperkalemia and hyperchloremia

2. Metabolic Alkalosis
• It is caused by bicarbonate excess.
• It is seen in vomiting (with the loss of chloride from the stomach).
• Compensation: breathing rate decreases to increase pCO2 – hypoventilation
• After compensation: high HCO3− + high pCO2 + pH > 7.4
• The maximal compensation is completed within 12 to 24 hours.
• Among the four types of acid-base disorders, compensation is least effective in metabolic alkalosis
– probably because hypoxemia, an inevitable consequence of hypoventilation, stimulates ventilation.
• For every 10 mEq/L rise in HCO3−, the pCO2 rises by 6 mmHg.
• Electrolyte imbalance: hypokalemia and hypochloridemia

3. Respiratory Acidosis
• It is due to excessive carbon dioxide accumulation.
• It is seen in chronic obstructive pulmonic disease (COPD), myasthenia gravis (partial paralysis of the
accessory muscles of breathing), CNS disease, drug overdose (morphine, barbiturates, and opiates),
botulism, stroke, myxedema, and pneumonia.
• Compensation: kidneys retain HCO3− because of increased pCO2
• After compensation: high pCO2 + high HCO3− + pH <7.4
• Maximal compensation requires 5 days but is 90% complete in 3 days.
• Excretion of acid is another way of compensating the rise of pCO2.
 • Restriction of NaCl intake during the recovery phase of chronic respiratory acidosis results in the
maintenance of a high serum HCO3−.
• HCO3− rises 1 mEq/L for each 10 mmHg rise in pCO2.

4. Respiratory Alkalosis
• It is due to excessive carbon dioxide loss (because of rapid breathing).
• It is observed during anxiety, severe pain, aspirin overdosage, hepatic cirrhosis, gram-negative
sepsis, salicylate, and progesterone drugs.
• Blood pH tends to be extremely high when respiratory alkalosis is caused by psychogenic stimulation
of the respiratory center, because the condition is usually superacute, and therefore there is no time
for compensation.
• High progesterone levels are responsible for chronic respiratory alkalosis of pregnancy.
• Compensation: decreased reabsorption of HCO3−
• After compensation: low pCO2 + low HCO3− + pH >7.4
• Compensation is completed within 2 to 3 days.
• Among the four types of acid-base disorders, compensation is most effective in respiratory alkalosis
– pH after compensation sometimes returns to normal levels.
• When complete compensation does occur, one should look for evidence of complicating metabolic
acidosis.
• HCO3− falls 2 mEq/L for each 10 mmHg fall in pCO2.
• Electrolyte imbalance: hypokalemia

Mixed Acid-Base Disorders

• It refers to a clinical condition in which two or more primary acid-base disorders coexist.
• They generally present with one obvious disturbance with what appears to be an inappropriate (excessive
or inadequate) compensation.
• The “inappropriateness” of the compensatory process is probably the result of a separate primary
disorder.
• When two disorders influence the blood pH in opposite directions, the blood pH will be determined by the
dominant disorder.
• If pCO2 and HCO3− have changed in opposite directions (e.g., pCO2 is high and HCO3 is low, or pCO2 is
low and HCO3 is high), the presence of a mixed acid-base disorder is certain.

Notes To Remember:
• The body's cellular and metabolic activities are pH dependent, thus, during compensation, the body
tries to return the pH toward normal whenever an imbalance occurs.
• After full compensation, pH would return to its normal range.
• After partial compensation, the pH would be near normal.
• The lungs can compensate immediately but the response is short term and incomplete; the kidneys
are slow in its response but long term and complete.
• Base excess is increased in metabolic and respiratory alkalosis and decreased in metabolic and
respiratory acidosis (reference values: -2 to +3 in adult; -4 to +2 among children).
Specimen Collection
Specimen: Arterial blood
Anticoagulant: 0.05 mL heparin/mL of blood
• The best method for blood gas collection in the newborn is by indwelling umbilical artery catheter.
• Syringe and needle for arterial blood collection must be preheparinized by drawing up heparin into the
syringe to wet its interior, excess heparin should be expelled.
• The use of butterfly infusion sets is not recommended.
• The liquid form of heparin is not recommended because excessive amounts can dilute the sample and
possibly contaminate the sample if equilibrated with room air.
• Any air trapped in the syringe during blood collection should be immediately expelled at the completion
of the draw.
• Arterial and venous blood differ in pH, pCO2, and pO2.

Common errors in specimen collection and handling: form and concentration of heparin, speed of syringe
filling, maintenance of anaerobiosis, mixing of samples, collection device, and transport and storage time
before analysis

Common analytical errors: temperature error, and protein coating of electrodes

Specimen Considerations:
1. On standing, pH and pO2 (decreases), and pCO2 (increases) are affected.
2. Blood samples should be chilled to prevent oxygen consumption by the RBC and release of acidic
metabolites, thereby altering the pH.
3. Glycolysis results to a decreased blood pH.
4. Excess heparin causes downward shifting of blood pH – most common pre-analytic error.
5. Lower temperatures cause increased oxygen solubility in blood and a left shift in the oxyhemoglobin
curve resulting in more oxygen combining with hemoglobin.

Quality Control
• The minimum requirement for blood gas quality control is one sample every 8 hours and three levels
(acidosis, normal, alkalosis) of control every 24 hours.
• A single-point calibration is performed between each gas sample to correct electrode and instrument
drift.

Methods:
I. Gasometer II. Electrodes
A. Van Slyke A. pH (potentiometry)
B. Natelson 1. Silver-silver chloride electrode – reference electrode
1. Mercury – to produce vacuum 2. Calomel electrode (Hg2Cl2) – reference electrode
2. Caprylic alcohol – anti-foam 3. Glass electrode – most commonly used for pH
reagent B. pO2 – Clark electrode (polarography-amperometry)
3. Lactic acid C. pCO2 – Severinghaus electrode (potentiometry)
4. NaOH and NaHSO3
• Modern blood gas analyzers routinely contain three electrodes that give very rapid and accurate
results for direct measurement of pH, pCO2, and pO2.
Continuous monitoring for pO2
• This is done by using transcutaneous (TC) electrodes placed directly on the skin of the patient.
• It is commonly used for neonates and infants; a noninvasive procedure.

Factors affecting blood gases and pH measurement:

1. Temperature (37°C ± 0.1°C) – most important factor.
• It is essential that the electrode sample chamber be maintained at constant temperature for all
measurements.
• For each degree of fever in the patient, pO2 will fall by 7% and pCO2 will rise by 3%.
2. Elevated plasma protein concentrations.
• pO2 test is affected by build-up of proteins on the surface of the membrane.
3. Bacterial contamination within the measuring chamber, if present, will consume oxygen and cause low
value of pO2.
4. Improper transport of the blood specimen.
• When blood samples are not transported on ice (during transport to another laboratory), the pO2
changes rapidly than pH and pCO2.
• Samples should be kept at room temperature and analyzed immediately (in less than 30 minutes)
after blood collection.

Notes To Remember:
• Blood gas results are affected by the gas mixture the patient is breathing and by the patient's body
temperature.
• When serum is used to measure total CO2, the dissolved CO2 is insignificant because all CO2 gas
has escaped into the air.
• The total CO2 in arterial blood (plasma or serum) is equal to HCO3− in arterial blood.
• Calculations of base excess uses pH and pCO2 values.
• Blood gas results should be back to the physician preferably within 10 minutes after draw to obtain
maximum benefit from them.
• Total CO2 = 19 – 24 mmol/L (arterial whole blood)
= 22 – 26 mmol/L (venous whole blood)

~nalpas~

Prepared by: Giles D. Dumangeng, RMT