OVERVIEW OF ACID-BASE BALANCE

Acid-Base Balance is the balance between the input (intake and production) and output (elimination) of
hydrogen ions. The body's balance between acidity and alkalinity is referred to as acid-base balance.

Blood acidity increases when the level of acidic compounds in the body rises (through increased intake
or production, or decreased elimination) while the level of basic (alkaline) compounds in the body falls
(through decreased intake or production, or increased elimination). Blood alkalinity increases when the
level of acid in the body decreases or when the level of base increases.

To maintain homeostasis, the human body employs many physiological adaptations. One of these is
maintaining an acid-base balance. In the absence of pathological states, the pH of the human body
ranges between 7.35 to 7.45, with the average at 7.40. Why this number? Why not a neutral number of
7.0 instead of a slightly alkaline 7.40? A pH at this level is ideal for many biological processes, one of the
most important being the oxygenation of blood. Also, many of the intermediates of biochemical
reactions in the body become ionized at a neutral pH, which causes the utilization of these
intermediates to be more difficult. A pH below 7.35 is an acidemia, and a pH above 7.45 is an alkalemia.
Due to the importance of sustaining a pH level in the needed narrow range, the human body contains
compensatory mechanisms.

Types of Acid-Base disorders

The human body experiences four main types of acid-based disorders:

i. metabolic acidosis,

ii. metabolic alkalosis,

iii. respiratory acidosis, and

iv. respiratory alkalosis.

If one of these conditions occurs, the human body should induce a counterbalance in the form of an
opposite condition. For example, if a person is experiencing a metabolic acidemia, their body will
attempt to induce a respiratory alkalosis to compensate. It is rare for the compensation to make the pH
completely normal at 7.4.

Metabolic Acidosis

A. Increased Anion Gap Metabolic Acidosis

A primary metabolic acidosis, that is, one which is the primary acid-base disorder, has many causes.
These are separated into those which cause a high anion gap and those that do not. The plasma anion
gap is a way to help clinicians determine the cause of a metabolic acidosis. When there is a metabolic
acidosis present, certain ions in the blood are measured that help determine the etiology of an acidemia.
The anion gap increases whenever bicarbonate is lost due to it combining with a hydrogen ion that was
previously attached to a conjugate base. When bicarbonate combines with a hydrogen ion, the result is
carbonic acid (H2CO3). The conjugate base can be any negatively charged ion that isn’t a bicarbonate or
a chloride.

Humans are electrically neutral, but all cations and anions are not being measured. The normal anion
gap is equal to 8 +/- 4. Most of this number is due to albumin; this anion is not accounted for in the
formula which is a large reason why the gap is not closer to zero. Albumin is normally 4 mg/dL. Because
of the large effect of albumin on anion gap, if a patient’s albumin level is abnormal, their expected anion
gap will not be accurate. This can be corrected using simple math. The normal anion gap and albumin
level differ by a factor of three (normal anion gap of 12, normal albumin of 4 mg/dL). If a patient has an
anion gap of 24, that means there are 12 units of the conjugate base present that normally would not be
due to the combination of hydrogen ions with bicarbonate. If this same patient has an albumin level of
3mg/dL, their expected anion gap should actually be about 9. This means that, rather than 12 units of
the conjugate base present, there are really 15 units.

B. Narrow Anion Gap Metabolic Acidosis

If the acidosis involves a normal anion gap, there is a loss of bicarbonate rather than an increased
amount of hydrogen ions, with a concomitant increase in chloride ions. To keep a physiological neutral
state, chloride ions migrate out of the cells and into the extracellular space. This causes the patient’s
serum chloride to increase and keeps the anion gap at a normal level. This means that a metabolic
acidosis without an abnormal anion gap is also a hyperchloremic metabolic acidosis. A metabolic
acidosis without an increased anion gap results from many processes including severe diarrhea, type I
renal tubular acidosis (RTA), long-term use of carbonic anhydrase inhibitors, and suctioning of gastric
contents. When a patient has a narrow ion gap hyperchloremic acidosis, the provider can calculate the
urine anion gap (UAG) to help determine etiology.

Respiratory Acidosis

During exhalation, carbon dioxide produced by cellular respiration is projected into the environment. In
the human body, carbon dioxide combines with water via carbonic anhydrase and forms carbonic acid
which dissociates into a hydrogen ion and bicarbonate. This is why a reduced respiratory rate will lead to
a decreased pH; the more carbon dioxide is exhaled, the less carbon dioxide present for this reaction.
Respiratory acidosis as a primary disorder is often caused by hypoventilation. This can be due to
multiple causes including chronic obstructive pulmonary disease, opiate abuse/overdose, severe obesity,
and brain injury. When respiratory acidosis occurs, the metabolic response should be to increase the
amount of bicarbonate via the renal system. This does not always occur, and renal pathology can easily
hinder the appropriate physiological response, leading to increased danger for the patient.

Metabolic Alkalosis

Metabolic alkalosis also can be divided into two main categories that help ascertain the cause: chloride
responsive vs. non-chloride responsive. In non-chloride-responsive metabolic alkalosis, the urine
chloride is < 20 mEq/L. Some causes include vomiting, hypovolemia, and diuretic use.

Respiratory Alkalosis

Any pathology that leads to the increased expiration of carbon dioxide can result in respiratory alkalosis.
When excess CO2 is expired, the pH of the human body is increased due to less carbonic acid being
created. Physiologically, the appropriate compensation is a decreased amount of bicarbonate being
created by the renal system. Some causes of respiratory alkalosis include panic attacks with
hyperventilation, pulmonary embolism, pneumonia, and salicylate intoxication.

Control of Acid-Base Balance

A basic comprehension of respiration at the cellular level is important in understanding acid-base

equilibrium in the human body. Aerobic cellular respiration is necessary for human life; humans are
obligate aerobes. While individual cells can perform anaerobic respiration, in order to sustain life,
oxygen must be present. One of the byproducts of aerobic cellular respiration is carbon dioxide. The
simplified chemical equation denoting aerobic cellular respiration is:

C6H12O6 (glucose) + 6O2 --> 6CO2 + 6H20 + energy (38 ATP molecules and heat)

As noted above, carbon dioxide is produced as a byproduct of the TCA cycle. This carbon dioxide is
instrumental to acid-base balance in the body which is demonstrated with the following reaction:

CO2 + H20 <-> H2C03 <-> HCO3- + H+

The blood's acid-base balance is precisely controlled because even a minor deviation from the normal
range can severely affect many organs. The body uses different mechanisms to control the blood's acid-
base balance. These mechanisms involve the

1. Lungs

2. Kidneys
 3. Buffer systems

Role of the lungs

One mechanism the body uses to control blood pH involves the release of carbon dioxide from the lungs.
Carbon dioxide, which is mildly acidic, is a waste product of the processing (metabolism) of oxygen and
nutrients (which all cells need) and, as such, is constantly produced by cells. It then passes from the cells
into the blood. The blood carries carbon dioxide to the lungs, where it is exhaled. As carbon dioxide
accumulates in the blood, the pH of the blood decreases (acidity increases). The brain regulates the
amount of carbon dioxide that is exhaled by controlling the speed and depth of breathing (ventilation).
The amount of carbon dioxide exhaled, and consequently the pH of the blood, increases as breathing
becomes faster and deeper. By adjusting the speed and depth of breathing, the brain and lungs are able
to regulate the blood pH minute by minute. When the respiratory system is utilized to compensate for
metabolic pH disturbances, the effect occurs in minutes to hours.

Role of the kidneys

The renal system affects pH by reabsorbing bicarbonate and excreting fixed acids. Whether due to
pathology or necessary compensation, the kidney excretes or reabsorbs these substances which affect
pH. The nephron is the functional unit of the kidney. Blood vessels called glomeruli transport substances
found in the blood to the renal tubules so that some can be filtered out while others are reabsorbed into
the blood and recycled. This is true for hydrogen ions and bicarbonate. If bicarbonate is reabsorbed
and/or acid is secreted into the urine, the pH becomes more alkaline (increases). When bicarbonate is
not reabsorbed or acid is not excreted into the urine, pH becomes more acidic (decreases). The
metabolic compensation from the renal system takes longer to occur: days rather than minutes or hours.

Role of the buffer systems

The carbon dioxide formed during cellular respiration combines with water to create carbonic acid.
Carbonic acid then dissociates into bicarbonate and a hydrogen ion. This reaction is one of the many
buffer systems in the human body; it resists dramatic changes in pH to allow a person to remain within
the narrow physiological pH range. This buffer system is in equilibrium, that is, all components of the
reaction exist throughout the body and are shifted to the side of the equation appropriate for the
environment. This reaction can and does occur without an enzyme; however, carbonic anhydrase is an
enzyme that assists with this process. It catalyzes the first reaction above to form carbonic acid which
can then freely dissociate into bicarbonate and a hydrogen ion. Carbonic anhydrase is located in red
blood cells, renal tubules, gastric mucosa, and pancreatic cells.
Other buffer systems in the human body include the phosphate buffer system, proteins, and
hemoglobin. All of these contain bases which accept hydrogen ions which keep the pH from plummeting.
The phosphate buffer system, while present globally, is important for the regulation of urine pH.
Proteins assist with intracellular pH regulation. Red blood cells use the reaction above to help
hemoglobin buffer; carbon dioxide can diffuse across red blood cells and combine with water. This alone
would cause an increase in hydrogen ions; however, hemoglobin can bind hydrogen ions. Hemoglobin
also can bind carbon dioxide without this reaction. This depends on the amount of oxygen that is bound
to hemoglobin. This is called the Haldane effect and the Bohr effect. When hemoglobin is saturated with
oxygen, it has a lower affinity for CO2 and hydrogen ions and is able to release it.

Compensation for acid-base disorders

Each acid-base disturbance provokes automatic compensatory mechanisms that push the blood pH back
toward normal. In general, the respiratory system compensates for metabolic disturbances while
metabolic mechanisms compensate for respiratory disturbances. At first, the compensatory mechanisms
may restore the pH close to normal. Thus, if the blood pH has changed significantly, it means that the
body's ability to compensate is failing. In such cases, doctors urgently search for and treat the underlying
cause of the acid-base disturbance.

Function of maintaining pH

The physiological pH of the human body is essential for many processes necessary to life including
oxygen delivery to tissues, correct protein structure, and innumerable biochemical reactions that rely on
the normal pH to be in equilibrium and complete.

1. Oxygen Delivery to Tissues

The oxygen dissociation curve is a graph depicting the relationship of the partial pressure of oxygen to
the saturation of hemoglobin. This curve relates to the ability of hemoglobin to deliver oxygen to tissues.
If the curve is shifted to the left, there is a decreased p50, meaning that the amount of oxygen needed
to saturate hemoglobin 50% is lessened and that there is an increased affinity of hemoglobin for oxygen.
A pH in the alkalotic range induces this left shift. When there is a decrease in pH, the curve is shifted to
the right, denoting a decreased affinity of hemoglobin for oxygen.

2. Protein Structure

It would be hard to overstate the importance of proteins in the human body. They makeup ion channels,
carry necessary lipophilic substances throughout our mostly lipophobic body, and participate in
innumerable biological processes. For proteins to complete necessary functions, they must be in the
proper configuration. The charges on proteins are what allow their proper shape to exist. When pH is
altered outside of the physiological range, these charges are altered. The proteins are denatured leading
to detrimental changes in architecture that cause a loss of proper function.

3. Biochemical Processes

Throughout the human body, many chemical reactions are in equilibrium. One of the most important
was previously mentioned with the equation:

H20 + CO2 <-> H2CO3<-> H+ + HCO3-

The Le Chatelier Principle states that when the variables of concentration, pressure, or temperature are
changed, a system in equilibrium will react accordingly to restore a new steady state. For the reaction
above, this states that if more hydrogen ions are produced, the equation will shift to the left so that
more reactants are formed, and the system can remain in equilibrium. This is how compensatory pH
mechanisms work; if there is a metabolic acidosis present, the kidneys are not excreting enough
hydrogen ions and/or not reabsorbing enough bicarbonate. The respiratory system reacts by increasing
minute ventilation (often by increasing respiratory rate) and expiring more CO2 to restore equilibrium.