ACID-BASE BALANCE

Learning Objectives

By the end of this section, you will be able to:

 Identify the most powerful buffer system in the body

 Explain the way in which the respiratory system affects blood pH

Proper physiological functioning depends on a very tight balance between the

concentrations of acids and bases in the blood. Acid-balance balance is measured
using the pH scale, as shown in Figure 1. A variety of buffering systems permits
blood and other bodily fluids to maintain a narrow pH range, even in the face of
perturbations. A buffer is a chemical system that prevents a radical change in fluid
pH by dampening the change in hydrogen ion concentrations in the case of excess
acid or base. Most commonly, the substance that absorbs the ions is either a weak
acid, which takes up hydroxyl ions, or a weak base, which takes up hydrogen ions.
 Figure 1. The pH
Scale. This chart shows where many common substances fall on the pH scale.
BUFFER SYSTEMS IN THE BODY
The buffer systems in the human body are extremely efficient, and different
systems work at different rates. It takes only seconds for the chemical buffers in
the blood to make adjustments to pH. The respiratory tract can adjust the blood pH
upward in minutes by exhaling CO2 from the body. The renal system can also
adjust blood pH through the excretion of hydrogen ions (H +) and the conservation
of bicarbonate, but this process takes hours to days to have an effect.
The buffer systems functioning in blood plasma include plasma proteins,
phosphate, and bicarbonate and carbonic acid buffers. The kidneys help control
acid-base balance by excreting hydrogen ions and generating bicarbonate that helps
maintain blood plasma pH within a normal range. Protein buffer systems work
predominantly inside cells.

PROTEIN BUFFERS IN BLOOD PLASMA AND

CELLS
Nearly all proteins can function as buffers. Proteins are made up of amino acids,
which contain positively charged amino groups and negatively charged carboxyl
groups. The charged regions of these molecules can bind hydrogen and hydroxyl
ions, and thus function as buffers. Buffering by proteins accounts for two-thirds of
the buffering power of the blood and most of the buffering within cells.

HEMOGLOBIN AS A BUFFER
Hemoglobin is the principal protein inside of red blood cells and accounts for one-
third of the mass of the cell. During the conversion of CO 2 into bicarbonate,
hydrogen ions liberated in the reaction are buffered by hemoglobin, which is
reduced by the dissociation of oxygen. This buffering helps maintain normal pH.
The process is reversed in the pulmonary capillaries to re-form CO 2, which then
can diffuse into the air sacs to be exhaled into the atmosphere. This process is
discussed in detail in the chapter on the respiratory system.

PHOSPHATE BUFFER
Phosphates are found in the blood in two forms: sodium dihydrogen phosphate
(Na2H2PO4−), which is a weak acid, and sodium monohydrogen phosphate
(Na2HPO42-), which is a weak base. When Na2HPO42- comes into contact with a
strong acid, such as HCl, the base picks up a second hydrogen ion to form the
weak acid Na2H2PO4− and sodium chloride, NaCl. When Na2HPO42− (the weak
acid) comes into contact with a strong base, such as sodium hydroxide (NaOH), the
weak acid reverts back to the weak base and produces water. Acids and bases are
still present, but they hold onto the ions.

HCl + Na2HPO4→NaH2PO4 + NaCl
(strong acid) + (weak base) → (weak acid) + (salt)
NaOH + NaH2PO4→Na2HPO4 + H2O
(strong base) + (weak acid) → (weak base) + (water)
BICARBONATE-CARBONIC ACID BUFFER
The bicarbonate-carbonic acid buffer works in a fashion similar to phosphate
buffers. The bicarbonate is regulated in the blood by sodium, as are the phosphate
ions. When sodium bicarbonate (NaHCO 3), comes into contact with a strong acid,
such as HCl, carbonic acid (H2CO3), which is a weak acid, and NaCl are formed.
When carbonic acid comes into contact with a strong base, such as NaOH,
bicarbonate and water are formed.

NaHCO3 + HCl →  H2CO3+NaCl
(sodium bicarbonate) + (strong acid) → (weak acid) + (salt)
H2CO3 + NaOH→HCO3- + H2O
(weak acid) + (strong base)→(bicarbonate) + (water)

As with the phosphate buffer, a weak acid or weak base captures the free ions, and
a significant change in pH is prevented. Bicarbonate ions and carbonic acid are
present in the blood in a 20:1 ratio if the blood pH is within the normal range. With
20 times more bicarbonate than carbonic acid, this capture system is most efficient
at buffering changes that would make the blood more acidic. This is useful because
most of the body’s metabolic wastes, such as lactic acid and ketones, are acids.
Carbonic acid levels in the blood are controlled by the expiration of CO 2 through
the lungs. In red blood cells, carbonic anhydrase forces the dissociation of the acid,
rendering the blood less acidic. Because of this acid dissociation, CO 2 is exhaled
(see equations above). The level of bicarbonate in the blood is controlled through
the renal system, where bicarbonate ions in the renal filtrate are conserved and
passed back into the blood. However, the bicarbonate buffer is the primary
buffering system of the IF surrounding the cells in tissues throughout the body.

RESPIRATORY REGULATION OF ACID-

BASE BALANCE
The respiratory system contributes to the balance of acids and bases in the body by
regulating the blood levels of carbonic acid (Figure 2). CO2 in the blood readily
reacts with water to form carbonic acid, and the levels of CO 2 and carbonic acid in
the blood are in equilibrium. When the CO2 level in the blood rises (as it does when
you hold your breath), the excess CO2 reacts with water to form additional carbonic
acid, lowering blood pH. Increasing the rate and/or depth of respiration (which you
might feel the “urge” to do after holding your breath) allows you to exhale more
CO2. The loss of CO2 from the body reduces blood levels of carbonic acid and
thereby adjusts the pH upward, toward normal levels. As you might have surmised,
this process also works in the opposite direction. Excessive deep and rapid
breathing (as in hyperventilation) rids the blood of CO 2 and reduces the level of
carbonic acid, making the blood too alkaline. This brief alkalosis can be remedied
by rebreathing air that has been exhaled into a paper bag. Rebreathing exhaled air
will rapidly bring blood pH down toward normal.
Figure 2. Respiratory
Regulation of Blood pH. The respiratory system can reduce blood pH by removing
CO2 from the blood.

The chemical reactions that regulate the levels of CO 2 and carbonic acid occur in
the lungs when blood travels through the lung’s pulmonary capillaries. Minor
adjustments in breathing are usually sufficient to adjust the pH of the blood by
changing how much CO2 is exhaled. In fact, doubling the respiratory rate for less
than 1 minute, removing “extra” CO2, would increase the blood pH by 0.2. This
situation is common if you are exercising strenuously over a period of time. To
keep up the necessary energy production, you would produce excess CO 2 (and
lactic acid if exercising beyond your aerobic threshold). In order to balance the
increased acid production, the respiration rate goes up to remove the CO 2. This
helps to keep you from developing acidosis.

The body regulates the respiratory rate by the use of chemoreceptors, which
primarily use CO2 as a signal. Peripheral blood sensors are found in the walls of the
aorta and carotid arteries. These sensors signal the brain to provide immediate
adjustments to the respiratory rate if CO2 levels rise or fall. Yet other sensors are
found in the brain itself. Changes in the pH of CSF affect the respiratory center in
the medulla oblongata, which can directly modulate breathing rate to bring the pH
back into the normal range.

Hypercapnia, or abnormally elevated blood levels of CO 2, occurs in any situation

that impairs respiratory functions, including pneumonia and congestive heart
failure. Reduced breathing (hypoventilation) due to drugs such as morphine,
barbiturates, or ethanol (or even just holding one’s breath) can also result in
hypercapnia. Hypocapnia, or abnormally low blood levels of CO 2, occurs with any
cause of hyperventilation that drives off the CO 2, such as salicylate toxicity,
elevated room temperatures, fever, or hysteria.

RENAL REGULATION OF ACID-BASE

BALANCE
The renal regulation of the body’s acid-base balance addresses the metabolic
component of the buffering system. Whereas the respiratory system (together with
breathing centers in the brain) controls the blood levels of carbonic acid by
controlling the exhalation of CO2, the renal system controls the blood levels of
bicarbonate. A decrease of blood bicarbonate can result from the inhibition of
carbonic anhydrase by certain diuretics or from excessive bicarbonate loss due to
diarrhea. Blood bicarbonate levels are also typically lower in people who have
Addison’s disease (chronic adrenal insufficiency), in which aldosterone levels are
reduced, and in people who have renal damage, such as chronic nephritis. Finally,
low bicarbonate blood levels can result from elevated levels of ketones (common
in unmanaged diabetes mellitus), which bind bicarbonate in the filtrate and prevent
its conservation.

Bicarbonate ions, HCO3–, found in the filtrate, are essential to the bicarbonate
buffer system, yet the cells of the tubule are not permeable to bicarbonate ions. The
steps involved in supplying bicarbonate ions to the system are seen in Figure 3 and
are summarized below:

 Step 1: Sodium ions are reabsorbed from the filtrate in exchange for H + by
an antiport mechanism in the apical membranes of cells lining the renal
tubule.
 Step 2: The cells produce bicarbonate ions that can be shunted to peritubular
capillaries.
 Step 3: When CO2 is available, the reaction is driven to the formation of
carbonic acid, which dissociates to form a bicarbonate ion and a hydrogen
ion.
 Step 4: The bicarbonate ion passes into the peritubular capillaries and
returns to the blood. The hydrogen ion is secreted into the filtrate, where it
can become part of new water molecules and be reabsorbed as such, or
removed in the urine.
Figure 3. Conservation of Bicarbonate in the Kidney. Tubular cells are not
permeable to bicarbonate; thus, bicarbonate is conserved rather than reabsorbed.
Steps 1 and 2 of bicarbonate conservation are indicated.

It is also possible that salts in the filtrate, such as sulfates, phosphates, or ammonia,
will capture hydrogen ions. If this occurs, the hydrogen ions will not be available
to combine with bicarbonate ions and produce CO 2. In such cases, bicarbonate ions
are not conserved from the filtrate to the blood, which will also contribute to a pH
imbalance and acidosis.

The hydrogen ions also compete with potassium to exchange with sodium in the
renal tubules. If more potassium is present than normal, potassium, rather than the
hydrogen ions, will be exchanged, and increased potassium enters the filtrate.
When this occurs, fewer hydrogen ions in the filtrate participate in the conversion
of bicarbonate into CO2 and less bicarbonate is conserved. If there is less
potassium, more hydrogen ions enter the filtrate to be exchanged with sodium and
more bicarbonate is conserved.

Chloride ions are important in neutralizing positive ion charges in the body. If
chloride is lost, the body uses bicarbonate ions in place of the lost chloride ions.
Thus, lost chloride results in an increased reabsorption of bicarbonate by the renal
system.

Disorders of the…

Acid-Base Balance: KetoacidosisDiabetic acidosis, or ketoacidosis, occurs most

frequently in people with poorly controlled diabetes mellitus. When certain tissues
in the body cannot get adequate amounts of glucose, they depend on the
breakdown of fatty acids for energy. When acetyl groups break off the fatty acid
chains, the acetyl groups then non-enzymatically combine to form ketone bodies,
acetoacetic acid, beta-hydroxybutyric acid, and acetone, all of which increase the
acidity of the blood. In this condition, the brain isn’t supplied with enough of its
fuel—glucose—to produce all of the ATP it requires to function.

Ketoacidosis can be severe and, if not detected and treated properly, can lead to
diabetic coma, which can be fatal. A common early symptom of ketoacidosis is
deep, rapid breathing as the body attempts to drive off CO 2 and compensate for the
acidosis. Another common symptom is fruity-smelling breath, due to the
exhalation of acetone. Other symptoms include dry skin and mouth, a flushed face,
nausea, vomiting, and stomach pain. Treatment for diabetic coma is ingestion or
injection of sugar; its prevention is the proper daily administration of insulin.

A person who is diabetic and uses insulin can initiate ketoacidosis if a dose of
insulin is missed. Among people with type 2 diabetes, those of Hispanic and
African-American descent are more likely to go into ketoacidosis than those of
other ethnic backgrounds, although the reason for this is unknown.

CHAPTER REVIEW
A variety of buffering systems exist in the body that helps maintain the pH of the
blood and other fluids within a narrow range—between pH 7.35 and 7.45. A buffer
is a substance that prevents a radical change in fluid pH by absorbing excess
hydrogen or hydroxyl ions. Most commonly, the substance that absorbs the ion is
either a weak acid, which takes up a hydroxyl ion (OH –), or a weak base, which
takes up a hydrogen ion (H+). Several substances serve as buffers in the body,
including cell and plasma proteins, hemoglobin, phosphates, bicarbonate ions, and
carbonic acid. The bicarbonate buffer is the primary buffering system of the IF
surrounding the cells in tissues throughout the body. The respiratory and renal
systems also play major roles in acid-base homeostasis by removing CO 2 and
hydrogen ions, respectively, from the body.