Chloride, Bicarbonate and

Lactate
Francis Ian L. Salaver, RMT, MD
 Chloride
• Major Extracellular Anion
• Functions:
• Maintains blood osmolality
• Maintains blood volume
• Maintains electroneutrality

• Chloride shifts secondary to

the movement of sodium and
bicarbonate
 Chloride
• Chloride in the diet is directly
absorbed in the intestine

• Freely filtered and passively

reabsorbed in the Proximal
convoluted tubule
 Chloride
• Excessive sweating causes loss
of Na and Cl

• Excessive sweating stimulates

aldosterone secretion, which
acts on the sweat glands to
conserve Na and Cl
 Chloride
• Chloride maintains electroneutrality
in two ways:

• (1) Na is reabsorbed along with Cl in

the proximal tubules. In effect, Cl
acts as the rate-limiting component,
in that Na reabsorption is limited by
the amount of Cl available.
 Chloride
• Chloride maintains electroneutrality
in two ways:

• (2) Electroneutrality is also

maintained by Cl through the chloride
shift.
• In this process, carbon dioxide (CO2)
generated by cellular metabolism within
the tissue diffuses out into both the
plasma and the red cell.
 Chloride
• Chloride maintains electroneutrality in
two ways:

• (2) Electroneutrality is also maintained

by Cl through the chloride shift.
• In the red cell, CO forms carbonic acid
2

(H2CO3), which splits into H and HCO3

(bicarbonate).

• Deoxyhemoglobin buffers H , whereas the

HCO3 diffuses out into the plasma and Cl
diffuses into the red cell to maintain the
electric balance of the cell
 Clinical application
• Cl disorders are often a result of the
same causes that disturb Na levels
because Cl passively follows Na.
There are a few exceptions.

• Hyperchloremia can occur when

there is an excess loss of HCO3 as a
result of GIT losses, RTA, or metabolic
acidosis
 Clinical application
• Hypochloremia may occur with
excessive loss of Cl from prolonged
vomiting, diabetic ketoacidosis,
aldosterone deficiency, or salt-losing
renal diseases such as pyelonephritis.

• A low serum level of Cl may also be

encountered in conditions associated
with high serum HCO3 concentrations,
such as compensated respiratory
acidosis or metabolic alkalosis.
 Specimen
• Serum or plasma may be used, with lithium heparin being the
anticoagulant of choice.

• Hemolysis does not cause a significant change in serum or plasma

values as a result of decreased levels of intracellular Cl
• However, with marked hemolysis, levels may be decreased as a result of a
dilutional effect.
 Specimen
• Serum or plasma may be used, with lithium heparin being the
anticoagulant of choice.

• Hemolysis does not cause a significant change in serum or plasma

values as a result of decreased levels of intracellular Cl
• However, with marked hemolysis, levels may be decreased as a result of a
dilutional effect.

• The specimen of choice in urine Cl analyses is 24-hour collection

because of the large diurnal variation. Sweat is also suitable for
analysis
 Method of Determination
• Ion-Selective Electrode
• Amperometric-Coulometric Determination
• Mercurometric Method
• Colorimetric Method
 Bicarbonate
• HCO3 is the major component of the
buffering system in the blood.

• Carbonic anhydrase in RBCs converts

CO2 and H2O to carbonic acid, which
dissociates into H and HCO3.

• HCO3 diffuses out of the cell in

exchange for Cl to maintain ionic
charge neutrality within the cell
(chloride shift)
 Bicarbonate
• Bicarbonate is the second most
abundant anion in the ECF.

• Total CO2 comprises the bicarbonate

ion(HCO3), carbonic acid (H2CO3), and
dissolved CO2 , with HCO3 accounting
for more than 90% of the total CO2 at
physiologic pH.
• Because HCO composes the largest fraction
of total CO2, total CO2 measurement is
3

indicative of HCO3 measurement

 Bicarbonate
• This process converts potentially
toxic CO2 in the plasma to an
effective buffer: HCO3.

• HCO3 buffers excess H by combining

with acid, then eventually
dissociating into H2O and CO2 in the
lungs where the acidic gas CO2 is
eliminated.
 Regulation
• Most of the HCO3 in the kidneys (85%) is
reabsorbed by the proximal tubules, with
15% being reabsorbed by the distal
tubules.

• Because tubules are only slightly

permeable to HCO3, it is usually
reabsorbed as CO .

• This happens as HCO3, after filtering into

the tubules, combines with H to form
carbonic acid, which then dissociates into
H2O and CO2.
 Regulation
• The CO2 readily diffuses back into the
ECF. Normally, nearly all the HCO3 is
reabsorbed from the tubules, with little
lost in the urine.

• When HCO3 is filtered in excess of H

available, almost all excess HCO3 flows
into the urine
 Regulation
• In alkalosis, with a relative increase in
HCO3, compared to CO2, the kidneys
increase excretion of HCO3. This loss of
HCO3 from the body helps correct pH.

• Among the responses of the body to

acidosis is an increased excretion of H
into the urine.
• In addition, HCO3 reabsorption is virtually
complete, with 90% of the filtered HCO3
reabsorbed in the proximal tubule and the
remainder in the distal tubule
 Clinical Applications
• Acid-base imbalances cause changes in HCO3 and CO2levels.

• A decreased HCO3 may occur from metabolic acidosis as HCO3 combines

with H to produce CO2 , which is exhaled by the lungs.
• The typical response to metabolic acidosis is compensation by hyperventilation,
which lowers pCO2.

• Elevated total CO2 concentrations occur in metabolic alkalosis as HCO3 is

retained, often with increased pCO2 as a result of compensation by
hypoventilation.
• Typical causes of metabolic alkalosis include severe vomiting, hypokalemia, and
excessive alkali intake.
 Specimen
• Serum or lithium heparin plasma is suitable for analysis. Although
specimens should be anaerobic for the highest accuracy, many
current analyzers (excluding blood gas analyzers) do not permit
anaerobic sample handling.

• In most instances, the sample is capped until the serum or plasma is

separated and the sample is analyzed immediately.
 Method of Determination
• Carbon dioxide measurements may be obtained in several ways;
however, the actual portion of the total CO2 being measured may
vary with the method used.

• Ion-selective electrode
• Enzymatic method
Enzymatic Method
 Lactate
• By-product of an emergency mechanism that
produces a small amount of ATP when oxygen
delivery is severely diminished.

• Pyruvate is the normal end product of glucose

metabolism (glycolysis).

• The conversion of pyruvate to lactate is activated

when a deficiency of oxygen leads to an
accumulation of excess NADH
 Lactate
• By-product of an emergency mechanism that
produces a small amount of ATP when oxygen
delivery is severely diminished.

• Pyruvate is the normal end product of glucose

metabolism (glycolysis).

• The conversion of pyruvate to lactate is activated

when a deficiency of oxygen leads to an
accumulation of excess NADH
 Lactate
• Normally, sufficient oxygen maintains a
favorably high ratio of NAD to NADH.

• Under these conditions, pyruvate is converted

to acetyl-coenzyme A (CoA), which enters the
citric acid cycle and produces 38 moles of ATP
for each mole of glucose molecule
 Lactate
• However, under hypoxic conditions, acetyl-CoA formation does not occur
and NADH accumulates, favoring the conversion of pyruvate to lactate
through anaerobic metabolism.

• As a result, only 2 moles of ATP are produced for each mole of glucose
metabolized to lactate, with the excess lactate released into the blood.

• This release of lactate into blood has clinical importance because the
accumulation of excess lactate in blood is an early, sensitive, and
quantitative indicator of the severity of oxygen deprivation
 Regulation
• Because lactate is a by product of anaerobic metabolism, it is not
specifically regulated.

• As oxygen delivery decreases below a critical level, blood lactate

concentrations rise rapidly and indicate tissue hypoxia earlier than pH.

• The liver is the major organ for removing lactate by converting lactate back
to glucose by a process called gluconeogenesis.
 Clinical importance
• Measurements of blood lactate are useful for metabolic monitoring in
critically ill patients, for indicating the severity of the illness, and for
determining patient prognosis.

• There are two types of lactic acidosis.

• Type A is associated with hypoxic conditions, such as shock, myocar- dial
infarction, severe congestive heart failure, pulmonary edema, or severe blood
loss.
 Clinical importance
• Measurements of blood lactate are useful for metabolic monitoring in
critically ill patients, for indicating the severity of the illness, and for
determining patient prognosis.

• There are two types of lactic acidosis.

• Type B is of metabolic origin, such as with diabetes mellitus, severe infection,
leukemia, liver or renal disease, and toxins (ethanol, methanol, or salicylate
poisoning).
 Specimen Processing
• Special care should be practiced when collecting and handling
specimens for lactate analysis.

• Ideally, a tourniquet should be not be used because venous stasis will

increase lactate levels. If a tourniquet is used, blood should be
collected immediately and the patient should not exercise the hand
before and during blood collection
 Specimen Processing
• After specimen collection, glucose is converted to lactose by way of
anaerobic glycolysis and should be prevented.

• Heparinized blood may be used but must be delivered on ice and the
plasma must be quickly separated.