RESPIRATION

• Respiratory system is charged both with

ensuring uptake of adequate oxygen to meet the
metabolic needs of the body’s cells and
disposing of the carbon dioxide produced during
metabolism by these cells.
Oxygen is the final electron acceptor for all the
metabolic processes taking place within the
mitochondria, including fatty acid oxidation, the
citric acid cycle, and the electron transport chain,
the last of which generates adenosine
triphosphate (ATP) for energy needs of the cell.
• In aggregate, these metabolic processes consume a
considerable amount of oxygen. To meet this ceaseless
demand for oxygen, three system must interact in a
seamless manner so that the individual can promptly
adjust to varying metabolic demands. These three
systems are:
1. The lungs and associated muscular pumping
mechanisms which take in oxygen from the air and
exhale carbon dioxude into the atmosphere.
2. The blood and circulatory system with hemoglobin
rich red blood cells that transport O2 and CO2.
3. The nervous system which controls the rhythmic
action of the respiratory system including the lungs,
airways, and muscular bellows in response to the body’s
needs.
• Surfactant and surface tension.
Even though surface tension is crucial to
maintaining the intimacy of two pleural suefaces,
this same physical force could obliterate the
alveolar spaces if there was not some substance
to mitigate alveolar surface tension. Fortunately, a
group of proteins and phospholipid, collectively
referred to as surfactant, decreases the surface
tension in the alveoli, thus maintaning their
patency, much as soap bubbles maintain
themselves.
To prevent alveolar collapse, the alveolar wall
contains a specialized, Type II, pneumocyte,
which is responsible for synthesis and secretion
of surfactant into the extracellular space
interposed between the alveolar air and the
epithelial cell surface.
• Surfactant functions to lower the surface tension
at the gas-liquid interface.
Approximately 90% of the composition of
surfactant is lipid in nature, of which virtually
90% is phospholipid
(dipamitoylphosphatidylcholine [DPPC] which
constitutes 70%-80% of the phospholipid).
By lowering the surface tension, surfactant
prevents alveolar collapse and reduces the effort
to expand the lungs after each expiration.
When, because of prematurity, surfactant is not
manufactured, respiratory distress syndrome
(RDS) of the neonate results. And when in any
age group, sepsis or other serious disease
damage the lung and consequently the
synthesis of surfactant, adult RDS results.
• Physical exchange of gases
The term of this kind of respiration is
applied to the interchange of the 2 gases,
oxygen and CO2, between the body and
its environment.
The atmospheric air which we inhale has
the following composition: oxygen, 20.96%
(PO2: 159 mm Hg) ; CO2, 0.04% (PCO2:
30.4 mm Hg); and nitrogen, 79% (PNO2:
570 mm Hg). Other gases present in trace
amount but are not of physiologic
importance.
• The expired air contains the same amount
of nitrogen as the inspired air; the total
pressure in the alveoli after correction for
the vapor pressure of water (47 mm Hg) is
713 mm Hg. In the alveoli, the oxygen has
been reduced to about 15% (PO2: 107
mm Hg), and the CO2 increased to about
5% (PCO2: 36 mm Hg). About one-fourth
of the oxygen of the inspired air has
passed into the blood and has been
replaced in the expired air by an equal
amount of CO2 which has left the blood
• When the gases of the inspired air come in
contact with the alveolar membrane of the
lung, it is assumed that the exchange of
gases takes place in accordance with the
usual physical laws of diffusion. Thus, the
gas passes through the membrane and
into the blood, or in the reverse direction,
in accordance with the difference in the
pressure of that particular gas on either
side of the membrane.
• The exchange of gases between the alveoli and
the blood is illustrated by the following:
Oxygen tension in alveolar air: 107 mm Hg
Oxygen tension in venous blood: 40 mm Hg
A pressure difference of 67 mm Hg serves to
drive oxygen from the alveoli of the lung into the
blood.
CO2 tension in alveolar air: 36 mm Hg
CO2 tension in venous blood: 46 mm Hg
• A relatively small difference of 10 mm Hg is
sufficient to drive CO2 from the blood into the
lung. This small difference in pressure is
adequate because of the rapidity of the diffusion
of CO2 through the alveolar membrane (the
diffusion coefficient for CO2 is 20 times that of
O2 because CO2 is much more soluble than O2
is).
After this exchange of gases has occured, the
blood becomes arterial (in chemical sense).
Arterial blood has an oxygen tension of about
100 mm Hg and a CO2 tension of 40 mm Hg.
• The transport of oxygen by the blood.
The transport of oxygen by the blood from the
lung to the tissues is due mainly to the ability of
hemoglobin to combine reversibly with oxygen.
Hb + O2 = HbO2
The degree of combination of oxygen with
hemoglobin or its dissociation of oxyhemoglobin
is determined by the tension of the oxygen in the
medium surrounding the hemoglobin.
At a tension of 100 mm Hg or more, hemoglobin
is completely saturated. Under these condition,
approximately 1.34 ml of oxygen are combined
with each gram of hemoglobin.
• Effect of CO2 on blood pH
Although the CO2 evolved from the tissues will
form carbonic acid, very little CO2 can actually
be carried in this form because the effect of
carbonic acid on the pH of the blood. Is is
estimated that in 24 hours the lungs remove the
equivalent of 20-40 liters of 1N acid as carbonic
acid. This large acid load is successfully
transported by the blood with hardly any
variation in the blood pH, since most of the
carbonic acid formed is promptly converted to
bicarbonate.

H2CO3 = H + + HCO3 + B+ = BHCO3 + H+.

• The buffer system of the blood
Although venous blood carried considerably
more CO2 than does arterial blood, the buffers
of the blood are so efficient that the pH of
venous blood is more acid than that of arterial
blood by only 0.01-0.03 units, ie, pH 7.40 vs pH
7,43.
These blood buffers consist of plasma protein,
hemoglobin, and oxyhemoglobin and
bicarbonate and inorganic phosphates.
• The hemoglobin buffers
Hemoglobin acts as a buffer because it carries the basic
amino acid histidine in a number of exposed position.
These histidine residues can combine reversibly with
hydrogen ions, producing protonated and unprotonated
forms of hemoglobin.
Most important, is the unique buffering role of
hemoglobin and oxyhemoglobin, which account for 60%
of the CO2 carrying capacity of whole blood.
The remarkable buffering capacity of hemoglobin is due
to the fact that this protein in the oxy form is a stronger
acid than in the reduced form.
• Bicarbonate distribution between plasma and
erythrocytes.
CO2 reacts with water to form carbonic acid
which undergoes partial dissociation to produce
the conyugate base, bicarbonate. The reaction
CO2 with water to carbonic acid is reversible
and mainly made inside the red blood cell since
the catalyzing enzyme, carbonic anhydrase, is
found within the erythrocyte and other cell types.
Bicarbonate and chloride exchanged freely
across the erythrocyte membrane.
Electrical neutrality must be maintained across
the membrane. Maintenance of this neutrality
can be accomplished by exchange mechanism
between bicarbonate and chloride which is
called chloride shift
• Acid-base balance
The buffers in the blood act in conyunction with
mechanisms in the kidneys for excreting protons as well
as with mechanisms in the lungs for exhaling CO2 to
maintain the pH within the normal range (acid-base
balance).
Although a buffer solution is most effective at mitigating
pH shift when its initial pH (7.35-7.45 in blood) is the
same as its pKa, this limitation for the HCO3-/H2CO3
system, with a pKa of 6,1, is overridden by the body’s
ability to eliminate CO2 via the lungs.
HCO3- and H2CO3 can be conveniently expressed in a
useful form as the familiar Henderson-Hasselbalch
equation:
pH = pKa + log [HCO3-]/{H2CO3]
or
pH = pKa + log (kidney/lungs), where kidney = [HCO3-]
and lungs = [H2CO3]
• Disturbances in acid-base balance
A. Metabolic acidosis
Caused by a decrease in the bicarbonate fraction.
It occurs in uncontrolled diabetes with ketosis, in renal disease, in
diarrhea.
Compensation by lungs (hyperventilation).
B. Respiratory acidosis
Caused by an increase in carbonic acid fraction.
It occurs in any disease which impaired respiration, in morphine
poisoning (depression of the respiratory center).
Compensation by the kidney (increase reabsorption of bicarbonate)
C. Metabolic alkalosis
Caused by an increase in the bicarbonate fraction.
It occurs in prolonged vomiting, after ingestion of large quantities of
alkali, in Cushing syndrome.
Compensation by the lungs (hypoventilation).
D. Respiratory alkalosis
Caused by a decrease in the carbonic acid fraction.
It occurs in hysterical hyperventilation, in the early stages of
salicylate poisoning (stimulate the respiratory center).