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 surfaces, 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.

The transport of CO2 in the blood

CO2 is carried by the blood both in the cells and in the plasma. The CO2 content of the arterial blood
is 50-53 vol%, and in venous blood it is 54-60 vol%.
The large majority of blood CO2 is not physically dissolved in the plasma but exist 3 main fractions:
- small amount of carbonic acid;
- the carbamino bound CO2, which is tranported in combination with protein (mainly hemoglobin)
- as bicarbonate in combination with the cations sodium or potassium.

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.
It 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).
Compensation by the kidney (decrease reabsorption of bicarbonate).
In the advanced stages of salicylate poisoning resulting metabolic acidosis because of renal failure
(salicylate in high dosis damage the kidney).