Introduction

Respiratory gases—oxygen and carbon dioxide—move between the air and the blood across the
respiratory exchange surfaces in the lungs. The structure of the human lung provides an immense
internal surface that facilitates gas exchange between the alveoli and the blood in the
pulmonary capillaries. The area of the alveolar surface in the adult human is about 50–100 square
metres. Gas exchange across the membranous barrier between the alveoli and capillaries
is enhanced by the thin nature of the membrane, about 0.5 μm, or 1/100 of the diameter of a
human hair. Respiratory gases move between the environment and the respiring tissues by two
principal mechanisms, convection and diffusion. Convection, or mass flow, is responsible for
movement of air from the environment into the lungs and for movement of blood between the lungs
and the tissues. Respiratory gases also move by diffusion across tissue barriers such as membranes.
Diffusion is the primary mode of transport of gases between air and blood in the lungs and between
blood and respiring tissues in the body. The process of diffusion is driven by the difference in partial
pressures of a gas between two locales. In a mixture of gases, the partial pressure of each gas is
directly proportional to its concentration. The partial pressure of a gas in fluid is a measure of its
tendency to leave the fluid when exposed to a gas or fluid that does not contain that gas. A gas will
diffuse from an area of greater partial pressure to an area of lower partial pressure regardless of the
distribution of the partial pressures of other gases. There are large changes in the partial pressures of
oxygen and carbon dioxide as these gases move between air and the respiring tissues. The partial
pressure of carbon dioxide in this pathway is lower than the partial pressure of oxygen, due to
differing modes of transport in the blood, but almost equal quantities of the two gases are involved
in metabolism and gas exchange.
External Respiration
External respiration is the formal term for gas exchange. It describes both the bulk flow of air into
and out of the lungs and the transfer of oxygen and carbon dioxide into the bloodstream through
diffusion. While the bulk flow of air from the external environment happens due to pressure changes
in the lungs, the mechanisms of alveolar gas exchange are more complicated. The primary three
components of external respiration are the surface area of the alveolar membrane, the partial pressure
gradients of the gasses, and the matching of perfusion and ventilation.
Surface Area
The alveoli have a very high surface area to volume ratio that allows for efficient gas exchange. The
alveoli are covered with a high density of capillaries that provide many sites for gas exchange.
The walls of the alveolar membrane are thin and covered with a fluid, extra-cellular matrix that
provides a surface for gas molecules in the air of the lungs to diffuse into, from which they can then
diffuse into the capillaries.
Partial Pressure Gradients
Partial pressure gradients (differences in partial pressure) allow the loading of oxygen into the
bloodstream and the unloading of carbon dioxide out of the bloodstream. These two processes occur
at the same time.

Oxygen has a partial pressure gradient of about 60 mmHg (100 mmHg in alveolar air and 40 mmHg
in deoxygenated blood ) and diffuses rapidly from the alveolar air into the capillary.
Equilibrium between the alveolar air and capillaries is reached quickly, within the first third of the
length of the capillary within a third of a second. The partial pressure of oxygen in the oxygenated
blood of the capillary after oxygen loading is about 100 mmHg.
The process is similar in carbon dioxide. The partial pressure gradient for carbon dioxide is much
smaller compared to oxygen, being only 5 mmHg (45 mmHg in deoxygenated blood and 40 mmHg
in alveolar air).
Based on Henry’s law, the greater solubility of carbon dioxide in blood compared to oxygen means
that diffusion will still occur very rapidly despite the lower partial pressure gradient. Equilibrium
between the alveolar air and the capillaries for carbon dioxide is reached within the first half of the
length of the capillaries within half a second. The partial pressure of carbon dioxide in the blood
leaving the capillaries is 40 mmHg.
Ventilation and Perfusion Matching
The exchange of gas and blood supply to the lungs must be balanced in order to facilitate efficient
external respiration. While a severe ventilation–perfusion mismatch indicates severe lung disease,
minor imbalances can be corrected by maintaining air flow that is proportional to capillary blood
flow, which maintains the balance of ventilation and perfusion.
Perfusion in the capillaries adjusts to changes in PAO2. Constriction in the airways (such as from the
bronchospasms in an asthma attack) lead to decreased PAO2 because the flow of air into the lungs is
slowed.In response, the arteries being supplied by the constricted airway undergo vasocontriction,
reducing the flow of blood into those alveoli so that the perfusion doesn’t become much greater
relative to the decreased ventilation (a type of ventilation–perfusion mismatch called a shunt).
Alternatively, breathing in higher concentrations of oxygen from an oxygen tank will cause
vasodilation and increased blood perfusion in the capillaries.
Ventilation adjusts from changes in PACO2. When airflow becomes higher relative to perfusion,
PACO2 decreases, so the bronchioles will constrict in order to maintain to the balance between
airflow (ventilation) and perfusion. When airflow is reduced, PACO2 increases, so the bronchioles
will dilate in order to maintain the balance.
Principle of pulmonary gas exchange
Based on the above, pulmonary gas exchange is considered as a continuous process involving: 1)
ventilation, 2) diffusion (including both physical diffusion across the pulmonary blood:gas barrier
and subsequent chemical reactions (between O2 and haemoglobin (Hb) and for CO2 conversion to
bicarbonate), and 3) perfusion. The fundamental principle that brings these three separate physical
processes together quantitatively is conservation of mass. All that this means is that within the lungs,
every O2 molecule that is inhaled but not exhaled diffuses from alveolar gas to blood and can be
found in that blood.

Internal Respiration
Cellular respiration is the metabolic process by which an organism obtains energy through the
reaction of oxygen with glucose.
Internal respiration refers to two distinct processes. The first is the exchange of gasses between the
bloodstream and the tissues. The second is the process of cellular respiration, from which cells utilize
oxygen to perform basic metabolic functions.
Gas Exchange with Tissues
Gas exchange occurs in the alveoli so that oxygen is loaded into the bloodstream and carbon dioxide
is unloaded from the bloodstream. Afterwards, oxygen is brought to the left side of the heart via the
pulmonary vein, which pumps it into systemic circulation.
Red blood cells carry the oxygen into the capillaries of the tissues of the body. Oxygen diffuses into
the cells of the tissues, while carbon dioxide diffuses out of the cells of the tissues and into the
bloodstream.
The factors that influence tissue gas exchange are similar to the factors of alveolar gas exchange, and
include partial pressure gradients between the blood and the tissues, the blood perfusion of those
tissues, and the surface areas of those tissues. Each of those factors generally increase gas exchange
as those factors are increased (i.e., more oxygen diffusion in tissues with more blood perfusion).
Regarding the partial pressure gradients in systemic capillaries, they have a PaO2 of 100mmHg and a
PaCO2 of 40mmHG within the capillary and a PaO2 of 40 mmHg and PaCO2 of 45 mmHg inside
issue cells, which allows gas exchange to occur.

Gas Laws and Air Composition

Gas molecules exert force on the surfaces with which they are in contact; this force is called pressure.
In natural systems, gases are normally present as a mixture of different types of molecules. For
example, the atmosphere consists of oxygen, nitrogen, carbon dioxide, and other gaseous molecules,
and this gaseous mixture exerts a certain pressure referred to as atmospheric pressure . Partial
pressure (Px) is the pressure of a single type of gas in a mixture of gases. For example, in the
atmosphere, oxygen exerts a partial pressure, and nitrogen exerts another partial pressure,
independent of the partial pressure of oxygen Total pressure is the sum of all the partial pressures of
a gaseous mixture. Dalton’s law describes the behavior of nonreactive gases in a gaseous mixture and
states that a specific gas type in a mixture exerts its own pressure; thus, the total pressure exerted by a
mixture of gases is the sum of the partial pressures of the gases in the mixture.

Partial Pressures of Atmospheric Gases (Table 22.2)

Partial pressure
Gas Percent of total composition
(mm Hg)

Nitrogen (N2) 78.6 597.4

Oxygen (O2) 20.9 158.8

Water (H2O) 0.04 3.0

Carbon dioxide (CO2) 0.004 0.3

Others 0.0006 0.5

Total composition/total atmospheric pressure 100% 760.0

Partial pressure is extremely important in predicting the movement of gases. Recall that gases tend to
equalize their pressure in two regions that are connected. A gas will move from an area where its
partial pressure is higher to an area where its partial pressure is lower. In addition, the greater the
partial pressure difference between the two areas, the more rapid is the movement of gases.

Cellular Respiration

Cellular respiration is the metabolic process by which an organism obtains energy through the
reaction of oxygen with glucose to produce water, carbon dioxide and ATP, which is the functional
source of energy for the cell. The oxygen supply for cellular respiration comes from the external
respiration of the respiratory system.

Cellular respiration includes three major steps, and occurs mainly in the cytoplasm of the cell and
within the mitochondria of the cell. The net formula for cellular respiration is:

1. Glycolysis: The breakdown of glucose into pyruvate, ATP, H2O, and heat.

2. Krebs Cycle: Produces NADH from pyruvate.

3. Oxidative Phosphorylation: Produces ATP from NADH, oxygen, and H+. The oxygen plays
the role of electron receptor in an electron transport chain to produce ATP.

The carbon dioxide waste is the result of the carbon from glucose (C6H12O6) being broken down to
produce the pyruvate and NADH intermediates needed to produce ATP at the end of respiration. The
energy stored in ATP can then be used to drive processes that require energy, including biosynthesis,
locomotion, or transportation of molecules across cell membranes.

Cellular respiration can occur anaerobically without oxygen, such as through lactic acid fermentation.
Human cells may use lactic acid fermentation in muscle tissue during strenuous exercise when there
isn’t enough oxygen to power the tissues. This process is very inefficient compared to aerobic
respiration, as without oxidative phosphorylation, the cell cannot produce nearly as much ATP (2
ATP compared to 38 during cellular respiration).
 List of reference
1- Prange, H. D. (1996). Respiratory Physiology: Understanding Gas Exchange. Boston: Springer US
2- https://www.britannica.com/science/human-respiratory-system/Transport-of-carbon-dioxide
3- Huet Y, Lemaire F, Brun-Buisson C, Knaus WA, Teisseire B, Payen D, Mathieu D. Hypoxemia in
acute pulmonary embolism. Chest.
4- https://courses.lumenlearning.com/boundless-ap/chapter/gas-exchange/
5- https://open.oregonstate.education/aandp/chapter/22-4-gas-exchange/
6- Wagner PD. The multiple inert gas elimination technique (MIGET). Intensive Care Med. 2008
7- https://erj.ersjournals.com/content/45/1/227
8- https://www.ncbi.nlm.nih.gov/books/NBK539907/
9- Wagner PD, Laravuso RB, Uhl RR, West JB. Continuous distributions of ventilation-perfusion
ratios in normal subjects breathing air and 100 per cent O2. J Clin Invest. 1974 Jul;54(1):54-68. .
10- Meyer, M., & Piiper, J. (1986). Pulmonary gas exchange. Basel: Karger