Option D.

6 Gas Transport

The inner surface of the alveolus is lined by a special type of alveolar cell called a
pneumocyte
■ Type I pneumocytes are very thin in order to mediate gas exchange with the
bloodstream (via diffusion)
■ Type II pneumocytes secrete a pulmonary surfactant in order to reduce the
surface tension within the alveoli

Alveolar air spaces are surrounded by a dense network of capillaries, which transport
respiratory gases to and from the lungs
■ The capillaries are located close to the pneumocytes and are composed of a very
thin, single-layer endothelium
■ The capillaries transport oxygen within red blood cells, while white blood cells
may extravasate into the lung tissue
Diagrammatic Representation of Lung Tissue

Light Micrograph of Lung Tissue (click to show / hide labels)

Electron Micrograph of Lung Tissue (click to show / hide labels)

Oxygen is transported throughout the body in red blood cells, which contain an
oxygen-binding protein called haemoglobin
■ Haemoglobin is composed of four polypeptide chains, each with an
iron-containing heme group that reversibly binds oxygen
■ As such, each haemoglobin can reversibly bind up to four oxygen molecules (Hb
+ 4O2 = HbO8)

As each O2 molecule binds, it alters the conformation of haemoglobin, making

subsequent binding easier (cooperative binding)
■ This means haemoglobin will have a higher affinity for O2 in oxygen-rich areas
(like the lung), promoting oxygen loading
■ Conversely, haemoglobin will have a lower affinity for O2 in oxygen-starved areas
(like muscles), promoting oxygen unloading
Cooperative Binding of Haemoglobin
Oxygen dissociation curves show the relationship between oxygen levels (as partial
pressure) and haemoglobin saturation
■ Because binding potential changes with each additional O2 molecule, the
saturation of haemoglobin is not linear
Adult Haemoglobin
■ The oxygen dissociation curve for adult haemoglobin is sigmoidal (i.e.
S-shaped) due to cooperative binding
■ There is a low saturation of haemoglobin when oxygen levels are low
(haemoglobin releases O2 in hypoxic tissues)
■ There is a high saturation of haemoglobin when oxygen levels are high
(haemoglobin binds O2 in oxygen-rich tissues)
Oxygen Dissociation Curve – Adult Haemoglobin
Fetal Haemoglobin
■ The haemoglobin of the foetus has a slightly different molecular composition to
adult haemoglobin
■ Consequently, it has a higher affinity for oxygen (dissociation curve is shifted to
the left)
■ This is important as it means fetal haemoglobin will load oxygen when adult
haemoglobin is unloading it (i.e. in the placenta)
■ Following birth, fetal haemoglobin is almost completely replaced by adult
haemoglobin (~ 6 months post-natally)
■ Fetal haemoglobin production can be pharmacologically induced in adults to treat
diseases such as sickle cell anaemia
Oxygen Dissociation Curve – Fetal Haemoglobin
Myoglobin
■ Myoglobin is an oxygen-binding molecule that is found in skeletal muscle tissue
■ It is made of a single polypeptide with only one heme group and hence is not
capable of cooperative binding
■ Consequently, the oxygen dissociation curve for myoglobin is not sigmoidal (it is
logarithmic)
■ Myoglobin has a higher affinity for oxygen than adult haemoglobin and becomes
saturated at lower oxygen levels
■ Myoglobin will hold onto its oxygen supply until levels in the muscles are very low
(e.g. during intense physical activity)
■ The delayed release of oxygen helps to slow the onset of anaerobic respiration
and lactic acid formation during exercise
Oxygen Dissociation Curve – Myoglobin
Carbon dioxide is transported between the lungs and the tissues by one of three
mechanisms:
■ Some is bound to haemoglobin to form HbCO2 (carbon dioxide binds to the
globin and so doesn’t compete with O2 binding)
■ A very small fraction gets dissolved in water and is carried in solution (~5% –
carbon dioxide dissolves poorly in water)
■ The majority (~75%) diffuses into the erythrocyte and gets converted into
carbonic acid
Transport as Carbonic Acid
■ When CO2 enters the erythrocyte, it combines with water to form carbonic acid
(reaction catalysed by carbonic anhydrase)
■ The carbonic acid (H2CO3) then dissociates to form hydrogen ions (H+) and
bicarbonate (HCO3–)
■ Bicarbonate is pumped out of the cell in exchange with chloride ions (exchange
ensures the erythrocyte remains uncharged)
■ The bicarbonate in the blood plasma combines with sodium to form sodium
bicarbonate (NaHCO3), which travels to the lungs
■ The hydrogen ions within the erythrocyte make the environment less alkaline,
causing haemoglobin to release its oxygen
 ■ The haemoglobin absorbs the H+ ions and acts as a buffer to maintain the
intracellular pH
■ When the red blood cell reaches the lungs, bicarbonate is pumped back into the
cell and the entire process is reversed
Carbon Dioxide Transport in the Bloodstream

Aqueous carbon dioxide may combine with water in blood plasma to form carbonic acid
(H2CO3)
■ Carbonic acid may then lose protons (H+) to form bicarbonate (HCO3–) or
carbonate (CO32–)
■ The released hydrogen ions will function to lower the pH of the solution, making
the blood plasma less alkaline

Chemoreceptors are sensitive to changes in blood pH and can trigger body responses
in order to maintain a balance
■ The lungs can regulate the amount of carbon dioxide in the bloodstream by
changing the rate of ventilation
■ The kidneys can control the reabsorption of bicarbonate ions from the filtrate and
clear any excess in the urine
The pH of blood is required to stay within a very narrow tolerance range (7.35 – 7.45) in
order to avoid the onset of disease
■ This pH range is, in part, maintained by plasma proteins which act as buffers

A buffering solution resists changes to pH by removing excess H+ ions (↑ acidity) or OH–

ions (↑ alkalinity)
■ Amino acids are zwitterions – they may have both a positive and negative charge
and hence can buffer changes in pH
■ The amine group may take on H+ ions while the carboxyl group may release H+
ions (which form water with OH– ions)
Plasma Proteins Act as pH Buffers

The oxyhaemoglobin dissociation curve demonstrates the saturation of haemoglobin by

oxygen under normal conditions
■ pH changes alter the affinity of haemoglobin for oxygen and hence alters the
uptake and release of O2 by haemoglobin

Carbon dioxide lowers the pH of the blood (by forming carbonic acid), which causes
haemoglobin to release its oxygen
■ This is known as the Bohr effect – a decrease in pH shifts the oxygen
dissociation curve to the right

Cells with increased metabolism (i.e. respiring tissues) release greater amounts of
carbon dioxide (product of cell respiration)
■ Hence haemoglobin is promoted to release its oxygen at the regions of greatest
need (oxygen is an input of cell respiration)
 The Bohr Shift

The respiratory control centre in the medulla oblongata responds to stimuli from
chemoreceptors in order to control ventilation
■ Central chemoreceptors in the medulla oblongata detect changes in CO2 levels
(as changes in pH of cerebrospinal fluid)
■ Peripheral chemoreceptors in the carotid and aortic bodies also detect CO2
levels, as well as O2 levels and blood pH

During exercise metabolism is increased, which results in a build up of carbon dioxide

and a reduction in the supply of oxygen
■ These changes are detected by chemoreceptors and impulses are sent to the
respiratory control centre in the brainstem
■ Signals are sent to the diaphragm and intercostal muscles to increase the rate of
ventilation (this process is involuntary)
■ As the ventilation rate increases, CO2 levels in the blood will drop, restoring blood
pH (also O2 levels will rise)
■ Long term effects of continual exercise may include an improved vital capacity
Respiratory Control
Partial pressure is the pressure exerted by a single type of gas when it is found within
a mixture of gases
The partial pressure of a given gas will be determined by:
■ The concentration of the gas within the mixture (e.g. oxygen forms roughly 21%
of the atmosphere)
■ The total pressure of the mixture (e.g. atmospheric pressure)

At high altitudes, air pressure is lower and hence there is a lower partial pressure of
oxygen (less O2 because less air overall)
■ This makes it more difficult for haemoglobin to take up and transport oxygen
(lower Hb % saturation)
■ Consequently, respiring tissue will receive less oxygen – leading to symptoms
such as fatigue, headaches and rapid pulse

Over time, the body may begin to acclimatise to the lower oxygen levels at high
altitudes:
■ Red blood cell production will increase in order to maximise oxygen uptake and
transport
 ■ Red blood cells will have a higher haemoglobin count with a higher affinity for
oxygen
■ Vital capacity will increase to improve rate of gas exchange
■ Muscles will produce more myoglobin and have increased vascularisation to
improve overall oxygen supply
■ Kidneys will begin to secrete alkaline urine (removal of excess bicarbonates
improves buffering of blood pH)
■ People living permanently at high altitudes will have a greater lung surface area
and larger chest sizes

Professional athletes will often incorporate high altitude training in order to adopt these
benefits prior to competition
■ Athletes may commonly either train at high altitudes (live low – train high) or
recover at high altitudes (live high – train low)
Relationship between Altitude and Air Pressure

Emphysema is a lung condition whereby the walls of the alveoli lose their elasticity due
to damage to the alveolar walls
■ The loss of elasticity results in the abnormal enlargement of the alveoli, leading
to a lower total surface area for gas exchange
■ The degradation of the alveolar walls can cause holes to develop and alveoli to
merge into huge air spaces (pulmonary bullae)

Causes
The major cause of emphysema is smoking, as the chemical irritants in cigarette smoke
damage the alveolar walls
 ■ The damage to lung tissue leads to the recruitment of phagocytes to the region,
which produce an enzyme called elastase
■ This elastase, released as part of an inflammatory response, breaks down the
elastic fibres in the alveolar wall
■ A small proportion of emphysema cases are due to a hereditary deficiency in this
enzyme inhibitor due to a gene mutation

Treatments
There is no current cure for emphysema, but treaments are available to relieve
symptoms and delay disease progression
■ Bronchodilators are commonly used to relax the bronchiolar muscles and
improve airflow
■ Corticosteroids can reduce the inflammatory response that breaks down the
elastic fibres in the alveolar wall
■ Elastase activity can be blocked by an enzyme inhibitor (α-1-antitrypsin),
provided elastase concentrations are not too high
■ Oxygen supplementation will be required in the later stages of the disease to
ensure adequate oxygen intake
■ In certain cases, surgery and alternative medicines have helped to decrease the
severity of symptoms
Consequences of Emphysema

Asthma is a common, chronic inflammation of the airways to the lungs (i.e. bronchi and
bronchioles)
 ■ Inflammation leads to swelling and mucus production, resulting in reduced airflow
and bronchospasm
■ During an acute asthma attack, constriction of the bronchi smooth muscle may
cause significant airflow obstruction
■ Common symptoms of an asthma attack include shortness of breath, chest
tightness, wheezing and coughing
■ Severe cases of asthma may be life threatening if left untreated

Asthma may be caused by a number of environmental triggers, including:

■ Allergens (e.g. pollen, moulds)

■ Smoke / scented products (e.g. perfumes, cigarettes)
■ Stress and anxiety
■ Food preservatives and certain medications
■ Arthropods (e.g. dust mites)
■ Cold air
■ Exercise (increases respiratory rate)

Mnemonic: ASS FACE

Lung cancer describes the uncontrolled proliferation of lung cells, leading to the
abnormal growth of lung tissue (tumour)
 ■ The abnormal growth can impact on normal tissue function, leading to a variety
of symptoms according to size and location
■ The tumours can remain in place (benign) or spread to other regions of the body
(malignant)

Lung cancers are the most common cause of cancer-related death worldwide for two
main reasons:
■ The lungs are vital to normal body function and thus the abrogation of their
normal function is particularly detrimental to health
■ The lungs possess a very rich blood supply, increasing the likelihood of the
cancer spreading (metastasis) to other body regions

The common symptoms of lung cancers include coughing up blood, wheezing,

respiratory distress and weight loss
■ If the cancer mass compresses adjacent organs it can cause chest pain, difficulty
swallowing and heart complications

There are many causes for lung cancer, including smoking, asbestos, air pollution,
certain infections and genetic predispositions