This web page contains notes to accompany lectures in Vertebrate Physiology, Biology 410, taught by Dr. Peter King in the Department of Biology, Francis Marion University, Florence, South Carolina, 29502, USA.

Cellular respiration
C₆H₁₂O₆ + O₂ -> 6CO₂ + 6H₂O

On an organismal level respiration is the uptake of oxygen and the release of carbon dioxide.

So let's have a look at the environments with which we exchange these gases.
The atmosphere around the earth is fairly constant in its make up.
Dry Air

Oxygen	20.95%
Carbon dioxide	0.03%
Nitrogen	78.09%
Argon	0.93%

Micro habitats can be very different
Darden (1972, J. Comp. Phys) in study of respiration of pocket gophers, air in burrows was 15% oxygen
In golden hamster hibernacula, carbon dioxide was 5% (Kuhnen, 1986 Comp. Biochem. Phys.).

Water vapor varies in air with changing temperature.
Cold air has less water vapor than warm air.
Air in lungs is always saturated with water.
At mammalian body temperature 37°C at sea level (atmospheric pressure 760mm Hg) water vapor pressure is 47mm Hg or 6.2% of air volume.

Why do climbers need oxygen climbing Mt. Everest?
Why do football players have trouble with their conditioning at Mile High Stadium in Denver?
Why do some athletes train at high altitudes?

Although the proportions of the gases in the air do not change significantly with altitude, air pressure does change.
What is pressure in a gas?
The force applied by the movement of molecules.
The more molecules in a given volume the greater the pressure.

The total pressure of a gas mixture such as air is equal to the sum of the partial pressures of the gases in the mixture.
i.e. at sea level, air pressure is 760 mm Hg
Partial pressure of oxygen is
760 x 0.2095 = 159 mm Hg

Back to the mountain top.
At the top of Mt. Everest the air pressure is only about 240 mm Hg.
Partial pressure of O₂ is
240 x 0.2095 = 50 mm Hg
i.e. about 1/3 of oxygen available at sea level.

At Mile High Stadium, air pressure is about 640 mm Hg.
Partial pressure of O₂ is
640 x 0.2095 = 134 mm Hg
i.e. about 85% of oxygen available at sea level.

So why would athletes want to train in such an environment?
Our bodies compensate for the low Po₂
Amongst some changes are:ventilation increases due to change in set point of blood CO₂ levels.red blood cells increase from 5 million/ml to 8 million/ml at altitudes around 4000m.

But air is not the only environment in which organisms live.
Aquatic organisms have to exchange gasses with water.

Gases are soluble in water and go into solution at the gas liquid interface.
After some time an equilibrium is reached between the number of gas molecules that enter the water and those that leave.
At equilibrium the solution is said to be saturated with the gas.

The amount of gas that is dissolved in water depends on:
1) solubility of the gas
2) pressure of the gas
3) temperature
4) presence of other solutes

You can work out the amount of gas that will dissolve in water at a certain pressure
Vg = a.(Pg/760). VH₂0
Vg = volume of gas at STPD (standard temperature and pressure dry)
a= solubility coefficient
Pg = partial pressure of gas
VH₂0 = volume of water

a , solubility coefficient

a for O₂ = 0.331
a for CO₂ = 9.30
a for N₂ = 0.164

Solubility of gases in water at 15°C, 760 mm Hg, are

oxygen	34.1 ml O2/L
nitrogen	16.9 ml N2/L
carbon dioxide	1019.0 ml CO2/L

Note how much more soluble CO₂ is than O₂. Low concentration gradient of O₂ causes O₂ to be the limiting factor in aquatic gas exchange.

The effect of solutes
Comparison of freshwater and saltwater 0₂ content (ml O₂ /L) at equilibrium at different temperatures.

Temp. °C	Fresh water	Sea water
0	10.29	7.97
10	8.02	6.35
15	7.22	5.79
20	6.57	5.31
30	5.57	4.46

Comparing air and water as respiratory mediums

	water	air	ratio
O2 conc. (L/L)	0.0007	0.209	1:30
Density (kg/L)	1.00	0.003	800:1
Dynamic viscosity	1 .00	0.02	50:1
Diffusion constant	0.000034	11	1:300,000

One liter of oxygen can be contained in 4.8 liters of air or 143 liters of water.
To ventilate a respiratory organ with this one liter of oxygen an organism would have to move 143 kg of water or .0062 kg of air.

Respiratory Organs
Any body surface is a potential respiratory organ.
Diffusion may take place at many sites but some body areas are specialized to facilitate diffusion of gases.

Fish, amphibians and reptiles use their buccopharynx.
Some fish swallow air into their stomach and extract the oxygen there.
Amphibians rely to varying degrees on diffusion of gases over their skin. Many amphibians have lungs but plethodont salamanders are lungless and have no gills and are terrestrial.
Aquatic reptiles use their skin.
Some turtles ventilate their cloaca and exchange gases over the surface of special cloacal bursae.

In general:
Most aquatic animals have evolved gills.
Most terrestrial animals have lungs.

Characteristics of a respiratory surface
1) small diffusion barrier
2) large surface area
3) blood supply
4) ventilation

Gills are more efficient with greater surface area.
For example:fast swimming mackerel have a gill surface area 50x that of a bottom dwelling goose fish.

Gill morphology
From each gill bar project two rows of gill filaments.
From each side of the gill filament protrude gill lamellae.
The surface of the gill lamellae is the respiratory surface.

Countercurrent exchange
Blood flows through a capillary bed in the opposite direction to the flow of water. This allows blood to reach levels of oxygen approaching that of the incoming water.
Contrast lungs where equilibrium is halfway between incoming blood and air. Mammals extract about 25% of the incoming oxygen.

Fish can either pump water by using their opercular and buccal cavities or swim forward with their mouth open and let the water flow past their gills (ram ventilation).
Ram ventilation saves energy and flow of water across gill surface (ventilation) increases as the fish swims faster and their is a greater demand for oxygen.

Lungs
Lungs are found commonly in amphibians, reptiles birds and mammals.
Evolved from an evagination of the digestive tract in fish, the swim bladder which is generally used to control buoyancy in the water column.

Swim bladder
The swimbladder in teleosts is a pouch in the foregut.
Physostome swimbladders have a duct to the esophagus. Fish can swallow air and push it into the swimbladder.
Physoclist swimbladders have no duct.How does gas move in and out of a physoclist swim bladder?

Fish move oxygen into the swim bladder against very high concentration gradients via the rete mirabile.
Rete mirabile consists of capillary networks with countercurrent exchange between arterial and venous capillaries. A gas gland increases the acidity of the blood (aided by the counter current exchange of CO₂ and other ions) and hemoglobin dumps its oxygen which diffuses into the swim bladder.

The swim bladder can contain oxygen at several times atmospheric pressure.
Gas is reabsorbed at the Oval body by infusion of capillaries with blood to allow diffusion.
Initially thought to be for buoyancy it is not hard to imagine its possible adaptive advantage for gas exchange.

From amphibians to reptiles to mammals there is a progressive increase in the complexity of the interior lung and increasing surface area.
This equates with the greater reliance on lungs for terrestrial animals and the higher metabolic rates (and need for oxygen) in endothermic mammals.

1 cm³ from frog lung has gas exchange surface of 20 cm².
1 cm3 from mouse lung has gas exchange surface of 800 cm².

Frogs have a positive pressure system of ventilating their lungs.
Air is taken into their buccopharynx. By closing their mouth and raising the floor of the buccopharynx they push the air into their lungs.
During inactivity, because of low oxygen demand, lung ventilation is not necessary for a terrestrial frog.
Ventilation of the buccopharynx and gas exchange over that surface is sufficient.

Reptiles, birds and mammals have negative pressure systems where air is drawn in by the increase in lung volume.

Mammalian lungs
Air enters the lungs through tubes reinforced with cartilage to prevent collapse i.e. trachea, bronchi and bronchioles.
After much branching tubes terminate in alveolar sacs with individual pockets called alveoli.
Total surface area of a human lung is about 100m².

Diffusion barrier between air and blood is 0.2mm.
Combination of large surface area and very small diffusion barrier makes mammalian lungs very efficient.
Lung capacity (volume) is about 5% of the body volume of all mammals.

Lungs are however a fairly inefficient mechanism.
A normal breath of a person at rest is about 500 ml (tidal volume). Of that volume inhaled about 150 ml will be left in the air passages (dead space) and has no possibility of exchanging gases. The 350 mls that reaches the alveoli sacs mixes with about 1650 mls left in the lungs after exhalation (functional residual volume).

Other terminology dealing with lung function.
Vital capacity is the amount exhaled after a maximal inhalation i.e. total lung capacity less residual volume.
Inspiratory reserve volume and expiratory reserve volume are the potential volumes between actual and maximal volumes.

When a fish comes out of water the surface tension at the air/water interface causes the gill lamellae to stick together.
Why doesn't this happen to lungs?
Why don't they collapse and stick together like a wet plastic bag?
Special cells within lungs secrete phospholipids collectively called surfactants that reduce the surface tension and prevent collapse.

Bird lungs
Birds the other endotherms have very different lungs to mammals.
Rather than a saccular lungs with alveoli at the end, birds have a flow through system and parabronchi provide the respiratory surface.

Within the parabronchi countercurrent (crosscurrent) exchange takes place increasing the efficiency of avian lungs over those of mammals.
In fact it takes two inhalation/exhalation cycles for air to move in and out of a bird.

Inhalation 1: air moves to posterior sacs
Exhalation 1: air moves into the lungs
Inhalation 2: air moves out of lungs to anterior sacs
Exhalation 2: air is expelled via the mouth

Efficiency of lungs allows high altitude respiration.

Oxygen transport in blood
As we have discussed earlier carbon dioxide is much more soluble in water than oxygen.

How then is oxygen able to efficiently distribute oxygen from the lung to other parts of the body?

The blood of vertebrate contains a respiratory pigment, hemoglobin, that reversibly binds O₂ (to form oxyhemoglobin HbO₂) in amounts about 100 X than that carried dissolved in blood plasma.

Hemoglobin is a protein made up of four subunits 2 a and 2 b, that together form a tetramer a₂ b₂ .
Each subunit contains an iron containing heme group in a pocket which can attract and bind O₂ molecules.
Hemoglobin is contained inside red blood cell (RBCs, erythrocytes).

RBCs of mammals differ from other vertebrates in having no nuclei. They are often smaller than other vertebrates also.
There is no clear reason why mammalian erythrocytes have these differences.
Mammalian RBCs are constantly produced in bone marrow and have a lifespan of about 120 days.

Control of ventilation
Because of differences in solubility there is a lot more CO₂ than O₂ dissolved in plasma.
Dissolved O₂ actually varies very little because most of the O₂ in whole blood is bound to hemoglobin.
CO₂ however does vary and chemoreceptors monitor the CO₂ levels
High blood CO₂ stimulates breathing response.

Peripheral chemoreceptors are in the carotid bodies in mammals birds and amphibians. Mammals also have chemoreceptors in the aorta.
Fish have O₂ receptors in their gills responding to blood and water O₂.
Chemoreceptors are also located in the medulla oblongata which pick up changes in cerebrospinal fluid.
Information is integrated in the medullary respiratory center.

Oxygen Dissociation Curve
The amount of oxygen bound to hemoglobin is dependent upon the partial pressure of oxygen in the air to which it has reached equilibrium.
At saturation 100% of hemoglobin is bound to oxygen.
As the pressure of oxygen is reduced the percent of hemoglobin binding oxygen declines.

Plotting percent saturation against oxygen pressure produces an oxygen-hemoglobin dissociation curve.
Curve is not linear indicating cooperativity.
Dissociation curves of hemoglobins for different animals vary indicating different oxygen affinity.

Oxygen affinity indicates the readiness of hemoglobin to give up oxygen to tissue.
As blood circulates through the body it gives up oxygen to other cells and so the pressure of oxygen drops.

Oxygen affinity is altered by a number of factors.
1. Increased acidity decreases the affinity (shifts the curve to the right).
2. Increased temperature decreases the affinity.
3. Increased carbon dioxide decreases the affinity.
4. Increase in certain organic phosphates (2,3 DPG; IPP; ATP) decreases affinity.

Myoglobin which resembles closely a single subunit of hemoglobin is found in skeletal muscle has a dissociation curve far to the left of hemoglobin and it facilitates movement of oxygen into muscle cells.
It is generally accepted that hemoglobin subunits evolved from myoglobin.

Animals change their hemoglobins during development.
In placental mammals fetal hemoglobin must be to the left of maternal hemoglobin to absorb oxygen.
Larval amphibians which are aquatic have hemoglobins with higher oxygen affinities than adults.

Many ectotherm adults have multiple hemoglobins.
Some have been found to demonstrate differing oxygen affinities.
It is thought that this is an adaptation to fluctuating environments and oxygen availability.

Animals evolved to live at high altitudes i.e. llamas have hemoglobins with higher oxygen affinities than other animals. (curve shift to left).
Animals including humans that evolved in low altitudes can acclimatize to high altitudes with a different strategy. Affinity is lowered making more oxygen leave hemoglobin at the tissues (curve shift to right).

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This page was created by Peter King. Please contact the author at pking@fmarion.edu with comments.
http://people.fmarion.edu/pking/vertphys/respiration.html
Last edit January 10, 2011.
Copyright Peter King.