Schematic diagram showing delivery of oxygen to
the tissues from air
--- Content provided by FirstRanker.com ---
1. Ventilation
2. Diffusion across the blood-gas barrier
--- Content provided by FirstRanker.com ---
3. Matching of ventilation and blood flow4. Pulmonary blood flow
5. Transport of gas in the blood
--- Content provided by FirstRanker.com ---
6. Diffusion from capil ary to cel
7. Utilization of oxygen by mitochondria
Gas Exchange in "Animals"
--- Content provided by FirstRanker.com ---
Cells require O 2 for aerobic respiration and expel
CO 2 as a waste product.
--- Content provided by FirstRanker.com ---
Claude Bernard's concept:A `milieu interior' that remains constant and stable
despite changes in the environment
--- Content provided by FirstRanker.com ---
Approximate timescale for the evolution of the gaseousenvironment
Oxygen: a paradoxical molecule
--- Content provided by FirstRanker.com ---
Oxygen first appeared in significant quantity some 2 billion years agoAnaerobic prokaryotes
2 bil ion years
--- Content provided by FirstRanker.com ---
Aerobic eukaryotes700 mil ion years
Multicellular eukaryotes
--- Content provided by FirstRanker.com ---
? Oxygen is the fire of lifeMax Kleiber (1961)
? Aerobic metabolism yielded more free metabolic energy than was
--- Content provided by FirstRanker.com ---
achievable through anaerobic pathways.
? About 350-400 million years back: A hyperoxic episode (atmospheric
--- Content provided by FirstRanker.com ---
O 2 rose to a high of 35%) allowed development of exceptionally largeanimals such as the giant dragonfly.
? The high intracellular diffusivity due to its `smal ' size and ability to
--- Content provided by FirstRanker.com ---
act as an electron acceptor in the energy production pathways of the
tricarboxylic cycle where it mops up protons (H+) to form water.
The paradox!
--- Content provided by FirstRanker.com ---
? Utilization of oxygen is accompanied formation of
reactive oxygen species (RORs).
--- Content provided by FirstRanker.com ---
? The assault by the RORs on the DNA, proteins andother macromolecules is profound..
? Oxygen toxicity could have necessitated the evolution
--- Content provided by FirstRanker.com ---
of the nucleus and the nuclear membrane in the
eukaryotic cel s to minimize assaults by RORs: The
--- Content provided by FirstRanker.com ---
mitochondrial DNA has more than 10 times the levelof oxidative DNA damage than does the nuclear one.
Gas exchangers
--- Content provided by FirstRanker.com ---
Ideal Gas Exchanger?1. There are no rules in respiration, but only necessities.
2. Gas exchangers have developed on a need-to-have basis.
--- Content provided by FirstRanker.com ---
3. Brain v/s lung
4. There are no tissues or cel s that are unique to gas exchangers e.g. a
--- Content provided by FirstRanker.com ---
neuron, osteocyte, a podocyte etc.5. The type I (granular) pneumocyte
6. Surfactant-like phospholipids are produced in many tissues and organs,
--- Content provided by FirstRanker.com ---
including the stomach, the intestines, the swim bladder, the gas mantle
of an air-breathing snail (Helix aspersa), the prostate gland, the female
--- Content provided by FirstRanker.com ---
reproductive tract, the lacrimal gland, the mesothelial cells of thepleura, the pericardium, the peritoneum, and the Eustachian tube
epithelium
--- Content provided by FirstRanker.com ---
`A clear historical record documents for us the evolutionary design process.
Looking into that record in detail can help us understand why certain things are the way
--- Content provided by FirstRanker.com ---
they are and help us understand how things in general come to take the forms that they do.'Petroski (2000)
`The only law that holds without exception in biology is that exceptions exist for every law'
--- Content provided by FirstRanker.com ---
Stebbins (1984)
Quantum leaps in morphological and physiological transformations of the
gas exchangers and the respiratory processes happened at:
--- Content provided by FirstRanker.com ---
1. change of anaerobiotic to aerobiotic life
2. accretion of diffusion-dependent unicel s into multicel ular organisms.
--- Content provided by FirstRanker.com ---
3. formation of a closed circulatory system from an open one.4. evolution of metal-based carrier pigments that improved oxygen
uptake and transfer by blood/ haemolymph.
--- Content provided by FirstRanker.com ---
5. formation of invaginated respiratory organs (`lungs'), a transition that
was requisite for water conservation .
--- Content provided by FirstRanker.com ---
6. physical translocation from water to land.7. development of double circulation from a single one, a transformation
that granted efficient delivery of oxygen to the tissues.
--- Content provided by FirstRanker.com ---
8. shift from buccal-force-pumping to suctional breathing.
9. progression from ectothermic-heterothermy to endothermic-
--- Content provided by FirstRanker.com ---
homeothermy, a high-level metabolic state that required evolution ofefficient respiratory organs.
10. capacity for highly energetic lifestyles (e.g. flight), performances that
--- Content provided by FirstRanker.com ---
exacted singularly efficient respiratory organs.
Water and air as respiratory media:
--- Content provided by FirstRanker.com ---
consequences on the design of gas exchangers? In the biosphere, over the biological range of temperature and pressure, the
only two naturally occurring respirable fluids: water (a liquid) and air (a gas).
--- Content provided by FirstRanker.com ---
? Gills and lungs have evolved for respiration in the respective media.
Gil s in air: closely packed, delicate, leaf-like respiratory units
--- Content provided by FirstRanker.com ---
i.dry out and become impermeable to oxygen.ii.cohere due to surface tension and collapse under their own weight.
iii.creates large diffusion distances in the lamellae
--- Content provided by FirstRanker.com ---
Lungs in water: High viscosity of water
the ventilatory rate is much slower.
--- Content provided by FirstRanker.com ---
Liquids physically destroy alveoli , dissolve and mechanically displace thesurfactant, osmotically interfere with the composition of the body fluids, cause
pathological changes such as interstitial oedema and produce intrapulmonary froth
--- Content provided by FirstRanker.com ---
and atelectasis upon re-exposure to air .
Macrophages are lost and airway constriction increases.
Fundamental principles in the design of gas exchangers
--- Content provided by FirstRanker.com ---
? The foremost factors that have jointly prescribed the design of the gas exchangers
include
--- Content provided by FirstRanker.com ---
i.respiratory medium utilized
i .
--- Content provided by FirstRanker.com ---
habitat occupied
i i.
--- Content provided by FirstRanker.com ---
phylogenetic level of development achievediv.
body size
--- Content provided by FirstRanker.com ---
v.
metabolic capacity and lifestyle pursued
--- Content provided by FirstRanker.com ---
? Gas exchangers display certain or al of the fol owing basic morphological featuresi.
evagination or invagination from the body surface
--- Content provided by FirstRanker.com ---
i .
stratification or compartmentalization, means by which an extensive surface area is
--- Content provided by FirstRanker.com ---
generated in a limited spacei i.
thin partitioning between internal and external compartments, a property that
--- Content provided by FirstRanker.com ---
promotes flux of respiratory gases
iv.
--- Content provided by FirstRanker.com ---
vascularization, an attribute that increases the volume of blood exposed to externalrespiratory medium
v.
--- Content provided by FirstRanker.com ---
geometric organization of the structural components, characteristics that determine
the interaction between the respiratory media.
--- Content provided by FirstRanker.com ---
Stratification and compartmentalization of gas exchangers? A large surface area is produced by internal subdivision of the parenchyma,
giving rise to narrow terminal gas exchange components alveoli in the
--- Content provided by FirstRanker.com ---
mammalian one.
? In the human lung, there are about 300 million alveoli of an average diameter of
--- Content provided by FirstRanker.com ---
250 ?m, giving an overal alveolar surface area of 143 m2.? Increasing the internal subdivision and hence the respiratory surface area of the
lung occurs at a cost: in a compliant lung, narrow terminal gas exchange
--- Content provided by FirstRanker.com ---
components demand more energy to dilate on ventilation and have a high
propensity of collapsing.
--- Content provided by FirstRanker.com ---
? Saving grace: Surfactant, a complex material consisting primarily ofphospholipid material (dipalmitoylphosphatidylcholine), reduces surface
tension, preserving stability of the narrow terminal respiratory units.
--- Content provided by FirstRanker.com ---
? A balance between maximization of respiratory surface area, ventilatory
capacity, size of the terminal gas exchange components and overal respiratory
--- Content provided by FirstRanker.com ---
efficiency must be established in every gas exchanger.Evagination and invagination of gas exchangers
? requisite for successful terrestrial habitation: water loss across an
--- Content provided by FirstRanker.com ---
extensive respiratory surface area was minimized.? If the mature human lungs, of which the alveolar surface is 143 m2 were
designed like gil s, water loss would be about 500 L per day.
--- Content provided by FirstRanker.com ---
? Dead space creation:
i.
--- Content provided by FirstRanker.com ---
While evaginated gas exchangers can be ventilated continuously andunidirectionally, lungs are invaginated organs.
i . Thus having a narrow entry/exit point to the ambient milieu, they can
--- Content provided by FirstRanker.com ---
only be ventilated tidally, i.e. bidirectional y (= in-and-out).
i i. In a resting person where the dead space is about 140 cm3, about 28%
--- Content provided by FirstRanker.com ---
of the 500 cm3 of the inhaled air (tidal volume) does not reach therespiratory region of the lung.
Possible configurations for a heat or gas exchanger
--- Content provided by FirstRanker.com ---
The flow-through arrangement for the gas-exchanging tissuein the bird,and the reciprocating pattern in mammals.
Reciprocating pattern of air movement in
--- Content provided by FirstRanker.com ---
mammalian lung
Three shortcomings arising due to reciprocating pattern:
--- Content provided by FirstRanker.com ---
1. Potential for uneven ventilation: increases during rapid breathing2. Low alveolar oxygen tension:
3. Large terminal air units: to reduce resistance
--- Content provided by FirstRanker.com ---
Separation of internal and external respiratory media in gasexchangers
? Respiratory media must be brought into very close proximity to each
--- Content provided by FirstRanker.com ---
other to optimize gas exchange by passive diffusion.
the thickness of the blood?gas (tissue) barrier of the lung of the
--- Content provided by FirstRanker.com ---
shrew (2.5 g)- 0.334 ?mthe thickness of the blood?gas (tissue) barrier of the lung of the
whale (150 tonnes)- 0.350 ?m
--- Content provided by FirstRanker.com ---
? In vertebrates, the thickness of the blood?water/air (tissue) barrier
increases from fish, amphibians, reptiles, mammals to birds.
--- Content provided by FirstRanker.com ---
? In the avian lung, epithelial- and endothelial cel s that constitute theblood?gas (tissue) barrier are separated only by a common basement
membrane.
--- Content provided by FirstRanker.com ---
Separation of the gas exchange and ventilatory functions
? Gas-exchanging units require extremely thin walls because gas movement
--- Content provided by FirstRanker.com ---
across them is by passive diffusion.? The ventilating structures need to be freely distortable so that they can
increase their volume during inspiration. In the bird lung, this is done by
--- Content provided by FirstRanker.com ---
nonvascular air sacs, which are robust, in contrast to the alveoli of the
mammalian lung, which are necessarily delicate because of their extremely
--- Content provided by FirstRanker.com ---
thin-walled capillaries.Shortcomings
? Occlusion of airways by aspiration or secretions
--- Content provided by FirstRanker.com ---
? Localised airway inclusion also commonly occurs in airway diseases such as
chronic bronchitis and asthma.
--- Content provided by FirstRanker.com ---
? Is repetitive distortion of alveolar tissue a factor in its destruction?Emphysema, characterised by breakdown of the alveolar walls, Ageing etc.
Abbreviations and symbols used in respiratory physiology
--- Content provided by FirstRanker.com ---
Abbreviations and symbols used inrespiratory physiology
Gas Laws
--- Content provided by FirstRanker.com ---
? Ambient (Atmospheric) conditions? Pressure is typically measured in mm Hg
? Atmospheric pressure is 760 mm Hg
--- Content provided by FirstRanker.com ---
? Atmospheric components
? Nitrogen = 78% of our atmosphere
--- Content provided by FirstRanker.com ---
? Oxygen = 21% of our atmosphere? Carbon Dioxide = .033% of our atmosphere
? Water vapor, krypton, argon, .... Make up the rest
--- Content provided by FirstRanker.com ---
? A few laws to remember
? Dalton's law
--- Content provided by FirstRanker.com ---
? Fick's Laws of Diffusion? Boyle's Law
? Ideal Gas Law
--- Content provided by FirstRanker.com ---
Dalton's Law
Law of Partial Pressures= P x= P T* Fx
--- Content provided by FirstRanker.com ---
? "each gas in a mixture of gases will exert a pressure independent of othergases present"
Or
--- Content provided by FirstRanker.com ---
? The total pressure of a mixture of gases is equal to the sum of the
individual gas pressures.
--- Content provided by FirstRanker.com ---
? Conventionally, fractional concentration always refers to the dry gas.? Practical application?
? If we know the total atmospheric pressure (760 mm Hg) and the relative
--- Content provided by FirstRanker.com ---
abundances of gases (% of gases)
? We can calculate individual gas effects!
--- Content provided by FirstRanker.com ---
? Patm x % of gas in atmosphere = Partial pressure of any atmospheric gas? P = 760mmHg x 21% (.21) =
O
--- Content provided by FirstRanker.com ---
160 mm Hg
2
--- Content provided by FirstRanker.com ---
Now that we know the partial pressures we know the gradients that will drivediffusion!
Boyle's Law
--- Content provided by FirstRanker.com ---
? Describes the relationship between pressure andvolume
? "the pressure and volume of a gas in a system are inversely
--- Content provided by FirstRanker.com ---
related" at a constant temperature
P V
--- Content provided by FirstRanker.com ---
1 1 = P V2 2
As the molecules are brought close together (smal er volume), the rate of bombardment
--- Content provided by FirstRanker.com ---
on a unit surface increases (greater pressure).
? How does Boyle's Law work in us?
--- Content provided by FirstRanker.com ---
? Increase in lung volume decreases intrapulmonary pressure: Air goes in.? Decrease in lung volume, raises intrapulmonary pressure above
atmosphere: Air goes out.
--- Content provided by FirstRanker.com ---
? Principle of Spirometry
? Charles Law: at constant pressure, the volume
is proportional to the absolute temperature
--- Content provided by FirstRanker.com ---
V/T = constant
A rise in temperature increases the speed and
--- Content provided by FirstRanker.com ---
momentum of the molecules, thus increasing theforce of bombardment on the container.
Avogadro's law: relates volume of a gas to
--- Content provided by FirstRanker.com ---
the amount of substance of gas present.
or
--- Content provided by FirstRanker.com ---
"equal volumes of al gases, at the sametemperature and pressure, have the same number
of molecules"
--- Content provided by FirstRanker.com ---
For a given mass of an ideal gas, the volume and
amount (moles) of the gas are directly proportional
--- Content provided by FirstRanker.com ---
if temperature and pressure are constant.? which can be written as:V/n=K
? A gram molecule (e.g. 32g of oxygen)occupies
--- Content provided by FirstRanker.com ---
22.4 liter at STPD
? Ideal Gas law: this law combines three laws
? The pressure and volume of a container of gas is
--- Content provided by FirstRanker.com ---
directly related to the temperature of the gas and
the number of molecules in the container
--- Content provided by FirstRanker.com ---
? PV = nRT? n = moles of gas
? T = absolute temp
? R = universal gas constant @ 8.3145 J/K?mol
--- Content provided by FirstRanker.com ---
? When the units employed are milliliters of mercury,liters and degrees absolute, then R=62.4
? Henry's law : the amount of dissolved gas is
--- Content provided by FirstRanker.com ---
proportional to its partial pressure in the gas
phase.
--- Content provided by FirstRanker.com ---
C = K * Px
x,
--- Content provided by FirstRanker.com ---
where K is the solubility cofficient of gas in the
liquid.
--- Content provided by FirstRanker.com ---
The partial pressure of a gas in solution is bestdefined as its partial pressure in a gas which is in
euilibrium with that solution
--- Content provided by FirstRanker.com ---
Graham's Law? the rate of diffusion of a gas is 1/ to the square root of
its molecular weight
--- Content provided by FirstRanker.com ---
Atmospheric Air vs. Alveolar Air? H2O vapor 3.7 mmHg
? H2O vapor 47 mmHg
--- Content provided by FirstRanker.com ---
? Oxygen 159 mmHg
? Oxygen 104 mmHg
--- Content provided by FirstRanker.com ---
? Nitrogen 597 mmHg? Nitrogen 569 mmHg
? CO2 .3 mmHg
--- Content provided by FirstRanker.com ---
? CO2 40 mmHg
Gas Pressures in a Mixture of Gases--"Partial Pressures" of Individual Gases
--- Content provided by FirstRanker.com ---
The pressure of a gas acting on the surfaces of the respiratory passages and alveoli isproportional to the summated force of impact of all the molecules of that gas striking
the surface at any given instant.
--- Content provided by FirstRanker.com ---
This means that the pressure is directly proportional to the concentration of the gas
molecules.
--- Content provided by FirstRanker.com ---
. The rate of diffusion of each of these gases is directly proportional to the pressurecaused by that gas alone, which is called the partial pressure of that gas. The concept
of partial pressure can be explained as follows.
--- Content provided by FirstRanker.com ---
Consider air, which has an approximate composition of 79 percent nitrogen and 21
percent oxygen. The total pressure of this mixture at sea level averages 760 mm Hg.
--- Content provided by FirstRanker.com ---
Therefore, 79 percent of the 760 mm Hg is caused by nitrogen (600 mm Hg) and 21percent by O2(160 mm Hg). Thus, the "partial pressure" of nitrogen in the mixture is
600 mm Hg, and the "partial pressure" of O2is 160 mm Hg; the total pressure is 760
--- Content provided by FirstRanker.com ---
mm Hg, the sum of the individual partial pressures.
Pressures of Gases Dissolved in Water and Tissues
Gases dissolved in water or in body tissues also exert pressure because the dissolved
--- Content provided by FirstRanker.com ---
gas molecules are moving randomly and have kinetic energy. Further, when the gas
dissolved in fluid encounters a surface, such as the membrane of a cell, it exerts its
--- Content provided by FirstRanker.com ---
own partial pressure in the same way that a gas in the gas phase does.Factors That Determine the Partial Pressure of a Gas Dissolved in a Fluid.
The partial pressure of a gas in a solution is determined not only by its concentration but also
--- Content provided by FirstRanker.com ---
by the solubility coefficient of the gas. That is, some types of molecules, especial y CO2, are
physical y or chemical y attracted to water molecules, whereas other types of molecules are
--- Content provided by FirstRanker.com ---
repel ed. When molecules are attracted, far more of them can be dissolved without buildingup excess partial pressure within the solution. Conversely, in the case of molecules that are
repel ed, high partial pressure wil develop with fewer dissolved molecules. These relations
--- Content provided by FirstRanker.com ---
are expressed by the following formula, which is Henry's law:
Partial Pressures of Gases in Blood
--- Content provided by FirstRanker.com ---
? When a liquid or gas (blood and alveolar air) areat equilibrium:
? The amount of gas dissolved in fluid reaches a
--- Content provided by FirstRanker.com ---
maximum value (Henry 's Law).
? Depends upon:
--- Content provided by FirstRanker.com ---
? Solubility of gas in the fluid.? Temperature of the fluid.
? Partial pressure of the gas.
--- Content provided by FirstRanker.com ---
? [Gas] dissolved in a fluid depends directly on its
partial pressure in the gas mixture.
Diffusion in the gas phase: Gas molecules tend to
--- Content provided by FirstRanker.com ---
distribute themselves uniformly throughout any available
space until the partial pressure is same everywhere.
--- Content provided by FirstRanker.com ---
? Diffusion? Light gases diffuse faster because mean velocity of the
molecule is higher.
--- Content provided by FirstRanker.com ---
Diffusion of dissolved gases: rate is inversely proportional
to the square root of the molecular weight of the gas.
--- Content provided by FirstRanker.com ---
? The amount of gas that moves through a film of liquid(or a membrane) is proportional to the solubility of the
gas.
--- Content provided by FirstRanker.com ---
? Fick's Laws of Diffusion: Gas exchange involves
the diffusion of gases across a membrane
--- Content provided by FirstRanker.com ---
? Things that affect rates of diffusion? Distance to diffuse
? Gradient sizes
--- Content provided by FirstRanker.com ---
? Diffusing molecule sizes
? TemperatureR = DA p
--- Content provided by FirstRanker.com ---
dD= diffusion constant (size of molecule, membrane permeability, etc)
A= area over which diffusion occurs
--- Content provided by FirstRanker.com ---
p = pressure difference between sides of the membrane
d = distance across which diffusion must occur
--- Content provided by FirstRanker.com ---
Question of the day!Using Fick's law of diffusion through a tissue
slice, if gas X is twice as soluble and 4 times a
--- Content provided by FirstRanker.com ---
dense as Y then the ratio of diffusion rates of X
to Y will be
--- Content provided by FirstRanker.com ---