Download MBBS (Bachelor of Medicine, Bachelor of Surgery) 1st Year, 2nd Year, 3rd Year and Final year Physiology 43 Introduction Respiratory System PPT-Powerpoint Presentations and lecture notes
Introduction
to
Respiratory System
Schematic diagram showing delivery of oxygen to
the tissues from air
1. Ventilation
2. Diffusion across the blood-gas barrier
3. Matching of ventilation and blood flow
4. Pulmonary blood flow
5. Transport of gas in the blood
6. Diffusion from capil ary to cel
7. Utilization of oxygen by mitochondria
Gas Exchange in "Animals"
Cells require O 2 for aerobic respiration and expel
CO 2 as a waste product.
Claude Bernard's concept:
A `milieu interior' that remains constant and stable
despite changes in the environment
Approximate timescale for the evolution of the gaseous
environment
Oxygen: a paradoxical molecule
Oxygen first appeared in significant quantity some 2 billion years ago
Anaerobic prokaryotes
2 bil ion years
Aerobic eukaryotes
700 mil ion years
Multicellular eukaryotes
? Oxygen is the fire of life
Max Kleiber (1961)
? Aerobic metabolism yielded more free metabolic energy than was
achievable through anaerobic pathways.
? About 350-400 million years back: A hyperoxic episode (atmospheric
O 2 rose to a high of 35%) allowed development of exceptionally large
animals such as the giant dragonfly.
? The high intracellular diffusivity due to its `smal ' size and ability to
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!
? Utilization of oxygen is accompanied formation of
reactive oxygen species (RORs).
? The assault by the RORs on the DNA, proteins and
other macromolecules is profound..
? Oxygen toxicity could have necessitated the evolution
of the nucleus and the nuclear membrane in the
eukaryotic cel s to minimize assaults by RORs: The
mitochondrial DNA has more than 10 times the level
of oxidative DNA damage than does the nuclear one.
Gas exchangers
Ideal Gas Exchanger?
1. There are no rules in respiration, but only necessities.
2. Gas exchangers have developed on a need-to-have basis.
3. Brain v/s lung
4. There are no tissues or cel s that are unique to gas exchangers e.g. a
neuron, osteocyte, a podocyte etc.
5. The type I (granular) pneumocyte
6. Surfactant-like phospholipids are produced in many tissues and organs,
including the stomach, the intestines, the swim bladder, the gas mantle
of an air-breathing snail (Helix aspersa), the prostate gland, the female
reproductive tract, the lacrimal gland, the mesothelial cells of the
pleura, the pericardium, the peritoneum, and the Eustachian tube
epithelium
`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
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'
Stebbins (1984)
Quantum leaps in morphological and physiological transformations of the
gas exchangers and the respiratory processes happened at:
1. change of anaerobiotic to aerobiotic life
2. accretion of diffusion-dependent unicel s into multicel ular organisms.
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.
5. formation of invaginated respiratory organs (`lungs'), a transition that
was requisite for water conservation .
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.
8. shift from buccal-force-pumping to suctional breathing.
9. progression from ectothermic-heterothermy to endothermic-
homeothermy, a high-level metabolic state that required evolution of
efficient respiratory organs.
10. capacity for highly energetic lifestyles (e.g. flight), performances that
exacted singularly efficient respiratory organs.
Water and air as respiratory media:
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).
? Gills and lungs have evolved for respiration in the respective media.
Gil s in air: closely packed, delicate, leaf-like respiratory units
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
Lungs in water: High viscosity of water
the ventilatory rate is much slower.
Liquids physically destroy alveoli , dissolve and mechanically displace the
surfactant, osmotically interfere with the composition of the body fluids, cause
pathological changes such as interstitial oedema and produce intrapulmonary froth
and atelectasis upon re-exposure to air .
Macrophages are lost and airway constriction increases.
Fundamental principles in the design of gas exchangers
? The foremost factors that have jointly prescribed the design of the gas exchangers
include
i.
respiratory medium utilized
i .
habitat occupied
i i.
phylogenetic level of development achieved
iv.
body size
v.
metabolic capacity and lifestyle pursued
? Gas exchangers display certain or al of the fol owing basic morphological features
i.
evagination or invagination from the body surface
i .
stratification or compartmentalization, means by which an extensive surface area is
generated in a limited space
i i.
thin partitioning between internal and external compartments, a property that
promotes flux of respiratory gases
iv.
vascularization, an attribute that increases the volume of blood exposed to external
respiratory medium
v.
geometric organization of the structural components, characteristics that determine
the interaction between the respiratory media.
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
mammalian one.
? In the human lung, there are about 300 million alveoli of an average diameter of
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
components demand more energy to dilate on ventilation and have a high
propensity of collapsing.
? Saving grace: Surfactant, a complex material consisting primarily of
phospholipid material (dipalmitoylphosphatidylcholine), reduces surface
tension, preserving stability of the narrow terminal respiratory units.
? A balance between maximization of respiratory surface area, ventilatory
capacity, size of the terminal gas exchange components and overal respiratory
efficiency must be established in every gas exchanger.
Evagination and invagination of gas exchangers
? requisite for successful terrestrial habitation: water loss across an
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.
? Dead space creation:
i.
While evaginated gas exchangers can be ventilated continuously and
unidirectionally, lungs are invaginated organs.
i . Thus having a narrow entry/exit point to the ambient milieu, they can
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%
of the 500 cm3 of the inhaled air (tidal volume) does not reach the
respiratory region of the lung.
Possible configurations for a heat or gas exchanger
The flow-through arrangement for the gas-exchanging tissue
in the bird,and the reciprocating pattern in mammals.
Reciprocating pattern of air movement in
mammalian lung
Three shortcomings arising due to reciprocating pattern:
1. Potential for uneven ventilation: increases during rapid breathing
2. Low alveolar oxygen tension:
3. Large terminal air units: to reduce resistance
Separation of internal and external respiratory media in gas
exchangers
? Respiratory media must be brought into very close proximity to each
other to optimize gas exchange by passive diffusion.
the thickness of the blood?gas (tissue) barrier of the lung of the
shrew (2.5 g)- 0.334 ?m
the thickness of the blood?gas (tissue) barrier of the lung of the
whale (150 tonnes)- 0.350 ?m
? In vertebrates, the thickness of the blood?water/air (tissue) barrier
increases from fish, amphibians, reptiles, mammals to birds.
? In the avian lung, epithelial- and endothelial cel s that constitute the
blood?gas (tissue) barrier are separated only by a common basement
membrane.
Separation of the gas exchange and ventilatory functions
? Gas-exchanging units require extremely thin walls because gas movement
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
nonvascular air sacs, which are robust, in contrast to the alveoli of the
mammalian lung, which are necessarily delicate because of their extremely
thin-walled capillaries.
Shortcomings
? Occlusion of airways by aspiration or secretions
? Localised airway inclusion also commonly occurs in airway diseases such as
chronic bronchitis and asthma.
? 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
Abbreviations and symbols used in
respiratory physiology
Gas Laws
? Ambient (Atmospheric) conditions
? Pressure is typically measured in mm Hg
? Atmospheric pressure is 760 mm Hg
? Atmospheric components
? Nitrogen = 78% of our atmosphere
? Oxygen = 21% of our atmosphere
? Carbon Dioxide = .033% of our atmosphere
? Water vapor, krypton, argon, .... Make up the rest
? A few laws to remember
? Dalton's law
? Fick's Laws of Diffusion
? Boyle's Law
? Ideal Gas Law
Dalton's Law
Law of Partial Pressures= P x= P T* Fx
? "each gas in a mixture of gases will exert a pressure independent of other
gases present"
Or
? The total pressure of a mixture of gases is equal to the sum of the
individual gas pressures.
? Conventionally, fractional concentration always refers to the dry gas.
? Practical application?
? If we know the total atmospheric pressure (760 mm Hg) and the relative
abundances of gases (% of gases)
? We can calculate individual gas effects!
? Patm x % of gas in atmosphere = Partial pressure of any atmospheric gas
? P = 760mmHg x 21% (.21) =
O
160 mm Hg
2
Now that we know the partial pressures we know the gradients that will drive
diffusion!
Boyle's Law
? Describes the relationship between pressure and
volume
? "the pressure and volume of a gas in a system are inversely
related" at a constant temperature
P V
1 1 = P V
2 2
As the molecules are brought close together (smal er volume), the rate of bombardment
on a unit surface increases (greater pressure).
? How does Boyle's Law work in us?
? Increase in lung volume decreases intrapulmonary pressure: Air goes in.
? Decrease in lung volume, raises intrapulmonary pressure above
atmosphere: Air goes out.
? Principle of Spirometry
? Charles Law: at constant pressure, the volume
is proportional to the absolute temperature
V/T = constant
A rise in temperature increases the speed and
momentum of the molecules, thus increasing the
force of bombardment on the container.
Avogadro's law: relates volume of a gas to
the amount of substance of gas present.
or
"equal volumes of al gases, at the same
temperature and pressure, have the same number
of molecules"
For a given mass of an ideal gas, the volume and
amount (moles) of the gas are directly proportional
if temperature and pressure are constant.
? which can be written as:V/n=K
? A gram molecule (e.g. 32g of oxygen)occupies
22.4 liter at STPD
? Ideal Gas law: this law combines three laws
? The pressure and volume of a container of gas is
directly related to the temperature of the gas and
the number of molecules in the container
? PV = nRT
? n = moles of gas
? T = absolute temp
? R = universal gas constant @ 8.3145 J/K?mol
? 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
proportional to its partial pressure in the gas
phase.
C = K * P
x
x,
where K is the solubility cofficient of gas in the
liquid.
The partial pressure of a gas in solution is best
defined as its partial pressure in a gas which is in
euilibrium with that solution
Graham's Law
? the rate of diffusion of a gas is 1/ to the square root of
its molecular weight
Atmospheric Air vs. Alveolar Air
? H2O vapor 3.7 mmHg
? H2O vapor 47 mmHg
? Oxygen 159 mmHg
? Oxygen 104 mmHg
? Nitrogen 597 mmHg
? Nitrogen 569 mmHg
? CO2 .3 mmHg
? CO2 40 mmHg
Gas Pressures in a Mixture of Gases--"Partial Pressures" of Individual Gases
The pressure of a gas acting on the surfaces of the respiratory passages and alveoli is
proportional to the summated force of impact of all the molecules of that gas striking
the surface at any given instant.
This means that the pressure is directly proportional to the concentration of the gas
molecules.
. The rate of diffusion of each of these gases is directly proportional to the pressure
caused by that gas alone, which is called the partial pressure of that gas. The concept
of partial pressure can be explained as follows.
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.
Therefore, 79 percent of the 760 mm Hg is caused by nitrogen (600 mm Hg) and 21
percent 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
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
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
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
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
repel ed. When molecules are attracted, far more of them can be dissolved without building
up 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
are expressed by the following formula, which is Henry's law:
Partial Pressures of Gases in Blood
? When a liquid or gas (blood and alveolar air) are
at equilibrium:
? The amount of gas dissolved in fluid reaches a
maximum value (Henry 's Law).
? Depends upon:
? Solubility of gas in the fluid.
? Temperature of the fluid.
? Partial pressure of the gas.
? [Gas] dissolved in a fluid depends directly on its
partial pressure in the gas mixture.
Diffusion in the gas phase: Gas molecules tend to
distribute themselves uniformly throughout any available
space until the partial pressure is same everywhere.
? Diffusion
? Light gases diffuse faster because mean velocity of the
molecule is higher.
Diffusion of dissolved gases: rate is inversely proportional
to the square root of the molecular weight of the gas.
? The amount of gas that moves through a film of liquid
(or a membrane) is proportional to the solubility of the
gas.
? Fick's Laws of Diffusion: Gas exchange involves
the diffusion of gases across a membrane
? Things that affect rates of diffusion
? Distance to diffuse
? Gradient sizes
? Diffusing molecule sizes
? TemperatureR = DA p
d
D= diffusion constant (size of molecule, membrane permeability, etc)
A= area over which diffusion occurs
p = pressure differe
nce between sides of the membrane
d = distance across which diffusion must occur
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
dense as Y then the ratio of diffusion rates of X
to Y will be
This post was last modified on 08 April 2022