Download MBBS Physiology Presentations 43 Introduction Respiratory System Lecture Notes

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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