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so, last time we talked of the importance of venous pO2 and critical pO2 
and critical pO2 being 35 to ensure adequate oxygenation of tissue.

now, how does this come about? 
you can say that unicellular organisms have respiratory exchange via 
simple diffusion. the simple diffusion process takes place across the 
cell wall (not cell window, cell door, cell floor) but anywhere on the 
surface of the cell. this is also the case in individual cells of 
mammals. but mammals are quite large ,and diffusion is slow over long 
distances. it's great for short distances, but sucks for long distances. 
this is why we stir the tea after adding sugar - we don't want it just 
sitting at the bottom...it would take too long to diffuse to the top, 
would be cold by then!

to speed up diffusion, you need some kind of convection or bulk flow. so 
in the body is specialized exchange membrane, to make the distance 
between gas phase (alveolus) and blood phase (pulmonary caps) very short. 
so the very thin membrane is this .1 micron membrane. the gas phase is 
outside an epithelial cell. so it's outside the body. the blood is inside 
an epi cell lining - inside the body. blood and gas are separated by only 
0.1 micron. so this thin delicate membrane is inside the thorax, 
protected. but it's far away from source of oxygen (outside air) and away 
from places that NEED oxygen (muscles) so you need two organ systems to 
accomplish resp exchange: you need lung and pump (chest wall/muscles), 
and you need circulatory system (blood and its pump)

the circulatory and respiratory systems constitute four link transport 
systems. four series linked transport systems.

convection (bulk flow) requires active mechanical pumps, which require 
muscle energy. 

two elements, alveolar gas exchange and capillary exchange, require 
diffusion, which needs concentration gradients.

pumps function to maintain concentration gradients and decrease diffusion 
distances.

the four links of PULMONARY TRANSPORT SYSTEM:

1.:PULMONARY VENTILATORY PUMP
the chest wall, muscles, diaphragm, intercostals, large conducting 
airways. this is an external fluid pump - pumps AIR which is external to 
the body. used for bulk flow of solution of gas. is the mechanism for 
changing the gas medium: washes in oxygen, washes out CO2. This process 
is known as BREATHING.
it must be adequate in VOLUME and DISTRIBUTION. Volume must be 
proportional to metabolic rate. also all alveoli should get equal 
distribution of gas, and should match distribution of blood flow to the 
lung.

2. ALVEOLO-CAPILLARY DIFFUSION: 
-molecular flow of oxygen
-across the air/blood barrier (alveolo-capillary membrane)

GOOD EXCHANGE MEMBRANE QUALITIES: large area, thin, high flows, low 
velocity.
always need large area...wanna move traffic? need big freeways. area in 
lungs is greatly increased by increasing partitioning. surface area 
should be proportional to metabolic rate. so higher the met rate, more 
surface area you want. large mammals use low amounts of O2 at rest; small 
mammals use large amts - have large metabolic rates - need HIGHLY divided 
lung. [slides: human lung vs shrew lung] animals with higher metabolic 
rate have MUCH more divided lung...smaller alveoli, more of them. so much 
BIGGER AREA. membrane has to be THIN because of distance factor. need 
high flows, to keep O2 concentration high on the outside and low on the 
inside, to maintain concentration gradient so you get good exchange. and 
you want low velocity of flow...need enough time for gas exchange to take 
place. if blood zips through capillary, doesn't have time to pick up 
oxygen!

so the ventilatory pump (thoracic musculature) and the blood pump (heart) 
both work to refresh concentration gradients.

3. CIRCULATORY PUMP: internal fluid pump. 
-bulk flow of gas in solution, aided by a carrier system: hemoglobin 
(Hb).
Hb binds O2, as you recall, and since solubility of O2 in blood/tissue 
normally low, Hb is needed to carry it around. And Hb has properties 
which allow it to pick up O2 in lung and deliver it to tissues as we 
learned in biochemistry. We'll go over that again next week. Blood must 
be adequate in volume, cardiac output must be adequate, and blood must be 
distributed adequately to all parts of the lung and indeed to all parts 
of the body. we'll get to this next week. next week will be an 
improvement over this week, i'm told.

4. CAPILLARY-TISSUE DIFFUSION: molecular flow, powered by concentration 
gradient. flow to the cellular oxidation sites (mitochondria) from the 
RBC - oxygen flows across blood-tissue barrier.

SO. each of the above links is a flow: bulk or diffusional.

FLOW = Quantity/Time
     = volume/time
     = liters/min
O2 Flow = V* O2
CO2 Flow = V* CO2

[note: really shoud be V with a dot over the top of the V. same symbol 
for O2 consumption. but i can't draw that with a plain text editor, so.]

each of these flows should be equal to each other and to the oxygen 
consumption, in a steady state. think bucket brigade. if flow isn't 
equal, you can't put out the fire. there's a bottleneck, you have a 
problem. in healthy animal at rest, shouldn't be any bottlenecks. when 
excercising, you see bottlenecks sometimes.

now go back to gross anatomy. remember that? we can say that despite 
there being hundreds of millions of alveoli..are they anatomically 
complex? there's a very intricate system of distributing air through the 
lungs...the arborization of the bronchial tree is complex, and the 
capillary network through the lungs is quite complex, but the alveoli 
themselves are pretty simple to think about. there's a diagram in the 
handout. remember this model

there's an airway, and alveolar gas volume, a diffusing membrane, a 
capillary, and an enclosure (chest wall.) page R1-4

AIRWAY: connects alveolus to outside. doesn't exchange gas. acts like a 
tube: offers frictional resistance to flow. so you have to think of it as 
"dead space." airways are highly complex branching tubes, but don't have 
to think of it that way.

ALVEOLAR GAS VOLUME: represents gas exchange surface. all gas exchange 
takes place in the alveoli. mechanical properties of it are like a 
balloon - offers elastic resistance to stretch, like a balloon. in 
reality, alveoli don't actually STRETCH, they kind of fold open like a 
paper bag. but think of them as a balloon. lung as a whole DOES stretch 
like balloon.

DIFFUSING MEMBRANE

CAPILLARY: vessel containing pulmonary capillary blood, to exchange gas 
w/alveolus. these are in walls of alveoli, and form rich network of 
vessels...it's like a sheet of blood surrounding alveolus

ENCLOSURE: notice that it surrounds alveolus and blood vessels and MOST 
of airway system - but not all. chest wall, contains muscles we learned 
in anatomy.
major forces of ventilation comes from contraction of respiratory msucles 
esp diaphragm. at rest, principle muscles are inspiratory: diaphragm and 
intercostals - this is true for many animals, and humans too. there are 
TWO species where inspiration is active, AND expiration is active: these 
are horses and dogs - highly athletic species (well, not english 
bulldogs...:)) but anyway, those two species have active contracting 
muscles during expiration as well. so, wehn inspiratory muscles contract, 
thorax enlarges and make a negative pressure pump - subatmospheric 
pressure in thorax sucks air in. 
also know that the thoracic pump is of large diameter (compared to heart) 
and is therefore inefficient - similar to dilated heart being 
inefficient. 
recall that lungs are plastered to inside of thorax, held open by pleural 
fluid linkage: adhesive forces between parietal and visceral pleura; 
therefore lungs passively follow movement of thorax.

look at diagram. some important consequences: forces generated by 
enclosure act on EVERYTHING inside thorax - including airways, esophagus, 
blood vessels, heart. all acted upon by respiratory muscles. vessel 
diameters increase on inspiration and decrease on expiration, affecting 
resistance to flow. important to consider during excercise. 
high pressure within chest can narrow airways and inhibit venous return. 
when excersising, expiration is always the limiting factor. if you take m ore gas in than you put out, you blow up! you have to get the gas OUT of 
the lung...need strong expiratory maneuvers. we'll talk about this more 
tomorrow.

in south bronx: didn't have playgrounds. they used to take a little kid 
and ask them to hyperventilate, causing them to blow off CO2, causing 
constriction of cerebral vessels. then told them to put thumb in mouth 
and blow (raising intrathoracic pressure) - reduces venous return, 
reduced cardiac output - makes kid faint. this is the game RO used to 
play as a child...

so for PPV you can't use too high a pressure or you'll shut off venous 
return.

important to realize ALL intrathoracic structures are affected.
how many conducting airways are there? ONE. air must come and leave via 
same airway. it's not a circulatory system. you don't have an in-way and 
an out-way.  so lungs are only intermittently ventilated. when you 
breathe out, you are not breathing IN. oxygen rich air enters only on 
inspiration. CO2 leaves only on expiration - so expiration is 
physiologically like holding your breath...not getting any new oxygen.

ventilation = volume of gas/unit of time = tidal volume * frequency

V* = Vt * f

if you have periodic ventilation, concentration of gas in alveolus will 
vary. 

[O2] in alveolus is high during inspiration, and low during expiration.
[C02] in alveolus low during inspiration and high during expiration.

you want to minimize the extremes. minimize the changes. so you need to 
have a large volume. the tidal volume is only a fraction of total lung 
volume. so each tidal volume you bring in is diluted by the FUNCTIONAL 
RESIDUAL CAPACITY which buffers the lung against changes.

if someone throws a bucket of ice into your bath, you will definitely 
notice.
if someone throws a bucket of ice into the ocean of the jersey shore 
while you're frolicking in the ocean off miami beach, you will not notice 
- large oceanic volume buffers against change in temperature.
large alveolar capacity buffers against change in gas concentration.

dead space: only part of air that enters with each tidal volume is fresh 
air. the first slug of gas to hit alveolus is the air that was sitting in 
the dead space after the last expiration. fresh air follows. also when 
you breathe out, the first thing you breathe out is the fresh air sitting 
in the dead space, followed by alveoloar CO2 rich gas. so dead space 
decreases efficiency. 

tidal volume Vt = alveolar volume Va (fresh air volume) + Vd (dead space 
volume)

Vt * f = [Va + Vd] * f

Va *f = [Vt-Vd] *f

V*a = V*t - V*d

alveolar ventilation = tidal volume ventilation minus dead space 
ventilation

If you keep total ventilation the same, and lower frequency f, you 
increase alveolar ventilation

if you keep alveolar ventilation constant at 5 L, at low frequency you 
need bigger tidal volume and as frequency increases tidal volume falls.

GIRAFFES: long necks, large dead space....so narrow trachea to minimize 
dead space, so need a lot of work to move gas through trachea. giraffes 
breathe at low frequency and high tidal volume to minimize velocity 
through trachea. excersising giraffes get tired very quickly.
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