---start physio 1.4.97----

RO's office is rm 211 E Old Vet
no office hrs,just go whenever.

he says it's easier to prepare for EXAMS than REEXAMS....

lab conference friday at 11:05 am.

we talked before about how in the alveolar compartment, pO2=100, pCO2=40. 
in room air, pO2=160, pCO2=0.

remember total pressure in alveolus = atmospheric pressure

Patm = PaCO2 + PaO2 + PaN2 + PaH2O

N2 is inert

It's important to know that if you breathe 100% oxygen you do NOT wash 
out CO2. If you breathe 100% O2 and metabolism/ventilation doesn't 
change, CO2 will stay constant. Also you will not wash out the water 
vapor. You will only wash out the nitrogen. No matter how hard you 
breathe, you won't get rid of CO2 or H2O.

So, the concentrations of O2 and CO2 in alveolus stay constant. There are 
reflexes involving the brain which keep them constant. despite our prior 
discussion, we'll consider that O2 and CO2 stay constant in time in 
alveolus - we're ignoring the slight variation w/each breath.

now if alveolar gas concentrations stay constant, then alveolar 
ventilation must be proportional to metabolism, in terms of O2 and CO2 
consumption/production. This is because amount = concentration * volume 
(conservation of matter)

V*CO2 =    FaCO2       x        V*a

metabolic =  concentration   x   alveolar ventilation
production  (CO2 fraction)
of CO2 

could also look at it in terms of pressure

V*CO2 is proportional to PaCO2 * V*a

PaCO2 is proportional to V*co2 * V*a

if ventilation is proportional to metabolism, CO2 stays constant.
what if we alter ventilation while metabolism stays same?

V*CO2 is proportional to V*a x PaCO2

If ventilation DECREASES, PaCO2 will rise. as you put out less CO2, the 
CO2 must rise, if being produced at constant level. so you have a new 
steady state, where amount CO2 produced is excreted at low volume and 
high concentration. This is HYPOVENTILATION: insufficient volume of fresh 
air relative to metabolic rate: decreased alveolar ventilation 
accompanied by increase in PaCO2 in alveolus and PCO2 in blood. 
Similarly, the concentration of oxygen falls.

If alveolar ventilation INCREASES, PaCO2 will FALL, assuming constant 
metabolism.  You are temporarily excreting more CO2 than normal. The 
level of oxygen will rise. This is HYPERVENTILATION: too large a volume 
of fresh air relative to metabolic rate. increased alveolar ventilation 
accompanied by decreased PaCO2 and increased PaO2.

HYPERPNEA is when the volume of ventilation RISES IN PARALLEL with 
metabolic rate. see graph of O2 uptake.

with increased metabolic rate, ventilation rises while O2 and CO2 
concentrations remain constant. (in handout, graph is on control of 
ventilation) This graph WILL be on exams, so make sure you understand - 
could increase in ventilation in exercise be caused by increase in CO2? 
NO NO NO - during moderate exercise, there IS NO RISE IN CO2.

Note also graph of metabolic hyperbola.
if ventilation goes up, CO2 goes down, if ventilation goes down, CO2 goes 
up. if you have a normal PCO2 of 40, the adequacy of ventilation can be 
measured by looking at alveolar PaCO2. Ventilation WRT metabolic rate is 
what is important, see.

PaCO2 is proportional to V*CO2/V*A

The best way to estimate alveolar CO2 is to measure arterial CO2.

PACO2 is proportional to PaCO2

Arterial				alveolar

if PACO2 is low, ventilation is too high, reflex will slow ventilation. 
if high, vice versa. This is what you do clinically as well.  You can do 
ABG to check PACO2 while animal is on ventilator, for example....

a single measure tells you if ventilation is adequate wrt metabolic rate. 
we'll need to know that it's an arterial PACO2 that is what you'd measure 
to see if ventilation is adequate....

ventilation provides to alveolus intermittent wash in of O2 and wash out 
of CO2. this affects gas concentration in alveolus, and blood 
equilibrates w/alveolus, picking up O2 and dropping off CO2. this will 
determine how well blood is "arterialized".

ROLE OF VENTILATION

1. increase alveolar PO2 above that of venous blood.
2. decrease alveolar PCO2 below that of venous blood.

gas exchange occurs via passive diffusion process, driven by 
concentration gradients. It's called PULMONARY DIFFUSION aka PULMONARY 
GAS TRANSFER. we're interested in flow of gas, mL/min, from alveolus to 
capillary and vice versa.

FLOW = Quantity/time
       volume/time
       liters/min

O2 flow = V*O2
CO2 flow = V*CO2

ventilation is intermittent, but GAS TRANSFER is CONTINUOUS!

FLOW = difference in pressure / resistance

V*O2 = change in P/Rz eg, concentration gradient over resistance.

the difference in PaO2 between alveolus and blood.

graph of "transit time in capillary"

Alveolar PO2 stays CONSTANT at about 100.
venous blood enters exchange membrane at PO2 of about 40. so, at the 
beginning, there's a driving force for oxygen from alv. to blood of 60 
mmHg. so blood continuously picks up O2, and the PO2 in blood rises until 
PO2 in blood = 100. Once this takes place, there is no more net exchange.


so we can say rate of O2 pick-up is dependent on pressure difference at 
each point along capillary. It's HIGH early while crossing membrane. Rate 
is also dependent on shape of the oxyhemoglobin dissociation curve.

Alveolar PCO2 is 40. Venous blood has PCO2 of about 46. So there's a 6 
mmHg gradient driving CO2 from blood into alveolus. This is a much 
smaller driving force than for oxygen. Blood will lose CO2 until the PCO2 
of blood is 40, then no more net exchange.

FLOW = DIFF in PRESSURE/ RESISTANCE

what are barriers to diffusion? 

1. terminal alveolar gas unit. gas moves mostly by bulk flow into 
respiratory 
   zone and then diffuses. (gas phase) - this is diffusion in the gas 
phase. 
  

2. Alveolo-capillary membrane: a tissue barrier from epithelium through 
red cell
   in the capillary. includes surface lining layer, epi layer, 
endothelium, 
   plasma, and rbc membrane
 
3. chemical rxns inside the RBC.


FACTORS influenceing diffusion in terminal alveolar unit: (gas phase)

absolute temperature....diffusion is due to thermal motion of molecules, 
so the higher the temp, the more diffusion, the higher rate of gas 
transfer. so during excercise, body temp rises to increase diffusion 
rates and gas transfer

molecular wt: kinetic energy = kmv^2, v = 1/root km (grahams law). O2 
diffuses faster in gas phase because it's heavier.

distance

area

mean free path: how far does molecule have to go before hitting another 
molecule? mols are far apart in gas phase, could go a ways before hitting 
another mol. CO2 and O2 diffuse very rapidly in gas phase. if distance is 
short and area large, mean free path long. in healthy animals at rest, 
it's considered to be instantaneous --> eg, "instant" mixing of new fresh 
air with functional residual capacity.

ALVEOLAR CAPILLARY MEMBRANE: factors influencing diffusion in tissue 
phase

thicker in some places than other...may have nuclei or extra CT in some 
places.
what does diffusion depend on here?

absolute temp, molecular wt as above

solubility: to diffuse in tissue phase, gases must dissolve in tissue.
this depends on how many molecules are present that can diffuse. the 
higher the solubility, the greater the rate of diffusion. CO2 is 24x more 
soluble than O2
henry's law: says amount dissolved is proportional to partial pressure. 
that proportionality concept is the solubility of the gas. what's 
important in body is that CO2 is 24x more soluble in tissue than oxygen 
is. this high solubility means diffusion transfer of CO2 is large.

thickness - length of diffusion path. is variable. some parts of membrane 
very thin, other parts are thicker. many dz cause increased thickness, eg 
pulmonary edema increases thickness. fibrosis will increase thickness.

area: relates to capillary beds that are open and contain flowing blood. 
must get gas into blood/out of blood. so it's the area of functioning 
alveoli in contact with functioning capillaries. this area will increase 
in exercise - can triple, in fact, due to opening previously unperfused 
capillaries. can decrease w/disease eg fibrosis - collagen closes off 
blood vessels. emphysema: destroys tissue, decreases diffusion area. high 
positive pressure ventilation can increase intrathoracic pressure such 
that it collapses the capillaries and decreases diffusion area.

CO2 retention:

results from hypoventilation
is never seen as a result of a diffusion block.

diffusion block --->
    decreased arterial PO2---->
      increased ventilation ------->
        decreased arterial PCO2

because CO2 diffuses faster than oxygen.
PO2 is first affected by diffusion block. so when you have this problem, 
you have low oxygen and low carbon dioxide. ****???

If CO2 is low, the animal CAN ventilate. may have other probs...

CHEMICAL RXNS INSIDE RBC

O2 + Hb ---> O2Hb (oxyhemoglobin)
not instantaneous, takes time. because it takes time, this constitutes a 
delay in loading of O2 or unloading of CO2. must have chemical rxns 
first. like at a tollbooth...if someone asks for instructions, you have 
to wait behind them, they're causing a delay in flow down the highway.

RBC COMPONENT DIFFUSION FACTORS

chemical rxn rates are temperature dependent --> rate increases as temp 
increases.

volume of capillary blood: more blood = faster rxn rate --> so can triple 
w/excercise again.

TIME DIFFUSION FACTORS:

contact time: time available to achieve equilibrium - eg time for a 
single rbc in capillary to exchange gas. time spent by an rbc in 
capillary. each rbc makes only one pass across the exchange surface - 
limited contact time. at rest in humans is about .75 sec. it varies in 
animals and isn't a huge deal to know species specific values. just know 
that it's an important factor. 

equilibration time: time needed to achieve equilibration. depends on 
amount of gas to be transferred (function of metabolic rate), difference 
in partial pressure - the driving force. the greater the driving force, 
the faster the exchnage - increases w/exercise. also depends on chemical 
rxn rates. 
requires about 0.35 sec in humans. 

so you can double the speed from .75 to .35 sec, and still get 
equilibration.
the relationship between contact time and equilibration determines the 
effectiveness/rate of gas transfer. you need the blood to go through 
slowly enough to equilibrate.

if CO goes up 5x in exercise, we can't allow velocity to increase 5 
times, only can let velocity increase 2 times. so capillary beds open, 
increasing area and limiting velocity increase due to increase in cross 
sectional area.

time factors figure very prominently in failure of equilibrium in 
pulmonary dz and heavy exercise in humans and horses.

---break----

R4-4 shows equilibration diagram

PULMONARY DIFFUSING CAPACITY

resistance = pressure / flow

conductance = flow/resistance

diffusing capacity = flow/mean driving pressure

a measurement of DC combrises area, thickness, solubiltiy, molecular wt, 
and something else at the bottom of slide. mainly area and thickness

--

CO2 is transported from tissues to lungs. transport = portion of total 
gas in blood that is actually exchanged - eg in tissues or lungs. 

TRANSPORT involves two main elements of circulatory apparatus

1. movement of blood: blood flow = volume/time = Q

2. carriage of gas in blood = content/unit volume = concentration

amt gas carried = concentration x volume

oxygen flow (arterial) = Q* x CaO2

tissue uptake (V*O2) = arterial flow - venous flow (amount brought in 
minus 
														amount that leaves.)

						
						= flow x extraction

you can increase oxygen delivery to tissue by increasing CO or increasing 
% extraction.
all animals do both in exercise, some one more than another. Increasing 
extraction saves cardiac work and is a good way to save energy. at high 
metabolic rates eg during exercise you see this occur.
see p R5-2 for equations.

what determines gas content in blood? Dr Pehrson already discussed this 
with us.

VARIABLES IN O2 TRANSPORT

1. oxygen capacity
2. oxygen affinity - eg, affinity of Hb for O2 - steady state, pertains 
to arterial blood.
3. bohr shift: change in affinity of Hb for O2 that occurs during 
transition from arterial to venous or venous to arterial blood in 
tissue/lung.

1. oxygen capacity:
oxygen is very poorly soluble in tissues. because of this it is poorly 
soluble in blood, plasma, and amt carried in physical solu'n is 
proportional to PO2, but is always a very small amt. so if animal is 
breathing air, this amount of dissolved oxygen is basically negligible. 
the amount carried in conjunction with hemoglobin is more important. now, 
if animal is breathing 100% oxygen, the dissolved O2 can be a significant 
amount. also under increasing pressures, there is no limit to amt of 
dissolved oxygen or to PO2. so hyperbaric chambers are used to treat 
gangrene or other conditions needing high oxygen concentrations in 
tissues.

so.

O2 capacity is proportional to Hb concentration (at standard 
air/pressure)

increased [Hb] --> increased transport capacity

[Hb] is regulated by a renal mechanism
decreased [Hb], decreased SaO2, increased HbO2 affinity -->erythropoietin 
is 					 O2 sat													made.

transport dependent on RED CELL MASS --eg, overal # of rbcs.

what changes red cell mass? 
CO poisoning - binds Hb, get decreased O2 transport
anemial - fewer RBC - decreased O2 transport

how to increase Rbc mass?
at altitude, make mroe RBC after about two weeks...increased O2 transport

horses/dogs: contract spleen when exercising - release stored RBC
"blood doping"
training at altitude

2. oxygen affinity:

properties of a good oxygen carrier: can load and unload O2 in 
appropriate places - picks up large amounts in lung, releases large amts 
in tissues. Forms a loose chemical combination w/O2. Amount of O2 
combined w/carrier should vary w/level of PO2.

in mammals, affinity of pure Hb for O2 is VERY high, and it won't release 
O2 well. so the affinity must be modified, which is done by 
"environmental factors" inside the RBC. those factors are increases in 
temperature, DPG aka BPG, CO2, and H+. increases in these four factors 
cause a DROP in affinity of Hb for O2, favoring the deoxy state -- eg, 
promoting shift from R to T state.

changes in affinity are "cheap and easy" way to change oxygen delivery.

p R5-3 has charts showing effects of temp and pH on Hb saturation.
try to begin to think not in terms of percent saturation but in terms of 
content. anemic blood and normal blood have same saturation, but 
different CONTENT.

see p R5-6

---see R5-2 and R5-3-----
note that at high supply of O2, eg when PO2 is high, there is 100% 
saturation.
see normal venous point. note that it is 75% sat - vs 100% arterial. so 
only 25% is being taken up by tissue.

note P50--falls at about PO2 = 25. 

this is a sigmoid curve.

so the top is flat, at high PO2, moderate at low PO2, and steep at 
midrange PO2.
so to extract 25, you go from PO2 100 to 75. then you get to steep part 
of curve, and you only have to drop a little to get more relase.

[note - see handout. i'm getting this confused]
animals with high metabolic rates should have steep part of curve at high 
PO2 to drive diffusion. s

content increases slowly as PO2 rises at high PO2. you can maintain high 
saturation/high content at high PO2. remember that Hb becomes saturated 
early, above PO2 of 100, but you can add more dissolved oxygen. but 
little additional O2 can be added to Hb over 100 = PO2. so if you 
increase ventilation above PO2=100, you are pretty much wasting energy. 
best you can do is raise PO2 to about 130 which hardly raises content at 
all. but if you lower PO2 below normal, you can decrease content. so this 
is non-linear.

if you change the affinity, the curve moves to left (increased affinity), 
or right (decreased affinity). the effect of changing affinity is not 
uniform - small effects at top and bottom of curve, large effects at 
shoulder of curve.

look at top: if you change affinity, minimal effect on O2 content (at 
high PO2)
at middle, there are large changes in Hb sat.

you want to maximize the O2 delivery to tissues.

suppose you open a can of coke and heat it up. what happens to the CO2 in 
the coke? it goes away. do you worry about it? no. now take closed can of 
coke and heat it. you have a closed system. CO2 solubility goes down as 
gas goes up. so if you try to open that can...it's under high pressure.

in tissues, you want high pressure. you can acidify/heat blood to raise 
pressure. in lungs, you want maximal content.
---from here to upper marker - see p R5-2, R5-3-----

last variable in O2 transport is BOHR SHIFT
we've seen that affinity of Hb for O2 can be altered by change in 
ligands, as noted above. most important aspect takes place in tissues as 
blood moves from art side to ven side as metabolites and heat are added 
to blood. also occurs in lungs as blood moves from venous to art side and 
CO2, H+ are removed and blood is cooled.

metabolic products facilitate the unloading of oxygen. these products 
come from O2 consumption, and cause O2 release, so this is very good, the 
more O2 you use, the more favorable O2 delivery becomes. vice versa in 
lungs: unloading CO2 favors O2 uptake.

muscle will use as much O2 as it needs. wants to deliver O2 at high 
pressure to reach all cells. realize you need to change affinity of Hb 
for O2 to favor oxygen diffusion into tissue. don't need MORE oxygen, 
need the RIGHT AMOUNT at a favorable pressure.

when you have high metabolic rate, you want large Bohr effects, large 
bohr shifts, lots of oxygen delivered at high enough pressure. not MORE 
O2 but A LOT of O2 at high enough pressure. small animals need large bohr 
effects.

elephants have small bohr effects, mice/shrews very large effects. horse, 
dog, people, moderate effects. so if you change pH in blood in elephant 
from 7.2 to 7.4 you have only a small change in P50, whereas in mouse, 
it's a HUGE change.


effect of H+ and CO2 and Temp == bohr effect.

due to effect of H+ on Hb...allosteric interaction...both H+ reacts
 w/Hb, affecting ability to bind O2.
H+ can't penetrate RBC membrane. CO2 can, it's freely permeable. so the 
CO2 diffuses into RBC, rxn w/H2O, forms carbonic acid, dissociates, and 
forms H+ so CO2 is carrier of pH change inside the RBC. 
this is a rapid rxn due to presence of carbonic anhydrase, found ONLY 
inside RBC. so this rxn occurs inside the RBC. but we're talking about O2 
delivery...now we're saying it's important to have carbonic anhydrase as 
well as CO2 to ensure oxygen delivery.

recall that PO2 is lowest on venous side of capillary bed.
so it's important that this rxn take place very RAPIDLY because the 
poorest oxygenation is on venous side, where there is very little time 
left for blood to deliver oxygen, because blood is leaving exhange area 
quickly.


CO2 transport:

in contrast to the HbO2 dissociation curve, the curve relating CO2 
content to PCO2 is nearly linear in physiological range (unlike sigmoidal 
Hb curve), and is not limited by saturation of a carrier.

like O2, CO2 is transported in several forms

-physical solution: is dissolved in plasma and intracellular fluid of 
RBC. about 10% of CO2 is carried this way - compare to negligible amt of 
O2. CO2 more soluble.

-CO2 capacity of blood is increased by chemical combination and buffering

-chemical combination: direct addition of CO2 to Hb - carbamino protein 
formation. DeoxyHb more readily forms this addition - carbamino compound 
more readily forms in venous blood, venous blood more readily transports 
CO2. CO2 addition to blood facilitates O2 removal, and O2 removal 
facilitates Carbamino formation - which accounts for 10-20% of CO2 in 
blood.
also forms BICARBONATE

Haldane effect: what is effect of change in O2 concentration on ability 
of Hb to bind H+?
----break---

back to CO2 transport.

CO2 is formed by oxygen consumption in tissues. diffuses into plasma, 
then into RBC, where it becomes hydrated via carbonic anhydride, 
producing H2CO3 which dissociates into H+ and HCO3-

the opposite happens in lungs, so rxn moves toward left.
it's very important, if you want to maximize transport, that this rxn 
doesn't reach equilibrium. when it reaches equilibrium, it will stop. so 
to prevent it from doing so you must remove the products. you must remove 
bicarb from the red cells - so it diffuses out into plasma. so lots of 
bicarb is carried in the plasma, and bicarb is the main method of CO2 
transport in the blood.

you must also prevent accumulation of H+ - how? you can buffer it. tie it 
up so there's no free H+. what is most important H+ buffer? HEMOGLOBIN. 
bicarb by itself is not a good buffer, though it does do some buffering. 
it's a great physiological buffer, but not a good physical/chemical 
buffer - something to do with its pk. so Hb is a good H+ buffer.

H+ + HbO2- <===> H*HbO2
H+ + Hb -- <===>H*Hb

so both oxy and deoxy forms are buffers for H+

what is definition of buffer?
it minimizes pH changes.
if something is a good buffer, there will be minimal pH changes despite 
addition of acid to it.

[note: i'm having an awful time concentrating today, sorry]

now  deoxygenated Hb binds H+ more tightly than oxy Hb. when not bound to 
O2, Hb can accept more H+ without a pH change. so venous blood can carry 
and buffer more CO2 than arterial blood: this is the haldane effect.

you can remove oxygen, change the pH, and add H+ to restore original pH 
-> that's called isohydric buffering (?) and is due only to fact that 
oxygen comes off. about 70-80% of CO2 added to blood can be perfectly 
buffered by this mechanism. 

if oxygen doesn't come off, there's no isohydric buffering, and then you 
aren't ---something.

if oxygen doesn't come off, if you breathe 100% oxygen, you have acid 
blood, poor buffering, acidosis, ventilation will increase.

so, venous blood usually a bit lower (7.35) than arterial (7.4)

What is effect of +/- O2 on ability of Hb to bind H+? Is a better binder 
of H+ in the absence of O2.

HbO2- + H+ <====> H*Hb + O2 see page R5-4. you only get this buffer if 
oxygen COMES OFF. So Hb is not only an O2 carrier, it's also a CO2 
carrier in the form of H+.

see CO2 content/pressure graph p R5-5
the PCO2 of venous blood is about 46, content about 52.
what's PCO2 after going through lung? 40, and CO2 content drops to about 
50.

what else happens in lung? Hb converted to oxyHb. so you go from having a 
good buffer (weak acid) to a worse buffer (stronger acid) and this tends 
to drive off the CO2 as gas - which exits lung, a Good Thing.

oxyHb = strong acid. frees H+ to react w/bicarb, releasing CO2.
deoxyHb = weak acid. good buffer

[argh argh argh]

so as far as CO2 transport is concerned, it's important to remove the 
oxygen to make a better carrier for H+ (CO2)

now...ventilation/perfusion relationships.
this isn't in the handout (oh great, i'm screwed)

anyone ever been to opera? understand german/italian? well, even w/o 
understanding you can get a flavor. he's trying to give us a flavor of 
how lung works. this new info will be like foreign language. relax. 
hopefully we can learn a few of these things, the rest won't be on exam, 
just for flavor

when you ventilate, you MUST VENTILATE BLOOD. what % of CO goes through 
pulmonary circulation and lungs? 98% (probably 100% but venous return not 
perfect) ok, say 100%. if 100% of CO goes to lung, and part of lung not 
well perfused, where does rest of blood go? to other part of lung. so 
part of lung has too little perfusion and part of lung has too much 
perfusion. that's bad, we want to maximize gas exchange, so we want all 
parts of lung participating equally.

suppose we have an animal and one lung is not working at all.
the lung that receives ventilation, however, gets no blood flow.
how long can this animal live? not long. you MUST VENTILATE BLOOD. oxygen 
must go from lung to blood. so this is an extreme case, obviously animal 
will die.

you want to ventilate blood so that you just saturate the Hb, and get rid 
of all accumulated CO2. when we look at ventilation/perfusion 
relationship, it shoud be and usually is about a 1:1 ratio. same amount 
of flow to each alveolus. if one alveolus gets too much blood, another 
gets too little. if one gets too much ventilation, another gets too 
little. you want it to be about 1:1 to end up w/PO2 of 100 and PCO2 of 
about 40. if you overventilate an alveolus you aren't adding O2 to blood. 
underventilating causes CO2 buildup. if you underventilate enough, you'll 
get into steep part of oxyHb curve. so you want it just right. it needs 
to be perfect in every alveolus.

a horse on its side....the down lung gets squeezed down and is hard to 
ventilate. blood flow in that lung is increased, so you have bad 
ventilation where you have good perfusion and vice versa. this is bad. so 
horses don't lie on side a lot.

in normal animal, most alveoli are close to ideal. in dz states, some 
alveoli get a lot of ventilation, some get very little, it gets separated 
and is clearly suboptimal.

[phew, this has been review. now, everything from here down is TRUE but 
not going to be on exam :) ]

he's plotting a curve of PO2 vs PCO2.
looking at ventilation/perfusion relationships. suppose you have an 
alveolus that's ventilated but not perfused. what's the ratio of 
ventilation/perfusion?

V/0 = infinity

what's the concentration of gas in alveolus?  this alveolus gets no CO2 
so
PCO2 = 0 and PO2 = 150. we can graph that on the graph...
150 on PO2 axis (x) and 0 on PCO2 axis (y)

can you do any better than outside air? no. 

now suppose you have an alveolus perfused, but not ventilated.

V = 0
perfusion = Q
 
0/Q = 0

PCO2 = 46
PO2 = 40

put this on graph also.
note: can't do any worse than venous blood.

now...what's IDEAL V/Q? 1.

PO2 = 100
PCO2 = 40

plot this on graph also.
now, you can't do better than the best or worse than the worst. all 
alveoli must lie somewhere between the two extreme points, and must 
include the idea/normal as well, so now we have a line...all alveoli will 
be on it.

now we can discuss alveoli that have a ventilation perfusion ratio 
between zero and one (left half of line) or greater than one (right half 
of line)

the V/Q between 0 and 1 alveoli are overperfused, and don't pick up 
enough oxygen. so we call them "underventilated." too little ventilation 
for blood supply, or "overperfused" - too much blood for air supply.

what happens when you underventilate - hypoventilation wrt metabolic 
rate. but when you underventilate w/respect to blood, you're 
overperfused..these alveoli have high CO2 and low O2. they are 
hypoventilated.

then, you have the right side of the line, where V/Q is greater than one. 
there's a high PO2 and low PCO2 in these alveoli. low CO2 == 
hyperventilation. realize we're not talking about ventilation wrt 
metabolic rate now, but wrt blood. you MUST VENTILATE BLOOD.

in normal animals, all alveoli are at or very very close to V/Q = 1. 
diseased animals have variations...areas of low or high blood flow. as 
you get more and mroe pulmonary dz, you get more variation. when you get 
to the extremes, you have a lot of oxygen-poor blood. single most 
important cause of hypoxemia in pulm dz is uneven ventilation/perfusion 
ratio.

one more point (that is still not going to be on the exam, i guess)

oxyHb association curve:

O2 content (y) vs PO2 (x)

why don't alveoli compensate for each other? one has too much blood, 
other not enough...why not share? what happens when we mix poorly 
oxygenated blood w/well oxygenated blood? imagine a 50% shunt: 50% of 
venous blood bypasses lung, and has O2 content 15, PO2 of 40. the regular 
blood has content of 20 and PO2 of 100. now, if you mix 50 cc of 
each...what's the mixed PO2? well, contents mix...molecules mix...so 
content will be 17.5 - halfway between 10 and 20. the PO2 will end up 
around 55 per the oxyHb association curve. so the well oxygenated blood 
can't compensate for poorly oxygenated blood because the association 
curve is not symmetric. you always end up lowering O2 level more. if you 
overventilate lung, say you raise mixed content to 18 and mixed PO2 of 
58. a good lung canNOT compensate for bad lung due to uneven shape of 
oxyHb association curve. this is very important in considering lung dz.

---end---