Structure and Function Flashcards
Partial pressure of water
47 mm Hg
What has the greatest % of air?
Nitrogen
Oxygen
Argon
CO2
Transpulmonary Pressure
Difference between the pressure in the air in the lung and the pleural space outside the lung
Conversion of pressure from mercury to H2O
1 mm Hg = 13 mm H2O
1 mm Hg = 1.3 cm H2O
Henry’s Lw
conentration of a dissolved gas = (solubility of the gas) x Partial Pressure of the gas
relates how much is in gas phase with how much is dissolved in the water
It just says that if you present a given pressure of the gas to the liquid it tells you how high the concentration of the gas goes into the liquid based on the solubility. If this s, the solubility is a higher number, then for the same partial pressure more of the gas would go into the water.
If a gas is more soluble, more will go intothe water,- the molarity will be greater (but the pressures will still equalize to the air!)
volume and surface area relationship
with increasing side, volume increases faster than SA
vol is proportinal to O2 demand
SA is proportional to O2 uptake
vol increases ^3, SA increasease ^2
Convection
flow = dP/R
for laminar flow, R is proportional to radius^4
Fick’s Law
the flux for a substance is proportional to the concentration gradient
flux of molecules per time across this membrane is again proportional to the concentration gradient, it’s just the difference in pressures of the two gases, times a constant.
const:
increase area –> increase flow (more space to go across)
thicker barrier = decreased flow
bigger gradient of P = bigger flow
D(L) = diffusion capacity
** ew want bigger SA, smaller diffusion barrier (big area and thin), bigger P gradient
fractal branching
every time it branches it goes down by the same scaling factor. That’s what a fractal geometry is
factor = 3/4 decrease - allows trachea plug into alveoli
dimensions of each geeration of re a fixed fraction of a previous generation
Hess-Murray Law
branching pattern with minimal energy cost
sum of the cubes of diameters stays the same for each generation
.79 = scaling factor
bigger tubes = lower resistange BUT more dead space (more E to make more blood)
You want the tubes as big as possible for low resistance but you want them as small as possible for other metabolic costs of having that space there and in the lung it’s this thing called dead space, which is the volume of air that you breath in that never gets to the alveoli to do what you want it to do.
as we branch out into the lung the total cross sectional area with each generation gets bigger and bigger and bigger. Each individual cross sectional area of those tubes gets smaller, but you have double the number of tubes at each generation and you balance those things. The total cross sectional area gets really big.
cross sectional area of the lungs
as get smaller - velocity slows and cross sectional area increases!
conducting airways
convection is used
trachea, bronchi, bronchioles, terminal bronchioles
Things are moving like bulk
dead space! wasted ventilation
acinar airways
respiratory brnchioles, alveolar ducts, alveolar sacs
diffusion here!
what happens to inhaled particle or droplet?
conducting airways - cough, mucociliary elevator
respiratory airways - alveolar macrophages
type 1 epithelial cells
branch into epithelial plates
1 cell can cover huge area with min nuc-cyto distance
connect multiple epithelial place
cost- complex cells make cell division difficult, so type 2 cells replace when type 1 cells die
interdependence
the network of fibers and cables connects the pleural surfaces, septal walls, airway walls, cables running through
So everything tends to expand and contract together.
structural elements of the lung aren’t necessarily under high tension inside the tissue under normal circumstances represented by this kind of floppy line here (orange arrow), but there’s another force that’s tending to contract the lung making it smaller represented by these arrows, which is the surface tension at the surface of the lung (turquoise arrow), where the liquid layer at the surface of the lung meets the gas there is a phenomenon called surface tension that’s trying to make everything smaller that bears a lot of the tension of the lung and is responsible for why the alveolar structures kind of join each other and look like soap bubbles. Surface tension is what explains the geometry of soap bubbles
flow-limitation
inherent despign prpblem - when expire (need P gradient to move air) - pressure in alveoli around the airwas is greater than the P inside the airways - lead to collapse!
cable system is a teather andhold sthe airways open - even when you push harder and harder and harder to push the air out the flow reaches a certain maximum and can’t get any higher. And this becomes more of a dramatic problem in emphysema.
bleeding in the lungs
almost alwas from bronchial artery - systemic arterial blood into airways!
RBC time in capillary
3/4 second in capilarry
traverse 2-3 alveoli in this time
breathing and work
expiration is passive
work done in inspiration is stored
Measuring here at the mouth (bottom point, point 1) the pressure it takes to inflate, like blowing up a balloon. You could imagine blowing up the lung to this volume and then stopping and measuring the pressure and then stopping (point 2) and slowly blowing it up again to this volume (point 3) and measuring the pressure and you come up with a pressure volume curve. If you go all the way out to this volume (point 5) you’ve expanded the lung and performed work on the lung which can be expressed as the product of pressure and volume. You probably learned this in cardiology and in chemistry and physics in college. But basically the area of this shape is the energy, the work that you’ve done on the lung. The energy you’ve put into the lung to expand it. And this is done in this experiment very slowly. We’re just at the static aspects of the lung.
elastin
stores energy when stretched
can be degraded by protease - emhysema
surface tnsion
Force/Length
measure of the force bringing the surface molecules together at a gas liquid inerface - can be thought of as the force needed to prvent a unit length cut in a surface from opening
surfactant
If you just had water on the surface of your lung in contact with air, that surface tension would be so high that you can’t really, you wouldn’t really be able to breathe.
The polar head is in contact with the water so the water at the surface is now happy. It’s attracted equally in all directions and there’s no longer this surface tension problem.
embryonic folding
day 22-28
folding of trilaminar germ disc
folding occurs due to rapid growth of embryo while yolg sac is same
lateral mesoderm parts
somatic mesoderm
splanchnic mesoderm
septum transversum
forms during folding (wk 4)
partially separates thoracic and abdominal cavities (remain connected via pericardioperitoneal canalcs)
pleuropericardial folds
grow in from lateral walls above septum transversm
join and form pericardial space and 2 pleural spaces
- In these cross sections, the pleuropericardial folds are coming in.
- Ultimately, they are going to fuse, in a way, as shown in C.
pleuroperitoneal membranes
grow in from posterior and close pericardioperitoneal canals (wks 5-7)
diaphragm
septum transversum
pleuroperitoneal membrane grows in to close peericardioperitoneal canals
paraxial mesoderm grown in too
•Once fully formed, the diaphragm is derived from the septum transversum, a small amount from the pleuroperitoneal membrane, some mesenchyme from the esophagus, and then what’s called paraxial mesoderm, coming from the chest wall.
•
congenital diaphragmatic hernia
most common = failure of pericardioperiotneal canal closure
more often in left posterior location (Bochdalek - back and to the left)
if large - lung growth is defective (mechanical signals)
- are as the septum transversum is forming.
- If the defects are really big, it’s a big problem for the developing fetus because the abdominal contents follow the pressure gradient and end up in the chest.
- You see in this picture the herniation of intestines up into the chest.
- This is a big problem because some of the signals for the normal lung growth are mechanical signals. The lung has to be sensing the proper mechanical forces to do all the branching and so forth.
GATA4
mutations in some CDH cases
fibroblasts migrate into diaphragm area and send signals to myocytes to survive and follow
if not there - apoptosis of muscle cells
lung bud
priginates from foregut above septum transversum
from foregut endoderm and splanchnic mesoderm (around)
development of the respiratory diverticulum
lung bud - fusion makes tracheoesophageal septum
•There is a fusion event that serves to separate the evolving passageway in the lung from the tube lumen of the gut, similar to the fusion for the embryonic coelom.
As a result, you end up with a discrete beginning for the larynx and trachea, and esophagus.
esophageal atresia
90%, most common
separation doesn’t occcur - esophagus ends as a blind pouch + tracheoesophageal fistula
feedings are aspirated - cause impaired gas exchange and penumonia
surgery
branching morphogenesis
- This is dichotomous branching: each endpoint of a branch splits into two new branches. It’s always one turning into two.
- You go through multiple rounds of branchings.
- The first 16 generations of branches are completed by 16 weeks
- Amazingly, this occurs in a stereotypical pattern.
- If you take the 10th generation and look at how it branches into two new tubes, it’s not random. It doesn’t branch in a random direction.
- It’s always occurring in a specific plane and direction, so that you form the correct lobes, geometry, etc., of the lung.
- Somehow the system “knows” how to do this.
- The final 7 generation to get the final 23 branches of generations occur as random dichotomous branching.
You always split into two. Therefore, you can calculate how many total generations you have
what does epitelium of lung branch into?
surrounding mesenchymal tissue
, the mesoderm that is going to become cells like fibroblasts, smooth muscle cells, vascular cells, endothelial cells, etc
branchless
(FGF)
secreted signalling molecule to endoderm
- there are areas in the mesoderm around it that are secreting a molecule called Branchless. If you don’t make that, you don’t get any branches, hence the name.
- It attracts outgrowth of this tracheal sack, in the direction towards the source of this growth factor.
inhibited by sprouty!!
FGF10
•mesenchymal cells releasing FGF-10 (in this case) to attract epithelial growth.
mesenchyme induces endodermal preanching and induce negative regulators from endoderm
Shh
epithelial cells release it to the mesoderm to inhibit FGF secretion
turn off FGF
domain branching
- you have a tube, and then proximal to distal, all of the branches are going off in one direction, to have a series of branches on one side.
- [See picture in a.]
- Then, at a 90 degree angle to that set, you start to get a second set, then 90 degrees to the second set you have another series of branches, and then another set, etc., so the whole things turns out looking like a bottle brush. This is one way of thinking abut it. They start out in one direction, then the second direction, and so on. In the end, they are growing out in all four directions.
planar bifurcation
•, the branch comes out and then splits into two, and then the next branches they stay in the same plane that the first two were in.
all in the same plane
orthoganal bifrucation
orthogonal bifurcation, has the next set of branches at right angles to the first, so that they go right and left rather than up and down
pleural space
derived from intraembryonic coelom!
potential space between the outside of the lung and the chest wall
•Normally there are only a few ccs of liquid in the pleural space to lubricate as the lungs slide against the chest wall.
visceral pleura
from splanchnic mesodierm
parietal pleura
from somatic mesoderm
influence of surface tension on lung inflation pressures
takes a ton of P to inflate lungs with air
takes very little P to fill lungs with saline
if use surfactant - less work to inflate lungs!
embryonic stage
4-5 wks, 3 branchings (initial branching of lung buds
pseudoglandular stage
terminal bronchioles formed - 5-16 wks
canalicular stage
terminal bronchioles divided into 2+ respiratory bronchioles
lung vasculature starts to form
16-26 wks
terminal sac stage
primitive alveoli form
type ii cells appear
capillaries next to sacs
26 wks - birth
- These are the structure that are just mature enough to get enough gas exchange.
- They get enough blood supply to start to exchange oxygen and carbon dioxide.
- For our purposes, the importance of this phase is that the type II epithelial cells start to appear.
alveolar stage
8 months - childhood
alveoli mature and increase
type ii begin surfactant secretion soon before birth!!
alveolar type II cells
more cupoisal than type I
metabolically active
make surfactant
drug for pre term labor
corticosteroids
induce surfctant production in fetus
premature infants without surfactant develop respiratory failure due to high surface tension at air ;iquid interface
RDS
respiratory distress syndrome
respiratory failure due to no surfactant and high surface tension
mechanical ventilation and exogenous surfactant
surfactant turnover and metabolism
•there are specialized vesicles in the type II cell that allow it to secrete the phospholipids that are initially in this aggregated form called tubular myelin.
deep breath = increased SA = need more surfactant from subphase to surface
•The ability to get the surfactant to the surface may be lagging behind the increase in surface area.
These movements of surfactant from the surface to the sub-phase and back and forth occur even in the timeframe of individual breaths
longer tem: , the surfactant can get resorbed from the surface and endocytosed back up either into type II cells or macrophage
llamelear body
secreted and packaged surfactant
unravel and coat the surface of the liquid
GM-CSF
- huge amounts of surfactant build up in the air spaces.
- People start to develop respiratory failure.
- GM-CSF has a specific effect on alveolar macrophages, activating their ability to turn over surfactant.
- If you have an animal without GM-CSF, the macrophages are there, but they don’t take up and metabolize and recycle the surfactant, so it builds up.
definicency causes buildup of surfactant material in alveolar space
pulmonary alveolar proteinosis
