Structure and Function

Question 1

Partial pressure of water

Answer 1

47 mm Hg

Question 2

What has the greatest % of air?

Answer 2

Nitrogen

Oxygen

Argon

CO2

Question 3

Transpulmonary Pressure

Answer 3

Difference between the pressure in the air in the lung and the pleural space outside the lung

Question 4

Conversion of pressure from mercury to H2O

Answer 4

1 mm Hg = 13 mm H2O

1 mm Hg = 1.3 cm H2O

Question 5

Henry’s Lw

Answer 5

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!)

Question 6

volume and surface area relationship

Answer 6

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

Question 7

Convection

Answer 7

flow = dP/R

for laminar flow, R is proportional to radius^4

Question 8

Fick’s Law

Answer 8

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

Question 9

fractal branching

Answer 9

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

Question 10

Hess-Murray Law

Answer 10

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.

Question 11

cross sectional area of the lungs

Answer 11

as get smaller - velocity slows and cross sectional area increases!

Question 12

conducting airways

Answer 12

convection is used

trachea, bronchi, bronchioles, terminal bronchioles

Things are moving like bulk

dead space! wasted ventilation

Question 13

acinar airways

Answer 13

respiratory brnchioles, alveolar ducts, alveolar sacs

diffusion here!

Question 14

what happens to inhaled particle or droplet?

Answer 14

conducting airways - cough, mucociliary elevator

respiratory airways - alveolar macrophages

Question 15

type 1 epithelial cells

Answer 15

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

Question 16

interdependence

Answer 16

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

Question 17

flow-limitation

Answer 17

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.

Question 18

bleeding in the lungs

Answer 18

almost alwas from bronchial artery - systemic arterial blood into airways!

Question 19

RBC time in capillary

Answer 19

3/4 second in capilarry

traverse 2-3 alveoli in this time

Question 20

breathing and work

Answer 20

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.

Question 21

elastin

Answer 21

stores energy when stretched

can be degraded by protease - emhysema

Question 22

surface tnsion

Answer 22

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

Question 23

surfactant

Answer 23

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.

Question 25

embryonic folding

Answer 25

day 22-28 folding of trilaminar germ disc folding occurs due to rapid growth of embryo while yolg sac is same

Question 26

lateral mesoderm parts

Answer 26

somatic mesoderm splanchnic mesoderm

Question 27

septum transversum

Answer 27

forms during folding (wk 4) partially separates thoracic and abdominal cavities (remain connected via pericardioperitoneal canalcs)

Question 28

pleuropericardial folds

Answer 28

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.

Question 29

pleuroperitoneal membranes

Answer 29

grow in from posterior and close pericardioperitoneal canals (wks 5-7)

Question 30

diaphragm

Answer 30

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. •

Question 31

congenital diaphragmatic hernia

Answer 31

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.

Question 32

GATA4

Answer 32

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

Question 33

lung bud

Answer 33

priginates from foregut above septum transversum from foregut endoderm and splanchnic mesoderm (around)

Question 34

development of the respiratory diverticulum

Answer 34

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.

Question 35

esophageal atresia

Answer 35

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

Question 36

branching morphogenesis

Answer 36

* 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

Question 37

what does epitelium of lung branch into?

Answer 37

surrounding mesenchymal tissue , the mesoderm that is going to become cells like fibroblasts, smooth muscle cells, vascular cells, endothelial cells, etc

Question 38

branchless

Answer 38

(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!!

Question 39

FGF10

Answer 39

•mesenchymal cells releasing FGF-10 (in this case) to attract epithelial growth. mesenchyme induces endodermal preanching and induce negative regulators from endoderm

Question 40

Shh

Answer 40

epithelial cells release it to the mesoderm to inhibit FGF secretion turn off FGF

Question 41

domain branching

Answer 41

* 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.

Question 42

planar bifurcation

Answer 42

•, 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

Question 43

orthoganal bifrucation

Answer 43

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

Question 44

pleural space

Answer 44

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.

Question 45

visceral pleura

Answer 45

from splanchnic mesodierm

Question 46

parietal pleura

Answer 46

from somatic mesoderm

Question 47

influence of surface tension on lung inflation pressures

Answer 47

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!

Question 48

embryonic stage

Answer 48

4-5 wks, 3 branchings (initial branching of lung buds

Question 49

pseudoglandular stage

Answer 49

terminal bronchioles formed - 5-16 wks

Question 50

canalicular stage

Answer 50

terminal bronchioles divided into 2+ respiratory bronchioles lung vasculature starts to form 16-26 wks

Question 51

terminal sac stage

Answer 51

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.

Question 52

alveolar stage

Answer 52

8 months - childhood alveoli mature and increase type ii begin surfactant secretion soon before birth!!

Question 53

alveolar type II cells

Answer 53

more cupoisal than type I metabolically active make surfactant

Question 54

drug for pre term labor

Answer 54

corticosteroids induce surfctant production in fetus premature infants without surfactant develop respiratory failure due to high surface tension at air ;iquid interface

Question 55

RDS

Answer 55

respiratory distress syndrome respiratory failure due to no surfactant and high surface tension mechanical ventilation and exogenous surfactant

Question 56

surfactant turnover and metabolism

Answer 56

•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

Question 57

llamelear body

Answer 57

secreted and packaged surfactant unravel and coat the surface of the liquid

Question 58

GM-CSF

Answer 58

* 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