Editing Respiration lecture notes

*started here on 02/24/10.

==Respiration==
*Respiration requires some stuff:
**We'll talk about convection system (that is, ventilation and cirulation).
**We'll also talk about mechanisms for gas transport int he blood.

===Respiratory functions===
*We're going to talk about ventilation in general and which muscles of the chest wall are used.
*We'll tlak about negative pressure that pulls the air into the lungs.
*We're  going to think about ...

===More requirements for respiration===
*We have to have a way for the air to flow.  Ventilation perfusion coupling.
**We'll look at some problems of this, too.
*We'll look at the CNS's involvement in respiration and circulation.
*Oxygen level is important, but CO2 is the primary regulator of respiration.
*Figure 23.5.

===Non-respiratory functions===

====Filter and moisten air====

====Facilitate olfaction by transporting airborne molecules====


====Defense against airborne pathogens - mucocilliary elevator====

====Sound production====

====Trap small emboli in pulmonary circulation where they are dissolved====

====Blood reservoir for left ventricle====
*Lungs contain 500 ml of blood.
*Two beats can be supplied if pulmonary artery is clamped.

====Biochemical reactions====
*ACE converts angiotensin I to antiotensin II.
*Some prostaglandins are removed at the lungs.
*ACE is released by endothelium or this all takes place in endothelium.

===Organization of the respiratory system===
*Can be divided into upper (down to the pharynx) and lower (everything lower).
*We could also look at the system in terms of function instead of structure.
**The transition of function (from conducting zone to respiratory zone) occurs when alveoli start to occur.
*The tubes branch significantly.  There are about 16 divisions (called generations) before there are any alveoli.
**At 17 is where alveoli start and the cartilage rings stop.
**Generation 11 is where bronchials start.
*There is also a change in type of cells found.
**We transition from columnar at the top to squamous at the bottom.
**We see a change from more to less (going down) of goblet cells because of the elevator.
**We see a decrease in cartilage because we have less and less structure.
**Elasticity goes the entire length.  They are important for recoil in the chest wall and the alveoli.
*Bronchials are susceptible to collapse during expiration.
*At generation 17, alveoli start.

====The mucocilliary elevator====
*Goblet cells are releasing mucus on surface.
*Cillia are beating upward.
*As we get to the lower region, the size of pathogens is important because the smaller they are the deeper they can get and the better they can get across the endothelial cells when they land.

====Nose====
*The air enters through the external nares.
*There is mucus secretion and tears coming through ducts, these help to trap crap.
*Air passes through conchae around the turbanates (an outcropping of bone).  This generates turbulance to facilitate smell and moistening.
*We have sinuses (four of them) which connect to the nose through the medemus (?).
**When this connection is blocked, pressure can build up.

====Palate====
*Separates nose to mouth.
*Hard and soft palate.
*Cleft can occur which is bad.  Usually happens where bones come together in top of mouth.
**Can happen in hard or soft palate or both.
*Soft separates oral cavity from nasal pharynx and hard palate separates nasal and oral cavities.

====Nasopharynx====
*This is in common with digestive and respiration tracts.
*There are three regions but we won't dwell on them.
*Nasal connection is called the internal nares.
**This is the location of the adenoid.
**This is also where the opening to the ear occurs and it is important for good sound conductance and balance.

====Oropharynx and laryngopharynx====

====Larynx functions====
*This structure is trying to keep the airway open.
*Behind it is the esophagus.
*Epiglottis sits on the top with some cartilage that allows the epiglottis to cover the glottis (a slit-like opening).
*The vocal cords are on either side of the glottis.
*There is upward movement that helps to close off the glottis.

====Anatomy of larynx====
*The thyroid cartilage forms the adams apple.
*The adam's apple is caused by hormones.
*Cricoid cartilage provides posterior and anterior support.

====Tracheal cartilages====
*Begins at the base of the larynx.
*You can feel the cartilage rings with connective tissue in between.
*The rings are c shaped with the open part in the back.
*There is a muscle and a ligament on the back which are responsible for changing the diameter to change resistance.
*The esophagus is posterior to the trachea.

====Primary bronchi====
*Our first bifurcation occurs.
*The right and left are not equal.
*The angle of division are not equal.
*The right has a short bronchial tube and left has a straighter angle.
*This is a problem when kids breath something.  Most likely it is in the right bronchial tube because the angle isn't as great.
*At the bifurction, the cartilage extends into the airway a little (think shelf).
**This is covered by endothelium and is very sensitive.
**This causes the coughing when you inhale something.

====Hilus====
*The hilus is the midline of the lung (theres one on the kidneys, too).
*This is the location where the major structures enter the organ (think veins, lymphatics, bronchii).
*The whole thing is held together by a mesh-work of connective tissue.

====Lungs====
*The right lobe is larger than left because the heart is taking up space on left side.
*You can see the fissure that helps separate the middle lobes from the upper lobes.
**Note that on the left there are only two lobes.
**Right has a middle lobe.

====Lung lobes====
*The lobes are divided into segments.
*The segments are able to be isolated by surrounding connective tissue.
**They can be removed for something like lung cancer or what-not.
*The reason for these sections is that the the lymphatics, respiratory, and circulation all branch together such that all the sections separate systems.
*Right has 10 lobes and left has 8 or 9.

====Lobules====
*Sections can be divided.
*Can be the size of a penny to an eraser.
*Respiration occurs at the level of the alveoli which are at the base of the lobules.
*Artery, vein, and lymphatics all supply each lobule and each alveoli.

===Smooth muscle control===
*The cartilage is gone, recall, so we rely on the muscle to keep the airway open.
*Therefore we can change the dilation.
*The sympathetic will open airways to reduce resistance and the parasympathetic will do the opposite.
*Histamine will also restrict to increase resistance.
*This is all further compounded by the fact that we need airpressure from the outside to help hold it open.

===Alveolar organization===
*There are capillaries that pass through avleolar, which means that we can get oxygen from either capillary.
*There are several cell types at this point: type 1 cells and type 2 cells.
**Type 1 are long and thin, these do gas exchange.
**Type 2 are important for generating surfactant.
*There are also macrophages in this space to help with protection.
*Neighboring alveoli have pores that connect them; we do not know the function.
**Might help to maintain stability; for example, gas may be able to move between alveoli.
*Surface area is very important:
**It increases significantly as we develop (3 to 75 square meters).
**Yet the number of alveoli stays about the same.

===Gas exchange===
*We have to oxygen and co2 across the respiratory membrane.
*We have to diffuse across the epithelial cell and the basement membrane that holds them together, then the interstitial space (not much), then the basal membrane, then the endothelial cells.
*So, there are 10 different diffusion steps that have to occur.
*If the wall is too wide, the time to cross will take too long and we're less likely to oxygenate the blood.
**We only have about 7/10ths of a second before the opportunity is lost.

====Respiratory membrane====
*The membrane works well when everything is functional.
*It is important that there is a difference in partial pressure (especially for O diffusion).
*Distance is small, which is good and key.
*Oxygen and Co2 and Co are lipid soluble so we don't have to have transporters but we do have to have a moist surface for efficient exchange.
**So we have to keep solublility issues in our minds.
*Large surface area is important.
*There must be good stability at the air-water interphase.
**Bad stability = alveolar collapse -> lung collapse = bad.
*Coordination of flow is important.
*The blood cell membrane must be thin with the blood cell close to the cell wall.

====10 stems to transport====
*Amazing it works at all, really.
*Notice that there are D1-d10 steps.
*from water-air place to inside a type 1 cell (step 1), 
*through the cytoplasm of the type 1 cell (step 2), 
*exiting the type 1 cell into the interstitial fluid (step 3), 
*moving across the interstitial space (step 4), 
*moving into the pulmonary capillary endothelial cell (step 5), 
*across the pulmonary capillary endothelial cell cytoplasm (step 6), 
*across the inner pulmonary endothelial cell membrane (step 7), 
*through the blood plasma (step 8), 
*across the blood cell membrane (step 9), 
*and through the RBC cytoplasm (step 10).

===Air replacement===
*We don't replace all of our air with each breath.
*Even after 16th breaths, there are still some of the original air molecules before total replacement.

===Integration of two processes (respiration and circulation)===

====External respiration====
*Involves:
**Ventilation (breathing)
**Diffusion over capillaries
**Exchange of CO2 and O with Hb.

====Respiratory laws====
*There are four laws.

=====Dalton's law=====
*This is looking at the gas mixture itself.
*There is some total pressure, added to by each individual gas, which is a percentage of the total--the partial pressure.
*Remember that the partial pressure is only calculated from the free molecules of gas.

=====Henry's law=====
*Takes dalton one step further.
*Here we look at solubility issues.
*This law is important to respiratory process because we need to think about getting the gas dissolved in the liquid interface on the surface of alveoli.
*There is a different solub coeff for different liquieds

=====Graham's law=====
*Rate of diffusion is inversely proportional to the square root of molecular mass.
*The rate of diffusion is driven by difference in partial pressure of the gasses.
*There are solublility issues, too, but overall, it's the difference in pp.
*Oxygen gets used up so there is an inward gradient while co2 has an exit gradient because we're generating it.

=====Fick's law=====
*Ties everything together.
*The greater the pp difference (that is, the concentration gradient), the greater the rate of diffusion.
*The greater the permeability of the membrane the better the diffusion.
*The more surface area the more diffusion.
*The larger the molecule the lower the diffusion.
*The thicker the membrane the less diffusion.

====Balance====
*We have to have blood and gas flow balance.
*Incoming air is not always equally distributed because of mucus or disease or whatever.
*Therefore, there will be differences in concentration of oxygen in these different areas.
*This can generate hypoxia in a certain area, which will cause vasoconstriction.

====Ventilation perfusion coupling====
*This is how pps of O and CO2 change vasodilation.
*Let's say there's a blockage and a reduction of air coming into a certain lobule.
*So CO2 goes up, O goes down in the alveoli.
*The arterioles will restrict because there's no reason to go there because there is no oxygen.
*On the other hand, you can open the vessels where there is more oxygen.
*So this all balances the air with the blood.

====Never perfect perfusion balance====
*Gravity has an effect.
*Circulation at the top of the lungs isn't as effective as the bottom of the lungs so there is more perfusion at the bottom than at the top.

===Normal and abnormal respiration===

====Tissue structure and its affect on perfusion====
*A normal lung has nice, open, alveoli.
*With pneumonia, you start to lose openness of alveoli.
**Because the pneumocytes aren't working correctly.
*In emphasema, you have coelescing of the alveoli.

====Pneumonia====
*There is an impedance in the alveoli of the sick lung.
*This causes there to be much lower venous return in terms of saturation.  So flow hasn't changed but there is a decrease of oxygen returned to the body because one lung is sucking at diffusion.
*Note that in pneumonia, you cannot change blood flow to compensate for the pneumonia.

====Collapsed lung====
*Edges are sticky, can't inflate.
*Now the circulation does change along with this problem.
*So circulation will be decreased to bad lung and it will be increased in the good lung such that we can offset the loss of oxygen.
*So, this person actually gets more oxygen returned than the penumonic lung patient.

====Surfactant and surface forces====
*We want the alveoli to be open, even while we exhale.
*The liquid on the inner interface interact differently as the surface becomes smaller.
*They then become part of the subphase and the surfactant keeps the alveoli from collapsing.
**More on this next time.

====Compliance====
*This is an indication of how well the lung is inflating relative to the pressure differences we're imposing.
*If it is highly compliant it won't expand as we expect.
*This can be affected by:
**Connective tissue of lung (elastic versus structural)
**amount of surfactant
**mobility of the thoracic cage
***For example, with arthritis and the inability to expand the rib cage.
*Hystoresis is the difference between lung volume during inspiration and expiration.
**Hystoresis: the lag of time between cause and effect.
**This won't occur if the lung is filled with saline.
**So looking at the volumes under some pleural pressure can tell us something about the tissue.
*Normal physiology will give a nice, steady change of volume relative to pressure.
*In emphasema, it will be high in compliance.  There will be a huge volume change relative to pressure.  That is, it is very easy to inflate (inhale).  The problem is that it is hard to deflate.  They make the last little 'hewh'.
*In low compliance, it is easy to exhale but hard to inhale.  These people tend to develop a barrel chest under the struggle to inflate lungs.
*So we would say that with good compliance you should have a large change in pressure and a large change in volume.
**In emphasema, there is high volume change but low pressure change, and therefore it is easy to breath in but hard to breath out.  This is called high compliance.
**In pneumonia (or a collapsed lunch), there is low volume change but high pressure change and therefore it is hard to breath in but easy to breath out.  This is called low compliance.
*Ultimately, we say that compliance is the ability of the lung to expand.  So high compliance is high ability to expand (easy to inhale).

====Pleural sac====
*The lungs are in the pleural sac.
*The pleural space is fluid-filled.
*The parietal membrane is right underneath the chest wall.
*The visceral membrane follows the Lung proper, including folds.

====Musculature====
*Diagraphm is main.
**Contraction means it is coming downward and inhaling.
**Relaxation causes a dome and exhaling.
*The intercostal muscles are between ribs and helps with expansion and reflexion.
*The sternocledomastoid muscles are also able to help lift the rib cage.

====Expriation====
*Generally passive.
*In active exercise, we can use muscles that make the chest smaller.
**REctus abdominus = pulling ndown.
**Intercostal pull ribs downward.
**External oblique muscle pull chest inward.

====Quiet breathing====
*Eupnea is normal, quiet breathing.
*Hypneria is the use of excessory muscles.

====Pressures of pleural sac====
*REcall that this is fluid filled.
*This is an area of lower pressure than atmospheric pressure (negative pressure).
*The transpulmonary pressure is that between the lung tissue and the pleural sac.
*We're not normally looking at much pressure change differences, usually just 1-2-3 mmHg changes.
*But when we really exercise hard, we can see big changes like -30 mmHg and +100 mmHg.  This may not be a good idea.

====Pressure changes associated with ventilation====
*When normally inhaling, we decrease the pressure in the pleural space because the space gets larger because of muscle movement.
*So the pressure difference across the pulmonary space will increase (that is the transpulmonary pressure).
**This makes sense because pressure is increasing in the lung but decreasing in the pleural sac.
*The negative pressure pulls on the lung tissue which causes it to inflate.
*Then the pressure in the alveoli will drop below atmospheric pressure.
*Air enters lung until reaching atmostpheric pressure.
*Then intrapelural pressure decreases and transpulmonary pressure increases and the lung exhales.

====Chest wall breach====
*In the case of collapsed lung, the pressure in the pleural space is equal to the atmospheric pressure.
*This can happen from gunshot wound or tear.
*The lung will collapse.
*So we have to close the tear and reinflate the lung.

*stopped here on 02/24/10.
*started here on 03/01/10.

*We're going to talk about control points for rates and volumes issues.
*We're also going to talk about surfactant.

===Respiratory Rates and volumes===
*In order to meet the chaning needs, there has to be a way to balance the production with the need.
*So we can change how often we breath and how much volume occurs during each breath.
*The respiratory curve defines the volumes and how they are linked.
*In a normal inhale-exhale, we move the tidal volume: how much we move with each breath.
*With excersize we have to accomadate more volume so we do this with reserve volume (both on the respiratory size and expiratory side).
*Our total inspiratory capacity includes the inspiratory reserve and the tidal volume.
*The numbers on the slide are averages.
*Our functional residual capacity is the respiratory reserve (that which can be forced out) and the residual volume (that which you cannot exhale)
*The vital capacity is the total amount of room that could be moved in and out.  Which is the two reserve volumes plus the tidal volume.
**There is always some that cannot be moved: residual volume.  It is in an unusable area.
**In a forensic lab, you could test to see if an infant was stillborn or not by testing the floating capacity of the lung because if the baby ever took a breath, the residual volume will be filled with air.

===Respiratory minute ventilation===
*This is defined as how much air is moved per minute.
*It is a function of how frequently we're breathing and the volume of each ventilation.
*It is generally about 500 ml at 12 times per minute which is about 6 liters of air per minute.
*It goes beyond this, however, because we wonder how much air actually gets to the alveoli.  This is important because that is hte only location where we can exchange air.

===Alveolar ventilation===
*So alveoloar ventilation is this idea of how much air gets to the alveoli.
*We include in this calculation any part of th elungs that can exchange, which begins at the respiratory bronchioles and includes everything deep to that.
*The dead space is all the area where air is conducted but cannot be exchanged with the blood (like in the bronchi).
*If you hold the minute ventilation constant and then increase dead space, you won't be able to keep exchanging well.
*There is a dynamic balance between our rate of ventilation and the tidal volume.
*We can put this dynamic into numbers, too, and generate some equations:
**Tidal volume - dead space ventiation x frequence = alveolar ventilation rate.
***Dead space is generally around 0.150 l
***Normal alveolar ventilation rate is 4.2 liters.
**This tells us how much is able to get to the alveoli and therefore is available for breathing.

*We wonder if there is an upper limit to all these things.
**We cannot exceed the oxygen levels of the partial pressure of oxygen in the environment's air.
**We can see that at lower oxygen levels, it will take a longer amount of time to reach the normal concentration of oxygen in the body.

===Oxygen transport===
*So we're thinking about the idea of oxygen and carbon dioxide transport.
*Plasma is not a good place for oxygen to disolve so 98% of it is bound to Hb.
*If you wanted to support a person simply on dissolved oxygen, you'd have o increase cardiac throughput by 17 fold!
*Iron is the binding site of the oxygen in Hb.  The iron is surrounded by four heme groups.
*So we have the possibility for one RBC to transport over 1 billion molecules of oxygen.  On average, it works out to be about 3.8 oxygens perl Hb.
*Oxygen binds to Hb in a cooperative manner: when one binds, the second and subsequent bind more and more easily.
**The opposite is true, also.
**The significance is that in a situation in which we really need oxygen, this increases our ability to carry oxygen.
*There are several ways we can affect Hb levels.
**We can increase RBC.
**We can increase Hb in a given RBC.
*In an anemic situation, we have decreased RBC counts and therefore Hb will only be 10% of the volume and we'll only transport 13.4 ml of oxygen to the alveoli.  Normally, hb is 15% and we deliver 20.1 ml.  With extra RBCs we have 30% and 26ish mls.

===Carbon dioxide transport===
*About 7% of CO2 is dissolved in blood.
*About 23% of it is combined with proteins and amino acids in blood (mostly those of Hb).
*And most (70%) of it is transported as HCO3-.
*In RBCs we have carbonic anhydrase which is a completely reversible enzyme so it can generate HCO3- and CO2 and subsequently Ho2.
**This enzyme converts CO2 and water into carbanic acid (H2CO3).
*So bicarbonate goes into the RBC exchanged for Chloride.  Then Carbonic anhydrase converts bicarbonate  into H20 and CO2.  CO2 then gets released via the alveoli.

*When Hb binds hydrogens, it becomes acidified and it releases oxygen.  This makes sense when thinking about lactic acid buildup and extra oxygen delivery of oxygen.

*So the cycle goes like this:
**A RBC arrives at peripheral tissue.
**CO2 moves from tissue to the plasma (and potentially lactic acid, too) via osmotic pressure such that acidity rises.
**Increase of acidity causes oxygen to be released.
***Note that it is the water and CO2 levels (which are high at the systemic tissues) that will drive pH changes and thus cause regulation.
***Hb can also bind CO2 and upon doing so it will favor release of oxygen.
**At the same time, carbanic anhydrase is converting CO2 to carbonic acid.
**Then carbonic acid gets converted to bicarbonate (via an unknown mechanism).
**Then bicarbonate is exchanged into the plasma in exchange for chloride ions (the '''chloride shift''').
**Bicarbonate is freely diffusable so it can go and dissolve in plasma.  However, if we're going to let the negative molecule into the plasma, we have kick one out, too (Cl-).  This is called the chloride shift.
**Then the blood travels back to the lung.
**At the lung, the partial pressure difference between the air and the RBC causes CO2 to move from the RBC to the air.
**This movement drives the previously described reaction in reverse.
***This causes carbonic acid to be converted to CO2.
***This causes bicarbonate to be converted to carbonic acid.
***This causes bicarbonate to be draw into the RBC (in exchange for chloride ions leaving the RBC).
*Oxygen is pretty much separate.  It is driven by partial pressure.

http://lh6.ggpht.com/_mqoliJqPnsw/S5FKDGH42UI/AAAAAAAAU1Y/C_SEqaCOwMc/s800/co2_exchange_cycle.jpg

===Hemoglobin saturation curves===
*Saturation occurs based on partial pressure.
*As the curve rises, it represents the oxygen that we use during exercise and normal ventilation.  And near the bottom, the curve represents the oxygen that never gets releases from Hb (which is common).
*Note the sigmoidal binding curve.
*Carbon monoxide binds very well to Hb and is very difficult to reverse which is bad because it binds much more readily than oxygen.  Oxygen must be at very high partial pressures to overcome carbon monoxide (poisoning).

*Ultimately, as temperature increases and pH decreases, Hb will more readily dump oxygen which makes sense because when you're exercising these things will occur.  So this is a shift to the right on a graph of Hb saturation versus partial pressure (of oxygen in the Hb).
**We see that oxygen binds more readily at the same partial pressure.  With increased temperature, saturation occurs at a higher partial pressure of oxygen.
**And if you have fever or are working hard, the metabolism of the tissue is going up so you want to be sure you have oxygen for the tissues to use.
*And lower temperatures and a higher pH will cause retention of oxygen on Hb which makes sense because  the Hb will be in its oxygen-binding conformation and will keep the oxygen (that is, when aa pK values drop, we see a conformational change in Hb such that oxygen can bind well) which is good because we need to conserve the oxygen in our hypothermic state (hybernation).

===Bohr effect===
*We can think about pH and CO2 and how they change the binding of oxygen.
*The bohr effect has to do with pH's effect on binding.
*Alkiline conditions will generate increased prevalance to bind at a given partial pressure.
**That is, as acidity goes up, oxygen deliver will go up.  As acidity goes down, oxygen deliver goes down.

===Hb as a buffer===
*Hb is a good buffer.
*This makes sense because it binds and releases H+.

===Adult / fetal Hb===
*The partial pressure in the maternal blood after having passed through tissue that took some of it will be even lower than the environmental partial pressure, so the fetal blood has a higher affinity such that it can still take the blood from the mom's blood.
*2,3 biphosphoglycerate is generated by RBCs as part of normal glycolysis.  It causes Oxygen to be dumped off of Hb.
*As you increase BPG (a right shift), one increases oxygen delivery because.
**We can increase BPG by an increase in pH, by some hormonal influence.
**BPG can be used as a marker for blood banks to determine how fresh and capable the blood is.
**BPG levels are decreased in the elderly.

===Haldane effect===
*Looks at CO2 levels as they affect oxygen binding.
*As CO2 rises, Hb will be less saturated with oxygen and vice versa.
*As CO2 goes up, the carbonic anhydrase reaction will generate bicarbonate and this will cause a shift to the right.

===Control of respiration===
*There are many things that occur to control ventilation; we need to think about changing the blood flow and oxygen delivery.
*We know we can change vessel diameter both in the periphery and in the lungs.
*There are many factors that affect dilation, including Hb, NO, and vasodilators.

*NO acts in both the tissue and the lung to control Hb saturation:
**In tissue:
***NO is released by endothelial cells, as the RBCs take up CO2 it also takes on NO, NO then binds to the globin portion of Hb, and increases dumping of oxygen at the tissue.
***NO causes vasodilation.
**In the lung:
***NO has been carried from the tissues via RBCs.  NO is then released at the lungs which allows for easier loading of O on the Hb.
***NO causes vasodilation which should only be considered a side effect.

*This means that NO increases oxygen deliver in peripheral tissues but in the lung it facilitates the uptake of oxygen (because it increases blood flow through the lung).

 How, exactly, does NO increase loading in lungs?

===Respiraotry centers of the brain===
*The voluntary centers are in the cerebral cortex but are only good for a period of time because involuntary (pons and medulla) are more important.
*The voluntary centers will only work as long as CO2 levels are low or normal.  As soon as CO2 goes up, it over-rides voluntary choice.

===Respiratory centers in the pons and medulla===
*They are in the brain stem.
*The medulla is the major location of control.  It has a location for inspiration and expiration (DRG, VRG).
*The pons has two different areas: pneumotaxic and apneustic areas.
**These are not necessary for life but it does help with fine tuning of rate and depth of respiration.

===Medulla===
*The dorsal respiratory group is primarily inspiratory.
**We inhale for 2-3 seconds and then shut fthe pathway off and let the passive time take over for exhalation.
**The DRG functions in quite and forced breathing.
*During exercise we induce force respiration and we start to rely on the extra space and volume.
*Ventral respiratory group is the one that is active in forced breathing when in need of O2.
**This center can stimulate inhalation or exhalation depending on the situation.
**Basically, the VRG boosts the rate one way or the other.

===Quiet breathing===
*The respiratory center turns on and off; primarily we're working only with the DRG.
*Basic pace and depth of respiration are determined by the balance of the DRG and VRG.

===Forced breathing===
*The VRG kicks in and we see an impact on depth and rate.
*This will activate the accessory breathing muscles and expand the chest cavity and thus draw on the reserve volume.

===Respiratory centers and reflex controls===
*The apneustic center provides a continual level to the DRG (which regulates normal in and out cycle).
*The pnuemotatctc center turns off the DRG and thus limits the duration of the inhalation.
*The penumotactic center also helps inhibit the apneustic center.

===SIDS===
*One of the things we think happens is that the respiratory centers become disrupted in some way (though we don't know how).  Then normal ventilation is affected and the baby dies.
*May result from connections between pacemaker complex and respiratory center.

===Sensory input modifies respiratory center activities===
*There are chemoreceptors in the body that are sensitive to co2, ph, or O2, (in that order) and can then feed back to (respiratory centers).
*There are also baroreceptors that will sense changes in blood pressure (caused by changes in vasoconstriction).
*We have stretch receptors, too, that respond to changes in lung volume.
*There is the brewer-reflex.  There are sensors that sense how stretched the lungs are and feed backs to the respiratory centers in order to control inhalation.
**Babies don't have a fully calcified set of ribs so they can sometimes overinhale and rip their lungs on the bones.
*We also have sensors for irritants which can causes us to hold our breath, or lock our larynx (jumping into cold water; be careful with cold drinks in heat), bronchial tree.
*Other sensations like pain or abnormal visceral sensations.

===Influence of cranial nerve===
*Number 10 is in the aorta and senses changes in the aorta.
*Number 9 is the glossiopharyngeal carries info from the carotid bodies, stimulated by changes in pH and PO2.

===Receptors monitoring the CSF===
*The receptors in the CNS respond to changes as a result of ventilation while those in the periphery change because of changes in metabolism.
*So as CO2 levels change, the cells of the CSF in the spinal cord have carbonic anhydrase as well.  So then CO2 levels change the pH of cerebral spinal fluid and thus can be used as a way to change respiratory rate and depth.

===CNS chemoreceptor responses to partial pressure of co2===
*This leads to increased depth and rate of respiration.
*There can be decreased sensitivity due to chronic stimulation.
*Hypoventilation: common cause of hypercapnia (elevated arterial Pco2), increase respiratory rate to fix
*Hyperventilation: results in abnormally low Pco2 (hypocapnia), decrease respiratory rate

===Baroreceptor reflexes===
*When BP falls, respiration rate goes up and ''vice versa''.
**This goes along quite nicely with needing to balance flow to demand.

===Hering-breuer relfexes===
*This has to do with over expansion of the lungs.

===Protective reflexes===
*The epithelium of the respiratory system and especially the korina (split in bronchials) have these receptors.
*This will turn off breathing so that you don't increase the irritant and in fact it increases the desire to breath out: sneezing / coughing.
*Apnea = lacking or suspending ventilation.
**Eupnea.
**Apnea can be used to balance out delivery of gasses.

===The cerebral cortex and respiratory centers===
*Strong emotions can activate the autonomic nervous system which can affect the airways and the diameter of the vessels, and thus can affect balance so as to change respiration.
*Anticipation is an involuntary summing up in the mind of how many motor units are needed.  In parallel, our brain calculates how much breathing is required.

===Changes of respiration over time===
*Before birth, we have a little blood running through the pulmonary vessels; only enough to supply the lungs with blood.
*During deliver, the fetal CO2 levels will begin to rise.  This will feed back on ventilation centers and cause an autostimulation  of those receptors in order to cause breathing.
*At the very least, it make take a combination of CO2 and some tactile stimulation.
*So we think about lungs being able to be ventilated in babies.  We have to overcome the surface tension that wants to keep the lung in a collapses position and overcome this collapsed state with the release of surfactant (a massive release, indeed).
*We also have to redirect blood flow (closing foramen valve).
*Add all this up and the lung should fully inflate.
*As we age, the chest wall becomes less elastic.  There is a drop in performance rate of the lung.
**It seems that if you quit smoking, as long as you're not really old, you start to recoup some of the good properties of the lung.

===3 affects of aging===
*When elastisticity goes down we have decreased performance.
*Arthritis can cause decreased movement of the chest and therefore a decrease in perforamnce.
*Emphasema affects individuals over 50 depending exposure to irritants.

===Surfactant===
*We really started to understand this as a result of people studying Hyaline Membrane Disease (IRDS).
**This is when alveoli become clogged with dead tissue that resulted from strained breathing.
 What is hysteresis?
*What is surfactant?
**He studied lipids of surfactnat for PhD.
**It's hard to find the proteins, easy to get lipids.
**There are two groups of proteins.
**We're tyring to decrease surface tensions.
**As the surface gets smaller, some of the molecules on the surface will go inward and the tension will become inward.  So the aveiolus will want to collapse.
*The surfactant also helps with trapping of debris and thus eject it via the escalator.
*Note that you can take samples of amniotic fluid, look at the proteins, and determine whether an infant will be able to survive on its own.  
**The ratio of lecithin to sphingomyelin must be greater than 2.  
**You use gluccocorticoids to stimulate lung maturation.
*80% of surfactant is phospholipid, 10% neutral lipids, and 10% proteins.
*If you look at the phospholipids, 60% is in the form of DPPC.  This lipid carries the property that lets the surface act the way it does.
*The second most important will be phosphotydl inositol.

*stopped here on 03/01/10.
*started here on 03/03/10.

*The DPPC is the major contributor to the reduction of surface tension.
*Phosphatidyl inositol makes up about 5-7% of the reduction of surface tension.

*There are two groups of proteins, either hydrophilic or hydrophobic.
*So while the lipids are important, the proteins were identified in the early eighties.
**The lipids have been around and known since the 50s.

===Hydrophilic surfactant proteins===
*SPA and SPD are hydrophillic.
**They are both glycosylated and in the aqueous (water soluble) phase.
**Both involved in defense through the activation of macrophages.
**So this is one of the ways we can take care of bacteria that get below the elevator.
**It is not odd to find macrophages at the air-water boundary.
*There are 28 types of cells in the lung.
*SPA is also involved in antiviral activity and surfactant cycling and secretion.
**It works closely with synthesis and secretion of miller bodies which is where something is located.
*SPB and SPC
**The spreading of the surfactant on the alveolar pocket is important and that's what B and C do.

===Lamellar bodies and tubular myelin===
*We're seeing a type II cell and a lamellar body inside.
**This is really a package of tubular myelin.
**The surfactant is on the tubular myelin.

*SPA / B are required for formation of lamellar bodies and tubular myelin.

*Respiratory distress in infants:
**One of the problems is that we're trying to open lungs without surfactant.
**This causes cellular and tissue damage because they are rubbed against each other.
**This can cause the tissue to become disfunctional.
**This can even tear the lung and cause lung collapse.

*continued on to [[Cystic fibrosis lectures]] on 03/03/10.