This chapter is most appropriate to Section F1(i) from the 2017 CICM Primary Syllabus, which expects the exam candidates to be able to "explain the attribute and framework of the ...alveolus".

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A minimalist college comment to Question 15 from the first paper of 2016 reveals that the college meant some fundamental anatomical details and descriptions of exactly how they influence alveolar function, yet not any kind of sort of comprehensive functional discussions, nor comprehensive diagrams, nor any kind of point out of surfactant. 

In summary:


Structure and Function Relationships of the Alveoli

Structure

Function

Alveolar macrostructure: huge number of (mainly spherical) air spaces associated by septa

Large surconfront area, to facilitate diffusion.The interconnected network-related of walls permits mechanical stress to be shared across a bigger location of lung parenchyma (this is alveolar interdependence)Spherical in full distension, however folding alengthy pleats with deflation to keep surchallenge area

Alveolar blood-gas barrier: a thin trilamellar membrane composed of three layers:

Capillary endothelial cellBasal laminaAlveolar Type 1 cell

Quick diffusion distance: 0.2-2 µm for the blood-gas interface

Flexibility (helped with by collagen and elastin fibres in the basement membrane)High permecapacity to gases, but low permecapacity to water, accomplished by the lipid bilayer of the alveolar cell membrane

Elastic basement membrane, containing the septal interstitial fibre network:

Axial collagen fibres(from the hila along the bronchi and also alveolar ducts)Peripheral fibres (from the visceral pleura via interlobular septa)Septal fibres (along the alveolar septa).
Increases the elastic recoil of the distfinished lungIncreases the resistance to atelectasis
Type I alveolar cells: think cels through extended cytoplasmic plates which cover a big surchallenge arreaBarrier attribute (incredibly negative permeability to water-soluble substances)Gas exadjust feature (very high permecapability to gases)
Type II alveolar cells: Secrete surfactant (which decreases the surface tension of the fluid on the alveolar walls, preveing their collapse)Act as stem cells to replenish Type I alveolar cells, which cannot replicate
Pores of Kohn: defects in alveolar septal wallsTheir main feature is to allow collateral ventilation between alveoliThis is one more system of matching ventilation and also perfusion

Of the publiburned literature the single finest reresource is probably Knudsen & Ochs (2018), which covers whatever you might perhaps have to recognize about this topic. This write-up has actually more indevelopment than the main CICM recommfinished resources, is much better structured, and is free. 

Structural and also practical needs for the alveolus

If one were to architecture the gas exchange surdeals with of the lungs from scratch, one would have to satisfy a number of engineering specifications. In order to job-related appropriately, these structures need to have the complying with characteristics:

Brief diffusion distance: 0.2-2 µm for the blood-gas interfaceMechanical form stability (resistance to collapse, promoted by surfactant)Flexibility (promoted by collagen and also elastin fibres in the basement membrane)High permecapacity to gases, yet low permecapability to water, accomplished by the lipid bilayer of the alveolar cell membrane

That last point is probably relatively vital. One would not desire one"s respiratory epithelium to leak fluid all over their gas exreadjust surencounters. Even though the blood-gas obstacle is created of capillary endothelial cells and pneumocytes, that obstacle feature appears to be mostly the province of Type I alveolar cells. 

Structure and shape of the alveoli

Alveoli are the basic unit of the gas exadjust surchallenge. In summary, the complying with things can be sassist about the alveolar shape and also structure:

Largely polyhedral shape Open at one end, choose a cupWalls of the alveoli are composed of the pulmonary capillary sheet Alveolar surencounters are extended in a thin (200nm) layer of surfactant which acts as the interface through the gas

Like the majority of points in medicine, our direct observations of alveolar shape come from cruel pet experiments. For example, Klingele & Staub (1970) acquired a host of some cat lungs and ventilated them (just the lower lobes) with recognized increments of transpulmonary push. Then, we froze each lobe by inundating it for 2 min with liquid propane coobrought about - 180 C in liquid nitrogen and moved it to a cryostat at -40 C"

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So, though they are depicted in a lot of textpublications as bit spherical sacks of gas, in reality this only holds true as soon as they are well-inflated. To "borrow" this diagram from Gill et al (1979), one deserve to check out that one"s alveoli are just vaguely spherical once they are distfinished, and in a fell down state they take on a sorry folded-looking shape.

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The point of this diagram is to impose upon the reader the significance of lung volume on alveolar form and also surconfront location changes. These little bit sacks execute not undergo orderly sphere-choose inflation as if they were a party balloon (which would have actually made their surconfront area predictable and also straightforward to calculate). Instead, they are complicated polyhedral shapes, which undergo volume change by folding alengthy pleated septa (wright here the folds tend to be at the corners between alveoli).

Interconnecting walls and alveolar interdependence

After seeing the diagram above, it probably does not should be shelp that alveoli are clearly not individual isolated air sacks but an interconnected honeycomb of cavities wbelow each cavity shares its wall surfaces with numerous others. As such, changes to one alveolus affect the surrounding alveoli. This device is variably recognized as "radial traction" or "alveolar interdependence". Discussion of this issue and its ramifications most likely belong even more in the chapters which relate to lung mechanics, but in brief:

Alveoli are linked by shared interconnecting wallsStress on one alveolus is therefore transmitted to adjoining alveoliThe interconnected network of wall surfaces enables mechanical tension to be mutual throughout a larger area of lung parenchymaThis mechanism contributes to the elastic recoil of the lung in disstress and anxiety and also resists the collapse of individual alveoli in atelectasis

Cellular population of the alveoli

If one were to inflate the usually flattened capillaries of the lung to make them even more influential, one might have the ability to depict the cells of the lung in this manner:

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This diagram was put together from miscellaneous sources, such as this electron microphotograph. If anybody is ever asked to describe the cellularity of the of alveoli in the create of an unstructured list, it can look a tiny choose this:

Cellular populace of the alveolar wall surfaces is composed of:Type I alveolar cells, which cover 95% of the surface areaType II alveolar cells, which secrete surfactant and replenish the Type I cell populationCapillary endothelial cellsFurther cell types Alveolar macrophagesMast cellsFibroblasts

Of these cell populations, for this lung-ish chapter the focus will be on Type I and Type II cells. It is sad that Ward & Nicholas" 1984 paper is paywalled by Wiley, bereason it is a great conversation of pneumocytes, yet luckily their juiciest the majority of examinable content is recreated below in a minimally altered state.

Type I cells are extremely facility topographically. A single cell body may have actually long flat plate-choose extensions which might expectancy across a number of alveoli branching out from the central nucleated region. Those plates are vanishingly thin and also largely devoid of organelles (wright here would certainly you fit them). Several micropinocytotic vesicles are seen in that membrane, yet it is otherwise a reasonably empty area of cytoplasm - which serves all the better to preserve its thinness, one might intend. The diagram below has a diagram of a Type I cell through 6 cytoplasmic plates and an informative SEM picture of isolated Type I cells in society. That last photo is from Fuchs et al (2003) and also mirrors them spanalysis throughout a plate, creating thin disks through centrally elevated blobs containing the nuclei and also all the other cellular machinery.

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Given this morphological complexity, the mind boggles as to exactly how a cell like this could undergo division. Along which line can it divide? Weibel (1974) expressed disidea that they also divide at all, and also on that basis progressed the hypothesis that they more than likely do not, and also that their populace is repleniburned by Type II cells, which turned out to be precise (Barkauskas et al, 2013).

One can sooner or later be asked in a viva to describe the function, quite than the structure, of Type I cells. What carry out these cells also do? Well. Two things: they carry out gas exchange and they do obstacle attribute.

Gas exreadjust functions are disputed well sufficient in the section on the blood-gas obstacle listed below, and also without also many kind of spoilers one can summarise that their primary means of fulfilling that attribute is by being thin (200-500 nm in thickness).

Barrier function of the entirety blood-gas obstacle is greatly the effect of alveolar cells being poorly permeable, whereas the promiscuous pulmonary capillary endothelial cells seem to enable any damn thing into the alveolar interstitium. Capillary endothelial junctions are "maculi adherentes",  leaky because they are full of gaps, whereas the alveolar epithelial junctions are "zonuli occludentes" and also are tight with all sorts of interlacing ridges and also overlapping grooves.

The most valuable outcome of this is that your circulating blood volume does not instantly escape your body fropoint with your lungs. To use an extra scientific tone, experiments (eg. Wangensteenager et al, 1969) display that the permeability of the overall blood-gas obstacle to water and water-soluble solutes to be very bad. The investigators were somewhat surprised that the diffusion coreliable was relatively comparable for all tested substances, consisting of water (in the order of 0.5-2.3 × 10-5 cm2/sec), with permecapacity properties similar to those of a cell membrane. They pertained to the conclusion that the barrier was permeable by virtue of little, reasonably non-selective leaks, most likely some type of water-filled pores.

This obstacle function is not absolutely exclusive, as one deserve to quickly develop of a situation wright here dissolved blood components might actually be necessary inside the alveolus. For example, the alveolar epithelium transports immunoglobulins to the alveolar surchallenge, so they might lay tright here like landmines waiting for pathogens. Proteins are likewise slowly absorbed from the alveolar surface and transported earlier into the blood, a mechanism which is thneed to be responsible for some of the resolution of pulmonary oedema. 

Type 2 cells are greatly practical quite than structural. They have actually 2 primary roles: manufacturing of surfactant and also proliferation to replace Type I cells. Structurally, these are unimpressive cuboidal cells, usually depicted as extended in microvilli (which are so little that they are normally just revealed by electron microscopy). The stolen picture below depicts a Type II cell from a rat lung (Evans et al, 1973).

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Probably the a lot of significant structural component of these cells after the nucleus are the lamellar bodies, so called bereason electron microscopy reveals them to be full of fine alternating layers. These are the vesicles which contain pulmonary surfactant.

Secretion of surfactant is probably one of their the majority of crucial functions of the Type II cells. The properties of lung surfactant are amazing enought that they merit a chapter all to themselves, additionally having attracted the attention of college inspectors (Question 6 from the second paper of 2012). It will suffice to say right here that it keeps the alveoli from collapsing, and so without surfactant, all the various other brilliant design services of the lungs would be pointless, and also we need to all simply go ago to gills.

Replenishment of Type I cells occurs as an outcome of injury or normal wear-and-tear. Type II cells clonally proliferated and also transdeveloped right into Type I cells over the course of 48-72 hrs when Evans et al (1973) blew nitrogen dixoide right into the lungs of elalso rats. As they divide, the daughter cells hug the basement membrane and move under the surrounding Type I cell.

The blood-gas barrier

Maine & West (2006) publiburned an excellent paper on this topic, which at the moment of creating is somejust how free from semanticscholar.org. The title of the paper is "Thin and also Strong", which actually explains the minimal intended knowledge of its properties for the CICM exam candidate. To intricate even more on its properties would waste valuable cognitive bandwidth, which is of course in maintaining via the unwritten mission statement of Deranged Physiology. Thus, in summary:

The blood-gas barrier is a thin trilamellar membraneIt is composed of 3 layers:Capillary endothelial cellBasal laminaAlveolar Type 1 cellThe total thickness is generally around 300-500 nmSeveral other components play a minor role:The thin layer of surfactant, which provides minimal resistance to gas exchangeThe variable layer of plasma in between the endothelial cell and also the erythrocyte surconfront, the thickness of which is minimised

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According to Maine & West (2006), this style was so successful for the Silurian Dipnoi that the fundamental elements have actually continued to be mainly untransformed in all the descendents ever before since they dragged themselves out onto land also. Presumably, the continual lethal faientice of anything various has actually defended this structure for millions of years. The authors describe these as Baupläne ("frozen cores") as "such constructions are most likely the just feasible and useful services to exacting sensible requirements". 

Role and origin of the alveolar basement membrane

The pulmonary capillaries and also alveolar endothelial cells are fundamentally suspended in mid-air on a loosely wstove hammock of fibroelastic tworry. This is the alveolar interstitial tworry, consisting of protein fibers and basal laminae for the endothelial and also epithelial cells. 

Tright here is also a potential interstitial space bounded by the aforementioned basal laminae, which contains a network of collagen and elastin fibres. Tbelow are some fibroblasts lurking in tright here, of which a number have actually contractile properties. This potential space is not uniformly existing in all alveolar walls, of which the thinswarm have actually a joint basal lamina for both alveolar epithelial and also vascular endothelial cells. About half of the full surface location is as thin as this, and the remainder has actually a potential room to accumulate oedema fluid.  

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The collagen and elastin fibres stretch throughout this space in a purposeful manner. Elastic fibres are focused roughly the openings of alveoli like purse strings, and also the collagen fibre network exoften tends from the hila and from the visceral pleura. Axial collagen fibres extend from the hila along the bronchi dvery own to the alveolar ducts, peripheral fibres extend inward from the visceral pleura by means of interlobular septal limits, and also septal fibres affix the axial and also peripheral netfunctions by extfinishing alengthy the alveolar septa. The septal fibres are therefore under some anxiety as soon as the lung disoften tends, as they are extended in between the various other networks. Weibel (2017) explains this a lot better, and with more useful diagrams

Pores of Kohn

These are basically holes in the alveolar walls, normally bounded by Type II cells. Their extremely existence was doubted in the time of the previously half of the 20th century, and also it took electron microscopy (eg. Boatguy & Martin, 1963) to confirm that they are actually a actual and also normal part of lung framework quite than an artireality of specimen processing or early on lesions of emphysema. "The cost-free edges are checked out notto be tears since the basement membrane passes intact round from the alveolar wall dealing with into one alveolus to the wall encountering the adjoining alveolus. Furthermore, the basement membraneis not denuded of epithelium" created Cordingley in 1972. In brief, these are intentional defects in the alveolar septa.

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The electron microscopy image above is from rat lungs investigated by Pastor et al (2006). The pores are the smallest of all the collateral ventilation passeras, the others being interbronchiolar Martin’snetworks (30 μm in diameter) and bronchoalveolar Lambert’s channels (120 μm in diameter). Incidentally, "collateral ventilation" is what you contact it when the ventilation of alveoli occurs through pathways that bypass normal airways (Terry et al, 2016). 

Factoids one might must learn about these pores for exam functions include:

They are missing in the newborn, and build by the fourth year of ageThey are even more common in the apical areas of the lobesThey are though to flourish in size and also become confluent through ageTheir major function is to allow collateral ventilation between alveoli

 In textpublications (eg. the 8th edition of Nunn"s), their useful definition is primarily sassist to be "interalveolar air drift" (Reich & Abouav, 1965), or some variation thereupon. Given that they are clogged with lung surfactant, one could intend that the duty of the pores of Kohn more than likely has actually more to perform via cell migration in between alveoli than gas exadjust, but in truth these pores are not totally pointless as mediators of ventilation. 

This hypothesis stands as much as the test of comparative biology. For instance, collateral circulation could be perceived as an additional mechanism of equivalent ventilation and also perfusion; for this reason wherever before such a mechanism is well-emerged the reliance on various other V/Q corresponding mechanisms (eg. hypoxic pulmonary vasoconstriction) is diminiburned. This is in reality exactly what you check out in pets. Kuriyama et al (1981) reasoned that "if collateral ventilation helps store interregional oxygen tensions homogeneous, then in its absence, neighborhood ventilation-perfusion balance must depend on arterial constriction", and tested this by looking at the muscularity of pulmonary arteries in animals, by means of measuring their propensity to develop pulmonary hyperstress and anxiety at high altitude. Cattle, via their thick septa and also bad collateral ventilation, are very at risk to high altitude pulmonary hyperstress and anxiety, whereas dogs and also lamb did not have actually this trouble.