Pressure-Volume Relationships in the Respiratory System

September 15, 2016 Physiology and Pathophysiology, Pulmonary Medicine, Respirology No comments , , , , , , , , , , , , ,

screen-shot-2016-09-15-at-3-04-48-pmThe relationship between changes in the pressure distending the alveoli and (transmural pressure) changes in the lung volume is important to understand because it dictates how easily the lung inflates with each breath. The alveolar-distending pressure is often referred to as the transpulmonary pressure. Strictly speaking, the transpulmonary pressure is equal to the pressure in the trachea minus the intrapleural pressure. Thus, it is the pressure difference across the whole lung. However, the pressure in the alveoli is the same as the pressure in the airways – including the trachea – at the beginning or end of each normal breath, that is, end-expiratory or end-inspiratory alveolar pressure is 0 cm H2O. Therefore, at the beginning or end of each lung inflation, alveolar-distending pressure can be referred to as the transpulmonary pressure.

Compliance of the Lung and the Chest Wall

Reference range: The total compliance of a nromal person near the FRC is about 0.1 L/cm H2O. The compliance of the lungs is about 0.2 L/cm H2O; that of the chest wall is also aobut 0.2 L/cm H2O.

Figure 2-6 shows that as the transpulmonary pressure increases, the lung volume increases. This relationship is not a straight line: The lung is composed of living tissue, and although the lung distends easily at low lung volumes, at high volumes the distensible components of alveolar walls have already been stretched, and large increases in trnaspulmonary pressure yield only small increases in volume.

The slope between 2 points on a pressure-volume curve is known as the compliance. Compliance is defined as the change in volume divided by the change in pressure (transmural pressure). Lungs with high compliance have a steep slope on their pressure-volume curves; that is, a small change in distending pressure will cause a large change in volume. It is important to remember that compliance is the inverse of elastance, elasticity, or elastic recoil. Compliance denotes the ease with which something can be stretched or distorted; elastance refers to the tendency for something to oppose stretch or distortion, as well as to its ability to return to its original configuration after the distorting force is removed.

There are several interesting things to note about the lung pressure-volume curve. From Figure 2-6 there is a difference between the pressure-volume curve for inflation and the deflation, as shown by the arrows. Such a difference is called hysteresis. One possible explanation for this hysteresis is the stretching on inspiration and the compression on expiration of the film of surfactant that lines the air-liquid interface in the alveoli. Surfactant has less effect on decreasing surface tension during inspiration than during expiration because of movement of surfactant molecules from the interior of the liquid phase to the surface during inspiration. Another explanationis that some alveoli or small airways may open on inspiration (recruitment) and close on expiration (decrecruitment); the recruitment of collapsed alveoli or small airways requires energy and may be responsible for the lower inflection point seen on  some inspiratory pressure-volume curves. Finally, it is helpful to think of each alveolus as having its own pressure-volume curve like that shown in Figure 2-6, although some researchers believe that lung volume changes primarily by recruitment and decrecruitment of alveoli rather than by volume changes of individual alveoli.

Clinical Evaluation of the Compliance of the Lung and the Chest Wall

The compliance of the lung and the chest wall provides very useful data for the clinical evaluation of a patient's respiratory system because many diseases or pathologic states affect the compliance of the lung, of the chest wall, or both. The lung and the chest wall are physically in series with each other, and therefore their compliances add as reciprocals:

screen-shot-2016-09-20-at-9-50-53-amConversely, the elastances of the lung and chest wall add directly.

Compliances in parallel add directly. Therefore, both lungs together are more compliant than either one alone; 2 alveoli in parallel are similarly more compliant than 1 alone.

Representative static compliance curves for the lungs are shown in Figure 2-7. Note that these curves correspond to the expiratory curve in Figure 2-6. Many pathologic states shift the curve to the right (i.e., for any increase in transpulmonary pressure there is less of an increase in lung volume). A proliferation of connective tissue called fibrosis may be seen in sarcoidosis or after chemical or thermal injury to the lungs. Such changes will make the lungs less compliant, or "stiffer," and increase alveolar elastic recoil. Conversely, emphysema increases the compliance of the lungs because it destroys the alveolar septal tissue that normally opposes lung expansion.

screen-shot-2016-09-20-at-10-26-47-amFor patients wtih decreased lung compliance, they must generate greater transpulmonary pressures to breath in the same volume of air. Therefore they must do more work to inspire than those with normal pulmonary compliance.

The compliance of the chest wall is decreased in obese people, for whom moving the diaphragm downward and the rib cage up and out is much more difficult. People suffering from a musculoskeletal disorder that leads to decreased mobility of the rib cage, such as kyphoscoliosis, also have decreased chest wall compliance. Similarly, people wtih decreased chest wall compliance must do more muscular work than people with normal chest wall compliance.

Lung Elastic Recoil and Alveoli Surface Tension

The elastic recoil of the lungs is partly due to the elastic properties of the pulmonary parenchyma itself. Elastin is more compliant or distensible and is important at low or normal lung volumes. Collagen is less compliant or distensible and is not usually stressed until lung volume is large. However, there is another component of the elastic recoil of the lung besides the elastin, collagen, and other constituents of the lung tissue. That other component is the surface tension at the air-liquid interface in the alveoli.

Surface tension is a force that occurs at any gas-liquid interface and is generated by the cohesive forces between the molecules of the liquid. These cohesive forces balance each other within the liquid phase but are unopposed at the surface of the liquid. Surface tension is what causes water to bead and form droplets. It causes a liquid to shrink to form the smallest possible surface area. The unit of measurement of surface tension is dynes per centimeter (dyn/cm).

Because the lung is inflated with air, an air-liquid interface is present in the lung, and surface tension forces contribute to alveolar elastic recoil. If all the gas is removed from the lung, and it is inflated again, but with saline instead of with air, the surface tension forces are absent because there is no air-liquid interface. In this circumstance, the elastic recoil is due only to the elastic recoil of the lung tissue itself. Thus, the hysteresis disappears under this condition.

Besides the surfactant's impact on elastic recoil, it has another critical importance, which would be described below. According to the Laplace's law, the transmural pressure of two alveoli with different radius would be different in the absence of surfactant (the surface tension of most liquids is constant and not dependent on the surface area of the air-liquid inteface). Consider what this would mean in the lung, where alveoli of different sizes are connected to each other by common airways and collateral ventilation pathways. If 2 alveoli of different sizes (radius) are connected by a common airway and the surface tension of the 2 alveoli is equal, then the pressure in the small alveolus must be greater than that in the larger alveolus and the smaller alveolus will empty into the larger alveolus. If surface tension is independent of surface area, the smaller the alveolus with smaller radius becomes, the higher the pressure in it. Thus, if the lung were composed of interconnected alveoli of different sizes with a constant surface tension at the air-liquid interface, it would be expected to be inherently unstable with a tendency for smaller alveoli to collapse into larger ones. Normally, this is not the case, which is fortunate because collapsed alveoli require very great distending pressures to reopen, partly because of the cohesive forces at the liquid-liquid interface of collapsed alveoli. At least two factors cause the alveoli to be more stable than this prediction based on constant surface tension. The first factor is a substance called pulmonary surfactant, which is produced by specialized alveolar cells, and the second is the structrual interdependence of the alveoli.

[Histology] Basic Four Types of Tissues – Connective Tissues

May 23, 2016 Anatomy, Histology No comments , , , , , , , , , , , , , , , , ,

The different types of connective tissue maintain the form of organs throughout the body. Differences in composition and amount of the cells, fibers, and ground substance make up variety of connective tissue types. Connective tissues provide a matrix that supports and physically connects other tissues and cells together in organs. The interstitial fluid of connective tissue gives metabolic support to cells as the medium for diffusion of nutrients and waste products. Unlike other tissue types, which consist mainly of cells, the major constituent of connective tissue is the extracellular matrix/ECM, which consists of different combinations of protein fibers (e.g., collagens and elastic fibers) and ground substance (a complex of anionic, hydrophilic proteoglycans, glycosaminoglycans/GAGs, and multiadhesive glycoproteins). The hydrated nature of connective tissue ground substance provides the medium for the exchange of nutrients and metabolic wastes between cells and the blood supply.


Fibroblasts and certain other cells are typically present in connective tissue proper. Fibroblasts originate locally from mesenchymal cells and are permanent residents of connective tissue; other cells found here, such as macrophages, plasma cells, and mast cells, originate from hematopoietic stem cells in bone marrow, circulate in the blood, and then move into connective tissue where they function. Leukocytes are transient cells of most connective tissues; they also originate in the bone marrow and move to the connective tissue where they function for a few days, the die by apoptosis.


Fibroblasts, the most common cells in connective tissue, produce and maintain most of the tissue's extracellular components. Fibroblasts synthesize and secrete collagen (the most abundant protein of the body) and elastin, which form large fibers, as well as the GAGs, proteoglycans, and multiadhesive glycoproteins that comprise the ground substance. After being secreted, most of the ECM components undergo further modification outside the cell before assembling as a matrix.

Two levels of fibroblast activity can be observed histologically. Cells with intense synthetic activity are morphologically distinct from the quiescent fibroblasts that are scattered within the matrix they have already synthesized.

Fibroblasts are targets of many families of proteins called growth factors that influence cell growth and differentiation. In adults, connective tissue fibroblasts rarely undergo division. However, stimulated by locally released growth factors, cell cycling and mitotic activity resume when the tissue requires additional fibroblasts.


Adipocytes are found in connective tissue of many organs. These cells are specialized for cytoplasmic storage of lipid as neutral fats, or less commonly for the production of heat.


Macrophages are characterized by their well-developed phagocytic ability and specialize in turnover of protein fibers and removal of dead cells, tissue debris, or other particulate material. Macrophages play an important role in the early stages of repair after tissue damage, and under such conditions of inflammation these cells accumulate in connective tissue by local proliferation of macrophages in addition to monocyte recruitment from the blood. In addition to debris removal, these cells are highly important for the uptake, processing, and presentation of antigens for lymphocyte activation.

They derive from bone marrow precursor cells that divide, producing monocytes that circulate in the blood. These monocytes cross the epithelial wall of venules to penetrate connective tissue, where they differentiate further, mature, and acquire the morphologic features of phagocytic cells. Therefore, monocytes and macrophages are the same cell at different stages of maturation.

The macrophage-like cells have been given different names in different organs, for example, Kupffer cells in the liver, microglial cells in the central nervous system, Langerhans cells in the skin, and osteoclasts in bone tissue. However, all are derived from monocytes and all are long-living cells and may survive for months in the tissues.

Mast cells

The cytoplasm of mast cells is filled with basophilic secretory granules many of which have the bioactive role in the local inflammatory response. A partial list of important molecules released from the secretory granules include:

  • Heparin
  • Histamine
  • Serine proteases
  • Eosinophil and neutrophil chemotactic factors
  • Cytokines
  • Phospholipid

Occurring in connective tissue of many organs, mast cells are especially numerous near small blood vessels in skin and mesenteries (perivascular mast cells) and in the tissue that lines digestive and respiratory tracts (mucosal mast cells); the granule content of the two populations di ers some what. These major locations suggest that mast cells place themselves strategically to function as sentinels detecting invasion by microorganisms.

Plasma cells

Plasma cells are B-lymphocyte-derived, antibody-producing cells. There are at least a few plasma cells in most connective tissues. Their average lifespan is only 10-20 days.


Besides macrophages and plasma cells, connective tissue normally contains other leukocytes derived from cells circulating in the blood. Leukocytes make up a population of wandering cells in connective tissue. They leave blood by migrating between the endothelial cells lining venules to enter connective tissue by a process called diapedesis. Most leukocytes function for a few hours or days in connective tissue and then die. However, some lymphocytes normally leave the interstitial fluid of connective tissue, enter blood or lymph, and move to selected lymphoid organs.


The fibrous components of connective tissue are elongated structures formed from protein that polymerize after secretion from fibroblasts. The three main types of fibers include collagen, reticular, and elastic fibers. Collagen and reticular fibers are both formed by proteins of the colagen family, and elastic fibers are composed mainly of the protein elastin. These fibers are distributed unequally among the different types of connective tissue, with the predominant fiber type usually responsible for conferring specific tissue properties.


The collagens constitute a family of proteins selected during evolution for their ability to form a variety of extracellular structures. The various fibers, sheets, and networks made of collagens are all extremely strong and resistant to normal shearing and tearing forces. Collagen is a key element of all connective tissues, as well as epithelial basement membranes and the external laminae of muscle and nerve cells.

Collagen is the most abundant protein in the human body, representing 30% of its dry weight. An unusually large number of posttranslational processing steps are required to prepare collagen for its final assembly in the ECM. They are many types of collagen and we will take a look at them in future.

Reticular fibers

Found in delicate connective tissue of many organs, reticular fibers consist mainly of collagen type III. This collagen forms an extensive network (reticulum) of extremely thin, heavily glycosylated fibers. Reticular fibers produced by fibroblasts occur in the reticular lamina of basement membranes and typically also surround adipocytes, smooth muscle and nerve fibers, and small blood vessels. Delicate reticular networks serve as the supportive stroma for the parenchymal secretory cells and rich microvasculature of the liver and endocrine glands. Abundant reticular fibers also characterize the stroma of hemopoietic tissue (bone marrow) and some lymphoid organs (eg, spleen and lymph nodes) where they support rapidly changing populations of proliferating cells and phagocytic cells.

Elastic fibers

Elastic fibers form sparse networks interspersed with collagen bundles in many organs,  particularly those subject to much bending or stretching. Elastic fibers have physical properties similar to those of rubber, allowing tissues to be stretched or distended and return to their original shape. Elastic fibers are a composite of fibrillin microfibrils embedded in a larger mass of cross-linked elastin.

Ground Substance

The ground substance of the ECM is a highly hydrated (with much bound water), transparent, complex mixture of macromolecules, principally of three classes: glycosaminoglycans/GAGs, proteoglycans, and multiadhesive glycoproteins. It fills the space between cells and fibers in connective tissue and, because it is viscous, acts as both a lubricant and a barrier to the penetration of invaders. GAGs bind large amounts of water, which causes the polyaminos to swell and occupy a large space in the tissue.

Types of Conenctive Tissue

Screen Shot 2016-05-23 at 10.43.00 PMLoose connective tissue is very common and generally supports epithelial tissue. It comprises a thick layer (lamina propria) beneath the epithelial lining of the digestive system and fills the spaces between muscle and nerve fibers. Usually well-vascularized whatever their location, thin layers of loose connective tissue surround most small blood vessels of the body. Also called areolar tissue, the loose connective tissue typically contain cells, fibers, and ground substance in roughly equal parts. The most numerous cells are fibroblasts, but the other types of connective tissue cells are also present, along with nerves and blood vessels. Collagen fibers predominate, but elastic and reticular fibers are also present. With a moderate amount of ground substance, loose connective tissue has a delicate consistency; it is flexible and not very resistant to stress.

Dense connective tissue is adapted to offer stress resistance and protection. It has the same components found in loose connective tissue, but with fewer cells and a clear predominance of collagen fibers over ground substance. Dense connective tissue is less flexible and far more resistant to stress than loose connective tissue. In dense irregular connective tissue bundles of collagen fibers appear randomly interwoven, with no definite orientation. The collagen fibers form a tough three-dimensional network, providing resistance to stress form all directions. Dense irregular connective tissue is often found closely associated with loose connective tissue, with the two types frequently grading into each other and making distinctions between them somewhat arbitrary. Collagen bundles of dense regular connective tissue are arranged according to a definite pattern, with fibers and fibroblasts aligned in parallel for resistance to prolonged or repeated stresses exerted in the same direction.

In reticular tissue fibers of type III collagen form a delicate 3D network that supports various types of cells. The fibrous network of this specialized connective tissue is produced by modified fibroblasts called reticular cells that remain associated with and partially covering the fibers. The loose disposition of glycosylated reticular fibers provides a framework with specialized microenvironments for cells in hemopoietic tissue and some lymphoid organs (bone marrow, lymph nodes, and spleen). The resulting cell-lined system creates a meshwork for the passage of lymphocytes and lymph. Macrophages and other cells of the mononuclear phagocyte system are also dispersed within these reticular tissues to monitor cells formed there or passing through and to remove debris.