Andrew B Lumb MB BS FRCA , in Nunn's Applied Respiratory Physiology (Eighth Edition), 2017
Pulmonary Capillaries
Pulmonary capillaries tend to arise abruptly from much larger vessels, the pulmonary metarterioles. The capillaries form a dense network over the walls of one or more alveoli, and the spaces between the capillaries are similar in size to the capillaries themselves (Fig. 1.7). In the resting state, ~75% of the capillary bed is filled but the percentage is higher in the dependent parts of the lungs. Inflation of the alveoli reduces the cross-sectional area of the capillary bed and increases resistance to blood flow (Chapter 6). One capillary network is not confined to one alveolus but passes from one alveolus to another, and blood traverses a number of alveolar septa before reaching a venule. This clearly has a bearing on the efficiency of gas exchange. From the functional standpoint it is often more convenient to consider the pulmonary microcirculation rather than just the capillaries. The microcirculation is defined as the vessels that are devoid of a muscular layer and it commences with arterioles with a diameter of 75 µm and continues through the capillary bed as far as venules with a diameter of 200 µm. Special roles of the microcirculation are considered in Chapters 11 and 28.
Capillaries are very thin-walled structures with no contractile properties. They divide and branch, without their caliber diminishing. They contain no more than 5% of the total blood volume. The radius of capillaries is 3000 times smaller than that of the aorta, and 100 times finer than a strand of hair.
There are 10 to 40 million capillaries, giving them an exchange surface on the order of 600 square miles. The number of capillaries in organs is determined by their metabolic function. Lungs have the largest capillary network, necessary for the transformation of venous blood into arterial blood. In organs such as the liver, spleen and thyroid, capillaries are also plentiful.
NB: Our viscoelasticity techniques have a large effect on capillary function.
Capillary bed
Capillaries are generally arranged in networks called capillary beds (Fig. 1.12). There are between 10 and 100 true capillaries in a capillary bed, depending on the organ or tissue supplied.
In most regions of the body, the capillary beds are made up of two types of vessel:
•
Vascular diversion vessels which consist of a metarteriole and a thoroughfare channel directly linking the arteriole and the venule, on either side of the bed
•
The true capillaries, where blood and interstitial fluid are exchanged.
Microcirculation
The circulation of blood from an arteriole to a venule across a capillary bed is called microcirculation. Blood flow slackens in the capillaries to permit the exchange of nutrients and other cellular material between the blood and the surrounding tissue. Red blood cells can pass through only singly, by deforming.
By altering the degree of tonus in their smooth muscle walls, arterioles can regulate blood pressure and thus the perfusion of a given region.
A cuff of smooth muscle called a precapillary sphincter surrounds the root of each true capillary that detaches itself from the metarteriole. Like a tiny valve, it controls the flow of blood through the capillary.
If the precapillary sphincters dilate, blood flows in the true capillaries and contributes to the exchange with the tissue cells. If the precapillary sphincter contracts, blood flows into the metarteriole and the thoroughfare channel, bypassing the true capillaries and the cells.
Depending on the requirement of the organism or of a given organ, blood can flood the capillary bed, or bypass it entirely.
Normal Cardiac Physiology and Ventricular Function
B.D. Hoit , in Reference Module in Biomedical Sciences, 2014
The Microcirculation
The microcirculation is comprised of arterioles, capillaries, and venules. Arterioles range from 10 to 150 μm in diameter and regulate the distribution of blood flow to capillaries (0.5–1 μm). Small arterioles (metarterioles) can bypass the capillary beds, shunting flow directly into the small venules (10–40 μm). The independent vasoactivity of different-sized arterioles produces blood flow patterns that vary in speed and direction. Although flow in the arterioles is usually rapid, continuous, and unidirectional, capillary flow is highly variable. Capillaries have a single layer of endothelial cells through which oxygen and nutrients diffuse to adjacent tissues. Venules have an endothelial cell layer surrounded by an adventitia and contractile pericytes and are involved in transvascular exchange of fluid and macromolecules across the vascular wall. The larger venules and veins collect and store blood for return to the heart. The cellular and molecular mechanisms that control blood flow in the microcirculation are only beginning to be understood (Segal, 2005).
Important determinants of capillary exchange through the endothelial cell membrane (diffusion) include (1) the capillary density, which is directly related to the metabolic activity of tissue, (2) lipid solubility of the material to be exchanged, (3) the free diffusion coefficient (small molecules and molecules with very little net electric charge have very high free diffusion coefficients), and (4) the relative concentrations of the material in the blood and the tissue interstitium. Thus the rate of diffusion for a substance Q, moving from the vessel to the interstitial space, dQ/dt is proportional to the capillary wall area (2πrl), the difference in concentration of the substance (ΔC), which represents the driving force for the movement across the vessel wall, and the permeability (P), which is a function of lipid solubility and the free diffusion coefficient: dQ/dt = (2πrl)(P)(ΔC). Permeability of substances varies by capillary bed. For example, capillaries in the brain restrict the diffusion of almost all solutes, whereas liver capillaries have a very high permeability to large solutes such as albumin. Endothelial transport across restrictive beds is accomplished by other processes such as pinocytosis and vesicular transport (Harris and Anderson, 1996).
The transvascular exchange of water occurs primarily through the bulk flow of water through the pores in the capillary walls. The amount of bulk flow is a function of the difference in hydrostatic pressure in the vessel (CHP) and interstitium (THP), the capillary filtration coefficient (CFC), the plasma colloid osmotic pressure (COP, caused by protein in the blood plasma, ∼20 mmHg), and the tissue colloid osmotic pressure (TOP, caused by proteins in the interstitial space, ∼4.5 mmHg). Thus, the net force out of the vessel (filtration) is a hydrostatic force and the net force into the vessel (reabsorption) is a colloid osmotic force. The effect of these forces on transvascular water flow is described in the Starling equation: , where σ is the reflection coefficient for the movement of proteins across the capillary wall (the inverse of the permeability of the vessel wall to protein). CFC is the product of capillary surface area and permeability and is related to number and size of the pores through which water can pass through the vessel. Because the balance of forces is different across the length of a capillary bed, filtration occurs near the arterial end and reabsorption near the venule end of the capillary.
Of these forces, capillary hydrostatic pressure (CHP) is the principal mechanism responsible for the transcapillary exchange of water. Capillary pressure is far more sensitive to changes in venous pressure than changes in arterial pressure. It can be shown that arterial pressure must increase 10 mmHg to cause a 1 mmHg increase in CHP, whereas a 1 mmHg increase in venous pressure will cause a similar increase in CHP. Greater filtration than reabsorption produces tissue lymph flow; the total volume of lymph fluid (important in returning plasma proteins that leaked from the microcirculation and transport of chylomicrons) is approximately 3–4 l per day.
DESIGN AND PHYSIOLOGY OF ARTERIES AND VEINS | Physiology of Resistance Vessels
K.R. Olson , in Encyclopedia of Fish Physiology, 2011
Anatomy of Resistance Vessels
Much of the resistance to blood flow in mammalian tissues is located in small (< 300 μm diameter) vessels. This is assumed to be the case in fish as well. Collectively, these vessels include small arteries, arterioles, and metarterioles. Resistance arteries and arterioles (∼300–30 μm) are characterized by an abundance of smooth muscle wrapped circumferentially around the vessel that allows exquisite control of their diameter. The terminal end of the arteriole (∼30–5 μm) has just a single smooth muscle cell encircling it at the very entrance to a capillary bed and is called the precapillary sphincter. Like all fish blood vessels, they are lined by a single layer of endothelial cells and they have less elastic tissues than the larger arteries. Larger arteries may be heavily innervated, but the degree of innervation becomes progressively less in smaller vessels and nerves are usually absent from the smallest arterioles.
Achilles J. Pappano PhD , Withrow Gil Wier PhD , in Cardiovascular Physiology (Tenth Edition), 2013
Arterioles are the Stopcocks of the Circulation
The arterioles, which range in diameter from about 5 to 100 µm, have a thick smooth muscle layer, a thin adventitial layer, and an endothelial lining (see Figure 1-2). The arterioles give rise directly to the capillaries (5 to 10 µm in diameter) or in some tissues to metarterioles (10 to 20 µm in diameter), which then give rise to capillaries (Figure 8-1). The metarterioles can serve either as thoroughfare channels to the venules, which bypass the capillary bed, or as conduits to supply the capillary bed. There are often cross-connections between the arterioles and venules as well as in the capillary network. Arterioles that give rise directly to capillaries regulate flow through their cognate capillaries by constriction or dilation. The capillaries form an interconnecting network of tubes of different lengths, with an average length of 0.5 to 1 mm.
Chaya Gopalan Ph.D., FAPS , Erik Kirk Ph.D. , in Biology of Cardiovascular and Metabolic Diseases, 2022
2.6 Capillaries
A capillary is the smallest blood vessel that allows the exchange of substances between the blood and the tissues. This process is referred to as perfusion. A capillary lumen diameter varies from 5 to 10 μm; the smallest are barely wide enough for a red blood cell to squeeze through. The capillary wall consists of the endothelial layer surrounded by a basement membrane with occasional smooth muscle fibers (Fig. 2.4).
Fig. 2.4. A cross-section of a capillary. Different types of capillaries include continuous capillaries, fenestrated capillaries, and sinusoids [4].
The arrangement of the endothelial cells varies from one capillary type to another. The continuous capillary is where cells are arranged without any space compared to a fenestrated capillary where the cells are apart from one another by a specific distance. Continuous capillaries are present in the neural tissue to limit the escape of unknown substances. Fenestrated capillaries are found in the glomerulus, endocrine structures, and small intestine, allowing large substances to move between blood vessels and tissues. Sinusoids are specialized capillaries where large spaces exist within the capillary wall to allow blood cells and proteins to be exchanged between the tissues and the blood. The liver, spleen, and bone marrow serve as examples of these capillaries (Fig. 2.4).
A metarteriole is a branch of the smallest arteriole that connects it to the capillary bed. It branches further to supply blood to a capillary bed that may consist of 10–100 capillaries. A metarteriole is slightly larger than a typical capillary and shares structural characteristics of both an arteriole and a capillary. The smooth muscle lining within the tunica media is not continuous but arranged as rings around the vessel. The circular smooth muscle arrangement surrounding the capillary at the junction between the metarteriole and the capillary is called a precapillary sphincter. It tightly regulates blood flow from a metarteriole to the capillaries it supplies. The sympathetic nervous system regulates the smooth muscle serving as the precapillary sphincter. The precapillary sphincters are typically closed and open when the surrounding tissues require O2 or have excess waste products removed, allowing blood to flow through and exchange to occur before closing once more (Fig. 2.5). The blood will bypass the capillary bed and flow from the metarteriole directly into the venous circulation via a thoroughfare channel if all of the precapillary sphincters in a capillary bed are closed. This arrangement is known as a vascular shunt, the redistribution of blood. An arteriovenous anastomosis is a similar arrangement where there is a direct connection between an artery and a vein, completely bypassing the capillary bed.
Fig. 2.5. A capillary bed along with a metarteriole and a venule. The precapillary sphincter regulates the flow of blood into the capillary bed. Arteriovenous anastomosis represents alternate blood flow bypassing capillary beds [5].
A spontaneous oscillation in the blood vessel wall referred to as vasomotion, independent of neuronal regulation, results in irregular, pulsating flow. Local chemical signals trigger such flow in response to changes in internal conditions, such as O2, CO2, H+, and lactic acid levels. For example, during strenuous exercise, when O2 levels decrease and CO2, H+, and lactic acid levels increase, the capillary beds in skeletal muscle become open, allowing increased local blood supply. In general, at rest, most capillary beds are closed but open only occasionally to allow supplies of O2 and nutrients to the tissues.
Ramón Muñoz-Chápuli , José M. Pérez-Pomares , in Heart Development and Regeneration, 2010
III.A The Basic Anatomy of Vertebrate Vasculature
Vertebrates are the only animals that have an endothelial-based circulatory system formed by a complex network of arteries, veins and capillaries that support a continuous stream of blood propelled by a chambered heart. As indicated above, all these vessel types are basically formed by a continuous, flattened, nonstratified epithelium of meso-dermal origin called endothelium. Endothelial cells "define" the vertebrate vascular system, so that a vertebrate vessel can lack smooth muscle or fibrous adventitial component, but not endothelium. Therefore, vascular growth (angiogenesis or vasculogenesis, see below) is always, and first, defined by endothelial activity.
Vertebrate arteries have thick, multilayered walls that are characteristically elastic. In the adult, three classic anatomical regions are found in an artery: an outer tunica adventitia, mainly constituted of fibrous cells; the tunica media, that includes circular and longitudinal smooth muscle fibers; and the tunica intima, formed by the innermost endothelium and the underlying elastic fibers, which are normally absent early in development. Arteries are capable of peristaltic blood pumping, and some of them even have their own blood supply (vasa vasorum). Arteries connect the heart to the capillary bed of tissues through arterioles and act as a pressure reservoir, as well as an absorber system for the oscillations of the circulatory flow (Eckert et al., 1988).
Capillaries are the smallest vessels of the body and are responsible for the cell-by-cell delivery of oxygen and nutrients. Capillaries consist of endothelial cells discontinuously covered by supporting cells called pericytes. These pericytes are embedded within the endothelial basal lamina, and make focal contacts with endothelial cells (reviewed in Armulik et al., 2005). Pericytes not only appear in capillaries, but also in pre-capillary metarterioles and post-capillary venules. They are modulators of blood vessel development, maturation and remodeling, and are especially abundant in the microvessels of the central nervous system. Pericytes are closely related to smooth muscle cells (SMCs), and many authors favor the idea that a molecular and phenotypical continuum ranging from pericytes to differentiated and functional smooth muscle cells exists, suggesting a complex reality that is even more obscure in the embryo (Hungerford and Little, 1999). Markers used to identify pericytes include α-smooth muscle actin (α-SMA), desmin, platelet-derived growth factor receptor beta (PDGFR-β), aminopeptidases A and N, and RGS5 (a protein involved in tuning heterotrimeric G-protein signaling by acting as GTPase-activating proteins for Gα subunits), but none of these markers is absolutely specific for pericytes, and many of them are also expressed by smooth muscle cells (Armulik et al., 2005). Very interestingly, pericytes also have some similarities with endothelial cells. Studies in adult cancer malignancy have shown that both pericytes and endothelial precursor cells (EPCs) are capable of tube and network formation, as well as response to kinase inhibitors selective for angiogenic pathways. The expression of cell surface proteins, including PDGFRVCAM, intercellular adhesion molecule, CD105, desmin and neural growth proteoglycan 2, was found to be very similar between pericytes and EPC (Bagley et al., 2005).
Normally, any given cell is at a distance of no more than three cell bodies from a capillary, and in some cases capillaries can irrigate, one by one, all the cells of a tissue (e.g., in the heart). Arterioles connect to capillaries through metarterioles that normally end in a pre-capillary sphincter (a ring formed by a few smooth muscle cells) that controls the blood flow in a capillary bed. For this reason, under normal conditions, the blood content of all the capillaries of an individual is only half (around 7%) of its total potential volume (around a 15% of all the blood of the body). Veins act as a return pathway for the blood circulating from the capillaries to the heart. Veins have a great inner diameter, and normally present a less complex wall than arteries (some veins lack a well-developed muscular layer). It is known that at least 50% of the total volume of the blood of vertebrates is found in veins which can act as a reservoir of blood to sustain arterial pressure in case of hemorrhage (McDonald, 1960; Eckert et al., 1988).
What advantage can the vertebrate endothelial cell type represent with respect to the nude vessels of invertebrates? Endothelial cells do not form a passive barrier, but can actively transport micro- and macromolecules. However, this control of molecular transportation might be a minor advantage when compared with other endothelial functions. Endothelial cells play a major direct role in the regulation of blood vessel contractility, blood coagulation and inflammatory responses. Finally, endothelial cells allow for guided blood vessel growth when needed.
Structure and Function of the Adult Vertebrate Cardiovascular System
J.D. Schultz , D.M. Bader , in Encyclopedia of Cardiovascular Research and Medicine, 2018
Capillaries
Capillaries are the most distal component of the cardiovascular system. Throughout the body, they are the anastomosing connection between arterial and venous vessels. Capillaries are by far the most prevalent members of the vascular tree, and approximately 60,000 miles of capillaries are present within the human body (Siddiqui, 2011). The human brain alone has 100 billion capillaries extending 400 miles (van Tellingen et al., 2015). Concerning gas, fluid, and material exchange, the capillary is the "business end" of the cardiovascular system. These beds anastomose within the connective tissue space of organs such that all cells of the supplied area are within one to three cell widths from a capillary. The luminal diameter of capillaries is approximately 9–10 μm, marginally larger than a red blood cell (RBC). White blood cells that have larger diameters reshape/redistribute their cytoplasm to pass through capillary beds. Interestingly, intermittent thoroughfare channels (also known as metarterioles and also depicted in Fig. 10) provide an "express route" to move blood more directly to the venous return virtually bypassing the capillary bed. These vessels do not have the robust layer of smooth muscle seen in arterioles at their proximal/arterial end. Instead, a single, discontinuous layer of smooth muscle is seen at the arterial/proximate region of the thoroughfare channel. This smooth muscle layer gradually subsides toward the venous/distal region of this channel. In this way, when arterioles in one region of the body collectively close, arterial blood is quickly shunted through these thoroughfares to the venous return making this blood available for other parts of the organism that are in greater need of blood.
The overarching function of capillaries is to enable exchange of oxygen, fluids, nutrients, carbon dioxide, and other substances between the cardiovascular system and other body compartments. Capillaries have the same basic structure throughout the body, although critical variation in structure/function is noted later. In essence, capillaries are a continuation of the tunica intima seen in arteries and veins. Capillaries consist of an inner endothelium resting on a basal lamina, which is secreted by the endothelium. While a definitive tunica media and adventitia are absent in capillaries, specific mesenchymal cells are seen intermittently adjacent to the basal lamina of the capillary. One of these cell types is called the pericyte. This cell is connective tissue cell with contractile properties. Other connective tissue cells with phagocytic and fibroblastic properties are also scattered along the capillary network. This basic structure is modified throughout the body depending on the particular function of each capillary bed.
There are three major subcategories of these vessels: continuous, fenestrated, and discontinuous capillaries. We give an example of each capillary as a means of describing their varying function.
Continuous capillaries, as the name implies, have a continuous endothelial sheet of cells at the luminal surface with a continuous subjacent basal lamina (Fig. 11). Cell/cell junctions insure that the luminal blood is restricted to the vessel while the attenuated endothelial cytoplasm promotes exchange of materials from the blood supply to the surrounding tissue. Let us consider the blood supply to the lung as a means of discussing the structure and function of continuous capillaries.
Fig. 11. Capillary structure. The three major types of capillaries are depicted. At the lower left, a continuous capillary is seen in cross section with its continuous endothelial lining, continuous basal lamina, and an associated pericyte. A fenestrated capillary with its "windowed" fenestrations is seen at the top and middle. At the lower right, a discontinuous capillary is shown with gaps in both the cellular endothelial lining and basal lamina of this vessel type. The relative size of these vessels can be discerned by comparing the diameter of the red-colored RBC (6–8 μm in the human) to the capillary lumen.
Deoxygenated blood originating from the right ventricle enters the lung via the elastic pulmonary artery. This artery quickly branches into muscular distributing arteries that roughly follow the branching pulmonary tree that supplies the lungs with air. Many orders of branching and subdivision follow in both systems until the airway is reduced to a single epithelial sheet called the terminal alveolus, while the cardiovascular system ends in continuous capillaries. As seen in the accompanying figure, these two simple squamous epithelia rest on a shared basal lamina. Thus, the structure between the air of the outside world and the lumen of your cardiovascular system is reduced to two attenuated epithelial sheets and a common basal lamina. It is important to remember that the endothelial cells in the lungs form a continuous capillary system. While the cells are very attenuated and very closely associated with the epithelia of the airways, the continuous nature of these capillaries keeps the blood within the cardiovascular system preventing you from drowning in your own blood. Thus, the complex branching of the airway and bloodstream results in a simple cellular arrangement where inhaled oxygen is in close proximity to RBCs.
A similar configuration of continuous capillaries is seen in the brain and spinal cord, in smooth, skeletal and cardiac muscle, and in most of the connective tissue compartments of your body. Indeed, continuous capillaries are the most prevalent capillary seen in the human body.
The next type of capillary seen in the body is the fenestrated capillary. These vessels are present where more extensive fluid interchange between the cardiovascular system and the organ/body compartment takes place. Examples are the glomeruli of the kidneys, villi of the small intestine, and endocrine glands. Fenestrated capillaries are continuous in nature with a continuous basal lamina but have domains within the endothelial cell where very thin windows or fenestrae reside (Fig. 11). These windows are thinner than the diameter of a single plasma membrane and vary in diameter. Interestingly, with the great advances science has made over the past years, the definitive structure of capillary fenestrae has not been resolved although factors influencing their development have been identified (Satchell and Braet, 2009).
Fenestrae vary in number and size in different populations of capillaries, but it should be noted that transport across these structures is in the range of molecules and not at the level of intact cells. Obviously, fluid exchange is a major function in the kidney. Glomeruli of the kidney are the most distal structures of the nephron and are intimately associated capillary beds. The capillaries within the glomeruli actually have small opening or gaps within their fenestrae and have a mildly elevated hydrostatic pressure that pushes fluids out of the vessel across the associated basal lamina. Glomerular epithelial cells (called podocytes) have gaps between cells allowing the passage of fluids, ions, and small molecules into the initial nephric space. This is the first step in production of urine and the elimination of excise fluids from the cardiovascular system. The configuration of the capillaries within the glomerulus promotes the movement of fluids out of the blood system to the urinary tract.
The third major capillary form is the discontinuous capillary. This type of capillary is found in regions of the body where whole-cell entry and exit from the cardiovascular system is observed and includes organs such as the liver, spleen, and bone marrow. In this setting, gaps in the endothelial cell sheet occur with accompanying spaces in the subjacent basal laminae (Fig. 11). Hematopoiesis is a major function of the blood marrow, and newly matured red and white cells can freely migrate from the stroma through discontinuous endothelial cells in the marrow to enter the blood stream. Conversely, blood flow in the spleen is virtually an open system where cells, such as RBCs, exit the cardiovascular system and are surveyed by resident splenocytes. These splenocytes can determine which RBCs are ready to be eliminated due to their age (remember that human RBCs function to deliver oxygen for 120 days and then are eliminated in the spleen by those splenocytes). RBCs that have not reached 120 days of maturity are not eliminated and return to the bloodstream through the same discontinuous capillaries and exit the spleen to continue their duties in gas exchange.
It is interesting how nature and evolution have conserved the overall function of capillaries in these three different settings while, at the same time, promoting variation to meet the varying needs of a complex organism such as the human being.
Pulmonary Gas Exchange, Oxygen Transport, and Tissue Oxygenation
Claude A. Piantadosi MD , in Physiology and Medicine of Hyperbaric Oxygen Therapy, 2008
SYSTEMIC MICROCIRCULATION AND TISSUE GAS EXCHANGE
The purpose of the systemic microcirculation is to provide a large area for the transfer of nutrients to and removal of waste products from the cells. This function includes, first and foremost, the exchange of O2 and CO2. The microcirculation is organized anatomically according to the special characteristics of each tissue or organ, but in general terms, the system is composed of arterioles—vessels of 20 μm or less in internal diameter—as well as the terminal arterioles (metarterioles) and capillaries.5 Capillary density varies among tissues, but usually, depending on the tissue type, a cell is no more than 30 to 60 μm away from a capillary.21 However, capillaries are also rarely perfused continuously; they open and close periodically, for instance, under the control of precapillary sphincters, most notably in relation to local O2 concentration.22 Thus, at high rates of O2 consumption, as PO2 decreases, the capillaries tend to remain open longer, whereas at low rates of O2 consumption, the capillaries may be closed much of the time. Moreover, the extraction of O2 along the length of the capillary means that PO2 is naturally higher at the arteriolar than at the venule end. It is also observed that the relatively sharp branching angles of different-sized vessels in the microcirculation cause plasma skimming to the smaller vessel. Thus, the microvascular hematocrit routinely declines to less than that in the central vessels by as much as a third.
If one picks a point on a capillary and makes a perpendicular slice through the tissue, as the distance away from the center of the capillary increases, the PO2 decreases because of O2 utilization by mitochondria. Plasma O2 is consumed first, allowing O2 to diffuse across the erythrocyte membrane, through the plasma layer, through the endothelial cell barrier, and across the cell membrane before it reaches the mitochondria. The main resistance (R) to O2 diffusion is across the red blood cell membrane and the vascular walls of terminal arterioles and capillaries. Little resistance occurs at the plasma membrane or across mitochondrial membranes. These resistances can be summed and expressed as the reciprocal 1/R, or the conductance (G) of O2 from capillary to the mitochondrion.11 The concept is shown in Figure 8.11.
Because of the multiple effects mentioned earlier, the PO2 in tissues is quite variable. Tissue PO2 measurements, for example, using platinum microelectrodes, are also difficult to perform accurately and may be even harder to interpret. Even a single relatively homogeneous tissue shows considerable spatial PO2 heterogeneity, which can be seen by plotting the measurements as a function of their frequency.23 Thus, a PO2 histogram emerges from which the median and scatter provide an estimate of the O2 dispersion in the tissue. Sample PO2 histograms of the beating guinea pig heart during air and O2 breathing are shown in Figure 8.12. The histograms illustrate the effect of O2 breathing on increasing the median and the dispersion of PO2 in the healthy heart. The pattern is similar among tissues exposed to HBO, although the histograms are shifted even further to the right.
Predictions of tissue PO2 from model calculations are also difficult to interpret and sometimes conflict with experimental measurements. However, since the development of the original cylinder model of Krogh and Erlang for skeletal muscle, models of tissue O2 distribution have proved instructive for understanding tissue oxygenation.24 The Krogh–Erlang model makes use of one or more parallel cylinders of highly organized and homogeneous (ideal) tissue, each surrounding a central uniform capillary of known length (L) that can be used to calculate the radius (r) of the PO2 distribution based on diffusion (Fig. 8.13).
The cylinder model is quite simple compared with the morphology of even an elementary capillary network, yet it is highly informative. Most notably, it emphasizes how diffusion limits the movement of O2 from capillary to tissues, especially at the venous ends of capillaries. In O2 insufficiency, hypoxia emerges first at the venous end—the so-called lethal corner. Interestingly, living tissues recognize this problem and capillary density tends to be greatest far away from the terminal arterioles.1 Thus, the microcirculation is not arranged anatomically as parallel cylinders.
The cylinder model does predict correctly the more stringent geometric limits of diffusion at high metabolic rates, as well as the appearance of longer distances for O2 diffusion when PO2 is high at the capillary entrance (see Fig. 8.13). However, the model overestimates O2 extraction in the capillary, which can be corrected by building in a precapillary O2 shunt from arteriole to venule. The presence of a small arteriovenous shunt provides for suitable estimates of venous O2 saturations in the model, and experimentally, their presence has been seen in a number of living tissues.
As already noted, there are conditions, especially in disease states such as hemorrhage or ischemia, in which O2 uptake is limited by local DO2 and not by diffusion. Not surprisingly, diffusion models do not fit such perfusionlimited conditions well, even for models that allow different numbers, types, and distributions of capillaries. The variable and intermittent rate of capillary blood flow observed in vivo is also particularly difficult to model, and there are still significant gaps in our understanding of microcirculatory function in disease.
The diffusion models are also informative for understanding the effects of HBOT on living tissue, especially because direct PO2 measurements are technically difficult to make in the chamber, even experimentally. In the 1960s, C. J. Lambertsen measured the arteriovenous O2 difference in the cerebral circulation in healthy human subjects and found that even at inspired PO2 of up to 3.5 ATA, jugular venous PO2 rarely exceeded 60 mm Hg (Fig. 8.14).25 Such profiles indicating high PO2 differences across organ vascular beds are typically caused by the low plasma O2 solubility and by O2-induced vasoconstriction. However, the mean capillary PO2 predicted at 3.5 ATA approached 900 mm Hg, an estimate later confirmed experimentally in animals by brain tissue PO2 measurements. Placing these observations into the context of the cylinder model, the fact that HBO arterializes the venous blood means that the radius of diffusion for O2 into tissue at the venous end of the capillary has been increased to approximately the same level as that of a normal arteriole.12 This concept is shown in Figure 8.15. Figure 8.15 also demonstrates that the tremendously high values of PaO2 found under hyperbaric conditions make HBO an exception to the normal rule that partial oxygen pressure in mixed venous blood (PvO2) is a good estimate of mean capillary PO2.21
The idea that HBO expands the effective radius of O2 diffusion in the capillary is useful for understanding its therapeutic role in relieving tissue hypoxia when local DO2 is impaired or when the mean intercapillary distance is increased, for instance, by microcirculatory smooth muscle dysfunction or in the presence of capillary damage or destruction. The latter processes contribute to disordered microcirculatory function in diabetes and in radiated tissues. The concept of an expanded diffusion radius is also useful to help explain the beneficial effect of HBOT in interstitial edema, which, in effect, increases the mean intercapillary distance.26 These principles are illustrated by Figure 8.16.
It should also be remembered that the maximum O2 diffusion distances in tissues are intrinsically short—on the order of a few hundred micrometers—and that the concepts of tissue PO2 discussed earlier do not account for the opposing tendencies by HBOT to suppress
T and constrict blood vessels. Nevertheless, HBOT clearly improves the oxygenation of both healthy and diseased tissues provided convective DO2 is adequately maintained in the distributive circulation.
Based on the earlier information and before describing organ-specific effects of HBOT, it is helpful to summarize the main physiologic factors that influence PO2 in tissues and their qualitative effects. These factors are listed in Table 8.1. For ease of understanding, Table 8.1 indicates only the independent role of each factor because the effects of combinations are difficult to predict, especially when the combined changes counteract each other. Note, however, that HBOT increases tissue PO2 despite O2-induced vasoconstriction under most of the listed conditions.
James S. Lowe BMedSci, BMBS, DM, FRCPath , Peter G. Anderson DVM, PhD , in Stevens & Lowe's Human Histology (Fourth Edition), 2015
Stem Cells and the Heart
Despite the dogma regarding regenerative limitations of the heart, endogenous adult cardiac stem cells have been isolated in many species on the basis of positive Sca-1 and c-kit stem cell markers (Fig. 9.25). These human cardiac stem cells have been identified, isolated and shown to differentiate into cardiomyocytes, smooth muscle cells, or endothelial cells both in vitro and in vivo. These studies engender hope that stem cell methodologies can in the future be used to regenerate damaged heart tissues in clinical settings.
Practical Histology
FIGURE 9.26. Histology of the heart.
(a) Low-power micrograph showing part of the wall of the left atrium (LAW) and left ventricle (LVW). Part of the mitral valve (MV), papillary muscles (PM) and chordae tendineae (CT) are also shown. Note that the left atrial wall has a relatively thick endocardium (E), whereas the thin endocardium of the left ventricle cannot be discerned at this magnification. Thick (Tk), thin (Tn) and medium (M) pericardium can all be seen on the outer surface of the heart. (b) Medium-power view of medium thickness pericardium from the area labelled M in (a). The outer layer (OL) is mesothelium-covered collagenous and elastic tissue, beneath which is a narrow adipose tissue layer (A) containing blood vessels (V).
Practical Histology
FIGURE 9.27. Small and large arteries.
(a) This photomicrograph shows a small muscular artery (A) cut in transverse section, together with some distended thin-walled small veins (V). With the H&E stain the elastic lamina can be difficult to see; it is more clearly seen in a special stain for elastic tissue (see Fig. 9.5b,c). (b) Micrograph showing the H&E appearance of a typical large elastic artery in the systemic circulation, in this case the aorta, at high magnification. The media is composed of alternate layers of relatively indistinct smooth muscle fibres and laminae of intensely eosinophilic, slightly refractile, elastic tissue.
FIGURE 9.28. Small blood and lymphatic vessels.
(a) Micrograph of small vessels in adipose tissue, showing capillaries (C). One capillary is opening into a postcapillary venule (PCV), into which a direct metarteriole (M) is also opening. (b) Micrograph of a large lymphatic vessel containing pink-staining lymph. Note that the muscle in the media merges into an indistinct adventitial layer. The nuclei of some of the endothelial cells are just visible.
Practical Histology
FIGURE 9.29. Anatomy of the heart.
(a) Opened right side of the heart. In the right atrium (RA), note the opening of the superior vena cava (SVC), the inferior vena cava (IVC), the coronary sinus (CS) and the thin atrial wall (AW). The arrow marks the site of the sinoatrial node. In the right ventricle (RV), note the flaps of the right atrioventricular (tricuspid) valve (TV) separating the ventricle from the atrium, the pulmonary outflow tract (PT) with the pulmonary valve (PV) between it and the pulmonary artery trunk (PA). (b) Opened left side of the heart. Blood enters the left atrium (LA) through the pulmonary veins (PV), and leaves through the left atrioventricular (mitral, bicuspid) valve (MV) into the left ventricle (LV). In the left ventricle, note the thick muscular wall (VW), the papillary muscles (PM) and the chordae tendineae (CT), which link them to the leaflets of the mitral valve. Blood leaves the left ventricle through the aortic outflow tract and the aortic valve (AV) and enters the aorta (A).
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End of Chapter Review
True/False Answers to the MCQs, as Well as Case Answers, Can be Found in the Appendix in the Back of the Book.
1.
Which of the following are true in the heart?
(a)
The main coronary arteries run in the epicardium
(b)
Myocardial cells have central nuclei and are striated
(c)
The endocardium contains elastic tissue
(d)
The valves are composed of dense collagenous tissue and lack an endocardial covering
(e)
The pericardial sac is lined by mesothelial cells
2.
In the arterial system, which of the following features are present?
(a)
Large elastic arteries that do not contain smooth muscle in their media
(b)
Muscular arteries that have both an internal and external elastic lamina
(c)
Muscular arteries that do not have an intimal layer
(d)
The tone of smooth muscle is regulated by factors secreted by the endothelium as well as innervation by the autonomic nervous system
(e)
Vasa vasorum supply blood to the walls of large arteries
3.
Which of the following is true regarding the cardiac conducting system?
(a)
Cardiac contractions originate in the sinoatrial node
(b)
Internodal atrial muscle carries signals directly to the left and right bundle branches
(c)
Purkinje fibres are indistinguishable from adjacent myocardial cells
(d)
The atrioventricular node gives rise directly to the bundle of His
(e)
The atrioventricular node is the only part of the conducting system composed of neuronal tissue
4.
In the lymphatic circulatory system, which of the following are seen?
(a)
Lymphatic capillaries take fluid from the extracellular space
(b)
The term 'chyle' is used to describe lipid-containing lymph draining from the intestines
(c)
Large lymphatic vessels have smooth muscle in their walls
(d)
Valves assist the flow of lymph
(e)
Lymph which goes to the lymph nodes returns to the venous system via a main lymphatic such as the thoracic duct
Case 9.1 Sudden Death in An Obese Woman
A 57-year-old obese woman collapses with acute breathlessness, becomes blue in the face and dies within a few minutes. According to her husband she had been unwell with flu for about 4 days, most of which time she had spent in bed. The family practitioner explains to the distraught husband that the death must be referred to the Coroner for the district, and that an autopsy will be necessary. He undertakes to meet the widower after the autopsy to explain to him the cause of death, and few days later the husband arrives with a Death Certificate issued by the Coroner, which states:
Cause of death
1(a) Massive pulmonary thromboembolism
(b) Deep vein thrombosis (Rt leg)
The family practitioner explains that a blood clot had formed in the veins deep in the muscles of the right calf and had probably enlarged over a few days. A piece of the blood clot had then broken off and passed into the main blood vessel of the lung which it had blocked off, leading to sudden death.
Q.Describe the structural and anatomical background to this case.
Case 9.2 A Man with Central Chest Pain
A 62-year-old cab driver is admitted to hospital as an emergency with a central crushing chest pain, persisting for 14 h. It came on while he was gardening but did not go away when he rested, nor overnight with complete bed rest. On examination, he was severely breathless, with white froth on his lips, cyanosed and in distress. He had a weak rapid pulse and was hypotensive (low blood pressure). The examining physician could hear widespread crepitations over both lung fields, and also could hear a scratching noise over the heart area in time with each systole; he explains to the attending students (of whom you are one) that this represents a pericardial friction rub. An ECG carried out in the Emergency Room (ER) shows changes that the physician explains as indicative of an anteroseptal myocardial infarction of the left ventricle.
After emergency treatment in ER, the patient is transferred to a coronary care unit, where his cardiac activity is continuously monitored and treatment is maintained.
He appears to be making a good recovery, but on the eighth day he suddenly collapses and dies. At postmortem his pericardial cavity is found to be greatly distended by blood.
Q.Describe the structural and anatomic background that explains this case. Include an explanation for the pericardial friction rub and the postmortem findings in the pericardium.
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