Blood Capillaries

The cells of the blood capillaries in brain have tight junctions, contrary to what prevails with capillaries in other tissues, leaving very little space between the cells for filtration of small-size, water-soluble molecules.

From: Encyclopedia of Toxicology (Third Edition) , 2014

Noninfectious Arthritis

Alicia L. Bertone , in Diagnosis and Management of Lameness in the Horse (Second Edition), 2011

Effusion

Increased blood flow and capillary leakage occur early and contribute to increased fluid volume in the joint interstitium and synovial fluid, recognized as effusion. The condition is stimulated by vascular changes and neurotransmitter release, particularly α2-adrenergic stimulation.2,8,9 Because of low intraarticular pressures in normal equine joints (−5 mm Hg6; −1.25 mm Hg12), effusion precedes interstitial edema, until intraarticular pressure is greater than 11 mm Hg.1 These physiological circumstances make detection of effusion one of the most sensitive indicators of early joint stress. Effusion, although common, is not normal and alters joint function. Congruent motion of joint surfaces depends on normal negative pressure and is important in decreasing shear force (side-to-side, sloppy movement).7 Effusion is not painful as long as capsular tension is normal. Through the phenomenon of creep-relaxation, capsular tension is reduced in distended joints. Normal joints are relatively compliant and can accommodate fairly large changes in fluid volume with minimal increase in pressure, but elastance profiles of these joints may be permanently altered.13 Joints with high structural congruence, such as the tarsocrural joint, are less affected biomechanically by joint effusion than are less congruent joints.7

High synovial fluid volume becomes more important during joint motion. Joint pressure profiles are profoundly altered by joint angle.6,7,13 With effusion, as initial intraarticular pressure is increased, the capacity to accommodate rapid changes in pressure goes down, causing a rapid rise in intraarticular pressure and capsular wall tension at extreme joint angles, resulting in sharp pain during maximal joint excursion and simultaneous reduction in synovial perfusion.14 These effects could be present even if synovitis is not recognized clinically. The influence of intermittent synovial ischemia is not elucidated fully, but it may be important in diseases of synovial proliferation.

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Pharmaceutical Perspectives of Nonviral Gene Therapy

Ram I. Mahato , ... Alain Rolland , in Advances in Genetics, 1999

A Anatomical and physiological considerations

The blood capillary walls are generally comprised of four layers, namely plasmaendothelial interface, endothelium, basal lamina, and adventia. The endothelium is a monolayer of metabolically active cells, which mediate and monitor the bidirectional exchange of fluid between the plasma and the interstitial fluid. There are several different pathways by which macromolecules can cross the endothelial barrier (Simionescu, 1983; Taylor and Granger, 1984): (i) through the cytoplasm of endothelial cells themselves; (ii) across the endothelial cell membrane vesicles; (iii) through interendothelial cell junctions; and (iv) through endothelial cell fenestrae. Based on the morphology and continuity of the endothelial layer and the basement membrane, capillary endothelium can be divided into three categories continuous, fenestrated, and discontinuous endothelium.

The continuous capillaries are found in skeletal, cardiac, and smooth muscles, as well as in lung, skin, and subcutaneous and mucous membranes. The endothelial layer of the brain microvasculature is the tightest endothelium, with no fenestrations. This endothelial barrier forms a continuous cellular layer between the blood and brain interstitium, which is impermeable to plasmids. Capillaries with fenestrated endothelia and a continuous basement membrane are generally found in the kidney, small intestine, and salivary glands. Most of these capillaries have diaphragmed fenestrae, which are circular openings of 40–60 nm in diameter. The discontinuous capillaries, also known as sinusoidal capillaries, are common in the liver, spleen, bone marrow, and other organs of the reticuloendothelial system. These capillaries show large interendothelial junction (fenestrations up to 150 nm). Depending on the tissue or organ, the basal membrane in sinusoidal capillaries is either absent (e.g., in liver) or present as a discontinuous membrane (e.g., in spleen and bone marrow) (Venkatachalam and Rennke, 1978). The sinusoids of the liver are lined by highly phagocytic Kupffer cells, and those of the bone marrow by flattened, phagocytic reticuloendothelial cells. In the spleen, the endothelial cells are greatly elongated and contain a large number of pinocytic vesicles (up to 100 nm in diameter).

Due to their large molecular weight (greater than 1000   kDa) and hydrodynamic diameter in aqeuous suspension of 100   nm (Ledley, 1996), plasmids extravasate poorly via continuous capillaries because of tight junctions between the cells. However, plasmids can easily extravasate to sinusoidal capillaries of liver and spleen. Formulating plasmids into unimeric particles of 20–40   nm in diameter may enhance extravasation of plasmids across continuous and fenestrated capillaries.

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Vascular Pharmacology: Cytoskeleton and Extracellular Matrix

Sofia Urner , ... Eckhard Lammert , in Advances in Pharmacology, 2018

3.2.1 Mechanical Forces During Interstitial Fluid Uptake at Lymphatic Capillaries

Whenever blood moves through blood capillaries, there is—in most tissues—a constant leakage of small fluid amounts into extracellular spaces, which creates an interstitial fluid pressure. Drainage of interstitial fluid is mainly driven by a gradient between the high interstitial fluid pressure and the low intraluminal pressure within lymphatic capillaries ( Benoit et al., 1989; Rahbar, Akl, Cote, Moore, & Zawieja, 2014). The latter can be generated by lymphatic valves further downstream (Fig. 2). A key aspect for lymph formation is the existence of discontinuous button-like intercellular junctions (positive for VE-Cadherin, PECAM-1, Occludin, and Claudin-5) that allow unidirectional entry of fluid into lymphatic capillaries (Baluk et al., 2007; Murfee, Rappleye, Ceballos, & Schmid-Schonbein, 2007). In addition, anchoring filaments connect the LECs of lymphatic capillaries to the ECM, and are thought to support opening of intercellular spaces in response to increased interstitial fluid accumulation. Deletion of the ECM glycoprotein Emilin1 leads to a reduced number of anchoring filament bundles, and results in inefficient lymph drainage and increased leakage (Danussi et al., 2008). However, Emilin1-deficient mice only develop a mild lymphedema, which suggests that there might be also alternative mechanisms of lymph drainage by lymphatic capillaries. For example, LECs might be pulled apart when their surrounding ECM swells due to interstitial fluid accumulation.

The endothelium of lymphatic capillaries expresses lymphatic-specific markers like PROX1, Podoplanin, Lyve1, and VEGFR3 (Makinen et al., 2005; Yang & Oliver, 2014) (Fig. 2). VEGFR3 responds to mechanical forces (like interstitial fluid pressure-induced LEC stretch or flow-induced shear stress) by tyrosine phosphorylation mediated by β1 integrin (Baeyens et al., 2015; Choi, Park, Jung, Seong, Hong, et al., 2017a; Coon et al., 2015; Planas-Paz et al., 2012).

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Effects of Green Tea Polyphenols under Hyperlipidemic Conditions through their Anti-Angiogenic Activity

George Agrogiannis MD, PhD , ... Efstratios Patsouris MD, PhD , in Tea in Health and Disease Prevention, 2013

Summary Points

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Angiogenesis, the process of blood capillary formation, plays a crucial role on the progression of atherosclerosis.

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Epidemiological studies have indicated an inverse relationship between the consumption of green tea and the risk of coronary heart disease.

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Green tea catechins seem to interfere with angiogenesis through multiple molecular pathways and retard the progression of atherosclerosis through their anti-angiogenic potential.

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The beneficial effects of epigallocatechin-3-gallate, the most active green tea derivative, on the inhibition of angiogenesis has become apparent over the last decades.

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Further in vitro research on green tea components needs to be carried out in order to supply more data on their anti-angiogenic action.

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Health Perspectives of an Isoflavonoid Genistein and its Quantification in Economically Important Plants

Ashwini Malla , Sathishkumar Ramalingam , in Role of Materials Science in Food Bioengineering, 2018

6.3 Antiangiogenic Effects

Angiogenesis is the formation of new blood capillaries, which is an essential physiological process. The solid tumors, which are beyond 1 mm in size, will foster the growth of fresh blood vessels with the proper supply of oxygen and glucose. Hence, antiangiogenic compounds are a focus of further exploration. Genistein is the most powerful plant-derived inhibitor in thwarting angiogenesis by the inhibition of vascular endothelial cells ( Polkowski and Mazurek, 2000). From the reports, it has been discovered that when genistein is injected subconjunctivally, it showed the reduction of blood vessels at the limbus and the vascularized area in the eye, resulting in prevention of neovascularization of the cornea (Kruse et al., 1997).

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Angiogenesis in aging hearts—Cardiac stem cell therapy

Vinu Ramachandran , Anandan Balakrishnan , in Stem Cells and Aging, 2021

2.2 Vascular changes (impaired angiogenesis) in cardiac aging

2.2.1 Angiogenesis

Angiogenesis is the sprouting of new blood capillaries from preexisting vascular structures. This mechanism is initiated by the migration and proliferation of endothelial cells. The new capillaries form as a network, consisting of endothelial cells as tubes, but lack smooth muscle cells and stabilizing cell structures [21]. An age-associated effect on cardiovascular function includes dysregulated angiogenic repair mechanism, which is responsible to restore blood flow after ischemia [22].

2.2.2 Impaired angiogenesis in aged hearts

Among the several cell types of the noncardiomyocyte population, the chief blood vessel types comprise vascular endothelial cells, vascular smooth muscle cells and pericytes. One of the clinical features in an aging elderly human heart is vascular aging characterized by endothelial dysfunction and increased stiffness of central arteries [23]. Irrespective of the proliferative capacity held by vascular cells in vitro and following injury in vivo, age-associated plaque deposits in the blood vessels result in stiffness of walls, inflammation, myocardial infarction and vascular cell death. Subsequently, resulting in impaired vascular structure and function [17, 24].

Evidences for age-associated impairment of angiogenesis are presented as decreased capillary density, defective functionality of eNOS, impaired sensitivity to insulin, reduced proliferative capacity of senescent endothelial cells, impaired telomerase activity, reduction in the production of angiogenic growth factors like VEGF-A, reduced endothelial migration, in hypoxia-inducible factor 1α (HIF1α) and Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) activity, and deterioration in amount and function of the stem and progenitor cells [6, 25–27]. Chronic psychological stress in mice caused a decline in angiogenic action (impaired aortic endothelial sprouting) and accelerated vascular (aortic) senescence [28].

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Physiology of Elasmobranch Fishes: Internal Processes

Phillip R. Morrison , ... Colin J. Brauner , in Fish Physiology, 2015

2.4.1 Carbon Dioxide and Blood pH

Metabolic carbon dioxide diffuses into the tissue capillary blood, elevating venous PCO2 and potentially affecting blood-oxygen transport owing to the concomitant decrease in blood pH. Blood-oxygen transport in many elasmobranchs appears to be relatively insensitive to CO2 (e.g., Graham et al., 1990), although some species exhibit modest Bohr effects in vitro (Table 3.3). The CO2 Bohr coefficient describes the changes in blood pH caused by altering PCO2, and it is this relationship between Hb-O2 affinity and CO2-dependent changes in whole blood pH (i.e., extracellular or plasma pH; pHe) that is most commonly reported in whole blood-O2 equilibria studies. The relationship between pHi and pHe is usually linear, but deviates from unity. If so, the extracellular Bohr coefficient (Φ pHe) can be divided by the ΔpHi/ΔpHe value to estimate the true or intracellular Bohr coefficient (Φ pHi). Interestingly, in the few species of elasmobranchs that have been investigated, ΔpHi/ΔpHe is close to unity, unlike teleosts. The whole blood Bohr coefficient for Scyliorhinus canicula (Φ pHe=−0.43; Pleschka et al., 1970) is only slightly increased when the ΔpHi/ΔpHe value (∼0.94; Wood et al., 1994) is taken into account (Φ pHi=−0.43/0.94=−0.46). Similarly, for Squalus acanthias blood the relationship between pHi and pHe is slightly nonlinear over the measured pH range but ΔpHi/ΔpHe averages about 0.9, which only slightly underestimates the Bohr coefficient (Φ pHe =−0.28 and Φ pHi =−0.28/0.9=−0.31; Wells and Weber, 1983).

The CO2 Bohr effect differs from the fixed-acid Bohr effect, which is usually reported in studies of hemolysates or isolated Hb and describes changes in P 50 caused by titration with non-CO2 or fixed acid. Inequality between the CO2 and fixed-acid Bohr coefficients indicates that CO2 also has a specific effect on Hb-O2 affinity that is caused by carbamate formation from the preferential binding of CO2 to the α-amino groups of deoxygenated Hb (Kilmartin and Rossi-Bernardi, 1973; Jensen et al., 1998). As in teleosts, the α-amino groups of the α-chains are acetylated in at least two elasmobranch Hbs (Fig. 3.1), and the α-amino groups of the β-chains are likely involved in organic phosphate binding in some selachian Hbs (see Section 2.1.5). Consequently, oxylabile carbamino formation may affect blood-O2 transport in some elasmobranchs more than others (Jensen, 2004). In Squalus acanthias, the whole blood Bohr effect is slightly greater than the fixed-acid Bohr effect measured on stripped hemolysates (Weber et al., 1983a; Wells and Weber, 1983), which is consistent with the allosteric interaction of RBC intracellular organic phosphates and possibly a specific CO2 effect because CO2 can potentially form carbamate with the non-acetylated α-chains of Squalus acanthias Hb (Weber et al., 1983a; Wells and Weber, 1983; Aschauer et al., 1985).

Butler and Metcalfe (1988) provided a brief review of published Bohr coefficients for elasmobranchs; here, this information will be updated. Bohr coefficients for stripped Hb and hemolysates are listed in Table 3.2, and those for whole blood are tabulated in Table 3.3. Interestingly, blood from the spotted ratfish, Hydrolagus colliei, shows no indication of cooperative O2 binding (n H=1.1) and CO2 tensions as high as 27   mmHg did not affect n H or P 50, indicating the lack of a Bohr effect in the blood of this holocephalan (Hanson, 1967). The Bohr effect also is absent or very small for a number of elasmobranchs, including the batoideans Leucoraja ocellata, Torpedo nobiliana, Amblyraja hyperborea, and Bathyraja eatonii, and the selachians Mustelus canis, Heterodontus portusjacksoni, and Squalus suckleyi (Tables 3.2 and 3.3; Dill et al., 1932; Lenfant and Johansen, 1966; Bonaventura et al., 1974a; Grigg, 1974; Scholnick and Mangum, 1991; Cooper and Morris, 2004; Verde et al., 2005). However, the presence of a fixed-acid Bohr effect in purified Hb from Squalus suckleyi (Table 3.2; Manwell, 1963) contradicts the absence of a Bohr shift in whole blood from this shark (Lenfant and Johansen, 1966), and consequently it may be worth revisiting species reported in the older studies.

Whole blood Bohr coefficients (Φ pHe) in elasmobranchs are typically lower than those reported for teleosts, ranging from −0.05 to −0.52 in the batoideans, and from −0.11 to −0.56 in the selachians (Table 3.3).Wells and Davie (1985) reported a slight reverse Bohr effect in blood from mako sharks, Isurus oxyrinchus, but the data were probably not representative of resting conditions because the sharks had been so exhaustively exercised that air-equilibrated blood had a pH of 6.2! Interestingly, a Bohr effect is present in whole blood from the marbled electric ray, Torpedo marmorata (Hughes, 1978), but is absent from stripped hemolysates of the congeneric Torpedo nobiliana (Bonaventura et al., 1974a). Whole blood from the bat eagle ray, Myliobatis californica, exhibits quite a substantial Bohr effect (Table 3.3; Hopkins and Cech, 1994a), and because all other rays in the order Myliobatiformes that have been studied to date (i.e., Dasyatis akajei, Dasyatis sabina, Potamotrygon spp., Rhinoptera bonasus) also possess a Bohr effect (see Tables 3.2 and 3.3) it seems reasonable to hypothesize that the mechanism responsible for the Bohr effect in Dasyatis akajei Hb (see Section 2.1.4) may have been inherited from the common ancestor of the Myliobatid families. The magnitude of the Bohr effect in Myliobatis californica is relatively temperature independent, whereas in the draughtsboard shark, Cephaloscyllium isabellum, the whole blood Bohr coefficient was greater in 5°C acclimated sharks than in 15°C acclimated sharks (Table 3.3; Tetens and Wells, 1984). Some studies have reported P 50 values and Bohr coefficients measured on washed RBCs that were resuspended in buffered elasmobranch saline (e.g., Scholnick and Mangum, 1991; Wells et al., 1992), but it is not known whether this method compromises the integrity of elasmobranch RBCs (e.g., see Caldwell et al., 2006).

The Bohr effect is generally considered beneficial for tissue O2 delivery. Lapennas (1983) proposed that a Bohr coefficient equal to half of the respiratory quotient (RQ,=CO2 eliminated/O2 consumed) should be optimal for O2 delivery to the tissues of the dog and the gray seal. Even though the assumptions (i.e., steady-state conditions, the absence of a specific CO2 effect on Hb-O2 affinity, and a RQ between 0.7 and 1.0) of Lapennas' "optimal" Bohr coefficient hypothesis are rarely met in fishes, it provides a starting point to evaluate the potential benefit of the Bohr effect. In teleosts, tissue O2 delivery is likely enhanced by the Root effect that reduces blood O2-carrying capacity at low pH (Rummer et al., 2013; Randall et al., 2014). Elasmobranchs lack a physiologically relevant Root effect (Lenfant and Johansen, 1966; Pennelly et al., 1975; Farmer et al., 1979; Ingermann and Terwilliger, 1982; Wells and Weber, 1983; Wells and Davie, 1985; Dafré and Wilhelm, 1989; Berenbrink et al., 2005; Brill et al., 2008), but some elasmobranchs (e.g., Myliobatis californica, Rhinoptera bonasus, Carcharhinus plumbeus, and Scyliorhinus canicula) have whole blood Bohr coefficients (Table 3.3) that are very similar to mammalian values (Φ≈−0.46 to −0.51; Reeves, 1980; Lapennas and Reeves, 1982; Reeves et al., 1982). Thus, it is very likely that the Bohr effect in elasmobranchs was under selection to take advantage of the arterial-venous pH difference (Table 3.3) to enhance O2 delivery to the tissues.

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ROLE OF THE KIDNEYS | Histology of the Kidney

D.B. McMillan , in Encyclopedia of Fish Physiology, 2011

Abstract

The kidney of fishes consists of knots of blood capillaries, the glomeruli, that are closely associated with kidney tubules. Several glomeruli may be aggregated into larger structures, the glomera. A filtrate of the blood plasma is gathered by a nephric capsule, which closely invests the capillaries. This fluid passes down the tubules where valuable components are restored to the blood in capillaries that entwine the tubules. Secretory cells in some of the blood vessels associated with the glomeruli secrete an enzyme, renin, into the blood. Renin has a profound effect on blood pressure and hence on filtration rate in the kidney.

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Dentine and Dental Pulp

Barry Berkovitz , Peter Shellis , in The Teeth of Non-Mammalian Vertebrates, 2017

Vasodentine

This is a rare form of dentine in which blood capillaries become incorporated into the dentine as it is deposited. Blood continues to flow through these vessels in the living animal, so that the teeth appear red (see Fig. 4.61). From our own material and the slides in the Tomes Collection (Royal College of Surgeons), we have identified vasodentine in several gadiform teleosts: cod (Gadus morhua; Gadidae), haddock (Melanogrammus aeglefinus; Gadidae), hake (Merluccius merluccius; Merluccidae), and ling (Molva molva; Lotidae; Fig. 11.35). It is also present in the pike-perch (Sander sp.; Percidae), the Atlantic wolf-fish (Anarhichas lupus; Anarhichidae) and a butterfly fish (Chaetodontidae) (see Fig. 4.103). In all cases the outer dentine was free of capillaries and was a form of orthodentine. It has also been reported that vasodentine fills the pulp chamber of the three-toed sloth (Bradypus: Mammalia, Xenarthra; Schmidt and Keil, 1971), but this observation requires further confirmation. Schmidt and Keil reported that the tissue in question is formed as the teeth wear down, rather than as a primary tissue as in other species. Moreover, the histological structure resembles osteodentine rather than typical vasodentine.

Figure 11.35. Longitudinal section of tooth from ling (Molva molva). At the bottom of the field is an outer layer of dentine lacking tubules. Most of the dentine thickness consists of vasodentine, which is permeated by blood capillaries that connect with the dental pulp (upper left). Image width   =   1.05   mm.

 Courtesy of Royal College of Surgeons. Tomes Slide Collection, Cat. no. 376.

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Neuroparasitology and Tropical Neurology

Fabrizio Bruschi , ... Edoardo Pozio , in Handbook of Clinical Neurology, 2013

Pathogenesis of neurotrichinellosis

The presence of larvae in the CNS causes damage to blood capillaries such as vasculitis and perivasculitis, which are responsible for diffuse or focal lesions. The NBL may wander, causing tissue damage before reentering the bloodstream, or remain trapped and are then destroyed by a granulomatous reaction. Neural cells may also be damaged by eosinophil degranulation products such as eosinophil-derived neurotoxin and major basic protein ( Durack et al., 1979). Moreover, heart and brain lesions are often associated and could result from the simultaneous intervention of local prothrombotic effects of eosinophil activation and vascular injury caused by the migrating larvae (Fourestié et al., 1993).

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