Clinical Hemorheology and Microcirculation - Volume 2, issue 5-6

Authors: Copley, Alfred L.

Article Type: Editorial

DOI: 10.3233/CH-1982-25-601

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. vii-vii, 1982

Authors: Witte, Siegfried

Article Type: Editorial

DOI: 10.3233/CH-1982-25-602

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. ix-x, 1982

Authors: Witte, S.

Article Type: Other

DOI: 10.3233/CH-1982-25-603

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 413-413, 1982

Authors: Meessen, Hubert

Article Type: Research Article

Keywords: Diapedesis, terminale Strombahn, histion, endothelium

DOI: 10.3233/CH-1982-25-604

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 415-423, 1982

Authors: Hammersen, F. | Hammersen, E.

Article Type: Research Article

Abstract: (I) The blood capillary endothelial cell (EC): Three different structures play a more or less decisive rôle in capillary permeability characteristics: (1) a delicate endothelial layer of glycoproteic nature, (2) intracytoplasmic vesicles and/or channels of different stereological configurations with a max. inner diameter of 50 nm, and (3) interendothelial clefts 15-20 nm wide of variable length and course, fitted with attachment decives of variant fine structure. (II) The interstitial space (ISS): To evaluate the barrier functions of this compartment with the limited arsenal of morphological techniques is extremely difficult, and therefore the results are controversial. Using electron-dense tracers of …variant molecular seizes, the very first component of the ISS directly beyond the endothelial cells, i.e. their basal lamina, does not seem to function as a general, ubiquitous sieve for molecules up to a seize of 5 nm. Caution, however, is emphasized against data obtained and conclusions drawn from model experiments performed with a very special, yet frequently employed representative of endothelial basal laminae, i.e. the glomerular basement membrane. The adjoining interstitial space proper (ISS) consists of three major components: (1) a fluid phase, (2) a phase of dissolved macromolecules, and (3) the matrix which is composed of long chain molecules of fibrous proteins (e.g. collagen) and glucosaminoglycans (mucopolysaccharides). While the first two of these constituents are more or less beyond the reach of any structural analysis, the third component can be studied more closely with both histochemical techniques and electron microscopy to elucidate its chemical and structural composition. Not this, however is the objective of the present contribution, but the barrier functions of the ISS, which depend to a variant extent on all its components. Off these it is the matrix again which allows to demonstrate at an ultramicroscopic level at least one of its permeability characteristics, namely the phenomenon of ‘exclusion’. Another proposition held over more recent years emphasized the regular occurence of nonendothelialized, preformed ‘tissue channels’ which should serve as ‘prelymphatics’ of variable length and diameter in almost every tissue and organ. The methods, between, however, by which the existence of such ‘channels’ has been proven are open for severe criticism due to the many artifacts involved in the techniques employed. At this stage it seems, therefore, to be premature to correlate already these structurally defined ‘channels’ with those postulated to exist on the grounds of permeability data and calculations. (III) The endothelium of the initial (terminal) lymphatics: As compared to the blood capillary endothelial cells, lymphatic endothelium appears to be more uniform with less topical spezializations. It differs from blood capillary ECs in several ways: (1) It is extremely thin over large areas except its nucleated portion. (2) Micropinocytic vesicles are less numerous and most of them tend to form lysosomal vacuoles instead of ferrying materials across the endothelial barrier. (3) The interendothelial clefts vary in width and they are often loosely arranged with no or less elaborate attachment decives. Open gaps of up to several microns width are regularly encountered. (4) The basement membrane is discontinous and ‘anchoring filaments’ insert in a densely staining substance of the abluminal endothelial plasmalemma. They extend into the surrounding connective tissue and they exert tension on the lymphatic wall thus stabilizing the vessel, keeping its lumen open and under certain conditions they may even pull adjoining ECs apart. Show more

Keywords: Endothelial cell, ultrastructure, interstitial space, initial lymphatic, vesicular transport

DOI: 10.3233/CH-1982-25-605

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 425-440, 1982

Authors: Hörmann, Helmut

Article Type: Research Article

Abstract: Connective tissue is a complex system consisting of cells, fibers and interstitial mucoproteins and glycoproteins. Among fibers collagen is the most important. Several genetically distinct types of this structural protein are known which are specific for various tissues. Their synthesis includes numerous steps beginning with the formation of procollagen peptide chains which subsequently are modified by hydroxylation and glycosylation and are twisted to triple-helical structures. Removal of terminal globular domains is required for assembly of monomers to fibrils which later on are stabilized by covalent cross-linking. Several inherited diseases like dermatosparaxis or special forms of Ehlers-Danlos syndrom are due to …the inability of performing one of these steps. In addition, incomplete processing of collagen can be the result of malnutrition e.g. lack of ascorbic acid, copper deficiency or lathyrogens in the food. Far more important among connective tissue diseases is an excess of fiber formation in soft tissues. Fibrosis of liver and lung, probably, is not the result of an increased collagen synthesis but of an increased conversion of soluble collagen precursors to fibrils. Unless fibrils are formed the soluble collagen derivatives are removed by proteolytic digestion. Regulation of fibrillogenesis, however, is little understood and, evidently, involves the participation of glycosaminoglycans and glycoproteins. One model assumes that collagen precursors deposit on preformed fibronectin fibrils constituting the pericellular matrix of fibroblasts and other adherent cells. The expression of this pericellular matrix, on the other hand, appears to be regulated by glycosaminoglycans on the cell surface and the near environment. It varies with the cell cycle, the cell density and the proliferation activity of the cells and is influenced by several drugs. Following establishment of collagen fibers the fibronectin guide-lines, evidently, are removed. The cell environment also influences the type of collagen expressed. Chondrocytes producing collagen type II, under special conditions, convert to fibroblast-like cells synthesizing type I and type III. Simultaneously the kind of glycosaminoglycans produced is changed. Show more

Keywords: Connective tissue, collagen, glycosaminoglycan, fibroblast, fibronectin

DOI: 10.3233/CH-1982-25-606

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 441-451, 1982

Authors: Lindner, J. | Lindner, Ch.

Article Type: Research Article

Abstract: The pathology of connective tissue is demonstrated by the most important example: the inflammation, summarizing the basic processes of pathological reactions of connective tissues on the several irritations and injuries. Comparative morphological and biochemical methods, employed on the same material as far as possible, allow a better insight into and investigation of the single stages of inflammation, which start very fast. They have been localized qualitatively and assayed quantitatively, esp. the processes occuring immediately after the start of inflammation as the several steps of the disturbed regulatory equilibrium between catabolism and anabolism in the involved connective tissue. The …primary increase of the catabolism at the beginning of inflammation is followed almost immediately by an increased anabolism of all 3 components of the vascularized connective tissue, i.e. the substrate of inflammation: cells, ground substance and fibres. Thus their turnover is remarkably increased in inflammation. The single phases of inflammation are regarded in relation to each other and summarized: the cell injuries, endothelial cells included, the several stages of disturbed blood flow (prestasis, stasis and poststasis), the enhanced permeability and their consequences (swelling, dissolution, degradation etc.), exudation and emigration, sticking processes and chemotaxis, mediators and their effects, granulocytes, lymphocytes, monocytes and macrophages, their functions, the immunological responses included, but esp. the processes of pinocytosis and phagocytosis, the whole degradation and breakdown of phlogistics as well as of the components of the injured, inflamed and damaged connective tissue. Its replacement is achieved by the new formation of capillarized granulation tissue, depending on the intensity and duration of the inflammation. So, finally scars can result, with reduction of capillaries, cells and ground substance. Then the collagen content prevails. The catabolic and anabolic processes during inflammation are regarded in their feedback relations, esp. of the proteoglycans and collagen, their several heterogeneities, their interrelations, interactions and interdependencies included. They are also described as main processes of the disturbed equilibrium of connective tissues, i.e.: the basic and fundamental processes of the “pathology of Connective Tissues”. Than many degenerative lesions are the final results of some of these main and general steps of connective tissue reactions. The disturbances of these several relations and phases during inflammation by drugs are discussed finally. The influences of the most common antiphlogistic agents on inflammation intervene in the various mechanisms of these turnover alterations of the 3 main components (cell, proteoglycans and collagen), i.e. as a rule, not only in one process. Often cell proliferations, lysosomal degradations, syntheses of catabolic and/or anabolic enzymes and of the intracellular macromolecular substances (= the differentiation products of connective tissue cells) can be influenced by application of one antiphlogistic drug. Since the extent and duration of inflammations strongly depend on the extent of degradation and/or of the extent of enhanced catabolism and anabolism during the start of inflammation, it is emphasized to influence inflammations as early as possible, best by previous antiphlogistic drug administrations. This is practicable in many cases of inflammation in human medicine. So the most important basic subjects of the “Pathology of Connective Tissue” are demonstrated and discussed from the theoretical and clinical point of view. Show more

Keywords: Connective tissue, inflammation, stasis, permeability, mediator substances, basement membrane

DOI: 10.3233/CH-1982-25-607

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 453-495, 1982

Authors: Silberberg, A.

Article Type: Research Article

Abstract: Mechanical and chemical communication between cells depends upon the structure and biophysical character of the connective tissue space. From the point of view of the microcirculation (mainly its extravascular part and lymph formation) the permeability, selective and unselective, of the connective tissue matrix is of most obvious interest. It turns out, however, that the mechanical properties of the tissue are of no less importance, since they help to determine the gradients in chemical potential which exist between the blood stream and the tissue interstitium on the one hand and the interstitium and the lymph collecting system on the other. These …biophysical features of the connective tissue space, the transport and the mechanical properties, depend upon connective tissue structure and composition. It is convenient to divide the materials composing connective tissue into two groups: Immobilized, or essentially immobilized, components and diffusible components. The former involve mainly the fiber network system. This provides the mechanical integrity both of the connective tissue matrix and of the cells which are embedded in it or are attached to it. The fiber system is composed mainly of highly organized collagen fibers but also involves fibers of elastin and a network of structural glycoprotein. The ultimate strength of the tissue is that of the collagen system. The mechanical response to smaller deformation, however, is determined both by collagen fiber bending and elastin fiber rubber-like extensibility. The structural glycoprotein seems to have a modifying role. While these components are truly immobilized they constitute only a minority volume fraction in the tissue space. The voids are filled with diffusible species (mainly water), but also with a system of extremely high molecular weight, hydrophilic proteoglycans/hyaluronic acid associates. The chains of these have the tendency to coil freely through space being charged and largely carbohydrate in nature. Their large size traps them in the fiber environment though they do not really seem to be linked to the fiber system, even by secondary chemical interactions. Because of their intimate contact with water and of the charges they carry, they strongly affect the chemical potential of water and thus determine the tendency of tissue to absorb water. The extent of swelling attained is limited by a pressure rise imposed by mechanical stress induced in the fiber network. In this respect the connective tissue space is behaving like any gel-like system. Of interest here is that the mechanical and concentration effects on water chemical potential are physically separated and arise in two distinctly different immobilized structural components. The diffusible species, which besides water fill the interstitium can also be graded into roughly two groups: A group of low molecular weight components, mainly sodium chloride, which cross the blood/tissue barrier, essentially without hindrance, along with water. A group of high molecular weight species, mainly serum albumin whose passage is severely restricted and which occur, therefore, in the interstitium at a concentration very different to their concentration in blood. The chemical potential of water in tissues thus differs from that in blood because of this concentration difference, because of the presence of the proteoglycan/hyaluronic acid system and because of a difference in hydrostatic pressure. Since the connective tissue space can support only small gradients (due to much faster diffusion than convection of the diffusible species) and the chemical potential of water in blood decreases as the hydrostatic pressure drops from the arterial to the venous end of the microcirculation, the driving force on water will be outward at the arterial end and inward at the venous end. This is the basis of the Starling balance. In addition, water (and diffusible protein) can be cleared from the tissue spaces as lymph. This is necessary since protein driving forces do not permit a direct return to the blood stream by reabsorption. Show more

Keywords: Connective tissue, collagen, proteoglycan, lymph, diffusion

DOI: 10.3233/CH-1982-25-608

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 497-508, 1982

Authors: Silberberg, A.

Article Type: Other

DOI: 10.3233/CH-1982-25-609

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 509-509, 1982

Authors: Lee-Kelland, S. | Floyer, M.A.

Article Type: Research Article

Abstract: There are two pressures in the tissues which affect the flow of fluid across the capillary wall: the interstitial hydrostatic and oncotic pressures. The methods used to measure these pressures have been the subject of controversy and this has led to some doubt about the correct values. The manometer described below was designed to minimise the problem of scar tissue formation, slow equilibration and inflammation encountered in other techniques. Two types of membrane are used. The first is a large pore membrane which allows the measurement of the sum of the hydrostatic pressure and the pressure due to the …interstitial matrix. The second is a small pore membrane which permits the determination of the sum of the hydrostatic and oncotic pressures in the interstitium. The aim of the manometer design is to achieve extremely rapid measurement of pressures. Equilibration can usually be obtained in 1–2 minutes, although with some membranes as little as 30 seconds is required. When the subcutaneous fascia of the ventral abdomen of the rat is rapidly exposed and the membranes place on it, the following pressures are found. The large pore membrane gives a mean pressure of −1.85 cmH2 O (S.D. 0.7, n = 20) in the superficial fascia and a mean pressure of −1.85 cmH2 O (S.D. 0.8, n = 7) on the fibrous tissue overlying the abdominal muscles. The small pore membrane gives a mean pressure of −12.53 cmH2 O (S.D. 2.57, n = 13) on the superficial fascia and the same pressure on the fibrous tissue overlying the muscles. Subtraction of the pressure found with the large pore membranes from that found with the small pore membranes gives the oncotic pressure due to plasma proteins in the tissues. This pressure was −10.7 cmH2 O. Show more

Keywords: Tissue pressure, interstitial space, oncotic pressure, oncometer, inflammation

DOI: 10.3233/CH-1982-25-610

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 511-522, 1982