Under special circumstances, the endothelium and epithelium will not be able to metabolize or restructure all of the protein. The surplus is then deposited on the basement membrane as well, which can cause pathological reactions. Thus, the basement membrane is, along with the connective tissue, an extra protein depot. It is considered pathological for the basement membrane to swell to more than 1400 A (Angstrom units) as a result of protein deposition. Optimal filtration and diffusion becomes disrupted. To ensure cellular nutrition, regulating forces spring into action. Blood pressure rises reflexively to guarantee diffusion and filtration.
The basement membrane's permeability to nutrient substances depends on how swollen it is, which in turn depends on the acid-base balance.
When the basement membrane protein depot is overstuffed with protein, the next step is a reflux of protein into the bloodstream. The proteins can be resorbed by the vascular endothelium and excreted at the intima of the arteries. This in part explains the genesis of arteriosclerosis.
Fig. 5: Cytopempsis-pinocytosis
Normally, after eating, the nutrient substances are driven through the blood capillaries and the basement membrane into the connective tissue by the high diffusion pressure which is generated by the high level of nutrients in the blood - thus satisfying, for the time being, the cell's nutritional requirements.
Excess nutrients are stored in connective tissue depots: protein in collagen and mucopolysaccharides, glucose in the sugar part of mucopolysaccharides, fat in fat cells, water in mucopolysaccharide molecules. By this means, the tissue becomes thicker in various spots. As long as the basement membrane is healthy, all nutrients for cell supply and storage go through it. The overfed parts may get thicker, but they are still healthy. This can turn pathological with an unbalanced diet, especially an excess of animal protein, since the basement membrane eventually becomes overtaxed.
The basement membrane gets thicker if protein deposits become excessive, which causes its permeability to decline.
Protein molecules leave the bloodstream in 24 to 48 hours, wind up in the tissues and are returned to the blood via the lymphatic system. The most important transport protein is albumin, with a molecular size of about 70 A. It transports vitamins, enzymes, hormones and metals. The gamma globulins, with a molecular size of over 100 A, also travel this route.
Plasma protein circulation is a transport mechanism for vital substances to the cells and for metabolic products from the cells. This protein cycle takes place in part via the lymphatic system, since some of it cannot get into the venous limb due to size. Therefore, protein metabolism requires a functioning lymphatic system. If proteins stay in the connective tissue too long because the transport system is not working, then it alters its molecular structure, giving rise to a new pathological factor.
The volume of extracellular fluid depends on the total amount of osmotically active substances. The most important factor here is the acid-base balance, particularly the extracellular fluid's sodium content. Numerically, the sodium ion and the chlorine ion are the dominant osmotically active mineral substances.
Regulating the sodium ion concentration takes place via a number of mechanisms. The most important organ in this is probably the kidney, but always working in concert with other organs.
The lymphatic system comes to the rescue by carrying off substances in order to maintain (or reestablish) the optimal state. However, in many pathological situations, this may not be enough. The activity of the lymphatic system can carry off substances, thus maintaining capillary permeability - or improving it before damage can occur or before other regulatory mechanisms are forced to spring into action. [2, 10]
2 Anatomical, Histological and Pathological Fundamentals
2.1 The Vascular System
The blood's vascular system is made up of a venous and an arterial limb. The construction of this piping system varies depending on size and function.
The inner wall of all blood vessels is covered with an endothelial sheath. For the aorta and the large arteries, the next layer outward is the Elastica interna. In the middle, one finds a layer of smooth muscle cells. Outside of that is the Elastica externa, which, along with the Elastica interna, consists of elastic fibers and makes possible continuous blood flow by means of peristaltic action.
The vessels are connected to the surrounding connective tissue by the outermost layer, the Adventitia.
In the periphery, the arteries branch and rebranch down to arterioles. In the arterioles, the elastic tissue is less well developed; the smooth muscle, on the other hand, is relatively well developed. It is innervated both adrenergically as well as cholinergically. For the most part, this is responsible for the phenomenon of peripheral resistance. Many organs have, between the arterioles and the capillaries, what are called metarterioles, which do not possess an enclosed muscle layer. Branching on further, after the arterioles come the precapillaries and then the capillaries.
The inflow opening of the capillaries is surrounded by a smooth muscle called the capillary sphincter. When energy requirements are low, this muscle closes the capillaries, causing the blood to flow through an arteriovenous shunt (anastomosis) directly into the venous limb. The arterioles' vasoconstrictive fibers extend up to the sphincters, which, says Curri, are shaped like cushions.
See Fig. 6.
Capillary diameter in a relaxed state is 7 micrometers - which means that the erythrocytes have to be forced through, deforming them. These capillaries then flow into the venoles. The capillaries are also termed the terminal vessels. In some terminal vessel regions there are, as we have said, direct connections from metarterioles to venoles (capillary shunts).
Fig. 6: Vessel walls
These arteriovenous anastomoses have strong muscular walls and are richly innervated. Their function depends on the state of activity of the neighboring tissue. At rest, the capillaries are collapsed and the bloodstream flows through the anastomoses. The precapillary sphincter shuts off the capillaries until the arterial pressure exceeds the shutoff pressure. Capillary pressure amounts to 30 mm Hg at the arterial end and 15 mm Hg at the venous end.
The progressive narrowing of blood vessels from the aorta to the capillaries is - along with variations in vessel wall construction in the individual segments - responsible for peripheral resistance. The product of cardiac output and peripheral resistance gives the arterial blood pressure, which is normally about 120 to 80 mm Hg on the sphygmomanometer.
Because of their function, capillaries must, on the one hand, not leak, so that the blood flows smoothly; on the other hand, substances must be able to diffuse into the surrounding tissue. Capillary walls consist of a single layer of endothelial cells which are held together by a mortar substance (calcium proteinate). There are pores between the individual endothelial cells (30–70 A in diameter) through which the molecules can drift. The construction of the capillary walls varies depending on the containing organ: the basement membrane can be interrupted or continuous.
The basement membrane consists of densely interwoven reticulum fibrils. The space between the fibrils is filled with an amorphous ground substance. In many organs, this basement membrane consists of two sheets, between which one finds cells called pericytes, which are responsible for pinocytosis.