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The metabolism of organs and cells depends on an intact circulation for the continuous delivery of oxygen, nutrients, hormones, electrolytes, and water, and for the removal of metabolic waste and carbon dioxide. Delivery and elimination at the cellular level are controlled by exchanges among the intra-vascular space, interstitial space, cellular space, and lymphatic space. The intra-vascular space is the sum of the volumes of the lumina of capillaries, veins, and arteries. The tightness of the capillary barrier varies from organ to organ ; the brain has a very tight barrier, called the "blood-brain barrier", while the liver has permeable sinuses with large gaps between the sinusoidal lining cells. The interstitial space between the blood capillaries and the membranes of parenchymal and connective tissue cells is filled by collagen fibers and interstitial substances, including glycosaminoglycans. This interstitial gel prevents fluid from moving freely but does not limit their filtration and reabsorption along the capillaries. Moreover, it does not significantly interfere with the movement of the molecules and metabolites. The pleural cavity, the pericardium and the peritoneal cavity are extensions of the interstitial space. The cellular space is the sum of the spaces within the confines of the plasma membranes of all cells. The plasma membrane controls access to the cellular space by the expenditure of energy. The lymphatic space is surrounded by the lymphatic endothelial cells. The driving force for lymph is the difference in pressure between the interstitial space and the thoracic duct system. Increased production of interstitial fluid increases interstitial pressure and leads to an elevated lymphatic flow. Interstitial fluid production may increase if capillary permeability increases or if hydrostatic pressure in capillaries increases. It has been proposed that the large lymphatics produce a slightly negative pressure, owing to contractile elements in their wall. The average lymph flow is 2 to 4 liters/ 24 hr, or 2 ml/min. Diffusion, Filtration, and Transport: The movement of solids, fluids, and gases across the barriers between compartments occurs by diffusion, filtration, and vesicular transport. The barrier between all compartments is modified by cells and cell membranes. In diffusing, lipid-soluble substances such as gases can utilize the entire endothelial capillary cell surface - a total of 6,000 square meters. This diffusion occurs at a rate of 55,000 ml/min in both directions. Oxygen, carbon dioxide, glucose and other nutrients are exchanged in this way. The movement of fluid between compartments is called filtration and occurs passively along pressure gradients - the hydrostatic pressure gradient and the osmotic pressure gradient. The hydrostatic pressure at the site of the arteriolar capillary is 32 mm Hg, while at mid-capillary it is 20mm Hg. This hydrostatic pressure difference, together with a 5 mm Hg interstitial osmotic pressure, represents an outward force in the intravascular space. The outward force is balanced by an interstitial hydrostatic pressure of 3 mm Hg plus an osmotic pressure of 26 mm in the intravascular space. The net pressure difference causes outward fluid filtration across the capillaries at a rate of 14 ml/min at the arterial end. Osmotic reabsorption produces an inward movement of 12 ml/min at the venous segment. Lymphatic flow drains the remaining 2 mm/min, so that in equilibrium there is no net fluid gain or loss. The major function of filtration is the regulation of plasma volume. The anatomic site of filtration still has not been precisely identified ; it is thought to be between endothelial cells, an area amounting to approximately 0.2% of the entire potential exchange area. The filtration fluid contains 0.2% protein, which, since it can not normally reenter the circulation, must be cleared by the lymphatics. The protein content of lymphatics varies with the organ (lymph from the extremities, for example, contains 1% protein, while that from the liver contains 6%). The Heart : [ Visit: Cardiac Path Online ] The heart is a two-chambered pump, with the two vascular circuits placed in series. The amount of blood pumped by the right ventricle must, over time, equal the amount of blood pumped by the left ventricle. The hemodynamically important parameters are cardiac output, perfusion pressure, and resistance. The function of the heart determines the cardiac output and perfusion pressure. Cardiac output is the volume of blood pumped by each ventricle per minute, and represents the blood flow in the pulmonary and systemic circulations. Perfusion pressure (also called "driving pressure") is the difference in the dynamic pressure between two points along a tube or vessel. Blood flow to any segment of the circulation is ultimately dependent on the arterial driving pressure. However, each organ can autoregulate flow and thereby determine the amount of blood that it receives from the circulation. The sum of the factors that determine regional flow in each organ determines the total vascular resistance. The sum of all regional flows equal the venous return, which in turn determines the cardiac output. The Aorta and Arteries: The aorta and major arteries are "conducting vessels" whose major functions are the transport of blood to the organs and the conversion of pulsatile flow into sustained regular flow. The latter function derives from the elastic properties of the aorta and the resistance produced by the arteriolar sphincters. The Microcirculation: The velocity of the blood in the microcirculation is 1 mm/sec. The average length of a capillary is 1 mm. Blood from an arteriole enters the capillaries, which freely anastomose with each other either directly or through metarterioles. Entry into the capillary system is guarded by precapillary sphincters, except in the cases of thoroughfare channels that bypass capillaries and are always open. Since not all capillaries are open at all times, blood flow can be increased by recruiting capillaries. The sum of the flow through the capillary bed, the thoroughfare channels, and the arteriovenous anatomoses determines the regional blood flow. In the heart, blood flow is adjusted on second-to-second basis. Proposed as factors that mediate and link metabolic vasodilatation to cellular metabolism are adenosine, other nucleotides, certain prostaglandins, carbon dioxide, and pH.
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