(USMLE topics, cardiology) Mechanisms of capillary exchange: diffusion, transcytosis, filtration and reabsorption; cause of edema.
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The major purpose of the circulatory system is to bring oxygen and nutrients to body tissues and remove wastes. This exchange happens in the smallest blood vessels called the capillaries. The walls of capillaries consist of a single layer of endothelial cells. Substances move between the blood and surrounding tissue in several ways:
- Diffusion through the plasma membranes of endothelial cells: the hydrophobic nature of the cell membrane makes it intrinsically permeable to small lipid-soluble molecules and small gases. Oxygen moves down its concentration gradient, from the blood to the surrounding tissue, while carbon dioxide diffuses in the reverse direction. Glucose and other small water-soluble molecules move, in part, by facilitated diffusion: they use special channels, called transporters, to cross the cell membrane. Water moves by osmosis.
- Transcellular vesicle transport, or transcytosis: some proteins and hormones are packaged into lipid vesicles and transported through endothelial cells by endocytosis and exocytosis.
- In most tissues, however, the bulk exchange of fluids and solutes is through the gaps between endothelial cells, called intercellular clefts; and, in some tissues, through the pores of so-called fenestrated capillaries. Blood plasma containing nutrients moves out of capillaries at the arterial end of capillary beds, in a process called filtration, while tissue fluid containing wastes reabsorbs back in at the venous end. This movement, called bulk flow, is driven by the balance between two forces:
- Hydrostatic force, generated by the difference in hydrostatic pressures inside and outside the capillaries. Hydrostatic pressure is defined as the pressure of fluids in a closed space. Inside capillaries, this is the same as capillary blood pressure. As tissues generally contain much less fluid than blood, hydrostatic pressure from inside capillaries is considerably higher than that from outside. Thus, hydrostatic force drives fluids, and blood solutes, out of capillaries.
- Hydrostatic force is opposed by osmotic force. Osmotic force, also called oncotic pressure, is generated mainly by the difference in protein concentrations between the blood and interstitial tissue. The blood has a much higher protein content, due to albumin, and this draws water into blood vessels.
Because the arterial end of a capillary bed is relatively closer to the heart than the venous end, capillary blood pressure and, by extension, hydrostatic pressure, is higher at the arterial end. With osmotic pressure remaining the same throughout, the balance shifts from net outward flow at the arterial end to net inward flow at the venous end. Note that the net outward filtration pressure is greater than the net inward reabsorption pressure. This means more fluid is filtered out than reabsorbed back in. In fact, about 15% of the fluid is left in the tissues after capillary exchange. This fluid is picked up by the lymphatic system and returned to the circulation at a later point.
Edema refers to abnormal accumulation of excess fluid in a tissue. It manifests as external swelling or enlarged internal organs. There are 3 principal groups of causes:
- Increased filtration, either from increased blood pressure or increased capillary permeability,
- Decreased reabsorption due to reduced blood albumin concentrations,
- and obstruction of lymphatic drainage.
Excess fluid hinders the exchange of nutrient/waste and gases and may lead to tissue necrosis. Severe edema may also be accompanied by critically reduced blood volume which may result in circulatory shock.