Porth's Essentials of Pathophysiology, 4e

16

Cell and Tissue Function

U N I T 1

a phagosome . The process of pinocytosis, which means “cell drinking,” is important in the transport of pro- teins and strong solutions of electrolytes. Phagocytosis, which means “cell eating,” involves the engulfment and subsequent killing or degradation of microorganisms and other particulate matter. Certain cells, such as mac- rophages and neutrophils, are adept at engulfing and disposing of invading organisms, damaged cells, and unneeded extracellular constituents. Exocytosis is the mechanism for the secretion of intracellular substances into the extracellular spaces. It may be considered a reverse of endocytosis in that the membrane of the secretory granule fuses with the cell membrane and allows the contents of the granule to be released into the extracellular fluid. Exocytosis is impor- tant in removing cellular debris and releasing substances, such as hormones and cytokines, synthesized in the cell. Receptor-mediated endocytosis involves the binding of substances to a receptor on the cell surface. Many of these receptor proteins are concentrated in clathrin- coated pits , which are specific areas of the cell where the membrane is lined on its cytoplasmic side by a periph- eral protein called clathrin . The interaction between the proteins in the receptor–ligand complex causes the membrane to invaginate. The edges of the membrane around the clathrin-coated pit then fuse, and a por- tion of the membrane pinches off as an endocytic ves- icle. Almost immediately after it is formed, the vesicle loses its clathrin coat and becomes fused with an early endosome in a manner similar to that involved in non– receptor-mediated endocytosis. The uptake of choles- terol transported in the blood as low-density lipoprotein (LDL) relies on receptor-mediated removal associated with clathrin-coated pits. This pathway for cholesterol removal is disrupted in persons who inherit defective genes for encoding LDL receptors (see Chapter 18). In addition to clathrin-coated pits and vesicles, there are a number of othermechanisms bywhich cells can form endocytotic vesicles. One of these pathways involves the formation of small invaginations or “little cavities” in the cell membrane, called caveolae , that extend inward, indenting the cell membrane and the cytoplasm. These cavities may pinch off and form free vesicles within the cytoplasm. Caveolae are considered to be sites for uptake of material into the cell, for expulsion of material from the cell, and for addition or removal of cell mem- brane components. In smooth muscle, caveolae project into the cytoplasm and, analogous to the T tubules in striated muscle, play an important role in regulating intracellular calcium concentration and smooth muscle tone. In addition to transport, caveolae are involved in a number of other functions such as signal transduction and may be involved in the pathogenesis of a number of diseases, including muscular dystrophy. Generation of Membrane Potentials Living organisms have electrical properties in which current flow involves the movement of ions in water. Electrical potentials exist across the membranes of most

cells in the body. Because these potentials occur at the level of the cell membrane, they are called membrane potentials . In excitable tissues, such as nerve or muscle cells, changes in the membrane potential are necessary for generation and conduction of nerve impulses and muscle contraction. In other types of cells, such as glan- dular cells, changes in the membrane potential contrib- ute to hormone secretion and other functions. Electrical potentials describe the ability of separated electrical charges of opposite polarity (+ and −) to do work. In regard to cells, the oppositely charged particles are ions, and the barrier that separates them is the cell membrane. Electrical potentials are measured in volts (V) or units of electromotive force (EMF). Voltage is always measured with respect to two points in a system. For example, the voltage in a car battery (6 or 12 V) is the potential difference between the two battery ter- minals. In a cell it is the potential difference between the inside and outside of the cell membrane. Because the total amount of charge that can be separated by a biologic membrane is small, the potential differences are small and are therefore measured in millivolts (mV), or 1/1000 of a volt. There are two main factors that alter membrane potentials: the difference in the concentration of ions on the inside and outside of the membrane and the perme- ability of the membrane to these ions. Extracellular and intracellular fluids are electrolyte solutions containing approximately 150 to 160 mmol/L of positively charged ions and an equal concentration of negatively charged ions. The diffusion of these current-carrying ions is responsible for generating and conducting membrane potentials. A diffusion potential describes the voltage generated by ions that diffuse across the cell membrane. An equilibrium potential is one in which there is no net movement of a particular ion across a membrane because the diffusion potential and electrical forces gen- erated by the movement of the ion are exactly balanced. The magnitude of the equilibrium potential, also known as the Nernst potential , is determined by the ratio of the concentration of a specific ion on the two sides of the membrane. The greater the ratio, the greater the ten- dency for the ion to diffuse in one direction, and there- fore the greater the electrical forces required to prevent further diffusion. The Nernst equation (described in the figure on Understanding Membrane Potentials) can be used to calculate the equilibrium potential for any uni- valent ion at a given concentration difference, assum- ing that membrane is permeable to the ion. When using the equation, it is generally assumed that the electrical potential of the extracellular fluid outside the membrane remains at zero and the potential being calculated is the electrical potential inside the membrane. It is also assumed that the sign of the potential is negative (−) if a positively charged ion diffuses from the inside to the outside of the membrane and positive (+) if a positively charged ion diffuses from the outside to the inside of the membrane. The resting membrane potential represents the period of time when excitable cells, such as nerve fibers, are not transmitting signals. Because resting cell membranes are