1.14 Passive Transport An intravenous (IV) drip is a common sight in a hospital's intensive care unit (ICU) (Figure 1). This piece of equipment allows liquids to flow directly into a patient's veins. In most cases, the liquids are aqueous solutions containing a variety of different solutes. Common solutions used in IV drips include aqueous sodium chloride, NaCl SUBSCRIPT (aq), and aqueous glucose, C SUBSCRIPT 6 H SUBSCRIPT 12 O SUBSCRIPT 6(aq). An aqueous solution of sodium chloride is administered when a patient's blood and other body fluids (extracellular fluids) have low concentrations of water and minerals. Minerals include the positive and negative ions of common salts such as sodium ions, Na SUPERSCRIPT + SUBSCRIPT (aq), potassium ions, K SUPERSCRIPT + SUBSCRIPT (aq), calcium ions, Ca SUPERSCRIPT 2+ SUBSCRIPT (aq), chloride ions, Cl SUPERSCRIPT - SUBSCRIPT (aq), and phosphate ions, PO SUBSCRIPT 4 SUPERSCRIPT 3- SUBSCRIPT (aq). Ions dissoved in aqueous solutions are called electrolytes. Careful inspection of labels on typical IV solutions reveals that the concentration of solute in the solution is always stated (Figure 2). Doctors and nurses are careful to administer a solution with a suitable solute concentration to their patients. Giving an IV solution with the wrong concentration could be fatal. Why is it important for patients to receive a solution of a particular concentration in an IV drip? The reasons have much to do with the structure of cell membranes and how substances move across these membranes. Simple Diffusion Cell membranes are selectively permeable--only certain substances are able to pass through them. As mentioned in section 1.2, cell membranes are largely composed of a phospholipid bilayer and proteins. Many small, uncharged molecules, such as water, oxygen, and carbon dioxide, pass through the cell membrane freely (Figure 3). These substances either go through the phospholipid bilayer directly or through channels formed by proteins in the membrane. Since the cell membrane has a hydrophobic middle section, small lipid molecules such as fatty acids are also able to pass through. PRINT PAGE 60 However, ions, small charged molecules, and large molecules such as amino acids, carbohydrates, nucleic acids, and large lipids (triglycerides) cannot pass through easily (Figure 3, on the previous page). Substances that can pass through the membrane do so by a process called simple diffusion. Simple diffusion is the movement of particles from an area where they are more highly concentrated to an area where they are less highly concentrated (Figure 4). A difference in concentration between two areas is called a concentration gradient, and diffusion always occurs down a concentration gradient (from high concentration to low concentration). Diffusion is a natural process that occurs because particles are in constant random motion and have a tendency to spread throughout a given volume. Simple diffusion does not use any of a cell's energy, and ends when the concentration of particles becomes equal everywhere within the given volume. However, this does not mean that the particles stop moving. In fact, particles continue moving randomly in all directions all the time. During diffusion, molecules move more in one direction than any other. When diffusion ends, we say that a state of dynamic equilibrium has been reached. Dynamic equilibrium is a state of balance, where particles move at equal rates in all directions. When diffusion occurs through a cell membrane, dynamic equilibrium is reached when particles move through the membrane in both directions at equal rates, and the concentration of particles remains the same on both sides of the membrane (Figure 5). PRINT PAGE 61 The rate (speed) of diffusion depends on temperature and the concentration of solute molecules in solution. Diffusion occurs faster at higher temperatures because molecules move faster. Faster-moving molecules spread out faster and reach dynamic equilibrium more quickly. Dynamic equilibrium will also be reached more quickly if there are a greater number of solute molecules in solution. Facilitated Diffusion Glucose, sodium ions, and chloride ions are three chemicals most cells need to survive. These substances must be able to get across the cell membrane in an efficient manner. However, large polar molecules such as glucose and large ions such as sodium and chloride cannot go through a membrane by simple diffusion because they cannot easily pass through the hydrophobic middle section of the phospholipid bilayer. To compensate, membranes have protein molecules that help some substances through. In general, there are three types of membrane proteins (Figure 6). Some membrane proteins go part way through the phospholipid bilayer, some are attached to the outside surface, and others go all the way through. Those that span the bilayer are called transmembrane proteins. Some transmembrane proteins act as carrier proteins that assist certain substances through a membrane. This method of transporting materials across a membrane is called facilitated diffusion, or assisted diffusion. As its name implies, facilitated diffusion is a form of diffusion. This means that particles move down a concentration gradient until dynamic equilibrium is reached. The key difference between simple diffusion and facilitated diffusion is that, in facilitated diffusion, the diffusing particles are assisted through the membrane by transmembrane carrier proteins, whereas in simple diffusion they pass directly through the membrane's phospholipid bilayer or through protein channels. Typically, a given carrier protein transports only one type of substance, or a small group of chemically related substances. An example of carrier protein facilitated diffusion is the movement of glucose into cells of the liver (Figure 7, on the next page). PRINT PAGE 62 Osmosis Water molecules move freely through cell membranes. Under normal conditions, large quantities of water molecules move into and out of a cell by simple diffusion. The cell remains the same size because equal amounts of water go into and out of the cell. There are, however, many cases in which a net amount of water flows into or out of a cell. This means that more water may enter the cell than leaves the cell, so that the cell gains water, or more water may leave the cell than enters it, so that the cell loses water. In such situations, water still moves through the cell membrane by simple diffusion, but the process is important enough to warrant a special name--osmosis. Osmosis is the net movement of water across a selectively permeable membrane from the side where water is more concentrated to the side where it is less concentrated. Note that solutions have a high concentration of water when they have a low concentration of solute, and vice versa. Osmosis occurs because more water molecules strike the membrane on the side with a higher concentration of water molecules (i.e., a lower solute concentration) than on the side with a lower concentration of water molecules (i.e., a higher solute concentration). More strikes result in more water molecules passing through the membrane and a net diffusion of water from one side to the other. The key point to remember about osmosis is that water moves through a membrane from the side with a lower solute concentration to the side with a higher solute concentration. Dynamic equilibrium is reached when sufficient water has moved to equalize the solute concentrations on both sides of the membrane, and at that point, net movement of water (osmosis) ceases (Figure 8). PRINT PAGE 63 Osmosis occurs whenever there is a difference in solute concentration across a selectively permeable membrane. A number of special terms are commonly used to describe differences in solute concentration (Figure 9). Isotonic solutions are solutions that have equal solute concentrations. When a selectively permeable membrane separates isotonic solutions, osmosis does not occur. A hypertonic solution is one with a higher concentration of solutes than another solution. The solution with the lower concentration of solutes is called a hypotonic solution. We may now understand why it is important for patients to receive a solution of a particular concentration in an IV drip. Blood serum (the liquid part of blood) is normally isotonic with respect to red blood cell cytoplasm. Under normal conditions, osmosis does not occur into or out of red blood cells. The cells maintain their normal size and shape (Figure 10(a)). When a patient receives an IV drip, the IV solution mixes directly with blood serum. If the solution contains a lower solute concentration than blood serum (i.e., a hypotonic solution), it may dilute the blood serum until it is hypotonic to blood cell cytoplasm. If so, osmosis will occur into the red blood cells, causing the cells to swell, and maybe burst (Figure 10(b)). This condition is called hemolysis, and may be fatal because the blood cells will be unable to transport oxygen to body tissues efficiently. If a patient receives an IV solution that is hypertonic to blood serum, it may concentrate blood serum until it is hypertonic to blood cell cytoplasm. Osmosis will occur out of the blood cells. The cells will lose water and become small and scallop-shaped (Figure 10(c)). Scallop-shaped cells have a tendency to stick to one another and clog small veins and arteries, preventing oxygen from reaching body tissues. This condition, called crenation, may also be fatal. PRINT PAGE 64 Any solution injected directly into veins and arteries must be isotonic with blood serum. Typical isotonic IV solutions include 5% glucose (also called 5% dextrose, or D5W) and 0.9% sodium chloride (also called isotonic saline). PRINT PAGE 65 BEGIN PRODUCER'S NOTE: Investigation is not reproduced. END PRODUCER'S NOTE. PRINT PAGE 66 BEGIN PRODUCER'S NOTE: Investigation is not reproduced. END PRODUCER'S NOTE. PRINT PAGE 67 1.16 Active Transport and Bulk Transport Simple diffusion (including osmosis) and facilitated diffusion are methods used by cells to move substances through membranes from areas of high concentration to areas of low concentration until concentrations are equal. These methods for moving materials are useful in many situations, but may be wasteful in others. The primary purpose of eating is to absorb nutrient molecules into the cells of your body. Nutrients include amino acids from proteins, fatty acids from fats, nucleotides from nucleic acids, and glucose from complex carbohydrates such as starch. Glucose is a particularly important nutrient because it is used as a source of energy by all the cells of your body. To ensure that the body absorbs the maximum amount of nutrients from food, energy may be used to "pump" nutrients across cell membranes. A compound called adenosine triphosphate (ATP) provides the energy needed in this process, and in many of the other energy-requiring processes of living cells. Energy, Cells, and ATP Living organisms need a continuous supply of energy to power the energy-requiring processes of life. Movement, reproduction, protein synthesis, and certain forms of transport across cell membranes all require energy. This energy is provided by the breakdown of ATP. The molecular structure of ATP is similar to that of the DNA nucleotide containing adenine, except that ATP contains three linked phosphate groups instead of just one (Figure 1). When ATP reacts with certain compounds in a cell, the reactions release energy that the cell can use to power energy-requiring activities (Figure 2). PRINT PAGE 68 Active Transport After a meal, partially digested food travels from the stomach into the small intestine, where most of the nutrient molecules are absorbed into cells (Figure 3). As the nutrients move through the small intestine, they must be absorbed efficiently to avoid being excreted with waste products that move through the digestive system. If glucose were absorbed into intestinal cells by simple diffusion or facilitated diffusion, only about half of the molecules would be absorbed, since diffusion ends when solute concentrations are equal on both sides of the cell membrane. To maximize the absorption of such an important nutrient, cells of the small intestine may "pump" glucose through their cell membranes against a concentration gradient. This means that glucose continues to enter intestinal cells even when the concentration inside the cytoplasm is greater than the concentration outside the cytoplasm (in the intestinal space). In order to accomplish this, the cells have special protein carriers that use chemical energy from ATP to transport substances such as glucose through their cell membranes. This process is called active transport (Figure 4). It is important PRINT PAGE 69 to note that simple diffusion and facilitated diffusion (unlike active transport) are processes that do not require a source of cellular energy (ATP). Various types of active-transport "pumps" are found in the membranes of different cells. Potassium ions and sodium ions are moved into and out of cells by a pump known as the sodiumpotassium pump (Figure 5). Without this pump, your nerve cells and muscle cells could not function properly. Other substances, such as vitamins, amino acids, and hydrogen ions, are also pumped across membranes. All of these pumps require cellular energy (ATP) to operate. Bulk Transport Diffusion and active transport are responsible for moving large amounts of material through cell membranes. However, in both cases, the substances move through the membranes as dissolved particles (atoms, ions, or molecules). Sometimes cells need to move large quantities of materials (bulk) into or out of their cytoplasm all at once. A process called bulk transport may accomplish this. As in active transport, all bulk-transport mechanisms use energy in the form of ATP. There are two forms of bulk transport, endocytosis and exocytosis. Endocytosis Endocytosis is the form of bulk transport used to bring large amounts of material into the cell from the extracellular fluid. There are two forms of endocytosis, phagocytosis and pinocytosis. Phagocytosis (cell eating) is the bulk transport of solids into the cell, and pinocytosis (cell drinking) is the bulk transport of (liquid) extracellular fluid into the cell. Phagocytosis Phagocytosis begins when a solid particle comes in contact with the plasma membrane of a cell (Figure 6, on the next page). The cell membrane sends out fingerlike projections called pseudopods that surround and eventually enclose the particle in a vesicle that is within the cell's cytoplasm. Such a vesicle is called a phagocytotic vesicle. Lysosomes containing digestive enzymes may fuse with the phagocytotic vesicle to digest the particles it contains. Nutrients formed by this digestion process move through the vesicle's membrane into the cell's cytoplasm. White blood cells called macrophages frequently engulf invading harmful bacteria by phagocytosis, removing them from the bloodstream and other body tissues (Figure 7, on the next page). PRINT PAGE 70 Pinocytosis Pinocytosis occurs when a cell's plasma membrane engulfs a drop of extracellular fluid in a process similar to phagocytosis (Figure 8). This results in the formation of a pinocytotic vesicle. Cells bring cholesterol molecules into their cytoplasm by a special form of pinocytosis called receptor-mediated pinocytosis. In this process, cholesterol molecules in the extracellular fluid attach to receptor molecules on the external surface of the cell membrane. A pinocytotic vesicle then forms that brings the cholesterol molecules into the cell. Exocytosis In exocytosis, cells move large amounts of material out of their cytoplasm by a process that is essentially the reverse of endocytosis. In some cases, cells produce substances, such as hormones or enzymes, that must be exported out of the cytoplasm. In these cases, the material is enclosed in a membrane sac called a secretory vesicle (Figure 9). The secretory vesicle fuses with the cell membrane and spills its contents into the extracellular fluid. In some cases, proteins produced in the rough endoplasmic reticulum are packaged into secretory vesicles by the Golgi apparatus and are subsequently transported out of the cell by exocytosis. QUESTIONS: 1. List 4 areas where a solute would move from an area with lots of it to an area with little solute inside your body. HINT: These things will NOT pass through a cell membrane. 2. List three things that your cells need that are moved by facilitated diffusion. HINTS: A. Main sugar for cell = B. Main charged atom for nerves to work = C. Main charged atom for nerves to work = HINT#2: B and C are in table salt. 3. List 4 areas where water would move from an area with lots of water to an area with little water inside your body. 4. List 3 items that are moved across a cell membrane using active transport. HINTS: A. People take supplements every morning that contain = B. Break down of proteins into = C.