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Exam notes - excitable cells, renal, and endocrine

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Western University
Physiology 3120
Tom Stavraky

Physiology 3120 April Exam Notes Body Fluids and Excitable Cells Physiology is the study of function of the living organism, and encompasses both normal and pathological states. The body can be divided into the internal and the external environment. The external environment is made up of the parts of the body that are directly connected to the outside world (i.e. the respiratory system, the GI system, and urogenital tract). The internal environment is basically the extracellular fluid, including the blood and interstitial fluid; put another way, the cells are bathed in the internal environment. The intracellular fluid is part of neither internal nor external environment. Homeostasis is the act of maintaining relatively stable internal conditions. It can be controlled by both the nervous system (responsible for fast, minute-to-minute changes) and endocrine system (responsible for slower, long-term changes), and is often maintained by a negative feedback mechanism. In this mechanism, a set point is stored in the comparator (HYPOTHALAMUS) and sensors (TEMPERATURE SENSORS) sense the current value of some controlled variable (TEMPERATURE); if the current value varies from the set point, the comparator sends signals to effector organs (VASCULAR SMOOTH MUSCLE CELLS) that causes a change that brings the controlled variable back to the set point. It is this counteraction of change that gives the mechanism its negative feedback name. About 60% of any person is made up of water; this volume is referred to as total body water (TBW). Intracellular fluid accounts for about 67% of TBW, whereas the ECF fluid accounts for the remaining 33% (7% in plasma, 26% in interstitial fluid). Because of the selective permeability of the cell membrane, ion concentrations in the ICF and ECF differ. Sodium (Na) is more concentrated in the ECF; potassium (K) is more concentrated in the ICF; calcium (Ca) is more concentrated in the ECF; and chloride (Cl) is more concentrated in the ECF. These ionic distributions create a chemical force that wants to move the ions down their concentration gradients (e.g. Na in, K out). The cell membrane itself is made up primarily of phospholipids that are amphipathic (hydrophobic at one end, hydrophilic at the other). Due to the nonpolar inner layer, charged particles have difficulty passing through the membrane, and because of the small spaces between phospholipid molecules, large molecules have the same difficulty. Membrane also contains many membrane proteins that serve a variety of functions, including transport, cytoskeletal anchorage, catalysis, acting as receptors for ligands, and serving as antigens for cell recognition. Although the cell membrane is useful in maintaining the ion concentration gradients, substances still need to pass through the membrane into the cell. There are various transport mechanisms that perform these functions 1. Simple diffusion This is the slowest and least efficient mechanism because it relies on the random thermal motion of the molecules. The end result is a uniform concentration throughout the medium as molecules move down their concentration gradient. The reason this mechanism is so inefficient is that the time required increases proportionally with the square of the distance, so doubling the radius will increase the time required 4-fold. 2. Diffusion across cell membrane In order to diffuse through the cell membrane directly, substances must be nonpolar in order to pass through the hydrophobic interior; examples of substances that use this route are O , CO , fatty acids, and steroids. The 2 2 driving force of this form is the concentration gradient of the substance, and the rate is predicted by Ficks first law of diffusion. The equation is preceded by a negative sign because the substance moves from high to low concentration, and therefore graphically will have a negative slope. Diffusion rate (flux) INCREASES when: (1) concentration gradient increases, (2) temperature increases, (3) total diffusion area increases, (4) viscosity decreases, and (5) atomic radius decreases Polar molecules cross the membrane by traversing through specialized pores or channels (i.e. aquaporins, ion channels, etc.). Once again the driving force is the concentration gradient, but movement is affected by a number of factors: (1) size of the molecule, (2) charge on the molecule, (3) the size of the concentration gradient, (4) the size of the pressure gradient, and (5) hydration energy of the molecule because the hydration shell around ions must be stripped off before passing through and this can only be done by its specific channel/pore. Factors (1), (2) and (5) are filtering mechanisms in that they prevent certain molecules from passing, but they are not the same as the specificity mechanisms described below 3. Facilitated diffusion A form of carrier- mediated transport that is used to transport substances that cant easily cross the cell membrane directly down their concentration gradients. The carriers, when bound to the molecule of interest, undergo a conformational change to help the molecules cross the membrane. This form of transport (1) is specific, (2) shows saturability, and (3) shows competitive inhibition. 4. Active transport Another form of carrier-mediated transport, but differs from facilitated diffusion in that it requires energy (in the form of ATP) to move substances against their concentration gradients. It also shows (1) specificity, (2) saturability, and (3) competitive inhibition. An example of a primary active transport mechanism is the Na/K ATPase, which moves 3 Na into the cell and 2 K out of the cell for every ATP molecule it hydrolyzes. Initially, 3 Na bind to their intracellular binding sites; ATP is then hydrolyzed, and when the ADP is released, the Na are pumped out of the cell. Then, 2 K attach to their extracellular binding sites, and release of the Pifollowed by attachment of a new ATP molecule shuffles the K into the cell. This pump has a number of functions, such as (1) maintaining concentration gradients, (2) maintaining relatively high negativity inside the cell, and (3) prevents the cell from swelling by pumping more ion out than in. This pump can be inhibited by ouabain, digoxin/digitalis, or hypoxia. Secondary active transport occurs when one molecule moves down its concentration and the energy released is used to move another molecule against its concentration gradient. The two molecules can move in the same (symporter) or opposite (antiporter) directions, and many physiological systems use secondary active transport to absorb nutrients (i.e. Na/glucose symporter in the intestinal lumen) and primary active transport to move nutrients into the blood and maintain concentration gradients. 5. Osmosis is the movement of water down its concentration gradient Water will move to where the osmolarity is the highest. Osmolarity is defined as the number of osmotically active particles are present in a given volume of solvent (for example, 1 mole of CaCl produ2es 3 osmoles of osmotically active particles). Just as with movement of other particles, the rate of osmosis is affected by the permeability of the membrane (must be more permeable to water than to the solute[s]), the concentration gradient, and the pressure gradient. The osmotic pressure is the pressure required to counteract osmosis. Tonicity is the ability of a solution to cause osmosis across a semi-permeable membrane. The normal tonicity of bodily fluids is about 290-300 mOsmoles/kg water An isotonic solution has the same osmolarity as the intracellular fluid (ICF) and therefore does not cause osmosis; a hypotonic solution has a lower osmolarity than the ICF and therefore cause osmosis INTO the cell; and a hypertonic solution has a higher osmolarity than the ICF and therefore causes osmosis OUT OF the cell. F
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