Membrane Transport Figure [-1-4. Heart Muscle Cell Another example of secondary active transport, the countertransport(molecules move in the opposite direction)of Na* and Ca2+ in heart muscle, is shown in Figure I-1-4. In this case, as in the cotransport of sodium and glucose, transport is dependent on the ATP utilized by the na/k- ATPase pump. VESICULAR TRAFFIC AND THE PLASMA MEMBRANE cytosiN Endocytosis is the movement of macromolecules from outside the cell to the inside of the cell by the active invagination of the plasma membrane Categories Based on State(Solid or in Solution) of the Substance Taken Up Phagocytosis: The process by which solid bits of material, (e.g, bacteria, dead tissue) are engulfed by cells Fluid-phase endocytosis or pinocytosis: The uptake of molecules in solution Categories Based on Uptake Mechanisms Constitutive endocytosis: A noninduced process whereby vesicles are continuously fus- ing with the cell membrane Receptor-mediated endocytosis: The molecule being internalized(the ligand)binds to a receptor on the surface of the cell. These receptor-ligand complexes concentrate at lathrin-coated pits on the plasma membrane. The pit then pinches off, forming a vesicle. In some cases the receptors recycle back to the membrane. This process is more rapid and more specific than constitutive endocytosis edical 7
..... Membrane Transport Na+ K+ Ca2+ Na+ Figure 1-1-4.Heart Muscle Cell Another example of secondary active transport, the countertransport (molecules move in the opposite direction) ofNa+ and Ca2+in heart muscle, is shown in Figure 1-1-4.In this case,as in the cotransport of sodium and glucose,transport is dependent on the ATPutilized by the Na/KATPasepump. VESICULARTRAFFICANDTHEPLASMAMEMBRANE Endocytosis Endocytosis is the movement of macromolecules from outside the cell to the inside of the cell by the activeinvagination of the plasma membrane. Categories Based on State (Solid or in Solution) of the SubstanceTaken Up Phagocytosis: The process by which solid bits of material, (e.g., bacteria, dead tissue) are engulfed by cells. Fluid-phase endocytosis or pinocytosis: The uptake of molecules in solution. CategoriesBasedon UptakeMechanisms Constitutive endocytosis: A noninduced process whereby vesicles are continuously fusing with the cell membrane. Receptor-mediated endocytosis: The molecule being internalized (the ligand) binds to a receptor on the surface of the cell. These receptor-ligand complexes concentrate at clathrin-coated pits on the plasma membrane. The pit then pinches off, forming a vesicle.In some cases the receptors recycleback to the membrane. This process is more rapid and more specificthan constitutive endocytosis. \ KAPLA~. meulca I 7
USMLE Step 1: Physiology Exocytosis Exocytosis is the process by which macromolecules are packaged in secretory vesicles and then extruded from the cell. This process requires both calcium and energy Constitutive secretion: The vesicles are not coated with clathrin and are continuously fusing with the cell membrane. Regulated exocytosis: The vesicles are coated with clathrin, and a signal is required before the vesicle will fuse with the membrane, (e.g, the release of vesicular-bound water-soluble hormones Graphical Representation of Transport Processes One method of testing your understanding of physiologic process is by presenting a graph to interpret, Figure 1-1-5 and the accompanying questions test your understanding of membrane transport. The graph simply represents extracellular concentration versus rate of transport across the cell membrane Flux Into Extracellular Review Questions The following questions refer to Figure I-1-5 (answers with explanations on the next page) 1. Which curves could represent simple diffusion? If the surface area for diffusion increased what would happen to the slope of the diffusion curve? 2. Which curves could represent protein-mediated transport? Could you separate active transport versus facilitated transport curves? 3. Which curves demonstrate a TM? Which curve has the lowest TM, and which curve has the greatest TM? 4. If"C "represents the movement of glucose into skeletal muscle under control conditions. which curve would represent glucose transport after adding additional insulin? What does insulin do to the number of functioning transporters in the system?
/" USMLE Step 1: Physiology 8 meilical Exocytosis Exocytosis is the process by which macromolecules are packaged in secretory vesicles and then extruded from the cell. This process requires both calcium and energy. Constitutive secretion: The vesicles are not coated with clathrin and are continuously fusing with the cell membrane. Regulated exocytosis: The vesicles are coated with clathrin, and a signal is required before the vesicle will fuse with the membrane, (e.g., the release of vesicular-bound water-soluble hormones). GraphicalRepresentationof TransportProcesses One method of testing your understanding of physiologic process is by presenting a graph to interpret. Figure 1-1-5 and the accompanying questions test your understanding of membrane transport. The graph simply represents extracellular concentration versus rate of transport across the cell membrane. A Flux Into Cell D B C Extracellular Concentration Figure 1-1-5 ReviewQuestions The following questions refer to Figure 1-1-5: (answers with explanations on the next page) 1. Which curves could represent simple diffusion? If the surface area for dfffusion increased, what would happen to the slope of the diffusion curve? Which curves could represent protein-mediated transport? Could you separate active transport versus facilitated transport curves? 2. 3. Which curves demonstrate aT M?Which curve has the lowest TM' and which curve has the greatest TM? If "c" represents the movement of glucose into skeletal muscle under control conditions, which curve would represent glucose transport after adding additional insulin? What does insulin do to the number of functioning transporters in the system? 4
Membrane Transport nswers Answer: A. It is a straight-line relationship: the greater the concentration gradient, the greater the rate of diffusion. If the surface area for diffusion increased, the slope would increase. This means that at a given concentration gradient the rate of diffusion would be would represent facilitated transport versus active transport. Facilitated transport is always down a concentration gradient, whereas active transport can be against a concen- tration gradient. This information is not presented in the graph 3. Answers: B, C, D. Again, this is a characteristic of all protein-mediated transport. TM is the rate of transport of the plateau(measured on the y axis). D has the lowest TM and B the greatest 4. Answer: B. Insulin simply places more transporters in the membrane system, which would increase T Chapter Summary A cell membrane is a lipid bilayer composed mainly of phospholipid Dynamic propenies are due to the protein component, which includes pumps, channels, receptors, and carriers Simple diffusion and facilitated transport are both passive processes(not energy-dependent) driven by concentration gradients. The rate of protein-mediated transport will increase with increased substrate delivery until the carriers are saturated. The maximum rate(camer saturation)is called TM, and this rate is directly proportional to the number of functioning carriers present in the system Secondary active transport is driven by the sodium gradient across the cell membrane, which is maintained by the Na/K-ATPase pump Endocytosis and exocytosis represent acive uptake and extrusion of macromolecules via vesicular medical 9
, MembraneTransport Answers 1. Answer: A. It is a straight-line relationship: the greater the concentration gradient, the greater the rate of diffusion. If the surface area for diffusion increased, the slope would increase. This means that at a given concentration gradient the rate of diffusion would be greater. 2. Answers: B, C, D. These three curves demonstrate saturation kinetics (plateau), which is a characteristic of all protein-mediated transport. You cannot determine which curves would represent facilitated transport versus active transport. Facilitated transport is always down a concentration gradient, whereas active transport can be against a concentration gradient. This information is not presented in the graph. 3. Answers: B, C, D. Again, this is a characteristic of all protein-mediated transport. TMis the rate of transport of the plateau (measured on the y axis). D has the lowest TMand B the greatest. 4. Answer: B. Insulin simply places more transporters in the membrane system, which would increase TM' ChapterSummary isalipidbilayercomposedmainlyof phospholipid.Dynamicpropertiesaredueto the proteincomponent,whichincludespumps,channels,receptors,andcarriers. Simplediffusionandfacilitatedtransportarebothpassiveprocesses(notenergy-dependent)drivenby concentrationgradients. Therateofprotein-mediatedtransportwillincreasewithincreasedsubstratedeliveryuntilthecarriers aresaturated.Themaximumrate(carriersaturation)iscalledTM'andthisrateisdirectlyproportionalto thenumberoffunctioningcarrierspresentinthesystem. Secondaryactivetransportisdrivenbythesodiumgradientacrossthecellmembrane,whichis maintainedbytheNajK-ATPasepump. Endocytosisandexocytosisrepresentactiveuptakeandextrusionofmacromoleculesviavesicular transport. mettical 9
Body compartments DISTRIBUTION OF FLUIDS WITHIN THE BODY What the USMLE Requires you to Know Total Body Water what determines the Intracellular Fluid (ICF): approximately 2/3 of total of body water effective osmotic pressure Extracellular fluid (ECF): approximately 1/3 of total body water between two compa Interstitial fluid (ISF): approximately 2/3 of the extracellular fluid The changes in body Vascular fluid (VF): approximately 1/3 of the extracellular fluid (plasma plus red blood molarity and intracellular cells). A normal vascular volume is close to 5 L(blood volume) and extracellular volumes in dinically relevant situations ICF ECF measuring the volume of a I VAS The solid-line division represents the cell membrane, and the dashed line capillary membranes Flgure 1-2-1 Intracellular Fluid (ICF)versus Extracellular Fluid (ECF) These two compartments are separated by cell membranes which generally have the following important characteristics In a steady state, intracellular and extracellular osmolarity will be the same. Normally, this is cl Impermeable to Sodium( Chloride) The difference in the concentration of impermeable partides determines the osmotic move- ment of water across membranes. The concentration of these particles is often referred to as the
BodyCompartments DISTRIBUTIONOFFLUIDSWITHIN THEBODY TotalBodyWater Intracellular fluid (ICF): approximately 2/3 of total of body water Extracellular fluid (ECF): approximately 1/3 of total body water Interstitial fluid (ISF): approximately 2/3 of the extracellular fluid Vascularfluid (VF): approximately 1/3 of the extracellular fluid (plasma plus red blood cells).A normal vascular volume is closeto 5 L (blood volume). rCF ECF ISF I I I I I I I I VAS I I I I I I The solid-line division represents the cell membrane, and the dashed line capillary membranes. Figure 1-2-1 IntracellularFluid(lCF)versusExtracellularFluid(ECF) These two compartments are separated by cell membranes which generally have the following important characteristics: FreelyPermeableto Water In a steadystate,intracellularand extracellularosmolaritywillbe the same.Normally,this is closeto 300mOsm. Impermeableto Sodium(Chloride) The difference in the concentration of impermeable particles determines the osmotic movement of water across membranes. The concentration of these particles is often referred to as the What the USMLE !!,~~!~ to KO!! .Whatdeterminesthe effectiveosmoticpressure betweentwocompartments .Thechangesinbody osmolarityandintracellular andextracellularvolumesin clinicallyrelevantsituations .Theprinciplesinvolvedin measuringthevolumeofa bodycompartment iileilical 11