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1. Importance of Homeostasis1). It can maintain the composition of the body in fairly strict limits. ( ion concentrations, pH, blood gasses, T etc).2). It results in normal functions. 2. How is the homeostasis achieved ? This is done by several regulation mechanisms, particularly the feedback control. 3. 3 patterns of regulation: Nervous Regulation (神经调节) Hormonal Regulation (体液调节) Autoregulation (自身调节)4. Nervous Regulation Characteristics: It responses fast. It acts exactly. Duration is short.5. Hormonal Regulation Characteristics : It responses slowly. It acts extensively. It lasts for long time.6. Auto-regulation Characteristics: Amplitude of its effect is smaller than other two types. Extension of its effect is smaller than other two types.Role: only a supplement to the actionsof other two types of regulations.7. Negative feedback Significance: Reverse effect of original stimulus. Prevent small changes from becoming too large. Help maintain homeostasis. This is the most common and important control mechanism in the body.8. Positive feedback Significance:amplify changes or response and enhance or reinforce action of original stimulus so as to promote an activity to finish. sometime useful ,But sometime it is known as vicious cycle (恶性循环)because it can lead to instability or even death ! 9. Interaction between two types of feedbackNormally the negative feedback can overcome the positive feedback, thus a vicious circle fails to develop. 10. Feed-Forward Control SignificanceIt makes human body to foresee and adapt the environment promptly and exactly. an adaptive control 11 . Summary of Control of Body Function Homeostasis is kept by feedback control. Negative feedback minimizes the changes, leading to stability. Positive feedback does not favor stability. But,it can promote activity, useful. Feed-forward makes human body to foresee and adapt the environment promptly. Dysfunction of homeostasis will lead to sickness or death.12. Types of transport via membrane 1)Simple diffusion ( 单纯扩散 ) 2)Transport mediated by membrane proteins Facilitated diffusion (易化扩散) Active transport (主动转运) Endocytosis and exocytosis (入胞、出胞)13. Lipid Bilayer Characteristics: It has fluidity Proteins flow literally in it. It has selective permeability. Functions:stand(支架)barrier(屏障)participation in signal transduction (PIP2)14. Membrane Proteins Characteristics : It is globular in shape. It is floating in bilayer. It combines with lipid in two forms. 15. Membrane Proteins Forms and Functions: 1) Integral protein(整合蛋白) channel 通道carrier 载体pump 离子泵 transporter 转运体 controller (G-p) 2) Peripheral protein(表面蛋白)enzymes 酶 controllers16. Membrane Carbohydrates Glycoprotein (糖蛋白) Glycolipid (糖脂) Functions chargednegatively.(荷负电) function as receptor or antigen.(受体,抗原)1) Negatively charged, let the cell to repel negative objects2) Attach cells one to another3) Acts as receptor substance for binding hormone such as insulin4) Participate in immune reaction as antigen17. Major function of the cell membranen Act as a barriern Receive informationn Import and export n Move and expandIt acts as a selective barrier to transport substances.18. Simple Diffusion Mechanism * a physical process * driving force: Potential energy (势能) of molecules themselves. does not need ATP! 19. Factors effecting simple diffusion The magnitude of concentration gradient. Driving force of diffusion. Permeability of the membrane. Lipid solubility. Molecular weight Charged Temperature. Higher temperature, faster diffusion rate. Surface area of the membrane. Microvilli increase surface area.20. Facilitated Diffusion Mechanism 1. by channel protein 2. by carrier protein Types A. Facilitated diffusion via carrier B. Facilitated diffusion via channel Facilitated Diffusion via Carrier Definition diffusion carried out by carrier protein. Substances glucose, amino acid. Mechanism a “ferry ” or “shuttling ” process. Characteristics Down concentration gradient Chemical specificity Saturation Competitive inhibition Facilitated Diffusion via Channel Substances ions: Na+, K+, Ca2+, Cl- Definition diffusion carried out by channel protein Channel, also called ion channel or channel proteins, It is one of the integral proteins with aqueous pore , through which ions can flow in or out . gate-aqueous pathway or aqueous pore Characteristics of the channel 1) Ionic selectivity: ion channel are often selectively permeable to certain substances Na+ channel, K+ channel, Ca2+ channel, Cl- channel 2) Gating channel: many of the channels can be opened or closed by gatesVoltage gated channel The molecular conformation of the gate responds to the electrical potential across the cell membrane, this type of channel is called voltage gated (or dependent) channel.Chemically gated channel Some protein channel gates are opened by the binding of another molecule with the protein;this causes a conformational change in the protein molecule that opens or closes the gate.This type of channel is called chemically-gated (or dependent) channelMechanically gated channel Some protein channel gates may be opened by the mechanical deformation of the cell membrane. This type of channel is called mechanically-gated channel. Organ of Corti: hair cellsNo gated channel 3) Functional states change: Close Resting, Non-conducting conformation(s). Gate will open when stimulated. Open or activation Activation, conducting conformation. Gate is open. Ion flow in or out. InactivationInactivation, Another Non-conducting Conformation. Gate still closed even stimulated. 4) Time dependence21. the Na+/K+ ATPase Na+ pump Characteristic of -subunit Spans the cell membrane , 3 receptors for binding Na+ inside, 2 receptors for binding K+ outside. 1 site for binding ATP inside, ATP enzyme that can converts ATP to ADP and PiCharacteristics of the Transport by Na+ pump1) Directional transport2) Coupling process3) ATP is directly required4) Electrogenic processImportance of the Na+-K+ Pump Maintain high intracellular K+ concentration gradients across the membrane. Develop and Maintain Na+ and K+ concentration gradients across the membrane Control cell volume and phase Maintain normal pH inside cell Electrogenic action influences membrane potential Provides energy for secondary active transport22. Summary of Active Transport 1). It occurs uphill against the chemical gradient by expending ATP. 2). Two forms: primary and secondary active transport. 3). Primary active transport uses ATP directly. 4). Secondary active transport uses ATP indirectly 5). It can create and maintain chemical gradient.23. Transport of ions and small moleculesPassiveTransport : Simple diffusion Facilitated diffusion Down chemical gradient Decrease ionic gradient ATP is not needed Active Transport: Primary active transport Secondary active transportAgainst chemical gradient ,Create & maintain gradient ,Expend energy(ATP)24. Resting Potential Property 1 Stable direct current2 Negative inside, positive outside. 3 Values differ in cells neuron: - 70- 90 mv skeletal muscle: -90 mv myocardium:- 40- 90 mv 25. Ionic Mechanisms of RP1) Two basic conditions for RP Na+ and Cl- are more concentrated outside the cell K+ and organic anions (organic proteins) are more concentrated inside.2) different membrane permeability for ions3) Driving force for ion transmembrane diffusion Electrochemical driving force K+ equilibrium potential Concentration differences of Na+ and K+ across the membrane exist. At rest, membrane is only permeable to K+ ion by leak channel. Resting membrane potential is closer to equilibrium potential of K+ ions. 26. Factors that affect resting potential1. Difference of K+ ion concentration across the membrane2 .Permeability of the membrane to Na+ and K+.3. Action of Na+ pump27. Action Potential Property1 It is an “all or none” phenomenon. Threshold / suprathreshold stimulus causes a complete action potential.“All or none” means that action potentials occur maximally or not at all. There is no such thing as a partial or weak action potential.2 It can be transmitted in two directions. 3 The wave form and amplitude do not reduce with its propagation 28. Types of stimulus:Threshold stimulus: The stimulus with the intensity equal to thresholdSubthreshold stimulus: The stimulus with the intensity weaker than the thresholdSuprathreshold stimulus: The stimulus with the intensity greater than the threshold.29. Initiation of an Action Potential Depolarization stage Na+ inflow Repolarization stage K+ outflow Summary Threshold stimulus cause the depolarization of membrane potential to threshold level leads to opening of Na+ channels, allowing Na+ to enter the cell Interior becomes positive Next K+ channels open, K+ leaves the cell and the interior again becomes negative. The Na+ channels then close automatically followed by a period of inactivation.Process lasts about 1/1000th of a second. 30. Propagation of the Action Potential(Signal Transmission along Nerve Fiber) “ local current flow ” theory 局部电流学说 Factors that affect the propagation1) Bioelectric properties of the membrane2) Velocity and amplitude of membrane depolarization31. Ion Permeability during the AP gNa increases quickly, but then inactivation kicks in and it decreases again. gK increases more slowly, and only decreases once the voltage has decreased. The Na+ current is autocatalytic. An increase in V increases gNa , which increases the Na+ current, and increases V, etc. Hence, the threshold for action potential initiation is where the inward Na+ current exactly balances the outward K+ current. During subthreshold stimulus, inward Na+ current does not balance the outward K+ current, which causes local response.32. Local response Property 1 It is a graded potential (not all or none). 等级性电位 2 Its propagation is electrotonic propagation 电紧张式传导3 It can be summed (summation). 总和现象 Spatial summation: 空间总和 Temporal summation: 时间总和33. Local Potential Role1 It may facilitate the cell. 易化作用2 It may cause cell to excite with its summation. 经总和引起兴奋 34. difference between action potential and local potentialAction Potential Local Potential1. Caused by threshold / subthreshold suprathreshold stimulus stimulus 2. Amplitude ofdepolarization high low3. All or none Yes No ( graded )4. Transmission distance: long short pattern: no attenuated electrotonic 5. Summation No Yes6. Significance sign/mark: Yes No role: elicit cell function facilitate cell7. Others: refractory period Yes No 35. Threshold Stimulation and ExcitabilityThreshold Excitability Threshold ExcitabilityThreshold stimulus / threshold intensity is the index for value excitability36. Four periods Absolute refractory period Relative refractory period Supranormal period Subnormal period37. Factors that Determine the Excitability1 The difference between resting potential and threshold potential2 State of ion channel38. Illustration of the Neuromuscular Junction (NMJ)(1) Nerve terminal, voltage gated Ca2+ channel mediates neurotransmitter release synaptic vesicle (Ach) quantum release of ACh The amount of ACh contained in one vesicle is called a quantum of ACh. About 10000 ACh molecules 250 vesicles ACh by an action potential (2) Space of junction, 50nm Extracellular fluid(3) End plate membrane, N2 -ACh channel End plate potential (EPP)a local depolarization at end plate membrane due to Na+ inflow ACh enzyme (ACHE, AChase) (Acetylcholinesterase)It can break down ACh in a few ms. (4) Normal membrane voltage gated Na+ channels voltage gated K+ channels excitation (action potential)39. Neuromuscular Transmission: Step by StepNerve action potential invades axon terminalDepolarization of terminal opens Ca channelsCa+2 induces fusion of vesicles with nerve terminal membrane.ACh is released and diffuses across synaptic cleft.ACh binds to its receptor on the postsynaptic membraneBinding of ACh opens channel pore that is permeable to Na+ and K+.The movement of Na+ and K+ depolarizes muscle membrane potential (EPP) ACh unbinds from its receptorso the channel closesACh is hydrolyzed by AChE into Choline and acetateCholine is taken up into nerve terminalCholine resynthesized into ACh and repackaged into vesicle40. Steps of Transmission at the Junction Nerve action potential invades axon terminal Depolarization of terminal opens Ca2+ channel Ca2+ induces fusion of vesicles with nerve terminal membrane. ACh is released and diffuses across synaptic cleft. ACh binds to its receptor on the postsynaptic membrane The movement of Na+ and K+ depolarizes muscle membrane potential (EPP) Excitation of whole normal membrane.41. Properties of Transmission a chemical process. 化学传递 ( 1:1) unidirectional 单向 It has time delay. 时间延搁 ( 20nm/0.5-1 ms) It is easily affected by drugs and some factors. 易受影响42. Sarcotubular system 肌管系统 Transverse tubule ( T管 )传导兴奋 Sarcoplasm reticulum (SR) JSR(Cisterna): 终池 Ca2+ pool Ca release channel LSR: Ca2+ pump 钙泵 Triad 三联管 兴奋收缩耦联43. Characteristics of Sarcomeres It is made of filaments It is rich in membrane tubule system Sarcomere is the basic contractile unit44. Molecular Characteristics of FilamentsThick filament 粗肌丝 :myosin (肌凝蛋白) 2 binding sites(结合点)to ATP and to actin ATP enzymeThin filament 细肌丝 3 types of molecules actin (肌动蛋白)binding site to cross bridgetropomyosin (原肌凝蛋白) troponin (T,C,I) (肌钙蛋白 T,C,I)Attachment of cross bridge to actin a cross bridge cycling 横桥周期 45. Process of Muscle Contraction Sliding filament theory 肌丝滑行学说 a cross bridge cycling 横桥周期 Myosin head is energized. Attachment of cross bridge to actin. Power stroke causes contraction. Detachments of heads from actin. Myosin head is energized again. 46. Summary of Mechanism of Muscle Contraction Sarcomere is the basic contractile unit. Two types of proteins: Contractile proteins: Actin Myosin Control proteins: Tropomyosin Troponin Cross bridge cycle includes 4 steps. Contraction & relaxation expend ATP. 47. Two results of filament sliding 滑行结果 force or tension shortening48. How many roles does ATP play in Muscle contraction ATP plays 3 roles in contraction Induce attachments and provide energy for power stroke . actin, initiating a new cross bridge cycle. Provide energy for Ca2+ pump to low intracellular Ca2+ , causing relaxation. 49. Steps of the Excitation Contraction Coupling AP moves down the t-tubule voltage change detected by DHP receptors DHP receptor is essentially a voltage-gated Ca channel DHP receptors is communicated to the ryanodine receptor which opens to allow Ca out of SR activates contractionControl of the Cytosol Ca2+ Concentration(1)Release by Ca2+ releasing channel(2)Reuptake by Ca2+ pumpCa2+ releasing channel =Ryanodine receptor,Ry-R = Ryanodine channel Ca2+ releases by Ryanodine channel in skeletal muscle differ with/from myocardium.50. Skeletal muscle骨骼肌 and Myocardium 心肌 Skeletal The trigger for SR release appears to be voltage (Voltage Induced Calcium Release- VICR) The t-tubule membrane has a voltage sensor (DHP receptor) The ryanodine receptor is the SR Ca release channel Ca release is proportional to membrane voltage Cardiacm The trigger for SR release appears to be calcium (Calcium Induced Calcium Release - CICR)m The t-tubule membrane has a Ca channel (DHP receptor)m The ryanodine receptor is the SR Ca release channelm The ryanodine receptor is Ca-gated & Ca release is proportional to Ca entry 51. Summary of Excitation-Contraction Coupling It is an intermediary process to link action potential with filament sliding. It includes 4 steps. 52Coupling structure is triad. Coupler is Ca2+ ion. Sources of Ca2+ for contraction differ in muscles. 99% of Ca2+ is stored in cistern of skeletal muscle. 80-90% Ca2+ ions is stored in myocardial cell. Initiation of skeletal muscle contractionTransmission of a Motor Signals at N-M JunctionExcitation of Muscle CellExcitation - Contraction Coupling Contr

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