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Example summary 2015-2016 PREFACE Dear medical students, After hopefully a great meeting with the most beautiful students city it´s time to meet your new study. It will be a fantastic period with a lot of new experiences. Slimstuderen.nl is an organization that makes summaries for every exam you have to make. Last year 75% of the Dutch students used these summaries. And from now on Slimstuderen.nl will also make English summaries for the international students! This is a small example of a summary we make. Working at Slimstuderen.nl We are always looking for new, enthusiastic authors who want to help us by making our summaries. If you are interested in a job at Slimstuderen.nl, you can send an email to [email protected]. Where can you buy a summary? Our summaries are available at the Copy-Copy at the Oude Kijk in ‘t Jatstraat 52! Or you can order it at Slimstuderen.nl! Like us on facebook! Everything about medicine: facebook.com/slimstuderengnkgroningen Everything about the city of Groningen and Slimstuderen.nl: facebook.com/SlimstuderenGroningen Do you want to win a half-year of free summaries? Join our campaign and win a half-year of free summaries! The only thing you have to do is to write down your email on the paper. If you are not the winner, you will use the discount code to get 25% discount. This discount code is only available in our online shop at Slimstuderen.nl. RUGGNK2015 Enjoy your time as a medical student in Groningen! SlimStuderen.nl Facebook.com/slimstuderengnkgroningen 1 Example summary 2015-2016 Table of contents PREFACE .................................................................................................. 1 TABLE OF CONTENTS ............................................................................... 2 A. CELL BIOLOGY ................................................................................... 3 B. FYSIOLOGY ........................................................................................ 7 C. EXAM QUESTIONS ........................................................................... 11 Facebook.com/slimstuderengnkgroningen 2 Example summary 2015-2016 A. CELL BIOLOGY All organisms are composed of cells. These are small units, enclosed within a membrane, and filled with a concentrated, watery, mixture of chemicals. They have the ability to replicate their content in order to grow, and then divide themselves into two new cells. Cells can communicate with each other and are the fundamental units of life. Unit and diversity of cells Cells differ from one another in size, form and chemistry. These variations make it possible for different cells to perform different functions. Some cells are specialised “factories” for the production of certain substances such as hormones, starches, fat, latex or pigments. Others serve a motor function, such as muscle cells, which burn calories to perform mechanical work. Each of these cells is so specialized that their survival is dependent on other cells. However different cell types might be, they all have the same basic chemistry. They consist of the same molecules, which participate in the same chemical reactions. Furthermore, all cells carry genetic information, in the form of genes, in DNA molecules. This information is written in the chemical code itself, composed of the same building blocks and able to replicate in the same way. It isn’t by chance that all cells are so similar to each other. All contemporary cells in a living organism originate from a common stem cell. Cells found in one organism at a certain time point can also differ due to mutations, which change and diversify their DNA. Mutations can be advantageous, providing cells with an advantage in survival and reproduction, compared to previous cells. On the contrary, mutations can also be a disadvantage, leading the mutated cells to living and reproducing less than non-mutant cells. It is also possible that, sometimes, a mutation doesn’t positively or negatively influence the fate of the mutated cell. In sexual reproduction, the resulting cell doesn’t originate from the division of another cell. Rather, the resulting cell originates from two cells, one from each parent, which fuses to form a new cell. Mutations and sexual reproduction lead to both genetic variability and natural selection and are the basis of evolution. The genome of a cell is the whole set of nucleotides in the DNA of an organism. This directs a cell on how it should behave. A fertilized egg cell can give rise to a wide variety of cells such as muscle cells and neurons. These cells are different, but contain the same DNA. Different cells express different genes, depending on their internal information and environmental influences. The prokaryotic and eukaryotic cell Organisms whose cells contain a nucleus are called “eukaryotic”, whereas organisms whose cells have no nucleus are called “prokaryotic”. Bacteria and Archea (single-cell microorganisms) are prokaryotes. Human cells are an example of “eukaryotic” cells. Organelles in the eukaryotic cell Figure 1 shows a eukaryotic cell. The most important organelle is the eukaryotic cell is the nucleus. It is enclosed between two concentric membranous layers, which form the nuclear envelope. It contains DNA molecules – large polymers encoding the genetic information of the whole organism. Mitochondria have a worm-like structure. Individual mitochondria (i.e. the mitochondrion) are enclosed within two separate membranes. The innermost membrane is formed by folds, which stick out inside the organelle. Mitochondria are responsible for generating usable energy by oxidizing foodstuff to produce ATP, the fundamental chemical fuel for most of a cell’s activities. Facebook.com/slimstuderengnkgroningen 3 Example summary 2015-2016 Mitochondria use oxygen and release carbon dioxide during their activity. Thus, this process is called cellular respiration. Furthermore, mitochondria possess their own DNA and reproduce via binary fission (dividing themselves in two). Figure 1: The eukaryotic cell: 1: Nucleus 2: Nuclear envelope 3: Endoplasmic reticulum 4: Golgi apparatus 5: Mitochondrion 6: Lysosome 7: Peroxisome 8: Transport vesicle Chloroplasts are big, green organelles exclusively found in cells in plants and algae. They contain two adjacent membranes which themselves contain membranous stacks filled with the green pigment chlorophyll. Chloroplasts resort to photosynthesis: their chlorophyll molecules gather energy from sunlight and use this energy in other processes. The Endoplasmic Reticulum (ER) is an irregular, maze-like structure of mutually connected spaces, enclosed within a membrane. It’s here where most parts of the cell membrane and a cell’s export products are formed. The Golgi apparatus is composed of flattened, stacked membranes, resembling discs. These modify and package ER molecules to be transported to another cell or organelle. Lysosomes are small, irregularly shaped organelles where intracellular digestion takes place: they break down food particles into smaller foodstuffs, as well as breaking down unwanted molecules, which are recycled or excreted. Peroxisomes are small, membrane-enclosed vesicles, responsible for providing a safe environment for several reactions. Toxic molecules are inactivated inside peroxisomes using hydrogen peroxide. Molecules are continuously transported between the ER, the Golgi apparatus and the lysosomes by means of transport vesicles. This happens via the processes of endo- and exocytosis. Exocytosis and endocytosis are also used to transport materials into and out from the cell. The cytosol is the fraction of the cytoplasm found outside the intracellular membrane. It contains many big and small molecules, which gives it more of a gel-like rather than fluid consistency. It is where many of the fundamental, vital chemical reactions in the cell take place (for example, it’s where the first step in the breaking down of nutrient molecules occurs). The cytoplasm and cytoskeleton of the cell The cytoplasm’s structural integrity is dependent on the cytoskeleton. This is a system of protein filaments frequently anchored to the plasma membrane and the nucleus. There are 3 kinds of protein filaments: Actin filaments: the thinnest filaments are abundantly found in muscle cells. These filaments are the central pieces in the mechanism responsible for muscle contration; Microtubuli: the thickest filaments resemble hollow tubes. These are intimately involved in cell division; Facebook.com/slimstuderengnkgroningen 4 Example summary 2015-2016 Intermediate filaments: responsible for strengthening the cell. Other proteins are also often found along these three filaments. Together, they form a system of beams, ropes and motors, which grant the cell its form and mechanical power, and assure its motility. The interior of a cell is in constant motion. Motor proteins use energy stored in ATP to transport organelles and other proteins through the cytoplasm. Eukaryotic cell Unicellular or multicellular Diameter 5 – 100 um Nucleus contains genetic information in the form of complexly organized chromosomes composed of DNA + protein. RNA-synthesis in the nucleus, protein synthesis in the cytoplasm, nucleoli present in the nucleus. Cytoplasm containing cytoskeleton composed of protein. Division through mitosis or meiosis. Mostly possess aerobic metabolism. Prokaryotic cell Exclusively unicellular Diameter 0,5 – 10 um Genetic information stored in circular DNA molecules in the cell (nucleoid). RNA and protein synthesis takes place in the same compartment, no nucleoli. No cytoskeleton, organelles poorly or not developed. Division through binary fission. May possess aerobic or anaerobic metabolism. Table 1: Differences between the eukaryotic and prokaryotic cell. Facebook.com/slimstuderengnkgroningen 5 Example summary 2015-2016 Facebook.com/slimstuderengnkgroningen 6 Example summary 2015-2016 B. FYSIOLOGY The global function of the Central Nervous System Many kinds of amazingly fast processes take place in the human body with the goal of transmitting a signal. This transmission occurs via neurons to the central nervous system, and in a special way. To understand it, it’s important to have knowledge of the concepts of resting membrane potential and action potential. Resting membrane potential There is always voltage in neurons, even when they’re not transmitting any impulses. This is called the resting membrane potential and is generated by an uneven trade of Na+ and K+ ions. There are more K+ ions than Na+ ions inside the cell, and more Na+ ions than K+ ions outside the cell. The resting membrane potential is around -90mV. This potential is maintained by means of leak channels, which allow the entrance of much more K+ ions than Na+ ions into the cell. Leaks channels function passively, obeying the concentration gradient. In addition to it, cells possess active Na+/K+ pumps. When “fed” ATP, these active pumps transport two K+ ions into the cell, exchanging them for three Na+ ions, which are pumped to the outside. This is what causes the negative potential on the inner side of the membrane. Action potential In response to a stimulus, cells (such as muscle cells and neurons) can alter the permeability of their cell membrane to ions. Stimulating a neuron, thus, leads to a localised increase in the membrane’s permeability to Na+ ions: an action potential. An action potential is generated every time the membrane potential reaches a certain, critical value. That threshold is usually 8-12 mV greater than the resting membrane potential. As with leak channels for keeping the resting membrane potential, there are specific channels playing a crucial role in the propagation of an action potential: voltage-gated channels. The voltage-gated Na+ channels are responsible for depolarization, whereas voltage-gated K+ channels are responsible for repolarization. The Na+/K+ pump, conversely, is responsible for the reestablishment of the original potential during the spread of an action potential. When an action potential starts, the voltage-gated Na+ channels open, allowing Na+ ions to diffuse into the cell and trigger a change in the membrane potential (a depolarization). After just a few milliseconds, these sodium channels close again. The voltage-gated K+ channels open somewhat more slowly and stay open for a longer period, allowing for repolarization to occur. Once the membrane potential becomes negative again, the voltage-gated K+ channels close. When this happens with a slight delay, hyperpolarization is said to occur. The refractory period is the period during which the voltage-gated Na+ channels cannot open. During this period, cells cannot process new action potentials (i.e. no new action potentials can be elicited in that cell). The refractory period ends when the membrane potential is reset to the basal value (resting membrane potential). The local depolarisation of a nerve fiber sends a wave of electrical current from the depolarised point to the adjacent micro-region. This happens because there is a change in electrical charge next to the depolarised point, so that the certain point on the inner side of the membrane is positively charged. This creates an even greater difference in potential with regard to the adjacent regions, which are “more negative”, thus causing the displacement of the excess positive charges to those more negative areas. The action potential spreads as this occurs repeatedly and continuously along the whole membrane of a nerve fiber. Facebook.com/slimstuderengnkgroningen 7 Example summary 2015-2016 Myelin A special characteristic of neurons that allows them to transmit signals as fast as they do is their isolation. Long neurons are myelinated, while short neurons are demyelinated. Myeline is responsible for the isolation that allows action potentials to spread the way they do. That is, myeline allows a much faster conduction along the neuron’s axon. The action potential “jumps” through the myeline sheath, from one node of Ranvier to the next, spreading much faster this way. The somatic nervous system The somatic nervous system, also named the voluntary nervous system, commands all interactions with the outside world. Sensory neurons bring a message from organs, which perceive multiple stimuli (for example, the skin). Motor sensors activate skeletal muscle. The somatic nervous system is composed of the somatic part of the central and peripheral nervous systems and is responsible for the general sensory and motor innervation of all parts of the body, apart from the intestines in the abdominal cavity, smooth muscle and the glands. The autonomous (visceral) nervous system is the part of the peripheral nervous system responsible for all reactions taking place unconsciously, such as breathing and the function of organs like the liver and the kidneys. Muscle tissue Each muscle fiber is composed of hundred to thousands myofibrils. Each myofibril is, in turn, composed of a mesh alternating around 1500 myosin filaments and 3000 action filaments. A-bands contain thick myosin filaments, which overlap with thin actin filaments at the end portion of a sarcomere. In the middle, there is no overlap of the myosin filaments with any actin filaments, and this are is called the H-band. The I-band contains myosin and actin filaments, which don’t overlap. That is what makes this band often lighter in colour. In the middle of the I-band is the Z-line, where actin filaments attach. The before mentioned sarcomere is the fraction between two consecutive Z-lines. The side-by-side position of actin and myosin filaments is easy to understand. They are kept in place by the protein titin, which is thread-shaped and thus very elastic. Titin keeps actin and myosin filaments in place, making it possible for the sarcomere to perform its contractile function. Titin is bound to the Z-line and changes in length upon contraction and relaxation. Mitochondria can be found next to the myofibrils, to which they provide energy. The space between myofibrils is filled with a liquid: sarcoplasm. Initiation and execution of a muscle contraction takes place in the following steps: An action potential spreads along a motor neuron until it reaches the proximity of a muscle fiber; Each neuron releases the neurotransmitter acetylcholine from vesicles in its endextremity; Acetylcholine is responsible for the opening of ion channels in the muscle fiber membrane; Opening these Ach-dependent channels leads to the inflow of large amounts of sodium ions. This originates a depolarization of the sarcolemma, the membrane of the muscle fiber which, in turn, causes voltage-gated sodium ion channels to open; The depolarization of the sarcolemma spreads to the myofibrils via T-tubuli; The depolarization of the myofibrils leads to the activation of the sarcoplasmic reticulum, which releases large amounts of the calcium ions it keeps stored; These calcium ions will bind to the troponin complex, causing it to undergo a shape change, and exposing its free binding sites. The head of the myosin filament can, then, bind to these free binding sites; Facebook.com/slimstuderengnkgroningen 8 Example summary 2015-2016 ATP is released everytimeevery time the head of a myosin filament becomes bound to troponin. The heads can then flex (pull back in a stroking motion), leading to the pulling of the actin and myosin filaments along each other. This is what causes muscle contraction; Contraction ends when calcium ions are pumped back into the sarcoplasmic reticulum. A myosin filament is composed of six polypeptide chains; two heavy and four light chains. The two heavy chains form a double helix, and are the tail of the myosin molecule. One end of one of these chains folds bilaterally and possesses a ball-shaped polypeptide structure: it’s called the myosin head. There are, thus, two myosin spheres atop the end of a double helix. The four light chains are part of these spheres; two in each myosin head. In a resting state, actin and myosin filaments overlap each other only partially. During contraction, these filaments interdigitate, so that the myosin filaments glide between the actin filaments. During a contraction, all the myosin and actin filaments in a sarcomere interdigitate as described above. This happens in the A-band. When a muscle is at rest, the binding site between actin and myosin becomes blocked by the troponin-tropomyosin complex in the actin filament, preventing any contraction from happening. Skeletal muscle tissue Cardiac muscle tissue Smooth muscle cells Observable characteristics Long, cilinder-shaped giant cells with many nuclei. Are arranged in parallel to each other Single nucleus, transversely striated. May have a “dendritic-like” form Spindle-shaped Formation/Structure Myoblasts (stem cells) divide and fuse to form a multi nucleated muscle cell Bifurcate and attach to each other’s end ramifications Dense bodies attach muscle cells to each other. Each muscle cell has a single nucleus Striation Transverse striations with parallel distribution Transverse striations No striation. Actin, myosin and dense bodies are present Location of the nucleus Directly under the sarcolemma Central in the cell In the middle of the cell Regeneration Through satellite cells (a single nucleated stem cell with the ability to divide and to fuse with each other or with another muscle cell to augment existing muscle fibers) Can’t regenerate Possible by cell division (also possess satellite cells) Table 2: Different types of muscle tissue Facebook.com/slimstuderengnkgroningen 9 Example summary 2015-2016 Two different substances can affect the normal function of the motor end plate: Cholinesterase inhibitors: these substances delay the breakdown of acetylcholine in the synaptic cleft, thus prolonging the neurotransmitter’s effect. This may cause a muscle to cramp; Curare: this substance blocks the binding of acetylcholine to the post-synaptic membrane receptors. This results in the opening of only an insufficient number of ion channels in the post-synaptic membrane, not enough to generate/transmit an action potential. The ultimate effect is that there is no contraction. An isometric contraction is a contraction in which force is exerted without any change in muscle length. An isotonic contraction is a contraction with unchanged tension but where there is a change in muscle length. The amount of force exerted during a contraction depends on several factors. It’s essential to know whether the muscle is stimulated by small, spaced stimuli (“shocks”) or if it is continuously stimulated. This is the difference between twitch and tetanus. A twitch is the time between the motor end-plate potential, the contraction and the relaxation of a muscle fiber, making twitch contractions intermittent. Conversely, in tetanic muscle contraction, the muscle fiber is continuously contracted and there is no relaxation. Facebook.com/slimstuderengnkgroningen 10 Example summary 2015-2016 C. EXAM QUESTIONS 1. Which event triggers the breakage of the actin-myosin bond? A. ATP hydrolysis B. Binding of Ca2+ to Troponin C C. Pumping of Ca2+ back into the Sarcoplasmic Reticulum D. Binding of ATP to myosin 2. A mutation always alters the end product of that mutated gene. A. True B. False Answers: 1=D; 2=B Facebook.com/slimstuderengnkgroningen 11 Example summary 2015-2016 Facebook.com/slimstuderengnkgroningen 12