Physiology Lecture Notes PDF

Slide 2 -​ In order to make sense of our body and be able to understand how all our body systems communicate with each other to keep us alive, we separate the structures in our body into “levels of organization”. -​ The levels of organization are (CCTOSO): 1)​ Chemicals: The combination of...

Slide 2 -​ In order to make sense of our body and be able to understand how all our body systems communicate with each other to keep us alive, we separate the structures in our body into “levels of organization”. -​ The levels of organization are (CCTOSO): 1)​ Chemicals: The combination of certain ions and molecules make the organelles that are found inside our cells and are also responsible for the homeostatic control between and among cells. 2)​ Cells: the most basic and simple structural unit that makes any tissue 3)​ Tissues: The combination of many cells of the same type working together towards a common goal 4)​ Organ: The combination of several different types of tissues that maintain chemical and electrical communication for a common overall function 5)​ System: The complex interaction that exists between several organs that share a similar ultimate goal in our body 6)​ Organism: The complex interaction, communication, and regulation of several systems that maintain our body at homeostatic levels and keep us alive. Humans have 11 body systems. Can you mention them? (try to come up with all 11 on your own, the answer is below)Answer: Integumentary, Respiratory, Digestive, Cardiovascular, Muscular, Neural, Lymphatic (aka Immune), Urinary, Reproductive, Endocrine, and Skeletal -​ There are 4 THEMES in physiology. Meaning there are four main concepts that we will cover in general 1)​ Homeostasis: It refers to the balance that is maintained by our physiological processes within a range given towards a set point. We have an ideal set point given for everything in our body that will keep us alive BUT we also have to have a range because as humans we are always in entropy (change/fluctuation). For example, the set point for pH is 7.4 but the range is 7.35 to 7.45 because everything we do, drink, and eat during the day makes us fluctuate within that range. 2)​ Energy: All our physiological mechanisms require the use of energy (ATP). We either get it from glucose or from aerobic respiration. We have stored energy (in chemical bonds and concentration gradients) and we have kinetic energy (which is our usable energy – glucose and ATP molecules directly). The conversion from one type of energy to the other (potential–kinetic) is possible at any moment. 3)​ Structure-function relationship: Everything in our body works because all of our structures (including the most basic ones such as receptors in a cell) have a specific structure that determines how it will work or what it will activate/inhibit it. It includes molecular interactions, the separation of our body into compartments, and the mechanical properties of our structures 4)​ Communication: In order to maintain balance and in order to function we depend on how and what molecules will signal our structures to do something. Our signals are separated into chemical or electrical. Answer: Integumentary, Respiratory, Digestive, Cardiovascular, Muscular, Neural, Lymphatic (aka Immune), Urinary, Reproductive, Endocrine, and Skeletal Slide 3 -​ Physiologically speaking which system would you consider to have a greater impact on your entire body and why? -​ Many students answer either nervous or endocrine. These two systems are the ones in charge of regulating/controlling the activities of all other systems, HOWEVER, they do not have the greatest impact on them. This is an example of questions on an exam- You want to make sure you read the entire question and you understand what is being asked. If the question said which system(s) has the greatest control or which system(s) can regulate all other systems then the nervous system or endocrine system would be the answer but that is not what is being asked. -​ NOW- to answer the questions we need to think about what system would AFFECT all other systems due to its structural proximity or due to the exchange that occurs between that system and all the other ones. So the answer is the Cardiovascular system. -​ Our body has different levels of compartmentalization. We have different spaces that separate our cells or our organs in order to be fully functional. The smallest compartmentalization system-wise that we have is the separation of our ECF (extracellular fluid) and ICF (intracellular fluid). The ECF is separated into two other compartments (except in the cardiovascular system since the cells are inside the plasma. The two compartments of the ECF are the interstitial space (ISF) and plasma. Shown in the diagram below ​ ​ ​ Inside a cell​ Outside a cell ​ ​ ​ ICF​ ECF ​ ​ ​ I​ I ISF : Plasma I as you can see, since within the Cardiov. system our blood cells are already inside the plasma, there is no ISF ​ ​ ​ I_______________I_______:___________I Slide 4 -​ The way that communication occurs in our body from cell to cell or even within one cell is referred to as a control system. -​ The three basic components of a control system are: -​ the input signal (aka cytokine or ligand) which is the stimulus – the controller (aka integrating center which can be a receptor or the CNS or a gland) which is the structure that receives the stimulus and causes a series of changes – and the output signal (a signal that will go to the last cell involved in the pathway and promote the final cellular response). -​ All control systems have an inducer or a repressor. Meaning the input signal can be something that promotes a change or increases the response; or something that inhibits a change or decreases the response. -​ Everything we do throughout the day (eat, drink, sleep, work out, smoke, tan, or simply go outside on a cold day, etc) promotes a change in a variable within our body. That change moves along a range within a set point, which is considered the optimal value of that variable. As we move away from that set point (in either direction) we reach the maximum value of that variable and once we cross it we set in place a response loop (or physiological pathway) that will “fix” for that stimulus. As the physiological pathway is in place it causes the variable to move towards the set point in the opposite direction from what the stimulus is causing; BUT we don’t want it to go beyond the maximum value on the other side so once the value reaches the other side, the new variable cancels the process or counteracts (opposes) the original Slide 5 -​ A negative feedback loop is a reaction that causes a decrease in function as a response to a stimulus. It stabilizes the system by stopping or lessening the output created by the original stimulus so that we are kept in homeostasis or equilibrium. So in other words, negative feedback loops is the response that opposes the original stimulus. For example: Your body temperature is controlled by negative feedback loops. When you get really hot, you stimulate a response to sweat and lose heat through evaporation, when your temperature drops and is now cold enough, the new temperature shuts down the response (sweating) so we don’t lose TOO much heat. Another example is our regulation of blood pressure: lets say your blood pressure is low and you set physiological mechanisms to increase your blood pressure (like vasoconstriction or increase cardiac output), once your blood pressure gets high enough, then your neg feedback loop will stop those mechanisms that increased your blood pressure in the first place. Or when you go through hypoxemia (low levels of oxygen in your blood) your kidneys secrete erythropoietin to stimulate RBC formation because RBC’s carry oxygen, the new levels of oxygen cause the stop of erythropoietin secretion. -​ Neg feedback loops are most common because they take us to homeostasis. They reduce the change or original output (response) of a physiological process. -​ Positive feedback loops are the opposite. They increase a function by reinforcing the change until the stimulus is removed. The response intensifies the original stimulus until the cycle is  broken by an external factor. Examples would be the contractions of the uterus leading to childbirth which do not stop until the child is pushed passed the cervical canal. Another example is blood clotting, where platelets are released until bleeding stops; Or the continuation of an Action Potential traveling through an axon. We don’t have many of those because they take us away from homeostasis. Slide 6 -​ Ligands as stated before are any signal molecule that binds to a receptor. Receptors are either intracellular (inside the cell in the cytoplasm or nucleus), or in the plasma membrane of cells (remember cells form tissues and tissues form organs so many books will say things like “receptors in your heart” which means receptors found in the cells that make up your heart. Slide 7 -​ This is something you will need to memorize. 1)​ A mole of any substance is equal to 6.02 x1023 particles regardless of their molecular weight. So even though glucose and NaCl are different molecular weights, 1 mole of glucose = 1 mole of NaCl. 2)​ Molarity is the concentration in moles of a substance in 1L of solution. So a solution that is 1M NaCl means that there is 1 mole of NaCl for every 1L of that solution. 1 mole of any substrate can be calculated by their molecular weight. So 1 mole of NaCl is equal to 58.5 gr of NaCl per Liter. Grams does NOT equal particles so do not get confused; this is why 1 mole (6.02 x1023 particles) of glucose (MW = 180gr) is equal to 1 mole (6.02 x1023 particles) of NaCl (MW = 58.5gr). 3)​ Osmolarity: it refers to the total concentration of particles in a solution. It is a countable measure. It takes into account dissociation and it happens as soon as you mix the solute with the fluid. -​ Dissociation refers to how many particles will be created when you introduce the solute into the solution. -​ Glucose is not dissociable but NaCl dissociates into 1Na and 1 Cl. So for every NaCl we mix in a solution we will get 2 particles. Na+ is important for these mechanisms but Cl- is not so don’t worry about Cl-. -​ Remember we mentioned before that we always try to maintain homeostasis (balance). This means that any specific substance will try to be the same in concentration in the three compartments we mentioned before (ICF and ECF). So whenever we have a higher concentration of a certain solute in one compartment, it will try to move across the membrane until it reaches equal, or as close to equal, concentrations. You can calculate the osmolarity (total number of dissociated particles) in any of the three compartments! -​ If the concentration is higher you say is hyper-osmotic, if the concentration is equal you say is iso-osmolar, and if the concentration is lower then you say is hypo-osmolar. -​ The NORMAL osmolarity of our blood and all our cells is between 290mOsm and 310mOsm so we will say for this class that the normal osmolarity is 300mOsm. 4) When we move solutes across membranes or if we cannot move solutes across because there is no diffusion possible or there aren’t any channels or receptors that allow movement, then water will move to wherever the concentration is higher. When water moves in or out of the cell it changes the shape of the cell and this is what we call Tonicity. -​ It refers to the EFFECT of the solution on the cell. -​ The solution/fluid is changing the osmolarity of the compartments and based on that osmolarity (concentration) water will move into the cell or out of the cell or it won’t move. -​ Tonicity therefore only refers to the solution but is based on what happens to the cell. Meaning you cannot ask what is the tonicity of a cell, you always ask what is the tonicity of the solution. -​ It is not countable -​ It takes into account penetrable and non-penetrable solutes because depending on the movement of the particles is that the final concentrations will be determined, and only then will water move to accommodate. -​ If water moves out of the cell you say the solution was hypertonic and it causes the cell to shrink, if water doesn’t move then you say is isotonic, and if water moves into the cell you say is hypotonic and it causes the cell to explode. -​ Since tonicity happens after particles move then tonicity happens AFTER osmolarity is measured. 5) You will need to understand Osmolarity and Tonicity very well and you will need to learn how to apply the information into clinical or normal scenarios. So please read the book on this topic focusing on those two (osmolarity and tonicity). Also, go to my website and go to extra documents - Download a file that says Osmolarity and Tonicity – look at those scenarios and try to understand them. You will need to remember that glucose does not dissociate but NaCl does, and you also need to know that glucose is innately permeable (meaning it ALWAYS moves because our cells are always hungry for energy) but Na+ is a non-permeable solute (meaning unless there are channels specific for the movement of it and is needed for a physiological process, then Na+ will stay in whatever fluid compartment you are putting it into). Also, when glucose moves into our cells it pulls water with it but since you are increasing the Osmolarity inside the cell for a brief moment, it pulls water into the cell without expanding it (it only hydrates it). Glucose then is used up by the cell so you are just hydrating the cell in general. This compared to if you just give plain water to someone then water is “forced” into our cells causing them to expand and might burst. When you look at that document on my website you will also learn about equilibriums. 6) These concepts of Osmolarity and tonicity are also similar (not the same) to Hydrostatic Pressure and Osmotic Pressure. Hydrostatic Pressure is the pressure that exists within/inside a vessel and is created by all the particles and fluid within it. It creates a “force” that pushes both solutes and fluid outside of the vessel into the interstitial space and is the main and first force of diffusion out of a capillary. Osmotic Pressure, on the other hand, is also a pressure that exists within a vessel but is created only by all the non-permeable solutes found inside it and it causes water to move back into the vessel. So in a way, HP is similar to osmolarity in that is caused by all the (dissociated) particles per volume promoting movement of solutes, while OP is similar to tonicity in that is caused by non-permeable solutes and causes water movement to the area with a higher concentration. The main difference is that Osmolarity and tonicity are at the cellular level while HP and OP are in a vessel such as a capillary. Slide 8 -​ We have four main organic molecules and one main non-organic molecule in our body. -​ Non-organic = water -​ Organic = proteins, carbs, lipids, and nucleic acids ​ 1) Carbs are the most complex. They are polar (water-soluble = non-permeable) and non-polar (lipid soluble – permeable) ​ 2) Lipids are the most abundant. They are all non-polar so they are freely permeable ​ 3) Nucleic acids are part of our genetic composition. They can be polar or non-polar ​ 4) Proteins are the most diverse (they can be many things) and are mostly polar but some are non-polar. -​ Since we already talked about the permeability of two other molecules (glucose and NaCl). Let’s talk a little bit more about that. -​ Permeability is based on Can they cross the plasma membrane of a cell freely or do they need a carrier or a channel to do so? -​ You should remember from pre-requisite course that the plasma membrane, also known as the phospholipid bilayer, is made out of phosphate hydrophilic (aka lipophobic) heads, and lipid hydrophobic (aka lipophilic) tails. The barrier created by the lipid tails is what makes the membrane selectively permeable and as such, lipid-soluble compounds will pass freely by diffusion but water-soluble compounds will need a carrier or a channel via facilitated diffusion or some sort of vesicle and this can be done either using energy (an active process) or not using energy (a passive process). Water and Glucose are unique because they are both needed a lot by the cells. Water can move by simple diffusion or by osmosis (a subtype of facilitated diffusion). Water molecules are so small that can squeeze through the phospholipid bilayer by simple diffusion, however, this process is very VERY slow because the lipid tails represent a barrier and thus is not used that much. MOST water moves by open channels found in all of our cells called aquaporins (that is why is fully permeable and its process is a subtype of facilitated diffusion called Osmosis). Glucose always moves by a carrier either by itself (the carrier is called uniport) or with Na+ (carrier is called symport because both move in the same direction). However, glucose is almost automatically used by the cell so it doesn’t add to the solute concentration. -​ Gases move freely because gasses are moved through any gaps found in between cells and even across our cells with no barriers -​ Free ions move based on the presence or absence of channels -​ Other non-permeable molecules move by channels or carriers and their size affects how fast they will move.  -​ In this slide, you can see all the different things that proteins can be. Make sure you understand (research if you don’t remember) what each of these are. Slide 9 -​ Protein binding can be affected by many things 1)​ Two main properties of every receptor: a)​ Specificity: Receptors only allow binding of some ligands based on their molecular shape. If the molecular shape of the ligand doesn’t match the molecular shape of the binding site in the receptor then it won’t bind. b)​ Affinity: Sometimes more than one ligand can bind to the same receptor because their molecular shape is similar. In those cases, the receptor will bind whichever ligand it “wants” more. This is called affinity. 2)​ Isoforms: When two or more ligands have similar molecular shape and can bind to the same receptor they are called isoforms. They can be agonistic (meaning they will cause the same cellular response) or antagonistic (they will cause the opposite response). In this cases we also see a concept called “competition” in which all ligands that can bind will try to do so. Affinity plays a big part in this scenario but sometimes affinity is the same for two or more ligands so in that case is pure competition that determines who will bind, 3)​ Activation: Some receptors are not functional all the time. In those cases, activation of the receptor will depend on cofactors (other molecules) that can bind to the receptor and either activate it functionally or inhibit it functionally. Sometimes the cofactors or other molecules will bind to the receptor and cause lysis (explosion) of the receptor so it won’t be functional at all anymore. 4)​ Modulation: Sometimes we have enzymes or cofactors or other molecules that will not determine if the ligand binds or not, but rather they will determine how many receptors are activated or how fast or slow. These will modulate the response of the cell by those receptors Slide 10 -​ In this picture you can see how the cofactor (which is another protein) binds to the receptor and upon binding, the cofactor forms (creates) a binding site so the ligand can bind and promote the cellular response. -​ You also see how competition can work. It either refers to the fact that two different ligands will bind because they are both similar in molecular shape, but it can also be a cofactor in which the binding blocks the interaction between the ligand and the receptor. This specific case where the cofactor doesn’t allow ligand binding is called competitive inhibition because since the ligand is not binding it is not causing any cellular response so the cofactor is inhibiting the response by the cell Slide 11 -​ In other cases, the cofactor doesn’t create the binding site but rather it causes a change in the shape of the receptor itself and this change causes the formation of the binding site in the actual receptor.  -​ Since the actual receptor is the one changing shapes then is called “allosteric” change. If the change is what causes the cellular response then is called “allosteric activation”, if the change prevents the response is called “allosteric inhibition”. Slide 12 -​ There are other factors that can affect the interaction between ligand and receptor. Since most ligands are proteins that is why the book focuses on protein interaction; but these factors affect all types of ligand-receptor binding. 1)​ Temperature: Warmer temperatures will cause an increase in the reaction, meaning they will increase the speed at which ligand-receptor binding is happening or the amount of ligand-receptor binding. BUT this has a limit because proteins can denature (break and lose function) if the temperature increases too much (the degree of temperature varies per protein). So you increase the speed of interaction or the amount of interaction but only for some time. Afterwards, the hot temperature can denature the protein that makes the ligand or the receptor and then the activity will cease. Cold temperature normally only decreases activity because it “freezes” the interaction. 2) pH: some proteins work better and more in acidic conditions and some work better and more in alkaline environments. Every protein is different. 3) Concentration of the protein. You can have 20 receptors but there are only 3 ligands then the activity won’t be maximized. Or you can have 20 ligands but only 3 receptors so many of the ligand molecules will go to waste. When it comes to receptors we have a physiological process called Up-regulation or Down-regulation in which we either form more receptors (Up-regulation) or we can promote the lysis of some receptors (Down-regulation). 4) Concentration of the ligand. Is explained in the previous statement 5) Maximum reaction rate: It refers to the fact that when ALL receptors in a cell for that ligand are being used and the receptors are moving at optimal speed, then we have reached the maximum rate which means the cell is working at maximum capacity. This happens when you reach saturation of the receptors (they are all being used) and you have reached maximum transport (the activity is maxed out). Slide 13 - You will need to remember the function of all the organelles in this slide. Make sure you go over your pre-requisite course for this Slide 14 -​ We have four main tissues in our body. Epithelial, Connective, Neural, and Muscular. -​ Each of them has an umbrella of classifications (except neural, neural is just neural) but the classification of these tissues is covered in anatomy not here. You won’t be required to know the different classifications for each. -​ You are required to know the four types, their unique features (found in this table) and their locations (found in this table as well). Slide 15 -​ As said before, neural tissue doesn’t have further classification. Neural tissue is just neural tissue.  -​ It has two main cells, the neuron and the neuroglia. The neuron is the main functional cell since is the one that transmits the sensory information to the CNS and transmits the commands to all the effectors (effector= all cells or organs in our body). -​ The picture is showing you a typical motor neuron. It is composed of the following structures: 1)​ The dendrites: These are extensions of the soma and they represent the “receiving” end of a neuron. They are the ones that get the signals from receptors or other neurons so that they can create a graded potential which then will become an action potential (this will be explained later in another lecture). The action potential then travels to the “giving” end. Both graded potential and action potential are voltages. 2)​ The soma: the body of the neuron. It also has receptors so it is part of the “receiving” end, but this body also has the nucleus, organelles and nissl bodies. The nissl bodies are important because they are the “organelles” of a neuron that synthesize neurotransmitters. 3)​ The axon hillock: is the connection between the soma and the axon. It is also known as the trigger zone because the threshold is found in this area. The threshold is the “voltage” needed to activate a neuron. A graded potential reaches the trigger zone and can either activate an action potential by reaching the threshold or it cannot activate an action potential and just “die”. So just because you reach the trigger zone doesn’t mean you reach threshold. If it reaches threshold is called a suprathreshold stimulus, if it doesn’t reach threshold is called a subthreshold stimulus. Stimulatory or excitatory signals that affect a graded potential are called EPSPs (again these are stimulatory so they are “+” charges), and inhibitory signals that affect a graded potential are called IPSPs (these are “-” charges). 4)​ The axon: if an action potential is generated then the signal (voltage) travels through the axon to reach the end of the neuron 5)​ Synaptic terminal: It is the end or “giving” end of a neuron. It is composed of telodendrions (which are just bifurcated extensions of the axon and are just used for transport) and the boutons/knobs (which are the pockets at the end of each telodendrion and these are the ones where the neurotransmitters of neurons are stored inside vesicles). When the action potential reaches the bouton then it promotes the release of the neurotransmitter (the mechanism for this will be discussed later). - Neurons can “connect” to other neurons, cells in glands or organs, and muscle cells. The “connection” is called a synapse. The pre-synaptic membrane is always the membrane of the bouton or a sensory receptor. The post-synaptic membrane depends on the cell that it is binding to. The space in between both membranes is called the synaptic cleft. Slide 16 -​ As I mentioned before you will need to know the location of the four main tissues, you do not need to know the classification. On a question I will use the correct classification of tissue but the name tells you what kind of tissue is it so you should be able to answer the question. -​ In this case, the answer would be “A” because epithelial tissue is found lining chambers or cavities or passageways. A vessel is a passageway for blood so the lining of it will be some kind of epithelium. In the options, the only one that has epithelial tissue is “A” so that is the answer.