Unit 1_ Homeostasis and the Cell PDF

Introduction to Physiology and Homeostasis Key Points: 1. What is the definition of physiology? 2. What is the definition of homeostasis? 3. What is the difference between the internal and external environment? 4. What are the components of a negative...

Introduction to Physiology and Homeostasis Key Points: 1. What is the definition of physiology? 2. What is the definition of homeostasis? 3. What is the difference between the internal and external environment? 4. What are the components of a negative feedback loop? 5. How do negative feedback loops maintain homeostasis? 6. How are positive and negative feedback loops different? 7. What is the organizational hierarchy of the body and how do cells contribute to physiology? Physiology: The study of how systems (ex. brain, heart, lungs, muscles, hormones) function in living organisms. - Explores the mechanism by which organisms control their internal environment regardless of what happens in the outside (or external) environment. - Physiology attempts to explain the physical and chemical factors responsible for both normal function and disease (called pathology). - The foundation of physiology lies in several key areas including genetics, anatomy, biochemistry, biophysics, and cell biology. Homeostasis: The maintenance of relatively stable conditions within the internal environment regardless of what is happening in the external environment. - A dynamic process that requires our body to constantly monitor the internal environment, and act on any changes it senses. Main variables maintained by homeostasis: 1. Body temperature 2. Blood sugar levels 3. Blood PH 4. Oxygen and carbon dioxide levels 5. Electrolyte balance 6. Electrolyte balance 7. Water balance Internal or External Environment: Our internal environment is constantly interacting with the external environment. - Many of our body systems have components that are actually considered part of the external environment. - Unless a substance passes a cell membrane and is absorbed, it is considered outside of the body, even if it might be something like food sitting in the digestive tract, or air in our lungs. - The circulatory system, including the heart and cardiovascular system, do not interact directly with the external environment. This system is considered an entirely internal system. Components of a Negative Feedback Loop: Homeostasis is maintained primarily through negative feedback loops. A negative feedback loop occurs when the effect of a reaction eventually loops back to shut itself off. The variables in the negative feedback loop become decreased. Control Centre: The control center integrates information from the sensors and compares it to a set point. - It then develops a plan to restore or maintain homeostasis.  - It sends the plan to the effectors. Effector: Organs or organ systems that respond to the plan from the control center. - By responding to the plan, they are effective at changing the variable. Regulated Variable: The variable is the internal condition that is being regulated through the negative feedback system. - Examples include temperature, water balance, sugar levels, to name a few. - The regulated variable will eventually reach homeostatic conditions and shut off the loop. Sensor: There are many different detection systems throughout our bodies. - Examples of what these specialized systems can detect include water balance, oxygenation, blood sugar levels, and temperature. - These sensors are constantly monitoring the internal environment and sending the information to the control center. How do negative feedback loops maintain homeostasis?: There are many variables in our body that need to be maintained in order to create ideal conditions for our cells to function properly. - These variables are regulated variables, meaning they can fluctuate and be maintained through negative feedback loops. - Negative feedback loops maintain the variable within a normal range and once the variable reaches its ideal level, it shuts off the mechanism that is regulating it. - If the variable once again falls outside the normal range, and is off balance, then the mechanism regulating the variable turns back on. How are positive and negative feedback loops different?: Our body generally uses negative feedback loops, although there are a few examples of positive feedback loops that exist. - Within a negative feedback loop the regulated variable becomes decreased, and within a positive feedback loop the regulated variable becomes increased. Positive Feedback Loops in the Body: A positive feedback loop occurs in the process that occurs during delivering a baby.  - As contractions of the uterus occur, this pushes the baby against the cervix, which then sends nerve signals (impulses) back to the brain, which triggers the secretion of a hormone that enters the bloodstream, and when it reaches the uterus, it causes the uterus to contract harder. - This positive feedback loop will continue until the baby is born, which is the external event that ends the loop. - Since the baby's head is no longer pushing on the cervix, there is no more positive feedback signaling to the brain. Organizational Hierarchy of the Body - Atoms to Macromolecules: Atoms are the building blocks of molecules, which then make macromolecules. - Macromolecules include Lipids, Carbohydrates, Proteins, DNA. Macromolecules to Organelles: Macromolecules then work together to create an organelle. For example, the membrane has a lipid bilayer and embedded glycoproteins (carbohydrates attached to proteins). Cells, tissues and organs: Organelles then work together to make a cell. Similar cells combine together to make tissues, such as epithelial tissues, connective tissues, muscle tissues, and neuronal tissues. These tissues work together to create organs. Organ Systems to Organisms: Organs then work together to form organ systems, such as the cardiovascular system. - Organ systems then work together to form an organism. - An example would be how the kidneys help to regulate blood pressure by sending signals to the brain, and by changing blood volume. - All these organs work together to maintain homeostasis and keep the organism alive. The Structure In the Cell: Cells can alter where proteins are expressed on their cell surface, such as one side of the cell expresses pumps and the other side expresses channels, or the cell expresses receptors to respond to signals in the body. - This means that the cells of the heart are going to be organized differently than the cells of the kidney. Nucleus: The nucleus is a membrane-bound organelle found in most human cells that contains the cell's genetic material (DNA) and controls its growth, metabolism, and reproduction. - It is often referred to as the control center of the cell, as it regulates gene expression and mediates the replication of DNA during the cell cycle. - Mature red blood cells do NOT have a nucleus. Endoplasmic Reticulum: The endoplasmic reticulum (ER) is a network of membranous tubules and sacs involved in protein and lipid synthesis. - It comes in two forms: rough ER, studded with ribosomes for protein synthesis, and smooth ER, which is involved in lipid synthesis and detoxification processes. Mitochondria: Mitochondria are membrane-bound organelles known as the powerhouses of the cell, as they generate ATP through cellular respiration. - They also play crucial roles in energy production, regulation of the cell cycle, and apoptosis (programmed cell death). Cell Membrane: The cell membrane, or plasma membrane, surrounds the cell's cytoplasm and organelles, serving as a protective barrier. - It regulates the passage of substances into and out of the cell through selective permeability, crucial for maintaining cellular homeostasis and communication with the external environment. Golgi Body: The Golgi apparatus, or Golgi body, is a stack of membrane-bound sacs responsible for processing, modifying, and packaging proteins and lipids synthesized in the cell. - It sorts and directs these molecules to their appropriate destinations within the cell or for secretion outside the cell. Ribosomes: Ribosomes are cellular structures composed of RNA and proteins that facilitate the synthesis of proteins by translating messenger RNA (mRNA) sequences into amino acid chains. - They are found either floating freely in the cytoplasm or attached to the endoplasmic reticulum, forming rough ER. Body Fluids Key Points: 1. What is the chemical composition of the intracellular fluid, interstitial fluid, and plasma in terms of sodium, potassium, chloride, and proteins? 2. How are ions distributed across a cell membrane?  3. What accounts for the differences in chemical composition of the intracellular and interstitial fluids and plasma? 4. What does the permeability of the lipid bilayer have to do with homeostasis? 5. What are the six functions of the membrane proteins? 6. What are the five major ways substances cross membranes and how do they occur? 7. What is the mechanism of diffusion? 8. What are four factors that affect the rate of movement of substances through protein channels? Our tissues, cells, and internal systems are all bathed in fluids. As a result, maintaining the correct volume and composition of fluid is part of maintaining homeostasis so that our organ systems can function at the optimal level. Different body compartments have different conditions: The body can be divided into two main compartments; intracellular and extracellular compartments. - Intracellular means anything that is inside the cell, and extracellular means anything outside the cell, and can be subdivided into interstitial fluid and blood plasma fluid. - Gasses and nutrients will move out of the capillary that contains blood plasma and into the interstitial fluid. From there, gasses and nutrients can then be supplied to cells and tissues. - Waste products are then released by cells and tissues into the interstitial fluids, and taken back up into the capillary. - Although the 'stuff' that makes up each body compartment is different, the amount of 'stuff' in each compartment is about the same. - This affects things like water and ion distribution. Intracellular Fluid: Fluid found inside the cell. - Makes up 67% of all fluid in the body.  - Has a relatively high concentration of K+ and protein compared to extracellular fluid. - Has a negative charge on the inside of the cell membrane. Blood Plasma Fluid: Fluid found in the blood that allows red and white blood cells, along with platelets to move throughout the circulation. - Makes up 6.6% of the fluid in our bodies and yellow liquid. - Is made up of 92% water and 8% substances, like ions, nutrients, gasses, and waste products. - It is a colloidal suspension where proteins, such as albumin, globulin, and fibrinogen remain in suspension in the plasma. - These proteins help play a role in drug distribution and absorption. Interstitial Fluid: Fluid that bathes the cells. - Nutrients and gasses move out of the capillary and into the interstitial fluid, where they are then distributed to the surrounding cells and tissues. - Makes up 26.4% of the fluid in our body. - Has relatively higher levels of Na+, Cl-, and Ca+ than inside the cell. Intracellular vs. Interstitial ion distribution: There is a relatively high concentration of Na+, Cl-, and Ca++ outside of the cell compared to inside the cell. - Inside the cell, K+ concentrations are relatively higher compared to outside the cell. - This distribution of ions keeps us alive! And is vigilantly maintained by our bodies as part of homeostasis.  - The common mnemonic to help remember the distribution of ions is called the 'salty banana'. Just like how a banana is high in potassium (K+) , so is the inside of the cell. Salt is made of Na+ and Cl-, and that's what is on the outside of the banana. What accounts for the differences in chemical composition of the intracellular and interstitial fluids, and plasma - The cell membrane acts as the primary mechanism for keeping the intracellular and interstitial compartments separate. - The cell membrane prevents the unregulated movement of ions across the cell membrane, creating a barrier that allows for the accumulation of Na+, Cl-, and Ca++ on the outside of the cell, and K+ on the inside of the cell. - It also provides the location and anchor for the Na+/K+ pump, which is regularly pumping out 3 Na+ ions, and pumping in 2 K+ ions. - The pump helps to continue to maintain the relative distributions of ions across the cell membrane. Non Charged Molecules: Noncharged or nonpolar molecules, such as O2 and CO2 can freely pass through the cell membrane. Phospholipid Bilayer: The phospholipid bilayer creates a hydrophobic (water fearing) (or lipophilic) environment that allows the movement of uncharged (non-polar) molecules across the cell membrane. Ions: Ions, which carry a charge, cannot freely pass through the cell membrane and have to rely on protein channels embedded into the membrane to move across the membrane. - K+ has a relatively high concentration inside the cell. Charged Particles: (ions) Carry a charge, cannot freely pass through the cell membrane and have to rely on protein channels embedded into the membrane to move across the membrane. - Na+ has a relatively high concentration outside the cell. Proteins Role and Function: Proteins have many roles to play in maintaining homeostasis and ensuring that systems are functioning properly.  - Proteins have many functions, such as building other proteins (DNA polymerase), providing structure to the cell (actin), acting as a messenger for signaling (neurotransmitters and hormones), helping chemical reactions occur (enzymes), and controlling the movement of substances across the cell membrane to name a few. Six Functions of membrane proteins - Cell Identity Marker: Serves as a cellular identification tab, distinguishes self from non-self cells, like foreign bacteria. - They are crucial for immune responses and tissue formation. The cell identity marker is often made up of both protein and carbohydrates (like glucose). These are called glycoproteins. Cell Surface Receptor: Receives extracellular signals from molecules like hormones or neurotransmitters, and transmits intracellular messages through other molecules. Examples: Nervous system - Neurotransmitters bind to cell surface receptors and create a change in the cell. Hormones - Some hormones bind to cell surface receptors and set off a cascade of messages within the cell, allowing the cell to respond. Ion Channel: Allows specific ions to move across the membrane along the ions concentration gradient (arrow indicates flow of molecules). Examples: K+ leak channels Na+ voltage-gated channels Transporters: Transporters facilitate the movement of molecules across the membrane. There are several types of transport across the membrane… Types of Transport Across The membrane - Facilitated Diffusion: Allows the passive movements of solutes along their concentration gradient (arrow indicates flow of molecules).  - Glucose can move into the cell through facilitated diffusion. Active Transport: the movement of molecules against a concentration gradient using ATP, the cell's form of energy (arrow indicates flow of molecules). - The Na+/K+ pump is an example as it moves Na+ out of the cell and K+ into the cell. Secondary Active Transport: Utilizes ion gradients to transport molecules across membranes, driven by energy from gradient-established primary active transport. - Glucose can be absorbed from the intestine through at the same time as Na+ due to a gradient of Na+ that is established on the other side of the cell. - More on this in the gastrointestinal tract module. Enzymes: Enzymes at the cell membrane catalyze reactions or facilitate processes such as signaling, transport, or breakdown of molecules. Example: Maltase. This enzyme is attached to the membrane of the small intestine and breaks down maltose into two glucose molecules so that glucose can be absorbed. Cell-Cell Adhesion Proteins: These proteins mediate cell-cell interactions and maintain tissues integrity and organization. Example: Tight-junction molecules. These proteins hold the cells of the heart together so that the tissue of the heart does not come apart with each heartbeat. Five Major Ways That Substances Cross the Membrane - Simple Diffusion: Molecules move from an area of high concentration to low concentration. - This can only occur if the molecule is small and non-polar and can easily move across the membrane. - This may also include small molecules that move through protein channels or pores in the membrane. Facilitated Diffusion: We define facilitated diffusion as the movement of a molecule, across the membrane AND along its concentration gradient that requires the help of a transport protein. - This means that the transport protein does NOT require any energy input. An example of this type of movement is the movement of glucose. - Glucose is too big to diffuse across the membrane, and cannot fit through a pore. It requires a transport protein, however, it will move along its concentration gradient, going from high in the bloodstream and interstitial fluid, to low in the cell, where it is getting metabolized. - Since it is getting metabolized, the concentration of glucose inside the cell will always be low. Pumps: Pumps will move molecules AGAINST their concentration gradients, that means they are pushing molecules from low concentration to high concentration, which is the exact opposite direction from diffusion, and this requires energy. - A pump works by moving molecules from an area of low concentration to high concentration. - An example of a pump that we will see repeatedly is the Na+/K+-ATPase also known as the Na+/K+ pump. Endocytosis: Some molecules are just too big to cross the cell membrane, and cannot even cross with the help of transport proteins. For these types of molecules, the cell uses the power of its flexible membrane, and engulfs the molecules to move them into the cell. The molecules might still bind to the cell membrane, which then caves in, and pinches off a piece of the membrane which then acts as an envelope for the molecules inside the cell.  Steps of Endocytosis - Step 1 - : The flexible membrane forms a pocket, allowing molecules to get engulfed by the membrane. Step 2 - Membrane Reforms: The membrane connects allowing the new package or envelope of molecules to be released into the cell so that it can be transported to its proper destination. Step 3 - Vesicles: The vesicle then transports the molecules throughout the cell. The vesicle will transport the molecule to where it can be broken down or incorporated into a cellular process. Exocytosis: As with endocytosis, some molecules are too big to leave the cell through a transport protein. These molecules are packaged into vesicles, where the envelope of the vesicle is made up of the same molecules as the cell membrane. - Vesicles are therefore sent to the membrane to release the molecules to the interstitial fluid.  Steps of Exocytosis - Step 1 - Vesicle: The vesicle contains molecules that need to be released into the interstitial fluid. - These can be all sorts of different things, such as hormones or neurotransmitters. Step 2 - Joining The Cell Membrane: The vesicle then connects to the cell membrane, which separates to incorporate the membrane of the vesicle into the cell membrane itself. - In doing so, it allows the molecules to be released. Step 3 - Exocytosis: Molecules are released from the inside of the cell to the outside of the cell. The membrane surrounding the vesicle is incorporated directly into the cell membrane. Osmosis Osmosis: The movement of water across a semipermeable membrane down its concentration gradient is called osmosis. Solvent: A solvent is the liquid that something is going to be dissolved in. - water is the solvent. - A different example of a solvent could be oils. Oils will help to dissolve things such as lipids, fats, or waxy substances. Solute: This is the substance being dissolved into a solvent. - For example, ice tea crystals, sugar, powdered fruit drinks, and even honey are all solutes. Solution: A solution is what you get when you dissolve a solute into a solvent. - For example, adding ice tea crystals to water. Factors That Affect The Movement of Water Across Membranes - 1. The permeability of the membrane: Our cell membrane can actually increase or decrease their permeability to water or ions.  2. The concentration of solutes in the intracellular and interstitial fluids: Ion distribution across the cell membrane is not equal. Differences in ion concentration will affect osmosis. 3. Pressure Gradient Across The Cell: When cells are closed off, this would cause pressure to build and prevent the water from rising up on the right side, thus inhibiting osmosis. Units of Osmosis: Looking at two different solutions, we may want to determine what the concentration of solute to solvent is, which will also help to determine if osmosis will occur between two solutions, and in which solution. - Solutes that can cause the movement of water are called osmotically active particles. - Na+, K+, Ca++, and glucose are all examples of osmotically active particles. - The units to describe the osmotically active particles in a solution are called osmoles. Osmolality: Equal to the number of osmoles per kg of water or the number of osmoles per liter of water. Calculating Osmolarity: To make a 1 molar solution of NaCl, you would take 1 mole ofNaCl and add it to 1 kg of water. - When NaCl is placed in water, it dissociates into Na+ and Cl-, which means we have 2 osmotically active particles in the solution. This would equal to 2 osmoles per kg of water. Osmotic pressure: Osmotic pressure is the force required to stop the movement of water. This is important physiologically as osmotic pressure plays a role in many organ systems. - The kidneys are a great example of osmotic pressure. As the kidneys filter the blood, water moves into the kidney and can be reabsorbed or can be turned into urine. - Filtration of the blood at the kidney will depend, in part, on osmotic pressure. Tonicity: The ability of a solution to cause the movement of water into or out of a cell. Hypertonic Solution: A hypertonic solution has a higher concentration of solutes (like salts or sugars) compared to the inside of a cell. - This means there are more solute particles and less water outside the cell than inside. - When a cell is placed in a hypertonic solution, water moves out of the cell through the process of osmosis. This causes the cell to shrink or shrivel. Isotonic Solution: An isotonic solution has the same concentration of solutes (like salts or sugars) as the inside of a cell. - This balance means that the amount of water entering and leaving the cell is equal, resulting in no net movement of water and maintaining the cell’s normal shape and function. Hypotonic Solution: A hypotonic solution has a lower concentration of solutes (like salts or sugars) compared to the inside of a cell. - This means there are fewer solute particles and more water outside the cell than inside. When a cell is placed in a hypotonic solution, water moves into the cell through the process of osmosis. - Although the cell will commonly burst (called lysing), this doesn't always happen. Sometimes the cell will simply swell up, but won't burst. Clinical Importance of Hypertonic Solutions: Hypertonic solutions can be used to reduce swelling in cells or tissues, such as in cases of cerebral edema (swollen brain cells) where a hypertonic saline solution may be administered to draw water out of swollen brain cells. - Since the osmolarity of the solution is higher than the cells, water will move out of the cells and shrink back to normal size. Clinical Importance of Hypotonic Solutions: Hypotonic solutions (like 0.45% saline) can be administered intravenously to patients who are dehydrated to rehydrate their cells. - Because the solution has a lower osmolarity than the inside of the cell, water will move into the cell and rehydrate the patient. Note: In each of these cases the net difference between the osmolarity of the solutions and the cells is not very big. This means that osmosis will occur slowly to allow the cells to adjust to the changes in size easily. Six factors that affect the rate of movement through a protein channel: - Water concentration // concentration gradient: (water moves from low to high areas of water concentration, along its concentration gradient) Greater the difference = greater the net flux - Electrical gradient: The difference in charge across the membrane - Lipid solubility: Higher the lipid solubility = higher the amount of substance moved in or out of the cell. - Molecular size: smaller = faster - Membrane area: Greater the area = greater the net flux - Composition of the lipid bilayer // membrane: Related to cell function (presence of transport mechanisms or proteins in the lipid bilayer dictate how permeable the lipid bilayer is and how easy molecules can move between intracellular and extracellular spaces) Resting Membrane Potential - Electrical Charge Difference: The inside of the cell is more negatively charged compared to the outside. Ion Distribution: Mainly due to differences in concentrations of sodium (Na⁺) and potassium (K⁺) ions. Sodium ions are more concentrated outside the cell, while potassium ions are more concentrated inside the cell. Ion Channels and Pumps: The sodium-potassium pump actively transports 3 Na⁺ ions out of the cell and 2 K⁺ ions into the cell, maintaining the ion gradient. Typical Value: The resting membrane potential is usually around -70 millivolts (mV). What Forces are Affecting the Ions Distributed Across the Cell: Two forces are affecting the distribution of ions across the membrane. The first is concentration gradients and the second is electrical gradients. - Together, they form the electrical-chemical gradient that will act on an ion. Sometimes these forces act together in one direction (say to move an ion inside the cell) and sometimes these two forces act in opposite directions.  QUESTION BANK 1. Which of the following help to maintain the correct distribution of ions across the cell membrane? 2. If a solution had a high concentration of solute (ex. sugar), what would that say about the concentration of solvent (ex. water)? 3. A jar is divided by a semipermeable membrane that is permeable to water. The solution on the right side of the jar is 3 osmoles, and the solution on the left side of the jab is 2.5 osmoles. Which way will osmosis occur? 4. Chamber A has a 300 mM of KCl into 1 kg of water, and Chamber B has 200 mM of CaCl2 into 1 kg of water. They are separated by a semipermeable membrane that only allows water to move through. What will happen? 5. What is the electrical-chemical equilibrium for K+? 6. How does the Na+/K+ pump help to maintain the distribution of ions across the membrane? 7. What would happen to the cell if the Na+/K+ pump did not work?  ANSWER BANK: 1. Mitochondria, Na+/K+ pump, and Phospholipid bilayer. 2. There would be a low concentration of solvent. 3. Osmosis will occur from the left side of the jar to the right side of the jar. 4. Chamber A will have a solution of 600 mOsm (300 K+ ions + 300 Cl- ions), while Chamber B will also have a solution of 600 mOsm (200 Ca++ ions + 200 Cl- ions + 200 Cl- ions). Since the two solutions have the same osmolarity, there will be no net movement of water. 5. -90 mV 6. The pump uses ATP to move 3 Na+ ions out of the cell, and 2 K+ ions into the cell against their concentration gradient. 7. The osmolarity would increase inside the cell and the cell would swell.